Learning quantum properties from short-range correlations using multi-task networks.

Characterizing multipartite quantum systems is crucial for quantum computing and many-body physics. The problem, however, becomes challenging when the system size is large and the properties of interest involve correlations among a large number of particles. Here we introduce a neural network model that can predict various quantum properties of many-body quantum states with constant correlation length, using only measurement data from a small number of neighboring sites. The model is based on the technique of multi-task learning, which we show to offer several advantages over traditional single-task approaches. Through numerical experiments, we show that multi-task learning can be applied to sufficiently regular states to predict global properties, like string order parameters, from the observation of short-range correlations, and to distinguish between quantum phases that cannot be distinguished by single-task networks. Remarkably, our model appears to be able to transfer information learnt from lower dimensional quantum systems to higher dimensional ones, and to make accurate predictions for Hamiltonians that were not seen in the training.

The Essential Function of Cathepsin X of the Orange-spotted Grouper, Epinephelus coioides during SGIV Infection.

Cathepsin X, a class of cysteine proteases in the lysosome, involved in intracellular protein degradation processes. Numerous reports revealed that many kinds of cysteine proteases played a crucial role in pathogen invasion. To investigate the relationship between cathepsin X of teleost fish and virus infection, EcCX was cloned and characterized in the orange-spotted grouper, Epinephelus coioides. The open reading frame (ORF) of EcCX included 909 nucleotides and encoded a protein consisting of 302 amino acids, which shared 75% and 56% identity with zebrafish and humans, respectively. The protein EcCX mainly consisted of a signal peptide (1-19 aa), a pro-pre-peptide region (20-55 aa), and a mature cysteine protease region (56-302 aa). Subcellular localization analysis showed that EcCX was mainly distributed in the cytoplasm, but EcCX ectoped to the vicinity of apoptotic vesicles in FHM cells during SGIV infection. Following stimulation with SGIV or Poly (dA:dT), there was a notable rise in the expression levels of EcCX. EcCX overexpression facilitated virus infection, upregulated the production of inflammatory factors, and induced the activation of the NF-κB promoter. Furthermore, the overexpression of EcCX also accelerated the process of SGIV-induced apoptosis, potentially by enhancing the promoter activity of P53 and AP-1. Overall, our findings demonstrated a correlation between the function of EcCX and SGIV infection, providing a new understanding of the mechanisms involved in fish virus infection.

Inhibition of DDR1 promotes ferroptosis and overcomes gefitinib resistance in non-small cell lung cancer.

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), which serves the critical pillar for the treatment of non-small cell lung cancer (NSCLC). However, the acquired resistance remains a challenge for its clinical application, for which, practical strategies to reverse gefitinib resistance in NSCLC are necessary. Ferroptosis, a programmed cell death driven by ferritin-dependent lipid peroxidation, involves in NSCLC progression and related chemoresistance. In our previous work, the self-synthesised EGFR inhibitor Yfq07 (N4, N6-disubstituted pyrimidine-4,6-diamine derivatives) displayed a considerable inhibitory effect on NSCLC both in vitro and in vivo. Herein, we observed that Yfq07 suppressed the proliferation of PC-9GR and HCC827GR cells, two gefitinib resistance NSCLC cell lines. Mechanically, Yfq07 inhibited the phosphorylation of the Discoidin Domain Receptor 1 (DDR1), a receptor tyrosine kinase (RTK) highly expressed in multiple cancers, accompanied by downregulated miR-3648 and upregulated SOCS2. Inhibition or knockdown of DDR1 suppressed the proliferation, migration, and invasion of gefitinib-resistant NSCLC cells, and on the other hand, also downregulated miR-3648 and promoted SOCS2 expression. More specifically, miR-3648 targeted the 3'UTR segment of SOCS2 mRNA and thus affecting the P-ERK signalling pathway to regulate the malignant behaviors of gefitinib-resistant NSCLC cells. Furthermore, Yfq07 also indirectly induced the ferroptosis of gefitinib-resistant NSCLC cells via SOCS2 triggered inhibition of xCT-GPX4 pathway. In conclusion, our study indicates that DDR1 inhibitor Yfq07 promotes ferroptosis and reverses gefitinib-resistance of NSCLC through DDR1-miR-3648-SOCS2 signalling pathway, which provides insights for targeted therapy of gefitinib-resistant NSCLC and drug developments targeting ferroptosis.

