Riding apoptotic bodies for cell-cell transmission by African swine fever virus.

African swine fever virus (ASFV), a devastating pathogen to the worldwide swine industry, mainly targets macrophage/monocyte lineage, but how the virus enters host cells has remained unclear. Here, we report that ASFV utilizes apoptotic bodies (ApoBDs) for infection and cell-cell transmission. We show that ASFV induces cell apoptosis of primary porcine alveolar macrophages (PAMs) at the late stage of infection to productively shed ApoBDs that are subsequently swallowed by neighboring PAMs to initiate a secondary infection as evidenced by electron microscopy and live-cell imaging. Interestingly, the virions loaded within ApoBDs are exclusively single-enveloped particles that are devoid of the outer layer of membrane and represent a predominant form produced during late infection. The in vitro purified ApoBD vesicles are capable of mediating virus infection of naive PAMs, but the transmission can be significantly inhibited by blocking the "eat-me" signal phosphatidyserine on the surface of ApoBDs via Annexin V or the efferocytosis receptor TIM4 on the recipient PAMs via anti-TIM4 antibody, whereas overexpression of TIM4 enhances virus infection. The same treatment however did not affect the infection by intracellular viruses. Importantly, the swine sera to ASFV exert no effect on the ApoBD-mediated transmission but can partially act on the virions lacking the outer layer of membrane. Thus, ASFV has evolved to hijack a normal cellular pathway for cell-cell spread to evade host responses.

IgA nephropathy: gut microbiome regulates the production of hypoglycosilated IgA1via the TLR4 signaling pathway.

BACKGROUND: IgA nephropathy (IgAN) is a major cause of primary glomerulonephritis characterized by mesangial deposits of galactose-deficient IgA1 (Gd-IgA1). Toll-like receptors (TLRs), particularly TLR4 are involved in the pathogenesis of IgAN. The role of gut microbiota on IgAN patients was recently investigated. However, whether gut microbial modifications of Gd-IgA1 through TLR4 play a role in IgAN remains unclear. METHODS: We recruited subjects into four groups, including 48 patients with untreated IgAN, 22 treated IgAN patients (IgANIT), 22 primary membranous nephropathy (MN), and 31 healthy controls (HCs). Fecal samples were collected to analyze changes in gut microbiome. Gd-IgA1 levels, expression of TLR4, B-cell stimulators, and intestinal barrier function were evaluated in all subjects. C57BL/6 mice were treated with a broad-spectrum antibiotic cocktail to deplete the gut microbiota and then gavaged with fecal microbiota transplanted fromclinical subjects of every group. Gd-IgA1 and TLR4 pathway were detected in peripheral blood mononuclear cells (PBMCs) from IgAN and HCs co-incubated with Lipopolysaccharide (LPS) and TLR4 inhibitor. RESULTS: Compared with other three groups, different compositions and decreased diversity demonstrated gut dysbiosis in un-treated IgAN, especially the enrichment of Escherichia -Shigella. Elevated Gd-IgA1 levels were found in un-treated IgAN patients and correlated with gut dysbiosis, TLR4, B-cell stimulators, indexes of intestinal barrier damage, and proinflammatory cytokines. In vivo, mice colonized with gut microbiota from IgAN and IgANIT patients, copied the IgAN phenotype with the activation of TLR4/MyD88/NF-κB pathway, B-cell stimulators in the intestine, and complied with enhanced proinflammatory cytokines. In vitro, LPS activated TLR4/MyD88/NF-κB pathway, B-cell stimulators and proinflammatory cytokines in the PBMCs from IgAN patients, which resulted in overproduction of Gd-IgA1 and inhibited by TLR4 inhibitor. CONCLUSIONS: Our results illustrated that gut-kidney axis was involved in the pathogenesis of IgAN. Gut dysbiosis could stimulate the overproduction of Gd-IgA1 by TLR4 signaling pathway production and B-cell stimulators.

Development of an 18F-labeled azobenzothiazole tracer for α-synuclein aggregates in the brain.

