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Abstract Background The growing body of research on kidney disease in children has identified a broad spectrum of genetic etiologies. Methods We conducted a prospective study to evaluate the efficacy of an optimized genetic test and subclinical changes in a real-world context before kidney transplantation. All cases involved recipients under the age of 18 who underwent whole exome sequencing (ES) between 2013 and 2022. Results The study population included 244 children, with a median age of 13.1 years at transplantation. ES provided a molecular genetic diagnosis in 114 (46.7%) probands with monogenic variants in 15 known disease-causing genes. ES confirmed the suspected clinical diagnosis in 74/244 (30.3%) cases and revised the pre-exome clinical diagnoses in 40/244 (16.4%) cases. ES also established a specific underlying cause for kidney failure for 19 patients who had previously had an unknown etiology. Genetic diagnosis influenced clinical management in 88 recipients (36.1%), facilitated genetic counseling for 18 families (7.4%), and enabled comprehensive assessment of living donor candidates in 35 cases (14.3%). Conclusions Genetic diagnosis provides critical insights into the pathogenesis of kidney disease, optimizes clinical strategies concerning risk assessment of living donors, and enhances disease surveillance of recipients.

Rheumatoid arthritis poses a significant threat to the well-being of individuals as an autoimmune disorder. Calycosin is a flavonoid isolated from the root of Astragalus that may be beneficial in treating rheumatoid arthritis. The anti-inflammatory role and mechanism of calycosin were validated in this study through the utilization of collagen-induced arthritis mice models and lipopolysaccharide/interferon gamma stimulated bone marrow-derived macrophages. By applying RNA sequencing technology and the network pharmacological method, it is demonstrated in the findings that the treatment with calycosin leads to a significant alleviation of arthritis symptoms, mitigation of synovial proliferation, impediment of bone and cartilage devastation, and suppression of activated synovial macrophages in collagen-induced arthritis. Mechanistically, activation of JNK and NF-κB pathways is inhibited by calycosin in lipopolysaccharide/interferon gamma stimulated bone marrow-derived macrophages. These results confirm the potential of calycosin, a natural compound, for attenuating rheumatoid arthritis by acting as an anti-inflammatory agent through multiple pathways.

Abstract Background In children, focal segmental glomerulosclerosis (FSGS) is the main cause of steroid resistant nephrotic syndrome (SRNS). To identify specific candidates and the mechanism of steroid resistance, we examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Methods Renal biopsies from seven steroid-sensitive (SS) and eleven steroid-resistant (SR) children FSGS patients were obtained. We examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) analysis, as well as the construction of protein-protein interaction (PPI) network were performed. Two proteins were further valiadated by immunohistochemistry staining in FSGS patients and mice models. Results In total, we quantified more than 4000 proteins, of which 325 were found to be differentially expressed proteins (DEPs) between the SS and SR group (foldchange ≥2, P

Proton Exchange Membrane Fuel Cell (PEMFC) is a multi-parameter and strongly coupled complex system, efficient and smooth operation is beneficial to the efficiency and stability of PEMFC. In this paper, aiming at improve the temperature and voltage management in PEMFC, a stack model is established, and a PEMFC temperature and voltage dynamic management controller based on Model Predict Control method (MPC) is proposed. The working temperature and output voltage are controlled by the mass flow rate of cooling water and hydrogen gas, respectively. The performances of PEMFC under different controller including MPC and traditional PID controllers are analyzed. Due to the optimization of future time step in MPC controller, the measured value will move close to the set value faster. The response time and overshoots of temperature and voltage are remarkably reduced. Compared with PID controller, MPC temperature control has smaller overshoot and faster response time, Moreover, with step current change, voltage overshoot of MPC controller is less than 1.2% which is better than other controllers.