Novel analgesic peptide derived from Cinobufacini injection suppressing inflammation and pain via ERK1/2/COX-2 pathway.

Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient's life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1ß) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.

Differences in HDL-related coronary heart disease risk between individuals with and without diabetes.

BACKGROUND AND AIMS: High-density lipoprotein (HDL) might lose atheroprotective functions in the presence of diabetes. We sought to examine associations of HDL cholesterol (HDL-C) and HDL particle (HDL-P) subclasses with risk of coronary heart disease (CHD) stratified by diabetes. METHODS: We included 393,516 participants (20,691 diabetics and 372,825 nondiabetics) from the UK Biobank. Restricted cubic splines cooperated with Cox model were used to estimate associations of HDL with CHD. RESULTS: During a median follow-up of 13.0 years, 3398 (16.4 %) and 24,772 (6.6 %) incident CHD events occurred among diabetics and nondiabetics, respectively. HDL-C showed inverse associations with CHD among nondiabetics, whereas U-shaped associations among diabetics. Compared to individuals with normal HDL-C (40th - 60th percentile, 1.32-1.51 mmol/L), those in the top percentile (95th, >2.16 mmol/L) had lower CHD risks among nondiabetics (Hazard Ratio, 0.79; 95 % confidence interval, 0.73-0.86), but higher risks among diabetics (1.38, 1.02-1.88). As for HDL-P, there were inverted U-shaped associations of very large HDL-P and linearly negative associations of large HDL-P with CHD among nondiabetics; however, linearly positive associations of very large HDL-P and null associations of large HDL were observed among diabetics. L-shaped associations of medium and small HDL-P were found both in diabetics and nondiabetics. CONCLUSIONS: Very high HDL-C levels were associated with lower CHD risks in nondiabetics, but higher risks in diabetics. Smaller HDL-P was negatively, whereas very large HDL-P was positively associated with CHD risk in diabetics. These data advance our knowledge about the interactions between HDL and diabetes.

Exploring autism via the retina: Comparative insights in children with autism spectrum disorder and typical development.

Autism spectrum disorder (ASD) is a widely recognized neurodevelopmental disorder, yet the identification of reliable imaging biomarkers for its early diagnosis remains a challenge. Considering the specific manifestations of ASD in the eyes and the interconnectivity between the brain and the eyes, this study investigates ASD through the lens of retinal analysis. We specifically examined differences in the macular region of the retina using optical coherence tomography (OCT)/optical coherence tomography angiography (OCTA) images between children diagnosed with ASD and those with typical development (TD). Our findings present potential novel characteristics of ASD: the thickness of the ellipsoid zone (EZ) with cone photoreceptors was significantly increased in ASD; the large-caliber arteriovenous of the inner retina was significantly reduced in ASD; these changes in the EZ and arteriovenous were more significant in the left eye than in the right eye. These observations of photoreceptor alterations, vascular function changes, and lateralization phenomena in ASD warrant further investigation, and we hope that this work can advance interdisciplinary understanding of ASD.

Estimating Haplotype Structure and Frequencies: A Bayesian Approach to Unknown Design in Pooled Genomic Data.

