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Sea fog particles have a serious impact on light wave propagation, resulting in low contrast and unrecognisable intensity images, which adversely affect transportation, marine fishing and development projects, as well as military activities. In this paper, a T-matrix-based transmission model is established to simulate polarised light. Using the polarised transmission model and a multi-layer sea fog simulator, the effects of different polarisation states, different wavelengths and different salinities on the degree of polarisation are investigated in multi-layers of different media and 14 cases of optical thickness. The results show that it is more difficult to depolarise circularly polarised light than linearly polarised light at the same sea spray optical thickness. The DOP(Degree of polarization) of near-infrared light is always greater than that of visible light, indicating that circularly polarised light is more polarisation preserving than linearly polarised light, and that the polarisation preserving properties of near-infrared light are better than those of visible light.

Glioma is the most common type of primary malignant brain tumor in adults. Our previous work discovered that plasma miR-454-3p may have some advantages in glioma prognosis, but the clinical significance and the regulatory mechanism of miR-454-3p in glioma have not been systematically investigated, especially regarding the relationship between circulating and tissue miR-454-3p. The expression level of miR-454-3p in glioma serum and tissues was analyzed through quantitative real-time PCR (qRT-PCR). Cell-Counting Kit 8 (CCK-8), wound healing, transwell invasion, apoptosis, and immunofluorescence assays were used to assess the role of miR-454-3p in glioma cancer cells. ATG12 was selected as the target gene of miR-454-3p by bioinformatic analysis. The relationship between ATG12 and miR-454-3p was further validated by luciferase reporter assays and Western blot analysis. miR-454-3p was significantly downregulated in tumor tissues, while it was remarkably upregulated in exosomes from the same patients with glioma. The area under curve (AUC) of exosomal miR-454-3p for glioma diagnosis was 0.8663. The exosomal miR-454-3p was prominently lower in the postoperative serums than that in the preoperative serums. High miR-454-3p expression in exosomes or low miR-454-3p expression in tissue was associated with poor prognosis. Restored expression of miR-454-3p suppressed cell proliferation, migration, invasion, and autophagy in glioma. ATG12 was validated as a direct target of miR-454-3p. The overexpression of ATG12 could partially reverse the effects induced by miR-454-3p suppression. Our data indicate that miR-454-3p may serve as an exosomal biomarker and may be developed into a novel treatment for glioma.

Supplementary Table 1. Univariate and multivariate analyses on survival in glioma patients. Supplementary Figure 1: Real-time PCR analysis of exosomal miR-454-3p in the serum of glioma patients and that of healthy controls in the combination group. Supplementary Figure 2: ATG12 is highly expressed in glioma. (A) ATG12 expression in different types of cancer and in their respective normal controls on GEPIA. GBM: glioblastoma, LLG: low grade glioma. (B) ATG12 expression in GBM and non-tumor on Gliovis. GBM: glioblastoma.

A defining feature of successful vaccination is the ability to induce long-lived antigen- specific memory cells. Follicular helper T (Tfh) cells specialize in providing help to B cells in mounting protective humoral immunity in infection and after vaccination. Memory Tfh cells that retain the CXCR5 expression can confer protection through enhancing humoral response upon antigen re-exposure but how they are maintained is poorly understood. CXCR5+ memory Tfh cells in human blood are divided into Tfh1, Tfh2 and Tfh17 cells by the expression of chemokine receptors CXCR3 and CCR6 associated with Th1 and Th17 respectively. Here, we developed a new method to induce Tfh1, Tfh2 and Tfh17-like (iTfh1, iTfh2 and iTfh17) cells in vitro. Although all three iTfh subsets efficiently support antibody responses in recipient mice with immediate immunization, iTfh17 cells are superior to iTfh1 and iTfh2 cells in supporting antibody response to a later immunization after extended resting in vivo to mimic memory maintenance. Notably, the counterpart human Tfh17 cells are selectively enriched in CCR7+ central memory Tfh (TfhCM) with survival and proliferative advantages. Furthermore, the analysis of multiple human cohorts that received different vaccines for HBV, influenza virus, tetanus toxin or measles revealed that vaccine-specific Tfh17 cells outcompete Tfh1 or Tfh2 cells for the persistence in memory phase. Therefore, the complementary mouse and human results showing the advantage of Tfh17 cells in maintenance and memory function supports the notion that Tfh17-induced immunization might be preferable in vaccine development to confer long-term protection.

