Combined untargeted and targeted lipidomics approaches reveal potential biomarkers in type 2 diabetes mellitus cynomolgus monkeys.

BACKGROUND: The significantly increasing incidence of type 2 diabetes mellitus (T2DM) over the last few decades triggers the demands of T2DM animal models to explore the pathogenesis, prevention, and therapy of the disease. The altered lipid metabolism may play an important role in the pathogenesis and progression of T2DM. However, the characterization of molecular lipid species in fasting serum related to T2DM cynomolgus monkeys is still underrecognized. METHODS: Untargeted and targeted LC-mass spectrometry (MS)/MS-based lipidomics approaches were applied to characterize and compare the fasting serum lipidomic profiles of T2DM cynomolgus monkeys and the healthy controls. RESULTS: Multivariate analysis revealed that 196 and 64 lipid molecules differentially expressed in serum samples using untargeted and targeted lipidomics as the comparison between the disease group and healthy group, respectively. Furthermore, the comparative analysis of differential serum lipid metabolites obtained by untargeted and targeted lipidomics approaches, four common serum lipid species (phosphatidylcholine [18:0_22:4], lysophosphatidylcholine [14:0], phosphatidylethanolamine [PE] [16:1_18:2], and PE [18:0_22:4]) were identified as potential biomarkers and all of which were found to be downregulated. By analyzing the metabolic pathway, glycerophospholipid metabolism was associated with the pathogenesis of T2DM cynomolgus monkeys. CONCLUSION: The study found that four downregulated serum lipid species could serve as novel potential biomarkers of T2DM cynomolgus monkeys. Glycerophospholipid metabolism was filtered out as the potential therapeutic target pathway of T2DM progression. Our results showed that the identified biomarkers may offer a novel tool for tracking disease progression and response to therapeutic interventions.

Compression Therapy after Thermal Ablation of Varicose Veins: A Meta-Analysis.

OBJECTIVE: To investigate whether compression therapy after thermal ablation of varicose veins can improve the prognosis of patients. METHODS: Systematic research were applied for Chinese and English electronic databases(PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, VIP Databases). Eligible prospective studies that comparing the efficacy of compression therapy and non-compression therapy on patients after thermal ablation of varicose veins were included. The interest outcome such as pain, quality of life (QOL), venous clinical severity score (VCSS), time to return to work and complications were analyzed. RESULTS: 10 studies were of high quality, and randomized controlled trials involving 1,545 patients met the inclusion criteria for this study. At the same time, the meta-analysis showed that the application of compression therapy improved pain (SMD: -0.51, 95% CI: -0.95, -0.07) but exhibited no statistically significant effect on QOL (SMD: 0.04, 95% CI: -0.08, 0.16), VCSS (MD: -0.05, 95% CI: -1.19, 1.09), time to return to work (MD: -0.43, 95% CI: -0.90, 0.03), total complications (RR: 0.54, 95% CI: 0.27, 1.09), and thrombosis (RR: 0.71, 95% CI: 0.31, 1.62). CONCLUSION: Compression therapy after thermal ablation of varicose veins can slightly relieve pain, but it has not been found to be associated with improvement in other outcomes.

Association between BMI and osteoporotic fractures at different sites in Chinese women: a case-control retrospective study in Changsha.