The estimation of haplotype structure and frequencies provides crucial information about the composition of genomes. Techniques, such as single-individual haplotyping, aim to reconstruct individual haplotypes from diploid genome sequencing data. However, our focus is distinct. We address the challenge of reconstructing haplotype structure and frequencies from pooled sequencing samples where multiple individuals are sequenced simultaneously. A frequentist method to address this issue has recently been proposed. In contrast to this and other methods that compute point estimates, our proposed Bayesian hierarchical model delivers a posterior that permits us to also quantify uncertainty. Since matching permutations in both haplotype structure and corresponding frequency matrix lead to the same reconstruction of their product, we introduce an order-preserving shrinkage prior that ensures identifiability with respect to permutations. For inference, we introduce a blocked Gibbs sampler that enforces the required constraints. In a simulation study, we assessed the performance of our method. Furthermore, by using our approach on two distinct sets of real data, we demonstrate that our Bayesian approach can reconstruct the dominant haplotypes in a challenging, high-dimensional set-up.

Depressive symptoms, lifestyle behaviors, and risk of cardiovascular disease and mortality in individuals of different socioeconomic status: A prospective cohort study.

BACKGROUND: Depression is a global health issue, associated with increased risk of cardiovascular disease (CVD) and premature death, but whether the association varied across different socioeconomic status (SES), and mechanisms responsible for this association is unclear. We aimed to evaluate the association of depressive symptoms with the risk of incident CVD and mortality in people of low, medium, and high SES, and determine the extent to which lifestyle behaviors could explain the association. METHODS: This study included 314,800 participants from the UK Biobank. Depressive symptoms were assessed using the Patient Health Questionnaire-2 (PHQ-2). Information on socioeconomic status and lifestyle was obtained from baseline assessment. RESULTS: During 12 years of follow-up, 29,074 incident CVD cases and 16,673 deaths were documented. The increased CVD risk in participants with depressive symptoms (versus without) was more pronounced as SES decreased, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.30 (1.22, 1.39), 1.27 (1.17, 1.37), and 1.17 (0.97, 1.41) in participants of low, medium, and high SES, respectively. The corresponding HRs (95% CIs) for all-cause mortality were 1.16 (1.07, 1.26), 1.21 (1.08, 1.36), and 1.24 (0.95, 1.61). In addition, multiple lifestyle factors together explained 14.4% to 32.8% of the elevated CVD and mortality risk due to depressive symptoms. LIMITATIONS: Moderate sensitivity of PHQ-2, lacked information on the severity of depression, baseline measurement of lifestyle. CONCLUSIONS: Depressive symptoms were associated with higher risks of incident CVD and mortality, especially in low SES groups, and lifestyle behaviors only explained a moderate proportion of the association. These findings indicated that health policies targeting healthy lifestyle promotion alone might not be sufficient, and other measures tackling social inequity are warranted to attenuate the elevated health risk due to depression.

Development and immune evaluation of LAMP1 chimeric DNA vaccine against Singapore grouper iridovirus in orange-spotted grouper, Epinephelus coioides.

Grouper is one of the most important and valuable mariculture fish in China, with a high economic value. As the production of grouper has increased, massive outbreaks of epidemic diseases have limited the development of the industry. Singapore grouper iridovirus (SGIV) is one of the most serious infectious viral pathogens and has caused huge economic losses to grouper farming worldwide due to its rapid spread and high lethality. To find new strategies for the effective prevention and control of SGIV, we constructed two chimeric DNA vaccines using Lysosome-associated membrane protein 1 (LAMP1) fused with major capsid proteins (MCP) against SGIV. In addition, we evaluated the immune protective effects of vaccines including pcDNA3.1-3HA, pcDNA3.1-MCP, pcDNA3.1-LAMP1, chimeric DNA vaccine pcDNA3.1-MLAMP and pcDNA3.1-LAMCP by intramuscular injection. Our results showed that compared with groups injected with PBS, pcDNA3.1-3HA, pcDNA3.1-LAMP1 or pcDNA3.1-MCP, the antibody titer significantly increased in the chimeric vaccine groups. Moreover, the mRNA levels of immune-related factors in groupers, including IRF3, MHC-I, TNF-α, and CD8, showed the same trend. However, MHC-II and CD4 were significantly increased only in the chimeric vaccine groups. After 28 days of vaccination, groupers were challenged with SGIV, and mortality was documented for each group within 14 days. The data showed that two chimeric DNA vaccines provided 87 % and 91 % immune protection for groupers which were significantly higher than the 52 % protection rate of pcDNA3.1-MCP group, indicating that both forms of LAMP1 chimeric vaccines possessed higher immune protection against SGIV, providing the theoretical foundation for the creation of novel DNA vaccines for fish.

