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Abstract Ménière’s disease (MD) is a complex inner ear disorder characterized by a range of symptoms, with its pathogenesis linked to immune-related mechanisms. Our previous research demonstrated that IL-1β maturation and release can trigger cell pyroptosis, exacerbating the severity of the endolymphatic hydrops in a mouse model; however, the specific mechanism through which IL-1β influences MD symptoms remains unclear. This study conducted on patients with MD examined changes in protein signatures in the vestibular end organs (VO) and endolymphatic sac (ES) using mass spectrometry. Gene ontology and protein pathway analyses showed that differentially expressed proteins in the ES are closely related to adhesion, whereas those in the VO are related to synapse processes. Additionally, the study found elevated expression of Glutaminase (GLS) in the VO of MD patients compared to controls. Further investigations revealed that IL-1β increased glutamate levels by upregulating GLS expression in HEI-OC1 cells. Treatment with a GLS inhibitor or an IL-1β receptor antagonist alleviated auditory-vestibular dysfunction and reduced glutamate levels in mice with endolymphatic hydrops. These findings collectively suggest that imbalanced neurotransmitter release and immune responses contribute to the pathology of MD, potentially explaining the hearing loss and vertigo associated with the disease and offering new avenues for therapeutic interventions.

Objective To obtain the monitoring measurement range of quality indicators of red blood cells, plasma and derivatives and leukocyte-reduced apheresis platelets provided by blood stations in Hebei province, explore the distribution of monitoring values and the change of monitoring level, so as to further strengthen the homogenization construction of quality control laboratories in blood stations in Hebei. Methods In 2023, the sampling data of 12 blood stations in Hebei from 2015 to 2022 were collected, scatter plots were made and the range markers were set, and the "mean±SD" line was taken as the upper limit and lower limit of the measurement range. In 2024, the monitoring values in 2023 were added, and the changes of two measurement ranges were compared to analyze the stability and overall level. Results Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the standard deviation of the content of deleukocyte suspension of red blood cells-hemoglobin, washed erythrocyte-hemoglobin, washed erythrocyte-supernatant protein, cryoprecipitate coagulation factor-FⅧ, fresh frozen plasma-FⅧ, leukocyte-reduced apheresis platelets-leukocyte residue and leukocyte-reduced apheresis platelet-red blood cell concentration decreased from 8.132 to 7.993, 6.252 to 6.104, 0.273 to 0.267, 57.506 to 56.276, 0.920 to 0.892, 0.653 to 0.644 and 2.653 to 2.603, respectively.The narrowing of the standard deviation range of the above items led to more concentrated monitoring values and reduced dispersion. Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the mean value of leukocyte residue of the deleukocyte suspension of red blood cells, hemoglobin content of the wash erythrocyte, protein content of supernatant of the wash erythrocyte, hemolysis rate of the wash erythrocyte, FⅧ content of the cryoprecipitate coagulation factor, plasma protein content of the fresh frozen plasma, FⅧ content of the fresh frozen plasma, platelet content of the leukocyte-reduced apheresis platelets changed from 0.362 to 0.476, 44.915 to 44.861, 0.280 to 0.283, 0.137 to 0.142, 133.989 to 133.271, 60.262 to 60.208, 1.301 to 1.277 and 3.036 to 3.033, respectively, and was closer to the national standard line, which reflects an increase in the number of unqualified monitoring values or values close to the national standard line in 2023. The long-term qualified rate of coagulation items was low, and no improvement has been observed. The stability of biochemical items has been enhanced but overall deviation has occurred, with the average value close to the national standard line. The possibility of subsequent testing failure has increased. The counting items showed no obvious common characteristics. Conclusion The use of "mean±SD" in the analysis can visually display the distribution of monitoring values of different items in Hebei, forming an indicator measurement range covering the past nine years. It shows the characteristics of each item, and provides reference for subsequent quality control laboratory data analysis of each blood stations to takes active measures to improve the monitoring level.

BackgroundHypothyroidism and coronary heart disease are both common diseases in life and both are increasing in prevalence. Many studies have found a strong association between the two. However, they have not been able to prove a causal relationship. Furthermore, numerous studies have demonstrated that glycemic traits play a role in both. Consequently, the objective of this study was to ascertain the causal estimation of the association between hypothyroidism and coronary heart disease and to quantify the potential mediating role of glycemic traits in this relationship.MethodsWe used two-sample Mendelian randomisation (UVMR) to explore causality between hypothyroidism and coronary heart disease. Additionally, multivariate Mendelian randomisation (MVMR) was applied to quantify the potential mediation of glycemic traits in this relationship. A variety of Mendelian randomization methods were employed in this study, including the inverse variance weighting (IVW) method, weighted median method, and MR-Egger test. Heterogeneity and horizontal pleiotropy were evaluated through MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis to ensure the robustness of the study results.ResultsThe results of the MR analyses indicated that hypothyroidism was associated with an increased risk of coronary heart disease (IVW: OR=2.75, 95% CI: 1.53-4.94). In mediation analyses, the proportion of HbA1c-mediated effects of hypothyroidism on coronary heart disease was 7.3% (2.2%-12.5%).ConclusionThe results of our study indicate a causal relationship between hypothyroidism and coronary heart disease. Furthermore, HbA1c partially mediated the causal effect of hypothyroidism on coronary heart disease. Consequently, intervention in this factor may reduce the risk of coronary heart disease associated with hypothyroidism.

BackgroundProstate cancer is the most common cancer in men and represents a major public health problem. The current method for the diagnosis or screening of prostate cancer is invasive and costly. There have been renewed and innovative studies searching for urinary biomarkers to aid in the diagnosis of prostate cancer, especially with technologies based on urinary exosomes. However, technologies based on urine exosomes usually need expensive machines such as an ultracentrifuge and they are difficult to standardize, which hinder their application in clinical laboratories. We have optimized and standardized the isolation of urinary exosomes with the precipitation method. We have found that urinary exosomal prostate-specific antigen (PSA) can be quantified by automatic Elecsys total PSA technique. ObjectiveIn this study, our objective is to utilize urinary exosomes from prostate cancer for the development of a test to aid in its diagnosis. MethodsExosomes from the prostate cancer cell line LNCaP was used to set up the technique. To analyze urine samples from patients, the methods include the collection of first-void urine using the Colli-Pee device, the isolation of urine exosomes using the optimized precipitation method, and the quantification of exosomal PSA by Elecsys total PSA. ResultsThis will be a 2-year study. We will start including patients and controls in the last quarter of 2024. We expect the results to be published in the second quarter of 2027. ConclusionsThis is the first study to quantify urinary exosomal PSA using the Elecsys total PSA technique for the diagnosis of prostate cancer. This study emphasizes techniques that are suitable for implementation in clinical laboratories, which will facilitate the application of urinary exosomes to simplify and improve the diagnosis and screening of prostate cancer. International Registered Report Identifier (IRRID)PRR1-10.2196/63551

A proton exchange membrane electrolyzer can effectively utilize the electricity generated by intermittent solar power. Different methods of generating electricity may have different efficiencies and hydrogen production rates. Two coupled systems, namely, PV/T- and CPV/T-coupling PEMEC, respectively, are presented and compared in this study. A maximum power point tracking algorithm for the photovoltaic system is employed, and simulations are conducted based on the solar irradiation intensity and ambient temperature of a specific location on a particular day. The simulation results indicate that the hydrogen production is relatively high between 11:00 and 16:00, with a peak between 12:00 and 13:00. The maximum hydrogen production rate is 99.11 g/s and 29.02 g/s for the CPV/T-PEM and PV/T-PEM systems. The maximum energy efficiency of hydrogen production in CPV/T-PEM and PV/T-PEM systems is 66.7% and 70.6%. Under conditions of high solar irradiation intensity and ambient temperature, the system demonstrates higher total efficiency and greater hydrogen production. The CPV/T-PEM system achieves a maximum hydrogen production rate of 2240.41 kg/d, with a standard coal saving rate of 15.5 tons/day and a CO2 reduction rate of 38.0 tons/day. Compared to the PV/T-PEM system, the CPV/T-PEM system exhibits a higher hydrogen production rate. These findings provide valuable insights into the engineering application of photovoltaic/thermal-coupled hydrogen production technology and contribute to the advancement of this field.

