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BackgroundIn the honey bee (Apis mellifera), queen and workers have different behavior and reproductive capacity despite possessing the same genome. The primary substance that leads to this differentiation is royal jelly (RJ), which contains a range of proteins, amino acids, vitamins and nucleic acids. MicroRNA (miRNA) has been found to play an important role in regulating the expression of protein-coding genes and cell biology. In this study, we characterized the miRNAs in RJ from two honey bee sister species and determined their possible effect on transcriptome in one species.Methodology/principal findingsWe sequenced the miRNAs in RJ either from A. mellifera (RJM) or A. cerana (RJC). We then determined the global transcriptomes of adult A. mellifera developed from larvae fed either with RJM (mRJM) or RJC (mRJC). Finally we analyzed the target genes of those miRNA that are species specific or differentially expressed in the two honey bee species. We show that there were differences in miRNA between RJM and RJC, and that transcriptomes of adult A. mellifera were affected by the two types of RJ. A high proportion (23.3%) of the affected genes were target genes of differential miRNAs.ConclusionWe show for the first time that there are differences in miRNAs in RJ between A. mellifera and A. cerana. Further, the differences in transcriptomes of bees reared from these two RJs might be related to miRNA differences of the two species. This study provides the first evidence that heterospecific royal jelly can modify gene expression in honey bees through an epigenetic mechanism.

BACKGROUND: The Eastern hive honey bee, Apis cerana cerana is a native and widely bred honey bee species in China. Molecular biology research about this honey bee species is scarce, and genomic information for A. c. cerana is not currently available. Transcriptome and expression profiling data for this species are therefore important resources needed to better understand the biological mechanisms of A. c. cerana. In this study, we obtained the transcriptome information of A. c. cerana by RNA-sequencing and compared gene expression differences between queens and workers of A. c. cerana by digital gene expression (DGE) analysis. RESULTS: Using high-throughput Illumina RNA sequencing we obtained 51,581,510 clean reads corresponding to 4.64 Gb total nucleotides from a single run. These reads were assembled into 46,999 unigenes with a mean length of 676 bp. Based on a sequence similarity search against the five public databases (NR, Swissport, GO, COG, KEGG) with a cut-off E-value of 10(-5) using BLASTX, a total of 24,630 unigenes were annotated with gene descriptions, gene ontology terms, or metabolic pathways. Using these transcriptome data as references we analyzed the gene expression differences between the queens and workers of A. c. cerana using a tag-based digital gene expression method. We obtained 5.96 and 5.66 million clean tags from the queen and worker samples, respectively. A total of 414 genes were differentially expressed between them, with 189 up-regulated and 225 down-regulated in queens. CONCLUSIONS: Our transcriptome data provide a comprehensive sequence resource for future A. c. cerana study, establishing an important public information platform for functional genomic studies in A. c. cerana. Furthermore, the DGE data provide comprehensive gene expression information for the queens and workers, which will facilitate our understanding of the molecular mechanisms of the different physiological aspects of the two castes.

BACKGROUND: All honey bee species (Apis spp) share the same sex determination mechanism using the complementary sex determination (csd) gene. Only individuals heterogeneous at the csd allele develop into females, and the homozygous develop into diploid males, which do not survive. The honeybees are therefore under selection pressure to generate new csd alleles. Previous studies have shown that the csd gene is under balancing selection. We hypothesize that due to the long separation from the mainland of Hainan Island, China, that the giant honey bees (Apis dorsata) should show a founder effect for the csd gene, with many different alleles clustered together, and these would be absent on the mainland. METHODOLOGY/PRINCIPAL FINDINGS: We sampled A. dorsata workers from both Hainan and Guangxi Provinces and then cloned and sequenced region 3 of the csd gene and constructed phylogenetic trees. We failed to find any clustering of the csd alleles according to their geographical origin, i.e. the Hainan and Guangxi samples did not form separate clades. Further analysis by including previously published csd sequences also failed to show any clade-forming in both the Philippines and Malaysia. CONCLUSIONS/SIGNIFICANCE: Results from this study and those from previous studies did not support the expectations of a founder effect. We conclude that because of the extremely high mating frequency of A. dorsata queens, a founder effect does not apply in this species.

Standardization on Shear wave ultrasound elastography (SWUE) technical settings will not only ensure that the results are accurate, but also detect any differences over time that may be attributed to true physiological changes. The present study evaluated the variations of elastic modulus of muscle and tendon using SWUE when different technical aspects were altered. The results of this study indicated that variations of elastic modulus of muscle and tendon were found when different transducer's pressure and region of interest (ROI)'s size were applied. No significant differences in elastic modulus of the rectus femoris muscle and patellar tendon were found with different acquisition times of the SWUE sonogram. The SWUE on the muscle and tendon should be performed with the lightest transducer's pressure, a shorter acquisition time for the SWUE sonogram, while measuring the mean elastic modulus regardless the ROI's size.

Young larvae of the honey bee (Apis mellifera) are totipotent; they can become either queens (reproductives) or workers (largely sterile helpers). DNA methylation has been shown to play an important role in this differentiation. In this study, we examine the contributions of diet and cell size to caste differentiation.We measured the activity and gene expression of one key enzyme involved in methylation, Dnmt3; the rates of methylation in the gene dynactin p62; as well as morphological characteristics of adult bees developed either from larvae fed with worker jelly or royal jelly; and larvae raised in either queen or worker cells. We show that both diet type and cell size contributed to the queen-worker differentiation, and that the two factors affected different methylation sites inside the same gene dynactin p62.We confirm previous findings that Dnmt3 plays a critical role in honey bee caste differentiation. Further, we show for the first time that cell size also plays a role in influencing larval development when diet is kept the same.

