Coexistence of liver abscess, hepatic cystic echinococcosis and hepatocellular carcinoma: A case report.

BACKGROUND: Human cystic echinococcosis (CE) is a life-threatening zoonosis caused by the Echinococcus granulosus (sensu lato). Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world. The coexistence of CE and HCC is exceedingly rare, and only several well-documented cases have been reported. In addition to this coexistence, there is no report of the coexistence of CE, HCC, and liver abscess to date. Herein, we aimed to report a case of coexistence of liver abscess, hepatic CE, and HCC. CASE SUMMARY: A 65-year-old herdsman presented to the department of interventional therapy with jaundice, right upper abdominal distension and pain for 10 d. Laboratory test showed that he had positive results for HBsAg, HBeAb, HBcAb, and echinococcosis IgG antibody. The test also showed an increased level of alpha fetoprotein of 3400 ng/mL. An abdominal computed tomography (CT) scan revealed an uneven enhanced lesion of the liver at the arterial phase with enhancement and was located S4/8 segment of the liver. In addition, CT scan also revealed a mass in the S6 segment of the liver with a thick calcified wall and according to current guideline and medical images, the diagnoses of hepatic CE (CE4 subtype) and HCC were established. Initially, transarterial chemoembolization was performed for HCC. In the follow-up, liver abscess occurred in addition to CE and HCC; thus, percutaneous liver puncture drainage was performed. In the next follow-up, CE and HCC were stable. The liver abscess was completely resolved, and the patient was discharged with no evidence of recurrence. CONCLUSION: This is the first reported case on the coexistence of liver abscess, hepatic CE, and HCC. Individualized treatment and multidisciplinary discussions should be performed in this setting. Therefore, treatment and diagnosis should be based on the characteristics of liver abscess, hepatic CE, and HCC, and in future clinical work, it is necessary to be aware of the possibility of this complex composition of liver diseases.

Computational design and preparation of water-compatible noncovalent imprinted microspheres.

Herein, 2,4-dichlorophenoxyacetic acid (2,4-D) was used as a model template in a rational design strategy to produce water-compatible noncovalent imprinted microspheres. The proposed approach involved computational modelling for screening functional monomers and a simple method for preparing monodisperse and highly cross-linked microspheres. The fabricated non-imprinted polymer (NIP) and 2,4-d-imprinted polymer (2,4-d-MIP) were characterised, and their adsorption capabilities in an aqueous environment were evaluated. Results reveal that the pseudo-second-order kinetics model was appropriate for representing the adsorption of 2,4-D on NIP and 2,4-d-MIP, with R2 values of 0.97 and 0.99, respectively. The amount of 2,4-D adsorbed on 2,4-d-MIP (97.75 mg g-1) was considerably higher than those of phenoxyacetic acid (35.77 mg g-1), chlorogenic acid (9.72 mg g-1), spiramycin (1.56 mg g-1) and tylosin (1.67 mg g-1). Furthermore, it exhibited strong resistance to protein adsorption in an aqueous medium. These findings confirmed the feasibility of the proposed approach, providing a reference for the development of water-compatible noncovalent imprinted polymers.

Asymmetric, Remote C(sp3)-H Arylation via Sulfinyl-Smiles Rearrangement.

An efficient asymmetric remote arylation of C(sp3)-H bonds under photoredox conditions is described here. The reaction features the addition radicals to a double bond followed by a site-selective radical translocation (1,n-hydrogen atom transfer) as well as a stereocontrolled aryl migration via sulfinyl-Smiles rearrangement furnishing a wide range of chiral α-arylated amides with up to >99 : 1 er. Mechanistic studies indicate that the sulfinamide group governs the stereochemistry of the product with the aryl migration being the rate determining step preceded by a kinetically favored 1,n-HAT process.

Oxygen Vacancy and Heterostructure Modulation of Co2P/Fe2P Electrocatalysts for Improving Total Water Splitting.

