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Emvododstat is a potent inhibitor of dihydroorotate dehydrogenase and is now in clinical development for the treatment of acute myeloid leukaemia and COVID-19. Following an oral dose administration in Long-Evans rats, 14C-emvododstat-derived radioactivity was widely distributed throughout the body, with the highest distribution in the endocrine, fatty, and secretory tissues and the lowest in central nervous system. Following a single oral dose of 14C-emvododstat in rats, 54.7% of the dose was recovered in faeces while less than 0.4% of dose was recovered in urine 7 days post-dose. Emvododstat was the dominant radioactive component in plasma and faeces. Following a single oral dose of 14C-emvododstat in dogs, 75.2% of the dose was recovered in faeces while 0.5% of dose was recovered in urine 8 days post-dose. Emvododstat was the dominant radioactive component in faeces, while emvododstat and its two metabolites (O-desmethyl emvododstat and emvododstat amide bond hydrolysis product) were the major circulating radioactivity in dog plasma. [ABSTRACT FROM AUTHOR]

To date, there has been little study of comparison between picosecond 532 nm laser and 755 nm Q-switched Alexandrite lasers in the treatment of freckles. To evaluate the efficacy and safety of picosecond 532 nm laser (PS 532) and 755 nm Q-switched Alexandrite laser (QSAL) for treatment of freckles in a split-face manner. Eighteen patients with freckles were enrolled in the study. The right and left sides of their faces were randomly assigned to either a QSAL-treated group or PS 532-treated group. The degree of pain, satisfaction with the results, and adverse events associated with the laser treatment were evaluated using a questionnaire. All of the patients were followed up at 4 and 12 weeks after one treatment session. Among the 18 patients, PS 532 was found to be associated with less pain (3.56 ± 2.431) than QSAL (3.94 ± 1.893), but the difference was not statistically significant. The curative effect and satisfaction associated with 755 nm Q-switched Alexandrite laser was greater than that of picosecond 532 nm laser (P <.001). Both picosecond 532 nm laser and QSAL are effective in the treatment of freckles, and QSAL has a greater rate of satisfaction and curative effect. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical manifestations, magnetic resonance imaging (MRI) features, and prognosis of patients diagnosed with bilateral cerebral peduncular infarction (BCPI) with the 'Mickey Mouse ears' sign. Methods: This study, retrospectively summarized the clinical features, MRI and magnetic resonance angiography (MRA) manifestations, and prognosis of 5 patients diagnosed with BCPI and with the 'Mickey Mouse ears' sign from our hospital. In the meantime, we also systematically analyzed and summarized the clinical and imaging features, and prognosis in combination with relevant cases from the national and international literature that had been reported. Results: In our study, five cases presented tetraplegia whereas 4 cases presented disturbance of consciousness. In all cases, the 'Mickey Mouse ears' sign was observed in the mid-brain level using a diffusion-weighted imaging (DWI) cross-section. The MRA images showed thrombosis on either the basilar artery (BA), posterior cerebral artery (PCA), or superior cerebellar artery (SCA). All the studied patients received standardized treatment for cerebral infarction. However, three patients died and the remaining two were left in a locked-in syndrome state. Conclusions: BCPI is a very rare stroke disease and its main clinical manifestations are locked-in syndrome and persistent vegetative states. However, the obtained imaging features on the brain-MRI of patients diagnosed with BCPI with the 'Mickey Mouse ears' sign can predict a bad prognosis. [ABSTRACT FROM AUTHOR]

Two new benzoic acid derivatives (1–2), together with four known compounds (3–6) have been isolated from the n-BuOH soluble fraction of ethanolic extract from Ailanthus altissima. The gross structures of the new compounds were deduced by detailed spectroscopic analysis including HRESIMS and 1D/2D NMR spectroscopy. The stereochemistry of 1 was determined by modified Mosher's method. All compounds were evaluated for their neuroprotective effects against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells and none of them displayed obvious neuroprotective activities. [ABSTRACT FROM AUTHOR]

Electrical resistivity of sedimentary rock-soil is highly variable and governed mainly by a wide range of properties including resistivities of both solid matrix and fluid, cracks or pores, fluid saturation, and crack fabric (e.g. crack shape and alignment). An anisotropic, three-phase, effective medium resistivity model is proposed in this article to describe the resistivity of cracked rock-soil medium of sediments in macroscale. The resistivities of both solid matrix and fluid are assumed to be isotropic. Anisotropic features are therefore caused by cracks. The model permits both solid and fluid phases to have arbitrary range of resistivity. We derive the differential form between resistivity changes and crack changes. Expressions of the volumetric sensitivity and saturation sensitivity are obtained. An amplification matrix is defined to describe the anisotropic changes in resistivity. The three electrical principle axes have different volumetric sensitivity. Therefore, the resistivity shows anisotropic changes when the cracks change. For water-bearing rock and soil medium, the minimum electrical axis is most sensitive to crack changes. However, the anisotropic changes of anhydrous rocks are not obvious. Apparent resistivity has been continuously monitored at fixed stations in China for more than 50 years, using Schlumberger arrays. Apparent resistivity monitored in the direction perpendicular or nearly perpendicular to the maximum principal stress axis has recorded the maximum magnitude of changes before earthquakes. While the magnitude is minimum when apparent resistivity is monitored in the direction parallel or sub-parallel to the axis. There is an angle difference of π / 2 between the resistivity changes and the apparent resistivity changes for Schlumberger array. The analytic results of anisotropic changes based on the model agree with the field monitoring results. [ABSTRACT FROM AUTHOR]

