Co-infection of H9N2 subtype avian influenza virus and QX genotype live attenuated infectious bronchitis virus increase the pathogenicity in SPF chickens.

Avian influenza virus (AIV) infection and vaccination against live attenuated infectious bronchitis virus (aIBV) are frequent in poultry worldwide. Here, we evaluated the clinical effect of H9N2 subtype AIV and QX genotype aIBV co-infection in specific-pathogen-free (SPF) white leghorn chickens and explored the potential mechanisms underlying the observed effects using by 4D-FastDIA-based proteomics. The results showed that co-infection of H9N2 AIV and QX aIBV increased mortality and suppressed the growth of SPF chickens. In particular, severe lesions in the kidneys and slight respiratory signs similar to the symptoms of virulent QX IBV infection were observed in some co-infected chickens, with no such clinical signs observed in single-infected chickens. The replication of H9N2 AIV was significantly enhanced in both the trachea and kidneys, whereas there was only a slight effect on the replication of the QX aIBV. Proteomics analysis showed that the IL-17 signaling pathway was one of the unique pathways enriched in co-infected chickens compared to single infected-chickens. A series of metabolism and immune response-related pathways linked with co-infection were also significantly enriched. Moreover, co-infection of the two pathogens resulted in the enrichment of the negative regulation of telomerase activity. Collectively, our study supports the synergistic effect of the two pathogens, and pointed out that aIBV vaccines might increased IBV-associated lesions due to pathogenic co-infections. Exacerbation of the pathogenicity and mortality in H9N2 AIV and QX aIBV co-infected chickens possibly occurred because of an increase in H9N2 AIV replication, the regulation of telomerase activity, and the disturbance of cell metabolism and the immune system.

Heterogeneous stiffness of the bone marrow microenvironment regulates the fate decision of haematopoietic stem and progenitor cells.

The bone marrow (BM) niches are the complex microenvironments that surround cells, providing various external stimuli to regulate a range of haematopoietic stem cell (HSC) behaviours. Recently, it has been proposed that the fate decision of HSCs is often correlated with significantly altered biophysical signals of BM niches. To thoroughly elucidate the effect of mechanical microenvironments on cell fates, we constructed 2D and 3D cell culture hydrogels using polyacrylamide to replicate the mechanical properties of heterogeneous sub-niches, including the inherent rigidity of marrow adipose tissue (2 kPa), perivascular tissue (8 kPa) and endosteum region (35 kPa) in BM. Our observations suggest that HSCs can respond to the mechanical heterogeneity of the BM microenvironment, exhibiting diversity in cell mechanics, haematopoietic pool maintenance and differentiated lineages. Hydrogels with higher stiffness promote the preservation of long-term repopulating HSCs (LT-HSCs), while those with lower stiffness support multi-potent progenitors (MPPs) viability in vitro. Furthermore, we established a comprehensive transcriptional profile of haematopoietic subpopulations to reflect the multipotency of haematopoietic stem and progenitor cells (HSPCs) that are modulated by niche-like stiffness. Our findings demonstrate that HSPCs exhibit completely distinct downstream differentiated preferences within hydrogel systems of varying stiffness. This highlights the crucial role of tissue-specific mechanical properties in HSC lineage decisions, which may provide innovative solutions to clinical challenges.

Review of clinical characteristics and mortality outcomes in patients on maintenance hemodialysis during the Omicron surge: a single center experience.

BACKGROUND: This hemodialysis center experienced the pandemic from December 2022 to January 2023. Therefore, we sought to describe the clinical characteristics and mortality outcomes in hemodialysis patients during this Omicron surge. METHODS: According to whether they are infected, they are divided into two groups: SARS-CoV-2-positive and SARS-CoV-2-negative. The SARS-CoV-2-positive group was divided into a survival group and a non-survival group for comparison. RESULTS: 366 of 457 hemodialysis patients were infected with SARS-CoV-2. The most common symptoms observed were fever (43.2%) and cough (29.8%), Followed by diarrhea (1.4%). Hemodialysis patients with hypertension were more susceptible to SARS-CoV-2 infection. The lymphocyte count, serum creatinine, serum potassium, and serum phosphorus in the SARS-CoV-2-positive group were significantly lower than those in the SARS-CoV-2-negative group. The all-cause mortality rate for infection with SARS-CoV-2 was 5.2%. Only 7 of 366 SARS-CoV-2-positive patients were admitted to the intensive care unit, but 6 of them died. Intensive care unit hospitalization rates were significantly higher in the non-survival group compared with the survival group. White blood cells count, neutrophil count, C-reactive protein, AST, and D-dimer in the non-survival group were higher than those in the survival group. The lymphocyte count, hemoglobin concentration, serum creatinine, serum albumin, serum phosphorus and parathyroid hormone in the non-survival group were lower than those in the survival group. Age > 65 years, elevated C-reactive protein and AST are independent risk factors for death. Finally, no significant difference in vaccination status was found between the SARS-CoV-2-positive group and the negative group. CONCLUSIONS: Hemodialysis patients are at high risk for SARS-CoV-2 infection. Ensuring the adequacy of hemodialysis treatment and maintaining good physical condition of patients are the top priorities.

