Plasmodium yoelii surface-related antigen (PySRA) modulates the host pro-inflammatory responses via binding to CD68 on macrophage membrane.

Malaria, one of the major infectious diseases in the world, is caused by the Plasmodium parasite. Plasmodium antigens could modulate the inflammatory response by binding to macrophage membrane receptors. As an export protein on the infected erythrocyte membrane, Plasmodium surface-related antigen (SRA) participates in the erythrocyte invasion and regulates the immune response of the host. This study found that the F2 segment of P. yoelii SRA activated downstream MAPK and NF-κB signaling pathways by binding to CD68 on the surface of the macrophage membrane and regulating the inflammatory response. The anti-PySRA-F2 antibody can protect mice against P. yoelii, and the pro-inflammatory responses such as IL-1ß, TNF-α, and IL-6 after infection with P. yoelii are attenuated. These findings will be helpful for understanding the involvement of the pathogenic mechanism of malaria with the exported protein SRA.

Association of acetaminophen use with perinatal outcomes among pregnant women: a retrospective cohort study with propensity score matching.

BACKGROUND: Although acetaminophen is widely used in women during pregnancy, its safety has not been clearly stated. The study aimed to investigate the association between acetaminophen use and adverse pregnancy outcomes in pregnant women in China. METHODS: We conducted a retrospective cohort study by collecting data on pregnant women who delivered in the Beijing Obstetrics and Gynecology Hospital from January 2018 to September 2023. An acetaminophen use group and a control group were formed based on prenatal exposure to acetaminophen. The pregnancy outcomes that we focused on were stillbirth, miscarriage, preterm birth, APGAR score, birth weight, and congenital disabilities. Pregnant women exposed to acetaminophen were matched to unexposed in a 1:1 ratio with propensity score matching, using the greedy matching macro. SPSS software was used for statistical analysis. Multivariable logistics regression was used to assess the association between acetaminophen use during pregnancy and adverse pregnancy outcomes. RESULTS: A total of 41,440 pregnant women were included, of whom 501 were exposed to acetaminophen during pregnancy, and 40,939 were not exposed. After the propensity score matching, the acetaminophen use and control groups consisted of 501 pregnant women each. The primary analysis showed that acetaminophen exposure during pregnancy was associated with an increased risk of stillbirth (adjusted OR (aOR) = 2.29, 95% CI, 1.19-4.43), APGAR score < 7 at 1 min (aOR = 3.28, 95% CI, 1.73-6.21), APGAR score < 7 at 5 min (aOR = 3.54, 95% CI, 1.74-7.20), APGAR score < 7 at 10 min (aOR = 3.18, 95% CI, 1.58-6.41), and high birth weight (HBW) (aOR = 1.75, 95% CI, 1.05-2.92). Drug exposure during the first and second trimesters increased the odds of stillbirth, miscarriage, APGAR < 7, and the occurrence of at least one adverse pregnancy outcome. In addition, the frequency of drug use more than two times was associated with a higher risk of preterm birth and APGAR score < 7. CONCLUSIONS: Exposure to acetaminophen during pregnancy was significantly associated with the occurrence of adverse pregnancy outcomes, particularly exposure in the first and second trimesters and frequency of use more than twice. It is suggested that acetaminophen should be prescribed with caution in pregnant women.

Nuclear KRT19 is a transcriptional co-repressor promoting histone deacetylation and liver tumorigenesis.

