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The presence of internal waves (IWs) in the ocean alters the isotropic properties of sound speed profiles (SSPs) in the water column. Changes in the SSPs affect underwater acoustics since most of the energy is dissipated into the seabed due to the downward refraction of sound waves. In consequence, variations in the SSP must be considered when modeling acoustic propagation in the ocean. Empirical orthogonal functions (EOFs) are regularly employed to model and represent SSPs using a linear combination of basis functions that capture the sound speed variability. A different approach is to use dictionary learning to obtain a learned dictionary (LD) that generates a nonorthogonal set of basis functions (atoms) that generate a better sparse representation. In this paper, the performance of EOFs and LDs are evaluated for sparse representation of SSPs affected by the passing of IWs. In addition, an LD-based supervised framework is presented for SSP classification and is compared with classical learning models. The algorithms presented in this work are trained and tested on data collected from the Shallow Water Experiment 2006. Results show that LDs yield lower reconstruction error than EOFs when using the same number of bases. In addition, overcomplete LDs are demonstrated to be a robust method to classify SSPs during low, medium, and high IW activity, reporting accuracy that is comparable to and sometimes higher than that of standard supervised classification methods.

RGB-Infrared person re-identification (RGB-IR ReID) aims to associate people across disjoint RGB and IR camera views. Currently, state-of-the-art performance of RGB-IR ReID is not as impressive as that of conventional ReID. Much of that is due to the notorious modality bias training issue brought by the single-modality ImageNet pre-training, which might yield RGB-biased representations that severely hinder the cross-modality image retrieval. This paper makes first attempt to tackle the task from a pre-training perspective. We propose a self-supervised pre-training solution, named Modality-Aware Multiple Granularity Learning (MMGL), which directly trains models from scratch only on multi-modal ReID datasets, but achieving competitive results against ImageNet pre-training, without using any external data or sophisticated tuning tricks. First, we develop a simple-but-effective 'permutation recovery' pretext task that globally maps shuffled RGB-IR images into a shared latent permutation space, providing modality-invariant global representations for downstream ReID tasks. Second, we present a part-aware cycle-contrastive (PCC) learning strategy that utilizes cross-modality cycle-consistency to maximize agreement between semantically similar RGB-IR image patches. This enables contrastive learning for the unpaired multi-modal scenarios, further improving the discriminability of local features without laborious instance augmentation. Based on these designs, MMGL effectively alleviates the modality bias training problem. Extensive experiments demonstrate that it learns better representations (+8.03% Rank-1 accuracy) with faster training speed (converge only in few hours) and higher data efficiency (, 13 pages, 8 figures

In order to improve air pressure utilization and working performance, the direct seed-metering device for rice was designed with spoiler blades embedded in the air cavity. The study was carried out using theoretical analysis and hydrodynamic methods to obtain the optimum structure of the spoiler blades. Taking the rotating speed of the air cavity, the negative pressure of the air cavity, and the filling height as the test factors, the multiple regression analysis and the response surface analysis were carried out to obtain the best working parameters of the seed-metering device with spoiler blades. The results showed that when the rotating speed of the air cavity was 23.56 r/min, the negative pressure of the air cavity was 4.97 kPa and the filling height was 12.82 cm, the qualified index was 95.21%, the missing index was 3.28% and the multiple index was 1.51%, which was the best seeding performance. Comparing the test with the seed-metering device without spoiler blades, the results showed that the installation of spoiler blades can improve the performance of the seed-metering device under the best working parameters. This study provide a reference for the design of direct seed-metering device for rice.

The most common genetic risk factor for Parkinson's disease (PD) is heterozygous mutationsGBA1, which encodes for the lysosomal enzyme, glucocerebrosidase. Reduced glucocerebrosidase activity associates with an accumulation of abnormal α-synuclein (α-syn) called Lewy pathology, which characterizes PD. PD patients heterozygous for the neuronotypic GBA1L444P mutation (GBA1+/L444P) have a 5.6-fold increased risk of cognitive impairments. In this study, we used GBA1+/L444Pmice of either sex to determine its effects on lipid metabolism, expression of synaptic proteins, behavior, and α-syn inclusion formation. At 3 months of age, GBA1+/L444Pmice demonstrated impaired contextual fear conditioning, and increased motor activity. Hippocampal levels of vGLUT1 were selectively reduced in GBA1+/L444Pmice. We show, using mass spectrometry, that GBA1L444P expression increased levels of glucosylsphingosine, but not glucosylceramide, in the brains and serum of GBA1+/L444Pmice. Templated induction of α-syn pathology in mice showed an increase in α-syn inclusion formation in the hippocampus of GBA1+/L444Pmice compared with GBA1+/+mice, but not in the cortex, or substantia nigra pars compacta. Pathologic α-syn reduced SNc dopamine neurons by 50% in both GBA1+/+and GBA1+/L444Pmice. Treatment with a GlcCer synthase inhibitor did not affect abundance of α-syn inclusions in the hippocampus or rescue dopamine neuron loss. Overall, these data suggest the importance of evaluating the contribution of elevated glucosylsphingosine to PD phenotypes. Further, our data suggest that expression of neuronotypic GBA1L444P may cause defects in the hippocampus, which may be a mechanism by which cognitive decline is more prevalent in individuals with GBA1-PD.SIGNIFICANCE STATEMENTParkinson's disease (PD) and dementia with Lewy bodies (DLB) are both pathologically characterized by abnormal α-synuclein (α-syn). MutantGBA1is a risk factor for both PD and DLB. Our data show the expression of neuronotypic GBA1L444P impairs behaviors related to hippocampal function, reduces expression of a hippocampal excitatory synaptic protein, and that the hippocampus is more susceptible to α-syn inclusion formation. Further, our data strengthen support for the importance of evaluating the contribution of glucosylsphingosine to PD phenotypes. These outcomes suggest potential mechanisms by which GBA1L444P contributes to the cognitive symptoms clinically observed in PD and DLB. Our findings also highlight the importance of glucosylsphingosine as a relevant biomarker for future therapeutics.