Designing a stable and highly active catalyst for hydrogen evolution and oxygen evolution reactions (HER/OER) is essential for the industrialization of hydrogen energy but remains a major challenge. This work reports a simple approach to fabricating coupled Co2P/Fe2P nanorod array catalyst for overall water decomposition, demonstrating the source of excellent activity in the catalytic process. Under alkaline conditions, Co2P/Fe2P heterostructures exhibit an overpotential of 96 and 220 mV for HER and OER, respectively, at 10 mA cm-2. For total water splitting, a low voltage of 1.56 V is required to provide a current density of 10 mA cm-2. And the catalyst exhibits long-term durability for 30 h at a high current density of 250 mA cm-2. The analysis of the results revealed that the presence of interfacial oxygen vacancies and the strong interaction between Co2P/Fe2P provided the catalyst with more electrochemically active sites and a faster charge transfer capability, which improved the hydrolysis dissociation process. Electrochemically active metal (oxygen) hydroxide phases were produced after OER stability testing. The results of this study prove its great potential in practical industrial electrolysis and provide a reasonable and feasible strategy for the design of nonprecious metal phosphide electrocatalysts.

Chiral arylsulfinylamides as reagents for visible light-mediated asymmetric alkene aminoarylations.

Two- or one-electron-mediated difunctionalizations of internal alkenes represent straightforward approaches to assemble molecular complexity by the simultaneous formation of two contiguous Csp3 stereocentres. Although racemic versions have been extensively explored, asymmetric variants, especially those involving open-shell C-centred radical species, are much more limited both in number and scope. Here we describe enantioenriched arylsulfinylamides as all-in-one reagents for the efficient asymmetric, intermolecular aminoarylation of alkenes. Under mild photoredox conditions, nitrogen addition of the arylsulfinylamide onto the double bond, followed by 1,4-translocation of the aromatic ring, produce, in a single operation, the corresponding aminoarylation adducts in enantiomerically enriched form. The sulfinyl group acts here as a traceless chiral auxiliary, as it is eliminated in situ under the mild reaction conditions. Optically pure ß,ß-diarylethylamines, aryl-α,ß-ethylenediamines and α-aryl-ß-aminoalcohols, prominent motifs in pharmaceuticals, bioactive natural products and ligands for transition metals, are thereby accessible with excellent levels of regio-, relative and absolute stereocontrol.

Aberrant immune programming in neutrophils in cystic fibrosis.

Cystic fibrosis is a life-shortening genetic disorder, caused by mutations in the gene that encodes cystic fibrosis transmembrane-conductance regulator, a cAMP-activated chloride and bicarbonate channel. Persistent neutrophilic inflammation is a major contributor to cystic fibrosis lung disease. However, how cystic fibrosis transmembrane-conductance regulator loss of function leads to excessive inflammation and its clinical sequela remains incompletely understood. In this study, neutrophils from F508del-CF and healthy control participants were compared for gene transcription. We found that cystic fibrosis circulating neutrophils have a prematurely primed basal state with significantly higher scores for activation, chemotaxis, immune signaling, and pattern recognition. Such an irregular basal state appeared not related to the blood environment and was also observed in neutrophils derived from the F508del-CF HL-60 cell line, indicating an innate characteristic of the phenotype. Lipopolysaccharides (LPS) stimulation drastically shifted the transcriptional landscape of healthy control neutrophils toward a robust immune response; however, cystic fibrosis neutrophils were immune-exhausted, reflected by abnormal cell aging and fate determination in gene programming. Moreover, cystic fibrosis sputum neutrophils differed significantly from cystic fibrosis circulating neutrophils in gene transcription with increased inflammatory response, aging, apoptosis, and necrosis, suggesting additional environmental influences on the neutrophils in cystic fibrosis lungs. Taken together, our data indicate that loss of cystic fibrosis transmembrane-conductance regulator function has intrinsic effects on neutrophil immune programming, leading to premature priming and dysregulated response to challenge.

