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Aim: We aimed to examine the effect of FHL1 in the diagnosis and prognosis of non-small-cell lung cancer and its relationship with tumor-infiltrating immune cells. Methods: FHL1 expression status and influence on clinical characteristics, diagnosis and prognosis in non-small-cell lung cancer were assessed. Interaction networks of FHL1 were revealed, and a correlation analysis between FHL1 expression and tumor immunity was performed. Results: FHL1 expression was significantly lower in tumors, and downregulated FHL1 predicted a worse prognosis for lung adenocarcinoma. FHL1 expression was correlated with tumor-infiltrating immune cells, immune checkpoints and chemokine levels. Conclusion: FHL1 is a powerful biomarker to evaluate the diagnosis and prognosis and immune infiltration level of lung adenocarcinoma.

Diabetic nephropathy (DN) is one of the most common microvascular diseases in diabetes. Primary membranous nephropathy (PMN) is one of the most common causes of nephrotic syndrome (NS) in adults. Incidence of DN and PMN are increasing. DN complicated with PMN is rarely reported. We report a case of DN with PMN. Early diagnosis is very important, and appropriate treatment can often achieve good results.

We present avidity sequencing, a sequencing chemistry that separately optimizes the processes of stepping along a DNA template and that of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase–polymer–nucleotide complexes bound to clonal copies of DNA targets. These polymer–nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar and yield negligible dissociation rates. Avidity sequencing achieves high accuracy, with 96.2% and 85.4% of base calls having an average of one error per 1,000 and 10,000 base pairs, respectively. We show that the average error rate of avidity sequencing remained stable following a long homopolymer.

Premise of the ResearchThe prevalence of sexual dimorphisms, which evolve due to contrasting strategies to maximize reproductive success in males and females, is variable among dioecious plant species. In theSalicaceae, many traits have been assessed across many studies, but direct or indirect associations between these traits and reproductive allocation are often neglected. Given the dynamic evolution of sex determination systems and the strong interest in wood production in the family, we wondered whether sexual dimorphisms related to reproduction may have gone unreported. Here, we assess sexual dimorphism in reproductive traits in two species ofSalix. Recognition of reproductive sexually dimorphic traits will contribute to understanding the evolution of sex determination systems in the Salicaceae.MethodologyWe conducted observational studies in natural populations to assess the presence of sexual dimorphisms in early spring bud density, catkin number, and flower number per catkin across four sampling periods inSalix exigua. We also analyzed flower number and catkin number per flower inSalix nigra.Pivotal ResultsWe observed no sexual dimorphism in pre-season buds per branch inS. exiguabut did find that males produced more flowers per catkin and more catkins per branch than females in bothS. exiguaandS. nigra.ConclusionsHigher flower numbers in males compared to females is consistent with expectations from intra-sexual selection among males. The presence of reproductive sexual dimorphisms inSalixsuggests that sexual selection may affect the evolution of mating strategies inSalixspecies, and the evolution of the sex determination system within this genus.

PURPOSE: The time-of-flight (TOF) information improves signal-to-noise ratio (SNR) for positron emission tomography (PET) imaging. Existing analytical algorithms for TOF PET usually follow a filtered back-projection process on reconstructing images from the sinogram data. This work aims to develop a back-projection-and-filtering-like (BPF-like) algorithm that reconstructs the TOF PET image directly from listmode data rapidly. METHODS: We extended the 2D conventional non-TOF PET projection model to a TOF case, where projection data are represented as line integrals weighted by the one-dimensional TOF kernel along the projection direction. After deriving the central slice theorem and the TOF back-projection of listmode data, we designed a deep learning network with a modified U-net architecture to perform the spatial filtration (reconstruction filter). The proposed BP-Net method was validated via Monte Carlo simulations of TOF PET listmode data with three different time resolutions for two types of activity phantoms. The network was only trained on the simulated full-dose XCAT dataset and then evaluated on XCAT and Jaszczak data with different time resolutions and dose levels. RESULTS: Reconstructed images show that when compared with the conventional BPF algorithm and the MLEM algorithm proposed for TOF PET, the proposed BP-Net method obtains better image quality in terms of peak signal-to-noise ratio, relative mean square error, and structure similarity index; besides, the reconstruction speed of the BP-Net is 1.75 times faster than BPF and 29.05 times faster than MLEM using 15 iterations. The results also indicate that the performance of the BP-Net degrades with worse time resolutions and lower tracer doses, but degrades less than BPF or MLEM reconstructions. CONCLUSION: In this work, we developed an analytical-like reconstruction in the form of BPF with the reconstruction filtering operation performed via a deep network. The method runs even faster than the conventional BPF algorithm and provides accurate reconstructions from listmode data in TOF-PET, free of rebinning data to a sinogram.