The statistical inference of high-order Markov chains (MCs) for biological sequences is vital for molecular sequence analyses but can be hindered by the high dimensionality of free parameters. In the seminal article by Bühlmann and Wyner, variable length Markov chain (VLMC) model was proposed to embed the full-order MC in a sparse structured context tree. In the key procedure of tree pruning of their proposed context algorithm, the word count-based statistic for each branch was defined and compared with a fixed cutoff threshold calculated from a common chi-square distribution to prune the branch of the context tree. In this study, we find that the word counts for each branch are highly intercorrelated, resulting in non-negligible effects on the distribution of the statistic of interest. We demonstrate that the inferred context tree based on the original context algorithm by Bühlmann and Wyner, which uses a fixed cutoff threshold based on a common chi-square distribution, can be systematically biased and error prone. We denote the original context algorithm as VLMC-Biased (VLMC-B). To solve this problem, we propose a new context tree inference algorithm using an adaptive tree-pruning scheme, termed VLMC-Consistent (VLMC-C). The VLMC-C is founded on the consistent branch-specific mixed chi-square distributions calculated based on asymptotic normal distribution of multiple word patterns. We validate our theoretical branch-specific asymptotic distribution using simulated data. We compare VLMC-C with VLMC-B on context tree inference using both simulated and real genome sequence data and demonstrate that VLMC-C outperforms VLMC-B for both context tree reconstruction accuracy and model compression capacity.

We study the properties of the lowest multiplet of light-flavor tensor meson resonances, i.e., f2(1270), a2(1320), K2*(1430), and f2′(1525), within the resonance chiral theory approach. The higher-order resonance chiral operators, including the light-quark mass and 1/NC corrections, are simultaneously incorporated in our study. The use of resonance chiral expressions allows us to analyze not only the relevant experimental data but also in the meantime the lattice results at unphysical quark masses, including the masses of the lowest multiplet of tensor resonances and their decay widths into two pseudoscalar mesons. In addition, the radiative decays of the tensor resonances into one photon plus one pseudoscalar meson and two photons are also studied.

To enhance the frictional wear performance of AZ31B magnesium alloy, a nanocrystalline layer was prepared by ultrasonic impact (UI) treatment on magnesium alloy samples, and the effects of different ultrasonic impact times (5 min, 10 min, and 15 min) on the organization and wear resistance of the composite coating were studied. The findings revealed that the maximum thickness of the composite coating was about 50 μm after 10 min of impact time, which was approximately 15 μm higher than that of the MAO coating. The elemental composition of the composite coating was mainly Mg, O, and Si elements, and the phase structure of the coating, mainly MgO and Mg2SiO4, was the same before and after UI. The microhardness value gradually decreased in a gradient with the increasing distance from the sample surface. The coating had a lower average coefficient of friction (0.18) and lower wear loss (1.56 mg) for the 15 min impact time. Moreover, a small amount of abrasive and adhesive wear served as the primary modes of wear.

Certifiably robust defenses against adversarial patches for image classifiers ensure correct prediction against any changes to a constrained neighborhood of pixels. PatchCleanser arXiv:2108.09135 [cs.CV], the state-of-the-art certified defense, uses a double-masking strategy for robust classification. The success of this strategy relies heavily on the model's invariance to image pixel masking. In this paper, we take a closer look at model training schemes to improve this invariance. Instead of using Random Cutout arXiv:1708.04552v2 [cs.CV] augmentations like PatchCleanser, we introduce the notion of worst-case masking, i.e., selecting masked images which maximize classification loss. However, finding worst-case masks requires an exhaustive search, which might be prohibitively expensive to do on-the-fly during training. To solve this problem, we propose a two-round greedy masking strategy (Greedy Cutout) which finds an approximate worst-case mask location with much less compute. We show that the models trained with our Greedy Cutout improves certified robust accuracy over Random Cutout in PatchCleanser across a range of datasets and architectures. Certified robust accuracy on ImageNet with a ViT-B16-224 model increases from 58.1\% to 62.3\% against a 3\% square patch applied anywhere on the image., 12 pages, 5 figures