Maize pre-cultivation was hypothesised to alleviate soil deterioration in replanted apple orchard, and this would be expected to be reflected in the nematode community in the soil. To test this hypothesis, soil parameters and nematode population composition were measured. Compared with replanted apple treatment, soil pH, soil organic matter, ammonium nitrogen and the available P and K content of the soil were enhanced after maize pre-planting cultivation. Maize pre-cultivation increased bacterivorous nematode populations and decreased herbivorous nematode populations, mainly Pratylenchus, Paratylenchus and Tylenchus spp. The Shannon-Weaver diversity index (H′) and the richness (SR) of the nematode population, the Wasilewska functional index (WI) (soil health index) and the maturity index (MI) were increased at the flowering stage after 2-year maize pre-planting treatment, and WI was increased at the maturity stage compared with replanted apple treatment. These results indicate that maize pre-cultivation can alleviate soil acidification and deterioration of the physicochemical properties of soil and improve soil health, food web stability and soil ecosystem sustainability in replanted apple orchard. These changes are accompanied by changes in the soil nematode communities. [ABSTRACT FROM AUTHOR]

The sea-land telluric current vector and its continuity during two geomagnetic storms are discussed using observation data of 13 geoelectric field stations within 100 km of the coastline in China and 5 similar stations in Canada. The results show that the amplitude of the geoelectric field varies up to 300–2600 mV/km at high latitudes and in the range 100–300 mV/km at low latitudes, below 100 mV/km at the middle latitudes, when the two geoelectric storms loading. The energy spectra of geoelectric field at RES in Canada is found to be concentrated in 16–48 min, and at CHL in China concentrated in 64–128 min. The telluric current flows directly to sea from the coastal land, except the two land-type stations with particular electrical structures. The sea-land current continuity model which was set up based on geological and geophysical data to deduce vertical circulation of current channels in continental and marginal seas area, which can explain the different current orientations in different regions. Our detailed analysis show that the direction of telluric current of Island stations is related to the deposition and river erosion and controlled by ocean currents during monsoon, are also included by the model. At last, the sea-land telluric current continuity model provides well understanding for the constraints of conductivity on the sea-land interface. [ABSTRACT FROM AUTHOR]

Little is known about how young high-tech ventures create openness in their knowledge networks. This paper explores the influence of antecedent resources on openness in knowledge networks, seen as diversity in knowledge partners, and explores the impact of openness on growth. The results from 105 university spin-off firms suggest that three antecedents positively influence openness, namely, founders’ prestart experience, education and innovation experience, and one negatively, namely, size of the founding team. Regarding non-linearity, there are signs of cubic influences, potentially in line with passing critical junctures. In addition, external factors tend to have no influence on openness, except for region of location. Further, shaping the right amount of openness and benefitting from it seem a struggle, as an increasing openness tends to influence growth with decreasing returns. [ABSTRACT FROM AUTHOR]

A new hydraulically interconnected inerter-spring-damper suspension (HIISDS) is developed to compensate for traditional passive suspension limitations, such as the imbalance of ride performance and handling stability. In this article, the structure and mechanism of the HIISDS system is briefly introduced at first, and compiled with hydraulically interconnected suspension (HIS) mode and hydraulic inerter-spring-damper (ISD) suspension mode. A vehicle dynamic model of HIISDS system is then derived through these two suspension modes by using Matlab/Simulink. Two different road excitations are used to validate the adaption of the two suspension modes. The effectiveness of HIISDS has been verified by simulation results, in which vehicle ride comfort and handling stability are effectively coordinated through the HIISDS model switch. Finally, an HIISDS suspension prototype is designed based on Simulink results, and test results reconfirm the partial performances of HIISDS modes effectively. [ABSTRACT FROM PUBLISHER]

The micro-cavities in the optical fiber by femtosecond laser direct writing in the water is investigated in this paper. The micro-cavity fabricated under different conditions such as laser pulse energies and translation speeds are discussed, and the optimal parameters are investigated for a particular application. The method of femtosecond laser induced water breakdown provided an alternative solution for high quality micro-structure fabrication. [ABSTRACT FROM PUBLISHER]

Disasters have substantial negative impacts on the transportation system performance. To be resilient, transportation systems should recover quickly and function effectively after disasters. However, reconstruction of road links has to be implemented as a multistage procedure due to limited budget. Hence, guidance needs to be provided on when and where to reconstruct to maintain high system performance during the recovery period. This article proposes a novel multi-stage network design model for identifying the optimal reconstruction sequence that maximizes the resilience of transportation networks with budget constraints. To achieve this, resilience is quantified as the sum of the recovery ratios of system performance during reconstruction. A day-to-day traffic assignment model and a logit-based loading model are integrated to describe the traffic flow evolution during reconstruction. The model is implemented on two test transportation networks. The results show that the optimal reconstruction sequence leads to the most significant improvement in postdisaster performance. Stability analysis indicates that effective traffic control strategies are necessary to ensure the flow stability during reconstruction. [ABSTRACT FROM AUTHOR]

