Screening for early rheumatoid arthritis using high-frequency ultrasound, serum RANKL, and OPG detection.

OBJECTIVE: To conduct a comparative study of high-frequency ultrasound and magnetic resonance imaging (MRI) combined with serum RANKL and OPG detection, and assess the efficacy of high-frequency ultrasound with RANKL and OPG detection in screening early rheumatoid arthritis (RA). METHOD: High-frequency ultrasound and MRI were performed on both carpal joints of 60 patients with early RA, and the frequencies of synovitis, joint effusion, tenosynovitis, and bone erosion detected by high-frequency ultrasound and MRI were observed. The serum levels of receptor activator for nuclear factor-κB ligand (RANKL) and osteoclastogenesis inhibitory factor (OPG) were also detected. The serum levels of RANKL and OPG were also detected in 80 normal healthy examinees. The data were recorded and statistically analyzed. RESULTS: The detection rates of carpal synovitis, joint effusion, tenosynovitis, and bone erosion in RA patients by high-frequency ultrasound were 81.66%, 69.16%, 63.33%, and 1.66%, respectively, while the detection rates by MRI were 80.00%, 71.66%, 65.00%, and 15.00%, respectively. There was no significant difference between high-frequency ultrasound and MRI in the detection rates of carpal synovitis, joint effusion, and tenosynovitis in RA patients (P > 0.05), while the detection rate of bone erosion by high-frequency ultrasound was significantly lower than that by MRI. The serum levels of RANKL and OPG in RA patients were 231.47 and 68.71, respectively, while the serum levels of RANKL and OPG in normal healthy examinees were 123.51 and 385.05, respectively. The serum RANKL levels of RA patients were significantly higher than those of healthy examinees, while the serum OPG levels of RA patients were significantly lower than those of healthy examinees, which were statistically significant (P < 0.01). The AUC values of the ROC curves obtained by high-frequency ultrasound and MRI combined with serum RANKL and OPG detection in Synovitis modeling were 0.955 and 0.954, respectively. The AUC values of the ROC curves obtained from the joint fusion modeling using high-frequency ultrasound and MRI combined with serum RANKL and OPG detection were 0.949 and 0.950, respectively. The AUC values of the ROC curves obtained from modeling Tenosynovitis using high-frequency ultrasound and MRI combined with serum RANKL and OPG detection were 0.941 and 0.949, respectively. The AUC values of ROC curves obtained by combining high-frequency ultrasound and MRI with serum RANKL and OPG detection in Bone erosion modeling were 0.908 and 0.923, respectively. CONCLUSION: High-frequency ultrasound combined with serum RANKL and OPG detection has comparable effects to MRI on screening early RA, providing a safe, simple, and cost-effective screening method for the early detection of RA patients. Key Points • High-frequency ultrasound and MRI can effectively detect early lesions of the wrist joints in RA patients. • Ultrasound diagnosis has the advantages of being quick, inexpensive, and repeatable, making it the preferred choice of imaging examination for RA patients at an early stage.

Variations of Habitat Quality and Ecological Risk and Their Correlations with Landscape Metrics in a Robust Human Disturbed Coastal Region-Case Study: Xinggang Town in Southern China.

This paper explores how landscape risk and habitat quality vary in coastal areas with strong anthropogenic disturbance based on a case study. We analyze the temporal-spatial variations of habitat quality and ecological risk in the coastal region by adopting the methods of theInVEST model and the ecological risk index. The correlations of habitat quality and ecological risk with landscape metrics are subsequently quantified. The results indicated the presence of obvious distance gradients in relation to the deterioration of habitat quality and the increase in ecological risk. Moreover, the gradient area close to the coastline exhibits significant habitat quality and ecological risk changes. The majority of landscape metrics show positive correlations with habitat quality and ecological risk, and these correlations vary with the distance gradients. Since the rapid urbanization of the coastal region, the marked expansion of built-up land and decrease in natural landscapes has significantly impacted the landscape pattern index and, consequently, changed the habitat quality and ecological risk level.

