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This paper proposes a new optimization method and its platform for automatically adjusting the control parameters of a digital active gate driver using a PWM inverter. The proposed optimization method applies the searching parameters for only any duration in an ac current cycle and fixed parameters for the other duration. This enables us to find the optimal operating points of power devices so as to reduce the surge voltage and switching loss with the consideration of their dependency on the load current. Additionally, the proposed optimization method also can find the operating points while the inverter performs a continuous switching operation. For this reason, the proposed optimization method can be applied to a continuous running test of PWM inverters, for example, in a manufacturing process. The validity of the proposed method and platform was evaluated by using a 10-kW three-phase PWM inverter with digital gate drives. The experimental results confirmed that the proposed optimization method makes it possible to find the optimal operating points for reducing the surge voltage and/or the power loss.

An easy-to-implement chemical solution deposition route using EG and CA additives is demonstrated to fabricate phase-pure AgNbO3 films on Pt/Ti/SiO2/Si substrates, where the films show an M2 antiferroelectric phase at room temperature.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 6.4 million deaths worldwide. The prevalent comorbidity between hypertension and severe COVID-19 suggests common genetic factors may affect the outcome of both diseases. As both hypertension and severe COVID-19 demonstrate sex-biased prevalence, common genetic factors between the two diseases may display sex-biased differential associations. By evaluating COVID-19 association signals of 172-candidate hypertension single nucleotide polymorphisms (SNPs) derived from more than 1 million European individuals in two sex-stratified severe COVID-19 genome-wide association studies from UK BioBank with European ancestry, we revealed one functional cis expression quantitative trait locus of SPEG (rs12474050) showing sex-biased association with severe COVID-19 in women. The risk allele rs12474050*T associates with higher blood pressure. In our study, we found it is significantly correlated with lower SPEG expression in muscle-skeletal but with higher expression in both brain cerebellum and cerebellar hemisphere. Additionally, nominal significances were detected for the association between rs12474050*T and lower SPEG expression in both heart left ventricle and atrial appendage; among these tissues, the SPEG expression is nominally significantly higher in females than in males. Further analysis revealed SPEG is mainly expressed in cardiomyocytes in heart and is upregulated upon SARS-CoV-2 infection, with significantly higher upregulation of SPEG only observed in female but not in male COVID-19 patients compared to both normal female and male individuals, suggesting upregulation of SPEG is a female-specific protective mechanism against COVID-19 induced heart damage. Taken together, our analyses suggest the involvement of SPEG in both hypertension and severe COVID-19 in women, which provides new insights for sex-biased effect of severe COVID-19 in women.

Taiwan government consolidated the kindergarten and daycare systems in 2012, and launched a new national curriculum framework, Early Childhood Education & Care Curriculum Framework (ECECCF), as a guidance for quality early childhood education programs. Research has shown that the effects of a new educational program highly depended on the fidelity of its implementation. It has thus been suggested that the degree of implantation of a program needs be evaluated before conducting further program evaluation. Thus, the purpose of this study was to construct an Early Childhood Education Curriculum Framework Implementation Scale (ECECCF Implementation Scale) for Taiwanese preschool programs. 216 preschool classes in Taiwan were involved. The study consisted of two stages: In Stage 1, the exploratory factor analysis showed that the implementation of ECECCF could mostly be explained by four factors, and all the factors extracted had acceptable reliability and validity. In Stage 2, rubrics were constructed for each item and factor analysis was re-conducted, resulting in a 19-item scale of four factors (Awareness and Adjustment, Learning Centers Arrangement, Teaching Guidance and Curriculum Development). The reliability and validity tests shows that: (1) the final version of the ECECCF Implementation Scale is a valid and reliable instrument, explaining 62.9% of the total variance; (2) the criterion validity indicated that the ECECCF scale can not only be used for assessing the implementation of ECECCF, but also can be used for understanding teachers’ needs in instructional and operational curriculum for further professional development.