Both endocrine and exocrine pancreatic cells arise from pancreatic-duodenal homeobox 1 (pdx1)-positive progenitors. The molecular mechanisms controlling cell fate determination and subsequent proliferation, however, are poorly understood. Unlike endocrine cells, less is known about exocrine cell specification. We report here the identification and characterization of a novel exocrine cell determinant gene, exocrine differentiation and proliferation factor (exdpf), which is highly expressed in the exocrine cell progenitors and differentiated cells of the developing pancreas in zebrafish. Knockdown of exdpf by antisense morpholino caused loss or significant reduction of exocrine cells due to lineage-specific cell cycle arrest but not apoptosis, whereas the endocrine cell mass appeared normal. Real-time PCR results demonstrated that the cell cycle arrest is mediated by up-regulation of cell cycle inhibitor genes p21(Cip), p27(Kip), and cyclin G1 in the exdpf morphants. Conversely, overexpression of exdpf resulted in an overgrowth of the exocrine pancreas and a severe reduction of the endocrine cell mass, suggesting an inhibitory role for exdpf in endocrine cell progenitors. We show that exdpf is a direct target gene of pancreas-specific transcription factor 1a (Ptf1a), a transcription factor critical for exocrine formation. Three consensus Ptf1a binding sites have been identified in the exdpf promoter region. Luciferase assay demonstrated that Ptf1a promotes transcription of the exdpf promoter. Furthermore, exdpf expression in the exocrine pancreas was lost in ptf1a morphants, and overexpression of exdpf successfully rescued exocrine formation in ptf1a-deficient embryos. Genetic evidence places expdf downstream of retinoic acid (RA), an instructive signal for pancreas development. Knocking down exdpf by morpholino abolished ectopic carboxypeptidase A (cpa) expression induced by RA. On the other hand, exdpf mRNA injection rescued endogenous cpa expression in embryos treated with diethylaminobenzaldehyde, an inhibitor of RA signaling. Moreover, exogenous RA treatment induced anterior ectopic expression of exdpf and trypsin in a similar pattern. Our study provides a new understanding of the molecular mechanisms controlling exocrine cell specification and proliferation by a novel gene, exdpf. Highly conserved in mammals, the expression level of exdpf appears elevated in several human tumors, suggesting a possible role in tumor pathogenesis.

Abstract Background Multiplex ligation-dependent probe amplification (MLPA) was originally described as an efficient and reliable technique for gene dosage or DNA copy number variation (CNV) analysis. Due to its low cost, reliability, sensitivity, and relative simplicity, MLPA has rapidly gained acceptance in research and diagnostic laboratories, and fills the gap between genome-wide analysis and single gene analysis. A number of new applications have been developed shortly after the introduction of MLPA, including methylation-specific MLPA (MS-MLPA), the use of MLPA in SNP genotyping, copy number analysis in segmentally duplicated regions, etc. However, probe design is time consuming and error prone. Recently software has been developed to help human genomic MLPA probe selection and optimization. For other genomes and MS-MLPA, probe design remains a challenge. Findings This paper describes a number of new features added to the previous H-MAPD software, which include: 1) probe selection for MS-MLPA; 2) support of mouse and rat genomes; 3) a set of new stuffer sequences. In addition, a physical-chemical property verification tool was implemented to verify user defined probes. Conclusions MAPD is a web-based tool which is freely available to non-commercial users. The previous H-MAPD software has been used by about 200 users from more than 30 countries. With the new features, the author hopes MAPD will bring more convenience to the MLPA community.

Abstract Background Multiplex ligation-dependent probe amplification (MLPA) is an efficient and reliable technique for gene dosage analysis. Currently MLPA can be conducted on two platforms: traditional electrophoresis-based, and FlexMAP bead-coupled. Since its introduction in 2002, MLPA has been rapidly adopted in both clinical and research situations. However, MLPA probe design is a time consuming process requiring many steps that address multiple criteria. There exist only one or two commercial software packages for traditional electrophoresis-based MLPA probe design. To our knowledge, no software is yet available that performs bead-coupled MLPA probe design. Results We have developed H-MAPD, a web-based tool that automates the generation and selection of probes for human genomic MLPA. The software performs physical-chemical property tests using UNAFold software, and uniqueness tests using the UCSC genome browser. H-MAPD supports both traditional electrophoresis-based assays, as well as FlexMAP bead-coupled MLPA. Conclusion H-MAPD greatly reduces the efforts for human genomic MLPA probe design. The software is written in Perl-CGI, hosted on a Linux server, and is freely available to non-commercial users.

This work proposes a microwave resonator built from gallium arsenide using integrated passive device (IPD) technology. It consists of a three-layered interlaced spiral structure with airbridges and inner interdigital structures. For integrated systems, IPD technology demonstrated outstanding performance, robustness, and a tiny size at a low cost. The airbridges were made more compact, with overall dimensions of 1590 × 800 µm2 (0.038 × 0.019 λg2). The designed microwave resonator operated at 1.99 GHz with a return loss of 39 dB, an insertion loss of 0.07 dB, and a quality factor of 1.15. Additionally, an experiment was conducted on the properties of the airbridge and how they affected resistance, inductance, and S-parameters in the construction of the resonator. To investigate the impact of airbridges on the structure, E- and H-field distributions of the resonator were simulated. Furthermore, its use in sensing applications was explored. Various concentrations of glucose solutions were used in the experiment. The proposed device featured a minimum detectable concentration of 0.2 mg/mL; high sensitivity, namely, 14.58 MHz/mg·mL−1, with a linear response; and a short response time. Thus, this work proposes a structure that exhibits potential in integrated systems and real-time sensing systems with high sensitivity.