Predictive models built upon annotated and validated intake biomarkers in urine using paired or unpaired analysis helped to classify cranberry juice consumers in a randomized, double-blinded, placebo-controlled, and crossover study.

Intake biomarkers of cranberry juice in women can assess consumption in clinical trials. Discriminant biomarkers in urine may explain urinary tract infection (UTI) preventive activities. We hypothesized that validated and annotated discriminant metabolites in human urine could be used as intake biomarkers in building predictive multivariate models to classify cranberry consumers. Urine samples were collected from 16 healthy women aged 18 to 29 years at baseline and after 3- and 21-day consumption of cranberry or placebo juice in a double-blind, crossover study. Urine metabolomes were analyzed using ultra high-performance liquid chromatography coupled with Orbitrap mass spectrometry. Paired and unpaired multivariate analyses were used to annotate or identify discriminant metabolic features after cranberry consumption. Twenty-six discriminant metabolic features (paired analysis) and 27 (unpaired analysis) after cranberry consumption in an open-label intervention were rediscovered in the blinded study. These metabolites included exogenous (quinic acid) and endogenous ones (hippuric acid). The paired analysis showed better model fitting with partial least-square discriminant analysis models built on all metabolites than the unpaired analysis. Predictive models built on shared metabolites by the unpaired analysis were able to classify cranberry juice consumers with 84.4% to 100% correction rates, overall better than the paired analysis (50%-100%). The double-blind study validated discriminant metabolites from a previous open-label study. These urinary metabolites may be associated with the ability of cranberries to prevent UTIs and serve as potential cranberry intake biomarkers. It reveals the importance of selecting the right predictive models to classify cranberry consumers with higher than 95% correction rates.

Envelope-based partial partial least squares with application to cytokine-based biomarker analysis for COVID-19.

Partial least squares (PLS) regression is a popular alternative to ordinary least squares regression because of its superior prediction performance demonstrated in many cases. In various contemporary applications, the predictors include both continuous and categorical variables. A common practice in PLS regression is to treat the categorical variable as continuous. However, studies find that this practice may lead to biased estimates and invalid inferences (Schuberth et al., 2018). Based on a connection between the envelope model and PLS, we develop an envelope-based partial PLS estimator that considers the PLS regression on the conditional distributions of the response(s) and continuous predictors on the categorical predictors. Root-n consistency and asymptotic normality are established for this estimator. Numerical study shows that this approach can achieve more efficiency gains in estimation and produce better predictions. The method is applied for the identification of cytokine-based biomarkers for COVID-19 patients, which reveals the association between the cytokine-based biomarkers and patients' clinical information including disease status at admission and demographical characteristics. The efficient estimation leads to a clear scientific interpretation of the results.

Sensitivity of Ostracods to U, Cd and Cu: The Case of Cypridopsis vidua.

The development of uranium mines has been necessary to obtain abundant and scarce uranium resources, but they also bring inevitable radioactive contamination to the surrounding soil, rivers and lakes. This paper explores the sensitivity of Cypridopsis vidua to the radioactive element uranium and the heavy elements cadmium and copper with single and combined acute toxicity experiments and combined toxicity model predictions. The results from the single toxicity experiments showed that the degree of toxic effects was cadmium > copper > uranium. The combined toxicity experiments showed that the compound toxicity of U-Cd and U-Cu was higher than the weakest component and lower than the strongest component, whereas the compound toxicity of Cd-Cu was higher than either of its components. When the overall proportion of a more toxic metal was increased, its mixed toxicity also increased, and vice versa. Combined toxicity predictions showed that the U-Cd combination was best described by the concentration additive (CA) model, the independent action (IA) model was more applicable to the Cd-Cu combination, and the most applicable model for the U-Cu combination changed depending on the concentration gradient. The acute toxicity data from this study provide a reference for the development of wastewater discharge standards for uranium mines, enriches the data related to the toxicity of uranium for ostracods and deepens the understanding of the threat of uranium pollution to aquatic ecosystems.

Nicotinamide N-methyltransferase ameliorates renal fibrosis by its metabolite 1-methylnicotinamide inhibiting the TGF-ß1/Smad3 pathway.