We introduce a simple and compact diode-pumped Pr:YLF-Cr:LiCAF laser, operating at 813.42 nm and providing a 130-mW, single-frequency output tunable over a 3-GHz range. The laser has a short-term intrinsic linewidth estimated to be 700 Hz (β-separation method), while exhibiting a free-running wavelength stability of below 1 pm in one hour. Using a feed-forward technique we demonstrate the integration of the laser output into a fully stabilized, 1-GHz Ti:sapphire laser frequency comb, resulting in a heterodyne beat note between the laser and the comb with a bandwidth of 65 kHz. Combining feed-forward control with a low-bandwidth servo feedback loop permits stable long-term locking with an rms beat note variation of 15 kHz over 2 minutes. This performance makes the laser a potential candidate for the lattice laser in a 87Sr optical lattice clock.

Odorant binding proteins (OBPs) play an important role in insect peripheral olfactory systems and exploring the physiological function of OBPs could facilitate the understanding of insects' chemical communication. Here, the functional analysis of an antenna-based NlugOBP8 from brown planthopper (BPH)

The coarse aggregate–mortar interface transition zone (ITZ) has a great influence on the mechanical properties of concrete, which cannot be easily studied using laboratory tests in the mesoscale. In this paper, a series of axial compression tests were conducted using the discrete element method (DEM) on concrete specimens for four phases: coarse aggregates, mortars, aggregate–mortar interface transition zones, and voids. The effects of ITZ strength on macroscopic stress and microscopic cracks under different strength reduction factors were investigated through axial compression testing. With the increase in interface transition strength, the compressive strength of the concrete becomes stronger; moreover, the number of cracks decreases, and the anisotropy of contact orientation becomes weaker. Meanwhile, the direction of crack development and the damage mode of compressed concrete specimens were also dependent on the coarse aggregate–mortar interface strength coefficient.

Background: Whether infection with the hepatitis C virus (HCV) causes schizophrenia — and whether the associated risk reverses after anti-HCV therapy — is unknown; we aimed to investigate these topics. Methods: We conducted a nationwide, population-based cohort study using the Taiwan National Health Insurance Research Database (TNHIRD). A diagnosis of schizophrenia was based on criteria from the International Classification of Diseases, 9th revision (295.xx). Results: From 2003 to 2012, from a total population of 19 298 735, we enrolled 3 propensity-score-matched cohorts (1:2:2): HCV-treated (8931 HCV-infected patients who had received interferon-based therapy for ≥ 6 months); HCV-untreated (17 862); and HCV-uninfected (17 862) from the TNHIRD. Of the total sample (44 655), 82.81% (36 980) were 40 years of age or older. Of the 3 cohorts, the HCV-untreated group had the highest 9-year cumulative incidence of schizophrenia (0.870%, 95% confidence interval [CI] 0.556%–1.311%; p < 0.001); the HCV-treated (0.251%, 95% CI 0.091%–0.599%) and HCV-uninfected (0.118%, 95% CI 0.062%–0.213%) cohorts showed similar cumulative incidence of schizophrenia (p = 0.33). Multivariate Cox analyses showed that HCV positivity (hazard ratio [HR] 3.469, 95% CI 2.168–5.551) was independently associated with the development of schizophrenia. The HCV-untreated cohort also had the highest cumulative incidence of overall mortality (20.799%, 95% CI 18.739%–22.936%; p < 0.001); the HCV-treated (12.518%, 95% CI 8.707%–17.052%) and HCV uninfected (6.707%, 95% CI 5.533%–8.026%) cohorts showed similar cumulative incidence of mortality (p = 0.12). Limitations: We were unable to determine the precise mechanism of the increased risk of schizophrenia in patients with HCV infection. Conclusion: In a population-based cohort (most aged ≥ 40 years), HCV positivity was a potential risk factor for the development of schizophrenia; the HCV-associated risk of schizophrenia might be reversed by interferon-based antiviral therapy.