Objectives: Estrogen regulates a wide variety of nonreproductive functions in the central nervous system. Cortical neurons contain a diverse range of voltage-gated ion channels, including calcium (Ca2+) channels, and Ca2+ channels play an important role in the regulation of action potential generation and neuronal excitability. In this study, the effect of estradiol (E2) on high-voltage-activated (HVA) Ca2+ channels in cultured rat cortical neurons was examined. Methods: We used the whole-cell patch-clamp technique to measure the HVA Ca2+ channels. Results: We found that HVA Ca2+ channel currents was inhibited by 17β-E2 in a rapid, reversible and concentration-dependent manner. Moreover, 17β-E2 shifted the steady-state inactivation curve in the hyperpolarizing direction without changing the activation curve. We also found that the inhibitory effects of 17β-E2 on Ca2+ currents were unaffected by the estrogen receptor (ER) antagonist ICI 182780; however, the protein kinase C (PKC) inhibitor rottlerin and protein kinase A (PKA) inhibitor H-89 blocked the 17β-E2-induced inhibition of Ca2+ currents. Conclusions: E2 inhibited HVA Ca2+ currents via PKC and PKA-dependent signaling pathway in cortical neurons, and the effects of BPA were independent of classical ER. [ABSTRACT FROM AUTHOR]

Objectives: Estrogen regulates a wide variety of nonreproductive functions in the central nervous system. Cortical neurons contain a diverse range of voltage-gated ion channels, including calcium (Ca2+) channels, and Ca2+ channels play an important role in the regulation of action potential generation and neuronal excitability. In this study, the effect of estradiol (E2) on high-voltage-activated (HVA) Ca2+ channels in cultured rat cortical neurons was examined. Methods: We used the whole-cell patch-clamp technique to measure the HVA Ca2+ channels. Results: We found that HVA Ca2+ channel currents was inhibited by 17β-E2 in a rapid, reversible and concentration-dependent manner. Moreover, 17β-E2 shifted the steady-state inactivation curve in the hyperpolarizing direction without changing the activation curve. We also found that the inhibitory effects of 17β-E2 on Ca2+ currents were unaffected by the estrogen receptor (ER) antagonist ICI 182780; however, the protein kinase C (PKC) inhibitor rottlerin and protein kinase A (PKA) inhibitor H-89 blocked the 17β-E2-induced inhibition of Ca2+ currents. Conclusions: E2 inhibited HVA Ca2+ currents via PKC and PKA-dependent signaling pathway in cortical neurons, and the effects of BPA were independent of classical ER. [ABSTRACT FROM AUTHOR]

The poly(methyl methacrylate/butyl acrylate/acrylic acid) [P(MMA/BA/AA)] and poly (styrene/butyl acrylate/acrylic acid) [P(St/BA/AA)] latexes were synthesized using the emulsifier octylphenol polyoxyethylene(10) ether (OP-10) and ammonium sulfate allyloxy nonylphenoxy poly(ethyleneoxy)(10) ether(DNS-86). The optimum amount of OP-10 and DNS-86 was 1.5% and 2.5% respectively. The P(MMA/BA/AA) and P(St/BA/AA) latex containing 1.5% OP-10 or 2.5% DNS-86 were blended pairwise. The performances of latex blends and parent latexes as a function of emulsifiers content in parent latexes were determined. The results indicated that the stability of latex blends is favorable, and particle size distribution was more uniform and thermal stability was improved after blending. [ABSTRACT FROM AUTHOR]

Epoxy resin is a commonly used material in the manufacture of tissue-equivalent phantoms. The complex refractive index (RI) of a series of epoxy resin phantoms with different scattering ability was measured using a recently developed extended derivative total reflection method (EDTRM). Al2O3 particles were added into the epoxy resin substrate as the scattering constituent. An increase of the real and imaginary part of the RI with the amount of Al2O3 particles was observed. The real part of the RI values reached an impressive precision of 0.002 using EDTRM, which provides a means for the improvement in accuracy for analysis related to RI values in phantom studies. [ABSTRACT FROM PUBLISHER]

In this work, microwave-assisted extraction (MAE) followed by gas chromatography with flame ionization detector (GC-FID) was developed for the rapid determination of camphor and borneol in three traditional Chinese medicines (TCM): Chrysanthemi indici, Flos Chrysanthemi indici and Amomum villosum lour. The optimal MAE conditions obtained were: acetone for solvent, with solvent having sample ratio of 12:1 (v/w); microwave power of 380 W, and an irradiation time of 4 min. Method validations were also studied. To demonstrate the proposed method, ultrasonic-assisted extraction (UAE) and steam distillation (SD), followed by GC-FID, were used to analyze camphor and borneol in thethree TCMs. The close results were obtained by the three methods. The results showed that the proposed MAE-GC-FID is a simple, rapid, and reliable method for quantitative analysis of camphor and borneol in TCM, and is also a potential tool for TCM quality assessment. [ABSTRACT FROM AUTHOR]