BACKGROUND AND AIMS: Epigenetic reprogramming and escape from terminal differentiation are poorly understood enabling characteristics of liver cancer. Keratin 19 (KRT19), classically known to form the intermediate filament cytoskeleton, is a marker of stemness and worse prognosis in liver cancer. This study aimed to address the functional roles of KRT19 in liver tumorigenesis and to elucidate the underlying mechanisms. APPROACH AND RESULTS: Using multiplexed genome editing of hepatocytes in vivo, we demonstrated that KRT19 promoted liver tumorigenesis in mice. Cell fractionation revealed a previously unrecognized nuclear fraction of KRT19. Tandem affinity purification identified histone deacetylase 1 (HDAC1) and REST co-repressor 1 (RCOR1), components of the co-repressor of RE-1 silencing transcription factor (CoREST) complex as KRT19-interacting proteins. KRT19 knockout markedly enhanced histone acetylation levels. Mechanistically, KRT19 promotes CoREST complex formation by enhancing HDAC1 and RCOR1 interaction, thus increases the deacetylase activity. ChIP-seq revealed hepatocyte-specific genes, such as hepatocyte nuclear factor 4 alpha (HNF4A), as direct targets of KRT19-CoREST. In addition, we identified forkhead box P4 (FOXP4) as a direct activator of aberrant KRT19 expression in liver cancer. Furthermore, treatment of primary liver tumors and patient-derived xenografts in mice suggest that KRT19 expression has the potential to predict response to HDAC inhibitors especially in combination with Lenvatinib. CONCLUSIONS: Our data show that nuclear KRT19 acts as a transcriptional co-repressor through promoting the deacetylase activity of the CoREST complex, resulting in dedifferentiation of liver cancer. These findings reveal a previously unrecognized function of KRT19 in directly shaping the epigenetic landscape in cancer.

Trajectories of maternal depressive symptoms from infancy through early childhood: The roles of perceived financial strain, social support, and intimate partner violence.

Although new mothers are at risk of heightened vulnerability for depressive symptoms, there is limited understanding regarding changes in maternal depressive symptoms over the course of the postpartum and early childhood of their child's life among rural, low-income mothers from diverse racial backgrounds. This study examined distinct trajectories of depressive symptoms among rural low-income mothers during the first five years of their child's life, at 6, 15, 24, and 58 months, using data from the Family Life Project (N = 1,292). Latent class growth analysis identified four distinct trajectories of maternal depressive symptoms, including Low-decreasing (50%; n = 622), Low-increasing (26%; n = 324), Moderate-decreasing (13%; n = 156), and Moderate-increasing (11%; n = 131) trajectories. Multinomial logistic regression demonstrated that higher perceived financial strain and intimate partner violence, and lower social support predicted higher-risk trajectories (Low-increasing, Moderate-decreasing, and Moderate-increasing) relative to the Low-decreasing trajectory. Compared to the Low-decreasing trajectory, lower neighborhood safety/quietness predicted to the Low-increasing trajectory. Moreover, lower social support predicted the Moderate-increasing trajectory, the highest-risk trajectory, compared to those in Moderate-decreasing. The current analyses underscore the heterogeneity on patterns of depressive symptoms among rural, low-income mothers, and that the role of both proximal and broader contexts contributing to distinct trajectories of maternal depressive symptoms over early childhood.

Based on the prognosis model of immunogenes, the prognosis model was constructed to predict the invasion of immune genes and immune cells related to primary liver cancer and its experimental validation.

Background: Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. Purpose: Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. Methods: PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. Results: Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. Conclusion: Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.

The significance of single-cell transcriptome analysis in epididymis research.

As a crucial component of the male reproductive system, the epididymis plays multiple roles, including sperm storage and secretion of nutritive fluids for sperm development and maturation. The acquisition of fertilization capacity by sperm occurs during their transport through the epididymis. Compared with the testis, little has been realized about the importance of the epididymis. However, with the development of molecular biology and single-cell sequencing technology, the importance of the epididymis for male fertility should be reconsidered. Recent studies have revealed that different regions of the epididymis exhibit distinct functions and cell type compositions, which are likely determined by variations in gene expression patterns. In this research, we primarily focused on elucidating the cellular composition and region-specific gene expression patterns within different segments of the epididymis and provided detailed insights into epididymal function in male fertility.

The Plasmodium vivax MSP1P-19 is involved in binding of reticulocytes through interactions with the membrane proteins band3 and CD71.