Effect of tocilizumab plus corticosteroid on clinical outcome in patients hospitalized with severe fever with thrombocytopenia syndrome: A randomized clinical trial.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. METHODS: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). RESULTS: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone. CONCLUSIONS: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.

Development of a machine learning model for predicting pneumothorax risk in coaxial core needle biopsy (≤3 cm).

PURPOSE: The aim is to devise a machine learning algorithm exploiting preoperative clinical data to forecast the hazard of pneumothorax post-coaxial needle lung biopsy (CCNB), thereby informing clinical decision-making and enhancing perioperative care. METHOD: This retrospective analysis aggregated clinical and imaging data from patients with lung nodules (≤3 cm) biopsies. Variable selection was done using univariate analysis and LASSO regression, with the dataset subsequently divided into training (80 %) and validation (20 %) subsets. Various machine learning (ML) classifiers were employed in a consolidated approach to ascertain the paramount model, which was followed by individualized risk profiling showcased through Shapley Additive eXplanations (SHAP). RESULTS: Out of the 325 patients included in the study, 19.6% (64/325) experienced postoperative pneumothorax. High-risk factors determined were Cancer, Lesion_type, GOLD, Size, and Depth. The Gaussian Naive Bayes (GNB) classifier demonstrated superior prediction with an Area Under the Curve (AUC) of 0.82 (95% CI 0.71-0.94), complemented by an accuracy rate of 0.8, sensitivity of 0.71, specificity of 0.84, and an F1 score of 0.61 in the test cohort. CONCLUSION: The formulated prognostic algorithm exhibited commendable efficacy in preoperatively prognosticating CCNB-induced pneumothorax, harboring the potential to refine personalized risk appraisals, steer clinical judgment, and ameliorate perioperative patient stewardship.

A universal three-dimensional hydrogel electrode for electrochemical detection of SARS-CoV-2 nucleocapsid protein and hydrogen peroxide.

Coronavirus disease 2019 (COVID-19) is a highly contagious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in a global health crisis. The primary diagnostic method for COVID-19 is quantitative reverse transcription PCR, which is time-consuming and requires expensive instrumentation. Here, we developed an electrochemical biosensor for detecting SARS-CoV-2 biomarkers using a 3D porous polyacrylamide/polyaniline hydrogel (PPG) electrode prepared by UV photopolymerization and in situ polymerization. The electrochemical immunosensor for detecting SARS-CoV-2 N protein via the immune sandwich principle demonstrated a lower detection limit of 42 pg/mL and comparable specificity to a commercial enzyme-linked immunosorbent assay, which was additionally validated in pseudoviruses. The electrochemical sensor for hydrogen peroxide showed a low detection limit of 0.5 µM and excellent selectivity, which was further confirmed in cancer cells under oxidative stress. The biomarkers of SARS-CoV-2 were successfully detected due to the signal amplification capability provided by 3D porous electrodes and the high sensitivity of the antigen-antibody specific binding. This study introduces a novel three-dimensional electrode with great potential for the early detection of SARS-CoV-2.

The {332}<113> Twinning Behavior of a Ti-15Mo Medical Alloy during Cyclic Deformation and Its Effect on Microstructure and Performance.

In this study, the microstructural evolution of a Ti-15Mo medical alloy was investigated, when the in situ cyclic tensile strain had 2% amplitude and the tension-compression cyclic deformation had 1%, 2%, and 3% amplitude. The Vickers hardness and wear resistance of the alloy were also optimized due to the grain-refining effect after cyclic deformation and annealing. The twinning-induced plasticity (TWIP) was considered the main deformation mechanism of the Ti-15Mo alloy during the tensile-compressive cycle deformation with suitable strain amplitude. The {332}<113> twins and boundaries were the main contributors to the grain refinement. The optimal microstructure, hardness, and wear resistance were obtained in the alloy deformed by tension-compression cyclic strain with a 3% strain amplitude. The wear resistance of the annealed alloy in Hank's solution was excellent in contrast to the original Ti-15Mo alloy due to its reasonable microstructure and hardness. It is clear that abundant twins were formed and retained in the coarse grains of the original alloy after cyclic deformation and annealing, which provided the expected refined grains and performance.