Polysaccharides derived from Spirulina platensis inhibited Singapore grouper iridovirus by impeding the entry of viral particles.

Attributable to the rapid dissemination and high lethality of Singapore grouper iridovirus (SGIV), it has caused significant economic losses for marine fish aquaculture in China and Southeast Asian nations. Hence, there is an urgent need to find antiviral drugs that are both safe and effective. In this study, a novel heteropolysaccharide named Spirulina platensis polysaccharides (SPP) was purified and characterized from S. platensis. The molecular weight of SPP is 276 kDa and it mainly consists of Glc and Rha, followed by minor components such as Gal, Xyl, and Fuc. The backbone of SPP was determined to be →2) -ß-Rhap-(1 â†’ 4) -α-Fucp-(1 â†’ [2) -α-Rhap-(1] 2[→6)-α-Glcp-(1] 4[→ 4) -α-Glcp-(1] 8[→ 4) -ß-Glcp-(1]2→, with branches of ß-Galp, α-Xylp and α-Glcp. SPP significantly inhibited SGIV-induced cytopathic effects (CPEs), viral gene replication and viral protein expression. The antiviral mechanism of SPP was associated with the disruption of SGIV entry to host cells. Furthermore, it was not observed that SPP made statistically significant impact on the expression of interferon-related cytokines. Our results offered novel insights into the potential utilization of spirulina polysaccharides for combating aquatic animal viruses.

The triple-drug combination DBDx enhances the antitumor efficacy of PD-1 antibody associated with Treg modulation.

OBJECTIVE: This study investigated the antitumor efficacy of programmed cell death protein-1 (PD-1) antibody and DBDx, a triple-drug combination of dipyridamole, bestatin, and dexamethasone, and their related immunomodulation. MATERIALS AND METHODS: Mouse melanoma B16, mouse Lewis lung carcinoma, and mouse breast carcinoma 4T1 were used for evaluating the in vivo therapeutic efficacy of DBDx, PD-1 antibody, and their combination. The peripheral blood and tumor tissues of 4T1 tumor-bearing mice were collected to analyze regulatory T cells and measured using flow cytometry. RESULTS: The combination of PD-1 antibody and DBDx enhanced the therapeutic efficacy against B16 melanoma. The suppression of tumor growth by PD-1 antibody and DBDx was more significant than that by anti-PD-1 monotherapy. The tumor growth inhibition rates of PD-1 antibody, DBDx, and their combination were 54.0%, 72.4%, and 83.1%, respectively, suggesting a synergistic effect as determined by the coefficient of drug interaction. No significant changes were found in the body weights in all the above groups, indicating that the treated mice tolerated the applied drug doses. Similarly, enhanced therapeutic efficacy of the PD-1 antibody and DBDx combination was observed in murine Lewis lung carcinoma and 4T1 breast cancer models. In 4T1 breast cancer-bearing mice, the immunotherapy-related changes in lymphocytes in peripheral blood and tumor microenvironment were evaluated with flow cytometry. Compared with anti-PD-1 monotherapy, peripheral blood and tumor-infiltrating lymphocytes were found a lower ratio of regulatory T cell (Treg) subset cells and a higher ratio of CD8+/Treg cells. CONCLUSIONS: The combination of PD-1 antibody and DBDx could achieve enhanced therapeutic antitumor efficacy than anti-PD-1 monotherapy, suggesting potential for using the triple-drug combination DBDx in cancer immunotherapy.