BACKGROUND: Osteoporotic fractures are a growing problem in an aging society. The association between body mass index (BMI) and osteoporotic fractures varies by fracture site and ethnicity. Limited knowledge exists regarding this association in native Chinese, particularly utilizing local databases as reference sources. OBJECTIVE: To investigate the association between BMI and osteoporotic fractures at different sites in Chinese women. METHODS: Three thousand ninety-eight female patients with radiographic fractures and 3098 age- and sex-matched healthy controls without fractures were included in the study. Both of them underwent assessment using dual-energy X-ray absorptiometry (DXA), with BMD measurements calculated using our own BMD reference database. Participants were classified into underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24.0 kg/m2), overweight (24 ≤ BMI < 28 kg/m2) and obese (BMI ≥ 28 kg/m2) according to the Chinese BMI classification standard. RESULTS: There were 2296 (74.1%) vertebral fractures, 374 (12.1%) femoral neck fractures, and 428 (13.8%) other types of fractures in the case group. Bone mineral density (BMD) was almost lower in the fracture groups compared to the control groups (p = 0.048 to < 0.001). Compared with normal weight, underweight had a protective effect on total [odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.49 -0.75; P< 0.001], and lumbar fractures (OR = 0.52; 95% CI, 0.41 - 0.67; P < 0.001), while obesity was associated with an increased risk for total (OR = 2.26; 95% CI, 1.85 - 2.76; P < 0.001), lumbar (OR = 2.17; 95% CI, 1.72 - 2.73; P < 0.001), and femoral neck fractures (OR = 4.08; 95% CI, 2.18 - 7.63; P < 0.001). Non-linear associations were observed between BMI and fractures: A J-curve for total, lumbar, and femoral neck fractures, and no statistical change for other types of fractures. Underweight was found to be a risk factor for other types of fracturess after adjusting for BMD (OR = 2.29; 95% CI, 1.09 - 4.80; P < 0.001). Osteoporosis and osteopenia were identified as risk factors for almost all sites of fracture when compared to normal bone mass. CONCLUSIONS: Underweight has a protective effect on total and lumbar spine fractures in Chinese women, while obesity poses a risk factor for total, lumbar, and femoral neck fractures. The effect of BMI on fractures may be mainly mediated by BMD.

GGC Repeat Expansion of RILPL1 is Associated with Oculopharyngodistal Myopathy.

OBJECTIVE: Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ptosis, dysarthria, ophthalmoplegia, and distal muscle weakness. Recent studies revealed that GGC repeat expansions in 5'-UTR of LRP12, GIPC1, and NOTCH2NLC are associated with OPDM. Despite these advances, approximately 30% of OPDM patients remain genetically undiagnosed. Herein, we aim to investigate the genetic basis for undiagnosed OPDM patients in two unrelated Chinese Han families. METHODS: Parametric linkage analysis was performed. Long-read sequencing followed by repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to determine the genetic cause. Targeted methylation sequencing was implemented to detect epigenetic changes. The possible pathogenesis mechanism was investigated by quantitative polymerase chain reaction, immunoblotting, RNA fluorescence in situ hybridization, and immunofluorescence staining of muscle biopsy samples. RESULTS: The disease locus was mapped to 12q24.3. Subsequently, GGC repeat expansion in the promoter region of RILPL1 was identified in six OPDM patients from two families, findings consistent with a founder effect, designated as OPDM type 4. Targeted methylation sequencing revealed hypermethylation at the RILPL1 locus in unaffected individuals with ultralong expansion. Analysis of muscle samples showed no significant differences in RILPL1 mRNA or RILPL1 protein levels between patients and controls. Public CAGE-seq data indicated that alternative transcription start sites exist upstream of the RefSeq-annotated RILPL1 transcription start site. Strand-specific RNA-seq data revealed bidirectional transcription from the RILPL1 locus. Finally, fluorescence in situ hybridization/immunofluorescence staining showed that both sense and antisense transcripts formed RNA foci, and were co-localized with hnRNPA2B1 and p62 in the intranuclear inclusions of OPDM type 4 patients. INTERPRETATION: Our findings implicate abnormal GGC repeat expansions in the promoter region of RILPL1 as a novel genetic cause for OPDM, and suggest a methylation mechanism and a potential RNA toxicity mechanism are involved in OPDM type 4 pathogenesis. ANN NEUROL 2022;92:512-526.

Application value of EV/EV71/CA16-SAT detection in children with hand-foot-mouth disease.