Objective To investigate the changes in Treg and Th17 cells and explore the significance of Treg/Th17 balance in adult primary membranous nephropathy (PMN) patients. Materials and methods A total of 60 PMN patients and 50 healthy adults from June 2013 to October 2016 were enrolled in this study. The levels of Treg, Th17, and related cytokines were assessed. Pearson correlation was used for conducting correlation analysis. Results There was a significant increase in Th17 frequencies and IL-17 (Th17-related cytokines) in the peripheral blood mononuclear cells (PBMCs), as well as a significant decrease in Treg frequencies and IL-10 (Treg-related cytokines). The IL-17 concentrations in the peripheral blood of PMN patients were positively correlated with urinary protein, while IL-10 levels were negatively correlated with urinary protein. Protein expression of Treg transcription factor (Foxp3) was significantly low in the renal tissues of PMN patients, while the expression of IL-17 was much higher. Th17/Treg imbalance was reversed to normal after effective treatment with tacrolimus in 15 PMN patients. Conclusion These results suggested the existence of Treg/Th17 imbalance in PMN patients, showing the importance of Treg/Th17 imbalance in PMN pathogenesis.

We present a novel sequencing chemistry implemented as part of the AVITI system. Relying on the proximal DNA binding sites created through DNA amplification on a solid support, avidity sequencing uses multivalent nucleotide ligands on dye-labeled cores to simultaneously form polymerase-polymer nucleotide complexes bound to clonal copies of DNA targets. These polymer-nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides by 100x and yield a negligible dissociation rate. We demonstrate the use of avidites within a novel sequencing technology that surpasses Q40 accuracy and enables a diversity of applications that include single cell RNA-seq and whole human genome sequencing.

We present avidity sequencing - a novel sequencing chemistry that separately optimizes the process of stepping along a DNA template and the process of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase-polymer nucleotide complexes bound to clonal copies of DNA targets. These polymer-nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar, and yield negligible dissociation rates. We demonstrate the use of avidites as a key component of a sequencing technology that surpasses Q40 accuracy and enables a diversity of applications that include single cell RNA-seq and whole human genome sequencing. We also show the advantages of this technology in sequencing through long homopolymers.

Renal fibrosis, a common pathological manifestation of virtually all types of chronic kidney disease (CKD), ultimately predisposes patients to end-stage renal disease. However, there is no effective therapy for renal fibrosis. Our earlier studies proved that RIP3-mediated necroptosis might be an important mode of renal tubular cell death in rats with chronic renal injury. Under transmission electron microscopy (TEM), we found morphological changes in the necrosis of human renal tissue, and the percentage of necrotic cells increased significantly in patients with stages 2 and 3a CKD. Immunofluorescence analyses showed that the percentages of TUNEL

Manufactured parts are meticulously engineered to perform well with respect to several conflicting metrics, like weight, stress, and cost. The best achievable trade-offs reside on the Pareto front , which can be discovered via performance-driven optimization. The objectives that define this Pareto front often incorporate assumptions about the context in which a part will be used, including loading conditions, environmental influences, material properties, or regions that must be preserved to interface with a surrounding assembly. Existing multi-objective optimization tools are only equipped to study one context at a time, so engineers must run independent optimizations for each context of interest. However, engineered parts frequently appear in many contexts: wind turbines must perform well in many wind speeds, and a bracket might be optimized several times with its bolt-holes fixed in different locations on each run. In this paper, we formulate a framework for variable-context multi-objective optimization. We introduce the Pareto gamut , which captures Pareto fronts over a range of contexts. We develop a global/local optimization algorithm to discover the Pareto gamut directly, rather than discovering a single fixed-context "slice" at a time. To validate our method, we adapt existing multi-objective optimization benchmarks to contextual scenarios. We also demonstrate the practical utility of Pareto gamut exploration for several engineering design problems.

The roles of long non-coding RNAs (lncRNAs) have been discussed and analysed in previous studies. The messenger RNAs (mRNAs) are frequently reported to be regulated by lncRNAsin colorectal cancer (CRC).Here,we elucidated the role of themRNAactin gamma 2 (

Context The double burden of malnutrition (DBM), undernutrition in early life and an obesogenic environment later on, influences later risk of chronic disorders. The Great Famine in China from 1959 to1962 and remarkable economic development from the 1980s provided such a burden for a large number of people in their 60s. Objective We aimed to analyze the effect of economic status on the association between famine exposure in early life and hyperuricemia in adulthood. Design and Setting Participants numbering 12 666 were enrolled in China based on the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) Study from 2014 to 2016. Participants Participants with fetal or childhood famine exposure (birth year 1949-1962) formed the exposure group. Main Outcome Measure Hyperuricemia was defined as uric acid (UA) > 420 μmol/L for men and > 360 μmol/L for women. The association of famine with hyperuricemia was assessed via regression analyses. Results Early-life famine exposure was negatively associated with UA levels (P = .045) but was not associated with hyperuricemia (P = .226) in the whole study population. Economic status could moderate the association of famine exposure with UA and hyperuricemia (P ≤ .001). In participants with high economic status, early-life famine exposure was positively associated with UA levels (unstandardized coefficients 7.61, 95% CI 3.63-11.59, P < .001), and with hyperuricemia (odds ratio 1.47, 95% CI 1.19-1.81, P < .001). Conclusions Economic status could moderate the association between exposure to famine in early life and hyperuricemia in adulthood, indicating that the DBM might affect hyperuricemia in an opposite direction of the effects of undernutrition in early life alone.