Dual-branch multi-information aggregation network with transformer and convolution for polyp segmentation.

Computer-Aided Diagnosis (CAD) for polyp detection offers one of the most notable showcases. By using deep learning technologies, the accuracy of polyp segmentation is surpassing human experts. In such CAD process, a critical step is concerned with segmenting colorectal polyps from colonoscopy images. Despite remarkable successes attained by recent deep learning related works, much improvement is still anticipated to tackle challenging cases. For instance, the effects of motion blur and light reflection can introduce significant noise into the image. The same type of polyps has a diversity of size, color and texture. To address such challenges, this paper proposes a novel dual-branch multi-information aggregation network (DBMIA-Net) for polyp segmentation, which is able to accurately and reliably segment a variety of colorectal polyps with efficiency. Specifically, a dual-branch encoder with transformer and convolutional neural networks (CNN) is employed to extract polyp features, and two multi-information aggregation modules are applied in the decoder to fuse multi-scale features adaptively. Two multi-information aggregation modules include global information aggregation (GIA) module and edge information aggregation (EIA) module. In addition, to enhance the representation learning capability of the potential channel feature association, this paper also proposes a novel adaptive channel graph convolution (ACGC). To validate the effectiveness and advantages of the proposed network, we compare it with several state-of-the-art (SOTA) methods on five public datasets. Experimental results consistently demonstrate that the proposed DBMIA-Net obtains significantly superior segmentation performance across six popularly used evaluation matrices. Especially, we achieve 94.12% mean Dice on CVC-ClinicDB dataset which is 4.22% improvement compared to the previous state-of-the-art method PraNet. Compared with SOTA algorithms, DBMIA-Net has a better fitting ability and stronger generalization ability.

Plant hypersensitive induced reaction protein facilitates cell death induced by secreted xylanase associated with the pathogenicity of Sclerotinia sclerotiorum.

Necrotrophic fungal plant pathogens employ cell death-inducing proteins (CDIPs) to facilitate infection. However, the specific CDIPs and their mechanisms in pathogenic processes of Sclerotinia sclerotiorum, a necrotrophic pathogen that causes disease in many economically important crop species, have not yet been clearly defined. This study found that S. sclerotiorum secretes SsXyl2, a glycosyl hydrolase family 11 xylanase, at the late stage of hyphal infection. SsXyl2 targets the apoplast of host plants to induce cell death independent of xylanase activity. Targeted disruption of SsXyl2 leads to serious impairment of virulence, which can be recovered by a catalytically impaired SsXyl2 variant, thus supporting the critical role of cell death-inducing activity of SsXyl2 in establishing successful colonization of S. sclerotiorum. Remarkably, infection by S. sclerotiorum induces the accumulation of Nicotiana benthamiana hypersensitive-induced reaction protein 2 (NbHIR2). NbHIR2 interacts with SsXyl2 at the plasma membrane and promotes its localization to the cell membrane and cell death-inducing activity. Furthermore, gene-edited mutants of NbHIR2 displayed increased resistance to the wild-type strain of S. sclerotiorum, but not to the SsXyl2-deletion strain. Hence, SsXyl2 acts as a CDIP that manipulates host cell physiology by interacting with hypersensitive induced reaction protein to facilitate colonization by S. sclerotiorum. These findings provide valuable insights into the pathogenic mechanisms of CDIPs in necrotrophic pathogens and lead to a more promising approach for breeding resistant crops against S. sclerotiorum.

Loss of CFTR function in macrophages alters the cell transcriptional program and delays lung resolution of inflammation.

Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CF Transmembrane-conductance Regulator (CFTR) gene. The most severe pathologies of CF occur in the lung, manifesting as chronic bacterial infection, persistent neutrophilic inflammation, and mucopurulent airway obstruction. Despite increasing knowledge of the CF primary defect and the resulting clinical sequelae, the relationship between the CFTR loss of function and the neutrophilic inflammation remains incompletely understood. Here, we report that loss of CFTR function in macrophages causes extended lung inflammation. After intratracheal inoculation with Pseudomonas aeruginosa, mice with a macrophage-specific Cftr-knockout (Mac-CF) were able to mount an effective host defense to clear the bacterial infection. However, three days post-inoculation, Mac-CF lungs demonstrated significantly more neutrophil infiltration and higher levels of inflammatory cytokines, suggesting that Mac-CF mice had a slower resolution of inflammation. Single-cell RNA sequencing revealed that absence of CFTR in the macrophages altered the cell transcriptional program, affecting the cell inflammatory and immune responses, antioxidant system, and mitochondrial respiration. Thus, loss of CFTR function in macrophages influences cell homeostasis, leading to a dysregulated cellular response to infection that may exacerbate CF lung disease.

Variable Tandem Glycine-Rich Repeats Contribute to Cell Death-Inducing Activity of a Glycosylphosphatidylinositol-Anchored Cell Wall Protein That Is Associated with the Pathogenicity of Sclerotinia sclerotiorum.

Glycosylphosphatidylinositol (GPI) anchoring of proteins is a conserved posttranslational modification in eukaryotes. GPI-anchored proteins are widely distributed in fungal plant pathogens, but the specific roles of the GPI-anchored proteins in the pathogenicity of Sclerotinia sclerotiorum, a devastating necrotrophic plant pathogen with a worldwide distribution, remain largely unknown. This research addresses SsGSR1, which encodes an S. sclerotiorum glycine- and serine-rich protein named SsGsr1 with an N-terminal secretory signal and a C-terminal GPI-anchor signal. SsGsr1 is located at the cell wall of hyphae, and deletion of SsGSR1 leads to abnormal cell wall architecture and impaired cell wall integrity of hyphae. The transcription levels of SsGSR1 were maximal in the initial stage of infection, and SsGSR1-deletion strains showed impaired virulence in multiple hosts, indicating that SsGSR1 is critical for the pathogenicity. Interestingly, SsGsr1 targeted the apoplast of host plants to induce cell death that relies on the glycine-rich 11-amino-acid repeats arranged in tandem. The homologs of SsGsr1 in Sclerotinia, Botrytis, and Monilinia species contain fewer repeat units and have lost their cell death activity. Moreover, allelic variants of SsGSR1 exist in field isolates of S. sclerotiorum from rapeseed, and one of the variants lacking one repeat unit results in a protein that exhibits loss of function relative to the cell death-inducing activity and the virulence of S. sclerotiorum. Taken together, our results demonstrate that a variation in tandem repeats provides the functional diversity of GPI-anchored cell wall protein that, in S. sclerotiorum and other necrotrophic pathogens, allows successful colonization of the host plants. IMPORTANCE Sclerotinia sclerotiorum is an economically important necrotrophic plant pathogen and mainly applies cell wall-degrading enzymes and oxalic acid to kill plant cells before colonization. In this research, we characterized a glycosylphosphatidylinositol (GPI)-anchored cell wall protein named SsGsr1, which is critical for the cell wall architecture and the pathogenicity of S. sclerotiorum. Additionally, SsGsr1 induces rapid cell death of host plants that is dependent on glycine-rich tandem repeats. Interestingly, the number of repeat units varies among homologs and alleles of SsGsr1, and such a variation creates alterations in the cell death-inducing activity and the role in pathogenicity. This work advances our understanding of the variation of tandem repeats in accelerating the evolution of a GPI-anchored cell wall protein associated with the pathogenicity of necrotrophic fungal pathogens and prepares the way toward a fuller understanding of the interaction between S. sclerotiorum and host plants.

Fingertip Proximity-Based Grasping Pattern Prediction of Transradial Myoelectric Prosthesis.