Heme oxygenase function is highly conserved between vertebrates where it plays important roles in normal embryonic development and controls oxidative stress. Expression of the zebrafish heme oxygenase 1 genes is known to be responsive to oxidative stress suggesting a conserved physiological function. In this study, we generate a knockout allele of zebrafish

Pidotimod (PDT) is a synthetic dipeptide molecule which can improve immune responses in mice and humans, protecting hosts from infection. However, the exact mechanism of protection remains ill-defined. The effect of pidotimod has not yet been investigated in the inflammatory response of zebrafish. In this study, we used tail wound and infection models of zebrafish to study the effect of PDT on inflammation. We found that zebrafish larvae were sensitive to PDT immersion causing toxicity at doses above 50 μg/mL. The tail wound assay showed that PDT increased the recruitment of neutrophils and macrophages to the wound site and promoted the transcription of the pro-inflammatory cytokine il1b. However, we did not observe protection of uropathogenic Escherichia coli or Mycobacterium marinum infected zebrafish larvae following PDT treatment. This study provides a new platform for PDT research, which is worthy of further research to identify further effects of PDT therapy.

Gut dysbiosis is an important modifier of pathologies including cardiovascular disease but our understanding of the role of individual microbes is limited. Here, we have used transplantation of mouse microbiota into microbiota-deficient zebrafish larvae to study the interaction between members of a mammalian high fat diet-associated gut microbiota with a lipid rich diet challenge in a tractable model species. We find zebrafish larvae are more susceptible to hyperlipidaemia when exposed to the mouse high fat-diet-associated microbiota and that this effect can be driven by two individual bacterial species fractionated from the mouse high fat-diet-associated microbiota. We find Stenotrophomonas maltophilia increases the hyperlipidaemic potential of chicken egg yolk to zebrafish larvae independent of direct interaction between S. maltophilia and the zebrafish host. Colonisation by live, or exposure to heat-killed, Enterococcus faecalis accelerates hyperlipidaemia via host Myd88 signalling. The hyperlipidaemic effect is replicated by exposure to the Gram positive Toll-like receptor agonists peptidoglycan and lipoteichoic acid in a MyD88-dependent manner. In this work, we demonstrate the applicability of zebrafish as a tractable host for the identification of gut microbes that can induce conditional host phenotypes via microbiota transplantation and subsequent challenge with a high fat diet.

Iron homeostasis is essential for both sides of the host-pathogen interface. Restricting access of iron slows bacterial growth while iron is also a necessary co-factor for host immunity. Heme oxygenase 1 (HMOX1) is a critical regulator of iron homeostasis that catalyses the liberation of iron during degradation of heme. It is also a stress-responsive protein that can be rapidly upregulated and confers protection to the host. Although a protective role of HMOX1 has been demonstrated in a variety of diseases, the role of HMOX1 in Mycobacterium tuberculosis infection is equivocal across experiments with different host-pathogen combinations. Here, we use the natural host-pathogen pairing of the zebrafish-Mycobacterium marinum infection platform to study the role of zebrafish heme oxygenase in mycobacterial infection. We identify zebrafish Hmox1a as the relevant functional paralog of mammalian HMOX1 and demonstrate a conserved role for Hmox1a in protecting the host from M. marinum infection. Using genetic and chemical tools, we show zebrafish Hmox1a protects the host against M. marinum infection by reducing infection-induced iron accumulation and ferrostatin-sensitive cell death.