Glioma is the most common primary tumour in the central nervous system in adults, and at present, there is no effective treatment to cure this malignancy. Long noncoding RNAs (lncRNAs) are closely related to tumour progression and have attracted increasing attention in tumour research. However, the role of lncRNA FGF14-AS2 in glioma tumorigenesis has not been determined. In the present study, we found that FGF14-AS2 expression was significantly elevated in glioma tissues and was associated with poor survival in glioma patients. Silencing FGF14-AS2 inhibited the proliferation, migration and invasion ability of glioma cells. In vivo assay showed that silencing FGF14-AS2 led to inhibition of tumour growth. In addition, FGF14-AS2 was observed to promote glioma progression via the miR-320a/E2F1 axis. Moreover, E2F1 could bind to the promoter region of FGF14-AS2, thereby enhancing FGF14-AS2 expression. In conclusion, FGF14-AS2 could accelerate tumorigenesis of glioma by forming a feedback loop with the miR-320a/E2F1 axis which suggested that FGF14-AS2 could serve as a therapeutic target for glioma.

The recent development of dendritic cell (DC)-based immunotherapy has resulted in advances in glioblastoma multiforme (GBM) treatment. However, the cell fate of DCs in the GBM microenvironment, especially in microenvironments in which glioma stem cell (GSC)-mediated remodeling has resulted in highly immuno-suppressive conditions, has not yet been fully investigated. The current study observed direct and active mutual interactions between GSCs and primary cultured DCs in a dual-color tracing model. Highly proliferative DCs could be monoclonal and continuously passaged, and these cells exhibited acquired tumorigenicity in vivo, indicating their malignant transformation. Transformed DCs (t-DCs) still expressed DC-specific surface markers, namely, CD80 and CD11c, and immune-related costimulatory molecules, namely, CD80, CD86, CD40, and ICAM-1. However, the expression levels of these molecules in t-DCs decreased moderately compared to those in naive DCs. Mechanistic studies revealed the upregulation of the proliferation-related gene pentraxin 3 (PTX3) in t-DCs. Stable overexpression of PTX3 further promoted the proliferation and migration of t-DCs in vitro, decreased the expression of costimulatory molecules, and increased the tumorigenicity of t-DCs in vivo. Bioinformatics prediction, qRT‒PCR verification, and luciferase reporter gene analysis indicated that the transcription factor zinc finger protein 148 (ZNF148) directly bound to the PTX3 promoter region and enhanced PTX3 expression. Downregulation of ZNF148 significantly decreased PTX3 expression and reduced the proliferation and migration of t-DCs. Overexpression of ZNF148 significantly increased PTX3 expression and promoted the proliferation and migration of t-DCs, achieving the same biological effects as PTX3 overexpression in t-DCs. Simultaneously, downregulation of ZNF148 partially reversed the effect of PTX3 overexpression in t-DCs. In conclusion, the ZNF148/PTX3 axis played an important role in regulating the malignant transformation of DCs after cross-talk with GSCs, and this axis may serve as a new target for sensitizing GBM to DC-based immunotherapy.