The objective of this work was to explore the application value of a new type of fluorescent nucleic acid isothermal amplification (SAT) to detect EV/EV71/CA16-SAT in children with hand-foot-mouth disease (HFMD). For this purpose, from March 2017 to September 2019, Chengdu Children's Specialized Hospital collected throat swabs from children with clinical manifestations of hand, foot and mouth disease, and used SAT technology to screen and detect universal enterovirus (EV) nucleic acid (There were 1860 children with EV-RNA) positive. Patients who are EV-RNA positive at any time: first use the same throat swab specimen to detect EV71/CA16-RNA; secondly, collect venous blood and use the colloidal gold method to detect IgM antibodies in EV71/CA16 serum. The patients with positive EV71/CA16-RNA or EV71/CA16-IgM (or both) were repeated the above two methods 2 weeks and 4 weeks after standard treatment for review and comprehensive analysis. Results showed that 763 cases were enrolled for the first time: 59.76% were male and 40.24% were female; the age ranged from 1 month to 13 years, of which 69.06% were from 1 to 4 years old; CA16-RNA positive 56.23%, EV71-RNA positive 21.89%, CA16/EV71 -RNA were all positive in 1.57%; CA16-IgM was positive in 64.48%, EV71-IgM was positive in 54.26%, and CA16/EV71-IgM were both positive in 18.74%. After 2 weeks, 722 cases were reexamined: 26.73% were positive for CA16-RNA, 7.89% were positive for EV71-RNA, 0.28% were both positive for CA16/EV71-RNA; 66.21% were positive for CA16-IgM, 51.52% were positive for EV71-IgM, and IgM were all positive in 17.73%. Four weeks later, 489 cases were reexamined: among them, CA16-RNA positive 5.73% of which were positive for EV71 color RNA (0.005%), and 12.68% of them were all positive for EV71lym. The strategy of combining SAT technology and colloidal gold method to detect EV/EV71/CA16 nucleic acid (RNA) and serum IgM antibody in children HFMD can improve the early detection rate and accuracy of HFMD; According to the comprehensive analysis of the detection results of children with HFMD at the early stage, 2 weeks and 4 weeks of the present study, it is suggested that EV/EV71/CA16-SAT nucleic acid detection can be used to judge the prognosis, follow-up treatment, set isolation time, return students to school, and community management in children with HFMD. and prevention and control have more clinical application value.

Clinical effects of multi-oil versus pure soybean oil-based lipid emulsions for preterm infants: An observational study.

BACKGROUND AND OBJECTIVES: Conventional soybean oil-based intravenous lipid emulsions (SO-ILEs) have high polyunsaturated fatty acid (PUFA) contents and phytosterols that may have adverse effects in preterm infants. Recently, the multi-oil-based intravenous lipid emulsion (MO-ILE), SMOFlipid, has been widely utilized in the neonatal intensive care unit (NICU), but significant benefits over SO-ILEs in low gestational age neonates have yet to be demonstrated. This study was performed to compare the effects of the SO-ILE, Intralipid, and the MO-ILE, SMOFlipid, on neonatal health outcomes in preterm infants. METHODS AND STUDY DESIGN: We performed a retrospective review of preterm infants born at gestational week (GW) <32 receiving parenteral nutrition for longer durations (≥14 d) in the NICU between 2016 and 2021. The primary aim of this study was to investigate differences in morbidity between preterm infants receiving SMOFlipid and Intralipid. RESULTS: A total of 262 preterm infants were included in the analysis, with 126 receiving SMOFlipid and 136 receiving Intralipid. The SMOFlipid group had lower rates of ROP (23.8% vs 37.5%, respectively; p=0.017), although the rate of ROP was not different in multivariate regression analysis. The length of hospi-tal stay was significantly shorter in the SMOFlipid than SO-ILE group (median [IQR]=64.8 [37] vs 72.5 [49] days; p<0.001). CONCLUSIONS: The use of SMOFlipid as the lipid emulsion was associated with higher clinical efficacy than SO-ILE in preterm infants.

Post-traumatic growth in caregivers of children hospitalized in the PICU due to traffic accident: a qualitative study.