To solve the problems of poor stability and low monitoring precision in the online detection of rice moisture in the drying tower, we designed an online detection device for rice moisture at the outlet of the drying tower. The structure of a tri-plate capacitor was adopted, and the electrostatic field of the tri-plate capacitor was simulated using COMSOL software. A central composite design of three factors and five levels was carried out with the thickness, spacing, and area of the plates as the influencing factors and the capacitance-specific sensitivity as the test index. This device was composed of a dynamic acquisition device and a detection system. The dynamic sampling device was found to achieve dynamic continuous sampling and static intermittent measurements of rice using a ten-shaped leaf plate structure. The hardware circuit of the inspection system with STM32F407ZGT6 as the main control chip was designed to realize stable communication between the master and slave computers. Additionally, an optimized BP neural network prediction model based on the genetic algorithm was established using the MATLAB software. Indoor static and dynamic verification tests were also carried out. The results showed that the optimal plate structure parameter combination includes a plate thickness of 1 mm, plate spacing of 100 mm, and relative area of 18,000.069 mm2 while satisfying the mechanical design and practical application needs of the device. The structure of the BP neural network was 2-90-1, the length of individual code in the genetic algorithm was 361, and the prediction model was trained 765 times to obtain a minimum MSE value of 1.9683 × 10−5, which was lower than that of the unoptimized BP neural network with an MSE of 7.1215 × 10−4. The mean relative error of the device was 1.44% under the static test and 2.103% under the dynamic test, which met the accuracy requirements for the design of the device.

The prevalence of carotid stenosis is considerably higher in asymptomatic individuals with multiple risk factors than in the general population. We investigated the validity and reliability of carotid point-of-care ultrasound (POCUS) for rapid carotid atherosclerosis screening. We prospectively enrolled asymptomatic individuals with carotid risk scores of ≥7 who underwent outpatient carotid POCUS and laboratory carotid sonography. Their simplified carotid plaque scores (sCPSs) and Handa’s carotid plaque scores (hCPSs) were compared. Of 60 patients (median age, 81.9 years), 50% were diagnosed as having moderate- or high-grade carotid atherosclerosis. The overestimation and underestimation of outpatient sCPSs were more likely in patients with low and high laboratory-derived sCPSs, respectively. Bland–Altman plots indicated that the mean differences between the participants’ outpatients and laboratory sCPSs were within two standard deviations of their laboratory sCPSs. A Spearman’s rank correlation coefficient revealed a strong positive linear correlation between outpatient and laboratory sCPSs (r = 0.956, p < 0.001). An intraclass correlation coefficient analysis indicated excellent reliability between the two methods (0.954). Both carotid risk score and sCPS were positively and linearly correlated with laboratory hCPS. Our findings indicate that POCUS has satisfactory agreement, strong correlation, and excellent reliability with laboratory carotid sonography, making it suitable for rapid screening of carotid atherosclerosis in high-risk patients.

Plant variety rights are essential for agricultural development and food security. This paper mainly starts with the cost-benefit issue of plant variety rights that enterprises are concerned about, and introduces the cost-benefit analysis method into the research and development, application, and protection of plant variety rights. This research takes the new plant variety rights as the research object, clarifies the development status of the world plant variety rights from the perspective of time series development characteristics and spatial distribution pattern, explores the location of the variety rights in the world, and uses methods such as knowledge measurement and data mining, to carry out in-depth research on the application and authorization of plant variety rights, the scope of protection catalogues, the structure of variety rights, and the applicant unit. Finally, the regression model is tested from five aspects: regression model significance test, model goodness-of-fit test, Hosmer goodness-of-fit test, goodness-of-fit test, and overall accuracy test of model prediction. The regression coefficient of plant variety rights cooperation in the research process was 1.908, and the statistical test value was significant at the 5% level ( P = 0.022 < 0.05 ). Using system dynamics to evaluate its risks, it provides new ideas for the risk analysis and prevention of seed industry enterprises’ variety rights capitalization operation.

Hemorrhagic cystitis (HC) is a severe complication of allo-HSCT, characterized by irritative symptoms of the urinary tract and a higher morbidity rate. The risk factors and prognosis of HC are still unclear.The objective of this study is to identify risk factors and outcomes to improve treatment in pediatric SAA patients undergoing HSCTs in the Children's Hospital of Soochow University.A total of 97 SAA patients as a cohort were enrolled from 2010 to 2019 in the Children's Hospital of Soochow University and a number of factors related to HC and outcomes were analysed. In all transplants (except UCBT), patients received a combination of G-CSF stimulated bone marrow (BM) and peripheral blood stem cell (PBSC). The minimum number of CD34 + cells is 5 × 10Mononuclear cells dose (MNC, cut off: 8.53 × 10We concluded that aGVHD and MNC dose in graft might play an important role in the development of HC in pediatric SAA patients undergoing allo-HSCT. HC is also a key complication affecting the prognosis of children with SAA after allo-HSCT.

