Enhancing Chemical Reaction Monitoring with a Deep Learning Model for NMR Spectra Image Matching to Target Compounds.

In the synthetic laboratory, researchers typically rely on nuclear magnetic resonance (NMR) spectra to elucidate structures of synthesized products and confirm whether they match the desired target compounds. As chemical synthesis technology evolves toward intelligence and continuity, efficient computer-assisted structure elucidation (CASE) techniques are required to replace time-consuming manual analysis and provide the necessary speed. However, current CASE methods typically aim to derive precise chemical structures from spectroscopic data, yet they suffer from drawbacks such as low accuracy, high computational cost, and reliance on chemical libraries. In meticulously designed chemical synthesis reactions, researchers prioritize confirming the attainment of the target product based on NMR spectra, rather than focusing on identifying the specific product obtained. For this purpose, we innovatively developed a binary classification model, termed as MatCS, to directly predict the relationship between NMR spectra image (including 1H NMR and 13C NMR) and the molecular structure of the target compound. After evaluating various feature extraction methods, MatCS employs a combination of the Graph Attention Networks and Graph Convolutional Networks to learn the structural features of molecular graphs and the pretrained ResNet101 network with a Convolutional Block Attention Module to extract features from NMR spectra images. The results show that on a challenging Testsim data set, which poses difficulty in distinguishing spectra of similar molecular structures, MatCS achieves comprehensive evaluation metrics with an F1-score of 0.81 and an AUC value of 0.87. Simultaneously, it exhibited commendable performance on an external SDBS data set containing experimental NMR spectra, showcasing substantial potential for structural verification tasks in real automated chemical synthesis.

Two-mirror aerial mapping camera design with a tilted-aplanatic secondary mirror for image motion compensation.

The optical compensation method is a promising method to compensate the image motion by driving the optical element of the system. However, the tilt motion of the optical element could induce the degradation of the image quality. Based on the Nodal Aberration Theory (NAT), this paper proposes a novel optical image motion compensation design with a secondary tilt-aplanatic two-mirror optical system (STATOS), which achieves the insensitivity on the image quality of the optical system. First, the properties of coma-free pivot point depending on the location of stop at primary mirror or secondary mirror have been analyzed respectively. Then the calculating method about construction parameters in terms of STATOS is developed. Further, the maximum tilt angle of secondary mirror could be solved using NAT under ordered specific restriction. Finally, a prototype is designed with SM-tilting result of MTF value maintain above 0.32 at the cut-off frequency of detector, where the principal distance could remain stable and the changed distortion is better than 0.03%. A test flight has been carried out to prove the desired results and feasibility of STATOS used in an aerial mapping camera.

Urinary epidermal growth factor predicts complete remission of proteinuria in Chinese children with IgA nephropathy.

BACKGROUND: This study investigated the association between urinary epidermal growth factor (EGF) and complete remission (CR) of proteinuria in children with IgA nephropathy (IgAN). METHODS: We included 108 patients from the Registry of IgA Nephropathy in Chinese Children. The urinary EGF at the baseline and follow-up were measured and normalized by urine creatinine (expressed as uEGF/Cr). The person-specific uEGF/Cr slopes were estimated using linear mixed-effects models for the subset of patients with longitudinal data of uEGF/Cr. Cox models were used to analyze the associations of baseline uEGF/Cr and uEGF/Cr slope with CR of proteinuria. RESULTS: Patients with high baseline uEGF/Cr were more likely to achieve CR of proteinuria (adjusted HR 2.24, 95% CI: 1.05-4.79). The addition of high baseline uEGF/Cr on the traditional parameters significantly improved the model fit for predicting CR of proteinuria. In the subset of patients with longitudinal data of uEGF/Cr, high uEGF/Cr slope was associated with a higher likelihood of CR of proteinuria (adjusted HR 4.03, 95% CI: 1.02-15.88). CONCLUSIONS: Urinary EGF may be a useful noninvasive biomarker for predicting and monitoring CR of proteinuria in children with IgAN. IMPACT: High levels of baseline uEGF/Cr (>21.45 ng/mg) could serve as an independent predictor for CR of proteinuria. The addition of baseline uEGF/Cr on the traditional clinical pathological parameters significantly improved the fitting ability for the prediction of CR of proteinuria. Longitudinal data of uEGF/Cr were also independently associated with CR of proteinuria. Our study provides evidence that urinary EGF may be a useful noninvasive biomarker in the prediction of CR of proteinuria as well as monitoring therapeutic response, thus guiding treatment strategies in clinical practice for children with IgAN.