Background: The correlation between microRNA, obesity, and glycemic intolerance in patients on peritoneal dialysis (PD) is unknown. We aimed to measure the adipose and plasma miR-221 and -222 levels, and to evaluate their association with adiposity, glucose intolerance, and new onset diabetes mellitus (NODM) after the commencement of PD. Methods: We prospectively recruited incident adult PD patients. miR-221 and -222 were measured from adipose tissue and plasma obtained during PD catheter insertion. These patients were followed for 24 months, and the outcomes were changes in adiposity, insulin resistance, and NODM after PD. Results: One hundred and sixty-five patients were recruited. Patients with pre-existing DM had higher adipose miR-221 (1.1 ± 1.2 vs. 0.7 ± 0.9-fold, p = 0.02) and -222 (1.9 ± 2.0 vs. 1.2 ± 1.3-fold, p = 0.01). High adipose miR-221 and -222 levels were associated with a greater increase in waist circumference (miR-221: beta 1.82, 95% CI 0.57–3.07, p = 0.005; miR-222: beta 1.35, 95% CI 0.08–2.63, p = 0.038), Homeostatic Model Assessment for Insulin Resistance (HOMA) index (miR-221: beta 8.16, 95% CI 2.80–13.53, p = 0.003; miR-222: beta 6.59, 95% CI 1.13–12.05, p = 0.018), and insulin requirements (miR-221: beta 0.05, 95% CI 0.006–0.09, p = 0.02; miR-222: beta 0.06, 95% CI 0.02–0.11, p = 0.002) after PD. The plasma miR-222 level predicted the onset of NODM (OR 8.25, 95% CI 1.35–50.5, p = 0.02). Conclusion: miR-221 and -222 are associated with the progression of obesity, insulin resistance, and NODM after PD.

Ancestry impacts the likelihood of hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). To identify ancestry-linked genetic risk variants associated with COVID-19 hospitalization, we performed an integrative analysis of two genome-wide association studies (GWASs) evaluating genetic variation among ancestrally diverse cohorts. We resolved four single nucleotide polymorphisms (SNPs) that are more frequent in COVID-19 hospitalized patients with non-European ancestry than the general population. Among them, the COVID-19 risk SNP rs16831827 shows the largest difference in allele frequency between African and European populations. The minor allele frequency of rs16831827*T was significantly higher in hospitalized COVID-19 patients with African ancestry. SNP rs16831827 also associates with COVID-19 hospitalization in an independent GWAS from the UK Biobank wherein both the hospitalized and control patients are entirely of African ancestry. rs16831827 is an expression quantitative trait locus (eQTL) of MAP3K19. Apart from rs16831827, two rare SNPs of MAP3K19, rs186150828 and rs192473276, were also significantly associated with COVID-19 hospitalization among African populations in the Regeneron COVID-19 hospitalization GWAS (p < 5x10-7). MAP3K19 expression is induced during ciliogenesis and most abundant in ciliated tissues including the lung and testis. Multiple COVID-19 related single-cell RNA sequencing data revealed that MAP3K19 is highly expressed in nasal multiciliated epithelial cells, nasopharyngeal ciliated cells, and airway ciliated cells. The COVID-19 hospitalization risk allele rs16831827*T is associated with reduced MAP3K19 expression. Hence, rs16831827 may increase the risk of severe COVID-19 by reducing baseline MAP3K19 expression.

The decay width of the $$D_s^{*}$$ D s ∗ meson is dominated by the electromagnetic mode $$D_s^*\rightarrow D_s \gamma $$ D s ∗ → D s γ , and it is thus the longest-lived charged vector meson. In light of this point, we perform the first QCD LCSRs calculation of $$D_s^{*}\rightarrow \phi $$ D s ∗ → ϕ helicity form factors and discuss the experiment potential of discovering exclusive $$D_s^{*}$$ D s ∗ weak decays. The main result is the partial decay widths, which read as $$\varGamma _{D_s^*\rightarrow l \nu } = 2.44 \times 10^{-12} \, \textrm{GeV}$$ Γ D s ∗ → l ν = 2.44 × 10 - 12 GeV , $$\varGamma _{D_s^*\rightarrow \phi l \nu } = (3.28^{+0.82}_{-0.71}) \times 10^{-14} \, \textrm{GeV}$$ Γ D s ∗ → ϕ l ν = ( 3 . 28 - 0.71 + 0.82 ) × 10 - 14 GeV , $$\varGamma _{D_s^{*} \rightarrow \phi \pi } = ( 3.81^{+1.52}_{-1.33} ) \times 10^{-14} \, \textrm{GeV}$$ Γ D s ∗ → ϕ π = ( 3 . 81 - 1.33 + 1.52 ) × 10 - 14 GeV and $$\varGamma _{D_s^{*}\rightarrow \phi \rho } = ( 1.16^{+0.42}_{-0.39} ) \times 10^{-13} \, \textrm{GeV}$$ Γ D s ∗ → ϕ ρ = ( 1 . 16 - 0.39 + 0.42 ) × 10 - 13 GeV . We show that these channels are promising in the near future, serving as the first experimental observation of weak decays of a vector meson, and would open up a new playground for precision test of the standard model.