For transradial amputees, especially those with insufficient residual muscle activity, it is challenging to quickly obtain an appropriate grasping pattern for a multigrasp prosthesis. To address this problem, this study proposed a fingertip proximity sensor and a grasping pattern prediction method base on it. Rather than exclusively utilizing the EMG of the subject for the grasping pattern recognition, the proposed method used fingertip proximity sensing to predict the appropriate grasping pattern automatically. We established a five-fingertip proximity training dataset for five common classes of grasping patterns (spherical grip, cylindrical grip, tripod pinch, lateral pinch, and hook). A neural network-based classifier was proposed and got a high accuracy (96%) within the training dataset. We assessed the combined EMG/proximity-based method (PS-EMG) on six able-bodied subjects and one transradial amputee subject while performing the "reach-and-pick up" tasks for novel objects. The assessments compared the performance of this method with the typical pure EMG methods. Results indicated that able-bodied subjects could reach the object and initiate prosthesis grasping with the desired grasping pattern on average within 1.93 s and complete the tasks 7.30% faster on average with the PS-EMG method, relative to the pattern recognition-based EMG method. And the amputee subject was, on average, 25.58% faster in completing tasks with the proposed PS-EMG method relative to the switch-based EMG method. The results showed that the proposed method allowed the user to obtain the desired grasping pattern quickly and reduced the requirement for EMG sources.

WFDC12-overexpressing contributes to the development of atopic dermatitis via accelerating ALOX12/15 metabolism and PAF accumulation.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczema-like skin lesions, dry skin, severe itching, and recurrent recurrence. The whey acidic protein four-disulfide core domain gene WFDC12 is highly expressed in skin tissue and up-regulated in the skin lesions of AD patients, but its role and relevant mechanism in AD pathogenesis have not been studied yet. In this study, we found that the expression of WFDC12 was closely related to clinical symptoms of AD and the severity of AD-like lesions induced by DNFB in transgenic mice. WFDC12-overexpressing in the epidermis might promote the migration of skin-presenting cells to lymph nodes and increase Th cell infiltration. Meanwhile, the number and ratio of immune cells and mRNA levels of cytokines were significantly upregulated in transgenic mice. In addition, we found that ALOX12/15 gene expression was upregulated in the arachidonic acid metabolism pathway, and the corresponding metabolite accumulation was increased. The activity of epidermal serine hydrolase decreased and the accumulation of platelet-activating factor (PAF) increased in the epidermis of transgenic mice. Collectively, our data demonstrate that WFDC12 may contribute to the exacerbation of AD-like symptoms in DNFB-induced mouse model by enhancing arachidonic acid metabolism and PAF accumulation and that WFDC12 may be a potential therapeutic target for human atopic dermatitis.

Interleukin-37 promotes DMBA/TPA skin cancer through SIGIRR-mediated inhibition of glycolysis in CD103+DC cells.

Interleukin 37 (IL-37), a member of the IL-1 family, is considered a suppressor of innate and adaptive immunity and, hence is a regulator of tumor immunity. However, the specific molecular mechanism and role of IL-37 in skin cancer remain unclear. Here, we report that IL-37b-transgenic mice (IL-37tg) treated with the carcinogenic 7,12-dimethylbenzoanthracene (DMBA)/12-o-tetradecylphorbol-13-acetate (TPA) exhibited enhanced skin cancer and increased tumor burden in the skin by inhibiting the function of CD103+ dendritic cells (DCs). Notably, IL-37 induced rapid phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), and via single immunoglobulin IL-1-related receptor (SIGIRR), inhibited the long-term Akt activation. Specifically, by affecting the SIGIRR-AMPK-Akt signaling axis, which is related to the regulation of glycolysis in CD103+DCs, IL-37 inhibited their anti-tumor function. Our results show that a marked correlation between the CD103+DC signature (IRF8, FMS-like tyrosine kinase 3 ligand, CLEC9A, CLNK, XCR1, BATF3, and ZBTB46) and chemokines C-X-C motif chemokine ligand 9, CXCL10, and CD8A in a mouse model with DMBA/TPA-induced skin cancer. In a word, our results highlight that IL-37 as an inhibitor of tumor immune surveillance through modulating CD103+DCs and establishing an important link between metabolism and immunity as a therapeutic target for skin cancer.