Curcumin Alleviates Singapore Grouper Iridovirus-Induced Intestine Injury in Orange-Spotted Grouper (Epinephelus coioides).

Singapore grouper iridovirus (SGIV) is a new ranavirus species in the Iridoviridae family, whose high lethality and rapid spread have resulted in enormous economic losses for the aquaculture industry. Curcumin, a polyphenolic compound, has been proven to possess multiple biological activities, including antibacterial, antioxidant, and antiviral properties. This study was conducted to determine whether curcumin protected orange-spotted grouper (Epinephelus coioides) from SGIV-induced intestinal damage by affecting the inflammatory response, cell apoptosis, oxidative stress, and intestinal microbiota. Random distribution of healthy orange-spotted groupers (8.0 ± 1.0 cm and 9.0 ± 1.0 g) into six experimental groups (each group with 90 groupers): Control, DMSO, curcumin, SGIV, DMSO + SGIV, and curcumin + SGIV. The fish administered gavage received DMSO dilution solution or 640 mg/L curcumin every day for 15 days and then were injected intraperitoneally with SGIV 24 h after the last gavage. When more than half of the groupers in the SGIV group perished, samples from each group were collected for intestinal health evaluation. Our results showed that curcumin significantly alleviated intestine damage and repaired intestinal barrier dysfunction, which was identified by decreased intestine permeability and serum diamine oxidase (DAO) activity and increased expressions of tight junction proteins during SGIV infection. Moreover, curcumin treatment suppressed intestinal cells apoptosis and inflammatory response caused by SGIV and protected intestinal cells from oxidative injury by enhancing the activity of antioxidant enzymes, which was related to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Moreover, we found that curcumin treatment restored the disruption of the intestinal microbiota caused by SGIV infection. Our study provided a theoretical basis for the functional development of curcumin in aquaculture by highlighting the protective effect of curcumin against SGIV-induced intestinal injury.

Bayesian inference of polymerase dynamics over the exclusion process.

Transcription is a complex phenomenon that permits the conversion of genetic information into phenotype by means of an enzyme called RNA polymerase, which erratically moves along and scans the DNA template. We perform Bayesian inference over a paradigmatic mechanistic model of non-equilibrium statistical physics, i.e. the asymmetric exclusion processes in the hydrodynamic limit, assuming a Gaussian process prior for the polymerase progression rate as a latent variable. Our framework allows us to infer the speed of polymerases during transcription given their spatial distribution, while avoiding the explicit inversion of the system's dynamics. The results, which show processing rates strongly varying with genomic position and minor role of traffic-like congestion, may have strong implications for the understanding of gene expression.

Association of healthy sleep pattern with risk of recurrent cardiovascular events among patients with coronary heart disease.

AIMS: To examine the association of a healthy sleep pattern with the risk of recurrent cardiovascular events among patients with coronary heart disease (CHD). METHODS AND RESULTS: This prospective cohort study included 21 193 individuals with CHD from the UK Biobank. A healthy sleep score was generated based on a combination of chronotype, sleep duration, insomnia, and excessive daytime sleepiness. Cox proportional hazards regression models were applied to estimate the associations between healthy sleep score and recurrent cardiovascular events. During a median of 11.1 years of follow up, we documented 3771 recurrent cardiovascular events, including 1634 heart failure cases and 704 stroke cases. After multivariable adjustment, including lifestyle factors, medical history, and CHD duration, sleep 7-8 h/day, never/rarely insomnia, and no frequent daytime sleepiness were each significantly associated with a 12-22% lower risk of heart failure. In addition, compared with participants who had a healthy sleep score of 0-1, the multivariable-adjusted HR (95% CI) for participants with a healthy sleep score of 4 was 0.86 (0.75, 0.99) for recurrent cardiovascular events, 0.71 (0.57, 0.89) for heart failure, and 0.72 (0.51, 1.03) for stroke. CONCLUSIONS: Adherence to a healthy sleep pattern was significantly associated with a lower risk of recurrent cardiovascular events among patients with CHD, especially for heart failure. These findings indicate that healthy sleep behaviours could be beneficial in the prevention of cardiovascular event recurrence.