Cadherin-catenin complexes are integral components of the adherens junctions crucial for cell-cell adhesion and tissue homeostasis. Dysregulation of these complexes is linked to cancer development via alteration of cell-autonomous oncogenic signaling pathways and extrinsic tumor microenvironment. Advances in multiomics have uncovered key signaling events in multiple cancer types, creating a need for a better understanding of the crosstalk between cadherin-catenin complexes and oncogenic pathways. In this review, we focus on the biological functions of classical cadherins and associated catenins, describe how their dysregulation influences major cancer pathways, and discuss feedback regulation mechanisms between cadherin complexes and cellular signaling. We discuss evidence of cross regulation in the following contexts: Hippo-Yap/Taz and receptor tyrosine kinase signaling, key pathways involved in cell proliferation and growth; Wnt, Notch, and hedgehog signaling, key developmental pathways involved in human cancer; as well as TGFβ and the epithelial-to-mesenchymal transition program, an important process for cancer cell plasticity. Moreover, we briefly explore the role of cadherins and catenins in mechanotransduction and the immune tumor microenvironment.

Emerging isoniazid resistance in the 1970s allowed M. tuberculosis strains to spread and form into large multidrug-resistant tuberculosis clusters in the isolated plateau of Tibet, China. The epidemic was driven by the high risk of transmission as well as the potential of acquiring further drug resistance from isoniazid-resistant strains.

BackgroundFecal microbiota transplantation (FMT) may be helpful in the treatment of autism spectrum disorder (ASD) as rebalancing the gut microbiome has been shown to potentially improve behavioral symptoms in children with ASD.MethodsThis systematic review was conducted to assess the effect of FMT for children with ASD. The Embase, PubMed, Web of Science, and Cochrane Library databases were searched for articles published from inception to October 6, 2022. Two reviewers independently screened the identified records and undertook data extraction.ResultsThe search identified a total of five studies: two prospective open-label studies, two retrospective observational studies, and a case report; however, no randomized controlled trial was identified. All five studies reported a significant post-FMT-treatment improvement in neuropsychological assessment of ASD. The two prospective open-label studies suggested that the Autism Behavior Checklist (ABC) score, and the Social Responsiveness Scale (SRS) score at the posttreatment assessment decreased from the baseline (Wilcoxon signed-rank test; all p < 0.01]). The two retrospective observational studies suggested that FMT helped to improve the ASD symptoms. One observational study reported that the Childhood Autism Rating Scale (CARS) score and ABC score of the constipation group decreased from the baseline after the second course assessment (CARS [baseline: mean 35.25 ± standard deviation 4.36, second course: 32.5 ± 3.1, p = 0.015]; ABC [baseline: 56.21 ± 16.08, second course: 46.54 ± 16.54, p = 0.046]). Another observational study found that both ABC and CARS scores decreased as the number of FMT courses increased, and significant differences were found at the end of each course as compared with the baseline.ConclusionCompared with the baseline, FMT significantly improved symptoms of autism in children with ASD in observational studies. However, rigorously designed randomized controlled clinical trials are needed to establish the safety and efficacy of FMT as a treatment for ASD.

A recent line of research focuses on crowd density estimation from RGB images for a variety of applications, for example, surveillance and traffic flow control. The performance drops dramatically for low-quality images, such as occlusion, or poor light conditions. However, people are equipped with various wireless devices, allowing the received signals to be easily collected at the base station. As such, another line of research utilizes received signals for crowd counting. Nevertheless, received signals offer only information regarding the number of people, while an accurate density map cannot be derived. As unmanned aerial vehicles (UAVs) are now treated as flying base stations and equipped with cameras, we make the first attempt to leverage both RGB images and received signals for crowd density estimation on UAVs. Specifically, we propose a novel network to effectively fuse the RGB images and received signal strength (RSS) information. Moreover, we design a new loss function that considers the uncertainty from RSS and makes the prediction consistent with the received signals. Experimental results show that the proposed method successfully helps break the limit of traditional crowd density estimation methods and achieves state-of-the-art performance. The proposed dataset is released as a public download for future research.

The immunohistochemical determination of the Ki67 expression is regarded as a reliable method to monitor non small cell lung cancer (NSCLC) proliferation. However, cancer tissues are not uniform and the use of a small tumor sample in biopsy may not be accurate. Although positron emission tomography (PET) represents an alternative to biopsy, by providing the 3D functional and morphological distribution of cancer cells across the entire tumor volume, standardized uptake values (SUVs) exhibit poor accuracy. The purpose of this study is to identify quantitative features in 2-18FFDG PET images uniquely correlated with proliferating lung cancer cells that may perform better than SUVs in the evaluation of lung cancer proliferation. By using a xenograft NSCLC model implanted in 19 mice, we found that 89 textural parameters extracted from 3D 2-18FFDG uptake can be described by 6 independent principal components accounting for 95% of the total variance. One of these components features a significant and univocal correlation with 3D-stacked Ki67 staining immunohistochemical images (|r|>0.6;P

Within the effective Lagrangian approach, we carry out a unified study of the J/ψ(ψ′)→VP, J/ψ→Pγ and relevant radiative decays of light-flavor hadrons. A large amount of experimental data, including the various decay widths and electromagnetic form factors, is fitted to constrain the numerous hadron couplings. Relative strengths between the strong and electromagnetic interactions are revealed in the J/ψ→VP and ψ′→VP processes. The effect from the strong interaction is found to dominate in the J/ψ→ρπ decay, while the electromagnetic interaction turns out to be the dominant effect in ψ′→ρπ decay, which provides an explanation to the ρπ puzzle. For the J/ψ→K*K¯+K¯*K and ψ′→K*K¯+K¯*K, the former process is dominated by the strong interactions, and the effects from the electromagnetic parts are found to be comparable with those of strong interactions in the latter process. Different SU(3) breaking effects from the electromagnetic parts appear in the charged and neutral channels for the ψ′→K*K¯+K¯*K processes explain the rather different ratios between B(ψ′→K*+K−+K*−K+)/B(J/ψ→K*+K−+K*−K+) and B(ψ′→K*0K¯0+K¯*0K0)/B(J/ψ→K*0K¯0+K¯*0K0).