Nuclear imaging of aggregated α-synuclein pathology is an urgent clinical need for Parkinson's disease, yet promising tracers for brain α-synuclein aggregates are still rare. In this work, a class of compact benzothiazole derivatives was synthesized and evaluated for α-synuclein aggregates. Among them, azobenzothiazoles exhibited specific and selective detection of α-synuclein aggregates under physiological conditions. Fluoro-pegylated azobenzothiazole NN-F further demonstrated high-affinity binding to α-synuclein aggregates and efficient 18F-radiolabeling via nucleophilic displacement of a tosyl precursor. [18F]NN-F was stable in plasma in vitro and showed efficient brain uptake with little defluorination in vivo.

The Prevalence of Marine Lipophilic Phycotoxins Causes Potential Risks in a Tropical Small Island Developing State.

Tropical small island developing states (SIDS), with their geographical isolation and limited resources, heavily rely on the fisheries industry for food and revenue. The presence of marine lipophilic phycotoxins (MLPs) poses risks to their economy and human health. To understand the contamination status and potential risks, the Republic of Kiribati was selected as the representative tropical SIDS and 55 species of 256 coral reef fish encompassing multiple trophic levels and feeding strategies were collected to analyze 17 typical MLPs. Our results showed that the potential risks of ciguatoxins were the highest and approximately 62% of fish species may pose risks for consumers. Biomagnification of ciguatoxins was observed in the food web with a trophic magnification factor of 2.90. Brevetoxin-3, okadaic acid, and dinophysistoxin-1 and -2 were first reported, but the risks posed by okadaic acid and dinophysistoxins were found to be negligible. The correlation analysis revealed that fish body size and trophic position are unreliable metrics to indicate the associated risks and prevent the consumption of contaminated fish. The potential risks of MLPs in Kiribati are of concern, and our findings can serve as valuable inputs for developing food safety policies and fisheries management strategies specific to tropical SIDS contexts.

The impact of COVID-19 on the prognosis of deep vein thrombosis following anticoagulation treatment: a two-year single-center retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been proved as a significant risk factor for deep vein thrombosis (DVT) after several waves of pandemic. This study aims to further investigate impact of COVID-19 on prognosis of DVT following anticoagulation treatment. METHODS: A total of 197 patients with initially detected DVT and meanwhile accomplishing at least 3 months anticoagulation treatment were identified from our hospital between January 2021 and December 2022. DVT characteristics, clinical data, and exposure to COVID-19 were recorded for multivariable logistic regression analysis to identify DVT aggravation related risk factors. Propensity score matching (PSM) was used to balance baseline covariates. Kaplan-Meier curves and Log-Rank test were performed to exhibit distribution of DVT aggravation among different subgroups. RESULTS: In 2022, patients exhibited higher incidence rates of DVT aggravation compared to those in 2021 (HR:2.311, P = 0.0018). The exposure to COVID-19, increased red blood cell count, increased D-dimer level and reduced prothrombin time were found to be associated with DVT aggravation (P < 0.0001, P = 0.014, P < 0.001, P = 0.024), with only exposure to COVID-19 showing a significant difference between two years (2022:59/102, 57.84%, 2021:7/88, 7.37%, P < 0.001). In PSM-matched cohorts, the risk for DVT aggravation was 3.182 times higher in COVID-19 group compared to the control group (P < 0.0001). Exposure to COVID-19 increased the risk of DVT aggravation among patients who completed three months anticoagulant therapy (HR: 5.667, P < 0.0001), but did not increase incidence rate among patients who completed more than three months anticoagulant therapy (HR:1.198, P = 0.683). For patients with distal DVT, COVID-19 was associated with a significant increased risk of DVT recurrence (HR:4.203, P < 0.0001). Regarding principal diagnoses, incidence rate of DVT aggravation was significantly higher in COVID-19 group compared to the control group (Advanced lung cancer: P = 0.011, surgical history: P = 0.0365, benign lung diseases: P = 0.0418). CONCLUSIONS: Our study reveals an increased risk of DVT aggravation following COVID-19 during anticoagulation treatment, particularly among patients with distal DVT or those who have completed only three months anticoagulant therapy. Adverse effects of COVID-19 on DVT prognosis were observed across various benign and malignant respiratory diseases. Additionally, extended-term anticoagulant therapy was identified as an effective approach to enhance DVT control among patients with COVID-19.