Combined Alport syndrome, Klinefelter syndrome and Fanconi syndrome in a Chinese boy.

Alport syndrome (AS) is a progressive renal disease characterized by hematuria and progressive renal failure. X-linked dominant (XLAS) is the major inheritance form, accounting for almost 80% of the cases, caused by mutations in COL4A5 genes. Klinefelter syndrome (KS) is the most common genetic cause of human male gonadal dysgenesis. AS and KS are both rare disease, there are only three cases of combined AS and KS in the literatures. Fanconi syndrome (FS) caused by AS is also very rare. We report here the first case combined AS, KS and FS in a Chinese boy. We suggest that the severe renal phenotype and FS might be due to the two homozygous COL4A5 variants in our boy, and cases of AS combined KS will be good research objects for X chromosome inactivation.

Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation.

Autophagy plays a critical role in the physiology and pathophysiology of hepatocytes. High level of homocysteine (Hcy) promotes autophagy in hepatocytes, but the underlying mechanism is still unknown. Here, we investigate the relationship between Hcy-induced autophagy level and the expression of nuclear transcription factor EB (TFEB). The results show that Hcy-induced autophagy level is mediated by upregulation of TFEB. Silencing of TFEB decreases the level of autophagy-related protein LC3BII/I and increases p62 expression level in hepatocytes after exposure to Hcy. Moreover, the effect of Hcy on the expression of TFEB is regulated by hypomethylation of the TFEB promoter catalyzed by DNA methyltransferase 3b (DNMT3b). In summary, this study shows that Hcy can activate autophagy by inhibiting DNMT3b-mediated DNA methylation and upregulating TFEB expression. These findings provide another new mechanism for Hcy-induced autophagy in hepatocytes.

A Phase Recovery Technique Using the Genetic Algorithm for Aberration Correction in a Coherent Imaging System.

For traditional imaging systems, high imaging quality and system miniaturization are often contradictory. In order to meet the requirements of high imaging quality and system miniaturization, this paper proposes a method to correct the aberration of coherent imaging optical systems. The method is based on the idea of phase recovery and the imaging principle of a coherent imaging system to recover the aberrations at the exit pupil of the system. According to the recovered aberrations, conjugate filters are constructed to correct the image quality in the frequency domain. The imaging quality of the system is improved without changing the original optical path, and the simplicity of the system is guaranteed. To solve the pupil frequency domain aberration more accurately, this paper adopts the dual competition and parallel recombination strategy based on the genetic algorithm and introduces the disaster model. The improved genetic algorithm can effectively restrain the appearance of the "precocity" phenomenon. Finally, the paraxial imaging optical path is simulated and verified by experiments. The results show that, after aberration correction, the image sharpness is improved and the edge information is richer, which verifies the feasibility of the coherent imaging system image quality enhancement method proposed in this paper.

Contributions of Support Point Number to Mirror Assembly Thermal Sensitivity Control.