Diabetic cardiomyopathy (DCM) presents as myocardial fibrosis, left ventricular hypertrophy, and myocardial diastolic abnormalities. Cardiac magnetic resonance (CMR) technology can quickly and accurately determine the myocardial structure and cardiac function of diabetic patients and plays a crucial role in the diagnostic and prognostic evaluation of subclinical DCM. Evaluation of subclinical DCM using CMR technology primarily involves cardiac magnetic resonance-feature tracking (CMR-FT), magnetic resonance spectroscopy (MRS), T1 mapping technology, and magnetic resonance myocardial perfusion imaging. This paper reviews the research progress of CMR technology in the diagnosis of subclinical diabetic cardiomyopathy.

Shrub species Caragana korshinskii Kom. dominates slope protection and soil and water conservation in the loess area of the northeastern Qinghai–Tibet Plateau. However, the root anchoring mechanism and the effects of soil consolidation and slope protection of this shrub species remain unclear. This study aimed to elucidate the anchoring mechanism of roots of the C. korshinskii roots and establish a calculation model to evaluate their contribution to the stability of shallow loess slopes. C. korshinskii plants with an 11-year growth period were selected as the study subject. The anchoring force of C. korshinskii roots was determined through in-situ excavation tests, in-situ root pullout tests, and theoretical analysis, along with their impact on the stability of shallow loess soil slopes. The results showed that, due to the absence of a “bolt head” structure on the root surface, it was reasonable to consider the anchoring force provided by the roots as the minimum value between the maximum pullout resistance of the roots below the sliding surface and the anchoring reaction force of the roots above the sliding surface, based on the geometric characteristics of the sliding surface. When the roots of an 11-year-old C. korshinskii roots were anchored on different sliding blocks of a shallow landslide with a maximum thickness of 2 meters, the stability coefficient of the potential sliding surface increased by 0.020% to 0.408%. When the roots of a single plant were anchored in the middle and upper parts of the potential sliding surface, the stability coefficient of the potential sliding surface was relatively higher than when the plant roots were anchored at the top and bottom positions. Moreover, when four C. korshinskii roots were anchored to the shallow landslide with a row spacing of two sliding blocks (approximately 3 m), the stability coefficient of the potential sliding surface increased by 1.035% to 1.111%, which was significantly higher than when a single C. korshinskii root was anchored (P

Waterborne polyurethane, renowned for its lightweight properties, excellent insulation capabilities, and corrosion resistance, has found extensive application in fields such as construction, automotive, leather, and thermal insulation. Nevertheless, during operational usage, waterborne polyurethane materials, akin to other polymeric substances, are susceptible to oxidative aging manifestations like yellowing, cracking, and diminished mechanical performance, significantly curtailing their utility. Consequently, the synthesis of yellowing-resistant polyurethane assumes pivotal significance. This study integrates dynamic reversible reactions into the synthesis process of polyurethane by introducing the dynamic reversible compound 2-hydroxyethyl disulfide as a chain extender, alongside the incorporation of a UV absorber to enhance the polyurethane’s resistance to yellowing. When the disulfide bonds absorb heat, they undergo cleavage, yielding thiols that spontaneously recombine into disulfide bonds at ambient temperatures, allowing for the continuous breaking and reformation of disulfide bonds to absorb heat. Concurrently, in collaboration with the UV absorber, the detrimental effects of ultraviolet radiation on the polyurethane material are mitigated, thereby augmenting its resistance to yellowing. This study scrutinizes the positioning of UV absorber addition, the quantity of UV absorber, and the molar ratio of 1,4-butanediol to 2-hydroxyethyl disulfide, characterizing the functional groups of polyurethane through infrared and Raman spectroscopy. It is observed that the successful preparation of yellowing-resistant polyurethane is achieved, and evaluations on the modified polyurethane through color difference, tensile, and centrifugal tests reveal that the optimal yellowing resistance is attained by adding a UV absorber at a mass fraction of 1% to 3% prior to chain extension, resulting in a color change grade of 2, denoting slight discoloration. Simultaneously, the other properties of polyurethane exhibit relative stability. Notably, when the molar ratio of 1,4-butanediol to 2-hydroxyethyl disulfide is 3:2, the overall performance of the polyurethane remains stable, with exceptional yellowing resistance capabilities attaining a color change grade of 2.

Local electric-field around multitype pores (dielectric pore, interface pore, electrode pore) in multilayer ceramic capacitors (MLCCs) was investigated using Kelvin probe force microscopy combined with the finite element simulation to understand the effect of pores on the electric reliability of MLCCs. Electric-field is found to be concentrated significantly in the vicinity of these pores and the strength of the local electric-field is 1.5–5.0 times of the nominal strength. Unexpectedly, the concentration degree of the pores in the inner electrode is much higher than that in the dielectrics and dielectric-electrode interfaces. Meanwhile, geometry orientations are found to have a remarkable influence on the local electric field strength. The pores act as an insulation degradation precursor via local electric, thermal center, and oxygen vacancies accumulation center. Such unusual local electric field concentration of multitype pores can provide new insights into the understanding of insulation degradation evolution, processing tailoring and design optimization for MLCCs.

[Objective] The effects of different factors on the shear strength index and shear strength of the root-soil interface were analyzed, in order to provide an understanding of the mechanism of shrub root soil fixation and slope protection in the loess region of the Northeastern Tibetan Plateau. [Methods] The dominant shrub (Caragana korshinskii) for this region was selected as the study object, and the effects of the dry density, moisture content, and salt content of soil, and of root diameter on the shear characteristics of the root-soil interface and their mechanisms were analyzed and discussed using the direct shear test (i. e., one factor was varied at a time) for root diameters of (2.20±1.00—32.00±1.80) mm and moisture contents, dry densities, and salt contents of the soil of 6.00%—22.00%, 1.20—1.60 g/cm3, and 0.59%—2.50% respectively. [Results] Root diameter had no significant effect on the shear strength indexes and shear strength of the root-soil interface (p>0.05) when other influencing factors were held constant. As soil moisture content increased from 6.00% to 22.00%, the root-soil interface cohesion initially increased and then decreased, reaching a maximum value of 6.74 kPa at a soil moisture content of 14.00%. The root-soil interface friction angle decreased linearly from 21.40° to 15.75°. The shear strength of the root-soil interface decreased linearly. As the soil dry density increased from 1.20 g/cm3 to 1.60 g/cm3, the cohesion of the root-soil interface increased exponentially from 5.70 kPa to 6.85 kPa, and the friction angle increased linearly from 20.67° to 21.67°. The shear strength of the root-soil interface increased linearly. As the soil salt content increased from 0.59% to 2.50%, the root-soil interface cohesion increased linearly from 6.71 kPa to 7.31 kPa, and the shear strength increased linearly. However, there was no significant change in the root-soil interface friction angle (p>0.05). The gray correlation analysis of these results showed that dry density had the greatest influence on the cohesion, the friction angle, and the shear strength of the root-soil interface. [Conclusion] The dry density, moisture content, and salt content of soil can all affect the shear characteristics of the root-soil interface, however, the degree of influence is different. The influence of rainfall infiltration on the shear characteristics of the root-soil interface should be fully considered when evaluating the protective effect of plant roots on the shallow soil of loess slopes.

Sintering in a reducing atmosphere, in comparison with sintering in air, greatly improves the electrical performance of ZnO-based thermoelectric materials. However, it also raises a question concerning their chemical stability in air for applications at high temperatures. The influence of annealing in air at temperatures up to 1000°C on the characteristics of ZnO-based ceramics synthesized in a reducing atmosphere of N2 + H2 was studied. The annealing process primarily results in acceptor states at the grain boundaries with the formation of electrostatic Schottky barriers, leading to decreased charge-carrier mobility and a lowering of the electrical conductivity and consequently 4-times lower power factor in comparison with the ceramics before annealing. The annealing in air does not affect the enhanced solid solubility of the donor dopants (i.e., Al) in the ceramics by sintering in a reducing atmosphere; however, it lowers the concentration of intrinsic donor defects, i.e. zinc interstitials (Zni) and oxygen vacancies (VO), thus decreasing the concentration of charge carriers. Nevertheless, the power factor of air-annealed ceramics was still 8-times higher than for ZnO ceramics prepared only by sintering in air. These results provide guidelines for the development of ZnO ceramics with annealing in air at high temperatures up to 1000°C after sintering in a reducing atmosphere, which not only enhanced thermoelectric characteristics, but also improved stability for applications in air at high temperatures, compared to the samples synthesis in air only.