Follicular helper T (TFH) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate TFH function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying TFH regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human TFH differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs TFH generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of TFH cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure., T follicular helper (TFH) cell numbers are increased after vaccination and fewer of these cells might result in reduced vaccine responses. Here the authors show in mice and humans that leptin promotes TFH differentiation and that low leptin levels can impair TFH response to vaccines and virus protection in mice.

Iron homeostasis is essential for both sides of the host-pathogen interface. Restricting access of iron slows bacterial growth while iron is also a necessary co-factor for host immunity. Heme oxygenase 1 (HMOX1) is a critical regulator of iron homeostasis that catalyses the liberation of iron during degradation of heme. It is also a stress-responsive protein that can be rapidly upregulated and confers protection to the host. Although a protective role of HMOX1 has been demonstrated in a variety of diseases, the role of HMOX1 in Mycobacterium tuberculosis infection is equivocal across experiments with different host-pathogen combinations. Here we use the natural host-pathogen pairing of the zebrafish-Mycobacterium marinum infection platform to study the role of zebrafish heme oxygenase in mycobacterial infection. We identify zebrafish Hmox1a as the relevant functional paralog of mammalian HMOX1 and demonstrate a conserved role for Hmox1a in protecting the host from mycobacterial infection. Using genetic and chemical tools, we show zebrafish Hmox1a protects the host against mycobacterial infection by reducing infection-induced iron accumulation and ferroptosis.

Additional file 1: Table S1. Top five up/downregulated circRNAs in the microarray.

Background As one of the most common chronic diseases in the world, osteoporosis occurs especially in postmenopausal women. Circular RNAs (circRNAs) are emerging as major drivers in human disease. The aim of the present study was to analyse circRNA expression profiles in osteoporosis and to explore the clinical significance and the regulatory molecular mechanism of hsa_circ_0006859 during osteoporosis. Methods Exosomes were isolated from clinically collected serum samples. A circRNA microarray was performed to screen differentially expressed circRNAs. Quantitative real-time PCR (qRT-PCR) and western blot were performed to analyse target gene mRNA expression and protein expression. Alizarin red staining (ARS) was performed to evaluate the mineralization ability of human bone marrow mesenchymal stem cells (hBMSCs). Oil Red O staining was performed to evaluate the lipid droplet formation ability of hBMSCs. Bioinformatics analysis and the luciferase reporter assay were performed to investigate the interaction between two genes. Results Hsa_circ_0006859 was identified as one of the most upregulated circRNAs in the microarray analysis. Hsa_circ_0006859 in exosomes was upregulated in osteoporosis patients compared to healthy controls. Hsa_circ_0006859 differentiated osteopenia or osteoporosis patients from healthy controls with high sensitivity and specificity. Hsa_circ_0006859 suppressed osteoblastic differentiation and promoted adipogenic differentiation of hBMSCs. Hsa_circ_0006859 directly bound to miR-431-5p, and ROCK1 was identified as a novel target gene of miR-431-5p. Hsa_circ_0006859 is a competing endogenous RNA (ceRNA) of miR-431-5p that promotes ROCK1 expression. Hsa_circ_0006859 suppressed osteogenesis and promoted adipogenesis by sponging miR-431-5p to upregulate ROCK1. Conclusions Exosomal hsa_circ_0006859 is a potential biomarker for postmenopausal osteoporosis and controls the balance between osteogenesis and adipogenesis in hBMSCs by sponging miR-431-5p.

