Beat-Notes Acquisition of Laser Heterodyne Interference Signal for Space Gravitational Wave Detection.

In space gravitational wave detection missions, the laser heterodyne interference signal (LHI signal) has a high-dynamic characteristic due to the Doppler shift. Therefore, the three beat-notes frequencies of the LHI signal are changeable and unknown. This may further lead to the unlocking of the digital phase-locked loop (DPLL). Traditionally, fast Fourier transform (FFT) has been used as a method for frequency estimation. However, the estimation accuracy cannot meet the requirement of space missions because of the limited spectrum resolution. In order to improve the multi-frequency estimation accuracy, a method based on center of gravity (COG) is proposed. The method improves the estimation accuracy by using the amplitude of the peak points and the neighboring points of the discrete spectrum. For different windows that may be used for signal sampling, a general expression for multi-frequency correction of the windowed signal is derived. Meanwhile, a method based on error integration to reduce the acquisition error is proposed, which solves the problem of acquisition accuracy degradation caused by communication codes. The experimental results show that the multi-frequency acquisition method is able to accurately acquire the three beat-notes of the LHI signal and meet the requirement of space missions.

Profiling of Urine Carbonyl Metabolic Fingerprints in Bladder Cancer Based on Ambient Ionization Mass Spectrometry.

The diagnosis of bladder cancer (BC) is currently based on cystoscopy, which is invasive and expensive. Here, we describe a noninvasive profiling method for carbonyl metabolic fingerprints in BC, which is based on a desorption, separation, and ionization mass spectrometry (DSI-MS) platform with N,N-dimethylethylenediamine (DMED) as a differential labeling reagent. The DSI-MS platform avoids the interferences from intra- and/or intersamples. Additionally, the DMED derivatization increases detection sensitivity and distinguishes carboxyl, aldehyde, and ketone groups in untreated urine samples. Carbonyl metabolic fingerprints of urine from 41 BC patients and 41 controls were portrayed and 9 potential biomarkers were identified. The mechanisms of the regulations of these biomarkers have been tentatively discussed. A logistic regression (LR) machine learning algorithm was applied to discriminate BC from controls, and an accuracy of 85% was achieved. We believe that the method proposed here may pave the way toward the point-of-care diagnosis of BC in a patient-friendly manner.

Ultrafast machine vision with artificial neural network devices based on a GaN-based micro-LED array.

GaN-based micro-LED is an emerging display and communication device, which can work as well as a photodetector, enabling possible applications in machine vision. In this work, we measured the characteristics of micro-LED based photodetector experimentally and proposed a feasible simulation of a novel artificial neural network (ANN) device for the first time based on a micro-LED based photodetector array, providing ultrafast imaging (∼133 million bins per second) and a high image recognition rate. The array itself constitutes a neural network, in which the synaptic weights are tunable by the bias voltage. It has the potentials to be integrated with novel machine vision and reconfigurable computing applications, acting as a role of acceleration and similar functionality expansion. Also, the multi-functionality of micro-LED broadens its application potentials of combining ANN with display and communication.

[Perlman syndrome research progress].

Perlman syndrome is a rare autosomal recessive congenital overgrowth syndrome caused by pathogenic variants of the DIS3L2 gene at 2q37 region. Clinically this syndrome is characterized by polyhydramnios, macrosomia, distinctive facial appearance, and renal dysplasia. Prognosis of the disease is poor, and survivors usually have mental delay and a high risk of developing Wilms tumor. At present, the pathogenesis of this disease is still poorly understood. This article intends to provide a review for this disease.

Hydrogen-Bonding Catalyzed Ring-Closing C-O/C-O Metathesis of Aliphatic Ethers over Ionic Liquid under Metal-Free Conditions.

O-heterocycles have wide applications, and their efficient and green synthesis is very interesting. Herein, we report hydrogen-bonding catalyzed ring-closing metathesis of aliphatic ethers to O-heterocycles over ionic liquid (IL) catalyst under metal- and solvent-free conditions. The IL 1-butylsulfonate-3-methylimidazolium trifluoromethanesulfonate ([SO3 H-BMIm][OTf]) is discovered to show outstanding performance, better than the reported catalysts. An interface effect plays an important role in mediating the reaction rate due to the immiscibility between the products and the IL catalyst, and the products can be spontaneously separated. NMR analysis and DFT calculation suggest that a pair of cation and anion of [SO3 H-BMIm][OTf] could form three strong H-bonds with an ether molecule, which catalyze the ether transformation via a cyclic oxonium intermediate. A series of O-heterocycles including tetrahydrofurans, tetrahydropyrans, morpholines and dioxane can be obtained from their corresponding ethers in excellent yields (e.g., >99 %). This work opens an efficient and metal-free way to produce O-heterocycles from aliphatic ethers.