The parasite Plasmodium vivax preferentially invades human reticulocytes. Its merozoite surface protein 1 paralog (PvMSP1P), particularly the 19-kDa C-terminal region (PvMSP1P-19), has been shown to bind to reticulocytes and this binding can be inhibited by antisera obtained by PvMSP1P-19 immunization. The molecular mechanism of interactions between PvMSP1P-19 and reticulocytes during P. vivax invasion, however, remains unclear. In this study, we analyzed the ability of MSP1P-19 to bind to different concentrations of reticulocytes and confirmed its reticulocyte preference. LC-MS analysis was used to identify two potential reticulocyte receptors, band3 and CD71, that interact with MSP1P-19. Both PvMSP1P-19 and its sister taxon Plasmodium cynomolgi MSP1P-19 (PcMSP1P-19) were found to bind to the extracellular loop (loop 5) of band3, where the interaction of MSP1P-19 with band3 was chymotrypsin-sensitive. Antibodies against band3-P5, CD71, and MSP1P-19 reduced the binding activity of PvMSP1P-19 and PcMSP1P-19 to reticulocytes, while MSP1P-19 proteins inhibited P. falciparum invasion in vitro in a concentration-dependent manner. To sum up, identification and characterization of the reticulocyte receptor is important for understanding the binding of reticulocytes by MSP1P-19.

Effect of Diabetes on Wound Healing: A Bibliometrics and Visual Analysis.

Objective: The quality of life of diabetic patients is seriously affected by wound healing difficulty, which can lead to increased infection, skin deep tissue injury and continuous pain. By analyzing the research trends and hot spots in this field, the visualization analysis map is constructed. Methods: The contents of the selected articles were sorted out and analyzed by bibliometrics. We use CiteSpace, Vosviewer and HistCite to visualize literature information, including national publication statistics, institutions, authors, journal partnerships, and citations of published articles. Results: Among the 2942 articles, the United States and China ranked first in both article circulation and TGCS, and many countries also cooperated. The collaboration between schools and research institutions is a core part of dissertation research institution collaboration, with most authors coming from the same institution. Most of the literature studies on the mechanisms and methods of promoting diabetic wound healing. Improving cell function or making innovative attempts in local treatment are the fruits of researchers' efforts to promote diabetic wound healing in recent years. Conclusion: Through the metrology method, the time distribution, author institution, cooperation network, research status, research hotspot and development trend of the literature on the influence of diabetes on wound healing were intuitively displayed, which provided a reference for further research and development direction.

Bovine Milk Derived Exosomes Affect Gut Microbiota of DSS-Induced Colitis Mice.

The objective of this study was to investigate the effect of bovine milk derived exosomes (MDEs) on the gut microbiota of Dextran sodium sulfate (DSS)-induced colitis mice. Total of 42 specific pathogen free (SPF) male BALB/c mice (3 weeks old) were randomly assigned to three groups including control group, DSS group (DSS) and bovine milk derived exosome group (Exo), with 7 replicates/cages per treatment and two mice in one cage. 16S rRNA gene sequencing of cecal digesta samples was conducted. DSS significantly decreased the average daily feed intake of mice in DSS and Exo groups (P = 0.03). Shannon index of the DSS group was significantly lower than the control group (P < 0.05) whereas no difference between the control group and Exo group was observed. Administration of MDEs tended to increase the relative abundance of Campylobaterota. Compared to the control group, the relative abundance of Roseburia was significantly decreased in the DSS group (P < 0.05) whereas no difference between the Exo group and control group was observed. MDEs also tended to increase the relative abundance of Lachnospiraceae_UCG_006. In conclusion, oral administration of 10 µL MDEs (1 mg/mL) positively affected gut microbiota of DSS-induced colitis mice. The results of this study provided valuable reference for MDEs application in the prevention and treatment of colitis.

Antibacterial conductive polyacrylamide/quaternary ammonium chitosan hydrogel for electromagnetic interference shielding and strain sensing.