Study on the Equivalence Transformation between Blasting Vibration Velocity and Acceleration.

The evaluation of blasting vibrations primarily hinges on two physical quantities: velocity and acceleration. A significant challenge arises when attempting to reference the two types of vibration data in relation to one another, such as different types of seismometers, noise, etc., necessitating a method for their equivalent transformation. To address this, a transformation method is discussed in detail with a case study, and equations for the ratio (Ra) of the particle peak velocity (PPV) to the particle peak acceleration (PPA) are proposed. The findings are twofold: (1) The conventional data conversion processes often suffer from low accuracy due to the presence of trend terms and noise in the signal. To mitigate this, the built-in MATLAB function is used for trend term elimination, complemented by a combined approach that integrates CEEMDAN with WD/WDP for noise reduction. These significantly enhance the accuracy of the transformation. (2) This analysis reveals a positive power function correlation between Ra and the propagation distance of the blast vibrations, contrasted by a negative correlation with the maximum charge per delay. Intriguingly, the Ra values observed in pre-splitting blasting operations are consistently lower than those in bench blasting. The established Ra equations offer a rapid, direct method for assessing the transformation between the PPV and PPA, providing valuable insights for the optimization of blasting design.

High-Sensitivity Self-Powered Photodetector Fibers Using Hierarchical Heterojunction Photoelectrodes Enable Wearable Amphibious Optoelectronic Textiles.

Fiber-shaped photodetectors (FPDs) with multidirectional light absorption properties offer exciting opportunities for intelligent optoelectronic textiles. However, achieving FPDs capable of working in ampule environments, especially with high sensitivity, remains a fundamental challenge. Here, quasi-solid-state twisted-fiber photoelectrochemical photodetectors (FPPDs) consisting of photoanode, gel electrolyte, and counter electrode are successfully assembled. In situ decorated n-type one-dimensional (1D) TiO2 nanowire arrays with 2D Ni-Fe metal-organic framework (NiFeMOF) nanosheets serve as hierarchical heterojunction photoanodes, thereby optimizing carrier transfer dynamics at the photoanode/electrolyte interface. As expected, the resulting self-powered FPPD exhibits 88.6 mA W-1 high responsiveness and a < 30 ms fast response time. Significantly, our FPPD can operate in both terrestrial and aquatic environments thanks to its intrinsic ionic properties, making it a versatile tool for detecting ultraviolet light on land and facilitating optical communication underwater. These high-sensitivity self-powered FPPDs with hierarchical heterojunction photoelectrodes hold promise for the development of wearable amphibious optoelectronic textiles.

Pan-Cancer analyses of Necroptosis-Related genes as a potential target to predict immunotherapeutic outcome.

Necroptosis is a unique programmed death mechanism of necrotic cells. However, its role and specific mechanism in cancer remain unclear, and a systematic pan-cancer analysis of necroptosis is yet to be conducted. Thus, we performed a specific pan-cancer analysis using The Cancer Genome Atlas and Genotype-Tissue Expression databases to analyse necroptosis expression in terms of cancer prognosis, DNA methylation status, tumour mutative burden, microsatellite instability, immune cell infiltration in different types of cancer and molecular mechanisms. For the first time, we explored the correlation between necroptosis and immunotherapy prognosis. Thus, our study provides a relatively comprehensive understanding of the carcinogenicity of necroptosis in different types of cancer. It is suggested that necroptosis can be used to evaluate the sensitivity of different patients to immunotherapy and may become a potential target for tumour immunotherapy.

Cellular liquid-liquid phase separation: Concept, functions, regulations, and detections.

Liquid-liquid phase separation is a multicomponent system separated into phases with different compositions and structures. It has been identified and explored in organisms after being introduced from the thermodynamic field. Condensate, the product of phase separation, exists in different scales of cellular structures, such as nucleolus, stress granules, and other organelles in nuclei or cytoplasm. And also play critical roles in different cellular behaviors. Here, we review the concept, thermodynamical and biochemical principles of phase separation. We summarized the main functions including the adjustment of biochemical reaction rates, the regulation of macromolecule folding state, subcellular structural support, the mediation of subcellular location, and intimately linked to different kinds of diseases, such as cancer and neurodegeneration. Advanced detection methods to investigate phase separation are collected and analyzed. We conclude with the discussion of anxiety of phase separation, and thought about how progress can be made to develop precise detection methods and disclose the potential application of condensates.