Due to the extreme environmental temperature variations, solutions that enable ultra-low thermal sensitivity in a mirror assembly are crucial for high-performance aerial optical imaging sensors (AOIS). Strategies such as the elimination of the coefficient of thermal expansion (CTE) mismatch and the employment of a flexure connection at the interface cannot be simply duplicated for the application involved, demanding specific design constraints. The contributions of support point number to the surface thermal sensitivity reduction and support stiffness improvement have been studied. A synthetic six-point support system that integrates equally spaced multiple ultra-low radial stiffness mirror flexure units and assembly external interface flexure units has been demonstrated on a 260 mm apertured annular mirror that involves significant CTE mismatch and demanding support stiffness constraint. The surface deformation RMS, due to the 35 °C temperature variation, is 16.7 nm.

Development and validation of a hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the quantification of regadenoson in human plasma and its pharmacokinetic application.

Regadenoson, the first selective adenosine A2A receptor agonist, is used to perform exercise stress test during radionuclide myocardial perfusion imaging. To detect the concentration of regadenoson in human plasma, a simple, fast, and sensitive tandem mass spectrometry method was established herein. Acetonitrile was used as a protein precipitation agent. Chromatographic separation was completed in 6.5 min using a BEH HILIC column (50 × 2.1 mm, 1.7 µm). The mobile phase consisted of 10 mmol/L ammonium acetate/acetonitrile (gradient elution). To quantify regadenoson and regadenoson-d3, an API 4000 mass spectrometry in multiple reaction monitoring mode with transitions of 391.3→259.2 and 394.3→262.2, respectively, was utilized. The calibration curve was linear in the range of 0.100-50.0 µg/L, and the intrabatch and interbatch precisions were <9.7% and <13.0%, respectively, and the accuracy was 2.0-6.9%. There was no apparent matrix effect for regadenoson or regadenoson-d3. The developed method was used to study the pharmacokinetic characteristics of regadenoson in healthy Chinese subjects.

Warming/cooling effect of cropland expansion during the 1900s ~ 2010s in the Heilongjiang Province, Northeast of China.

Land cover change (LCC) significantly changed the local/regional temperature. This paper attempts to reveal the effects of cropland expansion in different ways on temperature change from the 1900s to 2010s in Heilongjiang Province. To reach this goal, we conducted four simulation research schemes with the coupled Weather Research and Forecast (WRF)-Noah model to investigate the warming/cooling effect of cropland expansion. The results show that cropland expansion exerted different effects with different land-use type conversions. In the last century, the areas with grassland-to-cropland and wetland-to-cropland transition show the warming effect, and the average surface temperature in Heilongjiang Province increased by 0.023 ℃ and 0.024 ℃, respectively. The areas with forest-to-cropland transition show the cooling effect, in which the average temperature decreased by 0.103 ℃. The variation of air temperature is mainly caused by the variation of surface reflectance and surface net radiation flux. The results provide evidence that cropland expansion changes to biophysical landscape characteristics, warming/cooling the land surface and thus enhancing/reducing the temperature, and lead to regional climate change eventually.

Precise Target Geo-Location of Long-Range Oblique Reconnaissance System for UAVs.

High-precision, real-time, and long-range target geo-location is crucial to UAV reconnaissance and target strikes. Traditional geo-location methods are highly dependent on the accuracies of GPS/INS and the target elevation, which restricts the target geo-location accuracy for LRORS. Moreover, due to the limitations of laser range and the common, real time methods of improving the accuracy, such as laser range finders, DEM and geographic reference data are inappropriate for long-range UAVs. To address the above problems, a set of work patterns and a novel geo-location method are proposed in this paper. The proposed method is not restricted by conditions such as the accuracy of GPS/INS, target elevation, and range finding instrumentation. Specifically, three steps are given, to perform as follows: First, calculate the rough geo-location of the target using the traditional method. Then, according to the rough geo-location, reimage the target. Due to errors in GPS/INS and target elevation, there will be a re-projection error between the actual points of the target and the calculated projection ones. Third, a weighted filtering algorithm is proposed to obtain the optimized target geo-location by processing the reprojection error. Repeat the above process until the target geo-location estimation converges on the true value. The geo-location accuracy is improved by the work pattern and the optimization algorithm. The proposed method was verified by simulation and a flight experiment. The results showed that the proposed method can improve the geo-location accuracy by 38.8 times and 22.5 times compared with traditional methods and DEM methods, respectively. The results indicate that our method is efficient and robust, and can achieve high-precision target geo-location, with an easy implementation.