Chronic kidney disease (CKD), a disease involving damage to the kidney structure and function, is a global public health problem. Tubulointerstitial fibrosis (TIF) is both an inevitable pathological change in individuals with CKD and a driving force in the progression of renal fibrosis. Nicotinamide N-methyltransferase (NNMT) and its metabolite 1-methylnicotinamide (MNAM) have been shown to protect against lipotoxicity-induced kidney tubular injury. However, the biological roles of NNMT and MNAM in regulating TIF remain elusive. This study aimed to investigate the protective effect of NNMT and MNAM on TIF and the mechanisms involved. We explored the functions and mechanisms of NNMT and MNAM in TIF, as well as the interaction between NNMT and MNAM, using unilateral ureteral obstruction (UUO) mice and cultured mouse tubular epithelial cells (mTECs) stimulated with transforming growth factor-ß1 (TGF-ß1). Several important findings were obtained as follows: (1) NNMT expression was upregulated in the kidneys of UUO mice and TGF-ß1-induced mTECs, and this upregulation was proposed to be a protective compensatory response to TIF. (2) MNAM was a potentially effective antifibrotic and anti-inflammatory medication in UUO mice. (3) The antifibrotic effect of NNMT overexpression was exerted by increasing the concentration of MNAM. (4) The renoprotective role of MNAM depended on the selective blockade of the interaction of Smad3 with TGFß receptor I. Overall, our study shows that NNMT is involved in the development and progression of CKD and that its metabolite MNAM may be a novel inhibitor of the TGF-ß1/Smad3 pathway with great therapeutic potential for CKD.

Identifying Cranberry Juice Consumers with Predictive OPLS-DA Models of Plasma Metabolome and Validation of Cranberry Juice Intake Biomarkers in a Double-Blinded, Randomized, Placebo-Controlled, Cross-Over Study.

SCOPE: Methods to verify cranberry juice consumption are lacking. Predictive multivariate models built upon validated biomarkers may help to verify human consumption of a food using a nutrimetabolomics approach. METHODS: A 21-day double-blinded, randomized, placebo-controlled, cross-over study was conducted among healthy young women aged 1829. Plasma was collected at baseline and after 3-day and 21-day consumption of cranberry or placebo juice. Plasma metabolome was analyzed using UHPLC coupled with high resolution mass spectrometry. RESULTS: 18 discriminant metabolites in positive mode and 18 discriminant metabolites in negative mode from a previous 3-day open-label study were re-discovered in the present blinded study. Predictive orthogonal partial least squares discriminant analysis (OPLS-DA) models were able to identify cranberry juice consumers over a placebo juice group with 96.9% correction rates after 3-day consumption in both positive and negative mode. This present study revealed 84 and 109 additional discriminant metabolites in positive and negative mode, respectively. Twelve of them were tentatively identified. CONCLUSION: Cranberry juice consumers were classified with high correction rates using predictive OPLS-DA models built upon validated plasma biomarkers. Additional biomarkers were tentatively identified. These OPLS-DA models and biomarkers provided an objective approach to verify participant compliance in future clinical trials.

Modifications of the urinary metabolome in young women after cranberry juice consumption were revealed using the UHPLC-Q-orbitrap-HRMS-based metabolomics approach.

The objectives of this research were to investigate urinary metabolome modifications and discover potential intake biomarkers in young women after cranberry juice consumption. Fifteen female college students were given either cranberry juice or apple juice for three days using a cross-over design. Urine samples were collected before and after juice consumption. The metabolome in the urine was analyzed using UHPLC-Q-orbitrap-HRMS-based metabolomics followed by orthogonal partial least squares-discriminant analyses (OPLS-DA). An S-plot was used to identify discriminant metabolites. Validated OPLS-DA analyses showed that cranberry juice consumption significantly altered the urinary metabolome. Compared to the baseline urine or urine after apple juice consumption, cranberry juice consumption increased urinary excretion of both exogenous and endogenous metabolites. The tentatively identified exogenous metabolites included quinic acid, coumaric acid, 4-hydroxy-5-(hydroxyphenyl)-valeric acid-O-sulphate, 5-(dihydroxyphenyl)-γ-valerolactone sulfate, diphenol glucuronide, 3,4-dihydroxyphenyl propionic acid, 3-(hydroxyphenyl) propionic acid, 4-O-methylgallic acid, trihydroxybenzoic acid and 1,3,5-trimethoxybenzene. Modifications of endogenous metabolites after cranberry juice consumption included the increases in homocitric acid, hippuric acid, 3-hydroxy-3-carboxymethyl-adipic acid, (2)3-isopropylmalate, pimelic acid and N-acetyl-l-glutamate 5-semialdehyde. These metabolites may serve as urinary biomarkers of cranberry juice consumption and contribute to the bioactivities of cranberries against urinary tract infection.