A Cooperative Cobalt-Driven System for One-Carbon Extension in the Synthesis of (Z)-Silyl Enol Ethers from Aldehydes: Unlocking Regio- and Stereoselectivity.

The research presented herein explores a cobalt-based catalytic system, distinctively featuring a cooperative boron-centric element within its intricate ligand architecture. This system is strategically engineered to enable the integration of a singular carbon atom into aldehydes, a process culminating in the production of (Z)-silyl enol ethers. Beyond offering an efficient one-pot synthesis route, this method adeptly overcomes challenges inherent to conventional techniques, such as the need for large amounts of additives, restrictive functional group tolerance, and extreme reaction temperatures. Initial mechanistic studies suggest the potential role of a cobalt-carbene complex as a catalytically significant species and underscore the importance of the borane segment. Collectively, these observations highlight the potential of this system in advancing complex bond activation pursuits.

Compact Luminol Chemiluminophores for In Vivo Detection and Imaging of ß-Sheet Protein Aggregates.

Protein aggregation has been found in a wide range of neurodegenerative protein-misfolding diseases. The demand for in vivo technologies to identify protein aggregation is at the leading edge for the pathogenic study, diagnostic development, and therapeutic intervention of these devastating disorders. Herein, we report a series of luminol analogues to construct a facile chemiluminescence (CL)-based approach for in vivo detection and imaging of ß-sheet protein aggregates. The synthesized compounds exhibited a distinct chemiluminescent response with long emission wavelengths toward reactive oxygen species under physiological conditions and displayed signal amplification in the presence of ß-sheet protein aggregates, including α-synuclein, ß-amyloid, and tau. Among them, CyLumi-3 was further evaluated as a chemiluminescent probe in preclinical models. By intravenous administration into the model mice via the tail vein, in vivo CL imaging noninvasively detected the specific CL of the probe targeting the α-synuclein aggregates in the brains of living mice. Based on its structural characteristics, CyLumi-3 can readily interact with α-synuclein aggregates with significantly enhanced fluorescence and can identify α-synuclein aggregates in vivo via distinctive CL amplification, which could pave the way for a more comprehensive understanding of protein aggregation in preclinical studies and would provide new hints for developing small-molecule chemiluminophores for protein aggregates.

Efficacy of Mesenchymal Stem Cell Therapy on Lupus Nephritis and Renal Function in Systemic Lupus Erythematosus: A Meta-Analysis.

PURPOSE: The purpose of this meta-analysis is to determine the efficacy of mesenchymal stromal/stem cell (MSC) transplantation therapy on lupus nephritis (LN) and renal function of patients with systemic lupus erythematosus (SLE). METHODS: Articles that reported the data of MSC therapy on the renal function as well as disease activity of LN in patients with SLE were searched in PubMed, Web of Science, Embase and the Cochrane Library. Mean difference for disease activity and laboratory parameters were pooled to evaluate the efficacy of MSC, and incidence was pooled for clinical remission, death and severe adverse event. RESULTS: A total of 12 studies with 586 patients were included. The disease activity indices, including SLEDAI and BILAG, were significantly decreased within 12 months after MSC therapy (P< 0.05). Laboratory parameters for renal function and disease control including estimated glomerular filtration rate, creatinine, blood urea nitrogen, complement C3, albumin and urine protein, were also significantly improved after therapy. The pooled rate of clinical remission at 12 months was 28.1% and the total rate during follow-up was 33.7%. The pooled rate of death at 12 months was 5.2% and the total rate during follow-up was 5.5%. Severe adverse events were rare and not associated with the treatment of MSC. CONCLUSIONS: This is the first meta-analysis that focuses on the effect of MSC on LN and renal function of patients with SLE, and the results shows a favorable safety profile and encouraging results of MSC for improving the disease activity of LN as well as the renal function of SLE patients.

Effects of 30% vs. 60% inspired oxygen fraction during mechanical ventilation on postoperative atelectasis: a randomised controlled trial.