Due to the current limitations of three-dimensional (3D) simulation graphics technology, mind wandering commonly occurs in virtual reality tasks, which has impeded it being applied more extensively. The right ventrolateral prefrontal cortex (rVLPFC) plays a vital role in executing continuous two-dimensional (2D) mental paradigms, and transcranial direct current stimulation (tDCS) over this cortical region has been shown to successfully modulate sustained 2D attention. Accordingly, we further explored the effects of electrical activation of the rVLPFC on 3D attentional tasks using anodal high-definition (HD)-tDCS. A 3D Go/No-go (GNG) task was developed to compare the after effects of real and sham brain stimulation. Specifically, GNG tasks were periodically interrupted to assess the subjective perception of attentional level, behavioral reactions were tracked and decomposed into an underlying decision cognition process, and electroencephalography data were recorded to calculate event-related potentials (ERPs) in rVLPFC. The p-values statistically indicated that HD-tDCS improved the subjective mentality, led to more cautious decisions, and enhanced neuronal discharging in rVLPFC. Additionally, the neurophysiological P300 ERP component and stimulation being active or sham could effectively predict several objective outcomes. These findings indicate that the comprehensive approach including brain stimulation, 3D mental paradigm, and cross-examined performance could significantly lengthen and robustly compare sustained 3D attention. [ABSTRACT FROM AUTHOR]

ObjectiveLocal invasion is the first step of metastasis, the main cause of colorectal cancer (CRC)-related death. Recent studies have revealed extensive intertumoral and intratumoral heterogeneity. Here, we focused on revealing local invasion-related genes in CRC. MethodsWe used spatial transcriptomic techniques to study the process of local invasion in four CRC tissues. First, we compared the pre-cancerous, cancer center, and invasive margin in one section (S115) and used pseudo-time analysis to reveal the differentiation trajectories from cancer center to invasive margin. Next, we performed immunohistochemical staining for RPL5, STC1, AKR1B1, CD47, and HLA-A on CRC samples. Moreover, we knocked down AKR1B1 in CRC cell lines and performed CCK-8, wound healing, and transwell assays to assess cell proliferation, migration, and invasion.ResultsWe demonstrated that 13 genes were overexpressed in invasive clusters, among which the expression of CSTB and TM4SF1 was correlated with poor PFS in CRC patients. The ribosome pathway was increased, while the antigen processing and presentation pathway was decreased along CRC progression. RPL5 was upregulated, while HLA-A was downregulated along cancer invasion in CRC samples. Pseudo-time analysis revealed that STC1, AKR1B1, SIRPA, C4orf3, EDNRA, CES1, PRRX1, EMP1, PPIB, PLTP, SULF2, and EGFL6 were unpregulated along the trajectories. Immunohistochemic3al staining showed the expression of STC1, AKR1B1, and CD47 was increased along cancer invasion in CRC samples. Knockdown of AKR1B1 inhibited CRC cells’ proliferation, migration, and invasion.ConclusionsWe revealed the spatial heterogeneity within CRC tissues and uncovered some novel genes that were associated with CRC invasion.

Virtual reality (VR), a rapidly evolving technology that simulates three-dimensional virtual environments for users, has been proven to activate brain functions. However, the continuous alteration pattern of the functional small-world network in response to comprehensive three-dimensional stimulation rather than realistic two-dimensional media stimuli requires further exploration. Here, we aimed to validate the effect of VR on the pathways and network parameters of a small-world organization and interpret its mechanism of action. Fourteen healthy volunteers were selected to complete missions in an immersive VR game. The changes in the functional network in six different frequency categories were analyzed using graph theory with electroencephalography data measured during the pre-, VR, and post-VR stages. The mutual information matrix revealed that interactions between the frontal and posterior areas and those within the frontal and occipital lobes were strengthened. Subsequently, the betweenness centrality (BC) analysis indicated more robust and extensive pathways among hubs. Furthermore, a specific lateralized channel (O1 or O2) increment in the BC was observed. Moreover, the network parameters improved simultaneously in local segregation, global segregation, and global integration. The overall topological improvements of small-world organizations were in high-frequency bands and exhibited some degree of sustainability. [ABSTRACT FROM AUTHOR]

Due to the current limitations of three-dimensional (3D) simulation graphics technology, mind wandering commonly occurs in virtual reality tasks, which has impeded it being applied more extensively. The right ventrolateral prefrontal cortex (rVLPFC) plays a vital role in executing continuous two-dimensional (2D) mental paradigms, and transcranial direct current stimulation (tDCS) over this cortical region has been shown to successfully modulate sustained 2D attention. Accordingly, we further explored the effects of electrical activation of the rVLPFC on 3D attentional tasks using anodal high-definition (HD)-tDCS. A 3D Go/No-go (GNG) task was developed to compare the after effects of real and sham brain stimulation. Specifically, GNG tasks were periodically interrupted to assess the subjective perception of attentional level, behavioral reactions were tracked and decomposed into an underlying decision cognition process, and electroencephalography data were recorded to calculate event-related potentials (ERPs) in rVLPFC. The p-values statistically indicated that HD-tDCS improved the subjective mentality, led to more cautious decisions, and enhanced neuronal discharging in rVLPFC. Additionally, the neurophysiological P300 ERP component and stimulation being active or sham could effectively predict several objective outcomes. These findings indicate that the comprehensive approach including brain stimulation, 3D mental paradigm, and cross-examined performance could significantly lengthen and robustly compare sustained 3D attention.