Metal-organic frameworks as affinity agents to enhance the microdialysis sampling efficiency of fatty acids.

Microdialysis (MD) has been extensively used for in vivo sampling of hydrophilic analytes such as neurotransmitters and drug metabolites. In contrast, there have been few reports on sampling of lipophilic analytes by MD. Lipophilic analytes are easily adsorbed on the surfaces of the dialysis membrane and the inner wall of tubing, which leads to a very low relative recovery (RR). In this work, a strategy to develop an enhanced MD sampling of fatty acids (FAs) by using metal-organic frameworks (MOFs) as affinity agents in the perfusion fluid was investigated. Two MOFs, MIL-101 and ZIF-8, were synthesized and tested for the first time. A 2 times higher RR, about 70% RR, was obtained. The FT-IR experiment showed that the unsaturated metal sites in MOFs could coordinate with FAs, therefore the FAs were encapsulated into MOFs, avoiding FAs to be absorbed on the surfaces of the dialysis membrane and the inner wall of tubing. Moreover, incorporation of FAs into MOFs led to a decrease of free concentration of FAs inside the MD membrane and an increase of concentration gradient, allowing more FAs to diffuse across the membrane. Consequentially, an enhanced RR was obtained. The approach was successfully used to monitor the time profile of targeted FAs in cell culture media after lipopolysaccharide (LPS)-induced inflammation.

Compensation method for temperature error of fiber optical gyroscope based on relevance vector machine.

Aiming to improve the bias stability of the fiber optical gyroscope (FOG) in an ambient temperature-change environment, a temperature-compensation method based on the relevance vector machine (RVM) under Bayesian framework is proposed and applied. Compared with other temperature models such as quadratic polynomial regression, neural network, and the support vector machine, the proposed RVM method possesses higher accuracy to explain the temperature dependence of the FOG gyro bias. Experimental results indicate that, with the proposed RVM method, the bias stability of an FOG can be apparently reduced in the whole temperature ranging from -40°C to 60°C. Therefore, the proposed method can effectively improve the adaptability of the FOG in a changing temperature environment.

A uniform 2,5-dihydroxybenzoic acid layer as a matrix for MALDI-FTICR MS-based lipidomics.

A very uniform 2,5-dihydroxybenzoic acid (DHB) layer was for the first time constructed and used as a matrix for matrix-assisted laser desorption ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) for quickly exploring the changes in lipids within biological systems. Lipid extracts from biological samples were dissolved in chloroform and deposited onto the DHB layer. Benefiting from the insolubility of DHB in chloroform, the uniform matrix crystals were still maintained, and more importantly, the lipid analytes were distributed homogeneously on the layer, which significantly increased the reproducibility of analysis using MALDI-FTICR MS. Taking advantage of the benefit of high resolution of FTICR MS and the fragment ions obtained by MS/MS, lots of lipids were identified. This method was used for exploring the changes of lipids in drug-resistant tumor cells compared with paired drug-sensitive tumor cells. The principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were employed for discovery of the changed lipids. This method, characterized by the simplicity and the speediness, demonstrated a new and promising approach for lipidomics study.

Mass spectrometry methodology in lipid analysis.

Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS) is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease.

Aqueous phototransformation of bisphenol S: the competitive radical-attack pathway to p-hydroxybenzenesulfonic acid.

The kinetics, environmental influencing factors, products and reaction mechanism of aqueous phototransformation of bisphenol S (BPS), as an alternative to bisphenol A, which is of environmental concern, were investigated. p-Hydroxybenzenesulfonic acid, as the major transformation product was confirmed by gas chromatography - mass spectrometry, electrospray ionization, ¹H nuclear magnetic resonance and fluorescence spectrum analysis. A reaction pathway was proposed based on the reactive oxygen species related results by electron paramagnetic resonance and radical traps. The competition of the excited state of BPS between transferring electron to O2 to •O2(-) and directly oxidizing H2O to •OH was revealed.

Upcycling poly(succinates) with amines to N-substituted succinimides over succinimide anion-based ionic liquids.