Aorto-right-atrial fistula is an uncommon condition with an unclear pathogenesis. We present the case of a 3-year-old girl with a giant omphalocele repaired days after birth and incidentally discovered with a celiacomesenteric trunk-to-right atrium fistula. Three-dimensional reconstruction CT unveiled its anatomical pattern, and the fistula was successfully closed using a Amplatzer vascular plug II percutaneously.

Ovarian cancer is one of the most lethal gynecological malignancies. Recurrence or acquired chemoresistance is the leading cause of ovarian cancer therapy failure. Overexpression of ATP-binding cassette subfamily B member 1 (ABCB1), commonly known as P-glycoprotein, correlates closely with multidrug resistance (MDR). However, the mechanism underlying aberrant ABCB1 expression remains unknown. Using a quantitative high-throughput combinational screen, we identified that terfenadine restored doxorubicin sensitivity in an MDR ovarian cancer cell line. In addition, RNA-seq data revealed that the Ca2+-mediated signaling pathway in the MDR cells was abnormally regulated. Moreover, our research demonstrated that terfenadine directly bound to CAMKIID to prevent its autophosphorylation and inhibit the activation of the cAMP-responsive element-binding protein 1 (CREB1)-mediated pathway. Direct inhibition of CAMKII or CREB1 had the same phenotypic effects as terfenadine in the combined treatment, including lower expression of ABCB1 and baculoviral IAP repeat-containing 5 (BIRC5, also known as survivin) and increased doxorubicin-induced apoptosis. In this study, we demonstrate that aberrant regulation of the Ca2+-mediated CAMKIID/CREB1 pathway contributes to ABCB1 over-expression and MDR creation and that CAMKIID and CREB1 are attractive targets for restoring doxorubicin efficacy in ABCB1-mediated MDR ovarian cancer.

Glioma is the most common malignant tumor of the central nervous system, with high heterogeneity, strong invasiveness, high therapeutic resistance, and poor prognosis, comprehending a serious challenge in neuro-oncology. Until now, the mechanisms underlying glioma progression have not been fully elucidated.The expression of DExH-box helicase 9 (DHX9) in tissues and cells was detected by qRT-PCR and western blot. EdU and transwell assays were conducted to assess the effect of DHX9 on proliferation, migration and invasion of glioma cells. Cocultured model was used to evaluate the role of DHX9 on macrophages recruitment and polarization. Animal study was performed to explore the role of DHX9 on macrophages recruitment and polarization in vivo. Bioinformatics analysis, dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP)-qPCR assay was used to explore the relation between DHX9 and TCF12/CSF1.DHX9 was elevated in gliomas, especially in glioblastoma multiforme (GBM). Besides promoting the proliferation, migration, and invasion of glioma cells, DHX9 facilitated the infiltration of macrophages into glioma tissues and polarization to M2-like macrophages, known as tumor-associated macrophages (TAMs). DHX9 silencing decreased the expression of colony-stimulating factor 1 (CSF1), which partially restored the inhibitory effect on malignant progress of glioma and infiltration of TAMs caused by DHX9 knockdown by targeting the transcription factor 12 (TCF12). Moreover, TCF12 could directly bind to the promoter region of CSF1.DHX9/TCF12/CSF1 axis regulated the increases in the infiltration of TAMs to promote glioma progression and might be a novel potential target for future immune therapies against gliomas.