In order to obtain a nitride ceramic material with good flexural and dielectric properties, using silicon nitride whiskers (Si3N4w) as raw material, three kinds of Si3N4w spherical particle powders with different particle size distributions were prepared by spray drying process at first in this work, and the effect of the rotating speed of the atomizing disc on the particle size distribution of Si3N4w spherical particles was studied. Then, using the Si3N4w spherical particles obtained by spray drying as raw materials, three kinds of Si3N4w preforms with different particle gradations were prepared by dry pressing method, and the pore size distribution of the particle gradation Si3N4w preforms was studied. Si3N4 matrices were further prepared in three kinds of particle gradation Si3N4w preforms by chemical vapor infiltration (CVI) and precursor impregnation and pyrolysis (PIP) methods, and the phase and microstructure evolution of Si3N4w/Si3N4 composites during the preparation process were investigated. Finally, the effect of particle gradation on the microstructure, density, flexural and dielectric property of Si3N4w/Si3N4 composites was studied. The results show that the three kinds of particle gradation Si3N4w preforms all have bimodal pore structure characteristics, in which the pore sizes of small pores are all about 0.7 μm, and the pore sizes of large pores are 45.2, 30.1 μm and 21.3 μm, respectively. Among the as-prepared three types of Si3N4w/Si3N4 composites with particle gradation, the flexural strength of the S13 composites reaches 81.59 MPa since it has the best particle gradation effect. In addition, the dielectric constant and dielectric loss of this sample are 5.08 and 0.018, respectively. Good flexural strength and dielectric properties indicate that the as-prepared Si3N4w/Si3N4 composites are expected to be used in the field of missile radomes.

Tumor necrosis factor receptor-related factor 7 (TRAF7) can regulate cell differentiation and apoptosis, but its specific functional mechanism in the pathological process of acute myeloid leukemia (AML) closely related to differentiation and apoptosis disorders is largely unclear. In this study, TRAF7 was found to be lowly expressed in AML patients and a variety of myeloid leukemia cells. TRAF7 was overexpressed in AML Molm-13 and chronic myeloid leukemia (CML) K562 cells by transfection with pcDNA3.1-TRAF7. CCK-8 assay and flow cytometry analysis showed that TRAF7 overexpression induced growth inhibition and apoptosis in K562 and Molm-13 cells. Measurements of glucose and lactate suggested that TRAF7 overexpression impaired glycolysis of K562 and Molm-13 cells. Cell cycle analysis indicated that most of K562 and Molm-13 cells were captured in G0/G1 phase by TRAF7 overexpression. PCR and western blot assay revealed that TRAF7 increased Kruppel-like factor 2 (KLF2) expression but decreased 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) expression in AML cells. KLF2 knockdown can counteract TRAF7-triggered PFKFB3 inhibition, and abolish TRAF7-mediated glycolysis inhibition and cell cycle arrest. KLF2 knockdown or PFKFB3 overexpression both can partially neutralize TRAF7-induced growth inhibition and apoptosis of K562 and Molm-13 cells. Moreover, Lv-TRAF7 decreased human CD45+ cells in mouse peripheral blood in the xenograft mice established by NOD/SCID mice. Taken together, TRAF7 exerts anti-leukemia effects by impairing glycolysis and cell cycle progression of myeloid leukemia cells via modulating the KLF2-PFKFB3 axis.

Core-shell thermally expandable microspheres (TEMs) were prepared via Pickering suspension polymerization. Acrylonitrile (AN), methacrylic acid (MAA) and N,N-dimethylacrylamide (DMAA) were used as the comonomers, the 2,2′-azobisisobutyronitrile (AIBN) was used as the initiator and the ethyleneglycol dimethacrylate (EGDMA) was used as the crosslinker. The effects of initiator concentration, cross-linking agent concentration and modified monomer type on the morphology, thermal properties and encapsulation content of TEMs were investigated. The results show that the small change in initiator concentration had a significant effect on the properties of TEMs. When the initiator concentration was 0.55%, the microspheres showed core-shell structure and the maximum expansion ratio was 3.06 times. According to the scanning electron microscope (SEM) image, the heat resistance of the microspheres increased with the increase of the content of crosslinking agent. The lower the water solubility of the modified monomer, the more stable the foaming of the TEMs. When methyl acrylate (MA) was used as a modified monomer, the initial expansion temperature of the microspheres was 163.2°C, the maximum expansion temperature was 223.5 °C, and the encapsulation content of the blowing agent was 14.70%.