Maintaining frequency stability is a prerequisite to ensure safe and reliable operation of the power grid. Based on the purpose of improving the frequency regulation performance of the power grid and efficiently utilizing the frequency regulation resources, a improved particle swarm optimization-based thermal power-energy storage combined automatic power generation control (AGC) frequency regulation control method is proposed. In this method, the AGC frequency regulation control optimization model is established, the dynamic weight coefficient based on the power change rate and acceleration is adopted, the improved particle swarm optimization algorithm is used to optimize the frequency modulation responsibility allocation in real time, and the energy storage SOC real-time management scheme is formulated. By building a regional power grid frequency regulation dynamic model, the simulation and comparison experiments are carried out to verify the effectiveness of the proposed method. This method comprehensively considers the frequency regulation output characteristics of thermal power units and energy storage systems, the operating characteristics and sustainability of energy storage systems and the impact of different types of load disturbances on the AGC frequency regulation responsibility allocation method, which effectively reduces unit loss, increases frequency regulation compensation income and can improve the frequency regulation performance of the power grid while ensuring continuous and efficient operation of the energy storage battery.

Background: The present study evaluated the potential of hsa_circ_0001445 as a biomarker in plasma for postmenopausal patients with osteoporosis (OPO). Materials & methods: The expression levels of hsa_circ_0001445 in plasma were detected in healthy controls, patients with osteopenia (OPE) and patients with OPO by using quantitative reverse-transcriptase PCR. Results: The expression levels of hsa_circ_0001445 in plasma were much lower in OPO patients compared with OPE patients and healthy controls. Its expression was positively correlated with the T-score and was negatively correlated with β-isomerized C-terminal telopeptides (β-CTx). It could distinguish OPE or/and OPO patients from healthy controls. Moreover, its expression was significantly upregulated in the plasma of OPO patients after anti-osteoporotic treatment. Conclusion: Hsa_circ_0001445 in plasma may be a novel potential diagnostic biomarker for OPO.

With the continuous development of UHVDC transmission and renewable energy power generation, large number of synchronous generators have been replaced, and the risk of transient frequency security after faults has increased. Electrochemical energy storage is developed as a flexible control resource. Based on the fast power regulation characteristics, the function of energy storage in the prevention, emergency, and correction control of frequency stability for three defense lines is analyzed. The technical points of capacity allocation for electrochemical energy storage to support transient frequency security are discussed. Meanwhile, this paper researches the optimal configuration of energy storage adapting to multiple application scenarios and optimal operation modes of energy storage power stations.

Energy storage being developing rapidly can’t be ignored in the operation of power system. In this paper, the regulation of energy storage on the power side of renewable energy power station is considered to ensure that the output of power station can be adjusted and participate in the grid dispatching. Firstly, the renewable energy power station is regarded as the adjustable power source and optimize the power grid scheduling; Then, according to the results of the first stage of optimization, the output of energy storage and thermal power units in the power grid is adjusted to ensure the stable operation of the power system based on the actual output of renewable energy. Considering the advantages of energy storage, the optimal dispatching method of power grid proposed in this paper ensures that the output of renewable energy power storage power station can be adjusted in the dispatching process, and this method which avoids the curtailment of wind power and photovoltaic, reduces the impact of renewable energy fluctuation, also provides a new way for the power grid to absorb renewable energy.

Prevalence of Mycobacterium abscessus infections is increasing in patients with respiratory comorbidities. After initial colonisation, M. abscessus smooth colony (S) variants can undergo an irreversible genetic switch into highly inflammatory, rough colony (R) variants, often associated with a decline in pulmonary function. Here, we use an adult zebrafish model of chronic infection with R and S variants to study M. abscessus pathogenesis in the context of fully functioning host immunity. We show that infection with an R variant causes an inflammatory immune response that drives necrotic granuloma formation through host TNF signalling, mediated by the tnfa, tnfr1 and tnfr2 gene products. T cell-dependent immunity is stronger against the R variant early in infection, and regulatory T cells associate with R variant granulomas and limit bacterial growth. In comparison, an S variant proliferates to high burdens but appears to be controlled by TNF-dependent innate immunity early during infection, resulting in delayed granuloma formation. Thus, our work demonstrates the applicability of adult zebrafish to model persistent M. abscessus infection, and illustrates differences in the immunopathogenesis induced by R and S variants during granulomatous infection.