The utilization of biomass-based conductive polymer hydrogels in wearable electronics holds great promise for advancing performance and sustainability. An interpenetrating network of polyacrylamide/2-hydroxypropyltrimethyl ammonium chloride chitosan (PAM/HACC) was firstly obtained through thermal-initiation polymerization of AM monomers in the presence of HACC. The positively charged groups on HACC provide strong electrostatic interactions and hydrogen bonding with the PAM polymer chains, leading to improved mechanical strength and stability of the hydrogel network. Subsequently, the PAM/HACC networks served as the skeletons for the in-situ polymerization of polypyrrole (PPy), and then the resulting conductive hydrogel demonstrated stable electromagnetic shielding performance (40 dB), high sensitivity for strain sensing (gauge factor = 2.56). Moreover, the incorporation of quaternary ammonium chitosan into PAM hydrogels enhances their antimicrobial activity, making them more suitable for applications in bacterial contamination or low-temperature environments. This conductive hydrogel, with its versatility and excellent mechanical properties, shows great potential in applications such as electronic skin and flexible/wearable electronics.

Food selection and effect of home preparation procedure for antibiotic food mixtures on homogeneity, stability, and dissolution.

Amoxicillin, doxycycline, and clindamycin are among the commonly used antibiotics to treat bacterial infections. However, dosage forms of antibiotics for pediatric patients may not be as readily available as the formulations for adult patients. As such, it is anticipated that during a public health emergency, special instruction may need to be provided on home preparation and administration procedures to dose pediatric patients using available stockpiles of oral tablet and capsule dosage forms. Mixing crushed tablets or capsule contents with soft- or liquid- foods is one of the most common home preparation procedures. To gain knowledge for safe and effective use of prepared drug product instead of the intended intact dosage form, the impact of manipulation of the dosage form was studied. Capsule opening, capsule content assay and uniformity, dissolution, homogeneity, and stability studies of drug mixed with various liquid and soft foods were carried out using intact capsules of amoxicillin, doxycycline, and clindamycin. Higher recovery of capsule contents was achieved when using hands or knives to open capsules compared to using scissors. The capsules of all three antibiotic products contained the labeled amount of active pharmaceutical ingredients (API). The peanut butter-drug mixtures failed both United States Pharmacopeia (USP) assay and dissolution criteria because the peanut butter significantly affected the solubility of the drugs, and hence it was omitted from further study. All drug-food mixtures of the three antibiotic products and 15 selected foods exhibited fast dissolution (e.g., >80 % in 60 min) in the tested medium, except for the amoxicillin-chocolate pudding mixture. Three household containers (cups, plates, and bowls) and four mixing times (0.5 min, 1 min, 2 min, and 5 min) were found to be suitable for preparation of homogeneous mixtures of the antibiotics and foods. For practical purposes, 1 to 2 min mixing time is sufficient to produce homogeneous mixtures. The results of this study provided product quality data on the interactions between the antibiotics and the foods and can potentially support future development of home preparation instructions of antibiotics for pediatric patients or patients with swallowing difficulties.

Metagenomic evidence for antibiotic-associated actinomycetes in the Karamay Gobi region.

Due to the misuse of antibiotics, there is an increasing emergence and spread of multidrug-resistant (MDR) bacteria, leading to a human health crisis. To address clinical antibiotic resistance and prevent/control pathogenic microorganisms, the development of novel antibiotics is essential. This also offers a new approach to discovering valuable actinobacterial flora capable of producing natural bioactive products. In this study, we employed bioinformatics and macro-genome sequencing to collect 15 soil samples from three different locations in the Karamay Gobi region. First, we assessed the diversity of microorganisms in soil samples from different locations, analyzing the content of bacteria, archaea, actinomycetes, and fungi. The biodiversity of soil samples from outside the Gobi was found to be higher than that of soil samples from within and in the center of the Gobi. Second, through microbial interaction network analysis, we identified actinomycetes as the dominant group in the system. We have identified the top four antibiotic genes, such as Ecol_fabG_TRC, Efac_liaR_DAP, tetA (58), and macB, by CARD. These genes are associated with peptide antibiotics, disinfecting agents and antiseptics, tetracycline antibiotics, and macrolide antibiotics. In addition, we also obtained 40 other antibiotic-related genes through CARD alignment. Through in-depth analysis of desert soil samples, we identified several unstudied microbial species belonging to different families, including Erythrobacteriaceae, Solirubrobacterales, Thermoleophilaceae, Gaiellaceae, Nocardioidaceae, Actinomycetia, Egibacteraceae, and Acidimicrobiales. These species have the capability to produce peptide antibiotics, macrolide antibiotics, and tetracycline antibiotics, as well as disinfectants and preservatives. This study provides valuable theoretical support for future in-depth research.