Metal Halide Perovskite Based Heterojunction Photocatalysts.

With fascinating photophysical properties and a strong potential to utilize solar energy, metal halide perovskites (MHPs) have become a prominent feature within photocatalysis research. However, the effectiveness of single MHP photocatalysts is relatively poor. The introduction of a second component to form a heterojunction represents a well-established route to accelerate carrier migration and boost reaction rates, thus increasing the photoactivity. Recently, there have been several scientific advances related to the design of MHP-based heterojunction photocatalysts, including Schottky, type II, and Z-scheme heterojunctions. In this Review, we systematically discuss and critically appraise recent developments in MHP-based heterojunction photocatalysis. In addition, the techniques for identifying the type of active heterojunctions are evaluated and we conclude by briefly outlining the ongoing challenges and future directions for promising photocatalysts based on MHP heterojunctions.

Studies on Hydrophobic Silica/Silicone Rubber Composite Microspheres with Dual-Size Microstructures.

In this study, a series of microsphere composites were prepared by the hydrosilylation of nanospherical SiO2 and silicon rubber microspheres. The influence of different host-guest size ratios on the wettability of the SiO2/silicone rubber composite microspheres was explored. The structures and performance of the composite microspheres were investigated using scanning electron microscopy and contact angle testing. The results showed that the prepared SiO2/silicone rubber composite microspheres had a raspberry-like structure and exhibited a rose petal effect. When the SiO2 content was 30%, the water contact angle of the SiO2/silicone rubber composite microspheres reached a maximum, and 30% was used as the optimal ratio for compounding SiO2 having different particle diameters with silicone rubber microspheres. Wettability calculations and analyses were performed for the surface with the composite microspheres. The results indicated that the structure with dual-size roughness could significantly improve surface hydrophobicity. As the ratio of the host-guest size increased, the contact angle of the water phase also increased. However, the surface structures of the composite microspheres were not uniform because of the surface chemical composition and the uncontrollable distribution of the small spheres on the surface of the large spheres during compounding. As a result, water droplets appeared in the Cassie-impregnated state on the composite microsphere particle coating, resulting in the phenomenon of high hydrophobicity and high adhesion.

Metabolic disposition of [14 C]-abivertinib, an epidermal growth factor receptor tyrosine kinase inhibitor: Role of glutathione conjugation.

AIMS: To determine the absorption, distribution, metabolism and excretion of abivertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Seven patients with advanced NSCLC were given a single 200 mg/83 µCi oral suspension of [14 C]-abivertinib. Blood, urine and faeces were collected. Mass balance of radioactivity, the pharmacokinetics of abivertinib, and the total radioactivity were determined. Metabolite profiling and characterisation were performed. RESULTS: The mean recovery was 82.16%, with 2.38 and 79.78% of the radioactive dose excreted in urine and faeces, respectively. The unchanged abivertinib was the major radioactive component detected in plasma within the first 24 hours after dosing, accounting for 59.17% of the total drug-related radioactivity. Abivertinib in urine accounted for only 0.96% of the administered dose, whereas in faeces it accounted for 33.36%. Eight metabolites were detected and characterised in plasma, among which MII-7, a product of cysteine glycine conjugate, was the only circulating metabolite, accounting for approximate 10.6% of the total drug-related exposure. MII-2 (an abivertinib cysteine-glycine adduct) and M7 (a reduced product of abivertinib) were the 2 major metabolites in the excreta, accounting for 20.0 and 12.4%, respectively, of the drug-related radioactivity in faeces. CONCLUSION: Following a single oral administration, the unchanged abivertinib was the predominant drug-related material in plasma, urine and faeces. The drug-related materials were primarily eliminated via the faecal route. Direct glutathione conjugation of abivertinib played a significant role in the metabolic clearance and metabolite exposure of abivertinib.