Abstract Simultaneously employing light and vibration energy by piezoelectric material to realize environmental remediation is an advanced oxidation method. Silver niobate (AgNbO3) is a visible light driven photocatalyst for the removal of organic pollutants. However, the high recombination rate of photo-generated electrons and holes suppresses its photocatalytic activity. Piezoelectric potential excited by vibration can facilitate the separation of light induced charges. Unfortunately, AgNbO3 is an antiferroelectric. In this work, distinct photo-/vibration-bi-catalysis has been achieved in ferroelectric (1−x)AgNbO3–xLiTaO3 solid solution. The results show that ~96% Rhodamine B (RhB) can be decomposed under the bi-excitation of ultrasound and visible light within 120 min with 0.95AgNbO3–0.05LiTaO3 catalyst. The synergy effect from efficient visible light excitation and enhanced separation of the photo-induced charges from the electric field by the mechanical strain results in the distinct decomposition performance of catalysts.

Visible and near-infrared spectroscopy (Vis–NIR, 350–1100 nm) has great potential for predicting soil properties. However, current research on the hyperspectral prediction of soil parameters in agricultural areas of alpine regions and the types of parameters included is limited, and optimal spectral treatments and predictive models applicable to different parameters have not been sufficiently investigated. Therefore, we evaluated the accuracy of predicting total nitrogen (TN), phosphorus pentoxide (TP2O5), total potassium oxide (TK2O), alkali-hydrolyzable nitrogen (AHN), effective phosphorus (AP), effective potassium (AK), soil organic matter (SOM), and pH in the Qinghai–Tibet Plateau using the Vis–NIR technique in combination with spectral transformations, correlation analysis, feature selection, and machine learning. The results show that spectral transformations improve the correlation between spectra and parameters but are dependent on the parameter type and the method used. Continuum removal (CR), logarithmic first-order differential (FDL), and inverse first-order differential (FDR) had the most significant effects. The feature bands were extracted using the SPA and modeled using partial least squares (PLSR), random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and backpropagation neural networks (BPNNs). The accuracy was evaluated based on R2, RMSE, RPD, and RPIQ. We found that the PLSR model only enables the prediction of SOM and pH with lower accuracy than the remaining models. XGBoost can predict all of the parameters but only for AHN; the prediction performance is better than other methods (R2 = 0.776, RMSE = 0.043 g/kg, and RPIQ = 2.88). The RF, SVM, and BPNN models cannot predict AK, AP, and AHN, respectively. In addition, TP2O5, AP, and pH are best suited for modeling using RF (RPIQ = 2.776, 3.011, and 3.198); TN, AK, and SOM are best suited for modeling using BPNN (RPIQ = 2.851, 2.394, and 3.085); and AHN and TK2O are best suited for XGBoost and SVM, respectively (RPIQ = 2.880 and 3.217). Therefore, this study can provide technical and data support for the accurate and efficient acquisition of soil parameters in alpine agriculture.

An internal built electric field can suppress the recombination of electron–hole pairs and distinctly enhance the catalytic activity of a photocatalyst. Novel t-Ag/0.95AgNbO3-0.05LiTaO3 heterojunction was prepared by reducing silver nanoparticles (Ag NPs) on the surface of the piezoelectric powder 0.95AgNbO3-0.05LiTaO3 (0.05-ANLT) using a simple mechanical milling method. The effects of milling time and excitation source used for the degradation of organic dye by heterojunction catalysts were investigated. The results demonstrate that the optimized 1.5-Ag/0.05-ANLT heterojunction removes 97% RhB within 40 min, which is 7.8 times higher than that of single piezoelectric catalysis and 25.4 times higher than that of single photocatalysis. The significant enhancement of photocatalytic activity can be attributed to the synergistic coupling of the surface plasmon resonance (SPR) effect and the piezoelectric effect.

To study the reinforcement to soil by herb roots along the Qinghai-Tibet railway, an artificially restored grassland along the Qinghai-Tibet railway is selected as test site. By conducting tensile tests to a single root and direct shear tests to the root-soil composite system with its growth period of one year, such mechanical indices as roots’ tensile strength and shear strength of root-soil composite system are quantitatively assessed. The results show that the values of the mean root diameter, tensile resistance and tensile strength for the combination I (Agropyron cristatum + Puccinellia distans + Poa crymophila) are greater than those for the other combinations. Moreover, a positive power function can be introduced to describe the relationship between the root diameter and its tensile resistance for the three species, while a negative power function is introduced to describe the relationship between the root diameter and its tensile strength. In addition, the cohesion of the root-soil composite system for the three species exhibits a decreasing trend with the increasing soil depth. Of the values for cohesion for the three species, the cohesion for the combination I is 32.62 kPa, greater than that of the other two combinations by 15.3 % and 57.7%, respectively, suggesting the excellent capacity in reinforcing soil. The results may provide a theoretical basis for the prevention and control of the alpine grassland degradation, soil erosion, shallow landslides and other geo-hazards and eco-hazards along the Qinghai-Tibet railway, and are of a practical guiding significance for ecological restoration by planting vegetation along the railway.

Abstract G protein-coupled receptor (GPCR) heterodimers are new targets for the treatment of depression. Increasing evidence supports the importance of serotonergic and orexin-producing neurons in numerous physiological processes, possibly via a crucial interaction between 5-hydroxytryptamine 1A receptor (5-HT1AR) and orexin receptor 1 (OX1R). However, little is known about the function of 5-HT1AR/OX1R heterodimers. It is unclear how the transmembrane domains (TMs) of the dimer affect its function and whether its modulation mediates antidepressant-like effects. Here, we examined the mechanism of 5-HT1AR/OX1R dimerization and downstream G protein-dependent signaling. We found that 5-HT1AR and OX1R form constitutive heterodimers that induce novel G protein-dependent signaling, and that this heterodimerization does not affect recruitment of β-arrestins to the complex. In addition, we found that the structural interface of the active 5-HT1AR/OX1R dimer transforms from TM4/TM5 in the basal state to TM6 in the active conformation. We also used mutation analyses to identify key residues at the interface (5-HT1AR R1514.40, 5-HT1AR Y1985.41, and OX1R L2305.54). Injection of chronic unpredictable mild stress (CUMS) rats with TM4/TM5 peptides improved their depression-like emotional status and decreased the number of endogenous 5-HT1AR/OX1R heterodimers in the rat brain. These antidepressant effects may be mediated by upregulation of BDNF levels and enhanced phosphorylation and activation of CREB in the hippocampus and medial prefrontal cortex. This study provides evidence that 5-HT1AR/OX1R heterodimers are involved in the pathological process of depression. Peptides including TMs of the 5-HT1AR/OX1R heterodimer interface are candidates for the development of compounds with fast-acting antidepressant-like effects.

Based on comprehensive analysis of seismic, logging, core, thin section data, and stable isotopic compositions of carbon and oxygen, the sedimentary filling characteristics of the Lower Cretaceous Barra Velha Formation sequence in H oil field, Santos Basin, are studied, and the high-frequency sequence stratigraphic framework is established, and the spatial distribution of reef-shoal bodies are predicted and the controlling factors are discussed. During the depositional period of the Barra Velha Formation, the study area is a slope-isolated platform-slope sedimentary pattern from southwest to northeast and the change of climate background from rift to depression periods has resulted in the variation of sedimentary characteristics from the lower third-order sequence SQ1 (BVE 300 Member) of low-energy deep water to the upper third-order sequence SQ2 (BVE 200 and 100 members) of high-energy shallow water in the Barra Velha Formation. The activities of extensional faults and strike-slip faults in rift period and the sedimentary differentiation from platform margin to intra-platform in depression period made the sedimentary paleogeomorphology in these two periods show features of “three ridges and two depressions”. The reef-shoal bodies mainly developed in the SQ2-LHST period, with vertical development positions restricted by the periodic oscillation of the lake level, and developed on the top of each high-frequency sequence stratigraphic unit in SQ2-LHST in the platform. The strike-slip fault activity controlled the distribution of the reef-shoal bodies on the plane by changing the sedimentary paleogeomorphology. The positive flower-shaped strike-slip faults made the formation of local highlands at the margins of and inside the shallow water platforms and which became high-energy sedimentary zones, creating conditions for the development of reef-shoal bodies.