We study the properties of the lowest multiplet of light-flavor tensor meson resonances, i.e. $f_2(1270)$, $a_2(1320)$, $K_2^*(1430)$ and $f_2'(1525)$, within the resonance chiral theory approach. The higher-order resonance chiral operators by including the light-quark mass and $1/N_C$ corrections are simultaneously incorporated in our study. The use of resonance chiral expressions allows us to analyze not only the relevant experimental data but also in the meantime the lattice results at unphysical quark masses, including the masses of the lowest multiplet of tensor resonances and their decay widths into two pseudoscalar mesons. In addition, the radiative decays of the tensor resonances into one photon plus one pseudoscalar meson and two photons are studied as well., 18 pages, 3 tables, no figure

Within the effective Lagrangian approach, we carry out a unified study of the $J/\psi (\psi')\to VP$, $J/\psi \to P\gamma$ and relevant radiative decays of light-flavor hadrons. Large amount of experimental data, including the various decay widths and electromagnetic form factors, are fitted to constrain the numerous hadron couplings. Relative strengths between the strong and electromagnetic interactions are revealed in the $J/\psi \to VP$ and $\psi' \to VP$ processes. The effect from the strong interaction is found to dominate in the $J/\psi \to \rho\pi$ decay, while the electromagnetic interaction turns out to be the dominant effect in $\psi' \to \rho\pi$ decay, which provides an explanation to the $\rho\pi$ puzzle. For the $J/\psi\to K^{*}\bar{K}+\bar{K}^{*}K$ and $\psi' \to K^{*}\bar{K}+\bar{K}^{*}K$, the former process is dominated by the strong interactions, and the effects from the electromagnetic parts are found to be comparable with those of strong interactions in the latter process. Different $SU(3)$ breaking effects from the electromagnetic parts appear in the charged and neutral channels for the $\psi' \to K^{*}\bar{K}+\bar{K}^{*}K$ processes explain the rather different ratios between $B(\psi'\to K^{*+}K^{-}+K^{*-}K^{+})/B(J/\psi\to K^{*+}K^{-}+K^{*-}K^{+})$ and $B(\psi'\to K^{*0}\bar{K}^{0}+\bar{K}^{*0}K^{0})/B(J/\psi\to K^{*0}\bar{K}^{0}+\bar{K}^{*0}K^{0})$., Comment: 20 pages, 5 figures

Neuromyelitis optica spectrum disorder (NMOSD), a severe demyelinating disease, is rare among children. Plasma exchange (PE) is widely used as a salvage therapy for severe and corticosteroid-unresponsive patients with NMOSD. Presently, there are limited studies on the safety and efficacy of PE in children with NMOSD. Herein, we report the case of six children with NMOSD who received PE along with the outcomes and adverse events. All six children (female, age at onset 4 years 9 months–13 years 2 months) were AQP4-IgG positive and received standard PE using the COM.TEC Cell Separator. The interval between NMOSD onset and PE was 29 days (range 10–98). Only one patient (P3) who received PE 10 days after acute exacerbations exhibited clinical improvement. Her left visual acuity increased from 0.06 to 0.6 (spectacle-corrected visual acuity was 1.0) and her EDSS score decreased from 4 to 3 points. The other five patients had no clinical improvement and no EDSS scores changes after PE. Adverse events included rashes (P1, P3), acute non-occlusive thrombosis of the internal jugular vein (P1), and thrombocytopenia (P2). In conclusion, the timing of PE initiation as a rescue therapy for severe and corticosteroid-unresponsive pediatric AQP4-IgG positive NMOSD may be crucial to treatment efficacy, and early initiation of PE may be associated with a better outcome. Furthermore, PE has the potential risk for clinically significant adverse effects that should be considered before initiating the therapy and should be weighed against potential benefits.