During the operation of high-power proton exchange membrane (PEM) fuel cell, huge heat is generated in the chemical reaction, which need be removed by efficient cooling design. To solve the problem of local overheating during PEMFC, a novel multi-input and multi-output (MIMO) cooling flow field is proposed. The maximum temperature, temperature uniformity and pressure drop characteristics of the U-shaped and Z-shaped cooling flow fields with different MIMO channels configurations are researched by computational fluid dynamics (CFD) method. The results demonstrate that comparing with U-shaped cooling flow field, Z-shaped design can provide better temperature distribution with the same MIMO channel configuration. Moreover, the serpentine cooling flow field provides better cooling performance than parallel cooling flow field, but leads to higher pressure loss. Compared to other cases, Z-shaped serpentine MIMO channel presents the best cooling performance, reducing the maximum temperature value to 322.7 K.

Abstract Background Pathogenic variants of PAX2 cause autosomal-dominant PAX2-related disorder, which includes variable phenotypes ranging from renal coloboma syndrome (RCS), congenital anomalies of the kidney and urinary tract (CAKUT) to nephrosis. Phenotypic variability makes it difficult to define the phenotypic spectrum associated with genotype. Methods We collected the phenotypes in patients enrolled in the China national multicenter registry who were diagnosed with pathogenic variant in PAX2 and reviewed all published cases with PAX2-related disorders. We conducted a phenotype-based cluster analysis by variant types and molecular modeling of the structural impact of missense variants. Results Twenty different PAX2 pathogenic variants were identified in 32 individuals (27 families) with a diagnosis of RCS (9), CAKUT (11) and nephrosis (12) from the Chinese cohort. Individuals with abnormal kidney structure (RCS or CAKUT group) tended to have likely/presumed gene disruptive (LGD) variants (Fisher test, p

The lack of funding is one of the most important challenges in achieving the 2030 Sustainable Development Goals (SDGs) in African countries. Can foreign direct investment (FDI) from China as an important source of external financing help African countries achieve their SDGs? This study used the panel data random effects model to analyze the influence of China’s direct investment on SDG scores. Then, the study conducted the ordered probit model to examine the influence of FDI from China on the trend of achieving each SDG in Africa, with the SDGs being grouped into social, economic, and environmental dimensions. Results showed that China’s direct investment contributed to the achievement of SDGs in Africa. FDI from China positively influenced the SDG score in general and some of the 17 SDG scores including SDG 7 (Affordable and Clean Energy), SDG 8 (Decent Work and Economic Growth), SDG 9 (Industry, Innovation, and Infrastructure), SDG 12 (Responsible Consumption and Production), SDG 13 (Climate Action), and SDG 15 (Life on Land). The relationship between FDI from China and the trends for SDG 7, 8, 9, 11 (Sustainable Cities and Communities), and 14 (Life below Water) was significantly positive. However, the SDG scores above belonged to the economic and environmental dimensions, whereas FDI from China had no significant influence on the social-dimension SDG scores and trends. To further expand the scale of China’s direct investment, more investment scopes, particularly those in the social dimension, should be developed. Moreover, China–Africa cooperation should be deepened to create a good investment environment for the achievement of African countries’ SDGs and to facilitate China’s implementation of promoting the development of developing countries as mentioned in the 2030 Agenda of Sustainable Development and building the China–Africa community with a shared future.

Adverse intrauterine and early postnatal environment cause reduced nephron endowment and subsequent hypertension, chronic kidney disease (CKD). Exploring modifiable approaches is particularly important to alleviate the global burden of CKD. Enhanced glomerular progenitor cell apoptosis is a major contributor to renal developmental programming. The differentially expressed protein perlecan, which we previously identified using proteomics, is an important extracellular matrix glycoprotein, and its domain V (endorepellin) can inhibit apoptosis through a paracrine form. In explanted mice embryonic metanephros, we found that endorepellin can rescue glomeruli-deficit phenotype resulting from malnutrition, and this protective effect was also verified in vivo using a renal developmental programming model which was given a low-protein diet during pregnancy. We further demonstrated that endorepellin significantly inhibited glomerular progenitor cell apoptosis which activates ERK1/2 phosphorylation. Our results show that endorepellin rescues the nephron number reduction in renal developmental programming, possibly through the inhibition of progenitor cell apoptosis via the ERK1/2 pathway.