BackgroundA change in weight or metabolic status is a dynamic process, yet most studies have focused on metabolically healthy obesity (MHO) and the transition between MHO and metabolically unhealthy obesity (MUO); therefore, they have not fully revealed the nature of all possible transitions among metabolism-weight phenotypes over the years.MethodsThis was a longitudinal study based on a retrospective health check-up cohort. A total of 9,742 apparently healthy individuals aged 20–60 years at study entry were included and underwent at least two health check-ups. Six metabolism-weight phenotypes were cross-defined by body mass index (BMI) categories and metabolic status as follows: metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), MHO, metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and MUO. A multistate Markov model was used to analyse all possible transitions among these phenotypes and assess the effects of demographic and blood indicators on the transitions.ResultsThe transition intensity from MUNW to MHNW was the highest (0.64), followed by the transition from MHO to MUO (0.56). The greatest sojourn time appeared in the MHNW state (3.84 years), followed by the MUO state (2.34 years), and the shortest sojourn time appeared in the MHO state (1.16 years). Transition intensities for metabolic improvement gradually decreased with BMI level as follows: 0.64 for MUNW to MHNW, 0.44 for MUOW to MHNW, and 0.27 for MUO to MHO; however, transition intensities for metabolic deterioration, including MHNW to MUNW, MHOW to MUOW, and MHO to MUO, were 0.15, 0.38, and 0.56, respectively. In the middle-aged male group, elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and uric acid (UA) increased the risk of deterioration in weight and metabolic status and decreased the possibility of improvement.ConclusionMaintaining a normal and stable BMI is important for metabolic health. More attention should be given to males and elderly people to prevent their progression to an unhealthy metabolic and/or weight status. MHO is the most unstable phenotype and is prone to convert to the MUO state, and individuals with abnormal ALT, AST and UA are at an increased risk of transitioning to an unhealthy weight and/or metabolic status; therefore, we should be alert to abnormal indicators and MHO. Intervention measures should be taken early to maintain healthy weight and metabolic status.

A high-throughput screening method embracing 756 multiclass chemical contaminants in aquaculture products was developed using modified QuEChERS extraction coupled with liquid chromatography/quadrupole time-of-flight mass spectrometry. A mega-database with retention time/accurate mass data for 524 pesticides, 182 veterinary drugs, 32 persistent organic pollutants and 18 marine toxins was established for compound identification via retrospective library searching. In the four representative matrices (muscle tissues of tilapia and grouper, and edible portions of oyster and scallop), all the database compounds showed acceptable recovery and repeatability with the screening detection limit and limit of quantification below 0.01 mg/kg for >90% of them. The matrix-matched calibration revealed acceptable quantitative property of the method in terms of linear range, linearity, and matrix effect, and fish muscle samples showed stronger matrix effect than shellfish samples. Analysis of 64 real-life samples from aquaculture farms and retail markets evidenced applicability of the proposed method to high-throughput screening scenarios.

Due to the extrinsic contribution of domain wall motions to electro-strains, the incompatibility of the large electro-strain with a low hysteresis in piezoelectric ceramics is a stumbling block for designing high-performance piezoelectrical actuators. Herein, we report a critical state in relaxor ferroelectric systems enables to enhance the electro-strain and to reduce the hysteresis simultaneously. A room temperature ergodic relaxor state dominated by nanodomains with different local symmetries can be obtained by introducing Bi(Zn1/2Ti1/2)TiO3 into 0.73 Pb(Mg1/3Nb2/3)O3-0.27PbTiO3 matrix. Like the morphotropic phase boundary (MPB) in ferroelectrics, the coexistence of different local symmetries is capable of facilitating the transition from the ergodic relaxor state to the ferroelectric under the applied field due to the ease of polarization rotation, thereby leading to a giant electro-stain (0.24%) under an electric field of 50 kV/cm. Furthermore, the field-induced ferroelectric state with the long-range ferroelectric order can spontaneously reverse back to the initial ergodic relaxor state during unloading the electric field, which contributes to a low hysteresis (15.4%). The present work not only introduces a solid solution system with excellent electro-strain properties but also affords a guidance for manipulating the electro-strain behavior by modulating phase structures and domain configurations of piezoelectric ceramics.

Background: We hypothesized that the fine needle aspiration (FNA) supernatant from tumor might contain tumor-derived exosomes. The objective of this pilot study was to test if tumor-derived exosomal RNA could be found in FNA supernatants for molecular diagnosis of cancer.Methods: 10 FNA samples from pancreatic tumor were included. After the routine recuperation of cellular material by centrifugation, the cell-free Cytolyt liquid was collected instead of being discarded. 10 ml Cytolyt was used to isolate the exosomes. Transmission electronic microscopy (TEM) was used to examine the presence of exosomes. The exosomal marker CD63 was analyzed by flow cytometry. The exosomal RNA was extracted. RT-qPCR was performed to detect the GAPDH and the tumor marker of glypican 1 gene expression.Results: TEM confirmed the presence of exosomes from FNA supernatants. Flow cytometry showed a strong positive expression of exosome marker CD63. The concentration of exosomal RNA ranged from 18.81 to 354.75 ng/μl with an average of 81.76 ng/μl. The average exosomal RNA quantity was 1390.01 ng (range from 319.77 to 6030.75 ng) with an average 260/280 ratio of 2.12. GAPDH was detectable in all samples. Exosomal glypican 1 was detected in all samples of pancreatic ductal adenorcarcinomas (3/3) and absent from benign cystic samples (3/3). Furthermore, exosomal glypican 1 was positive in one sample with a non-contributive cytology and in one sample in which no malignant cell was found.Conclusion: This is the first report that the supernatants from FNA biopsy may contain tumor-derived exosomal RNA. These tumor-derived exosomes from FNA may provide a new liquid biopsy for the molecular diagnosis of cancer.

Abstract The optimization of molecular conformation and aggregation modes is of great significance in creation of new luminescent materials for biochemical research and medical diagnostics. Herein, a highly emissive macrocycle (1) is reported, which is constructed by the cyclization reaction of triphenylamine with benzyl bromide and exhibits very distinctive photophysical performance both in aqueous solution and the solid state. Structural analysis reveals that the 1 can form self‐interpenetrated complex and emit bright yellow fluorescence in the crystal lattice. The distorted yet symmetrical structure can endow 1 with unique two‐photon absorption property upon excitation by near‐infrared light. Also, 1 can be utilized as an efficient photosensitizer to produce singlet oxygen (1O2) both in inanimate milieu and under cellular environment. More intriguingly, due to the strong association of 1 with negatively charged biomacromolecules, organelle‐specific migration is achieved from lysosome to nucleus during the 1O2‐induced cell apoptosis process. To be envisaged, this conformationally confined cationic macrocycle with photocontrolled lysosome‐to‐nucleus translocation may provide a feasible approach for in situ identifying different biospecies and monitoring physiological events at subcellular level.

Soil nutrients play vital roles in vegetation growth and are a key indicator of land degradation. Accurate, rapid, and non-destructive measurement of the soil nutrient content is important for ecological conservation, degradation monitoring, and precision farming. Currently, visible and near-infrared (Vis–NIR) spectroscopy allows for rapid and non-destructive monitoring of soil nutrients. However, the performance of Vis–NIR inversion models is extremely dependent on the number of samples. Limited samples may lead to low prediction accuracy of the models. Therefore, modeling and prediction based on a small sample size remain a challenge. This study proposes a method for the simultaneous augmentation of soil spectral and nutrient data (total nitrogen (TN), soil organic matter (SOM), total potassium oxide (TK2O), and total phosphorus pentoxide (TP2O5)) using a generative adversarial network (GAN). The sample augmentation range and the level of accuracy improvement were also analyzed. First, 42 soil samples were collected from the pika disturbance area on the QTP. The collected soils were measured in the laboratory for Vis–NIR and TN, SOM, TK2O, and TP2O5 data. A GAN was then used to augment the soil spectral and nutrient data simultaneously. Finally, the effect of adding different numbers of generative samples to the training set on the predictive performance of a convolutional neural network (CNN) was analyzed and compared with another data augmentation method (extended multiplicative signal augmentation, EMSA). The results showed that a GAN can generate data very similar to real data and with better diversity. A total of 15, 30, 60, 120, and 240 generative samples (GAN and EMSA) were randomly selected from 300 generative samples to be included in the real data to train the CNN model. The model performance first improved and then deteriorated, and the GAN was more effective than EMSA. Further shortening the interval for adding GAN data revealed that the optimal ranges were 30–40, 50–60, 30–35, and 25–35 for TK2O, TN, TP2O5, and SOM, respectively, and the validation set accuracy was maximized in these ranges. Therefore, the above method can compensate to some extent for insufficient samples in the hyperspectral prediction of soil nutrients, and can quickly and accurately estimate the content of soil TK2O, TN, TP2O5, and SOM.