Associations of Clinical Risk Factors and Novel Biomarkers With Age at Onset of Type 2 Diabetes.

CONTEXT: Younger onset of type 2 diabetes (T2D) was associated with higher risks of vascular complications and mortality. OBJECTIVE: To prospectively assess risk profiles for incident T2D stratified by age at onset. METHODS: A total of 471 269 participants free of T2D at baseline were included from the UK Biobank. Approximately 70 clinical, lipid, lipoprotein, inflammatory, and metabolic markers, and genetic risk scores (GRSs) were analyzed. Stratified Cox proportional-hazards regression models were used to estimate hazard ratios (HRs) for T2D with age of diagnosis divided into 4 groups (≤50.0, 50.1-60.0, 60.1-70.0, and >70.0 years). RESULTS: During 11 years of follow-up, 15 805 incident T2D were identified. Among clinical risk factors, obesity had the highest HR at any age, ranging from 13.16 (95% CI, 9.67-17.91) for 50.0 years and younger to 4.13 (3.78-4.51) for older than 70.0 years. Other risks associated with T2D onset at age 50.0 years and younger included dyslipidemia (3.50, 2.91-4.20), hypertension (3.21, 2.71-3.80), cardiovascular disease (2.87, 2.13-3.87), parental history of diabetes (2.42, 2.04-2.86), education lower than college (1.89, 1.57-2.27), physical inactivity (1.73, 1.43-2.10), smoking (1.38, 1.13-1.68), several lipoprotein particles, inflammatory markers, liver enzymes, fatty acids, amino acids, as well as GRS. Associations of most risk factors and biomarkers were markedly attenuated with increasing age at onset (P interaction <.05), and some were not significant for onset at age older than 70.0 years, such as smoking, systolic blood pressure, and apolipoprotein B. CONCLUSION: Most risk factors or biomarkers had stronger relative risks for T2D at younger ages, which emphasizes the necessity of promoting primary prevention among younger individuals. Moreover, obesity should be prioritized.

Associations of Serum 25(OH)D With Risk of Recurrent Cardiovascular Events in Individuals With Coronary Heart Disease.

CONTEXT: Few studies have examined the relationship between vitamin D and the risk of recurrent cardiovascular (CV) events in people with coronary heart disease (CHD). OBJECTIVE: This study aimed to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentration and the vitamin D receptor (VDR) polymorphisms with the risk of recurrent CV events in individuals with established CHD. METHODS: A total of 22 571 participants with CHD were included from the UK Biobank. Recurrent CV events, including myocardial infarction (MI), heart failure (HF), stroke, and CV disease mortality, were identified from electronic health records. Cox proportional-hazard models were used to calculate hazard ratios (HRs) and 95% CIs. RESULTS: The median (interquartile range) of serum 25(OH)D concentration was 44.8 nmol/L (range, 30.3-61.4 nmol/L), and 58.6% of participants had 25(OH)D below 50 nmol/L. During a median follow-up of 11.2 years, a total of 3998 recurrent CV events were documented. After multivariable adjustment, there was a nonlinear inverse relationship between serum 25(OH)D and recurrent CV events (P nonlinearity <.01), and the decreasing risk gradually leveled off at around 50 nmol/L. Compared with participants with serum 25(OH)D less than 25.0 nmol/L, the HRs (95% CIs) for participants with serum 25(OH)D of 50.0 to 74.9 nmol/L were 0.64 (0.58-0.71) for recurrent CV events, 0.78 (0.65-0.94) for MI, 0.66 (0.57-0.76) for HF, and 0.66 (0.52-0.84) for stroke. In addition, these associations were not modified by genetic variants in the VDR. CONCLUSION: In people with established CHD, higher serum 25(OH)D concentrations were nonlinearly associated with a lower risk of recurrent CV events, with a potential threshold around 50 nmol/L. These findings highlight the importance of maintaining adequate vitamin D status in the prevention of recurrent CV events among individuals with CHD.