Flexoelectric and dielectric effects in uniform lying helix cholesteric liquid crystals under cell boundary conditions.

 Flexoelectric effect and dielectric effect in uniform lying helix (ULH) cholesteric liquid crystals under cell boundary conditions of periodic anchoring at the bottom and vertical anchoring at the top are studied. They can be quantitatively analyzed by theoretically simulation of the polar angle and the tilt angle. It is found that a good ULH texture can be formed inside under periodic boundary conditions and the bulk director is not affected by the surface anchoring strength. The induced rotation angle of the helical axis by the flexoelectric effect is slightly non-uniform with the position, and the coupling of the flexoelectric effect and dielectric effect increases the inhomogeneous change. Our results will provide an accurate theory basis for the formation of a good ULH texture and the influence of dielectric effect on the optical axis.

Factors predicting the recovery from acute kidney injury in children with primary nephrotic syndrome.

BACKGROUND: The prognosis of acute kidney injury (AKI) varies in children with nephrotic syndrome (NS), data on factors predicting the recovery and recurrence of AKI in children with NS are limited. This study aimed to explore the possible factors predicting the recovery from and recurrence of AKI in children with primary NS. METHODS: Children with primary NS complicated with AKI from 1993 to 2017 in a single centre were reviewed retrospectively. The clinical pictures and possible factors predicting the recovery from and recurrence of AKI in children with primary NS were investigated. RESULTS: Sixty-eight episodes of AKI in 59 children with NS were analysed: 88.2% of AKI recovered within 3 months, and 2.9% of AKI did not recover after 3 months. Survival analysis revealed that leucocyturia is significantly related to the AKI recovery time (P = 0.001), and children with leucocyturia [22 (4, 79) days] recovered significantly slower than did children without leucocyturia [12.0 (2, 39) days]. Renal tubular and interstitial injury were prominent in children with leucocyturia, and 11.9% of children with index AKI experienced the recurrence of AKI. CONCLUSIONS: Most episodes of AKI that occurred in children with NS recovered completely. Leucocyturia is a significant factor predicting the recovery time of AKI.

Impact of CYP2C19 genotype on voriconazole exposure and effect of voriconazole on the activity of CYP3A in patients with haematological malignancies.

Voriconazole (VRC) is a first-line drug for the treatment of invasive fungal infections (IFIs) and an inhibitor of CYP3A activity. The aims of this study are to investigate the influence of related factors on the plasma concentration of voriconazole and the effect of voriconazole on the activity of CYP3A in patients with haematological malignancies.A total of 89 patients received an initial dose of 6 mg/kg followed by 4 mg/kg every 12 h were included in the study. Blood samples were collected before and 2 h after administration for subsequent testing and for the extraction of DNA samples. Voriconazole and voriconazole N-oxide in the plasma were detected by LC-MS/MS. The effect of voriconazole on CYP3A activity was evaluated by the ratio of the endogenous biomarkers 6ß-hydroxycortisol and cortisol.During the study period, the overall incidence of adverse reactions was 33.6% (with no deaths). The metabolite type of CYP2C19 and combined use of CYP2C19 enzyme inhibitors both had a significant impact on voriconazole exposure. Voriconazole has a long-lasting and potent inhibitory effect on CYP3A activity. The exposure of CYP3A substrate in combination with metabolic enzyme inhibitors voriconazole could increase. Therefore, the combination uses with voriconazole need to be considered carefully and assessed adequately.

Tolerability, safety, pharmacokinetics and pharmacodynamics of SHR0534, a potent G protein-coupled receptor 40 (GPR40) agonist, at single- and multiple-ascending oral doses in healthy Chinese subjects.