BACKGROUND: There is the ongoing debate over the effect of inspired oxygen fraction (FiO2) during mechanical ventilation on postoperative atelectasis. We aimed to compare the effects of low (30%) and moderate (60%) FiO2 on postoperative atelectasis. The hypothesis of the study was that 30% FiO2 during mechanical ventilation could reduce postoperative atelectasis volume compared with 60% FiO2. METHODS: We performed a randomized controlled trial with 120 patients. Subjects were randomly assigned to receive 30% or 60% FiO2 during mechanical ventilation in a 1:1 ratio. The primary outcome was the percentage of postoperative atelectasis volume in the total lung measured using chest CT within 30 min after extubation. The secondary outcomes included different aeration region volumes, incidence of clinically significant atelectasis, and oxygenation index. RESULTS: In total, 113 subjects completed the trial, including 55 and 58 subjects in the 30% and 60% FiO2 groups, respectively. The percentage of the postoperative atelectasis volume in the 30% FiO2 group did not differ from that in the 60% FiO2 group. Furthermore, there was no significant difference in the atelectasis volume between the two groups after the missing data were imputed by multiple imputation. Additionally, there were no significant differences in the volumes of the over-aeration, normal-aeration, and poor-aeration regions between the groups. No significant differences in the incidence of clinically significant atelectasis or oxygenation index at the end of surgery were observed between the groups. CONCLUSIONS: Compared with 60% FiO2, the use of 30% FiO2 during mechanical ventilation does not reduce the postoperative atelectasis volume. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ). Identifier: ChiCTR1900021635. Date: 2 March 2019. Principal invetigator: Weidong Gu.

Rosuvastatin suppresses TNF-α-induced matrix catabolism, pyroptosis and senescence via the HMGB1/NF-κB signaling pathway in nucleus pulposus cells.

Intervertebral disc degeneration is mainly caused by irregular matrix metabolism in nucleus pulposus cells and involves inflammatory factors such as TNF-α. Rosuvastatin, which is widely used in the clinic to reduce cholesterol levels, exerts anti-inflammatory effects, but whether rosuvastatin participates in IDD remains unclear. The current study aims to investigate the regulatory effect of rosuvastatin on IDD and the potential mechanism. In vitro experiments demonstrate that rosuvastatin promotes matrix anabolism and suppresses catabolism in response to TNF-α stimulation. In addition, rosuvastatin inhibits cell pyroptosis and senescence induced by TNF-α. These results demonstrate the therapeutic effect of rosuvastatin on IDD. We further find that HMGB1, a gene closely related to cholesterol metabolism and the inflammatory response, is upregulated in response to TNF-α stimulation. HMGB1 inhibition or knockdown successfully alleviates TNF-α-induced ECM degradation, senescence and pyroptosis. Subsequently, we find that HMGB1 is regulated by rosuvastatin and that its overexpression abrogates the protective effect of rosuvastatin. We then verify that the NF-κB pathway is the underlying pathway regulated by rosuvastatin and HMGB1. In vivo experiments also reveal that rosuvastatin inhibits IDD progression by alleviating pyroptosis and senescence and downregulating HMGB1 and p65. This study might provide new insight into therapeutic strategies for IDD.

Identification of Anhydrodebromoaplysiatoxin as a Dichotomic Autophagy Inhibitor.

Dysfunctional autophagy is associated with various human diseases, e.g., cancer. The discovery of small molecules modulating autophagy with therapeutic potential could be significant. To this end, we screened the ability of a series of metabolites isolated from marine microorganisms to modulate autophagy. Anhydrodebromoaplysiatoxin (ADAT), a metabolite yielded by the marine red algae Gracilaria coronopifolia, inhibited autophagosome-lysosome fusion in mammalian cells, thereby inducing the accumulation of autophagosomes. Treatment of cells with ADAT alkalinized lysosomal pH. Interestingly, ADAT also activated the mTOR/p70S6K/FoxO3a signaling pathway, likely leading to the inhibition of autophagy induction. ADAT had little effect on apoptosis. Our results suggest that ADAT is a dichotomic autophagy inhibitor that inhibits both late-stage (autophagosome-lysosome fusion) and early-stage (autophagy induction) autophagy.