Abstract Background This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods Patients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2 twice daily on days 1–14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8–2.0 Gy per fraction to a total dose of 50–60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups. Results A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3–4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%, p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3–4 adverse events than younger patients (58.1% vs. 31.3%, p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%, p = 0.275). Conclusion CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

In the context of tax sharing reform and land reform during the 1990s, local governments in China relied heavily on land finance. Local governments have fierce competition in attracting investment, omitting the development of green economy. Based on the data of industrial land sales and carbon dioxide emissions, this study constructed the panel data of 196 cities in China from 2007 to 2017 and analyzed the spatial and temporal evolution characteristics of urban industrial land price distortion and carbon emission intensity. Furthermore, a multiple linear regression model was constructed from the aspects of scale effect to empirically analyze the overall impact and differential impact of urban industrial land price distortion on carbon emission intensity. With the help of the mediating effect model, the mechanism of urban industrial land price distortion on carbon emission intensity was investigated from the perspective of industrial structure upgrading. The results showed that (1) the higher the price distortion of industrial land is, the more detrimental it is to the development of green and low-carbon economy. (2) The regional heterogeneity test showed that the impact of industrial land price distortion on carbon emission intensity is most significant in the central region, medium cities, and cities with low fiscal self-sufficiency rates, respectively. (3) The higher the distortion degree of industrial land price, the greater the restriction on the upgrading of industrial structure, further increasing the carbon emission intensity. This paper provides policy implications for the market-oriented reform of land factors and the realization of the “double carbon” goal.

Virtual reality (VR), a rapidly evolving technology that simulates three-dimensional virtual environments for users, has been proven to activate brain functions. However, the continuous alteration pattern of the functional small-world network in response to comprehensive three-dimensional stimulation rather than realistic two-dimensional media stimuli requires further exploration. Here, we aimed to validate the effect of VR on the pathways and network parameters of a small-world organization and interpret its mechanism of action. Fourteen healthy volunteers were selected to complete missions in an immersive VR game. The changes in the functional network in six different frequency categories were analyzed using graph theory with electroencephalography data measured during the pre-, VR, and post-VR stages. The mutual information matrix revealed that interactions between the frontal and posterior areas and those within the frontal and occipital lobes were strengthened. Subsequently, the betweenness centrality (BC) analysis indicated more robust and extensive pathways among hubs. Furthermore, a specific lateralized channel (O1 or O2) increment in the BC was observed. Moreover, the network parameters improved simultaneously in local segregation, global segregation, and global integration. The overall topological improvements of small-world organizations were in high-frequency bands and exhibited some degree of sustainability.

BackgroundSarcopenia has been associated with treatment-related toxicities and poor survival in cancer patients. Our aim was to investigate the prevalence of sarcopenia in postoperative recurrent esophageal squamous cell carcinoma (ESCC) patients receiving chemoradiotherapy (CRT) and evaluate associations with treatment-related toxicity and prognosis.MethodsOne hundred and eighty-four patients with postoperative locoregional recurrent ESCC receiving CRT between January 2014 and December 2016 were included. The skeletal muscle area (SMA) was measured at the third lumbar vertebra level. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) less than 47.24/cm2/m2 for men and 36.92/cm2/m2 for women. Association of sarcopenia with overall survival (OS) was analyzed using univariate and multivariate cox regression models.ResultsSarcopenia was observed in 94 of 184 (51.1%) patients. Sarcopenic patients had significantly higher rates of grade 3-4 toxicities compared to those without sarcopenia (36.2% vs 21.1%, p = 0.034). The survival rate at 12 and 24 months was 36.2% and 3.2% in the sarcopenic patients and 57.8% and 17.8% in the non-sarcopenic patients (p < 0.001). Multivariate cox regression analysis showed that sarcopenia was significantly associated with decreased OS (HR = 1.729, 95% CI 1.231-2.428, p = 0.002).ConclusionsSarcopenia is an independent indicator of poor survival in postoperative locoregional recurrent ESCC patients treated with CRT. Early nutritional interventions before treatment may improve the prognosis.

Structural health monitoring of towers for offshore wind turbines (OWTs) is critical because they serve as support structures. Although the modal parameters of the tower can be identified through operational modal analysis, evaluating the realistic characteristics of structures is challenging, and the modal parameters are susceptible to fluctuations owing to shifting environmental and operational conditions (EOCs). In this study, we aim to improve the vibration-based structural health monitoring strategy for monitoring OWT towers. Remote-sensing products from ERA5, which provide information regarding the marine state, are used to extend the data source. Machine learning (ML) with Bayesian optimisation is utilised to minimise the effects of EOCs on modal parameters. We demonstrate that the modal parameters of the tower are significantly influenced by the EOCs by applying the developed approach to an offshore wind turbine. Moreover, the effects of the EOCs on the modal parameters are minimised by applying ML models with Bayesian optimisation. A comparison between the monitoring divided into different operating conditions and the monitoring of all operating conditions indicate that there is minimal room for performance improvement of ML models with thorough condition segmentation. Consequently, employing global models directly is preferred in the present application environment. • An improved vibration-based SHM strategy for OWT towers is proposed. • The remote-sensing data products of ERA5 are employed to expand the data source. • Machine learning with Bayesian Optimisation is applied to minimise the effects of the EOCs. • It is better to employ global ML models in the present application environment. [ABSTRACT FROM AUTHOR]