Background: Assessment of renal lesions and deficiency accurately remains critical in the diagnosis of congenital anomalies of the kidneys and urinary tracts (CAKUT) in children. Advanced imaging such as Magnetic resonance Imaging (MRI) and Diffusion weighted Imaging (DWI) allows structural and functional insufficiency to be detected. Currently, radiomics machine learning models are being explored as full-automated diagnostic tools. We aimed to develop a machine learning integrated radiomics model to predict renal anomalies and deficiency in children.Methods: A retrospective study of 280 children with MRI/DWI were enrolled between 2018 and 202 at a children’s hospital. A total of 1,037 radiomics features were extracted from the DWI images of each participant, which were divided into training set and test set (8:2 split). Using 5-fold cross-validated method, multiple machine learning algorithms were employed to predict renal lesions and deficiency when compared with the radiologist’s diagnosis based on DWI, 99mTc-labeled dimercaptosuccinic acid (DMSA) SPECT cortical renal scintigraphy or 99mTc-labeled diethylenetriamine pentaacetate (DTPA) renal scan.Results: For detecting the kidney lesions, the LASSO + Random Forest algorithm outperformed other classifiers with an accuracy of 0.750 (95% confidence interval, 0.734–0.766) and area under the curve (AUC) of 0.765 (95% confidence interval, 0.700–0.831). The performance of classifiers did not show a significant difference (p > 0.05) in detecting bilateral or unilateral kidney lesions by DWI scanning. The classifiers performed significantly better in bilateral kidney deficit than in unilateral kidney deficit (p < 0.05). We next built prediction models for renal deficiency using the radiomics signature and clinical features compared to renal scintigraphy. The ensemble model had a high-test accuracy of 80.9% ± 4.2% and a sensitivity of 91.7% ± 7.1% with a moderate calibration.Conclusion: An ensemble model integrated with DWI-radiomic and clinical features can be utilized to predict renal lesions and deficiency in children with CAKUT.

Abstract Determining the etiology of end-stage renal disease (ESRD) constitutes a great challenge in the context of renal transplantation. Evidence is lacking on the genetic findings for adult renal transplant recipients through exome sequencing (ES). Adult patients on kidney transplant waitlist were recruited from 2017 to 2019. Trio-ES was conducted for the families who had multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early onset or extrarenal features. Pathogenic variants were confirmed in 62 from 115 families post sequencing for 421 individuals including 195 health family members as potential living donors. Seventeen distinct genetic disorders were identified confirming the priori diagnosis in 33 (28.7%) families, modified or reclassified the clinical diagnosis in 27 (23.5%) families, and established a diagnosis in two families with ESRD of unknown etiology. In 14.8% of the families, we detected promising variants of uncertain significance in candidate genes associated with renal development or renal disease. Furthermore, we reported the secondary findings of oncogenes in 4.4% of the patients and known single-nucleotide polymorphisms associated with pharmacokinetics in our cohort to predict the drug levels of tacrolimus and mycophenolate. The diagnostic utility of the genetic findings has provided new clinical insight in most families that help with preplanned renal transplantation.