ObjectiveMethodsResultsConclusionThe objective of this study was to explore the associations between a family history of type 2 diabetes (T2D) and beta-cell function, as well as lipid profile, in pediatric patients newly diagnosed with type 1 diabetes (T1D).A retrospective analysis was conducted on children under 14 years of age who were newly diagnosed with T1D at the Children’s Hospital of Zhejiang University between August 2018 and August 2022. Clinical features, metabolic profiles, beta-cell function, and lipid profile were evaluated.A total of 316 children were diagnosed with new-onset T1D. Among them, 28.2% had a family history of T2D. Patients with T1D who had a family history of T2D experienced a later onset of the disease (p = 0.016), improved HOMA2-%B levels (p = 0.003), and increased concentrations of HDL-C (p = 0.005). In addition, no statistically significant differences in age at onset, HOMA2-%B levels, or HDL-C were found when assessing the interaction between family history of T2D and type of diabetes mellitus (autoimmune T1D/idiopathic T1D).A family history of T2D may contribute to the heterogeneity of T1D patients in terms of HOMA2-%B levels and lipid profile. This highlights the significance of taking into account T2D-related factors in the diagnosis and treatment of T1D. [ABSTRACT FROM AUTHOR]

A new neolignan glucoside denchyside B along with three known lignans have been isolated from the herbs of Dendrobium chrysanthum Wall. (Orchidaceae). The structures were elucidated on the basis of spectroscopic methods. [ABSTRACT FROM AUTHOR]

Visualization experiments and numerical simulations of two-phase flow are conducted to study the pressure fluctuation characteristics of oil-gas flow in horizontal pipes. The two-fluid model based on the Eulerian–Eulerian method is adopted, and the bubble number density equation (BNDE) is introduced to the simulation to predict the bubble size and distribution within the pipe. The bubble size and pressure variations in the pipe obtained from the simulations agree well with the recorded values from the experiments. The fast Fourier transform (FFT) algorithm is used to analyze the characteristics of pressure fluctuations, and the results show that the sudden pressure increase in the pipe sections is related to gas injection. The bubble number density increases with liquid flow rate (Ql), which causes the oil-gas flow to be more turbulent while increasing the amplitude of high-frequency fluctuations. The maximum amplitude for the dominant frequency is observed near the pump inlet for low liquid flow rates. At high liquid flow rates, more liquid vortices are found near the gas orifice, and there is a maximum amplitude for the dominant frequency in this section. Due to the high swirling strength at larger inlet gas volume fraction (IGVF), there is an obvious increase in the amplitude of low-frequency fluctuations, while the amplitude of high-frequency fluctuations is nearly the same under all IGVF. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to assess the predictive value of diabetic retinopathy (DR) on further diabetic nephropathy (DN) risk in patients with type 2 diabetes (T2D) based on the prospective cohort studies. PubMed, Embase, and the Cochrane Library were systematically searched for eligible prospective cohort studies through March 2020. The predictive value of DR was assessed using sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) through the bivariate generalized linear mixed model and the random-effects model. Ten prospective cohort studies recruited 635 patients with T2D. The pooled sensitivity and specificity of DR for predicted DN were noted to be 0.64 (95% CI, 0.54–0.73) and 0.77 (95% CI, 0.60–0.88), respectively. The pooled PLR and NLR of DR for predicted DN were 2.72 (95% CI, 1.42–5.19) and 0.47 (95% CI, 0.33–0.67), respectively. The summary DOR for the relationship between DR and subsequent DN for T2D patients was 5.53 (95% CI, 2.00–15.30), and the AUC of DR for predicted DN was 0.73 (95% CI, 0.69–0.77). This study found significant associations between DR and subsequent DN risk for patients with T2D. Moreover, the predictive value of DR on subsequent DN risk was relatively lower. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) becomes the third leading cause of cancer-related deaths worldwide recently. The prognosis of CRC is still poor in decades, and targeted therapy is still a potential effective treatment. Long non-coding RNAs (lncRNAs) could regulate series of cellular functions and developmental processes. LncRNA-SPRY4-IT1 (GenBank ID AK024556) is derived from an intron of the SPRY4 gene, which was highly expressed in melanoma cells and affected the progression of multiple types of cancers. However, the mechanism of SPRY4-IT1 in CRC progression remains unclear. Herein, we found the high level of SPRY4-IT1 in human colorectal cancer (CRC) tissues and cells, and correlated with patients' prognosis. We further noticed that SPRY4-IT1 regulated CRC cell growth and glycolysis, and promoting PDK1 expression. Our data further confirmed that SPRY4-IT1 regulated CRC progression targeting PDK1. We therefore thought SPRY4-IT1 could serve as a promising molecular target for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Vatiquinone is a potent inhibitor of 15-lipoxygenase and is in clinical development for the treatment of mitochondrial diseases and other disorders characterised by high levels of oxidative stress and dysregulation of energy metabolism. In rats, 14C-vatiquinone-derived radioactivity was quickly and widely distributed throughout the body and cleared from most tissues by 24 h post-dose following a single oral dose of 14C-vatiquinone. Following oral administration, 94% of dose was recovered within seven days in rats, approximately 61% of dose was recovered within seven days in dogs and approximately 93% of dose was recovered within nine days in human subjects (IND 119220). Faecal excretion was the major route (>56% dose) in all species; urinary excretion was minimal in rats and dogs (<3% dose) but was higher in humans (∼ 22% dose). Following oral administration, vatiquinone was the dominant circulating component in rats and dogs but was minor in human subjects. There were no plasma metabolites that were more than 10% of total drug related exposures in all species. Following oral administration, vatiquinone was not detectable in urine but was the most prominent component in faeces in rats, dogs, and humans. [ABSTRACT FROM AUTHOR]