Infections caused by Mycobacterium abscessus are increasing in prevalence within patient groups with respiratory comorbidities. Initial colonisation by the smooth colony M. abscessus (S) can be followed by an irreversible genetic switch into a highly inflammatory rough colony M. abscessus (R), often associated with a decline in pulmonary function. Our understanding of the role of adaptive immunity in M. abscessus pathogenesis is largely unknown. Here, we have used intraperitoneal infection of adult zebrafish to model M. abscessus pathogenesis in the context of fully functioning host immunity. We find infection with the R variant penetrates host organs causing an inflammatory immune response leading to necrotic granuloma formation within 2 weeks. The R bacilli are targeted by T cell-mediated immunity and burden is constrained. Strikingly, the S variant colonises host internal surfaces at high loads and is met with a robust innate immune response but little T cell-mediated immunity. Invasive granuloma formation is delayed in S variant infection compared to R variant infection upon which T cell-mediated immunity is required to control infection. In mixed infections, the S variant outcompetes the R variant. We also find the R variant activates host immunity to the detriment of S variant M. abscessus in mixed infections. These findings demonstrate the applicability of the adult zebrafish to model persistent M. abscessus infection and provide insight into the immunopathogenesis of chronic M. abscessus infection.

Background Glioma is the most common central nervous system (CNS) tumour. p62, an important autophagy adaptor, plays a crucial role in cancer. However, the role of p62 in the progression of glioma is poorly characterized. Methods We examined the expression of p62 in glioma tissues and cell lines. Then we investigated the function of p62 in vitro, and clarified the mechanism underlying the regulation of p62 expression. Results We revealed that p62 was upregulated at both the mRNA and protein levels in human glioma tissues irrelevant to isocitrate dehydrogenase (IDH) status. Then, we found that overexpression of p62 promoted glioma progression by promoting proliferation, migration, glycolysis, temozolomide (TMZ) resistance and nuclear factor κB (NF-κB) signalling pathway, and repressing autophagic flux and reactive oxygen species (ROS) in vitro. In accordance with p62 overexpression, knockdown of p62 exerted anti-tumour effects in glioma cells. Subsequently, we demonstrated that miR-124-3p directly targeted the 3′-UTR of p62 mRNA, leading to the downregulation of p62. Finally, we found that p62 function could be partially reversed by miR-124-3p overexpression. Conclusions Our results demonstrate that p62 can be targeted by miR-124-3p and acts as an oncogene in glioma, suggesting the potential value of p62 as a novel therapeutic target for glioma.

An emergency control strategy of electric vehicle charging station (EVCS) is proposed to avoid transmission line overload, where the second order power sensitivity is considered. In this paper, EVCSs are considered to be flexible load, which can be controlled for enhancing the system security. Compared to the traditional sensitivity method, the second order sensitivity can capture the nonlinearity better, especially when the system is with heavy load. Case studies show that the proposed method can provide more effective results, when the system nonlinearity is strong.