Impact of Stent Size Selection and Vessel Evaluation on Skull Base Cerebrovascular Diseases Treated With Willis Covered Stents: A Multicenter Retrospective Analysis.

PURPOSE: This study aimed to evaluate the impact of the diverse stent size selection on the clinical and angiographic outcomes of Willis covered stent (WCS) for the treatment of skull base cerebrovascular diseases. MATERIALS AND METHODS: A total of 147 patients with 151 skull base cerebrovascular diseases treated with WCS in 3 centers between January 2015 and July 2022 were included in this study. Several parameters depicting stent size and parent artery condition were incorporated into the analysis of the outcomes. RESULTS: Complete occlusion was found in 106 cases (68.2%) immediately after deployment and 126 cases (83.4%) after technical adjustment. In the multivariate logistics analysis, the difference between stent diameter and parent artery diameter (DD) was significantly associated with immediate endoleak without adjustment (odds ratio [OR]=0.410; p=0.005) and late endoleak (OR=0.275; p=0.028). In addition, differences between stent diameter and parent artery diameter at wide landing point (DSW) and differences between stent diameter and parent artery diameter at narrow landing point (DSN) was also was significant associated with immediate endoleak without adjustment and balloon re-dilation respectively. CONCLUSIONS: This study demonstrated that the diameter selection of the WCS was associated with the occurrence of endoleak during the treatment of skull base cerebrovascular diseases. Precise selection and evaluation of stent size and vessel condition were significant factors for skull base cerebrovascular diseases treated by WCS. CLINICAL IMPACT: This study demonstrates a significant association between the diameter selection of the Willis covered stent (WCS) and the occurrence of endoleak in the management of skull base cerebrovascular diseases. The results offer valuable medical evidence that can inform stent selection for WCS. The study emphasizes the significance of precise evaluation of stent size and vessel condition as crucial factors in WCS procedures. These findings underscore the importance of meticulous consideration and individualized approaches to stent selection, ultimately improving treatment outcomes in clinical practice.

SNX8 enables lysosome reformation and reverses lysosomal storage disorder.

Lysosomal Storage Disorders (LSDs), which share common phenotypes, including enlarged lysosomes and defective lysosomal storage, are caused by mutations in lysosome-related genes. Although gene therapies and enzyme replacement therapies have been explored, there are currently no effective routine therapies against LSDs. During lysosome reformation, which occurs when the functional lysosome pool is reduced, lysosomal lipids and proteins are recycled to restore lysosome functions. Here we report that the sorting nexin protein SNX8 promotes lysosome tubulation, a process that is required for lysosome reformation, and that loss of SNX8 leads to phenotypes characteristic of LSDs in human cells. SNX8 overexpression rescued features of LSDs in cells, and AAV-based delivery of SNX8 to the brain rescued LSD phenotypes in mice. Importantly, by screening a natural compound library, we identified three small molecules that enhanced SNX8-lysosome binding and reversed LSD phenotypes in human cells and in mice. Altogether, our results provide a potential solution for the treatment of LSDs.

Total cucurbitacins from Herpetospermum pedunculosum pericarp do better than Hu-lu-su-pian (HLSP) in its safety and hepatoprotective efficacy.

The pericarp of Herpetospermum pedunculosum (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl4-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD50 and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD50) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD50 of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components.

Stem Leydig cells support macrophage immunological homeostasis through mitochondrial transfer in mice.