The purpose of this study was to use the neural network to distinguish optic edema (ODE), and optic atrophy from normal fundus images and try to use visualization to explain the artificial intelligence methods. Three hundred and sixty-seven images of ODE, 206 images of optic atrophy, and 231 images of normal fundus were used, which were provided by two hospitals. A set of image preprocessing and data enhancement methods were created and a variety of different neural network models, such as VGG16, VGG19, Inception V3, and 50-layer Deep Residual Learning (ResNet50) were used. The accuracy, recall, F1-score, and ROC curve under different networks were analyzed to evaluate the performance of models. Besides, CAM (class activation mapping) was utilized to find the focus of neural network and visualization of neural network with feature fusion. Our image preprocessing and data enhancement method significantly improved the accuracy of model performance by about 10%. Among the networks, VGG16 had the best effect, as the accuracy of ODE, optic atrophy and normal fundus were 98, 90, and 95%, respectively. The macro-average and micro-average of VGG16 both reached 0.98. From CAM we can clearly find out that the focus area of the network is near the optic cup. From feature fusion images, we can find out the difference between the three types fundus images. Through image preprocessing, data enhancement, and neural network training, we applied artificial intelligence to identify ophthalmic diseases, acquired the focus area through CAM, and identified the difference between the three ophthalmic diseases through neural network middle layers visualization. With the help of assistant diagnosis, ophthalmologists can evaluate cases more precisely and more clearly. [ABSTRACT FROM AUTHOR]

In this paper, the problem of intercepting a maneuvering target is formulated as a two-player zero-sum differential game framework affected by matched uncertainties. By introducing an appropriate cost function that reflects the uncertainties, the robust control is transformed into a two-player zero-sum differential game control problem and therefore ensures the compensation of the matched uncertainties. Additionally, the corresponding Hamilton--Jacobi--Isaacs (HJI) equation is solved by constructing a critic neural network (NN). The closed-loop system and the critic NN weight estimation error are proved to be uniform ultimate boundedness (UUB) by utilising Lyapunov approach. Finally, the effectiveness of the proposed robust guidance law is demonstrated by using a nonlinear two-dimensional kinematics, assuming first-order dynamics for the interceptor and the target. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is a heterogeneous entity that can be categorized into related but different subtypes. In this study, we analyzed the gray matter structural changes of amnestic MCI (aMCI) and non-amnestic MCI (naMCI), and how it resulted in diverse cognitive impairment.Methods: Altogether 77 individuals were recruited, including 28 cognitively normal controls (NC), 25 naMCI subjects, and 24 aMCI subjects. All participants underwent a 3.0 T magnetic resonance (MR) scan and a detailed neuropsychological examination. Cortical thickness and subcortical nuclei volume were extracted by Freesurfer software and compared among groups. The areas with significant differences were further analyzed by general linear regression to identify the risk factors of each cognitive impairment subtypes.Results: Significant differences were observed in bilateral hippocampi, amygdala, thalamus, accumbens, left transverse temporal gyrus and left precuneus among groups. AMCI and naMCI were significantly different in the right hippocampus, bilateral amygdala, left precuneus, and left transverse temporal gyrus. Linear regression analysis revealed that the atrophy of left precuneus was a risk factor of memory, executive function (EF) and visuospatial impairment (p < 0.001). The atrophy of left amygdala, right accumbens and left thalamus were risk factors of memory, EF and language impairment respectively (p < 0.05).Conclusions: These findings confirmed that different gray matter structural changes could lead to specific neuropsychological features in MCI subtypes. Thorough understanding of MCI subtypes and the underlying pathology would be beneficial for precise diagnosis and intervention. [ABSTRACT FROM AUTHOR]

One new terpenylated coumarin ailanthuscoumarin was isolated from the root barks of Ailanthus altissima (Mill.) Swingle. The high oxidation of the compound led to the difficulty of structure elucidation by 2D-NMR spectra. Its structure was determined with the aid of computer-assisted structure elucidation (CASE) expert systems and Gauge-independent atomic orbital (GIAO) NMR calculations. The absolute configuration of ailanthuscoumarin was determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. The anti-hepatoma activity of ailanthuscoumarin against two human hepatoma cells (Hep3B, HepG2) was also reported. [ABSTRACT FROM AUTHOR]

Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. We recruited 252 patients and divided them into a high-TMAO group (>4.73 μg/mL) and a low-TMAO group (≤4.73 μg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001). High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients. [ABSTRACT FROM AUTHOR]