Nano-copper (NC) has been developed recently with good potential for electronic packaging applications. In this work, the interfacial reaction between NC and Sn-3.5Ag and the adhesion between NC and different metallizations were investigated. Thermal Gravimetric Analysis (TGA) results of NC paste were used to help determine the best sintering condition of NC paste. Heating NC paste at 230 ºC for 10 min at N2 atmosphere is the optimal sintering condition. The sintered NC paste shows a porous nanocrystal structure. In the solder interfacial reaction study with Sn-3.5Ag, plated Cu was used as a reference. Both sintered NC/Sn-3.5Ag and plated Cu/Sn-3.5Ag samples were reflowed for different time spans to obtain their morphology and kinetic information. The morphology changes from 10s to 5 hours reflow showed that the interfacial reaction of NC/Sn-3.5Ag is quite different from Cu/Sn-3.5Ag. NC/Sn-3.5Ag produces porous and elongated scallop-type Intermetallic Compounds (IMCs) while Cu/Sn-3.5Ag only forms scallop-type IMCs. The cause of this morphology difference is due to nano-copper’s unique porous structure. Based on the Scanning Electron Microscope (SEM) and (Energy Dispersive X-ray Spectroscopy) EDS analysis of samples of different reflow times, an IMC growth mechanism in NC/Sn-3.5Ag has been proposed. To quantify NC/Sn-3.5Ag and Cu/Sn-3.5Ag interfacial reaction, a kinetics analysis of the interfacial IMC growth was carried out. Results show that NC/Sn-3.5Ag reaction is faster than Cu/Sn-3.5Ag reaction. The growth of Cu6Sn5 in Cu/Sn-3.5Ag follows t1/3 growth kinetics while the growth of Cu6Sn5 in NC/Sn-3.5Ag follows t1/2 growth kinetics. By comparing experiment result with kinetics model, we conclude that the IMC growth in Cu/Sn-3.5Ag is controlled by diffusion through fast diffusion channel such as the IMC grooves while NC/Sn-3.5Ag reaction is mainly controlled by diffusion through the existing IMC layers. In the adhesion study between NC and different metallzations, NC as a potential joining material was evaluated by cross-cut test and die-shear test. Different metallizations were prepared by either sputtering or electrochemical method. These metallizations are chosen because they are either commercialized in the industry or have shown very good performance in lead-free solder applications. Even though NC can directly bond with Cu surface without forming IMCs, for the purpose of its potential as a joining material used in the future, it is essential to understand its adhesion conditions with different metallizations. Different metallizations were prepared and analyzed by SEM, EDS and Atomic Force Microscope (AFM). The surface roughness, element concentration and metallization layer thickness were obtained and analyzed. Cross-cut adhesion test shows that Cu, ENIG, Cr/Ni/Au and Ni-Sn-P have relatively better adhesion with NC than Ni-P, Ni-W-P, Ni-Co-P. Shear test result reveals that Cu has the best adhesion with NC. By fractographic analysis of the shear test result, NC/Cu failure mode is verified as bulk (cohesive) failure, which resulted in higher failure strength. The failure mode of Ni-Sn-P/NC is bulk-partial IMC failure. The failure mode of Cr/Ni/Au and ENIG is bulk-partial pad peeling failure. In summary, the morphology and kinetics study of NC/Sn-3.5Ag interfacial reaction have been carried out. The obtained information could be used as a reference in electronic packaging applications involving NC and Sn-based solders. Besides, the adhesion study between NC and different metallizations examines the potential of NC paste as a die-attach joining material. Experiment result shows that pure Cu has the best adhesion with NC after reflow at 230 ºC for 10 min. MASTER OF ENGINEERING (MSE)

Additional file 5: Figure S3. Role of p62 knockdown in cell autophagy and NF-κB signalling pathway. (A) Relative p62 protein levels in U87 and U251 cells after transfection with nc-siRNA or p62-siRNAs and treatment with CQ. (B) Statistical quantitation of the role of p62 knockdown in cell autophagy detected with western blot. (C) Nuclear NF-κB protein levels in p62 KD cells detected with western blot. (D to G) Relative mRNA levels of CCL2, IL-6, TGFβ1 and CSF3 in p62 KD cells. **P