BACKGROUND: Globally, tens of millions of children are hospitalized every year for non-fatal traffic accident injuries, being confronted with an injured child can be extremely stressful for parents. Understandably, a significant level of psychological distress may ensue. Traumatic losses may lead parents to find new insights in life and develop a greater sense of spirituality and strength. METHOD: Semi-structured interviews were conducted with caregivers of children who were hospitalized in the pediatric intensive care unit (PICU) with traffic accident injuries at children's hospitals in China between January and June 2022. Caregivers were selected using a purposive sampling method until no new data were generated (n = 24). RESULTS: We identified eleven sub-themes and four higher-order themes based on these sub-themes: (1) changes in their life philosophy, (2) personal strength enhancement, (3) relationship improvements, and (4) effective responses. The findings of our research contribute to a better understanding of the psychological status of the caregivers of children injured by traffic accidents. CONCLUSION: Professionals should guide caregivers from a positive perspective, stimulate their strengths and potential, increase personnel support and communication, promote positive coping, formulate targeted management countermeasures to improve the PTG level of caregivers, and develop strategies to maintain stable mental health and well-being.

LncRNA XIST facilitates S1P-mediated osteoclast differentiation via interacting with FUS.

INTRODUCTION: The diagnosis and treatment of osteoporosis, a frequent age-related metabolic bone disorder, remain incomprehensive and challenging. The potential regulatory role of lncRNA XIST and sphingosine kinase 1 (SPHK1) pathway need experimental investigations. MATERIALS AND METHODS: RAW264.7 cells and BMMs were obtained for in vitro studies and 30 ng/mL RANKL was implemented for induction of osteoclast differentiation. The suppressing of lncRNA XIST, SPHK1 and fused in sarcoma (FUS) was achieved using small hairpin RNA, while overexpression of XIST and FUS was constructed by pcDNA3.1 vector system. Tartrate-resistant acid phosphatase (TRAP) staining was used for observation of formation of osteoclasts. RNA-pulldown analysis and RNA binding protein immunoprecipitation (RIP) was implemented for measuring mRNA and protein interactions. RT-qPCR was conducted to determining mRNA expression, whereas ELISA and Western blotting assay was performed for monitoring protein expression. RESULTS: RANKL induced osteoclast differentiation and upregulated expression of osteoclastogenesis-related genes that included NFATc1, CTSK, TRAP and SPHK1 and the level of lncRNA XIST in both RAW264.7 cells and BMMs. However, knockdown of lncRNA XIST or suppressing SPHK1 significantly reserved the effects of RANKL. LncRNA XIST was further demonstrated to be interacted with FUS and increased the stability of SPHK1, indicating its ability in promoting osteoclast differentiation through SPHK1/S1P/ERK signaling pathway. CONCLUSION: LncRNA XIST promoted osteoclast differentiation via interacting with FUS and upregulating SPHK1/S1P/ERK pathway.

QTL mapping of the genetic basis of stem diameter in soybean.

MAIN CONCLUSION: QTL mapping of stem diameter was carried out in three RIL populations using a high-density genetic map, and candidate genes related to stem diameter were predicted. Stem diameter is an important agronomic trait affecting soybean lodging and productivity. However, this trait is underexploited, and the underlying genetic mechanism in soybean remains unclear. In this study, three recombinant inbred line (RIL) populations, including 156 F10 lines from Nannong 94-156 × Bogao (N × B), 127 F9 lines from Dongnong 50 × Williams 82 (D × W), and 146 F9 lines from Suinong 14 × Enrei (S × E), were used to identify QTLs for soybean stem diameter across multiple environments. Phenotype analysis revealed that stem diameter exhibited strong positive correlations with plant height and 100-seed weight, two of the most important yield components. A total of 12 QTLs for stem diameter were identified on eight chromosomes across three RIL populations and five environments. The most influential QTL that was stably identified across all the populations and environments, q11, explained 12.58-26.63% of the phenotypic variation. Detection of several environment-specific QTLs, including q14, q16, and q20, suggests that environments may also have important effects in shaping the natural variation in soybean stem diameter. Furthermore, we predicted candidate genes underlying the QTLs and found that several promising candidate genes may be responsible for the variation in stem diameter in soybean. Overall, the markers/genes linked closely or underlying the major QTLs may be used for marker-assisted selection of soybean varieties to enhance lodging resistance and even yield. Our results lay the foundation for the fine mapping of stem development-related genes to reveal the molecular mechanisms.