Tracing solute sources and carbon dynamics under various hydrological conditions in a karst river in southwestern China.

Understanding the mechanisms that lead various hydrological conditions to influence solute and carbon dynamics in karst rivers is a crucial issue. In this study, high-frequency sampling and analyses of water chemistry and ẟ13CDIC were conducted from October 2013 to September 2014 in a typical karst river, the Beipan River in southwestern China. The major ions (such as Ca2+, Mg2+, HCO3-, K+, SO42-, Na+, and Cl-) in the river are mainly from the weathering of carbonates and silicates and present temporal hydrological variabilities. Sr and U are mainly derived from carbonate weathering and show chemostatic behaviors responding to increasing discharge, similar to carbonate-sourced ions Ca2+, Mg2+, and HCO3-. Silicate weathering is the primary source of Al and Li, which show significant dilution effects similar to those of Na+ responding to high discharge. Meanwhile, most dissolved trace elements (such as Zn, Cu, Ba, Sb, Mn, Mo, and Pb) are strongly impacted by anthropogenic overprints and also exhibit a significant seasonal variability, which may be related with mining activities in the investigated area. A simultaneous increase of ẟ13CDIC and decrease in ∆DIC contents and pCO2 values suggests that photosynthesis is the primary control on riverine DIC variability during the high-flow season. Besides, the pCO2 values display significant chemostatic behaviors owing to the influx of biological CO2, which is produced by microbiological activities and ecological processes, and enhanced by monsoonal climatic conditions. A two-dimensional endmember mixing model demonstrates that carbonate weathering (averaging 62%) along with biological carbon (averaging 38%) are main sources to the riverine DIC, with temporal variability. Consequently, these results show that carbonate weathering and involved plant photosynthesis are the dominant processes controlling the riverine DIC contents under high discharge and temperature conditions. This work provides insight into the crucial influence of hydrological variability on solute sources and carbon dynamics under monsoonal climate for the karst rivers.

UHPLC-Q-Orbitrap-HRMS-based global metabolomics reveal metabolome modifications in plasma of young women after cranberry juice consumption.

Plasma metabolome in young women following cranberry juice consumption were investigated using a global UHPLC-Q-Orbitrap-HRMS approach. Seventeen female college students, between 21 and 29 years old, were given either cranberry juice or apple juice for three days using a cross-over design. Plasma samples were collected before and after juice consumption. Plasma metabolomes were analyzed using UHPLC-Q-Orbitrap-HRMS followed by orthogonal partial least squares-discriminant analyses (OPLS-DA). S-plot was used to identify discriminant metabolites. Validated OPLS-DA analyses showed that the plasma metabolome in young women, including both exogenous and endogenous metabolites, were altered following cranberry juice consumption. Cranberry juice caused increases of exogenous metabolites including quinic acid, vanilloloside, catechol sulfate, 3,4-dihydroxyphenyl ethanol sulfate, coumaric acid sulfate, ferulic acid sulfate, 5-(trihydroxphenyl)-gamma-valerolactone, 3-(hydroxyphenyl)proponic acid, hydroxyphenylacetic acid and trihydroxybenzoic acid. In addition, the plasma levels of endogenous metabolites including citramalic acid, aconitic acid, hydroxyoctadecanoic acid, hippuric acid, 2-hydroxyhippuric acid, vanilloylglycine, 4-acetamido-2-aminobutanoic acid, dihydroxyquinoline, and glycerol 3-phosphate were increased in women following cranberry juice consumption. The metabolic differences and discriminant metabolites observed in this study may serve as biomarkers of cranberry juice consumption and explain its health promoting properties in human.