Dolostones of tidal flat facies are the major reservoir rock type of the fourth member of Leikoupo Formation, Longmen Mountain front, western Sichuan Basin. The reservoir controls are dominated by phase belt, dolomitization and denudation. Core observation, cast thin section identification, laser carbon and oxygen isotopes, cathode luminescence, electron probe and inclusion thermometry were used to study the denudation effect. This reservoir went through three periods of denudation, including penecontemporaneous period, epidiagenetic period and buried period, which separately formed intragranular and moldic pores, gypsum caves, and fault-line cavities. The studies of karstification and gypsum dissolution in the paleo-epigenetic period showed that, the distinguishing signs of meteoric water impacts in episode I of the Indosinian Movement include the irregular network of weathering cracks, karst and gypsum breccia, de-anointed calcite maintaining gypsum board shape or right-angle edge shape, widely developed paste mold holes and paste-dissolved holes. These products are featured by low carbon and oxygen stable isotope values, a wide range of strontium isotope values, low content of Sr-Mn-Fe-K-Na trace elements, low-temperature single-phase water-soluble inclusions. The dissolution of gypsum in episode I of the Indosinian Movement is the key for reservoir generation.

BackgroundClear cell renal cell carcinoma (ccRCC) is known for its high drug resistance. The tumor-immune crosstalk mediated by the epigenetic regulation of N6-methyladenosine (m6A) modification has been demonstrated in recent studies. Therefore, m6A modification-mediated immune cell infiltration characteristics may be helpful to guide immunotherapy for ccRCC.MethodsThis study comprehensively analyzed m6A modifications using the clinical parameters, single-cell RNA sequencing data, and bulk RNA sequencing data from the TCGA-ccRC cohort and 13 external validation cohorts. A series of bioinformatic approaches were applied to construct an m6A regulator prognostic risk score (MRPRS) to predict survival and immunotherapy response in ccRCC patients. Immunological characteristics, enriched pathways, and mutation were evaluated in high- and low-MRPRS groups.ResultsThe expressional alteration landscape of m6A regulators was profiled in ccRCC cell clusters and tissue. The 8 regulator genes with minimal lambda were integrated to build an MRPRS, and it was positively correlated with immunotherapeutic response in extent validation cohorts. The clinicopathological features and immune infiltration characteristics could be distinguished by the high- and low-MRPRS. Moreover, the MRPRS-mediated mutation pattern has an enhanced response to immune checkpoint blockade in the ccRCC and pan-cancer cohorts.ConclusionsThe proposed MRPRS is a promising biomarker to predict clinical outcomes and therapeutic responses in ccRCC patients.

BackgroundChildhood stunting is still a public health issue in developing countries. However, the traditional risk factors in underdeveloped areas are not suitable for developed areas. Moreover, childhood stunting is influenced by several aspects, including genetic factors, perinatal conditions, maternal conditions, and feeding practices, but researchers have not yet clearly determined which aspect of risk accumulation exerts the strongest effect on stunting. A matched case-control study was performed to assess the effect of different aspects of risk accumulation on childhood stunting.MethodsIn total, 173 non-stunted children aged under 7 years were matched in our study from June 2015 to August 2015. The children's heights and weights were measured, and a self-administered questionnaire was used to collect information from the children and their parents. The risk factors were assigned to the following five aspects: genetic factors, family socioeconomic status, perinatal conditions, maternal conditions, and feeding practices. The risk accumulation (cumulative risk score) in each aspect was defined as the total number of risk factors that occurred in a certain aspect. A conditional logistic regression model was used to assess the effect of risk accumulation in different aspects on stunting, and a decision-tree model was used to predict the children's stunting based on the cumulative risk scores.ResultsRisk accumulation in perinatal conditions, genetic factors, maternal conditions, and feeding practices was significant in the conditional logistic regression model (P < 0.05). Perinatal conditions showed the strongest association with stunting in both the regression analysis and the decision-tree model. The risk of stunting increased by 1.199 times if the cumulative risk score for perinatal conditions increased by one, and the probability of stunting was 75.8% if the cumulative risk score for perinatal conditions was ≥1.ConclusionRisk accumulation in perinatal conditions, genetic factors, maternal conditions, and feeding practices substantially increased the probability of stunting in childhood. Perinatal conditions were the main aspect associated with stunting. Prevention and intervention measures should be adopted to avoid risk accumulation in stunting.

Introduction Ischaemic stroke is the leading cause of adult disability. Thus, a strategy based on an efficient antiplatelet therapy has been developed. The monitoring of antiplatelet therapy is now limited to high risk and poor prognosis patients. Indeed, the biological monitoring of the antiplatelet therapy with available platelet function assays do not provide a global integrative approach. Platelet transmission electron microscopy, recently validated for assessing distinct ultrastructural abnormalities is a reliable morphological platelet structural analysis tool which could be used to collect all the ultrastructural platelet characteristics and assess the degree of activation of platelets.Methods and analysis Our pilot prospective and descriptive study will include 50 consecutive patients hospitalized for an ischaemic stroke. We expect to identify ultrastructural characteristics that will be correlated with the degree of platelet activation to guide clinicians in decision making regarding the antiplatelet therapy strategy.Ethics and dissemination The French Ethics Committee (comité de protection des personnes d’Ile-de-France VII) approved the information notice that will be given to participants and the protocol of this trial (protocol No 21-031).The results of the trial will be disseminated through scientific publications.Trial registration number NCT05004233.

A type of nonstoichiometric piezoceramics, [(Na0.825K0.175)0.5Bi0.5]1+x TiO3 (BKNT-x, x = 0–0.009), was synthesized by the conventional sintering method. The effects of Bi3+, Na+ and K+ content on the structure and electrical properties of 0.825Bi0.5Na0.5TiO3-0.175Bi0.5K0.5TiO3 piezoceramics were investigated.The XRD patterns demonstrated that BKNT-x piezoceramics form a solid solution without a secondary phase. Meanwhile, SEM micrographs indicated that excess [(Na0.825K0.175)0.5Bi0.5]2+ suppresses grain growth and that BKNT-x ceramics become considerably denser. BKNT-0.002 ceramics offer the following enhanced properties: d33 = 154 pC/N, kp = 33%, εr = 1087, tanδ = 0.036, and Qm = 116. This improvement of properties is most likely related to the dense structure and the maintenance of morphotropic phase boundaries through the introduction of a proper A-site cation excess. For ceramics containing volatile elements, stoichiometric control is an efficacious method of enhancing performance.

High-performance gas sensors can offer great potentials for monitoring and detection of volatile organic compounds (VOCs) in both domestic and industrial environment. In the present work, a new HCHO gas sensor was constructed with reduced graphene oxide (RGO) induced by the oximation reaction. The gas-sensing performance test results suggested that the RGO hydroxylamine hydrochloride (RGO/HA-HCl) sensor presented a high response of 75% at 16 ppm HCHO at room temperature, and a high selectivity for HCHO suffering little interference with high concentrations of volatile organic compounds, including methanol, ethanol, and methylbenzene, dichloromethane and water. Additionally, the RGO/HA-HCl sensor also showed a good long-term stability with RSD of 5.83% for a 15-day continuous sensing test, and the detection limit (DL) could reach 0.023 ppm under ambient conditions. Moreover, the mechanism for the high sensitivity and selectivity of formaldehyde was further established by in-situ gas chromatography mass spectrometry (GC–MS). This work would provide a reliable new HCHO gas sensor which could be used for monitoring and forewarning the emission of HCHO for a better protection and improvement of our environment. Keywords: Oximation reaction, Reduced graphene oxide, Gas sensor, Formaldehyde, Selectivity

In multi-label learning, each object belongs to multiple class labels simultaneously. In the data explosion age, the size of data is often huge, i.e., large number of instances, features and class labels. The high dimension of both the feature and label spaces has posed great challenges to multi-label learning problems, e.g., high time and memory costs. In this paper, we propose a new framework for multi-label learning with a large number of class labels and features, i.e., Multi-Label Learning via Feature and Label Space Dimension Reduction, namely MLL-FLSDR. Specifically, both the feature space and label space are reduced to low dimensional spaces respectively, in which the local structure of data points is utilized to constrain the geometrical structure on both the learned low dimensional spaces and guarantee the qualities of them. Then, an effective multi-label classifier is constructed from the low dimensional feature space to the latent label space. Last, the final prediction for new test data examples can be obtained by recovering from their prediction results in the latent label space with an encoding matrix learned in the previous stage. Extensive comparison experiments with the state-of-the-art approaches manifest the effectiveness of the proposed method MLL-FLSDR.