The effect of gemcitabine combined with AMD3100 applying to cholangiocarcinoma RBE cell lines to CXCR4/CXCL12 axis.

PURPOSE: To evaluate the effect of AMD3100 treatment to cholangiocarcinoma by analyzing the relationship between them, and provide experimental evidence for whether AMD3100 can become a clinical treatment drug for cholangiocarcinoma. MATERIALS AND METHODS: Cholangiocarcinoma RBE cell lines were used in this study. MTT cell proliferation test was used for evaluating the effect of gemcitabine and AMD3100 to cell. CXCR4, N-cadherin, VEGF-C and MMP-9 were detect by RT-PCR and western. Transwell was used for evaluating the invasion effect. RESULTS: We demonstrated that as the concentration of gemcitabine increasing from 0.33, 3.33 to 33.33 uM, the cell survival rate was 76.65%, 71.40%, 52.25%, respectively. RT-PCR and Western blot that gemcitabine could affect the expression of CXCR4 protein and the level of mRNA transcription in a dose-dependent manner. N-cadherin VEGF-C, MMP-9 mRNA transcription level showed a significant upward trend in gemcitabine group. In Transwell test, the number of cells in the gemcitabine group was significantly higher than that in the no-medication group (p < .05), the AMD3100 group and the combination group of gemcitabine and AMD3100, the difference between the no-medication group and the AMD3100 monotherapy group was not significant, and the combination group was between them. CONCLUSIONS: This study showed that gemcitabine significantly inhibited the growth of cholangiocarcinoma RBE cells in a dose-dependent manner, and gemcitabine can affect the expression of CXCR4, N-cadherin, VEGF-C, MMP-9 protein and mRNA. Cell invasion and metastasis-related factors decreased after AMD3100 combined with gemcitabine.

Ultrasonography to detect cardiovascular damage in children with essential hypertension.

BACKGROUND: Essential hypertension in adults may begin in childhood. The damages to the heart and blood vessels in children with essential hypertension are hidden and difficult to detect. We noninvasively examined changes in cardiovascular structure and function in children with hypertension at early stage using ultrasonography. METHODS: All patients with essential hypertension admitted from March 2020 to May 2021 were classified into simple hypertension (group 1, n = 34) and hypertension co-existing with obesity (group 2, n = 11) isolation. Meanwhile 32 healthy children were detected as control heathly group (group 3). We used pulse-wave Doppler to measure carotid-femoral pulse wave velocity (cfPWV), intimal-medial thickness (cIMT) and distensibility of carotid artery (CD). Cardiac structure and function (left atrial diameter [LAD], left ventricular mass [LVM], LVM index [LVMI], relative wall thicknes [RWT], end-diastolic left ventricular internal diameter [LVIDd], diastolic interventricular septum thickness [IVSd], diastolic left ventricular posterior wall thickness [LVPWd], root diameter of aorta [AO], E peak, A peak, E' peak, A' peak, E/E' ratio, and E/A ratio) were measured by echocardiography. RESULTS: The cfPWV of children in group 1 and group 2 were significantly higher than healthy children in group 3. Significant differences were observed in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak, and E/E' among three groups. CONCLUSION: Children and adolescents with essential hypertension demonstrate target organ damages in the heart and blood vessels.

Metallization and superconductivity in methane doped by beryllium at low pressure.

As one of the simplest hydrocarbons, methane (CH4) has great potential in the research of superconductors. However, the metallization of CH4 has been an issue for a long time. Here, we report the structure, metallization, and superconductivity of CH4 doped by Be at low pressures, based on first-principles calculations. The result shows that the thermodynamically stable BeCH4 with P1[combining macron] space-group can transform into a metal at ambient pressure. This ternary hydride BeCH4 exhibits a superconductivity of ∼6 K below 25.6 GPa. Interestingly, the superconducting critical temperature of BeCH4 can reach ∼30 K at 80 GPa in the form of an a-P1 space-group phase. The charge transfer from Be to CH4 molecules plays an important role in the superconductivity. Our results present a novel way to realize the metallization of methane at relative pressures and indicate that the doped methane is a potential candidate for seeking high temperature and low pressure superconductivity.

Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway.

Microglia-mediated neuroinflammation is a crucial risk factor for neurological disorders. Recently, dopamine receptors have been found to be involved in multiple immunopathological processes and considered as valuable therapeutic targets for inflammation-associated neurologic diseases. In this study we investigated the anti-neuroinflammation effect of isosibiricin, a natural coumarin compound isolated from medicinal plant Murraya exotica. We showed that isosibiricin (10-50 µM) dose-dependently inhibited lipopolysaccharide (LPS)-induced BV-2 microglia activation, evidenced by the decreased expression of inflammatory mediators, including nitrite oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). By using transcriptomics coupled with bioinformatics analysis, we revealed that isosibiricin treatment mainly affect dopamine receptor signalling pathway. We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. Treatment with dopamine D1/2 receptor antagonists SCH 23390 (1 µM) or sultopride (1 µM) could reverse the inhibitory effects of isosibiricin on NLRP3 expression as well as the cleavages of caspase-1 and IL-1ß. Collectively, this study demonstrates a promising therapeutic strategy for neuroinflammation by targeting dopamine D1/2 receptors.

Highly selective inhibition of IMPDH2 provides the basis of antineuroinflammation therapy.

Inosine monophosphate dehydrogenase (IMPDH) of human is an attractive target for immunosuppressive agents. Currently, small-molecule inhibitors do not show good selectivity for different IMPDH isoforms (IMPDH1 and IMPDH2), resulting in some adverse effects, which limit their use. Herein, we used a small-molecule probe specifically targeting IMPDH2 and identified Cysteine residue 140 (Cys140) as a selective druggable site. On covalently binding to Cys140, the probe exerts an allosteric regulation to block the catalytic pocket of IMPDH2 and further induces IMPDH2 inactivation, leading to an effective suppression of neuroinflammatory responses. However, the probe does not covalently bind to IMPDH1. Taken together, our study shows Cys140 as a druggable site for selectively inhibiting IMPDH2, which provides great potential for development of therapy agents for autoimmune and neuroinflammatory diseases with less unfavorable tolerability profile.

Meta-analysis of vitamin D and lung function in patients with asthma.

BACKGROUND: There is growing literature suggesting a link between vitamin D and asthma lung function, but the results from systematic reviews are conflicting. We conducted this meta-analysis to investigate the relation between serum vitamin D and lung function in asthma patients. METHODS: Major databases, including OVID, MEDLINE, Web of Science and PUBMED, were searched until 10th October 2018. All published observational studies related to vitamin D and asthma were extracted. All meta-analyses were performed using Review Manager 5.3.5. RESULTS: This quantitative synthesis found that asthma patients with low vitamin D levels had lower forced expiratory volume In 1 s (FEV1) (mean difference (MD) = - 0.1, 95% CI = - 0.11 to - 0.08,p < 0.01;I2 = 49%, p = 0.12) and FEV1% (MD = - 10.02, 95% CI = - 11 to - 9.04, p < 0.01; I2 = 0%, p = 0.82) than those with sufficient vitamin D levels. A positive relation was found between vitamin D and FEV1 (r = 0.12, 95% CI = 0.04 to 0.2, p = 0.003; I2 = 59%,p = 0.01), FEV1% (r = 0.19, 95% CI = 0.13 to 0.26, p < 0.001; I2 = 42%, p = 0.11), forced vital capacity (FVC) (r = 0.17, 95% CI = 0.00 to 0.34, p = 0.05; I2 = 60%, p = 0.04), FEV1/FVC (r = 0.4, 95% CI = 0.3 to 0.51, p < 0.001; I2 = 48%, p = 0.07), and the asthma control test (ACT) (r = 0.33, 95% CI = 0.2 to 0.47, p < 0.001; I2 = 0%, p = 0.7). Subgroup analysis indicated that the positive correlation between vitamin D and lung function remained significant in both children and adults. CONCLUSIONS: Our meta-analysis suggested that serum vitamin D levels may be positively correlated with lung function in asthma patients. Future comprehensive studies are required to confirm these relations and to elucidate potential mechanisms.