Groupwise envelope models for imaging genetic analysis.

Motivated by searching for associations between genetic variants and brain imaging phenotypes, the aim of this article is to develop a groupwise envelope model for multivariate linear regression in order to establish the association between both multivariate responses and covariates. The groupwise envelope model allows for both distinct regression coefficients and distinct error structures for different groups. Statistically, the proposed envelope model can dramatically improve efficiency of tests and of estimation. Theoretical properties of the proposed model are established. Numerical experiments as well as the analysis of an imaging genetic data set obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study show the effectiveness of the model in efficient estimation. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

NMR-based metabolomics reveals urinary metabolome modifications in female Sprague-Dawley rats by cranberry procyanidins.

A (1)H NMR global metabolomics approach was used to investigate the urinary metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) or partially purified apple procyanidins (PPAP). After collecting 24-h baseline urine, 24 female Sprague-Dawley rats were randomly separated into two groups and gavaged with PPCP or PPAP twice using a dose of 250 mg extracts per kilogram body weight. The 24-h urine samples were collected after the gavage. Urine samples were analyzed using (1)H NMR. Multivariate analyses showed that the urinary metabolome in rats was modified after administering PPCP or PPAP compared to baseline urine metabolic profiles. 2D (1)H-(13)C HSQC NMR was conducted to assist identification of discriminant metabolites. An increase of hippurate, lactate and succinate and a decrease of citrate and α-ketoglutarate were observed in rat urine after administering PPCP. Urinary levels of d-glucose, d-maltose, 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid, formate and phenol increased but citrate, α-ketoglutarate and creatinine decreased in rats after administering PPAP. Furthermore, the NMR analysis showed that the metabolome in the urine of rats administered with PPCP differed from those gavaged with PPAP. Compared to PPAP, PPCP caused an increase of urinary excretion of hippurate but a decrease of 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid and phenol. These metabolome changes caused by cranberry procyanidins may help to explain its reported health benefits and identify biomarkers of cranberry procyanidin intake.

Graphene oxide liquid crystals for reflective displays without polarizing optics.

The recent emergence of liquid crystals of atomically thin two-dimensional (2D) materials not only has allowed us to explore novel phenomena of macroscopically aligned 2D nanomaterials but also has provided a route toward their controlled assembly into three-dimensional functional macrostructures. Using flow-induced mechanical alignment, we prepared flakes of graphene oxide (GO) in different orientational orders and demonstrated that GO liquid crystals (LC) can be used as rewritable media for reflective displays without polarizing optics. With a wire or stick as a pen, we can make the surface of GO LC reflective and bright, and we can then manually draw lines, curves, and any patterns with dark appearance. The contrast between bright and dark features is due to anisotropic optical responses of ordered GO flakes. Since optical anisotropy is an intrinsic property of 2D structures, our observations and demonstration represent one of many potential applications of macroscopically aligned 2D nanomaterials.

Broadband infrared photoluminescence in silicon nanowires with high density stacking faults.

Making silicon an efficient light-emitting material is an important goal of silicon photonics. Here we report the observation of broadband sub-bandgap photoluminescence in silicon nanowires with a high density of stacking faults. The photoluminescence becomes stronger and exhibits a blue shift under higher laser powers. The super-linear dependence on excitation intensity indicates a strong competition between radiative and defect-related non-radiative channels, and the spectral blue shift is ascribed to the band filling effect in the heterostructures of wurtzite silicon and cubic silicon created by stacking faults.

Four-fold Raman enhancement of 2D band in twisted bilayer graphene: evidence for a doubly degenerate Dirac band and quantum interference.