Neutrophil defect and lung pathogen selection in cystic fibrosis.

Cystic fibrosis is a life-threatening genetic disorder caused by mutations in the CFTR chloride channel. Clinically, over 90% of patients with cystic fibrosis succumb to pulmonary complications precipitated by chronic bacterial infections, predominantly by Pseudomonas aeruginosa and Staphylococcus aureus. Despite the well-characterized gene defect and clearly defined clinical sequelae of cystic fibrosis, the critical link between the chloride channel defect and the host defense failure against these specific pathogens has not been established. Previous research from us and others has uncovered that neutrophils from patients with cystic fibrosis are defective in phagosomal production of hypochlorous acid, a potent microbicidal oxidant. Here we report our studies to investigate if this defect in hypochlorous acid production provides P. aeruginosa and S. aureus with a selective advantage in cystic fibrosis lungs. A polymicrobial mixture of cystic fibrosis pathogens (P. aeruginosa and S. aureus) and non-cystic fibrosis pathogens (Streptococcus pneumoniae, Klebsiella pneumoniae, and Escherichia coli) was exposed to varied concentrations of hypochlorous acid. The cystic fibrosis pathogens withstood higher concentrations of hypochlorous acid than did the non-cystic fibrosis pathogens. Neutrophils derived from F508del-CFTR HL-60 cells killed P. aeruginosa less efficiently than did the wild-type counterparts in the polymicrobial setting. After intratracheal challenge in wild-type and cystic fibrosis mice, the cystic fibrosis pathogens outcompeted the non-cystic fibrosis pathogens and exhibited greater survival in the cystic fibrosis lungs. Taken together, these data indicate that reduced hypochlorous acid production due to the absence of CFTR function creates an environment in cystic fibrosis neutrophils that provides a survival advantage to specific microbes-namely, S. aureus and P. aeruginosa-in the cystic fibrosis lungs.

The value of magnetic resonance ultrashort echo time imaging to evaluate non-calcified cartilage of the knee joint and its damage.

Objectives: To image knee osteochondral specimens using magnetic resonance (MR) ultrashort echo time imaging with pointwise encoding time reduction with radial acquisition combined fat suppression (PETRA-FS) sequence to determine whether it can reveal non-calcified cartilage, including the deep radial layer, and to assess its effectiveness in cartilage damage diagnosis. Materials and methods: PETRA-FS imaging was performed on 58 osteochondral specimens of the lower femur and upper tibia to observe depth of cartilage damage, combined with histological results to observe signal intensity composition. Sensitivity, specificity, and reliability of PETRA-FS sequence for diagnosing cartilage damage were evaluated using histological results as the gold standard. Diagnostic efficacy was assessed using receiver operating characteristic (ROC) curve. Results: MR ultrashort echo time imaging PETRA-FS sequence showed non-calcified cartilage, including tangential, transitional, and radial layers, which showed a high signal. PETRA-FS sequence showed 37 cases of cartilage damage and 21 cases of no damage among 58 specimens, kappa value of 0.75. Histological analysis of the 58 osteochondral specimens revealed 38 cases of cartilage injury and 20 cases of undamaged cartilage. Using histological results as the gold standard, PETRA-FS sequence had a sensitivity of 87.00%, specificity of 80.00%, kappa value of 0.81, and an area under the ROC curve (AUC) of 0.83 for cartilage injury diagnosis. Conclusion: MR ultrashort echo time imaging PETRA-FS sequence can show non-calcified cartilage, including the deep radial layer (which cannot be shown by conventional MR), by exhibiting a high signal in knee osteo-chondral specimens. Thus, PETRA-FS sequences may have important diagnostic value for cartilage injury diagnosis.