Primary membranous nephropathy (PMN) is associated with the anti-phospholipase A2 receptor (anti-PLA2R) antibody in 70% of cases. Some anti-PLA2R-negative patients have the PLA2R antigen in renal tissue. This study examined the prognosis of patients with PMN according to their serum anti-PLA2R antibody (SAb) and glomerular PLA2R antigen (GAg) status. Patients diagnosed with PMN were included retrospectively. Patients were grouped according to their PLA2R status into the SAb−/GAg−, SAb−/GAg+, and SAb+/GAg + groups. Baseline data, renal biopsy results, treatment, and clinical data were compared among the groups. Cox univariable and multivariable analyses examined the factors related to complete remission (CR). A total of 114 patients were enrolled; 10 (9%) in the SAb−/GAg−, 23 (20%) in the SAb−/GAg+, and 81 (71%) in the SAb+/GAg+ groups. Cumulative CR rate showed a significant difference between the SAb−/GAg − and SAb+/GAg+ groups (log-rank p = 0.003). The multivariable Cox proportional hazard analysis showed that age (HR = 0.968; 95%CI = 0.946–0.990; p = 0.005), SAb+/GAg+ versus SAb−/GAg− (HR = 0.387; 95%CI = 0.190–0.788; p = 0.009), SAb−/GAg+ versus SAb−/GAg− (HR = 0.398; 95%CI = 0.169, 0.939; p = 0.035), total renal chronicity score ≥2 (HR = 0.461, 95%CI: 0.277–0.766, p = 0.003), and IgA deposition (HR = 2.596; 95%CI = 1.227–5.492; p = 0.013) were all independently related (p < 0.05) to CR. The SAb and GAg status was an indicator of PMN prognosis. The patients with SAb−/GAg − had an increased likelihood of achieving CR than those with SAb−/GAg+ and SAb+/GAg+. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the clinical characteristics, risk factors, and outcomes of infection-related hospitalization (IRH) in patients with lupus nephritis (LN) and ANCA glomerulonephritis after intensive immunosuppressive therapy. Patients diagnosed with LN or ANCA glomerulonephritis who received intensive immunosuppressive therapy at the First Affiliated Hospital of Sun Yat-sen University from 2005 to 2014 were enrolled. Demographics, laboratory parameters, immunosuppressive agents, and IRH details were collected. Multivariable Cox regression was used, and hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. Totally, 872 patients with 806 LN and 66 ANCA glomerulonephritis were enrolled, and 304 (34.9%) patients with 433 episodes of IRH were recorded. ANCA glomerulonephritis patients were more vulnerable to IRH than LN patients (53.0% vs. 33.4%, p =.001). Multivariable Cox regression analysis showed that ANCA glomerulonephritis (HR = 1.62, 95% CI: 1.06–2.49, p =.027), diabetes (HR = 1.82, 95% CI: 1.03–3.22, p =.039) and a higher initial dose of prednisone (HR = 1.01, 95% CI: 1.00–1.02, p =.013) were associated with a higher likelihood of IRH. Higher albumin (HR = 0.96, 95% CI: 0.94–0.98, p <.001), globulin (HR = 0.98, 95% CI: 0.96–0.99, p =.008), and eGFR (HR = 0.99, 95% CI: 0.99–1.00, p <.001), were associated with a lower likelihood of IRH. The rates of transfer to ICU and mortality for ANCA glomerulonephritis patients were higher than those for LN patients (22.9% vs. 1.9%, p <.001, and 20.0% vs. 0.7%, p <.001, respectively). ANCA glomerulonephritis patients had a higher risk of IRH and poorer outcome once infected after intensive immunosuppressive therapy than LN patients. More strict control for infection risks is required for ANCA glomerulonephritis patients who undergo intensive immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

In order to optimise the selection of landslide monitoring points and save the cost of monitoring, a geological constitutive model was constructed by using 3D laser scanning and geological borehole data to simulate the relationship between rainfall and deformation. Thus, the main occurrence area and maximum deformation of the landslide were determined. Aiming at the deficiency of the single-epoch redundancy of the single-frequency GNSS receiver and the poor accuracy, this paper proposes a single-frequency BDS/GPS combined positioning and monitoring scheme with constraint of deformation features to restrict the search range of single-frequency ambiguity, obviously increase the ambiguity fixed success rate and then improve the BDS/GPS positioning accuracy. By contrast experiments, the landslide area obtained by numerical simulation basically matches with the on-site landslide area. The BDS/GPS combined positioning with constraint is consistent with the deep displacement changes, which can well reflect the displacement of the landslide body and make an early warning of disasters. [ABSTRACT FROM AUTHOR]

Objective: The objective of study is to report the feasibility of non-invasive prenatal screening (NIPS) combined with invasive detection by chromosomal analysis in identifying fetal duplication, providing clinical performance of NIPS on copy number variations (CNVs) detection.Material and Methods: NIPS was offered to a 35-year-old pregnant woman. Amniocentesis was performed to confirm the positive screening result. Fetal sample was detected by karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA). Parental karyotyping was also conducted.Results: NIPS result was positive for chromosome 16, indicating an extra copy of chromosome 16. FISH and chromosomal karyotyping revealed that the fetus had a marker chromosome derived from chromosome 16. CMA further demonstrated an approximately 19-Mb duplication in chromosome 16. The final fetal karyotype was 47,XY,+mar. ish der (16)(D16Z3+).arr 16p11.2q12.1 (30 624 186-49 696 337 × 3). Ultrasound scan and MRI showed some structure malformations.Conclusions: A protocol for CNVs detection by combining a series of genetic methods was presented in this study and a novel marker duplication 16p11.2q12.1 was reported. With the ability to identify subchromosomal deletions and duplications in fetus, NIPS could reduce the possibility of invasive diagnosis. The followed confirmation test for positive sample is necessary and ensures the accuracy of the diagnosis. [ABSTRACT FROM AUTHOR]