This paper describes the implementation of a miniaturized quad flat no-lead (QFN)-packaged bandpass filter (BPF) with a combination of an intertwined circular spiral inductor and two types of integrated center-located capacitors using gallium-arsenide-based integrated passive device (IPD) fabrication technology. Air-bridge structures were introduced into the outer circular spiral inductor to save space and to provide the filter with a compact chip area of 1192.5 × 1012.7 μm2. An equivalent circuit was modeled, the current density and variable dimensional parameters were simulated, and the fabrication process was introduced to achieve a better understanding of the IPD BPF. The proposed device was packaged using the QFN-packaging technology and was measured to possess a single passband with a central frequency of 1.91 GHz (return loss: 28.8 dB) and a fractional bandwidth of 72.69% (insertion loss: 0.62 dB). One transmission zero was obtained on the right side of the passband at 4.78 GHz with an amplitude of 35.95 dB. The fabricated BPF can be used in various L-band applications, such as mobile service, satellite navigation, telecommunications, and aircraft surveillance, due to its miniaturized chip size and high-performance characteristics.

Long-term glucocorticoid use may result in sustained suppression of one or more secreted components from the hypothalamo-pituitary-adrenal axis, and often results in apoptosis. Yougui Pill (YGP), a 10-component traditional Chinese herbal medicine, has been shown to be clinically effective for glucocorticoid-induced suppression of the hypothalamo-pituitary-adrenal axis. However, the pharmacological and molecular mechanisms remain unclear. We hypothesized that YGP would exert an anti-apoptosis effect on dexamethasone-treated anterior pituitary cells. In vivo experiments showed that YGP significantly reduced the number of apoptotic cells, down-regulated mRNA expression of cytochrome c, caspase-3, and caspase-9, and up-regulated mRNA expression of Bcl-2. These findings suggest that YGP reduced glucocorticoid-induced apoptosis in rat anterior pituitary cells by regulating the mitochondria-mediated apoptosis pathway.

Astaxanthin is a natural product gaining increasing attention due to its safety and anti-cancer properties. In this study, we investigated the mechanisms of the anti-cancer effects of astaxanthin on prostate cancer (PCa) cell lines using aggressive PCa DU145 cells. Also an instantaneous silenced cell line (si-STAT3) derived from DU145 and a control cell line (si-NK) were used for the MTT and colony formation assays to determine the role of astaxanthin in proliferation and colony formation abilities. Flow cytometry assays were used to detect the apoptosis of tumor cells. Migration and invasion assays detected the weakening of the respective abilities. Western blot and RT-PCR tests detected the levels of STAT3 protein and mRNA. Astaxanthin resulted in suppression of the proliferation of DU145 cells and the level of STAT3. The treatment of DU145 cells with astaxanthin decreased the cloning ability, increased the apoptosis percentage and weakened the abilities of migration and invasion of the cells. Furthermore, astaxanthin reduced the expression of STAT3 at protein and mRNA levels. The effects were enhanced when astaxanthin and si-STAT3 were combined. The results of animal experiments were consistent with the results in cells. Thus, astaxanthin inhibits the proliferation of DU145 cells by reducing the expression of STAT3.

This article presents a compact quad flat no-lead (QFN)-packaged second-order bandpass filter (BPF) with intertwined inductors, a dendritic capacitor, and four air-bridge structures, which was fabricated on a gallium arsenide (GaAs) substrate by integrated passive device (IPD) technology. Air-bridge structures were introduced into an approximate octagonal outer metal track to provide a miniaturized chip size of 0.021 × 0.021 λ0 (0.8 × 0.8 mm2) for the BPF. The QFN-packaged GaAs-based bandpass filter was used to protect the device from moisture and achieve good thermal and electrical performances. An equivalent circuit was modeled to analyze the BPF. A description of the manufacturing process is presented to elucidate the physical structure of the IPD-based BPF. Measurements were performed on the proposed single band BPF using a center frequency of 2.21 GHz (return loss of 26.45 dB) and a 3-dB fractional bandwidth (FBW) of 71.94% (insertion loss of 0.38 dB). The transmission zero is located at the 6.38 GHz with a restraint of 30.55 dB. The manufactured IPD-based BPF can play an excellent role in various S-band applications, such as a repeater, satellite communication, and radar, owing to its miniaturized chip size and high performance.

The toroidal tuned liquid column damper (TTLCD) can be applied in flexible structures to improve the structural dynamic responses. This study focuses on the impact of size effects of TTLCD on the control efficiency. Two types of size effects are experimentally addressed using the real-time hybrid simulation (RTHS) technique: (1) the effects of experimental scale, and (2) the effects of length ratio. A large number of RTHSs are performed, in which a monopile wind turbine is numerically simulated as the numerical substructure, and five TTLCDs with various experimental scales or length ratios are experimentally tested as the physical substructure. The RTHS results show that the effects of experimental scale on the control efficiency and liquid response are insignificant, and a larger length ratio leads to a stronger performance. Besides, the TTLCD is found to be an efficient additional damping device in monopile wind turbines. The comparison between the RTHS results and the simulation results from a theoretical model is made, and it demonstrates that the theoretical model can capture the dynamic interaction process between the structure and TTLCD with good accuracy. • Real-time hybrid simulations are performed for a wind turbine-toroidal TLCD system. • The experimental scale effects are insignificant using the Froude scaling law. • The length ratio effects on the dynamic performance are experimentally revealed. • The toroidal TLCD can be used as an efficient damping device in wind turbines. • Good agreement between the experimental and numerical results is obtained. [ABSTRACT FROM AUTHOR]