Daphnia magna uptake and excretion of luminescence-labelled polystyrene nanoparticle as visualized by high sensitivity real-time optical imaging.

The environmental and ecological consequences of nanoplastics (NPs) draw increasing research interests and social concerns. However, the in situ and real-time detection of NPs from living organisms and transferring media remains as a major technical obstacle for scientific investigation. Herein we report a novel time-gated imaging (TGI) strategy capable of real-time visualizing the intake of NPs by an individual living organism, which is based on the polystyrene NPs labelled with lanthanide up-conversion luminescence. The limit of detection (LOD) of the TGI apparatus was 600 pg (SNR = 3) in a field of view of 2.4 × 3.8 mm. Taking Daphnia magna as the aquatic model, we investigated the dynamics of uptake and accumulation of NPs (500 µg/L) for 24 h, and the subsequent excretion process (in clean medium) for 48 h, and quantitively analyzed the distribution and the overall mass of NPs deposited in D. magna. The uptake of NPs via filter-feeding occurred in a few minutes, whereas a longer accumulation was found, in a timescale of several hours. And similar behaviors (bi-phase elimination) were also seen in the excretion, indicating the migration of NPs into the circulatory system. The average mass of NPs accumulated in an individual D. magna was ∼12 ng after 24 h exposure, indicating that D. magna as a filter feeder tends to retain NPs. The observed NPs accumulation in D. magna exemplifies the potential risk of aquatic ecosystem on exposure to NP contamination.

ABERRANT IMMUNE PROGRAMMING IN NEUTROPHILS IN CYSTIC FIBROSIS.

Cystic fibrosis (CF) is a life-shortening genetic disorder, caused by mutations in the gene that encodes Cystic Fibrosis Transmembrane-conductance Regulator (CFTR), a cAMP-activated chloride and bicarbonate channel. Although multiple organ systems can be affected, CF lung disease claims the most morbidity and mortality due to chronic bacterial infection, persistent neutrophilic inflammation, and mucopurulent airway obstruction. Despite the clear predominance of neutrophils in these pathologies, how CFTR loss-of-function affects these cells per se remains incompletely understood. Here, we report the profiling and comparing of transcriptional signatures of peripheral blood neutrophils from CF participants and healthy human controls (HC) at the single-cell level. Circulating CF neutrophils had an aberrant basal state with significantly higher scores for activation, chemotaxis, immune signaling, and pattern recognition, suggesting that CF neutrophils in blood are prematurely primed. Such an abnormal basal state was also observed in neutrophils derived from an F508del-CF HL-60 cell line, indicating an innate characteristic of the phenotype. LPS stimulation drastically shifted the transcriptional landscape of HC circulating neutrophils towards a robust immune response, however, CF neutrophils were immune-exhausted. Moreover, CF blood neutrophils differed significantly from CF sputum neutrophils in gene programming with respect to neutrophil activation and aging, as well as inflammatory signaling, highlighting additional environmental influences on the neutrophils in CF lungs. Taken together, loss of CFTR function has intrinsic effects on neutrophil immune programming that leads to premature priming and dysregulated response to challenge.

Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism.

The intestinal microbiota has been associated with host immunity as well as psoriasis; however, the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically. Here, we sought to examine its role and mechanism of action in the pathogenesis of psoriasis. We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota. We performed co-housing and fecal microbial transplantation (FMT) experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms, including increasing the infiltration and differentiation of Th17, and increased the abundance of Prevotella, while decreasing that of Parabacteroides distasonis, in the colon. These alterations affected fatty acid metabolism, increasing the abundance of oleic and stearic acids. Meanwhile, gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod (IMQ)-induced psoriasis-like mice. Indeed, administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo, as well as increased the secretion of IL-23 by stimulating DCs in vitro. At last, we found that, treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota, including the decrease of Prevotella and increase of Parabacteroides distasonis. Overall, our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice, suggesting a new target for the clinical diagnosis and treatment of psoriasis.