Fanconi anemia (FA) group D2 (FANCD2) is a ferroptosis-related gene crucial for DNA damage repair and negative ferroptosis regulation. Our study aimed to evaluate its prognostic value as well as its association with ferroptosis and immune infiltration in lung adenocarcinoma (LUAD). Transcriptome sequencing data, clinical information, and immunohistochemistry data were collected from the TCGA, GEO, and HPA databases, respectively, for three independent cohorts. Univariate and multivariate analyses were used to assess the correlations between FANCD2 expression and overall survival or clinicopathological parameters. cBioPortal was utilized to investigate the FANCD2 alteration status. Gene and protein networks based on FANCD2 interactions were generated using GeneMANIA and STRING, respectively. Based on the CancerSEA database, the function of FANCD2 was explored at the single-cell level. The relationships between FANCD2 expression levels and tumor-infiltrating immune cells and their equivalent gene signatures were analyzed using TIMER, GEPIA, TISIDB, and ssGSEA databases. CIBERSORT was used to analyze the relevance of the infiltration of 24 types of immune cells. The results revealed that FANCD2 expression was significantly upregulated in LUAD and lung squamous cell carcinoma (LUSC) tissues than that in normal tissues. Further, the overexpression of FANCD2 was closely associated with poor survival for Patients with LUAD but not for patients with LUSC. FANCD2 expression levels were related to tumor-infiltrating immune cells and their matching gene signatures, including CD8+ T cells, natural killer (NK) cells, dendritic cells (DC), and Th2 cells in cases of LUAD. Therefore, FANCD2 was identified as a crucial molecule underlying the synergistic effects of ferroptosis and immunotherapy for Patients with LUAD.

In recent years, with the deepening global energy crisis and greenhouse effect, the trend of the power industry towards low-carbon and clean development has gradually increased. This is manifested in the power supply side and the load side, i.e., the power imbalance brought about by the uncertainty and volatility of both. Therefore, based on the above background, this paper first proposes a new power system consisting of renewable energy, hybrid electric-hydrogen energy storage, and fuel cells. Secondly, this paper proposes a commercial load dispatching strategy with a time-of-use tariff, which is solved by complex optimization to verify its economic advantages and feasibility.

In the present study, genome-wide CNVs were detected in a total of 301 samples from 10 Chinese indigenous horse breeds using the Illumina Equine SNP70 Bead Array, and the candidate genes related to adaptability to high temperature and humidity in Jinjiang horses were identified and validated. We determined a total of 577 CNVs ranging in size from 1.06 Kb to 2023.07 Kb on the 31 pairs of autosomes. By aggregating the overlapping CNVs for each breed, a total of 495 CNVRs were detected in the 10 Chinese horse breeds. As many as 211 breed-specific CNVRs were determined, of which 64 were found in the Jinjiang horse population. By removing repetitive CNV regions between breeds, a total of 239 CNVRs were identified in the Chinese indigenous horse breeds including 102 losses, 133 gains and 4 of both events (losses and gains in the same region), in which 131 CNVRs were novel and only detected in the present study compared with previous studies. The total detected CNVR length was 41.74 Mb, accounting for 1.83% of the total length of equine autosomal chromosomes. The coverage of CNVRs on each chromosome varied from 0.47% to 15.68%, with the highest coverage on ECA 12, but the highest number of CNVRs was detected on ECA1 and ECA24. A total of 229 genes overlapping with CNVRs were detected in the Jinjiang horse population, which is an indigenous horse breed unique to the southeastern coast of China exhibiting adaptability to high temperature and humidity. The functional annotation of these genes showed significant relation to cellular heat acclimation and immunity. The expression levels of the candidate genes were validated by heat shock treatment of various durations on fibroblasts of horses. The results show that the expression levels of HSPA1A were significantly increased among the different heat shock durations. The expression level of NFKBIA and SOCS4 declined from the beginning of heat shock to 2 h after heat shock and then showed a gradual increase until it reached the highest value at 6 h and 10 h of heat shock, respectively. Breed-specific CNVRs of Chinese indigenous horse breeds were revealed in the present study, and the results facilitate mapping CNVs on the whole genome and also provide valuable insights into the molecular mechanisms of adaptation to high temperature and humidity in the Jinjiang horse.