The crosstalk between exosomes and ferroptosis: a review.

Exosomes are a subtype of extracellular vesicles composed of bioactive molecules, including nucleic acids, proteins, and lipids. Exosomes are generated by the fusion of intracellular multivesicular bodies (MVBs) with the cell membrane and subsequently released into the extracellular space to participate in intercellular communication and diverse biological processes within target cells. As a crucial mediator, exosomes have been implicated in regulating ferroptosis-an iron-dependent programmed cell death characterized by lipid peroxide accumulation induced by reactive oxygen species. The involvement of exosomes in iron, lipid, and amino acid metabolism contributes to their regulatory role in specific mechanisms underlying how exosomes modulate ferroptosis, which remains incompletely understood, and some related studies are still preliminary. Therefore, targeting the regulation of ferroptosis by exosomes holds promise for future clinical treatment strategies across various diseases. This review aims to provide insights into the pathophysiology and mechanisms governing the interaction between exosomes and ferroptosis and their implications in disease development and treatment to serve as a reference for further research.

Application and evaluation of topical amphotericin B for the treatment of respiratory fungal infections.

BACKGROUND: In recent years, the prevalence of respiratory fungal diseases has increased. Polyene antifungal drugs play a pivotal role in the treatment of these conditions, with amphotericin B (AmB) being the most representative drug. This study aimed to evaluate the efficacy and safety of topical administration of AmB in the treatment of respiratory fungal infections. METHODS: We conducted a retrospective study on hospitalized patients treated with topical administered AmB for respiratory fungal infections from January 2014 to June 2023. RESULTS: Data from 36 patients with invasive pulmonary fungal infections treated with topical administration of AmB were collected and analyzed. Nebulization was administered to 27 patients. After the treatment, 17 patients evidenced improved conditions, whereas 10 patients did not respond and died in the hospital. One patient experienced an irritating cough as an adverse reaction. Seven patients underwent tracheoscopic instillation, and two received intrapleural irrigation; they achieved good clinical therapeutic efficacy without adverse effects. CONCLUSION: The combined application of systemic antifungal treatment and topical administration of AmB yielded good therapeutic efficacy and was well-tolerated by the patients. Close monitoring of routine blood tests, liver and kidney function, and levels of electrolytes, troponin, and B-type natriuretic peptide supported this conclusion.

Reendothelialization of Acellular Adipose Flaps under Mimetic Physiological Dynamic Conditions.

The extensive soft-tissue defects resulting from trauma and tumors pose a prevalent challenge in clinical practice, characterized by a high incidence rate. Autologous tissue flap transplantation, considered the gold standard for treatment, is associated with various drawbacks, including the sacrifice of donor sources, postoperative complications, and limitations in surgical techniques, thereby impeding its widespread applicability. The emergence of tissue-engineered skin flaps, notably the acellular adipose flap (AAF), offers potential alternative solutions. However, a critical concern confronting large-scale tissue-engineered skin flaps currently revolves around the reendothelialization of internal vascular networks. In our study, we have developed an AAF utilizing perfusion decellularization, demonstrating excellent physical properties. Cytocompatibility experiments have confirmed its cellular safety, and cell adhesion experiments have revealed spatial specificity in facilitating endothelial cells adhesion within the adipose flap scaffold. Using a novel mimetic physiological fluid shear stress setting, endothelial cells were dynamically inoculated and cultured within the acellular vascular network of the pedicled AAF in our research. Histological and gene expression analyses have shown that the mimetic physiological fluid dynamic model significantly enhanced the reendothelialization of the AAF. This innovative platform of acellular adipose biomaterials combined with hydrodynamics may offer valuable insights for the design and manufacturing of 3D vascularized tissue constructs, which can be applied to the repair of extensive soft-tissue defects.

Avian leukosis virus usurps the cellular SERBP1 protein to enhance its transcription and promote productive infections in avian cells.