Systematic Exploration of the Potential Material Basis and Molecular Mechanism of the Mongolian Medicine Shudage-4 in Attenuating Stress-Induced Gastric Ulcer in Rat.

Shudage-4, an ancient and well-known formula in traditional Mongolian medicine comprising four different types of traditional Chinese medicine, is widely used in the treatment of gastric ulcers. However, the potential material basis and molecular mechanism of Shudage-4 in attenuating stress-induced gastric ulcers remain unclear. This study aimed to first explore the potential material basis and molecular mechanism of Shudage-4 in attenuating gastric ulcers in rats. The chemical constituents and transitional components in the blood of Shudage-4 were identified by ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS). The rat gastric ulcer model was induced by water immersion restraint stress (WIRS). The ulcer damage to gastric tissue was measured at the gross anatomical level and pathological level by hematoxylin-eosin (HE) staining of gastric tissue. RNA sequencing of gastric tissue and plasma metabolomics were performed to analyze the mechanism of Shudage-4 against gastric ulcers. A Pearson correlation analysis was performed to explore the association between serum metabolites and gene expression of gastric tissue. A total of 30 chemical constituents were identified in Shudage-4 by UPLC-TOF-MS. Among 30 constituents, 13 transitional components in the blood were considered as the potential material basis. Shudage-4 treatment had a significant effect on WIRS-induced gastric ulcers in rats. HE staining of gastric tissue illustrated that WIRS-induced ulcer damage was suppressed by Shudage-4 treatment. RNA sequencing of gastric tissue showed that 282 reversed expression genes in gastric tissue were related to Shudage-4 treatment, and gene set enrichment analysis revealed that Shudage-4 treatment significantly inhibited gene set expression related to reactive oxygen species (ROS), which was also validated by detecting rat gastric tissue MDA, GSH, SOD, GSH-Px, and CAT activities. The plasma metabolomic data demonstrated that 23 significantly differential metabolites were closely associated with the Shudage-4 treatment. The further multiomics joint analysis found that significantly upregulated 5 plasma metabolites in Shudage-4-treated rats compared to model rats were negatively correlated with gene set expression related to ROS in gastric tissue. Shudage-4 alleviated WIRS-induced gastric ulcers by inhibiting ROS generation, which was achieved by regulating plasma metabolites level.

Quantum Similarity Testing with Convolutional Neural Networks.

The task of testing whether two uncharacterized quantum devices behave in the same way is crucial for benchmarking near-term quantum computers and quantum simulators, but has so far remained open for continuous variable quantum systems. In this Letter, we develop a machine learning algorithm for comparing unknown continuous variable states using limited and noisy data. The algorithm works on non-Gaussian quantum states for which similarity testing could not be achieved with previous techniques. Our approach is based on a convolutional neural network that assesses the similarity of quantum states based on a lower-dimensional state representation built from measurement data. The network can be trained off-line with classically simulated data from a fiducial set of states sharing structural similarities with the states to be tested, with experimental data generated by measurements on the fiducial states, or with a combination of simulated and experimental data. We test the performance of the model on noisy cat states and states generated by arbitrary selective number-dependent phase gates. Our network can also be applied to the problem of comparing continuous variable states across different experimental platforms, with different sets of achievable measurements, and to the problem of experimentally testing whether two states are equivalent up to Gaussian unitary transformations.

Ultra-low-coverage genome-wide association study-insights into gestational age using 17,844 embryo samples with preimplantation genetic testing.