Two aluminum chloride phthalocyanines with pyridyloxy substitution at α/β positions were synthesized. Their structures were characterized by infrared spectroscopy, proton nuclear magnetic resonance as well as elemental analysis. Tetra-α(β)-(2-pyridyloxy) aluminum chloride phthalocyanines were encapsulated into a diblock copolymer methoxy-poly(ethylene glycol)-block-poly(L-lysine) through a cosolvent method. The morphologies and photophysical properties of phthalocyanines encapsulated in nanoparticles were studied by transmission electron microscope, ultraviolet-visible, and fluorescence spectroscopic methods. The photophysical properties of phthalocyanines encapsulated into nanoparticles exhibited substitution positions dependence. The phthalocyanines with substitution at α positions were found to be an excellent candidate for use as photosensitizers for treatment of cancer by photodynamic therapy. [ABSTRACT FROM AUTHOR]

Refractive index dispersion (RID) of fresh tissue is highly related to water content. However, there is no experimental investigation about their relationship for a wide spectral range. In this study, with the aid of a previously proposed lab-made apparatus, the RID of fresh and fully-dehydrated mutton muscle samples were measured over the continuous spectral range from 400 to 750 nm. The mass fractions and volume fractions were also measured. Results showed that the RID of fresh muscle tissue equals to the sum of fully-dehydrated tissue RID and water RID multiplied by their respective volume fractions. The results in this study also experimentally proved that the effective medium theory of refractive index is applicable for tissue analysis. [ABSTRACT FROM PUBLISHER]

Background:Mutations in Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL), and CALR are highly relevant to Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms. Methods:Assessing the prevalence of molecular mutations in Chinese Han patients with essential thrombocythemia (ET), and correlating their mutational profile with disease characteristics/phenotype. Results:Of the 110 subjects studied, 62 carried the JAK2 V617F mutation, 21 had CALR mutations, one carried an MPL (W515) mutation, and 28 had non-mutated JAK2, CALR, and MPL (so-called triple-negative ET). Mutations in JAK2 exon 12 were not detected in any patient. Two ET patients had both CALR and JAK2 V617F mutations. Comparing the hematological parameters of the patients with JAK2 mutations with those of the patients with CALR mutations showed that the ET patients with CALR mutations were younger (p = 0.045) and had higher platelet counts (p = 0.043). Conclusion:Genotyping for CALR could be a useful diagnostic tool for JAK2/MPL-negative ET, since the data suggest that CALR is much more prevalent than MPL, therefore testing for CALR should be considered in patients who are JAK2 negative as its frequency is almost 20 times that of MPL mutation. [ABSTRACT FROM AUTHOR]

Residual upland planation surfaces serve as strong evidence of peneplains during long intervals of base-level stability in the peneplanation process. Multi-stage planation surfaces could aid the calculation of uplift rates and the reconstruction of upland plateau evolution. However, most planation surfaces have been damaged by crustal uplift, tectonic deformation, and surface erosion, thus increasing the difficulty in automatically identifying residual planation surfaces. This study proposes a peak-cluster assessment method for the automatic identification of potential upland planation surfaces. It consists of two steps: peak extraction and peak-cluster characterization. Three critical parameters, namely, landform planation index (LPI), peak elevation standard deviation, and peak density, are employed to assess peak clusters. The proposed method is applied and validated in five case areas in the Tibetan Plateau using a Shuttle Radar Topography Mission digital elevation model (SRTM DEM) with 3 arc-second resolution. Results show that the proposed method can effectively extract potential planation surfaces, which are found to be stable with different resolutions of DEM data. A significant planation characteristic can be obtained in the relatively flat areas of the Gangdise–Nyainqentanglha Mountains and Qaidam Basin. Several vestiges of potential former planation areas are also extracted in the hilly-gully areas of the western part of the Himalaya Mountains, the northern part of the Tangula–Hengduan Mountains, and the northeastern part of the Kunlun–Qinling Mountains despite the absence of significant topographical features characterized by low slope angles or low terrain reliefs. Vestiges of planation surfaces are also identified in these hilly-gully upland areas. Hence, the proposed method can be effectively used to extract potential upland planation surfaces not only in flat areas but also in hilly-gully areas. [ABSTRACT FROM AUTHOR]