Prognostic factors in patients with thymoma who underwent surgery.

PURPOSE: Thymoma is the most common primary tumor in the anterior mediastinum. The prognostic factors of patients with thymoma still need to be clarified. In this study, we aimed to investigate the prognostic factors of patients with thymoma who received radical resection and establish the nomogram to predict the prognosis of these patients. MATERIALS AND METHODS: Patients who underwent radical resection for thymoma with complete follow-up data between 2005 and 2021 were enrolled. Their clinicopathological characteristics and treatment methods were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the independent prognostic factors. According to the results of the univariate analysis in the Cox regression model, the predictive nomograms were created. RESULTS: A total of 137 patients with thymoma were enrolled. With a median follow-up of 52 months, the 5-year and 10-year PFS rates were 79.5% and 68.1%, respectively. The 5-year and 10-year OS rates were 88.4% and 73.1%, respectively. Smoking status (P = 0.022) and tumor size (P = 0.039) were identified as independent prognostic factors for PFS. Multivariate analysis showed that a high level of neutrophils (P = 0.040) was independently associated with OS. The nomogram showed that the World Health Organization (WHO) histological classification contributed more to the risk of recurrence than other factors. Neutrophil count was the most important predictor of OS in patients with thymoma. CONCLUSION: Smoking status and tumor size are risk factors for PFS in patients with thymoma. A high level of neutrophils is an independent prognostic factor for OS. The nomograms developed in this study accurately predict PFS and OS rates at 5 and 10 years in patients with thymoma based on individual characteristics.

Object Detection of Flexible Objects with Arbitrary Orientation Based on Rotation-Adaptive YOLOv5.

It is challenging to accurately detect flexible objects with arbitrary orientation from monitoring images in power grid maintenance and inspection sites. This is because these images exhibit a significant imbalance between the foreground and background, which can lead to low detection accuracy when using a horizontal bounding box (HBB) as the detector in general object detection algorithms. Existing multi-oriented detection algorithms that use irregular polygons as the detector can improve accuracy to some extent, but their accuracy is limited due to boundary problems during the training process. This paper proposes a rotation-adaptive YOLOv5 (R_YOLOv5) with a rotated bounding box (RBB) to detect flexible objects with arbitrary orientation, effectively addressing the above issues and achieving high accuracy. Firstly, a long-side representation method is used to add the degree of freedom (DOF) for bounding boxes, enabling accurate detection of flexible objects with large spans, deformable shapes, and small foreground-to-background ratios. Furthermore, the further boundary problem induced by the proposed bounding box strategy is overcome by using classification discretization and symmetric function mapping methods. Finally, the loss function is optimized to ensure training convergence for the new bounding box. To meet various practical requirements, we propose four models with different scales based on YOLOv5, namely R_YOLOv5s, R_YOLOv5m, R_YOLOv5l, and R_YOLOv5x. Experimental results demonstrate that these four models achieve mean average precision (mAP) values of 0.712, 0.731, 0.736, and 0.745 on the DOTA-v1.5 dataset and 0.579, 0.629, 0.689, and 0.713 on our self-built FO dataset, exhibiting higher recognition accuracy and a stronger generalization ability. Among them, R_YOLOv5x achieves a mAP that is about 6.84% higher than ReDet on the DOTAv-1.5 dataset and at least 2% higher than the original YOLOv5 model on the FO dataset.

Evaluation of Metagenomic and Targeted Next-Generation Sequencing Workflows for Detection of Respiratory Pathogens from Bronchoalveolar Lavage Fluid Specimens.