As testicular mesenchymal stromal cells, stem Leydig cells (SLCs) show great promise in the treatment of male hypogonadism. The therapeutic functions of mesenchymal stromal cells are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs remain unclear. Here, we observe that SLCs transplantation restore male fertility and testosterone production in an ischemia‒reperfusion injury mouse model. SLCs prevent inflammatory cascades through mitochondrial transfer to macrophages. Reactive oxygen species (ROS) released from activated macrophages inducing mitochondrial transfer from SLCs to macrophages in a transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated manner. Notably, knockdown of TRPM7 in transplanted SLCs compromised therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. These findings reveal a new mechanism of SLCs transplantation that may contribute to preserve testis function in male patients with hypogonadism related to immune disorders.

Suicide prevention for substance using youth experiencing homelessness: study protocol for a randomized controlled trial.

BACKGROUND: While research on substance using youth experiencing homelessness (YEH) is increasing, there is a dearth of information regarding effective prevention interventions for these youth. Suicide is the leading cause of death among YEH and most youth do not access services that may be available to them. Therefore, this study seeks to address this gap in the research literature with the goal to identify an effective suicide prevention intervention that can be readily adopted by communities that serve these youth. METHODS: Three hundred (N = 300) YEH with recent substance use and suicidal ideation or a recent suicide attempt will be recruited from the streets as well as a drop-in center serving YEH. After the baseline assessment, all youth will be randomly assigned to Cognitive Therapy for Suicide Prevention (CTSP) + Services as Usual (SAU) (N = 150) or to SAU alone (N = 150). SAU includes outreach, advocacy, and service linkage whereas YEH who receive CTSP will also receive ten CTSP sessions and an optional nine booster sessions. Follow-up assessments will be conducted at 3, 6, 9, and 12 months post-baseline. Theoretically derived mediators (e.g., cognitive distortions) will be tested to shed light on mechanisms associated with change, and the moderating effects of sex, race, sexual orientation, and baseline service connection will be examined. In order to ease future dissemination of the intervention to agencies serving YEH, we will rigorously assess acceptability, feasibility, fidelity, and cost associated with the delivery of our intervention approach using a mixed-methods approach. DISCUSSION: This study adds to a very small number of clinical trials seeking to prevent lethal suicide among a very high-risk group by addressing suicidal ideation directly rather than underlying conditions. It is hypothesized that youth receiving CTSP + SAU will show greater reductions in suicidal ideation (primary outcome), substance use, and depressive symptoms (secondary outcomes) over time compared to SAU alone, as well as improved risk and protective factors. TRIAL REGISTRATION: NCT05994612. Date of Registration: August 16, 2023.

First magnetic particle imaging to assess pulmonary vascular leakage in vivo in the acutely injured and fibrotic lung.

Increased pulmonary vascular permeability is a characteristic feature of lung injury. However, there are no established methods that allow the three-dimensional visualization and quantification of pulmonary vascular permeability in vivo. Evans blue extravasation test and total protein test of bronchoalveolar lavage fluid (BALF) are permeability assays commonly used in research settings. However, they lack the ability to identify the spatial and temporal heterogeneity of endothelial barrier disruption, which is typical in lung injuries. Magnetic resonance (MR) and near-infrared (NIR) imaging have been proposed to image pulmonary permeability, but suffer from limited sensitivity and penetration depth, respectively. In this study, we report the first use of magnetic particle imaging (MPI) to assess pulmonary vascular leakage noninvasively in vivo in mice. A dextran-coated superparamagnetic iron oxide (SPIO), synomag®, was employed as the imaging tracer, and pulmonary SPIO extravasation was imaged and quantified to evaluate the vascular leakage. Animal models of acute lung injury and pulmonary fibrosis (PF) were used to validate the proposed method. MPI sensitively detected the SPIO extravasation in both acutely injured and fibrotic lungs in vivo, which was confirmed by ex vivo imaging and Prussian blue staining. Moreover, 3D MPI illustrated the spatial heterogeneity of vascular leakage, which correlated well with CT findings. Based on the in vivo 3D MPI images, we defined the SPIO extravasation index (SEI) to quantify the vascular leakage. A significant increase in SEI was observed in the injured lungs, in consistent with the results obtained via ex vivo permeability assays. Overall, our results demonstrate that 3D quantitative MPI serves as a useful tool to examine pulmonary vascular integrity in vivo, which shows promise for future clinical translation.