BackgroundCongenital anomalies of the kidneys and urinary tracts (CAKUT) represent the most prevalent cause for renal failure in children. The RNA epigenetic modification N6-methyladenosine (m6A) methylation modulates gene expression and function post-transcriptionally, which has recently been revealed to be critical in organ development. However, it is uncertain whether m6A methylation plays a role in the pathogenesis of CAKUT. Thus, we aimed to explore the pattern of m6A methylation in CAKUT.MethodsUsing m6A-mRNA epitranscriptomic microarray, we investigated the m6A methylomic landscape in the ureter tissue of children with obstructive megaureter (M group) and primary vesicoureteral reflux (V group).ResultsA total of 228 mRNAs engaged in multiple function-relevant signaling pathways were substantially differential methylated between the “V” and “M” groups. Additionally, 215 RNA-binding proteins that recognize differentially methylated regions were predicted based on public databases. The M group showed significantly higher mRNA levels of m6A readers/writers (YTHDF1, YTHDF2, YTHDC1, YTHDC2 and WTAP) and significantly lower mRNA levels of m6A eraser (FTO) according to real-time PCR. To further investigate the differentially methylated genes, m6A methylome and transcriptome data were integrated to identified 298 hypermethylated mRNAs with differential expressions (265 upregulation and 33 downregulation) and 489 hypomethylated mRNAs with differential expressions (431 upregulation and 58 downregulation) in the M/V comparison.ConclusionThe current results highlight the pathogenesis of m6A methylation in obstructive and reflux uropathy.

Nitride-based ceramic materials have excellent comprehensive properties such as high strength, high modulus, high temperature resistance, thermal shock resistance and wave-transparent performance. They are the main candidates for high-temperature wave-transparent components. The reports about their application are few, and the preparation technologies and properties need to be improved. In this paper, the research progress of nitride ceramics, nitride composite ceramics and nitride ceramic matrix composites was summarized. It is found that the comprehensive properties of porous Si3N4 ceramics, BN-Si3N4 composite ceramics and BNw/Si3N4 composites are excellent, with the dielectric constant less than 5, the dielectric loss less than 0.01, and the room-temperature flexural strength higher than 200 MPa, respectively. In this paper, the existing problems of the studies on the nitride-based ceramic as high-temperature wave-transparent materials were analyzed, which is mainly that the mechanical properties and dielectric properties are difficult to improve in coordination, and the future development direction of the selection of high-temperature wave-transparent material systems and preparation technologies are prospected.

Cellular and humoral immunity are both important in host defense against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although defects in SARS-CoV-2-specific T cell immunity have been found in patients with severe lung pathology, it is still largely unclear whether virus-specific T cells are sufficient for host protection. Here, we found that in a previously characterized cohort of convalescent subjects, one individual, though lacking detectable anti-viral neutralizing IgG antibodies, showed virus-specific T cell responses, both in CD4+ and CD8+ T cells. SARS-CoV-2-specific T cells in this and other individuals are maintained for up to 10 months. This study thus further supports a critical role of T cells in host defense against SARS-CoV-2, offering new insights into the design and evaluation of COVID-19 vaccines.

ObjectiveTo evaluate the value of ultrasound screening for congenital anomalies of the kidney and urinary tract (CAKUT) during the early postnatal period.MethodsThis is a prospective study that enrolled all neonates born from August 2019 to July 2020 at one medical center. Postnatal ultrasound screening was conducted in all neonates at 1, 3, and 6 months old, respectively. Information on antenatal detection and pregnancy was collected. We performed logistic regression analyses and established a predictive model to assess the potential risk factors of abnormal ultrasound screening results.ResultsPostnatal ultrasound scanning in 4,877 infants identified 268 cases (5.5%) of anomalies of kidney and urinary tract by primary screening and 92 cases (1.9%) by tertiary screening. A specific diagnosis was identified in 47 cases within the 6-month screening and follow-up program. Logistic regression revealed that preterm birth, oligohydramnios, antenatal ultrasound screening anomalies, and gestational hypothyroidism were independent risk factors for the early detection of CAKUT by postnatal ultrasound screening. The above factors were adopted to develop a predictive model that showed good calibration in predicting ultrasound findings of CAKUT. Decision curve analysis demonstrated good clinical utility.ConclusionsPostnatal ultrasound screening should be conducted in infants with risk factors associated with CAKUT. Further study on prenatal and fetal factors could help establish the predictive model for the early detection of CAKUT.