Sex-biased difference in coronavirus disease 2019 (COVID-19) hospitalization has been observed as that male patients tend to be more likely to be hospitalized than female patients. However, due to the insufficient sample size and existed studies that more prioritized to sex-stratified COVID-19 genome-wide association study (GWAS), the searching for sex-biased genetic variants showing differential association signals between sexes with COVID-19 hospitalization was severely hindered. We hypothesized genetic variants would show potentially sex-biased genetic effects on COVID-19 hospitalization if they display significant differential association effect sizes between male and female COVID-19 patients. By integrating two COVID-19 GWASs, including hospitalized COVID-19 patients vs. general population separated into males (case = 1,917 and control = 221,174) and females (case = 1,343 and control = 262,886), we differentiated the association effect sizes of each common single nucleotide polymorphism (SNP) within the two GWASs. Twelve SNPs were suggested to show differential COVID-19 associations between sexes. Further investigation of genes (n = 58) close to these 12 SNPs resulted in the identification of 34 genes demonstrating sex-biased differential expression in at least one GTEx tissue. Finally, 5 SNPs are mapped to 8 genes, including rs1134004 (GADD45G), rs140657166 (TRIM29 and PVRL1), rs148143613 (KNDC1 and STK32C), rs2443615 (PGAP2 and TRIM21), and rs2924725 (CSMD1). The 8 genes display significantly differential gene expression in blood samples derived from COVID-19 patients compared to healthy controls. These genes are potential genetic factors contributing to sex differences in COVID-19 hospitalization and warranted for further functional studies.

To develop a superior diagnostic approach for pancreatic adenocarcinoma (PAAC), the present study prospectively included 338 PAAC patients, 294 normal healthy volunteers (NHV), 122 chronic pancreatitis (CP) patients and 100 patients with non-PAAC malignancies. In the identification phase, HuProt Human Proteome Microarray, comprising 21 065 proteins, was used to identify serum tumor-associated autoantibodies (TAAbs) candidates differentiating PAAC (n = 30) from NHV (n = 30). A PAAC-focused array containing 165 differentially expressed TAAbs identified was subsequently adopted in the validation phase (n = 712) for specificity and sensitivities. The multivariate TAAbs signature for differentiation PAAC from controls (NHV + CP) identified five candidates, namely the IgG-type TAAbs against CLDN17, KCNN3, SLAMF7, SLC22A11 and OR51F2. Multivariate logistic performance model of y = (22.893 × CA19-9 + 0.68 × CLDN17 - 4.012) showed a significant better diagnostic accuracy than that of CA19-9 and CLDN17 in differentiating PAAC from controls (NHV + CP) (AUC = 0.97, 0.92 and 0.82, respectively, P-value .0001). We further tested the autoantigen level of CLDN17 by ELISA in 82 sera samples from PAAC (n = 42), CP (n = 24) and NHV (n = 16). Similarly, the model showed superior diagnostic performance than that of CA19-9 and CLDN17 (AUC = 0.93, 0.83 and 0.81, respectively, P-value .0001) in differentiating PAAC from controls. In conclusion, our study is the first to characterize the circulating TAAbs signatures in PAAC. The results showed that CLDN17 combined with CA19-9 provided potentially clinical value and may serve as noninvasive novel biomarkers for PAAC diagnosis.