Background: Fanconi anemia (FA) group D2 (FANCD2) is a ferroptosis-related gene crucial for DNA damage repair and negatively regulates ferroptosis. Our study aimed to evaluate its prognostic value as well as its association with ferroptosis and immune infiltration in lung adenocarcinoma (LUAD). Methods: Transcriptome sequencing data and clinical information, three independent cohorts, as well as immunohistochemistry, were collected from the TCGA, GEO, and HPA databases, respectively. Univariate and multivariate analyses were used to assess the correlations between FANCD2 expression and overall survival or clinicopathological parameters. cBioPortal was utilized to investigate the FANCD2 alteration status. Gene and protein networks based on FANCD2 interactions were generated using GeneMANIA and STRING, respectively. Based on the CancerSEA database, the function of FANCD2 was explored at the single-cell level. The relationships between FANCD2 expression levels and tumor-infiltrating immune cells and their equivalent gene signatures were analyzed by TIMER, GEPIA, TISIDB, and ssGSEA databases. CIBERSORT was used to analyze the relevance of the infiltration of 24 types of immune cells. Results: The results revealed that FANCD2 expression was significantly upregulated in LUAD and lung squamous cell carcinoma (LUSC) tissues than in normal tissues. Further, the overexpression of FANCD2 was closely associated with poor survival for LUAD patients but not for LUSC patients. FANCD2 expression levels were related to tumor-infiltrating immune cells and their matching gene signatures, including CD8+ T cells, NK cells, DC cells, and Th2 cells in cases of LUAD. Conclusion: FANCD2 was identified as a crucial molecule underlying the synergistic effects of ferroptosis and immunotherapy for LUAD patients.

The gene encoding beta2-adrenergic receptor (β2-AR), adrenoceptor beta 2 (ADRB2), has been reported to closely associated with various cancers. However, its role in lung adenocarcinoma (LUAD) remains controversial. This research shed light on the prognostic value of ADRB2 in LUAD and further explored its association with immune cell infiltration. ADRB2 was significantly decreased in LUAD. ADRB2 expression in LUAD was significantly correlated with gender, smoking status, T classification, lymph node metastasis, and pathologic stage. Patients in the low ADRB2 expression group presented with significantly poorer overall survival (OS) and disease-specific survival (DSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) results showed that ADRB2 participates in immune response. The expression of ADRB2 was positively correlated with the infiltration level of most immune cells. Notably, ADRB2 is involved in LUAD progression partly by regulating the immune microenvironment, which may potentially serve as a significant prognostic biomarker as well as a potential drug target.

Background: We aimed to investigate the prognostic value of Four and a half LIM domain protein 1 (FHL1) and its correlation with FHL1 and tumor-infiltration immune cells (TIICs) in lung adenocarcinoma (LUAD). Methods: FHL1 expression status and its influence on clinical characteristics in LUAD and Lung squamous cell carcinoma (LUSC) were collected based on GEPIA, TCGA, GEO, CPTAC, the HPA database, and the GTEx Portal. The ROC curve and Kaplan-Meier plots were used to assess the value of FHL1 expression levels in the diagnosis and prognosis of LUAD and LUSC. The interaction network revealed the related genes and proteins of FHL1 by GeneMANIA and STRING. The functional enrichment analysis based on FHL1 and FHL1-related differentially expression genes (DEGs) was conducted by the “clusterProfile” package and Metascape, respectively. The correlation analysis between FHL1 expression and tumor immunity was performed using TISIH, TIMER, and TISIDB. cBioPortal was used to investigate the mutation status between FHL1 and representative immune checkpoints. Results: The results showed that FHL1 expression was significantly lower in tumors relative to adjacent standard samples, and downregulated FHL1 predicted a worse prognosis for LUAD than that for LUSC. Additionally, FHL1 participated in the interleukin 15 mediated signaling pathway, response to interleukin-9, and neutrophil-mediated cytotoxicity. It was also positively correlated with TIICs (B cells, CD8+T, CD4+T cells, macrophages, neutrophils, and DC), immune checkpoints (CD80, CD48, VTCN, and PVR), and chemokines (CCL5, CCL17, CCL20 and CXCL8). Conclusion: FHL1 is a powerful prognostic biomarker of immune infiltration.

The gene encoding beta2-adrenergic receptor (β2-AR), adrenoceptor beta 2 (ADRB2), has been reported to closely associated with various cancers. However, its role in lung adenocarcinoma (LUAD) remains controversial. This research shed light on the prognostic value of ADRB2 in LUAD and further explored its association with immune cell infiltration. ADRB2 was significantly decreased in LUAD. ADRB2 expression in LUAD was significantly correlated with gender, smoking status, T classification, and pathologic stage. Patients in the low ADRB2 expression group presented with significantly poorer overall survival (OS) and disease-specific survival (DSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) results showed that ADRB2 participates in immune response. The expression of ADRB2 was positively correlated with the infiltration level of most immune cells. Notably, ADRB2 is involved in LUAD progression partly by regulating the immune microenvironment, which may potentially serve as a significant prognostic biomarker as well as a potential drug target.