Next-generation sequencing (NGS) workflows applied to bronchoalveolar lavage (BAL) fluid specimens could enhance the detection of respiratory pathogens, although optimal approaches are not defined. This study evaluated the performance of the Respiratory Pathogen ID/AMR (RPIP) kit (Illumina, Inc.) with automated Explify bioinformatic analysis (IDbyDNA, Inc.), a targeted NGS workflow enriching specific pathogen sequences and antimicrobial resistance (AMR) markers, and a complementary untargeted metagenomic workflow with in-house bioinformatic analysis. Compared to a composite clinical standard consisting of provider-ordered microbiology testing, chart review, and orthogonal testing, both workflows demonstrated similar performances. The overall agreement for the RPIP targeted workflow was 65.6% (95% confidence interval, 59.2 to 71.5%), with a positive percent agreement (PPA) of 45.9% (36.8 to 55.2%) and a negative percent agreement (NPA) of 85.7% (78.1 to 91.5%). The overall accuracy for the metagenomic workflow was 67.1% (60.9 to 72.9%), with a PPA of 56.6% (47.3 to 65.5%) and an NPA of 77.2% (68.9 to 84.1%). The approaches revealed pathogens undetected by provider-ordered testing (Ureaplasma parvum, Tropheryma whipplei, severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], rhinovirus, and cytomegalovirus [CMV]), although not all pathogens detected by provider-ordered testing were identified by the NGS workflows. The RPIP targeted workflow required more time and reagents for library preparation but streamlined bioinformatic analysis, whereas the metagenomic assay was less demanding technically but required complex bioinformatic analysis. The results from both workflows were interpreted utilizing standardized criteria, which is necessary to avoid reporting nonpathogenic organisms. The RPIP targeted workflow identified AMR markers associated with phenotypic resistance in some bacteria but incorrectly identified blaOXA genes in Pseudomonas aeruginosa as being associated with carbapenem resistance. These workflows could serve as adjunctive testing with, but not as a replacement for, standard microbiology techniques.

MSCs cell fates in murine acute liver injury and chronic liver fibrosis induced by carbon tetrachloride.

Mesenchymal stem cells (MSCs) therapy has shown potential benefits in multiple diseases. However, their clinic performance is not as satisfactory as expected. This study aimed to provide an alternative explanation by comparing MSCs' fates in different liver diseases. The distribution and therapeutic effects of hMSCs were investigated in acute liver injury (ALI) and chronic liver fibrosis (CLF) mice models, respectively. The two models were induced by single or repeated injection of carbon tetrachloride (CCl4) separately. The increase of hMSCs exposure in the liver (AUCliver 0-72 h) were more significant in ALI than in CLF (177.1% vs. 96.2%). In the ALI model, the hMSCs exposures in the lung (AUClung 0-72 h) increased by nearly 50% while decreased by 60.7% in CLF. The efficacy satellite study indicated that hMSCs could significantly ameliorate liver injury in ALI, but its effects in CLF were limited. In the ALI, suppressed Natural Killer (NK) cell activities were observed, while NK cell activities were increased in CLF. The depletion of NK cells could increase hMSCs exposure in mice. For mice MSC (mMSCs), their cell fates in ALI were very similar to hMSCs in ALI: mMSCs' exposure in the liver and lung increased in ALI. In conclusion, our study revealed the distinct cell pharmacokinetic patterns of MSCs in ALI and CLF mice, which might be at least partially attributed to the different NK cell activities in the two liver diseases. This finding provided a novel insight into the varied MSCs' therapeutic efficacy in the clinic. Significance Statement Currently, there is little knowledge about the PK behavior of cell products like MSCs. This study was the first time investigating the influence of liver diseases on cell fates and efficacies of MSCs and the underneath rationale. The exposure was distinct between two representative liver disease models, which directly linked with the therapeutic performance that MSCs achieved. The difference could be attributed to the NK cells-mediated MSCs clearance.

Novel Coupled Channel Framework Connecting the Quark Model and Lattice QCD for the Near-threshold D_{s} States.

A novel framework is proposed to extract near-threshold resonant states from finite-volume energy levels of lattice QCD and is applied to elucidate structures of the positive parity D_{s}. The quark model, the quark-pair-creation mechanism and D^{(*)}K interaction are incorporated into the Hamiltonian effective field theory. The bare 1^{+} cs[over ¯] states are almost purely given by the states with heavy-quark spin bases. The physical D_{s0}^{*}(2317) and D_{s1}^{*}(2460) are the mixtures of bare cs[over ¯] core and D^{(*)}K component, while the D_{s1}^{*}(2536) and D_{s2}^{*}(2573) are almost dominated by bare cs[over ¯]. Furthermore, our model reproduces the clear level crossing of the D_{s1}^{*}(2536) with the scattering state at a finite volume.