The chemical transformation of waste polymers into value-added chemicals is of significance for circular economy and sustainable development. Herein, we report upcycling poly(succinates) (PSS) with amines into N-substituted succinimides over succinimide anion-based ionic liquids (ILs, e.g, 1,8-diazabicyclo[5.4.0]undec-7-ene succinimide, [HDBU][Suc]). Assisted with H2O, [HDBU][Suc]) showed the best performance, which could achieve complete transformation of a series of PSS into succinimide derivatives and corresponding diols under mild and metal-free conditions. Mechanism investigation indicates that the cation-anion confined hydrogen-bonding interactions among IL, H2O, ester group, and amino/amide groups, strengthens nucleophilicity of the N atoms in amino/amide groups, and improves electrophilicity of carbonyl C atom in ester group. The attack of the amino/amide N atom on carbonyl C of ester group results in cleavage of carbonyl C-O bond in polyester and formation of amide group. This strategy is also effective for aminolysis of poly(trimethylene glutarate) to glutarimides, and poly(1,4-butylene adipate) to caprolactone diimides.

Application of exosomes in tumor immunity: recent progresses.

Exosomes are small extracellular vesicles secreted by cells, ranging in size from 30 to 150 nm. They contain proteins, nucleic acids, lipids, and other bioactive molecules, which play a crucial role in intercellular communication and material transfer. In tumor immunity, exosomes present various functions while the following two are of great importance: regulating the immune response and serving as delivery carriers. This review starts with the introduction of the formation, compositions, functions, isolation, characterization, and applications of exosomes, and subsequently discusses the current status of exosomes in tumor immunotherapy, and the recent applications of exosome-based tumor immunity regulation and antitumor drug delivery. Finally, current challenge and future prospects are proposed and hope to demonstrate inspiration for targeted readers in the field.

Bilateral cadaveric Achilles tendon graft in reconstruction after Achilles tendon tumor resection.

The standard approach to reconstruction after resection of a diffuse-type tenosynovial giant cell tumor is a local patch with free flaps. However, in cases in which the Achilles tendon involvement is extensive, and the entire tendon must be removed, an autologous flap graft might not be adequate to allow a return to function. We report a case of a 52-year-old female patient who developed bilateral tumors of the Achilles tendon, with a 10-year duration. By the time, she sought medical help, both Achilles tendons required removal. We chose to use Achilles tendon allografts to replace the Achilles tendons. Postoperatively, the patient did well. The allograft shortened the recovery time, and the patient regained full ankle range of motion.

Genetically predicted serum testosterone and risk of gynecological disorders: a Mendelian randomization study.

Background: Testosterone plays a key role in women, but the associations of serum testosterone level with gynecological disorders risk are inconclusive in observational studies. Methods: We leveraged public genome-wide association studies to analyze the effects of four testosterone related exposure factors on nine gynecological diseases. Causal estimates were calculated by inverse variance-weighted (IVW), MR-Egger and weighted median methods. The heterogeneity test was performed on the obtained data through Cochrane's Q value, and the horizontal pleiotropy test was performed on the data through MR-Egger intercept and MR-PRESSO methods. "mRnd" online analysis tool was used to evaluate the statistical power of MR estimates. Results: The results showed that total testosterone and bioavailable testosterone were protective factors for ovarian cancer (odds ratio (OR) = 0.885, P = 0.012; OR = 0.871, P = 0.005) and endometriosis (OR = 0.805, P = 0.020; OR = 0.842, P = 0.028) but were risk factors for endometrial cancer (OR = 1.549, P < 0.001; OR = 1.499, P < 0.001) and polycystic ovary syndrome (PCOS) (OR = 1.606, P = 0.019; OR = 1.637, P = 0.017). dehydroepiandrosterone sulfate (DHEAS) is a protective factor against endometriosis (OR = 0.840, P = 0.016) and premature ovarian failure (POF) (OR = 0.461, P = 0.046) and a risk factor for endometrial cancer (OR= 1.788, P < 0.001) and PCOS (OR= 1.970, P = 0.014). sex hormone-binding globulin (SHBG) is a protective factor against endometrial cancer (OR = 0.823, P < 0.001) and PCOS (OR = 0.715, P = 0.031). Conclusion: Our analysis suggested causal associations between serum testosterone level and ovarian cancer, endometrial cancer, endometriosis, PCOS, POF.

Identification of metabolic biomarkers for diagnosis of epithelial ovarian cancer using internal extraction electrospray ionization mass spectrometry (iEESI-MS).