Fabrication condition greatly influences the microstructures and properties of Al alloys. However, most of the available reports focus on a single fabrication technique, indicating there is still a lack of systematic comparisons among wider ranges of fabrication methods. In this paper, with conventional casting (via sand/Fe/Cu mold) and additive manufacturing (AM, via selective laser melting, SLM) methods, the effects of cooling rate (Ṫ) on the microstructures and mechanical properties of hypoeutectic Al-10Si-0.5Mg alloy are systematically investigated. The results show that with increasing cooling rate from sand-mold condition to SLM condition, the grain size (d) is continuously refined from ~3522 ± 668 μm to ~10 μm, and the grain morphology is gradually refined from coarse dendrites to a mixed grain structure composed of columnar plus fine grains (~10 μm). The eutectic Si particles are effectively refined from blocky shape under sand/Fe-mold conditions to needle-like under Cu-mold conditions, and finally to fine fibrous network under SLM condition. The tensile yield strength and elongation is greatly improved from 125 ± 5 MPa (sand-mold) to 262 ± 3 MPa (SLM) and from 0.8 ± 0.2% (sand-mold) to 4.0 ± 0.2% (SLM), respectively. The strengthening mechanism is discussed, which is mainly ascribed to the continuous refinement of grains and Si particles and an increase in super-saturation of Al matrix with increasing cooling rate.

We present high-resolution, three-dimensional hydrodynamic simulations of the fueling of supermassive black holes in elliptical galaxies from a turbulent medium on galactic scales, taking M87* as a typical case. The simulations use a new GPU-accelerated version of the Athena++ AMR code, and span more than 6 orders of magnitude in radius, reaching scales similar to the black hole horizon. The key physical ingredients are radiative cooling and a phenomenological heating model. We find that the accretion flow takes the form of multiphase gas at radii less than about a kpc. The cold gas accretion includes two dynamically distinct stages: the typical disk stage in which the cold gas resides in a rotationally supported disk and relatively rare chaotic stages ($\lesssim 10\%$ of the time) in which the cold gas inflows via chaotic streams. Though cold gas accretion dominates the time-averaged accretion rate at intermediate radii, accretion at the smallest radii is dominated by hot virialized gas at most times. The accretion rate scales with radius as $\dot{M}\propto r^{1/2}$ when hot gas dominates and we obtain $\dot{M}\simeq10^\mathrm{-4}-10^\mathrm{-3}\,M_\odot\,\mathrm{yr^{-1}}$ near the event horizon, similar to what is inferred from EHT observations. The orientation of the cold gas disk can differ significantly on different spatial scales. We propose a subgrid model for accretion in lower-resolution simulations in which the hot gas accretion rate is suppressed relative to the Bondi rate by $\sim (r_\mathrm{g}/r_{\rm Bondi})^{1/2}$. Our results can also provide more realistic initial conditions for simulations of black hole accretion at the event horizon scale., Comment: 28 pages, 25 figures, 2 tables, accepted for publication in ApJ

In order to study the coupling vibration between a bridge and a train under the action of crosswind loads, a dynamic interaction model of the wind–train–bridge system is established considering the geometric nonlinear factors of a long-span suspension bridge. A calculation frame is composed, and a corresponding computer program is written. A long-span highway–railway suspension bridge scheme is studied as an example. The linear and nonlinear vibration responses of the bridge under the simultaneous action of both train loads and wind loads are compared using the self-written program, and the influence of wind velocity and train speed on the dynamic responses of the bridge is studied. The results show that the large displacement nonlinearity of the structure does not influence the changing tendency of bridge displacement and acceleration time histories, but reduces the maximum values of the responses. The geometric nonlinear influence on the bridge accelerations is more obvious than that on the displacements. The natural frequencies of this long-span suspension bridge are very low and it is sensitive to wind action. The changes in train speed and average wind velocity have a great influence on the maximum value of bridge displacement, especially when the lateral deformation and acceleration increase sharply with the wind velocity, and the coupling vibration between wind, train, and the bridge can easily occur. The research results can provide references for the safe operation and maintenance of long-span bridges.

Due to the important application in the study of vibrational circular dichroism and helical dichroism of chiral molecules, the tunable vortex beam at mid-infrared region has attracted increasing attention. Based on orbital angular momentum (OAM) conservation in nonlinear interactions, the vortex pumped singly resonant optical parametric oscillator (SRO) is recognized as a versatile source of coherent vortex radiation providing high power and broad wavelength coverage from a single device. However, the low parametric gain and high oscillation threshold under continuous wave (cw) pumping has so far been the most challenging factor in generating cw tunable vortex beams. To predict the output characteristic of vortex pumped SRO, a theoretical model describing the vortex pumped SRO is needed. In this study, the theoretical model describing the vortex pumped SRO is set up under collimated Gaussian beam approximation. Output characteristics of different SROs are simulated numerically. By proper selection of pump scheme (such as double-pass pumping scheme), the vortex pumped mid-infrared SRO can oscillate at a relatively low pump power. By controlling the gain (mode overlap ratio between the pump and resonant wave in the nonlinear crystal) and loss (employing a spot-defect mirror with different defect size as the output coupler) of the resonant signal mode in the SRO, the OAM of the pump beam can be directionally transferred to a specific down converted beam. The transfer mechanism of the OAM among the pump light and the down-converted beams and factors affecting the transfer are studied. Our study provides the guidelines for the design and optimization of vortex pumped SRO under cw operation.