In this work, a miniaturized bandpass filter (BPF) constructed of two spiral intertwined inductors and a central capacitor, with several interdigital structures, was designed and fabricated using integrated passive device (IPD) technology on a GaAs wafer. Five air-bridge structures were introduced to enhance the mutual inductive effect and form the differential geometry of the outer inductors. In addition, the design of the differential inductor combined with the centrally embedded capacitor results in a compact construction with the overall size of 0.037λ0 × 0.019λ0 (1537.7 × 800 μm2) where λ0 is the wavelength of the central frequency. For the accuracy evolution of the equivalent circuit, the frequency-dependent lumped elements of the proposed BPF was analyzed and modeled through the segment method, mutual inductance approach, and simulated scattering parameters (S-parameters). Afterward, the BPF was fabricated using GaAs-based IPD technology and a 16-step manufacture flow was accounted for in detail. Finally, the fabricated BPF was wire-bonded with Au wires and packaged onto a printed circuit board for radio-frequency performance measurements. The measured results indicate that the implemented BPF possesses a center frequency operating at 2 GHz with the insertion losses of 0.38 dB and the return losses of 40 dB, respectively, and an ultrawide passband was achieved with a 3-dB fraction bandwidth of 72.53%, as well. In addition, a transmission zero is located at 5.32 GHz. Moreover, the variation of the resonant frequency with different inductor turns and metal thicknesses was analyzed through the simulation results, demonstrating good controllability of the proposed BPF.

Objective: We aimed to explore the clinical characteristics and functional network properties of patients with late-onset Lennox-Gastaut syndrome (LGS)., Methods: Late-onset LGS was defined by the appearance of LGS features after 8 years of age. We reviewed the medical charts of 9 patients with late-onset LGS, and performed electroencephalography connectivity analysis using graph theory. We assessed the clustering coefficient (CC) and characteristic path length (CPL), which are common basic measures of functional networks that represent local segregation and global integration. The characteristics and brain parameters of late-onset LGS were compared with a typical age-onset LGS group., Results: Late onset LGS subjects were older than typical age onset LGS at the time of testing, but otherwise there were no significant differences in clinical characteristics. The late-onset group showed higher median CC values in the alpha (p = 0.045) and beta (p < 0.001) bands over brain regions implicated in cognitive processing. There were no significant differences in CPL between the LGS groups., Conclusions: Higher clustering coefficient values, in alpha/beta bands over brain regions implicated in cognitive processing, are consistent with increased cognitive network segregation in late onset LGS compared to typical age-onset LGS. Given network segregation is a normal aspect of brain maturation, these results imply that this process is less disturbed when the LGS process begins later in childhood., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This work proposes a microwave resonator built from gallium arsenide using integrated passive device (IPD) technology. It consists of a three-layered interlaced spiral structure with airbridges and inner interdigital structures. For integrated systems, IPD technology demonstrated outstanding performance, robustness, and a tiny size at a low cost. The airbridges were made more compact, with overall dimensions of 1590 × 800 µm 2 (0.038 × 0.019 λg 2 ). The designed microwave resonator operated at 1.99 GHz with a return loss of 39 dB, an insertion loss of 0.07 dB, and a quality factor of 1.15. Additionally, an experiment was conducted on the properties of the airbridge and how they affected resistance, inductance, and S-parameters in the construction of the resonator. To investigate the impact of airbridges on the structure, E- and H-field distributions of the resonator were simulated. Furthermore, its use in sensing applications was explored. Various concentrations of glucose solutions were used in the experiment. The proposed device featured a minimum detectable concentration of 0.2 mg/mL; high sensitivity, namely, 14.58 MHz/mg·mL -1 , with a linear response; and a short response time. Thus, this work proposes a structure that exhibits potential in integrated systems and real-time sensing systems with high sensitivity.

Introduction: It is essential to understand the underlying changes in the patients' metabolic profiles that may be indicative of the therapy's effectiveness., Aim: To prospectively analyse the clinical efficacy of ozone autohemotherapy in the treatment of acute herpes zoster and investigate its impact on serum metabolomics., Material and Methods: A total of 76 patients with acute herpes zoster between May 2018 and June 2020 were enrolled and divided into an experimental group and a control group. The pain location, Numeric Rating Scale (NRS) scores before and after treatment (1 week, 1 month, 3 months, and 6 months post-treatment), medication usage, and Quality of Sleep (QS) scores were prospectively analysed. Additionally, serum metabolomic data were obtained and analysed before and 6 months after the treatment., Results: There were statistically significant differences in the total NRS scores before and after ozone autohemotherapy ( p < 0.05). The NRS scores of both groups significantly decreased ( p < 0.05). At the 6-month follow-up, no patients were lost, and 83 patients completed the follow-up. The NRS improvement at 1 week, 1 month, 3 months, and 6 months post-treatment in the experimental group was significantly lower than that in the control group ( p < 0.05). There was no significant difference in the medication usage (pregabalin or tramadol sustained-release tablets) between the two groups ( p > 0.05). One month after treatment, the QS score improvement in the diabetes group was significantly lower than that in the non-diabetes group ( p < 0.05). Serum metabolomics analysis revealed three significantly decreased metabolites, namely creatine, adipate, and glucose, after treatment., Conclusions: Ozone autohemotherapy is an effective treatment for acute herpes zoster patients and can rapidly and effectively alleviate pain symptoms in the short term. The changes in serum metabolomics may provide further insights into the treatment mechanism., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia Sp. z o. o.)