BACKGROUND: Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies. The poor prognosis of EOC is mainly due to its asymptomatic early stage, lack of effective screening methods, and a late diagnosis in the advanced stages of the disease. OBJECTIVE: This study investigated metabolomic abnormalities in epithelial ovarian cancers. METHODS: Our study developed a novel strategy to rapidly identify the metabolic biomarkers in the plasma of the EOC patients using Internal Extraction Electrospray Ionization Mass Spectrometry (IEESI-MS) and Liquid Chromatography-mass Spectrometry (HPLC-MS), which could distinguish the differential metabolites in between plasma samples collected from 98 patients with epithelial ovarian cancer, including 78 cases with original (P), and 20 cases with self-configuration (ZP), as well as 60 healthy subjects, including 30 cases in the original sample (H), 30 cases in self-configuration (ZH), and 6 cases in a blind sample (B). RESULTS: Our study detected 880 metabolites based on criteria variable importance in projection (VIP) > 1, among which 26 metabolites were selected for further identification. They are mainly metabolism-related lipids, amino acids, nucleic acids, and others. The metabolic pathways associated with the differential metabolites were explored by the KEGG analysis, a comprehensive database that integrates genome, chemistry, and system function information. The abnormal metabolites of EOC patients identified by IEESI-MS and HPLC-MS included Lysophosphatidylcholine (16:0) [Lyso PC (16:0)], L-Phenylalanine, L-Leucine, Phenylpyruvic acid, L-Tryptophan, and L-Histidine. CONCLUSIONS: Identifying the abnormal metabolites of EOC patients through metabolomics analyses could provide a new strategy to identify valuable potential biomarkers for the screening and early diagnosis of EOC.

Clinical prediction of HBV-associated cirrhosis using machine learning based on platelet and bile acids.

OBJECTIVES: The present study was conducted to evaluate the performance of serum bile acids in the prediction of cirrhosis in chronic hepatitis B (CHB) population. METHODS: Dysregulated metabolites were explored using untargeted and targeted metabolomic analyses. A machine learning model based on platelet (PLT) and several bile acids was constructed using light gradient boosting machine (LightGBM), to differentiate HBV-associated cirrhosis (BAC) from CHB patients. RESULTS: Serum bile acids were dysregulated in BAC compared to CHB patients. The LightGBM model consisted of PLT, TUDCA, UDCA, TLCA, LCA and CA. The model demonstrated a strong discrimination ability in the internal test subset of the training cohort to diagnose BAC from CHB patients (AUC = 0.97). The high diagnostic accuracy of the model was further validated in an independent validation cohort. In addition, the model had high predictive efficacy in discriminating compensated BAC from CHB patients (AUC = 0.89). The performance of the model was better than AST/ALT ratio and the gradient boosting (GB)-based model reported in previous studies. CONCLUSIONS: Our study showed that this LightGBM model based on PLT and 5 bile acids has potential in clinical assessments of CHB progression and will be useful for early detection of cirrhosis in CHB patients.

Directly imaging excited state-resolved transient structures of water induced by valence and inner-shell ionisation.

Real-time imaging of transient structure of the electronic excited state is fundamentally critical to understand and control ultrafast molecular dynamics. The ejection of electrons from the inner-shell and valence level can lead to the population of different excited states, which trigger manifold ultrafast relaxation processes, however, the accurate imaging of such electronic state-dependent structural evolutions is still lacking. Here, by developing the laser-induced electron recollision-assisted Coulomb explosion imaging approach and molecular dynamics simulations, snapshots of the vibrational wave-packets of the excited (A) and ground states (X) of D2O+ are captured simultaneously with sub-10 picometre and few-femtosecond precision. We visualise that θDOD and ROD are significantly increased by around 50∘ and 10 pm, respectively, within approximately 8 fs after initial ionisation for the A state, and the ROD further extends 9 pm within 2 fs along the ground state of the dication in the present condition. Moreover, the ROD can stretch more than 50 pm within 5 fs along autoionisation state of dication. The accuracies of the results are limited by the simulations. These results provide comprehensive structural information for studying the fascinating molecular dynamics of water, and pave the way towards to make a movie of excited state-resolved ultrafast molecular dynamics and light-induced chemical reaction.

Preparation and SO2 capture kinetics of a DeSOx coating for the desulfurization of exhaust emission.