Weld defect segmentation (WDS) is widely used to detect defects from X-ray images for welds, which is of practical importance for manufacturing in all industries. The key challenge of WDS is that the labeled ground truth of defects is usually not accurate because of the similarities between the candidate defect and noisy background, making it difficult to distinguish some critical defects, such as cracks, from the weld line during the inference stage. In this paper, we propose boundary label smoothing (BLS), which uses Gaussian Blur to soften the labels near object boundaries to provide an appropriate representation of inaccuracy and uncertainty in ground truth labels. We incorporate BLS into dice loss, in combination with focal loss and weighted cross-entropy loss as a hybrid loss, to achieve improved performance on different types of segmentation datasets.

Statistically sound tests of scalar-tensor gravity theories in the strong-field regime usually involves computationally intensive calculations. In this study, we construct a reduced order surrogate model for the scalar-tensor gravity of Damour and Esposito-Far\`ese (DEF) with spontaneous scalarization phenomena developed for neutron stars (NSs). This model allows us to perform a rapid and comprehensive prediction of NS properties, including mass, radius, moment of inertia, effective scalar coupling, and two extra coupling parameters. We code the model in the pySTGROMX package, as an extension of our previous work, that speeds up the calculations at two and even three orders of magnitude and yet still keeps accuracy of $\sim1\%$. Using the model, we can calculate all the post-Keplerian parameters in the timing of binary pulsars conveniently, which provides a quick approach for us to place comprehensive constraints on the DEF theory. We perform Markov-chain Monte Carlo simulations with the model to constrain the parameters of the DEF theory with well-timed binary pulsars. Utilizing five NS-white dwarf and three NS-NS binaries, we obtain the most stringent constraints on the DEF theory up to now. Our work provides a public tool for quick evaluation of NSs' derived parameters to test gravity in the strong-field regime., Comment: 15 pages, 11 figures, 2 tables; accepted by PRD

Background: Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing’s syndrome (CS). This study aimed to explore molecular basis and treatment strategy in a patient with PPNAD.Methods: Whole-exome sequencing (WES) was used to reveal the mutation of PRKAR1A gene, with immunohistochemistry (IHC) to observe the expression of mutant PRKAR1A. Low-dose Mitotane followed by unilateral adrenalectomy were performed to control hypercortisolism. Results: A case of 45-year-old female present with classical hypercortisolism as excessive weight gain, central obesity, and intractable hypertension. She experienced adrenal adenoma surgery 10 years ago with no improvement. Low dosage of Mitotane was used for 7 months to control the severe hypercortisolism. Then laparoscopic unilateral adrenalectomy was performed and pathological features supporting PPNAD. The germline mutation (c.1A>G) in the start codon of PRKAR1A (Protein Kinase cAMP-Dependent Type I Regulatory Subunit Alpha) gene was identified. Notably, the body weight and hypertension were improved obviously one year later even if she discontinued with the Mitotane treatment.Conclusion: Low-dose Mitotane followed by unilateral adrenalectomy showed satisfied treatment effect in this patient, which may be an alternative treatment for PPNAD patient instead of bilateral adrenalectomy.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases related to several types of pathophysiological signs, including β-amyloid (Aβ) plaque accumulation, neuroinflammation, and neurofibrillary tangles. Similar to one of the three subunits of α-ketoglutarate dehydrogenase complex (KGDHC), oxoglutarate dehydrogenase-like (OGDHL) appears to be downregulated in triple-transgenic Alzheimer's (3 × Tg-AD) mice. KGDHC activity is specifically reduced in the brains of people with AD. However, the underlying mechanism of OGDHL in the cause of AD is still unknown. Herein, we confirmed the low expression of OGDHL in the brain of 3 × Tg-AD based on real-time quantitative PCR, Western blot, and immunohistochemistry. We also found that the upregulation of OGDHL can reduce the memory deficits of 3 × Tg-AD mice, thereby reminding its nervous system neuroprotective effect in AD. Next, we confirmed that the increase in OGDHL could reduce neuroinflammation, amyloid plaque load, and tau phosphorylation in 3 × Tg-AD mice. Additionally, we showed that the overexpression of OGDHL could activate Wnt/β-catenin signaling based on the expression of Wnt7B in vitro. Taken together, the results show that the rise of OGDHL reasonably improves the cognitive functions according to the activation of the Wnt/β-catenin signaling pathway. Therefore, this enzyme may be a potential strategy for AD treatment.