Smilacis Glabrae Rhizoma is a traditional food in China. Although phytochemical and pharmacology studies have been performed, the antioxidant constituents have not been characterized with the exception of astilbin. In the present study, six antioxidants in Smilacis Glabrae Rhizoma were determined by high-performance liquid chromatography with ultraviolet and mass spectrometry detection using 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis (3-ethylbenzthiazoline- 6-sulfonic acid) assays. These analytes were 5-O-caffeoylshikimic acid, polydatin, neoastilbin, astilbin, neoisoastilbin, and isoastilbin. The relative Trolox equivalent antioxidant capacity of each compound was determined using the two protocols. Moreover, antioxidant fingerprints were constructed for quality evaluation of Smilacis Glabrae Rhizoma and principal component analysis was performed to provide a guide for customers and producers to ensure the quality of the raw materials. The methodology may be used for the analysis of Smilacis Glabrae Rhizoma and potentially for other plant-based products. [ABSTRACT FROM AUTHOR]

Objective: Sites for subcutaneous insulin injections include the upper arms, abdomen, buttocks and outer sides of the thigh. No similar study has explored the feasibility of using the inner side of the thigh for insulin injection, since the 4 mm pen needles were introduced for clinical use. This study aimed to determine whether the inner side of the thigh is suitable for insulin injection.Research Design and Methods: Seventy-five patients with diabetes under insulin therapy from the Inpatient Department of Endocrinology were recruited for this non-blinded, non-randomized observational study. Subcutaneous adipose layer thicknesses of the upper, middle and lower area of the inner and outer thighs of 35 patients were measured by ultrasound, distance from the skin surface to the femoral deep vessels in 20 patients was measured, and insulin was injected at the upper inner and outer sides of the thigh in 20 patients. Pain perception, bleeding or bruising, leakage at the injection sites, blood glucose changes after insulin injection, and preferred ratings of the patients were measured.Clinical Trial Registration: ClinicalTrials.gov NCT02307968.Results: Subcutaneous adipose layer thicknesses at both the upper inner and outer thighs were more than 4 mm and the minimum distance was 10 mm. Among the 100 injections at the upper inner thigh, only three incidents of perceived pain occurred. No bleeding or bruising and leakage were observed from the inner or outer sides. Furthermore, the difference in blood glucose control between insulin injections at the inner side and outer sides was not statistically significant. Patient ratings for injections at the inner side were similar to injections at the outer side. The key limitation of this study was the small sample size of adult patients as well as the non-randomized controlled design of this study.Conclusion: The upper inner thigh might be a new option for insulin injection rotation. [ABSTRACT FROM AUTHOR]

Conclusion: Moxifloxacin was generally well tolerated and highly effective in the treatment of acute bacterial rhinosinusitis (ABS). The incidence of adverse events (AEs) and adverse drug reactions (ADRs) was low. The effectiveness, safety, and tolerability information collected in this study confirm the clinical safety profile of moxifloxacin and its benefit as a treatment option for ABS. Objective: To assess the effectiveness, safety, and tolerability of moxifloxacin under daily life treatment conditions in patients with ABS. Methods: The study was carried out in China between September 2005 and May 2007. Patients with ABS were treated with moxifloxacin tablets 400 mg once daily for a duration that was left to the physician's discretion. Data were collected on demography, diagnosis of infection, pretreatment, concomitant diseases and medications, moxifloxacin therapy, course of symptoms during investigations, and final assessment of therapy. Results: In all, 578 patients with ABS treated with moxifloxacin were valid for effectiveness analysis. An improvement was observed in 98.8% ( n = 571/578) of the patients. Cure was documented in 89.4% ( n = 517/578) of the patients. The physicians' overall tolerability rating was ‘very good’ or ‘good’ in 92.9% ( n = 537/578) of patients. The incidence rates of AEs and ADRs were 1.5% ( n = 10/681) and 0.6% ( n = 4/681), respectively. No serious AE was reported. [ABSTRACT FROM AUTHOR]

Objectives --As results with cochlear implants have continued to improve, patients with some remaining cochlear function have become eligible for cochlear implantation. Thus, preservation of acoustic hearing after implantation has gained importance. Hearing preservation can be considered a benchmark for atraumatic implantation preventing neural degeneration from loss of residual hair cells or subsequent to local trauma. In this prospective study, the possibility of preserving low-frequency hearing in cochlear implantation using a modified surgical technique has been explored. Material and Methods --In a prospective study design, 14 subjects with considerable low-frequency hearing of 20-60 dB in the frequency range 125-500 Hz but with unsatisfactory speech understanding with hearing aids of <35% monosyllabic word understanding were implanted with a MED-EL COMBI-40+ cochlear implant. The insertion depth was intentionally limited to 19-24 mm to prevent damage to low-frequency regions of the cochlea. Pre- and postoperative pure-tone thresholds were measured. Results --Hearing was conserved within 0-10 dB in 9/14 subjects and within 11-20 dB in 3/14; in 2/14 subjects hearing was completely lost in the implanted ear. Thus hearing could at least partially be conserved in 12/14 subjects (86%). Median threshold values decreased by 10, 15, 17.5 and 5 dB at 125, 250, 500 and 1000 Hz, respectively. Even high levels of hearing, e.g. 30 dB at 500 Hz, could be maintained after implantation in some subjects. Conclusions --This study reports successful conservation of hearing after cochlear implantation using a modified surgical technique. Even high levels of hearing could be maintained, showing that implantation of an intracochlear electrode can be performed atraumatically with preservation of functional structures. [ABSTRACT FROM AUTHOR]