Arabidopsis thaliana has been used regularly as a model plant in gene expression studies on transcriptional reprogramming upon pathogen infection, such as that by Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), or when subjected to stress hormone treatments including jasmonic acid (JA), salicylic acid (SA), and abscisic acid (ABA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) has been extensively employed to quantitate these gene expression changes. However, the accuracy of the quantitation is largely dependent on the stability of the expressions of reference genes used for normalization. Recently, RNA sequencing (RNA-seq) has been widely used to mine stably expressed genes for use as references in RT-qPCR. However, the amplification step in RNA-seq creates an intrinsic bias against those genes with relatively low expression levels, and therefore does not provide an accurate quantification of all expressed genes. In this study, we employed mass spectrometry-based label-free quantification (LFQ) in proteomic analyses to identify those proteins with abundances unaffected by Pst DC3000 infection. We verified, using RT-qPCR, that the levels of their corresponding mRNAs were also unaffected by Pst DC3000 infection. Compared to commonly used reference genes for expression studies in A. thaliana upon Pst DC3000 infection, the candidate reference genes reported in this study generally have a higher expression stability. In addition, using RT-qPCR, we verified that the mRNAs of the candidate reference genes were stably expressed upon stress hormone treatments including JA, SA, and ABA. Results indicated that the candidate genes identified here had stable expressions upon these stresses and are suitable to be used as reference genes for RT-qPCR. Among the 18 candidate reference genes reported in this study, many of them had greater expression stability than the commonly used reference genes, such as ACT7, in previous studies. Here, besides proposing more appropriate reference genes for Arabidopsis expression studies, we also demonstrated the capacity of mass spectrometry-based LFQ to quantify protein abundance and the possibility to extend protein expression studies to the transcript level.

Psoriasis in different body regions displays varying therapeutic responses to biologics, whereas currently relevant studies remain scarce. We retrospectively reviewed the treatment responses of patients with moderate-to-severe psoriasis, who completed the two-year reimbursed ustekinumab or secukinumab treatment in two medical centers in Southern Taiwan. Demographic profiles and body regional PASI scores (head/neck, trunk, upper and lower limbs) along the treatment course were recorded. The proportions of patients attaining PASI 75, 90, 100 and the extent of body regional PASI score improvements were compared in biologic naïve or experienced patients. A total of 57 and 67 patients receiving ustekinumab and secukinumab injections, respectively, were included. Overall, patients receiving secukinumab showed higher degrees of PASI score improvements along the two-year treatment course. The lower limbs had the highest, and the upper extremities and head/neck had the lowest post-treatment PASI scores regardless of prior biologic use in the groups of ustekinumab and secukinumab. The upper limbs showed the highest, while the lower limbs had the lowest complete remission rate (regional specific PASI 100) in response to ustekinumab (upper limbs 48.7%, lower limbs 25.6%) and secukinumab (upper limbs 77.1%, lower limbs 42.8%) in biologic naïve groups. Our study demonstrated that lower limbs were the most treatment-refractory area in response to ustekinumab and secukinumab injections, while the upper limbs and head/neck region had a better response.

Glioblastoma has high recurrence, while the sensitivity of recurrent glioblastoma to chemotherapy is lower than that of primary glioblastoma. Moreover, there is no standardized treatment for recurrent glioblastoma. Unfortunately, the biological mechanism of recurrent glioblastoma is still unclear, and there are few related studies. We compared the phenotypes of clinical glioblastoma specimens, in-vitro cultured glioma stem-like cells (GSCs) and patient-derived xenograft tumor (PDX) models to explore the molecular genetic characteristics of primary and recurrent glioblastoma from the same patient. In vitro, SU5-2, GSCs derived from recurrent glioblastoma specimens, had stronger proliferative activity and self-renewal ability. Meanwhile, SU5-2 was more resistant to temozolomide and invasive than SU5-1, which derived from primary glioblastoma specimens. Further analysis of the expression of costimulatory molecules showed that the expression of B7-H1, B7-H2 and B7-H3 of SU5-2 were upregulated. In vivo, Kaplan-Meier survival curve analysis showed that the median survival of the recurrent PDX group was worse. The results of gene detection in vitro, PDX model and clinical samples were consistent. Our results showed that the GSCs based on glioblastoma specimens and the PDX models could replicate the main molecular genetic characteristics of original tumors, which provided a reliable experimental platform for both tumor translation kinds of research and screening of molecular therapeutic targets.