In multi-label learning, each object is represented by a single instance and associated with multiple labels simultaneously. Existing multi-label learning approaches mainly construct classification models with a fixed set of target labels (observed labels). However, in the big data era, it is difficult to provide a fully complete label set for a data set. In some real applications, there are multiple labels hidden in the data set, especially for those large-scale data sets. In this paper, a novel approach named MLLHL is proposed to not only discover the hidden labels in the training data but also predict these hidden labels and observed labels for unseen examples simultaneously. We assume that the observed labels are just a subset of labels which are selected from the full label set, and the rest ones are omitted by the annotators during the labeling stage. Extensive experiments show the competitive performance of MLLHL against other state-of-the-art multi-label learning approaches.

The Nangqen and Qamdo (NQ-QD) basins in China have very rich geothermal and brine resources. The origin and spatiotemporal evolutionary processes of its hot and saline springs however remain unclear. Geochemical and isotopic (18O, 2H, 3H) studies have therefore been conducted on the water from the geothermal and saline springs in the NQ-QD Basin. All saline springs in the study area are of the Na-Cl geochemical type while geothermal waters show different geochemical types. The oxygen and hydrogen isotopic compositions of the springs in the NQ-QD Basin are primarily controlled by meteoric water or ice-snow melt water and are influenced by rock-water interactions. It is found that the saline springs in the study area are derived from the dissolution of halite and sulfate that occur in the tertiary Gongjue red bed, while the hot springs in the QD Basin are greatly influenced by the dissolution of carbonatites and sulfates from the Bolila (T3b) and Huakaizuo (J2h) formations. Results from silica geothermometry and a silicon-enthalpy hybrid model indicate that the apparent reservoir temperatures and reservoir temperatures for the hot springs in the QD Basin range from 57–130°C to75–214°C, respectively. Deuterium analysis indicates that most of the hot springs are recently recharged rain water. Furthermore, the saline springs have a weaker groundwater regeneration capacity than the hot springs. Tritium data shows that the ranges of calculated residence times for springs in this study are 25 to 55 years, and that there is a likelihood that hot springs in the QD Basin originated from two different hydrothermal systems. The geochemical characteristics of the NQ-QD springs are similar to those of the Lanping-Simao Basin, indicating similar solute sources. Thus, the use of water isotope analyses coupled with hydrogeochemistry proves to be an effective tool to determine the origin and spatiotemporal evolution of the NQ-QD spring waters.

There is a special interaction between the environment, soil microorganisms, and tea plants, which constitute the ecosystem of tea plantations. Influenced by environmental factors and human management, the changes in soil microbial community affected the growth, quality, and yield of tea plants. However, little is known about the composition and structure of soil bacterial and fungal communities in 100-year-old tea plantations and the mechanisms by which they are affected. In this regard, we characterized the microbiome of tea plantation soils by considering the bacterial and fungal communities in 448 soil samples from 101 ancient tea plantations in eight counties of Lincang city, which is one of the tea domestication centers in the world. 16S and Internal Transcribed Spacer (ITS) rRNA high-throughput amplicon sequencing techniques were applied in this study. The results showed that the abundance, diversity, and composition of the bacterial and fungal communities have different sensitivity with varying pH, altitude, and latitude. pH and altitude affect soil microbial communities, and bacterial communities are more sensitive than fungi in terms of abundance and diversity to pH. The highest α-diversity of bacterial communities is shown in the pH 4.50–5.00 and 2,200-m group, and fungi peaked in the pH 5.00–5.50 and 900-m group. Because of environmental and geographical factors, all microbes are similarly changing, and further correlations showed that the composition and structure of bacterial communities are more sensitive than fungal communities, which were affected by latitude and altitude. In conclusion, the interference of anthropogenic activities plays a more important role in governing fungal community selection than environmental or geographical factors, whereas for the bacterial community, it is more selective to environment adaptation than to adaptation to human activities.

Malus hupehensis (Pamp.) Rehd (MH) is a dual-purpose plant used as medicine and food, which possesses various biological activities including hepatoprotective effect. In this study, the hepatoprotective activity of extracts of MH (MHE) against RFP + INH-induced liver injury was investigated. Animals in model group were given saline and INH + RFP. Animals in MHE groups were given MHE and INH + RFP. Animals in normal control group were given equal volume of saline. Subsequently, blood and liver samples were collected and assessed. MHE significantly alleviated the liver injury, as evidenced by decreased activities of the ALT, AST, TBIL, MDA and GSH-ST, and increased levels of SOD and GSH. MHE also effectively reduced the pathological tissue damage. Moreover, the CYP450 levels, and expression of CYP3A4, CYP2C9 and NADPH4 protein were inhibited by MHE. MHE exerts a protective effect against RFP + INH-induced liver injury in mice, and could be developed as a liver protectant for treatment of DILI.

PurposeExosomes could be released directly into the urine by the urological tumoral cells, so testing urinary exosomes has great potential for non-invasive diagnosis and monitor of urological tumors. The objective of this study is to systematically review and meta-analysis of urinary exosome for urological tumors diagnosis.Materials and MethodsA systematic review of the recent English-language literature was conducted according to the PRISMA statement recommendations (CRD42021250613) using PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases up to April 30, 2021. Risk-of-bias assessment was performed according to the QUADAS 2 tool. The true diagnostic value of urinary exosomes by calculating the number of true positive, false positive, true negative, and false negative, diagnoses by extracting specificity and sensitivity data from the selected literature.ResultsSixteen eligible studies enrolling 3224 patients were identified. The pooled sensitivity and specificity of urinary exosomes as a diagnostic tool in urological tumors were 83% and 88%, respectively. The area under the summary receiver operating characteristic curve was 0.92 (95% CI: 0.89–0.94). Further subgroup analyses showed that our results were stable irrespective of the urinary exosome content type and tumor type.ConclusionUrinary exosomes may serve as novel non-invasive biomarkers for urological cancer detection. Future clinical trial designs must validate and explore their utility in treatment decision-making.Systematic Review Registration[ https://www.crd.york.ac.uk/prospero/], identifier [CRD42021250613].

Cell-free DNA (cf-DNA) has been reported to represent a suitable material for liquid biopsy in the diagnosis and prognosis of various cancers. We performed a meta-analysis of published data to investigate the diagnostic value of cf-DNA for renal cancer (RCa). Systematic searches were conducted using Pubmed, Embase databases, Web of Science, Medline and Cochrane Library to identify relevant publications until the 31st March 2021. For all patients, we evaluated the true diagnostic value of cf-DNA by calculating the number of true positive, false positive, true negative, and false negative, diagnoses by extracting specificity and sensitivity data from the selected literature. In total, 8 studies, featuring 754 RCa patients, and 355 healthy controls, met our inclusion criteria. The overall diagnostic sensitivity and specificity for cf-DNA was 0.71 (95% confidence interval (CI), 0.55–0.83) and 0.79 (95% CI, 0.66–0.88), respectively. The pooled positive likelihood ratio and pooled negative likelihood ratio were 3.42 (95% CI, 2.04–5.72) and 0.36 (95% CI, 0.23–0.58), respectively. The area under the summary receiver operating characteristic curve was 0.82 (95% CI, 0.79–0.85), and the diagnostic odds ratio was 7.80 (95% CI, 4.40–13.85). Collectively, our data demonstrate that cf-DNA has high specificity and sensitivity for diagnosing RCa. Therefore, cf-DNA is a useful biomarker for the diagnosis of RCa.