Sulfur dioxide (SO2) is an extremely harmful pollutant in diesel engine exhaust fumes, which must be controlled and removed effectively. In order to better integrate desulfurization materials into diesel exhaust systems, a new desulfurization powder coating (DeSOx coating) was prepared. The SO2 capture performance and kinetics of the DeSOx coating were subsequently studied. This study used a fixed-bed reactor to test the DeSOx coating SO2 capture performance and conduct kinetic analysis at various temperatures and gas flows. The analysis obtained the kinetic parameters of the activation energy and Arrhenius constant, with the derived rate control equations, under isothermal conditions. The DeSOx coating and filter which were prepared using metal oxide powders, SiO2 colloidal sol, and additives, exhibited an enhanced SO2 capture performance. In this experiment, an MnO2/SiO2/LiOH coating had the best SO2 removal rate and capture capacity at 400 °C. Under a reaction space velocity of 10700 h-1, the MnO2/SiO2/LiOH coating SO2 removal rate was 100% within the first hour of reaction. Under a reaction space velocity of 32000 h-1, the MnO2/SiO2/LiOH coating SO2 capture capacity was 132.7 mgSO2/gmaterial during the second hour of reaction. The SO2 capture conversion rate of the DeSOx coating and filter follows the second-order kinetic mechanism model. For the MnO2/SiO2/LiOH coating, the Arrhenius equation gives an activation energy of 4952 J/mol and the Arrhenius natural logarithmic constant is 8.969 s-1. For the MnO2/SiO2/LiOH filter, the activation energy of the rate constant is 214 J/mol, and the Arrhenius natural logarithmic constant is 3.744 s-1. Therefore, the desulfurization coating is an effective way to remove SO2 pollutants from diesel exhaust gases.

MicroRNA-155 is upregulated in the placentas of patients with preeclampsia and affects trophoblast apoptosis by targeting SHH/GLi1/BCL2.

The pathogenesis of preeclampsia (PE) is complicated and multiple risk factors have been associated with its occurrence. Still, the underlying molecular mechanisms involved in PE remain elusive. Aberrant apoptosis and insufficient invasion of trophoblasts have been observed and are considered vital pathological features in PE. Herein, we found that miR-155 can specifically degrade the mRNA of the Hedgehog ligand sonic hedgehog (SHH), using dual luciferase reporter assays. Quantitative real-time PCR found that administering miR-155 mimics or inhibitors could significantly decrease or increase the expression of SHH in the trophoblasts, respectively. The transcription levels of miR-155 in the placenta were higher in patients with PE compared to the levels in healthy pregnant women, as shown by quantitative real-time PCR. Serum levels of miR-155 could predict the diagnosis of PE by receiver operating characteristic curve analysis and diagnosis evaluation tests. A significant increase in apoptosis was observed after administering miR-155 in HTR8/SVneo cells cultured ex vivo, accompanied by reduced proliferation. Mechanistically, transcriptional activity and expression of GLi1 were also inhibited under treatment of miR-155, and could be recovered after supplying additional recombinant human SHH to primary trophoblasts from patients, as determined by luciferase activity assays and western blotting. We further found that inhibiting miR-155 increased the production of SHH and improved the phenotype in primary trophoblasts from patients with PE. Our data show that miR-155 regulates apoptosis of trophoblasts in PE, which has potential value for predicting PE risk and might be deemed as a therapeutic target for treating PE.

Distribution of perfluorooctane sulfonate in mice and its effect on liver lipidomic.

Perfluorooctane sulfonate (PFOS) is an emerging persistent organic pollutant (POP), and the harm caused by the enrichment of PFOS in living organism has attracted more and more attention. In this work, animal exposure model to PFOS was established. Mass spectrometry (MS), mass spectrometry imaging (MSI), hematoxylin and eosin (H&E) staining and lipidomics were combined for the study of the organ targeting of PFOS, the toxicity and possible mechanism caused by PFOS. PFOS most accumulated in the liver, followed by the lungs, kidneys, spleen, heart and brain. Combined with H&E staining and matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) results, it was found that the accumulation of PFOS indeed caused damage in particular areas of specific organ, like in the liver and in the marginal area of the heart. This work found that PFOS could cross the blood-brain barrier, entered the brain and caused the neurotoxicity, which was surprising and might be the reason that high dose of PFOS could cause convulsions. From the liver lipidomic analysis, we found that PFOS exposure mainly affected glycerophospholipid metabolism and sphingolipid metabolism. The up-regulated ceramide and lysophosphatidylcholine (LPC) might lead to liver cell apoptosis, and the decrease in liver triglyceride (TG) content might result in insufficient energy in mice and cause liver morphological damage. Phosphatidylcholine (PC) synthesis via phosphatidylethanolamine N-methyltransferase (PEMT) pathway might be a mechanism of self-protection in animals against PFOS induced inflammation. This study might provide new insight into underlying toxicity mechanism after exposure to PFOS.