Polymers are widely-studied materials with diverse properties and applications determined by different molecular structures. It is essential to represent these structures clearly and explore the full space of achievable chemical designs. However, existing approaches are unable to offer comprehensive design models for polymers because of their inherent scale and structural complexity. Here, we present a parametric, context-sensitive grammar designed specifically for the representation and generation of polymers. As a demonstrative example, we implement our grammar for polyurethanes. Using our symbolic hypergraph representation and 14 simple production rules, our PolyGrammar is able to represent and generate all valid polyurethane structures. We also present an algorithm to translate any polyurethane structure from the popular SMILES string format into our PolyGrammar representation. We test the representative power of PolyGrammar by translating a dataset of over 600 polyurethane samples collected from literature. Furthermore, we show that PolyGrammar can be easily extended to the other copolymers and homopolymers such as polyacrylates. By offering a complete, explicit representation scheme and an explainable generative model with validity guarantees, our PolyGrammar takes an important step toward a more comprehensive and practical system for polymer discovery and exploration. As the first bridge between formal languages and chemistry, PolyGrammar also serves as a critical blueprint to inform the design of similar grammars for other chemistries, including organic and inorganic molecules.

Electron density maps must be accurately estimated to achieve valid dose calculation in MR-only radiotherapy. The goal of this study is to assess whether two deep learning models, the conditional generative adversarial network (cGAN) and the cycle-consistent generative adversarial network (cycleGAN), can generate accurate abdominal synthetic CT (sCT) images from 0.35T MR images for MR-only liver radiotherapy. A retrospective study was performed using CT images and 0.35T MR images of 12 patients with liver (n=8) and non-liver abdominal (n=4) cancer. CT images were deformably registered to the corresponding MR images to generate deformed CT (dCT) images for treatment planning. Both cGAN and cycleGAN were trained using MR and dCT transverse slices. Four-fold cross-validation testing was conducted to generate sCT images for all patients. The HU prediction accuracy was evaluated by voxel-wise similarity metric between each dCT and sCT image for all 12 patients. dCT-based and sCT-based dose distributions were compared using gamma and dose-volume histogram (DVH) metric analysis for 8 liver patients. sCTcycleGAN achieved the average mean absolute error (MAE) of 94.1 HU, while sCTcGAN achieved 89.8 HU. In both models, the average gamma passing rates within all volumes of interest were higher than 95% using a 2%, 2 mm criterion, and 99% using a 3%, 3 mm criterion. The average differences in the mean dose and DVH metrics were within +/-0.6% for the planning target volume and within +/-0.15% for evaluated organs in both models. Results demonstrated that abdominal sCT images generated by both cGAN and cycleGAN achieved accurate dose calculation for 8 liver radiotherapy plans. sCTcGAN images had smaller average MAE and achieved better dose calculation accuracy than sCTcyleGAN images. More abdominal patients will be enrolled in the future to further evaluate two models., Comment: Review in progress

Recent works have shown that interval bound propagation (IBP) can be used to train verifiably robust neural networks. Reseachers observe an intriguing phenomenon on these IBP trained networks: CROWN, a bounding method based on tight linear relaxation, often gives very loose bounds on these networks. We also observe that most neurons become dead during the IBP training process, which could hurt the representation capability of the network. In this paper, we study the relationship between IBP and CROWN, and prove that CROWN is always tighter than IBP when choosing appropriate bounding lines. We further propose a relaxed version of CROWN, linear bound propagation (LBP), that can be used to verify large networks to obtain lower verified errors than IBP. We also design a new activation function, parameterized ramp function (ParamRamp), which has more diversity of neuron status than ReLU. We conduct extensive experiments on MNIST, CIFAR-10 and Tiny-ImageNet with ParamRamp activation and achieve state-of-the-art verified robustness. Code and the appendix are available at https://github.com/ZhaoyangLyu/VerifiablyRobustNN., Comment: Accepted to CVPR 2021 (Oral)

Objective The attraction and influx of monocytes into the retina has been considered a critical step in the development of diabetic retinopathy (DR). However, large population studies about the association between peripheral blood monocyte levels, an inexpensive and easily measurable laboratory index, and DR are limited. Thus, we aimed to investigate the association between peripheral blood monocyte levels and DR. Methods A total of 3223 participants out of 3277 adults with diabetes were enrolled from seven communities in China in this cross-sectional survey. Participants underwent several medical examinations, including the measurement of anthropometric factors, blood pressure, routinely analyzed leukocyte characteristics, glucose, lipid profiles, urine albumin/creatinine ratio and fundus photographs. Results The prevalence of DR among the participants in the highest quartile of peripheral blood monocyte levels significantly decreased by 41% (OR 0.59; 95% CI 0.43, 0.81) compared with the participants in the first quartile (P for trend P for trend > 0.05). Associations between leukocyte, neutrophil and lymphocyte levels and DR were also not found (all P for trend > 0.05). These associations were all fully adjusted for age, sex, education status, duration of diabetes history, current smoking, BMI, HbA1c, dyslipidemia, systolic blood pressure and insulin therapy. Conclusion Decreased peripheral blood monocyte levels were associated with increased odds of DR after adjusting for potential confounders in diabetic adults. However, causation remains to be demonstrated.