Sn57.6Bi0.4Ag solder has been reinforced successfully through the addition of tungsten (W) nanoparticles at a concentration of 0.5 wt%. With the addition of W nanoparticles, the solder matrix lamellar interphase spacing was reduced by 31.0%. Due to the dispersion of W nanoparticles and the consequently refined microstructure, the mechanical properties of the solder alloy were enhanced, as indicated by a 6.2% improvement in the microhardness. During the reflow of solder on Au/Ni/Cu pads, the entire Au layer dissolved into the molten solder rapidly and a large number of (Au,Ni)(Sn,Bi) 4 particles were formed. The fracture path of the as-reflowed joint was within the solder region, showing ductile characteristic, and the shear strength was reinforced by 8.2%, due to the enhanced mechanical properties of the solder. During the subsequent aging process, the Au migrated back towards the interface and a thick layer of interfacial (Au,Ni)(Sn,Bi) 4 IMC was formed, leading to the shift of the fracture path to the interfacial IMC region, the transformation to brittle fracture and the deterioration of the strength of the joint, due to Au embrittlement. By adding W nanoparticles, the migration of Au was mitigated and the thickness of the (Au,Ni)(Sn,Bi) 4 layer was reduced significantly, which reduced the Au embrittlement-induced deterioration of the strength of the joint. During electromigration, the segregation of the Bi-rich and Sn-rich phases and the accumulation of the (Au,Ni)(Sn,Bi) 4 layer at cathode interface were mitigated by the addition of W nanoparticles, which improved the electromigration resistance.

The evolution of microstructure in Cu/In–48Sn/Cu solder bump interconnects at a current density of 0.7 × 10 4 A/cm 2 and ambient temperature of 55 °C has been investigated. During electromigration, tin (Sn) atoms migrated from cathode to anode, while indium (In) atoms migrated from anode to cathode. As a result, the segregation of the Sn-rich phase and the In-rich phase occurred. A Sn-rich layer and an In-rich layer were formed at the anode and the cathode, respectively. The accumulation rate of the Sn-rich layer was 1.98 × 10 −9 cm/s. The atomic flux of Sn was calculated to be approximately 1.83 × 10 13 atoms/cm 2 s. The product of the diffusivity and the effective charge number of Sn was determined to be approximately 3.13 × 10 −10 cm 2 /s. The In–48Sn/Cu IMC showed a two layer structure of Cu 6 (Sn,In) 5 , adjacent to the Cu, and Cu(In,Sn) 2 , adjacent to the solder. Both the cathode IMC and the anode IMC thickened with increasing electromigration time. The IMC evolution during electromigration was strongly influenced by the migration of Cu atoms from cathode to anode and the accumulation of Sn-rich and In-rich layers. During electromigration, the Cu(In,Sn) 2 at the cathode interface thickened significantly, with a spalling characteristic, due to the accumulation of In-rich layer and the migration of Cu atoms - while the Cu(In,Sn) 2 at the anode interface reduced obviously, due to the accumulation of Sn-rich layer. The mechanism of electromigration-induced failure in Cu/In–48Sn/Cu interconnects was the cathode Cu dissolution-induced solder melt, which led to the rapid consumption of Cu in the cathode pad during liquid-state electromigration and this finally led to the failure.

Glioma is the most common type of primary malignant brain tumor in adults. Our previous work discovered that plasma miR-454-3p may have some advantages in glioma prognosis, but the clinical significance and the regulatory mechanism of miR-454-3p in glioma have not been systematically investigated, especially regarding the relationship between circulating and tissue miR-454-3p. The expression level of miR-454-3p in glioma serum and tissues was analyzed through quantitative real-time PCR (qRT-PCR). Cell-Counting Kit 8 (CCK-8), wound healing, transwell invasion, apoptosis, and immunofluorescence assays were used to assess the role of miR-454-3p in glioma cancer cells. ATG12 was selected as the target gene of miR-454-3p by bioinformatic analysis. The relationship between ATG12 and miR-454-3p was further validated by luciferase reporter assays and Western blot analysis. miR-454-3p was significantly downregulated in tumor tissues, while it was remarkably upregulated in exosomes from the same patients with glioma. The area under curve (AUC) of exosomal miR-454-3p for glioma diagnosis was 0.8663. The exosomal miR-454-3p was prominently lower in the postoperative serums than that in the preoperative serums. High miR-454-3p expression in exosomes or low miR-454-3p expression in tissue was associated with poor prognosis. Restored expression of miR-454-3p suppressed cell proliferation, migration, invasion, and autophagy in glioma. ATG12 was validated as a direct target of miR-454-3p. The overexpression of ATG12 could partially reverse the effects induced by miR-454-3p suppression. Our data indicate that miR-454-3p may serve as an exosomal biomarker and may be developed into a novel treatment for glioma.