BACKGROUND: Very low-coverage (0.1 to 1×) whole genome sequencing (WGS) has become a promising and affordable approach to discover genomic variants of human populations for genome-wide association study (GWAS). To support genetic screening using preimplantation genetic testing (PGT) in a large population, the sequencing coverage goes below 0.1× to an ultra-low level. However, the feasibility and effectiveness of ultra-low-coverage WGS (ulcWGS) for GWAS remains undetermined. METHODS: We built a pipeline to carry out analysis of ulcWGS data for GWAS. To examine its effectiveness, we benchmarked the accuracy of genotype imputation at the combination of different coverages below 0.1× and sample sizes from 2000 to 16,000, using 17,844 embryo PGT samples with approximately 0.04× average coverage and the standard Chinese sample HG005 with known genotypes. We then applied the imputed genotypes of 1744 transferred embryos who have gestational ages and complete follow-up records to GWAS. RESULTS: The accuracy of genotype imputation under ultra-low coverage can be improved by increasing the sample size and applying a set of filters. From 1744 born embryos, we identified 11 genomic risk loci associated with gestational ages and 166 genes mapped to these loci according to positional, expression quantitative trait locus, and chromatin interaction strategies. Among these mapped genes, CRHBP, ICAM1, and OXTR were more frequently reported as preterm birth related. By joint analysis of gene expression data from previous studies, we constructed interrelationships of mainly CRHBP, ICAM1, PLAGL1, DNMT1, CNTLN, DKK1, and EGR2 with preterm birth, infant disease, and breast cancer. CONCLUSIONS: This study not only demonstrates that ulcWGS could achieve relatively high accuracy of adequate genotype imputation and is capable of GWAS, but also provides insights into the associations between gestational age and genetic variations of the fetal embryos from Chinese population.

Differences in HDL-related mortality risk between individuals with and without hypertension: a prospective cohort study in UK Biobank.

BACKGROUND AND AIMS: Very high levels of high-density lipoprotein cholesterol (HDL-C) have been paradoxically linked to increased mortality risk. The present study aimed to examine associations of HDL-C and varied sizes of the HDL particle (HDL-P) with mortality risk stratified by hypertension. METHODS AND RESULTS: This prospective cohort study included 429 792 participants (244 866 with hypertension and 184 926 without hypertension) from the UK Biobank. During a median follow-up of 12.7 years, 23 993 (9.8%) and 8142 (4.4%) deaths occurred among individuals with and without hypertension, respectively. A U-shaped association of HDL-C with all-cause mortality was observed in individuals with hypertension after multivariable adjustment, whereas an L-shape was observed in individuals without hypertension. Compared with individuals with normal HDL-C of 50-70 mg/dL, those with very high HDL-C levels (>90 mg/dL) had a significantly higher risk of all-cause mortality among individuals with hypertension (hazard ratio, 1.47; 95% confidence interval, 1.35-1.61), but not among those without hypertension (1.05, 0.91-1.22). As for HDL-P, among individuals with hypertension, a larger size of HDL-P was positively whereas smaller HDL-P was negatively associated with all-cause mortality. After additional adjustment for larger HDL-P in the model, the U-shaped association between HDL-C and mortality risk was altered to an L-shape among individuals with hypertension. CONCLUSIONS: The increased risk of mortality associated with very high HDL-C existed only in individuals with hypertension, but not in those without hypertension. Moreover, the increased risk at high HDL-C levels in hypertension was likely driven by larger HDL-P.

This study examined the potential modification of hypertension on associations of high-density lipoprotein cholesterol (HDL-C), especially at a very high level, and varied sizes of HDL particle (HDL-P) with the risk of mortality.Very high HDL-C levels were associated with increased risk of mortality in individuals with hypertension, but not in those without hypertension.In individuals with hypertension, the increased risk at a high HDL-C level was attributed to a larger size of HDL-P, which was directly associated with mortality risk. An inverse association with mortality was observed for a smaller size of HDL-P.