Additional file 1: Table S1. Basic characteristics of the 173,807 Taiwan Biobank (TWB) participants stratified by smoking status. Table S2. (Based on 173,807 Taiwan Biobank participants) Results of regressing health outcomes on smoking variables while adjusting for six covariates (chronological age (in years), sex (male vs. female), BMI (in kg/m2), drinking status (yes vs. no), performing regular exercise (yes vs. no), and educational attainment (an integer ranging from 1 to 7)). Table S3. (Only in males) Basic characteristics of the 1243 male participants stratified by smoking status. Table S4. (Only in males) Results of regressing each DNAm marker on smoking variables (based on models 1, 3, and 5). Table S5. (Only in males) Results of six DNAm markers in mediating the associations between former smoking status and four health outcomes. Table S6. (Only in males) Results of six DNAm markers in mediating the associations between current smoking status and four health outcomes. Table S7. (Only in males) Results of six DNAm markers in mediating the associations between former smokers’ pack-years and four health outcomes. Table S8. (Only in males) Results of six DNAm markers in mediating the associations between current smokers’ pack-years and four health outcomes. Table S9. (Only in males) Results of six DNAm markers in mediating the associations between years since smoking cessation and four health outcomes. Figure S1. Boxplots of the seven DNA methylation (DNAm) markers. Figure S2. (Both males and females) Heatmap of Pearson’s correlation coefficients among variables. The numbers in cells are Pearson’s correlation coefficients between pairwise variables. Figure S3. (Only in males) Heatmap of Pearson’s correlation coefficients among variables. The numbers in cells are Pearson’s correlation coefficients between pairwise variables. Figure S4. (Only in males) 95% confidence intervals of the effects of six DNAm markers in mediating the associations between former smoking status and four health outcomes. Figure S5. (Only in males) 95% confidence intervals of the effects of six DNAm markers in mediating the associations between current smoking status and four health outcomes. Figure S6. (Only in males) 95% confidence intervals of the effects of six DNAm markers in mediating the associations between former smokers’ pack-years and four health outcomes. Figure S7. (Only in males) 95% confidence intervals of the effects of six DNAm markers in mediating the associations between current smokers’ pack-years and four health outcomes. Figure S8. (Only in males) 95% confidence intervals of the effects of six DNAm markers in mediating the associations between years since smoking cessation and four health outcomes. Figure S9. (Both males and females) The original p-values (without FDR adjustment) of the mediation effects. Figure S10. (Only in males) The original p-values (without FDR adjustment) of the mediation effects.

Within the effective Lagrangian approach, we carry out a unified study of the $J/ψ(ψ')\to VP$, $J/ψ\to Pγ$ and relevant radiative decays of light-flavor hadrons. Large amount of experimental data, including the various decay widths and electromagnetic form factors, are fitted to constrain the numerous hadron couplings. Relative strengths between the strong and electromagnetic interactions are revealed in the $J/ψ\to VP$ and $ψ' \to VP$ processes. The effect from the strong interaction is found to dominate in the $J/ψ\to ρπ$ decay, while the electromagnetic interaction turns out to be the dominant effect in $ψ' \to ρπ$ decay, which provides an explanation to the $ρπ$ puzzle. For the $J/ψ\to K^{*}\bar{K}+\bar{K}^{*}K$ and $ψ' \to K^{*}\bar{K}+\bar{K}^{*}K$, the former process is dominated by the strong interactions, and the effects from the electromagnetic parts are found to be comparable with those of strong interactions in the latter process. Different $SU(3)$ breaking effects from the electromagnetic parts appear in the charged and neutral channels for the $ψ' \to K^{*}\bar{K}+\bar{K}^{*}K$ processes explain the rather different ratios between $B(ψ'\to K^{*+}K^{-}+K^{*-}K^{+})/B(J/ψ\to K^{*+}K^{-}+K^{*-}K^{+})$ and $B(ψ'\to K^{*0}\bar{K}^{0}+\bar{K}^{*0}K^{0})/B(J/ψ\to K^{*0}\bar{K}^{0}+\bar{K}^{*0}K^{0})$., 20 pages, 5 figures

Proton pump inhibitors (PPI), one of the most commonly prescribed medications, carry a myriad of adverse events. For colorectal cancer (CRC) patients, it still remains unclear whether the concurrent use of proton pump inhibitors (PPI) would negatively affect chemotherapy. PubMed, Medline, Embase, and Cochrane Library were searched from inception to 10 June 2022, to identify relevant studies involving CRC patients receiving chemotherapy and reporting comparative survival outcomes between PPI users and non-users. Meta-analyses were performed using random-effects models. We identified 16 studies involving 8,188 patients (PPI = 1,789; non-PPI = 6,329) receiving either capecitabine-based or fluorouracil-based regimens. The overall survival (HR, 1.02; 95% CI, 0.91 to 1.15; I2 = 0%) and progression-free survival (HR, 1.15; 95% CI, 0.98 to 1.35; I2 = 29%) were similar between PPI users and non-users in patients taking capecitabine-based regimens, with low statis-tical heterogeneity. Although the subgroup analysis indicated that early-stage cancer patients taking capecitabine monotherapy with concurrent PPI had a significantly higher disease progression rate (HR, 1.96; 95% CI, 1.21 to 3.16; I2 = 0%) than those who did not use PPIs, both groups had comparable all-cause mortality (HR, 1.31; 95% CI, 0.75 to 2.29; I2 = 0%). On the other hand, there was little difference in both OS and PFS in both early- and end-stage patients taking capecitabine combination therapy between PPI users and non-users. Conversely, the use of concomitant PPI in patients taking fluorouracil-based regimens contributed to a marginally significant higher all-cause mortality (HR, 1.18; 95% CI, 1.00 to 1.40; I2 = 74%), but with high statistical heterogeneity. In conclusion, PPI has little survival influence on CRC patients treated with capecitabine-based regimens, especially in patients taking capecitabine combination therapy. Thus, it should be safe for clinicians to prescribe PPI in these patients. Although patients treated with fluorouracil-based regimens with concomitant PPI trended toward higher all-cause mortality, results were subject to considerable heterogeneity.Systematic Review Registration: identifier https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022338161