Avian leukosis virus subgroup K (ALV-K) is composed of newly emerging isolates, which cluster separately from the well-characterized subgroups A, B, C, D, E, and J in sequence analysis, and exhibits a specific host range and a unique pattern of superinfection interference. Avian leukosis virus subgroup K replicate more slowly in avian cells than other ALV strains, leading to escaped detection during ALV eradication, but the underlying mechanism are largely unknown. In our previous study, we have reported that JS11C1 and most of other suspected ALV-K strains possessed unique mutations in the U3 region. Here, we selected 5 mutations in some important transcriptional regulation elements to explore the possible factor contributing for the lower activity of LTR, including CA-TG mutation in the CAAT box, 21 nt deletion in the CAAT box, A-G and A-T mutations in the CArG boxes, 11 nt insertion in the PRE boxes, and C-T mutation in the TATA box. On the basis of infectious clone of JS11C1, we demonstrated that the 11 nt fragment in the PRE boxes was associated with the transcription activity of LTR, the enhancer ability of U3, and the replication capacity of the virus. Notably, we determined the differential U3-protein interaction profile of ALVs and found that the 11 nt fragment specifically binds to cellular SERPINE1 mRNA binding protein 1 (SERBP1) to increase the LTR activity and enhance virus replication. Collectively, these findings reveal that a 11 nt fragment in the U3 gene contributed to its binding ability to the cellular SERBP1 to enhance its transcription and the infectious virus productions in avian cells. This study highlighted the vital role of host factor in retrovirus replication and thus provides a new perspective to elucidate the interaction between retrovirus and its host and a molecular basis to develop efficient strategies against retroviruses.

Platelet bioenergetic profiling uncovers a metabolic pattern of high dependency on mitochondrial fatty acid oxidation in type 2 diabetic patients who developed in-stent restenosis.

Although platelet bioenergetic dysfunction is evident early in the pathogenesis of diabetic macrovascular complications, the bioenergetic characteristics in type 2 diabetic patients who developed coronary in-stent restenosis (ISR) and their effects on platelet function remain unclear. Here, we performed platelet bioenergetic profiling to characterize the bioenergetic alterations in 28 type 2 diabetic patients with ISR compared with 28 type 2 diabetic patients without ISR (non-ISR) and 28 healthy individuals. Generally, platelets from type 2 diabetic patients with ISR exhibited a specific bioenergetic alteration characterized by high dependency on fatty acid (FA) oxidation, which subsequently induced complex III deficiency, causing decreased mitochondrial respiration, increased mitochondrial oxidant production, and low efficiency of mitochondrial ATP generation. This pattern of bioenergetic dysfunction showed close relationships with both α-granule and dense granule secretion as measured by surface P-selectin expression, ATP release, and profiles of granule cargo proteins in platelet releasates. Importantly, ex vivo reproduction of high dependency on FA oxidation by exposing non-ISR platelets to its agonist mimicked the bioenergetic dysfunction observed in ISR platelets and enhanced platelet secretion, whereas pharmaceutical inhibition of FA oxidation normalized the respiratory and redox states of ISR platelets and diminished platelet secretion. Further, causal mediation analyses identified a strong association between high dependency on FA oxidation and increased angiographical severity of ISR, which was significantly mediated by the status of platelet secretion. Our findings, for the first time, uncover a pattern of bioenergetic dysfunction in ISR and enhance current understanding of the mechanistic link of high dependency on FA oxidation to platelet abnormalities in the context of diabetes.

High-beam-quality low-resistance vertical-cavity surface-emitting laser array with graphene electrode.

Thermal crosstalk and current crowding effects are pressing issues that significantly impact the beam quality and efficiency of vertical-cavity surface-emitting laser (VCSEL) arrays. In this paper, by taking advantage of the excellent current transmission characteristics of graphene, what we believe to be a novel VCSEL array based on graphene electrode is designed to realize vertical current injections. The series resistance and self-heating of arrays are reduced by controlling the transport direction of the current, effectively suppressing the thermal crosstalk effect. Furthermore, high array beam quality is obtained by optimizing the current density distribution in active regions. Ultimately, the high-power quasi-single mode emission of VCSEL arrays is achieved by introducing graphene electrodes (Gr-VCSEL array) designs. Compared to traditional VCSEL arrays, the 10 × 10 Gr-VCSEL array demonstrates a 41% reduction in series resistance, a side mode suppression ratio of 32 dB, and a divergence angle around 12 °. This structure simultaneously achieves quasi-single mode emission and effectively suppresses the thermal crosstalk effect, providing a new method for the development of high-beam quality VCSEL arrays.

Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system.