BackgroundApproximately 70%-80% of kidney cancers are clear cell renal cell carcinomas (CCRCCs). Patient management is based on imaging (abdominal ultrasound and computerized tomography), surgical excision of the tumor, and pathological analysis. A tissue biopsy is therefore necessary to confirm the diagnosis and avoid unnecessary nephrectomy. For metastatic cancers, a tissue biopsy is essential for establishing the targeted therapy. This biopsy of tumor material is invasive and painful. Other techniques such as liquid biopsy would help reduce the need for tissue biopsy. The development of a simple biological test for diagnosis is essential. CA9 is a powerful marker for the diagnosis of CCRCC. Exosomes have become a major source of liquid biopsy because they carry tumor proteins, RNA, and lipids. Urine is the most convenient biological liquid for exosome sampling. ObjectiveThe aim of this study (PEP-C study) is mainly to determine whether it is possible to detect urinary exosomal CA9 for the molecular diagnosis of CCRCC. MethodsThis study will include 60 patients with CCRCC and 40 noncancer patients. Exosomes will be isolated from urine samples and exosomal CA9 will be detected by transmission electron microscopy, flow cytometry, and reverse transcription-quantitative polymerase chain reaction. ResultsThis study is currently underway with funding support from the CHU Saint-Etienne of France. ConclusionsWe expect to demonstrate that urinary tumor exosomes could be a novel liquid biopsy to diagnose CCRCC and to guide clinicians in treatment decision-making. Trial RegistrationClinicalTrials.gov NCT04053855; https://clinicaltrials.gov/ct2/show/NCT04053855 International Registered Report Identifier (IRRID)DERR1-10.2196/24423

Hydrothermal activity played an important part in the formation of the Ordovician dolostone reservoirs in Tadong area (eastern Tarim Basin). By applying the technologies of thin rock section microscopic identification, cathodoluminescence analysis, carbon and oxygen isotope analysis, trace element, rare earth element analysis, among others, the mineralogical characteristics and geochemical characteristics of the hydrothermal process are studied. It can have seen that the Ordovician hydrothermal process has represented by dolomite in various forms in the aspect of petrology and mineralogy. It is mainly composed of medium-megacryst crystalline dirty dolomite and powder-megacryst crystalline cleaner dolomite. The geochemical characteristics are the hydrothermal origin, medium-megacryst crystalline dirty dolomite with lower δ18O value, high Mn-Fe content, and positive Eu anomaly. The powder-megacryst crystalline has cleaner dolomite, with higher δ18O value, the Mn content low, and the negative Eu anomaly. Provide a reference for the Ordovician carbonate in Tadong area oil and gas exploration in the study.

In multi-view multi-label learning, each object is represented by multiple data views, and belongs to multiple class labels simultaneously. Generally, all the data views have a contribution to the multi-label learning task, but their contributions are different. Besides, for each data view, each class label is only associated with a subset data features, and different features have different contributions to each class label. In this paper, we propose a novel framework VLSF for multi-view multi-label learning, i.e., multi-view multi-label learning with View-Label-Specific Features. Specifically, we first learn a low dimensional label-specific data representation for each data view and construct a multi-label classification model based on it by exploiting label correlations and view consensus, and learn the contribution weight of each data view to multi-label learning task for all the class labels jointly. Then, the final prediction can be made by combing the prediction results of all the classifiers and the learned contribution weights. The extensive comparison experiments with the state-of-the-art approaches manifest the effectiveness of the proposed method VLSF.

Deep learning has recently shown great potentials in learning powerful features for visual tracking. However, most deep learning-based trackers neglect localization accuracy in the evaluation process of candidates. What's more, they usually over-rely on the discriminative features in a single frame in the training process. Consequently, they may fail when the discriminative features are occluded or changed in the tracking phase. In this paper, we propose a novel localization-aware meta tracker (LMT) guided with adversarial features to address the above issues. First of all, we design a novel intersection over union guided method to effectively balance the problem of classification and localization accuracy. To further improve the robustness of our classifier, we creatively use adversarial features during offline training phase. Those adversarial features can effectively guide the classifier in learning how to better deal with the situation where the discriminative features are occluded or changed. Finally, benefiting from meta learning, our algorithm only needs to perform one iterative update on the first frame and it can perform well on the tracking sceneries. The extensive experiments demonstrate the outstanding performance of our LMT compared with the state-of-the-art trackers on three benchmarks: OTB-2015, VOT-2016, and VOT-2018.

Automatic image annotation is an important technique which has been widely applied in many fields such as social network image analysis and retrieval, face recognition and so on. Multi-view image annotation aims to utilize multi-view complementary information to achieve more effective annotation results. However, the existing multi-view image annotation methods cannot well handle the complex and diversified multi-view feature, and the label correlation is also ignored. In this paper, we propose an image annotation method by integrating deep multi-view latent space learning and label correlation guided image annotation into a unified framework, which is termed as Label Correlation guided Deep Multi-view image annotation (LCDM) method. LCDM first learns a consistent multi-view representation via deep matrix factorization, which well captures multi-view complementary information. Then, label correlation is exploited to improve the discriminating power of the classifiers. We propose a unified objective function so that multi-view data representation and classifiers can be jointly learned. Extensive experimental results on various image datasets demonstrate the effectiveness of our method.

Glucocorticoids are widely used as an ophthalmic medication. A common, sight-threatening adverse event of glucocorticoid usage is ocular hypertension, caused by dysfunction of the conventional outflow pathway. We report that netarsudil, a rho-kinase inhibitor, decreased glucocorticoid-induced ocular hypertension in patients whose intraocular pressures were poorly controlled by standard medications. Mechanistic studies in our established mouse model of glucocorticoid-induced ocular hypertension show that netarsudil both prevented and reduced intraocular pressure elevation. Further, netarsudil attenuated characteristic steroid-induced pathologies as assessed by quantification of outflow function and tissue stiffness, and morphological and immunohistochemical indicators of tissue fibrosis. Thus, rho-kinase inhibitors act directly on conventional outflow cells to prevent or attenuate fibrotic disease processes in glucocorticoid-induced ocular hypertension in an immune-privileged environment. Moreover, these data motivate the need for a randomized prospective clinical study to determine whether netarsudil is indeed superior to first-line anti-glaucoma drugs in lowering steroid-induced ocular hypertension.

This study aimed to investigate the effect of WeChat-based education and rehabilitation program (WERP) on anxiety, depression, health-related quality of life (HRQoL), major adverse cardiac/cerebrovascular events (MACCE)-free survival, and loss to follow-up rate in unprotected left main coronary artery disease (ULMCAD) patients after coronary artery bypass grafting (CABG). In this randomized controlled study, 140 ULMCAD patients who underwent CABG were randomly assigned to WERP group (n=70) or control care (CC) group (n=70). During the 12-month intervention period, anxiety and depression (using hospital anxiety and depression scale (HADS)) and HRQoL (using 12-Item Short-Form Health Survey (SF-12)) were assessed longitudinally. During the total 36-month follow-up period (12-month intervention and 24-month non-intervention periods), MACCE and loss to follow-up were recorded. During the intervention period, HADS-anxiety score at month 9 (M9) (P=0.047) and month 12 (M12) (P=0.034), anxiety rate at M12 (P=0.028), and HADS-D score at M12 (P=0.048) were all reduced in WERP group compared with CC group. As for HRQoL, SF-12 physical component summary score at M9 (P=0.020) and M12 (P=0.010) and SF-12 mental component summary score at M9 (P=0.040) and M12 (P=0.028) were all increased in WERP group compared with CC group. During the total follow-up period, WERP group displayed a trend of longer MACCE-free survival than that in CC group but without statistical significance (P=0.195). Additionally, loss to follow-up rate was attenuated in WERP group compared with CC group (P=0.033). WERP serves as an effective approach in optimizing mental health care and promoting life quality in ULMCAD patients after CABG.