Noninvasive measurement of myocardial work (MW) incorporates left ventricular (LV) pressure, and, therefore, allows correction of global longitudinal strain for changing afterload conditions. We sought to investigate MW as a tool to detect early signs of LV dysfunction in primary systemic hypertension patients, particularly with different predictive indices.None left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) patients established were all primary systemic hypertension with preserved ejection fraction. Forty in NLVH and forty in LVH according to left ventricular end-diastolic mass index (LVEDmassI) were prospectively enrolled. The following indices of MW were assessed: global work index, global constructive work, global wasted work (GWW), and global work efficiency (GWE). Both global work index (P=0.348) and global constructive work (P=0.225) were increased in NLVH and decreased in LVH, and GWW (P0.001) was increased significantly in NLVH and increased more in LVH, while GWE (P0.001) was decreased significantly in NLVH and decreased more in LVH. The clinical utility of GWW (95% CI: 0.802-0.951) and GWE (95% CI: 0.811-0.950) were verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with LVH and control comparisons. In multivariate linear regression analysis, 4-dimenaional LVEDmassI was independently associated with GWE (P=0.018) in systemic hypertension patients. Assessment of intraobserver and interobserver variability in the MW echocardiographic data documented good interclass correlation coefficients (all0.85).GWW and GWE derived from MW are more accurate, sensitive, and reproducible predictors to detect early LV dysfunction in primary systemic hypertension patients, especially in distinguishing the potential functional abnormality of NLVH and LVH, even though the ejection fraction is preserved.

Single-cell data integration can provide a comprehensive molecular view of cells. However, how to integrate heterogeneous single-cell multi-omics as well as spatially resolved transcriptomic data remains a major challenge. Here we introduce uniPort, a unified single-cell data integration framework that combines a coupled variational autoencoder (coupled-VAE) and minibatch unbalanced optimal transport (Minibatch-UOT). It leverages both highly variable common and dataset-specific genes for integration to handle the heterogeneity across datasets, and it is scalable to large-scale datasets. uniPort jointly embeds heterogeneous single-cell multi-omics datasets into a shared latent space. It can further construct a reference atlas for gene imputation across datasets. Meanwhile, uniPort provides a flexible label transfer framework to deconvolute heterogeneous spatial transcriptomic data using an optimal transport plan, instead of embedding latent space. We demonstrate the capability of uniPort by applying it to integrate a variety of datasets, including single-cell transcriptomics, chromatin accessibility, and spatially resolved transcriptomic data.

Decaprenylphosphoryl-β-D-ribose oxidase (DprE1) plays important roles in the biosynthesis of mycobacterium cell wall. DprE1 inhibitors have shown great potentials in the development of new regimens for tuberculosis (TB) treatment. In this study, an integrated molecular modeling strategy, which combined computational bioactivity fingerprints and structure-based virtual screening, was employed to identify potential DprE1 inhibitors. Two lead compounds (B2 and H3) that could inhibit DprE1 and thus kill Mycobacterium smegmatis in vitro were identified. Moreover, compound H3 showed potent inhibitory activity against Mycobacterium tuberculosis in vitro (MIC(Mtb) = 1.25 μM) and low cytotoxicity against mouse embryo fibroblast NIH-3T3 cells. Our research provided an effective strategy to discover novel anti-TB lead compounds.

This paper analyses the cognitive characteristics and cognitive laws of freshmen students in learning the C programming language. We have built a spirally ascending complete curriculum theory knowledge system and a practical teaching model of experience–verification–exploration. The knowledge system is established through programming thinking from the perspective of computer systems, designed according to the teaching structure of knowledge construction and trained based on the engineering literacy with a new engineering background. The implementation of the teaching reform has achieved the expected results. The curriculum theory knowledge system is complete, and the practical teaching content is novel and rich. It has stimulated students’ learning enthusiasm and innovative consciousness, cultivated students’ professional qualities and helped to cultivate talents that meet the needs of the industry. Keywords: Programming language, perspective, computer systems, knowledge construction.

Cancer metastasis accounts for nearly 90% of all cancer deaths. Metastatic cancer progression requires both cancer cell migration to the site of the metastasis and subsequent proliferation after colonization. However, it has long been recognized that cancer cell migration and proliferation can be uncoupled; but the mechanism underlying this paradox is not well understood. Here we report that TNFAIP8 (tumor necrosis factor-α-induced protein 8), a “professional” transfer protein of phosphoinositide second messengers, promotes cancer cell migration or metastasis but inhibits its proliferation or cancer growth. TNFAIP8-deficient mice developed larger tumors, but TNFAIP8-deficient tumor cells completely lost their ability to migrate toward chemoattractants and were defective in colonizing lung tissues as compared to wild-type counterparts. Mechanistically, TNFAIP8 served as a cellular “pilot” of tumor cell migration by locally amplifying PI3K–AKT and Rac signals on the cell membrane facing chemoattractant; at the same time, TNFAIP8 also acted as a global inhibitor of tumor cell growth and proliferation by regulating Hippo signaling pathway. These findings help explain the migration–proliferation paradox of cancer cells that characterizes many cancers.