Chemical vapor deposition (CVD) is a new technology for preparing inorganic materials which possess some advantages, such as lower preparation temperature, uniform and compact microstructure, and near-size molding, so it is one of the common methods to prepare functional ceramics. In the paper, several common chemical vapor deposition methods like atmospheric chemical vapor deposition, low-pressure chemical vapor deposition, plasma-enhanced chemical vapor deposition and laser-assisted chemical vapor deposition are reviewed, because the microstructure and performance of functional ceramics are greatly influenced by their fabrication methods. In addition, the deposition parameters of Si-C-N absorbing ceramics which are deposited at lower temperature by low-pressure chemical vapor deposition are optimized. It is proposed that low-pressure chemical vapor deposition is the main method for preparing the advanced EMW absorbing ceramics.

Congenital nephrogenic diabetes insipidus (NDI) is a rare genetic disorder characterized by renal inability to concentrate urine. We utilized a multicenter strategy to investigate the genotype and phenotype in a cohort of Chinese children clinically diagnosed with NDI from 2014 to 2019. Ten boys from nine families were identified with mutations in AVPR2 or AQP2 along with dehydration, polyuria–polydipsia, and severe hypernatremia. Genetic screening confirmed the diagnosis of seven additional relatives with partial or subclinical NDI. Protein structural analysis revealed a notable clustering of diagnostic mutations in the transmembrane region of AVPR2 and an enrichment of diagnostic mutations in the C-terminal region of AQP2. The pathogenic variants are significantly more likely to be located inside the domain compared with population variants. Through the structural analysis and in silico prediction, the eight mutations identified in this study were presumed to be disease-causing. The most common treatments were thiazide diuretics and non-steroidal anti-inflammatory drugs (NSAIDs). Emergency treatment for hypernatremia dehydration in neonates should not use isotonic saline as a rehydration fluid. Genetic analysis presumably confirmed the diagnosis of NDI in each patient in our study. We outlined methods for the early identification of NDI through phenotype and genotype, and outlined optimized treatment strategies.

Abstract Background Psoriasis is a chronic inflammatory dermatosis with complex genetic basis supported by family investigation. Renal involvement in psoriasis is sparsely studied and its pathogenesis is still unclear. Methods and Results We describe the case of a 7‐year‐old boy presented new onset of nephropathy two weeks after a flare‐up of psoriasis. His mother had a long history of psoriasis without abnormal urinalysis records. The case showed non‐nephrotic range proteinuria, microscopic hematuria without any other abnormal results including renal function, complement cascade, and ultrasound. Renal pathological demonstrated the diagnosis of C3 glomerulonephritis (C3GN) showing mesangial proliferative glomerulonephritis with C3 staining only, effacement of podocyte process and intramembranous electron dense deposit by electric microscopy. Parent‐child trio WES performed to screening the common variants of psoriasis susceptibility locus and also the rare variants associated with C3GN. We identified a missense single nucleotide polymorphism of CARD14 (*607211, rs34367357, p.Val585Ile) carried by the proband and his mother. Meta‐analysis proved the association of rs34367357 and psoriasis (p = 0.006, OR = 1.23). A hemizygouse mutation of CLCN5 (*300008, c.1904A＞G,p.Asn635Ser) was identified for diagnosis of Dent disease (*300009). Conclusion The case highlights the genetic study is necessary to facilitate disease differentiation in new onset of nephropathy with psoriasis in children.

Low dimension poly(3,4-ethylenedioxythiophene) poly (styrenesulfonate) (PEDOT: PSS) has been applied as resistor-type devices for temperature sensing applications. However, their response speed and thermal sensitivity is still not good enough for practical application. In this work, we proposed a new strategy to improve the thermal sensing performance of PEDOT: PSS by combined micro/nano confinement and materials doping. The dimension effect is carefully studied by fabricating different sized micro/nanowires through a low-cost printing approach. It was found that response speed can be regulated by adjusting the surface/volume (S/V) ratio of PEDOT: PSS. The fastest response (