Backgrounds Cytochrome P450 (P450) 2E1 is one of the primary enzymes responsible for the metabolism of xenobiotics, such as drugs and environmental carcinogens. The genetic polymorphisms of the CYP2E1 gene in promoter and coding regions have been identified previously in the Han Chinese population from four different geographic areas of Mainland China. Methods To investigate whether genetic variants identified in the CYP2E1 coding region affect enzyme function, the enzymes of four single nucleotide polymorphism (SNP) variants in the coding region (novel c.1009C>T, causing p.Arg337X, where X represents the translational stop codon; c.227G>A, causing p.Arg76His; c.517G>A, yielding p.Gly173Ser; and c.1263C>T, presenting the highest allele frequency), two novel alleles (c.[227G>A;1263C>T] and c.[517G>A;1263C>T]), and the wild-type CYP2E1 were heterologously expressed in COS-7 cells and functionally characterized in terms of expression level and chlorzoxazone 6-hydroxylation activity. The impact of the CYP2E1 variant sequence on enzyme activity was predicted with three programs: Polyphen 2, PROVEAN and SIFT. Results The prematurely terminated p.Arg337X variant enzyme was undetectable by western blotting and inactive toward chlorzoxazone 6-hydroxylation. The c.1263C>T and c.[517G>A;1263C>T] variant enzymes exhibited properties similar to those of the wild-type CYP2E1. The CYP2E1 variants c.227G>A and c.[227G>A;1263C>T] displayed significantly reduced enzyme activity relative to that of the wild-type enzyme (decreased by 42.8% and 32.8%, respectively; P A transfectant was increased by 31% compared with the wild-type CYP2E1 enzyme (P T (p.Arg337X), c.227G>A (p.Arg76His), and c.517G>A (p.Gly173Ser), could influence the metabolism of CYP2E1 substrates, such as chlorzoxazone.

Abstract A facile and efficient palladium-catalyzed borylation of aryl (pseudo)halides at room temperature has been developed. Arylboronic esters were expeditiously assembled in good yields and with a broad substrate scope and good functional group compatibility. This approach has been successfully applied to the one-pot two-step borylation/Suzuki–Miyaura cross-coupling reaction, providing a concise access to biaryl compounds from readily available aryl halides. Furthermore, a parallel synthesis of biaryl analogs is accomplished at room temperature using the strategy, which enhances the practical usefulness of this method.

Abstract Ancient Egyptian mummies were often covered with an outer casing, panels and masks made from cartonnage: a lightweight material made from linen, plaster, and recycled papyrus held together with adhesive. Egyptologists, papyrologists, and historians aim to recover and read extant text on the papyrus contained within cartonnage layers, but some methods, such as dissolving mummy casings, are destructive. The use of an advanced range of different imaging modalities was investigated to test the feasibility of non-destructive approaches applied to multi-layered papyrus found in ancient Egyptian mummy cartonnage. Eight different techniques were compared by imaging four synthetic phantoms designed to provide robust, well-understood, yet relevant sample standards using modern papyrus and replica inks. The techniques include optical (multispectral imaging with reflection and transillumination, and optical coherence tomography), X-ray (X-ray fluorescence imaging, X-ray fluorescence spectroscopy, X-ray micro computed tomography and phase contrast X-ray) and terahertz-based approaches. Optical imaging techniques were able to detect inks on all four phantoms, but were unable to significantly penetrate papyrus. X-ray-based techniques were sensitive to iron-based inks with excellent penetration but were not able to detect carbon-based inks. However, using terahertz imaging, it was possible to detect carbon-based inks with good penetration but with less sensitivity to iron-based inks. The phantoms allowed reliable and repeatable tests to be made at multiple sites on three continents. The tests demonstrated that each imaging modality needs to be optimised for this particular application: it is, in general, not sufficient to repurpose an existing device without modification. Furthermore, it is likely that no single imaging technique will to be able to robustly detect and enable the reading of text within ancient Egyptian mummy cartonnage. However, by carefully selecting, optimising and combining techniques, text contained within these fragile and rare artefacts may eventually be open to non-destructive imaging, identification, and interpretation.

Abstract Background Type VI collagen is supposed to be a regulation factor in adipogenesis. This study aimed to assess the promoting effect of vitamin C (VC) on adipogenic differentiation of preadipocytes as well as its mechanism. Methods Five sets of different combinations of chemicals were used to inhibit synthesis of type I to VI collagens, blocking ERK1/2 phosphorylation during adipogenesis of 3T3-L1 preadipocytes. Furthermore, to explore whether collagen VI plays a critical role during adipogenesis, specific knockdown of collagen VI was performed by using RNA interference. The morphology and expression patterns of several target factors involved in adipogenesis were assessed at various time points. Results A reduction in ERK1/2 phosphorylation and an increase in collagen VI and adipogenic-specific factors, such as C/EBPβ, PPARγ and C/EBPα, were observed after treating adipogenic 3T3-L1 cells with AA2P, a stable derivative of VC. Inhibition of collagen synthesis by ethyl-3, 4-dihydroxybenzoate (EDHB) or by specific knockdown of collagen VI by RNAi could promote ERK1/2 phosphorylation. The ERK1/2 phosphorylation in both cases could be attenuated by AA2P treatment. In addition, the inhibition of ERK1/2 phosphorylation by U0126, a highly selective inhibitor of both MEK1 and MEK2 and a type of MAPK/ERK kinase, up-regulated the expression of collagen VI, while it down-regulated the adipogenic-specific factors. Conclusion AA2P could up-regulate the expression of collagen VI by attenuating ERK1/2 phosphorylation, further up-regulating adipocyte-specific factors, thus finally promoting the adipogenesis of 3T3-L1 preadipocytes.

Abstract Glaucoma is a major cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP), which causes optic nerve damage and retinal ganglion cell death, is the primary risk factor for blindness in glaucoma patients. IOP is controlled by the balance between aqueous humor secretion from the ciliary body (CB) and its drainage through the trabecular meshwork (TM). How microRNAs (miRs) regulate IOP and glaucoma in vivo is largely unknown. Here we show that miR-143 and miR-145 expression is enriched in the smooth muscle and trabecular meshwork in the eye. Targeted deletion of miR-143/145 in mice results in significantly reduced IOP, consistent with an ~2-fold increase in outflow facilities. However, aqueous humor production in the same mice appears to be normal based on a microbeads-induced glaucoma model. Mechanistically, we found that miR-143/145 regulates actin dynamics and the contractility of TM cells, consistent with its regulation of actin-related protein complex (ARPC) subunit 2, 3, and 5, as well as myosin light chain kinase (MLCK) in these cells. Our data establish miR-143/145 as important regulators of IOP, which may have important therapeutic implications in glaucoma.

Pemetrexed, one of the most commonly used drugs in advanced non–small cell lung cancer (NSCLC) therapies, often leads to various therapeutic responses in patients. These therapeutic responses to pemetrexed, including adverse drug reactions (ADRs) and its intended therapeutic effects, have been demonstrated to be highly individual-specific. Such difference in therapeutic responses across individuals may be caused by the unique genetic variations in each patient. However, only a few pemetrexed-based studies have been performed using Han Chinese patients. In this study, we aimed to identify genetic signatures of therapeutic responses of pemetrexed-based treatment using 203 Han Chinese patients with advanced NSCLC. All the participants received two different types of therapies: 1) treatment with only pemetrexed and 2) treatment with both pemetrexed and platinum (mainly cisplatin and carboplatin). We then performed a genetic association analysis on 16 selected single-nucleotide polymorphisms (SNPs) in 7 genes using these 2 groups. The analysis of patients receiving only pemetrexed suggests that the SNP rs1051298 on the SLC19A1 gene (c.*746C > T) increased the risk of all ADRs (collected all types of ADRs) in different cycles of pemetrexed therapy [1-2 cycles: P = 0.0059, odds ratio (OR) = 3.143; 1-4 cycles: P = 0.0072, OR = 2.340; 1-6 cycles: P = 0.0071, OR = 2.243]. This influence of rs1051298 is particularly significant in terms of liver injury (1-4 cycles: P = 0.0056, OR = 3.863; 1-6 cycles: P = 0.0071, OR = 3.466). In all the patients, including patients who received both pemetrexed and platinum, SNP rs1801133 on the MTHFR gene (665C > T) was found to be significantly associated with hematological ADRs in 1 to 2 cycles (P = 0.0079, OR = 3.566). Additionally, we discovered that SNP rs12995526 (c.815-102T > C) in the ATIC gene and SNP rs11545077 (c.91G > T) in the GGH gene were associated with both ADRs and therapeutic effects. In summary, our study identified several potential biomarkers that were significantly associated with ADRs and therapeutic effects of pemetrexed-related treatments using Han Chinese patients. Our discoveries will provide important clues for personalized pemetrexed-based treatment design for Han Chinese NSCLC patients in the future.