Background/Aims: microRNAs (miRNAs) are known to act as oncogenes or tumor suppressors in diverse cancers. Although miR-10b is an oncogene implicated in many tumors, its role in cervical cancer (CC) remains largely unclear. Here, we investigated the function and underlying mechanisms of miR-10b in human CC. Methods: Quantitative RT-PCR was used to measure miR-10b expression in CC and normal tissues, and its association with clinicopathologic features was analyzed. Methylation of CpG sites in the miR-10b promoter was analyzed by methylation sequencing. Cell proliferation, apoptosis, migration, and invasion assays were used to elucidate the biological effects of miR-10b and expression of the target gene was assayed with Western blot. Results: miR-10b was downregulated in CC tissues compared with normal tissues, and less miR-10b expression was associated with larger tumors, vascular invasion and HPV-type 16 positivity. miR-10b expression decreased in HeLa (HPV18-positive) and SiHa (HPV16-positive) cells compared with C-33A (HPV-negative), but increased after treatment with 5-Aza-CdR. Methylation ratio of site -797 in the miR-10b promoter in C-33A was lower than that in HeLa and SiHa. Further analysis indicates that site -797 is located within a transcription factor AP-2A (TFAP2A) binding element. Functionally, overexpression of miR-10b in HeLa and SiHa suppressed cell proliferation, migration and invasion, and induced apoptosis and miR-10b downregulation had opposite effects. Mechanistically, T-cell lymphoma invasion and metastasis 1 (Tiam1) was identified as a direct and functional target of miR-10b. Conclusion: miR-10b acts as a tumor suppressor in CC by suppressing oncogenic Tiam1, and its expression may be downregulated through methylation of TFAP2A binding element by HPV.

Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot, and mouth disease (HFMD) in children. The host defense mechanisms against CVA16 infection remain almost entirely unknown. Unlike previous observations with enterovirus 71 (EV71) infection, here we show that gamma interferon (IFN-γ) or invariant NK T cell deficiency does not affect disease development or the survival of CVA16-infected mice. In contrast, type I interferon receptor deficiency resulted in the development of more severe disease in mice, and the mice had a lower survival rate than wild-type mice. Similarly, a deficiency of Toll-like receptor 3 (TLR3) and TRIF, but not other pattern recognition receptors, led to the decreased survival of CVA16-infected mice. TLR3-TRIF signaling was indispensable for the induction of type I interferons during CVA16 infection in mice and protected young mice from disease caused by the infection. In particular, TRIF-mediated immunity was critical for preventing CVA16 replication in the neuronal system before disease occurred. IFN-β treatment was also found to compensate for TRIF deficiency in mice and decreased the disease severity in and mortality of CVA16-infected mice. Altogether, type I interferons induced by TLR3-TRIF signaling mediate protective immunity against CVA16 infection. These findings may shed light on therapeutic strategies to combat HFMD caused by CVA16 infection. IMPORTANCE Hand, foot, and mouth disease (HFMD) is a major threat to public health in the Asia-Pacific region. Both CVA16 and EV71 are major pathogens that are responsible for HFMD. The majority of research efforts have focused on the more virulent EV71, but little has been done with CVA16. Thus far, host immune responses to CVA16 infection have not yet been elucidated. The present study discovered an initial molecular mechanism underlying host protective immunity against CVA16 infection, providing the first explanation for why CVA16 and EV71 cause different clinical outcomes upon infection of humans. Therefore, different therapeutic strategies should be developed to treat HFMD cases caused by these two viruses.