Sorafenib is one a first-line therapeutic drugs for advanced hepatocellular carcinoma (HCC). However, only 30% of patients benefit from sorafenib due to drug resistance. We and other groups have revealed that nuclear factor I B (NFIB) regulates liver regeneration and carcinogenesis, but its role in drug resistance is poorly known. We found that NFIB was more upregulated in sorafenib-resistant SMMC-7721 cells compared to parental cells. NFIB knockdown not only sensitized drug-resistant cells to sorafenib but also inhibited the proliferation and invasion of these cells. Meanwhile, NFIB promoted the proliferation and invasion of HCC cells in vitro and facilitated tumor growth and metastasis in vivo. Knocking down NFIB synergetically inhibited tumor growth with sorafenib. Mechanically, gene expression profiling and subsequent verification experiments proved that NFIB could bind with the promoter region of a complex I inhibitor NDUFA4L2 and promote its transcription. Transcriptional upregulation of NDUFA4L2 by NFIB could thus inhibit the sorafenib-induced reactive oxygen species accumulation. Finally, we found that NFIB was highly expressed in HCC tissues, and high NFIB expression level was associated with macrovascular invasion, advanced tumor stage, and poor prognosis of HCC patients (n = 156). In summary, we demonstrated that NFIB could transcriptionally upregulate NDUFA4L2 to enhance both intrinsic and acquired sorafenib resistance of HCC cells by reducing reactive oxygen species induction., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective: Local invasion is the first step of metastasis, the main cause of colorectal cancer (CRC)-related death. Recent studies have revealed extensive intertumoral and intratumoral heterogeneity. Here, we focused on revealing local invasion-related genes in CRC., Methods: We used spatial transcriptomic techniques to study the process of local invasion in four CRC tissues. First, we compared the pre-cancerous, cancer center, and invasive margin in one section (S115) and used pseudo-time analysis to reveal the differentiation trajectories from cancer center to invasive margin. Next, we performed immunohistochemical staining for RPL5, STC1, AKR1B1, CD47, and HLA-A on CRC samples. Moreover, we knocked down AKR1B1 in CRC cell lines and performed CCK-8, wound healing, and transwell assays to assess cell proliferation, migration, and invasion., Results: We demonstrated that 13 genes were overexpressed in invasive clusters, among which the expression of CSTB and TM4SF1 was correlated with poor PFS in CRC patients. The ribosome pathway was increased, while the antigen processing and presentation pathway was decreased along CRC progression. RPL5 was upregulated, while HLA-A was downregulated along cancer invasion in CRC samples. Pseudo-time analysis revealed that STC1, AKR1B1, SIRPA, C4orf3, EDNRA, CES1, PRRX1, EMP1, PPIB, PLTP, SULF2, and EGFL6 were unpregulated along the trajectories. Immunohistochemic3al staining showed the expression of STC1, AKR1B1, and CD47 was increased along cancer invasion in CRC samples. Knockdown of AKR1B1 inhibited CRC cells' proliferation, migration, and invasion., Conclusions: We revealed the spatial heterogeneity within CRC tissues and uncovered some novel genes that were associated with CRC invasion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Chen, Peng, Zhong, Zhou, Liao, Chen, Wang, He and Zhou.)

Objective: For patients with drug-resistant focal epilepsy, intracranial monitoring remains the gold standard for surgical intervention. Focal cortical dysplasia (FCD) is the most common cause of pharmacoresistant focal epilepsy in pediatric patients who usually develop seizures in early childhood. Timely removal of the epileptogenic zone (EZ) is necessary to achieve lasting seizure freedom and favorable developmental and cognitive outcomes to improve the quality of life. We applied brain network analysis to investigate potential biomarkers for the diagnosis of EZ that will aid in the resection for pediatric focal epilepsy patients with FCD type II., Methods: Ten pediatric patients with focal epilepsy diagnosed as FCD type II and that had a follow-up after resection surgery (Engel class I [ n = 9] and Engel class II [ n = 1]) were retrospectively included. Time-frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation were combined to calculate brain network parameters based on interictal epileptiform discharges from ECoG., Results: Clustering coefficient, local efficiency, node out-degree, and node out-strength with higher values are the most reliable biomarkers for the delineation of EZ, and the differences between EZ and margin zone (MZ), and EZ and normal zone (NZ) were significant ( p < 0.05; Mann-Whitney U -test, two-tailed). In particular, the difference between MZ and NZ was significant for patients with frontal FCD (MZ > NZ; p < 0.05) but was not significant for patients with extra-frontal FCD., Conclusions: Brain network analysis, based on the combination of time-frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation, can aid in the diagnosis of EZ for pediatric focal epilepsy patients with FCD type II., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Noh, Kim, Yang, Yang, Kim, Hur and Kim.)

The increase in the demand and popularity of smart biosensors has brought a novel and innovative concept to develop a diverse range of semen mutual biomarker (i.e., prostate-specific antigen, PSA)-based biodevices for our daily life applications. Using a versatile strategy, here we have developed a next-generation miniaturized capacitive biomarker-based sensor, which facilitates a direct, rapid quantitation and ultrafast detection of prostate-specific antigen (PSA) selectively. To fabricate an affordable PSA biosensor, an interdigitated capacitor (IDC) was functionalized and to detect PSA at concentrations varying from 0.1 to 10 μL/mL, with a response time of 3 s. Moreover, the PSA biosensor showed a high level of selectivity due to the successful probing of the capacitive response-generated biomolecular interactions using external stimuli at the bioelectrode. The resulting IDC-based PSA biosensors are capable of excellent reproducibility and reusability, which are required for real-time biosensing of any targeted biomolecules where low-concentration detection is a key for point-of-care, on-site sensing applications. We anticipate that this research could open exciting opportunities for PSA detection at a low concentration level.