Ma-Chao Li,1,&ast; Xiao-Yue Wang,1,&ast; Tong-Yang Xiao,2,&ast; Shi-Qiang Lin,3 Hai-Can Liu,1 Cheng Qian,4 Da Xu,1 Gui-Lian Li,1 Xiu-Qin Zhao,1 Zhi-Guang Liu,1 Li-Li Zhao,1 Kang-Lin Wan1 1State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3Department of Bioinformatics, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, People’s Republic of China; 4Beijing Center for Disease Control and Prevention, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Li Zhao; Kang-Lin Wan, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, P.O. Box 5, Changping, Beijing, 102206, People’s Republic of China, Tel/Fax +86 10 58900779, Email zhaolili@icdc.cn; wankanglin@icdc.cnObjective: To assess the relationship between the variant rpoB mutations and the degree of rifampin (RIF)/rifabutin (RFB) resistance in Mycobacterium tuberculosis (M. tuberculosis).Methods: We analyzed the whole rpoB gene in 177 M. tuberculosis clinical isolates and quantified their minimum inhibitory concentrations (MICs) using microplate-based assays.Results: The results revealed that of the 177 isolates, 116 were resistant to both RIF and RFB. There were 38 mutated patterns within the sequenced whole rpoB gene of the 120 isolates. Statistical analysis indicated that mutations, S450L, H445D, H445Y, and H445R, were associated with RIF and RFB resistance. Of these mutations, S450L, H445D, and H445Y were associated with high-level RIF and RFB MIC. H445R was associated with high-level RIF MIC, but not high-level RFB MIC. D435V and L452P were associated with only RIF, but not RFB resistance. Q432K and Q432L were associated with high-level RFB MIC. Several single mutations without statistical association with rifamycin resistance, such as V170F, occurred exclusively in low-level RIF but high-level RFB resistant isolates. Additionally, although cross-resistance to RIF and RFB is common, 21 RIF-resistant/RFB-susceptible isolates were identified.Conclusion: This study highlighted the complexity of rifamycin resistance. Identification of the rpoB polymorphism will be helpful to diagnose the RIF-resistant tuberculosis that has the potential to benefit from a treatment regimen including RFB.Keywords: Mycobacterium tuberculosis, rifampin resistance, rifabutin resistance, mutation

An electrochemical oxidative sulfoximido-oxygenation of alkenes has been developed by using

BackgroundVanishing bile duct syndrome is a rare drug-induced disease characterized by cholestasis and ensuing ductopenia. Dermatological manifestations of drug hypersensitivity such as Stevens-Johnson syndrome and toxic epidermal necrolysis may also present in such cases. Hemophagocytic lymphohistiocytosis is a hyperimmune response caused by unchecked stimulation of macrophages, natural killer cells, and cytotoxic T lymphocytes.Case presentationWe report a severe case who presented with concurrent Stevens-Johnson syndrome and vanishing bile duct syndrome complicated by hemophagocytic lymphohistiocytosis after the ingestion of non-steroidal anti-inflammatory drugs. Despite the fact that improvements in vanishing bile duct syndrome can be assumed when combining the clinical lab data clues, as well as repeated liver biopsies showing recovering ductopenia, the patient developed hypovolemic shock combined with septic shock episodes and died on day 236.ConclusionTo our knowledge, this is the fifteenth report of vanishing bile duct syndrome associated with Stevens-Johnson disease or toxic epidermal necrolysis. Mortality rate remains high without treatment guidelines established due to the rarity and heterogenicity of the population. Further studies are needed to identify possible risk factors, prognostic indicators, and the standard of care for vanishing bile duct syndrome associated with Stevens-Johnson disease or toxic epidermal necrolysis.

Nonequilibrium dynamics of many-body systems is challenging for classical computing, providing opportunities for demonstrating practical quantum computational advantage with analogue quantum simulators. It is proposed to be classically intractable to sample driven thermalized many-body states of Bose-Hubbard systems, and further extract multi-point correlations for characterizing quantum phases. Here, leveraging dedicated precise manipulations and number-resolved detection through a quantum gas microscope, we implement and sample a 32-site driven Hubbard chain in the thermalized phase. Multi-point correlations of up to 14th-order extracted from experimental samples offer clear distinctions between the thermalized and many-body-localized phases. In terms of estimated computational powers, the quantum simulator is comparable to the fastest supercomputer with currently known best algorithms. Our work paves the way towards practical quantum advantage in simulating Floquet dynamics of many-body systems., 18 pages, 14 figures

Featuring excellent coherence and operated parallelly, ultracold atoms in optical lattices form a competitive candidate for quantum computation. For this, a massive number of parallel entangled atom pairs have been realized in superlattices. However, the more formidable challenge is to scale-up and detect multipartite entanglement due to the lack of manipulations over local atomic spins in retro-reflected bichromatic superlattices. Here we developed a new architecture based on a cross-angle spin-dependent superlattice for implementing layers of quantum gates over moderately-separated atoms incorporated with a quantum gas microscope for single-atom manipulation. We created and verified functional building blocks for scalable multipartite entanglement by connecting Bell pairs to one-dimensional 10-atom chains and two-dimensional plaquettes of $2\times4$ atoms. This offers a new platform towards scalable quantum computation and simulation.