Flexible piezoelectric thin films are raising interest in energy harvesting and wearable electronics, although their direct fabrication is challenging in the selection of substrates and thermal processing. In this work, we developed direct fabrication of flexible lead-free (K, Na)NbO3 (KNN)-based piezoelectric films on commercially available metallic foils by sol-gel processing. Stainless steel and platinum foils are selected as flexible substrates because of their good thermal stability, robust flexibility, and cost-efficiency. The sol-gel-processed KNN-based thin films on both of the metallic foils show good flexibility, with the bending radii reaching ±3 mm. The flexible thin films grown on stainless steel and platinum foils present high breakdown electric fields that reach 1760 and 2530 kV/cm, respectively, resulting from the fine-grained dense structure, limited leakage current density, and suppressed mobility of charged carriers. Improved effective piezoelectric coefficient d33, eff* (75.4 pm/V) with a slight decrease after bending was obtained in the flexible thin films on Pt when compared to their rigid counterparts. The flexible lead-free piezoelectric thin films with combined high breakdown electric fields and piezoelectric and energy storage properties may pave the way for integrating KNN-based multifunctional thin films into flexible electronics.

Presbyphagia is age-related changes in swallowing function, which imposes a high risk of aspiration in older adults. Considering olfactory stimulation (OS) can influence behavioral activities by modulating neuronal excitability, the present study aims to determine whether OS could improve the swallowing function of aged rats through activating the central neuronal networks and downstream muscular activities participated in the control of swallowing. Aged male Wistar rats received OS by inhaling a mixture of plant-based volatile molecules twice a day for 12 days were subjected to functional magnetic resonance imaging (fMRI) and c-fos, choline acetyltransferase (ChAT) immunostaining to detect the neuronal activities of the orbitofrontal cortex (OFC) and medullary nuclei engaged in swallowing control, respectively. The functional effects of OS on downstream pharyngeal muscle activity were examined by evaluating the dihydropyridine receptor–ryanodine receptor (DHPR–RyR)-mediated intramuscular Ca2+ expression, and analyzing the amplitude/frequency of muscle contraction, respectively. In untreated rats, only moderate signal of fMRI and mild c-fos/ChAT expression was detected in the OFC and medullary nuclei, respectively. However, following OS, intense signals of fMRI and immunostaining were clearly expressed in the orbitofronto-medullary networks. Functional data corresponded well with above findings in which OS significantly enhanced DHPR–RyR-mediated intramuscular Ca2+ expression, effectively facilitated a larger amplitude of pharyngeal muscle contraction, and exhibited better performance in consuming larger amounts of daily dietary. As OS successfully activates the neuromuscular activities participated in the control of swallowing, applying OS may serve as an effective, easy, and safe strategy to greatly improve the swallow function of aging populations.

Mitochondrial DNA (mtDNA) resembles bacterial DNA and potentially triggers local and systemic inflammation. We evaluate the prognostic implications of PD effluent mtDNA level in peritoneal dialysis (PD) patients.We measured mtDNA in the PD effluent (PDE) sediment and supernatant of 168 incident PD patients. All patients were followed for hospitalization, technique and overall survival.The median PD effluent supernatant and sediment mtDNA levels were 255.4 unit (interquartile range [IQR] 157.5-451.3) and 201.6 unit (IQR 147.8-267.3), respectively. Serum C-reactive protein level closely with PDE sediment mtDNA level (r = 0.471, p 0.001) and less with supernatant mtDNA level (r = 0.156, p = 0.044). PDE supernatant mtDNA level correlates with dialysate-to-plasma creatinine ratio at 4 h (D/P4) (r = 0.361, p 0.001) but not with any clinical outcome. PDE sediment mtDNA was an independent predictor of technique survival (p = 0.011) and the duration of hospitalization (p = 0.044) after adjusting for clinical confounding factors.PDE sediment mtDNA level significantly correlated with systemic inflammation, while PDE supernatant mtDNA level correlated with peritoneal transport. PDE sediment mtDNA level also independently predicted technique survival and duration of hospitalization. The mechanism of the different implications between PDE sediment and supernatant mtDNA levels deserves further investigations.