SHR0534 is being developed for type-2 diabetes mellitus. Herein the tolerability, safety, pharmacokinetics and pharmacodynamics of SHR0534 in healthy Chinese subjects were assessed in a phase-I, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study. Forty subjects were randomized 4:1 to receive SHR0534 at the dose of 10, 25, 50 or 100 mg, or placebo, and another eleven subjects were allocated to either the 5 mg group or the placebo group at an 8:3 ratio. All subjects received a single dose on day 1, followed by a 9-day washout and once-daily administrations for 14 consecutive days. Serial samples were collected, and vital signs, electrocardiograms, laboratory tests, urinalysis and adverse events (AEs) were recorded. All doses of SHR0534 were safe and well tolerated with infrequent, generally mild-to-moderate AEs and no serious AEs in the study. SHR0534 was absorbed with a T max of approximately 4 hours, and systemic exposure increased with dose. Accumulation was minimal (2- to 3-fold) and steady state was reached after seven days of dosing. For pharmacodynamics, no significant hypoglycaemic effects were seen in healthy adults. Good pharmacokinetics and safety were demonstrated but no obvious effect was found.

Conceptual Design and Image Motion Compensation Rate Analysis of Two-Axis Fast Steering Mirror for Dynamic Scan and Stare Imaging System.

In order to enable the aerial photoelectric equipment to realize wide-area reconnaissance and target surveillance at the same time, a dual-band dynamic scan and stare imaging system is proposed in this paper. The imaging system performs scanning and pointing through a two-axis gimbal, compensating the image motion caused by the aircraft and gimbal angular velocity and the aircraft liner velocity using two two-axis fast steering mirrors (FSMs). The composition and working principle of the dynamic scan and stare imaging system, the detailed scheme of the two-axis FSM and the image motion compensation (IMC) algorithm are introduced. Both the structure and the mirror of the FSM adopt aluminum alloys, and the flexible support structure is designed based on four cross-axis flexural hinges. The Root-Mean-Square (RMS) error of the mirror reaches 15.8 nm and the total weight of the FSM assembly is 510 g. The IMC rate equations of the two-axis FSM are established based on the coordinate transformation method. The effectiveness of the FSM and IMC algorithm is verified by the dynamic imaging test in the laboratory and flight test.

The Hole-Tunneling Heterojunction of Hematite-Based Photoanodes Accelerates Photosynthetic Reaction.

Single-atom metal-insulator-semiconductor (SMIS) heterojunctions based on Sn-doped Fe2 O3 nanorods (SF NRs) were designed by combining atomic deposition of an Al2 O3 overlayer with chemical grafting of a RuOx hole-collector for efficient CO2 -to-syngas conversion. The RuOx -Al2 O3 -SF photoanode with a 3.0 nm thick Al2 O3 overlayer gave a >5-fold-enhanced IPCE value of 52.0 % under 370 nm light irradiation at 1.2 V vs. Ag/AgCl, compared to the bare SF NRs. The dielectric field mediated the charge dynamics at the Al2 O3 /SF NRs interface. Accumulation of long-lived holes on the surface of the SF NRs photoabsorber aids fast tunneling transfer of hot holes to single-atom RuOx species, accelerating the O2 -evolving reaction kinetics. The maximal CO-evolution rate of 265.3 mmol g-1 h-1 was achieved by integration of double SIMS-3 photoanodes with a single-atom Ni-doped graphene CO2 -reduction-catalyst cathode; an overall quantum efficiency of 5.7 % was recorded under 450 nm light irradiation.

Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors.

Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs. The gastric acid-suppressive effect of PPIs is affected by both gastric H+,K+-ATPase and CYP2C19 polymorphisms, although gastric H+,K+-ATPase polymorphisms may have larger effects. Ilaprazole and rabeprazole show relatively small differences in the pharmacokinetic and pharmacodynamic properties and clinical efficacy among the different CYP2C19 genotypes. Compared with oral administration, the intravenous infusion of PPIs is less affected by CYP2C19 polymorphism. At the same dose, each enantiomer has less variation among different CYP2C19 genotypes than a racemate mixture.