Objective: Vagus nerve stimulation (VNS) is a nonpharmacologic therapeutic option for patients who have pharmaco-resistant Dravet syndrome (DS). Plentiful efforts have been made for delivering VNS to DS patients, but its effectiveness still requires further verification. We investigated the effectiveness of the VNS treatment of DS patients using brain connectivity analysis with electroencephalography (EEG)., Approach: Twenty pharmaco-resistant DS patients were selected to undergo VNS implantation and classified into responder and non-responder groups after 24 months post-VNS. The effect of VNS between 6 months pre- and 6, 12, and 24 months post-VNS in all patients, responders, and non-responders on four different frequency categories of four brain parameters were compared using resting-state EEG., Main Results: In alpha and beta bands, all patients showed positive results for characteristic path length (CPL), global efficiency (GE), and transitivity after VNS treatment, and changes in betweenness centrality (BC) were not significant. The difference in transitivity between responders and non-responders is more pronounced than those in CPL and GE are, in both the alpha (p < 0.015) and beta (p < 0.001) bands. There was an obvious change in BC, especially in the alpha band, as the hubs tended to move from frontal lobe to parietal lobe for responders; however, there was no change for the non-responders., Significance: We investigated the alteration in brain connectivity of DS patients in alpha and beta bands during a long-term follow-up and found the responders have a decreased transitivity after the VNS treatment. Moreover, the hubs with high values in the alpha band tended to move from frontal lobe to parietal lobe for responders after VNS treatment.

Congenital heart disease (CHD) is a group of anatomic malformations in the heart with high morbidity and mortality. The mammalian heart is a complex organ, the formation and development of which are strictly regulated and controlled by gene regulatory networks of many signaling pathways such as TGF-β. KAT2B is an important histone acetyltransferase epigenetic factor in the TGF-β signaling pathway, and alteration in the gene is associated with the etiology of cardiovascular diseases. The aim of this work was to validate whether KAT2B variations might be associated with CHD. We sequenced the KAT2B gene for 400 Chinese Han CHD patients and evaluated SNPs rs3021408 and rs17006625. The statistical analyses and Hardy-Weinberg equilibrium tests of the CHD and control populations were conducted by the software SPSS (version 19.0) and PLINK. The experiment-wide significance threshold matrix of LD correlation for the markers and haplotype diagram of LD structure were calculated using the online software SNPSpD and Haploview software. We analyzed the heterozygous variants within the CDS region of the KAT2B genes and found that rs3021408 and rs17006625 were associated with the risk of CHD., (© 2020 The Author(s).)

Congenital heart diseases (CHD) are a large group of prevalent and complex anatomic malformations of the heart, with the genetic basis remaining largely unknown. Since genes or factors associated with the differentiation of human embryonic stem (HES) cells would affect the development of all embryonic tissues, including cardiac progenitor cells, we postulated their potential roles in CHD. In this study, we focused on ZW10, a kinetochore protein involved in the process of proper chromosome segregation, and conducted comparative studies between CHD patients and normal controls matched in gender and age in Chinese Han populations. We identified three variations in the ZW10 gene, including rs2885987, rs2271261 and rs2459976, which all had high genetic heterozygosity. Association analysis of these genetic variations with CHD showed correlation between rs2459976 and the risk of CHD. We conclude that rs2459976 in the ZW10 gene is associated with CHD in Chinese Han populations., Competing Interests: CONFLICTS OF INTEREST All the authors have declared that no competing interests exist.

The MADS box-containing transcription factors MEF2A-D regulate the expression of most skeletal and cardiac muscle structural genes. Recently, a zinc finger protein called HZF1 was identified as a transcription factor, and found to be highly expressed in cardiac muscle. By screening the transcription regulatory region of HZF1, we found that myocyte enhancer factor 2 (MEF2) potentially recognizes and binds the regulatory region of the HZF1 gene. We also found that the knockdown of MEF2A endogenous expression in human aortic smooth muscle cells decreases the expression of HZF1, while the enforced expression of MEF2A in turn promotes the expression of HZF1. Furthermore, we employed the luciferase reporter system and chromatin immunoprecipitation (ChIP) to demonstrate that MEF2A does in fact bind the regulatory region of HZF1, which suggests that HZF1 is the direct target of MEF2A. Based on the fact that MEF2 proteins function as essential regulators of cardiac development and as important pathological factors for certain cardiac diseases, our finding that MEF2 positively regulates the expression of HZF1 may contribute to further research investigating the role of the zinc finger protein HZF1 in cardiac development and disease.

Ectomycorrhizal fungus has the ability to enhance the growth of higher plants in the contaminated area, especially ruined by heavy metals. And much attention was focused on how the fungus could enhance the resistance of higher plants. We focused on the resistance of ectomycorrhizal fungus in vitro to heavy metals. In the first experiment, the mycelium biomasses of two ectomycorhizal funguses growing in the Kottke media treated with different concentrations of Cu and Cd were measured after growth as well as the pH value of the medium. The results indicated that heavy metals could reduce the biomasses of the two funguses. Gomplhidius viscidus has higher tolerance to Cu but less Cd than that of Boletus edulis. With development of fungal mycila, the pH value of medium dropped significantly, and this effect might play an important role in enhancing its tolerance. In addition, the higher pH value change per biomass indicated that the fungus treated with heavy metals had the ability to adjust environment of pH more significantly. In the second experiment, the cation exchange capacity (CEC) of the cell walls of the fungus treated with heavy metals was measured according to Marschner's. The results indicated that with the increasing of the concentrations of Cu or Cd, the CEC of Gomphidius viscidus increased, but the CEC of Boletus edulis dropped.