Silent information regulator 2 (Sir2) proteins typically catalyze NAD+-dependent protein deacetylation. The recently identified bacterial Sir2 domain-containing protein, defense-associated sirtuin 2 (DSR2), recognizes the phage tail tube and depletes NAD+ to abort phage propagation, which is counteracted by the phage-encoded DSR anti-defense 1 (DSAD1), but their molecular mechanisms remain unclear. Here, we determine cryo-EM structures of inactive DSR2 in its apo form, DSR2-DSAD1 and DSR2-DSAD1-NAD+, as well as active DSR2-tube and DSR2-tube-NAD+ complexes. DSR2 forms a tetramer with its C-terminal sensor domains (CTDs) in two distinct conformations: CTDclosed or CTDopen. Monomeric, rather than oligomeric, tail tube proteins preferentially bind to CTDclosed and activate Sir2 for NAD+ hydrolysis. DSAD1 binding to CTDopen allosterically inhibits tube binding and tube-mediated DSR2 activation. Our findings provide mechanistic insight into DSR2 assembly, tube-mediated DSR2 activation, and DSAD1-mediated inhibition and NAD+ substrate catalysis in bacterial DSR2 anti-phage defense systems.

Structure of the intact tail machine of Anabaena myophage A-1(L).

The Myoviridae cyanophage A-1(L) specifically infects the model cyanobacteria Anabaena sp. PCC 7120. Following our recent report on the capsid structure of A-1(L), here we present the high-resolution cryo-EM structure of its intact tail machine including the neck, tail and attached fibers. Besides the dodecameric portal, the neck contains a canonical hexamer connected to a unique pentadecamer that anchors five extended bead-chain-like neck fibers. The 1045-Å-long contractile tail is composed of a helical bundle of tape measure proteins surrounded by a layer of tube proteins and a layer of sheath proteins, ended with a five-component baseplate. The six long and six short tail fibers are folded back pairwise, each with one end anchoring to the baseplate and the distal end pointing to the capsid. Structural analysis combined with biochemical assays further enable us to identify the dual hydrolytic activities of the baseplate hub, in addition to two host receptor binding domains in the tail fibers. Moreover, the structure of the intact A-1(L) also helps us to reannotate its genome. These findings will facilitate the application of A-1(L) as a chassis cyanophage in synthetic biology.

Combined allergic bronchopulmonary mycosis and eosinophilic granulomatosis with polyangiitis: A case report and literature review.

A 27-year-old female visited our hospital with a history of asthma, peripheral blood eosinophilia, increased total IgE, Aspergillus fumigatus specific IgE, reversible mild bronchiectasis, sinusitis, bronchial mucus plugs and cultivation of Aspergillus from BALF. Glucocorticoids therapy is effective. These results met the diagnostic criteria for both allergic bronchopulmonary aspergillosis (ABPM) and eosinophilic granulomatosis with polyangiitis (EGPA). Special attention should be paid to the possibility of both diseases coexisting in the disease process.

A lightweight network for traffic sign recognition based on multi-scale feature and attention mechanism.

Traffic sign recognition is an important part of intelligent transportation system. It uses computer vision and traffic sign recognition technology to detect and recognize traffic signs on the road automatically. In this paper, we propose a lightweight model for traffic sign recognition based on convolutional neural networks called ConvNeSe. Firstly, the feature extraction module of the model is constructed using the Depthwise Separable Convolution and Inverted Residuals structures. The model extracts multi-scale features with strong representation ability by optimizing the structure of convolutional neural networks and fusing of features. Then, the model introduces Squeeze and Excitation Block (SE Block) to improve the attention to important features, which can capture key information of traffic sign images. Finally, the accuracy of the model in the German Traffic Sign Recognition Benchmark Database (GTSRB) is 99.85%. At the same time, the model has good robustness according to the results of ablation experiments.

Virome characterization of diarrheic red-crowned crane (G. japonensis).

BACKGROUND: The red-crowned crane is one of the vulnerable bird species. Although the captive population has markedly increased over the last decade, infectious diseases can lead to the death of young red-crowned cranes while few virological studies have been conducted. METHODS: Using a viral metagenomics approach, we analyzed the virome of tissues of the dead captive red-crowned crane with diarrhea symptoms in Dongying Biosphere Reserve, Shandong Province, China and feces of individual birds breeding at the corresponding captive breeding center, which were pooled separately. RESULTS: There is much more DNA and RNA viruses in the feces than that of the tissues. RNA virus belonging to the families Picornaviridae, and DNA viruses belonging to the families Parvoviridae, associated with enteric diseases were detected in the tissues and feces. Genomes of the picornavirus, genomovirus, and parvovirus identified in the study were fully characterized, which further suggested that infectious viruses of these families were possibly presented in the diseased red-crowned crane. CONCLUSION: RNA virus belonging to the families Picornaviridae, and DNA viruses belonging to the families Genomoviridae and Parvoviridae were possibly the causative agent for diarrhea of red-crowned crane. This study has expanded our understanding of the virome of red-crowned crane and provides a baseline for elucidating the etiology for diarrhea of the birds.