Herpetospermum pedunculosum (Ser.) C. B. Clarke (Family Cucurbitaceae) is a dioecious plant and has been used as a traditional Tibetan medicine for the treatment of hepatobiliary diseases. The component, content, and difference in volatile compounds in the female and male buds of H. pedunculosum were explored by using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology and multivariate statistical analysis. The results showed that isoamyl alcohol was the main compound in both female and male buds and its content in males was higher than that in females; 18 compounds were identified in female buds including 6 unique compounds such as (E)-4-hexenol and isoamyl acetate, and 32 compounds were identified in male buds, including 20 unique compounds such as (Z)-3-methylbutyraldehyde oxime and benzyl alcohol. (Z)-3-methylbutyraldehyde oxime and (E)-3-methylbutyraldehyde oxime were found in male buds, which only occurred in night-flowering plants. In total, 9 differential volatile compounds between female and male buds were screened out, including isoamyl alcohol, (Z)-3-methylbutanal oxime, and 1-nitropentane based on multivariate statistical analysis such as principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA). This is the first time to report the volatile components of H. pedunculosum, which not only find characteristic difference between female and male buds, but also point out the correlation between volatile compounds, floral odor, and plant physiology. This study enriches the basic theory of dioecious plants and has guiding significance for the production and development of H. pedunculosum germplasm resources.

Background/Aims: This study focused on investigating the expression of several inflammatory cytokines and chemokines, including regulatory proteins in the astrocytes of mice stimulated with IL-17. Materials and Methods: The cultured astrocytes from the spinal cords of mice were stimulated with IL-17. The expression of interleukin-6 (IL-6), tumor necrosis factor (TNF), monocyte chemotactic protein-1/5 (MCP-1/5) and macrophage inflammatory protein-2 (MIP-2) stimulated with IL-17 (50 ng/ml) at different time points (3 h, 6 h, 12 h, 24 h and 48 h) were determined using real-time PCR and ELISA. The expressions of A20 (tumor necrosis factor a inducible protein 3, TNFAIP3) and NF-κB were examined using real-time PCR and western blotting. Results: Compared with the control group, the mRNA expression levels of IL-6, TNF, MCP-1/5 and MIP-2 increased significantly at 6 h after IL-17 stimulation, while the protein expression levels also increased significantly and peaked at 12 h. The mRNA expression level of NF-κB increased and peaked at 6 h before gradually declining, while the expression of A20 decreased. The protein expression level of NF-κB increased and peaked at 12 h, while the expression A20 had an opposite response. Conclusion: The study showed that NF-κB may have an effect on the cytokines secreted by astrocytes after IL-17 stimulation. Moreover, both A20 and NF-κB could regulate the expression and secretion of inflammatory mediators.

Total internal reflection fluorescence (TIRF) microscopy has been widely used as a single molecule imaging technique to study various fundamental aspects of cell biology, owing to its ability to selectively excite a very thin fluorescent volume immediately above the substrate on which the cells are grown. However, TIRF microscopy has found little use in high content screening due to its complexity in instrumental setup and experimental procedures. Inspired by the recent demonstration of label-free evanescent wave biosensors for cell phenotypic profiling and drug screening with high throughput, we had hypothesized and demonstrated that TIRF imaging is also amenable to receptor pharmacology profiling. This paper reviews key considerations and recent applications of TIRF imaging for pharmacology profiling.

Nearly 1% of all clinically used drugs are catecholics, a family of catechol-containing compounds. Using label-free dynamic mass redistribution and Tango β-arrestin translocation assays, we show that several catecholics, including benserazide, catechol, 3-methoxycatechol, pyrogallol, (+)-taxifolin and fenoldopam, display agonistic activity against GPR35.

Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249.

Cell signaling mediated through a cellular target is encoded by spatial andtemporal dynamics of downstream signaling networks. The coupling of temporal dynamicswith spatial gradients of signaling activities guides cellular responses upon stimulation.Monitoring the integration of cell signaling in real time, if realized, would provide a newdimension for understanding cell biology and physiology. Optical biosensors includingresonant waveguide grating (RWG) biosensor manifest a physiologically relevant andintegrated cellular response related to dynamic redistribution of cellular matters, thusproviding a non-invasive means for cell signaling study. This paper reviews recentprogresses in biosensor instrumentation, and theoretical considerations and potentialapplications of optical biosensors for whole cell sensing.