We report the observation of a strong 2D band Raman in twisted bilayer graphene (tBLG) with large rotation angles under 638 nm and 532 nm visible laser excitations. The 2D band Raman intensity increased four-fold as opposed to the two-fold increase observed in single-layer graphene. The same tBLG samples also exhibited rotation-dependent G-line resonances and folded phonons under 364 nm UV laser excitation. We attribute this 2D band Raman enhancement to the constructive interference between two double-resonance Raman pathways, which were enabled by a nearly degenerate Dirac band in the tBLG Moiré superlattices.

Efficient solar water-splitting using a nanocrystalline CoO photocatalyst.

The generation of hydrogen from water using sunlight could potentially form the basis of a clean and renewable source of energy. Various water-splitting methods have been investigated previously, but the use of photocatalysts to split water into stoichiometric amounts of H2 and O2 (overall water splitting) without the use of external bias or sacrificial reagents is of particular interest because of its simplicity and potential low cost of operation. However, despite progress in the past decade, semiconductor water-splitting photocatalysts (such as (Ga1-xZnx)(N1-xOx)) do not exhibit good activity beyond 440 nm (refs 1,2,9) and water-splitting devices that can harvest visible light typically have a low solar-to-hydrogen efficiency of around 0.1%. Here we show that cobalt(II) oxide (CoO) nanoparticles can carry out overall water splitting with a solar-to-hydrogen efficiency of around 5%. The photocatalysts were synthesized from non-active CoO micropowders using two distinct methods (femtosecond laser ablation and mechanical ball milling), and the CoO nanoparticles that result can decompose pure water under visible-light irradiation without any co-catalysts or sacrificial reagents. Using electrochemical impedance spectroscopy, we show that the high photocatalytic activity of the nanoparticles arises from a significant shift in the position of the band edge of the material.

Nanowire thermometers.

We report the design and demonstration of nanowire temperature reporters. Metal alloys with tunable melting points were used to create nanowires in nanopores of anodic aluminum oxide using mechanical pressure injection. When exposed to temperature above their melting points, nanowires began to break up into disconnected shorter nanorods due to Rayleigh instability. A wide range of temperature can be probed conveniently by measuring electrical resistance of nanowires.

Photoinduced oxygen release and persistent photoconductivity in ZnO nanowires.

Photoconductivity is studied in individual ZnO nanowires. Under ultraviolet (UV) illumination, the induced photocurrents are observed to persist both in air and in vacuum. Their dependence on UV intensity in air is explained by means of photoinduced surface depletion depth decrease caused by oxygen desorption induced by photogenerated holes. The observed photoresponse is much greater in vacuum and proceeds beyond the air photoresponse at a much slower rate of increase. After reaching a maximum, it typically persists indefinitely, as long as good vacuum is maintained. Once vacuum is broken and air is let in, the photocurrent quickly decays down to the typical air-photoresponse values. The extra photoconductivity in vacuum is explained by desorption of adsorbed surface oxygen which is readily pumped out, followed by a further slower desorption of lattice oxygen, resulting in a Zn-rich surface of increased conductivity. The adsorption-desorption balance is fully recovered after the ZnO surface is exposed to air, which suggests that under UV illumination, the ZnO surface is actively "breathing" oxygen, a process that is further enhanced in nanowires by their high surface to volume ratio.

Control and characterization of individual grains and grain boundaries in graphene grown by chemical vapour deposition.

The strong interest in graphene has motivated the scalable production of high-quality graphene and graphene devices. As the large-scale graphene films synthesized so far are typically polycrystalline, it is important to characterize and control grain boundaries, generally believed to degrade graphene quality. Here we study single-crystal graphene grains synthesized by ambient chemical vapour deposition on polycrystalline Cu, and show how individual boundaries between coalescing grains affect graphene's electronic properties. The graphene grains show no definite epitaxial relationship with the Cu substrate, and can cross Cu grain boundaries. The edges of these grains are found to be predominantly parallel to zigzag directions. We show that grain boundaries give a significant Raman 'D' peak, impede electrical transport, and induce prominent weak localization indicative of intervalley scattering in graphene. Finally, we demonstrate an approach using pre-patterned growth seeds to control graphene nucleation, opening a route towards scalable fabrication of single-crystal graphene devices without grain boundaries.