Magnesium source with function of slowly releasing Mg and pH control for impurity-resistance synthesis ultra-large struvite from wastewater.

Struvite (MgNH4PO4·6H2O, Magnesium ammonium phosphate, MAP), recovered from wastewater, has potential application as a slow-release fertilizer. However, crystal size distribution (CSD) of recovered MAP typically lied in the range of 50-300 µm, due to fast nucleation rate and notably narrow metastable zone width (MSZW) of MAP, with purity levels 40-90 %. In order to control the rate of nucleation, a novel magnesium source with the form of MgHPO4·3H2O wrapped with Mg(OH)2 was prepared, referred to as P-3. This compound gradually released Mg2+ and PO43-, regulating solution concentration kept in MSZW to promote crystal growth. The inherent Mg(OH)2 within P-3 also acted as a pH regulator in wastewater, eliminating the necessity for additional acid or alkali adjustments during crystallization process. The MAP precipitated by P-3 exhibited an impressive CSD of 5000-7000 µm, with a maximum size reaching 10,000 µm. This represented the largest CSD reported in literature for recovered MAP from wastewater. The significance of the ultra-large MAP precipitated by P-3 lied in its enhanced resistance to impurity adsorption, resulting in MAP with a remarkable purity 97 %, under conditions of low heavy metal ion concentration approximately 5 mg/L. Furthermore, the removal efficiency of ammonia nitrogen (NH4+) can reach 92 %. In comparison, two other magnesium sources, soluble salts (MgCl2 and Na2HPO4, P-1) and a combination of insoluble salts (Mg(OH)2 and MgHPO4, P-2) were evaluated alongside P-3. The CSD of MAP precipitated from P-1, P-2 was both <100 µm, with purity levels of 90 and 92 % and NH4+ removal efficiency of 92 and 90 %, respectively. Importantly, the strategy of obtaining ultra-large size MAP from wastewater in this study provided novel insights into the crystallization of other insoluble salts with large sizes.

Protective effect of Enterococcus faecium against ethanol-induced gastric injury via extracellular vesicles.

Recently, Enterococcus has been shown to have gastric protective functions, and the mechanisms by which Enterococcus modulates gastric function are still being investigated. Herein, we investigated how Enterococcus faecium (Efm) and E. faecium-derived extracellular vesicles (EVs) (EfmEVs) exert protective effect against ethanol-induced gastric injury by investigating the effect of EfmEVs on gastric mucosal ulcer scoring, histological lesion, mucosal glycoprotein production, acidity, anti-oxidative function, and inflammatory responses in rat. Pretreatment with Efm showed significant reduction of ethanol-induced gastric injury, as evidenced by the lowering of ulcer index, histological lesion, gastric pH, and inflammatory responses and the enhancement of mucosal glycoprotein production and anti-oxidative function. Further functional studies on three bioactive components [inactivated Efm, EfmEVs (EVs), and EV-free supernatants] of the bacterial culture showed that EVs are mostly responsible for the gastroprotective effect. Moreover, EV secretion is beneficial for the gastroprotective effect of Efm. Hence, EVs mediated the protective effect of Efm against ethanol-induced gastric injury by lowering inflammatory responses and enhancing anti-oxidative function and may be a potent anti-inflammatory and anti-oxidative strategy to alleviate hyperinflammatory gastrointestinal tract conditions.IMPORTANCEThis study indicated that Enterococcus faecium provided a protective effect against rat gastric injury, which involved improvement of the mucosal glycoprotein production, anti-oxidative function, and inflammatory responses. Furthermore, we confirmed that three bioactive components (inactivated Efm, extracellular vesicles, and EV-free supernatants) of E. faecium culture also contributed to the gastroprotective effect. Importantly, E. faecium-derived EVs showed an effective impact for the gastroprotective effect.