Graphite oxide and its exfoliated counterpart, graphene oxide, are important precursors for the large-scale production of graphene-based materials and many relevant applications. The current batch-style preparation of graphite oxide suffers from safety concern, long reaction time, and nonuniform product quality, due to the large volume of reactors and slow energy exchange. Reaction in microchannels can largely enhance the oxidization efficiency of graphite due to the enhanced mass transfer and extremely quick energy exchange, by which the controllable oxidization of graphite is achieved in ≈2 min. Comprehensive characterizations show that the graphene oxide obtained through the microfluidic strategy has features like those prepared in laboratory beakers and industrial reactors, yet with the higher oxidization degree and more epoxy groups. More importantly, the microfluidic preparation allows for on-line monitoring of the oxidization by Raman spectroscopy, ready for the dynamical control of reaction condition and product quality. The capability of continuous preparation is also demonstrated by showing the assembly of fibers and reduction of graphene oxide in microfluidic channels, and the applicability of graphene oxide prepared from the microfluidic strategy for thermally and electrically conductive films.

Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE) caused by uncontrolled activation of the complement system. Mesenchymal stem cells (MSCs) exhibit clinical efficacy for severe LN in our previous studies, but the underlying mechanisms of MSCs regulating complement activation remain largely unknown. Here we show that significantly elevated C5a and C5b-9 were found in patients with LN, which were notably correlated with proteinuria and different renal pathological indexes of LN. MSCs suppressed systemic and intrarenal activation of C5, increased the plasma levels of factor H (FH), and ameliorated renal disease in lupus mice. Importantly, MSCs transplantation up-regulated the decreased FH in patients with LN. Mechanistically, interferon-α enhanced the secretion of FH by MSCs. These data demonstrate that MSCs inhibit the activation of pathogenic C5 via up-regulation of FH, which improves our understanding of the immunomodulatory mechanisms of MSCs in the treatment of lupus nephritis., Graphical Abstract Unlabelled Image, Highlights • Extensively activated C5 might contribute to the progression of lupus nephritis. • MSCs ameliorated renal disease in lupus mice through inhibiting systemic and intrarenal activation of C5. • MSCs increased plasma FH in lupus mice and patients, while interferon-α enhanced the secretion of FH from MSCs. Lupus nephritis (LN) is one of the most common manifestations of systemic lupus erythematosus (SLE). Here we show that obviously increased C5a and C5b-9 were found in patients with LN, and which were notably correlated with some clinical parameters of LN. Mesenchymal stem cells (MSCs) reduced renal disease in lupus mice through factor H (FH), one of complement regulatory proteins, suppressing C5 over-activation. Interestingly, enhanced secretion of FH from MSCs could be induced by interferon-α. The findings would expand our understanding of the complement regulatory mechanisms of MSCs in treating lupus nephritis.

The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33–treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages. Depletion of ILC2, but not Tregs, substantially abolished the protective effect of IL-33 on renal IRI. Adoptive transfer of ex vivo–expanded ILC2 prevented renal injury in mice subjected to IRI. This protective effect associated with induction of M2 macrophages in kidney and required ILC2 production of amphiregulin. Treatment of mice with IL-33 or ILC2 after IRI was also renoprotective. Furthermore, in a humanized mouse model of renal IRI, treatment with human IL-33 or transfer of ex vivo–expanded human ILC2 ameliorated renal IRI. This study has uncovered a major protective role of the IL-33–ILC2 axis in renal IRI that could be potentiated as a therapeutic strategy.

Patch-based methods and deep networks have been employed to tackle image inpainting problem, with their own strengths and weaknesses. Patch-based methods are capable of restoring a missing region with high-quality texture through searching nearest neighbor patches from the unmasked regions. However, these methods bring problematic contents when recovering large missing regions. Deep networks, on the other hand, show promising results in completing large regions. Nonetheless, the results often lack faithful and sharp details that resemble the surrounding area. By bringing together the best of both paradigms, we propose a new deep inpainting framework where texture generation is guided by a texture memory of patch samples extracted from unmasked regions. The framework has a novel design that allows texture memory retrieval to be trained end-to-end with the deep inpainting network. In addition, we introduce a patch distribution loss to encourage high-quality patch synthesis. The proposed method shows superior performance both qualitatively and quantitatively on three challenging image benchmarks, i.e., Places, CelebA-HQ, and Paris Street-View datasets., Comment: Published on TIP. Project Page: https://nbei.github.io/tmad.html

Additional file 1: Table S1. Associations between the monocytes level quartiles and the prevalence of DR among the participants without proliferative DR. Table S2. Associations between the monocytes level quartiles and the prevalence of DR among all the 3266 participants. Table S3. Associations between CRP level and diabetic complications.