ACCPG-Net: A skin lesion segmentation network with Adaptive Channel-Context-Aware Pyramid Attention and Global Feature Fusion.

The computer-aided diagnosis system based on dermoscopic images has played an important role in the clinical treatment of skin lesion. An accurate, efficient, and automatic skin lesion segmentation method is an important auxiliary tool for clinical diagnosis. At present, skin lesion segmentation still suffers from great challenges. Existing deep-learning-based automatic segmentation methods frequently use convolutional neural networks (CNN). However, the globally-sharing feature re-weighting vector may not be optimal for the prediction of lesion areas in dermoscopic images. The presence of hairs and spots in some samples aggravates the interference of similar categories, and reduces the segmentation accuracy. To solve this problem, this paper proposes a new deep network for precise skin lesion segmentation based on a U-shape structure. To be specific, two lightweight attention modules: adaptive channel-context-aware pyramid attention (ACCAPA) module and global feature fusion (GFF) module, are embedded in the network. The ACCAPA module can model the characteristics of the lesion areas by dynamically learning the channel information, contextual information and global structure information. GFF is used for different levels of semantic information interaction between encoder and decoder layers. To validate the effectiveness of the proposed method, we test the performance of ACCPG-Net on several public skin lesion datasets. The results show that our method achieves better segmentation performance compared to other state-of-the-art methods.

Zero Echo Time vs. T1-Weighted MRI for Assessment of Cortical and Medullary Bone Morphology Abnormalities Using CT as the Reference Standard.

BACKGROUND: Conventional MR pulse sequences result in poor signal from low T2 cortical bone because the minimum achievable echo time is limited. A sequence resulting in improved bone contrast is desirable. PURPOSE: To evaluate the image quality and diagnostic performance of grayscale inversion zero echo time imaging (GI-ZTE) and grayscale inversion T1-weighted imaging (GI-T1WI) compared with computed tomography (CT). STUDY TYPE: Prospective. SUBJECTS: A total of 50 patients with musculoskeletal tumors or tumor-like diseases of the lower extremities having MRI and CT studies. FIELD STRENGTH/SEQUENCE: GI-T1WI and GI-ZTE sequences at 1.5 T. ASSESSMENT: Assessed cortical and medullary bone morphology abnormalities using CT as the reference standard. Three radiologists scored the images quality and recorded nine metrics to assess the diagnostic performance. STATISTICAL TESTS: Differences in image quality were calculated using the Wilcoxon signed-rank test. The intraclass correlation coefficient (ICC) was used to analyze the agreement of quantitative lesion parameters between CT and MR sequences, as well as the interobserver reliability. A P value <0.05 was considered statistically significant. RESULTS: Image quality score was significantly higher for CT images than GI-TIWI images. Except for radiologist 3 [4(0) vs 4 (1)], there was no significant difference in scores between CT and GI-ZTE [radiologist 1: 4 (0) vs 4 (0), P = 0.133; radiologist 2: 4 (0) vs 4 (0), P = 0.085]. There was good-excellent agreement between both MR sequences and CT for size, lesion number, location, sclerotic rim, expanded shell, destruction pattern, and matrix mineralization for all radiologists (ICC: 0.636-1.000). The consistency of periosteal reaction and penetration of the cortex was fair to good (0.481-0.729) between GI-T1WI and CT and good to excellent between GI-ZTE and CT (0.682-0.852). DATA CONCLUSIONS: GI-ZTE images had superior intermodality agreement with CT images and allowed visualization of more cortical bone detail than GI-T1WI images. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.