Kawasaki disease OX40-OX40L axis acts as an upstream regulator of NFAT signaling pathway.

BACKGROUND: We investigated a costimulatory molecule OX40-OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD). METHODS: One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively. RESULTS: The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group. CONCLUSION: OX40-OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.

Anti-inflammatory pterocarpanoids from the roots of Pongamia pinnata.

A phytochemical study on the roots of Pongamia pinnata afforded 11 pterocarpanoids, including three new compounds. The structures of the isolated compounds were determined by 1D and 2D NMR and HRESIMS data. The absolute configurations of the new compounds were assigned via analysis of the specific rotations and electronic circular dichroism (ECD) spectra. The isolates were evaluated for their inhibitory effects on nitric oxide (NO) production in LPS-stimulated BV-2 microglial cells. Six compounds exhibited inhibitory effects against NO production, and compound 5 showed the best activity with an IC50 value at 12.0 µM.

High performance ultra-compact SOI waveguide crossing.

Waveguide crossing is an important integrated photonic component that will be routinely used for high-density and large-scale photonic integrated circuits, such as optical switches and routers. Several techniques have been reported in achieving high performance waveguide crossings on a silicon-on-insulator photonic platform, i.e., low-loss and low-crosstalk waveguide crossings based on multimode interference, bi-layer tapering, optical transformation, metamaterials, and subwavelength gratings. Until recently, not much attention has been given to the reduction of the footprint of waveguide crossings. Here we experimentally demonstrate an ultra-compact waveguide crossing on silicon photonic platform with a footprint only ~1 × 1 µm2. Our simulations show that it has a low insertion loss (< 0.175 dB) and low crosstalk (< -37dB) across the whole C-band, while the fabricated one has an insertion loss < 0.28 dB and crosstalk around -30 dB for the C-band.

Evaluation of Multislice Spiral Computed Tomography Perfusion Imaging for the Efficacy of Preoperative Concurrent Chemoradiotherapy in Middle-aged and Elderly Patients with Locally Advanced Gastric Cancer.

BACKGROUND This study aimed to investigate the predictive value of multislice spiral computed tomography (MSCT) perfusion imaging for the efficacy of preoperative concurrent chemoradiotherapy (CCRT) in middle-aged and elderly patients with locally advanced gastric cancer (LAGC). MATERIAL AND METHODS One-hundred twenty-six middle-aged and elderly patients with LAGC were selected. MSCT was performed before and after CCRT to obtain perfusion parameters: blood flow volume (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS). After CCRT, according to Response Evaluation Criteria in Solid Tumors (RECIST), patients were categorized into the effective group and the ineffective group. Overall survival rate was measured by Kaplan-Meier analysis. ROC curve was applied to evaluate the predictive value of perfusion parameters. Multiple logistic regression analysis was applied to analyze the association of perfusion parameters with the efficacy of preoperative treatment. RESULTS Tumor volume reduction rates of the effective and ineffective groups were 59.23±8.53% and 10.41±3.36%. BF, BV, and PS values in the effective group were significantly decreased after CCRT. ROC curves indicated high sensitivities and specificities of BF value (79.00%, 73.44%), BV value (71.00%, 75.00%), and PS value (82.30%, 90.63%). The incidence rate of weakness and anorexia in the effective group was much higher than that in the ineffective group. Patients with low BF, BV, and PS values (less their optimal cutoff values) had longer survival times than these with high BF, BV, and PS values. CONCLUSIONS MSCT might have predictive values for the efficacy of preoperative CCRT in the treatment of LAGC.

Pyrrolo[2,1-a]isoquinoline and pyrrole alkaloids from Sinomenium acutum.

Two pyrrolo[2,1-a]isoquinolines (1 and 2) and three pyrrole alkaloids (3-5), including three new ones, named sinopyrines A-C (1-3), were isolated from the 95% EtOH extract of the stems and rhizomes of Sinomenium acutum (Thumb.) Rehd. et Wils. The structures of the new compounds were elucidated on the basis of spectroscopic data. This is the first report of pyrrole-bearing natural compounds from the family Menispermaceae.