Serological investigation and isolation of Salmonella abortus equi in horses in Xinjiang.

BACKGROUND: Salmonella enterica subspecies enterica serovar abortus equi (S. abortus equi) is one of the main pathogens that causes abortion in pregnant horses and donkeys, which was highly infectious and greatly restricts the healthy development of the horse industry. OBJECTIVES: In order to investigate the prevalence and biological characteristics of S. abortus equi in different regions and breeds of horses in Xinjiang. METHODS: This study conducted ELISA detection of S. abortus equi antibodies on serum samples of 971 horses collected from three large-scale horse farms and five free-range horse farms in Yili Prefecture and Bayingol Mongolian Autonomous Prefecture of Xinjiang from 2020 to 2023. On this basis, bacterial isolation, culture, identification, and drug sensitivity tests were conducted on 42 samples of aborted foal tissues and 23 mare vaginal swabs. RESULTS: The results showed that the positive rate of S. abortus equi antibody was as high as 20.91% in 971 horse serum samples. Among them, the positive rate in the Ili region (29.09%) was significantly higher than that in the Bayingole region (11.24%), and the positive rate in mares (22.45%) was higher than that in stallions (14.05%). In terms of horse breeds, the positive rates of self-propagating thoroughbred horses, half-bred horses, Ili horses and Yanqi horses were 43.22%, 28.81%, 14.72% and 11.24% respectively. In addition, S. abortus equi was more susceptible to juvenile and elderly horses, with positive rates of 70.00%and 41.86%, respectively, both of which were significantly higher than young (10.97%) and adult (19.79%) horses. Further, 9 strains of S. abortus equi were obtained through bacterial isolation, culture and identification, which were resistant to five antibiotics (Clarithromycin, Clindamycin, penicillin, Sulfamethoxazole and Rifampicin), and sensitive to 13 antimicrobial agents (Amoxicillin, Ciprofloxacin and Gentamicin, et al.). CONCLUSION: There was a high infection rate of S. abortus equi in Ili Prefecture and self-propagating thoroughbred horses, and juvenile or old mares were more susceptible, which will provide scientific basis for the prevention of S. abortus equi infection in different regions and breeds of horses in Xinjiang.

Identification and genetic characterization of a recently identified enterovirus C116 in China.

Enterovirus C116 (EV-C116) is a new member of the enterovirus C group which is closely associated with several infectious diseases. Although sporadic studies have detected EV-C116 in clinical samples worldwide, there is currently limited information available. In this study, two EV-C-positive fecal specimens were detected in apparently healthy children, which harbored low abundance, through meta-transcriptome sequencing. Based on the prototypes of several EV-Cs, two lineages were observed. Lineage 1 included many types that could not cause EV-like cytopathic effect in cell culture. Three genogroups of EV-C116 were divided in the maximum likelihood tree, and the two strains in this study (XZ2 and XZ113) formed two different lineages, suggesting that EV-C116 still diffuses worldwide. Obvious inter-type recombination events were observed in the XZ2 strain, with CVA22 identified as a minor donor. However, another strain (XZ113) underwent different recombination situations, highlighting the importance of recombination in the formation of EV-Cs biodiversity. The EV-C116 strains could propagate in rhabdomyosarcoma cell cultures at low titer; however, EV-like cytopathic effects were not observed. HEp-2, L20B, VERO, and 293T cell lines did not provide an appropriate environment for EV-C116 growth. These results challenge the traditional recognition of the uncultured nature of EV-C116 strains and explain the difficulty of clinical detection.

Estimating the health effects of COVID-19-related immunisation disruptions in 112 countries during 2020-30: a modelling study.

BACKGROUND: There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered. METHODS: For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up. FINDINGS: We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073]). INTERPRETATION: Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption. FUNDING: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation. TRANSLATIONS: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section.

Integrated analysis of single-cell and bulk RNA sequencing data reveals the association between hypoxic tumor cells and exhausted T cells in predicting immune therapy response.

Continuous stimulation of tumor neoantigens and various cytokines in the tumor microenvironment leads to T cell dysfunction, but the specific mechanisms by which these key factors are distributed among different cell subpopulations and how they affect patient outcomes and treatment response are incompletely characterized. By integrating single-cell and bulk sequencing data of non-small cell lung cancer patients, we constructed a clinical outcome-associated T cell exhaustion signature. We discovered a significant association between the T cell exhaustion state and tumor cell hypoxia. Hypoxic malignant cells were significantly correlated with the proportion of exhausted T cells, and they co-occurred in patients at advanced stage. By analyzing the ligand-receptor interactions between these two cell states, we observed that T cells were recruited towards tumor cells through production of chemokines such as CXCL16-CXCR6 axis and CCL3/CCL4/CCL5-CCR5 axis. Based on 15 immune checkpoint blockade (ICB)-treatment cohorts, we constructed an interaction signature that can be used to predict the response to immune checkpoint blockade therapy. Among genes composed of the signature, CXCR6 alone has similarly high prediction efficacy (Area Under Curve (AUC) = 1, 0.89 and 0.73 for GSE126044, GSE135222 and GSE93157, respectively) with the signature and thus could serve as a potential biomarker for predicting immunotherapy response. Together, we have discovered and validated a significant association between exhausted T cells and hypoxic malignant cells, elucidating key interaction factors that significantly associated with response to immunotherapy.

Dissolving microneedle system containing Ag nanoparticle-decorated silk fibroin microspheres and antibiotics for synergistic therapy of bacterial biofilm infection.

Most cases of delayed wound healing are associated with bacterial biofilm infections due to high antibiotic resistance. To improve patient compliance and recovery rates, it is critical to develop minimally invasive and efficient methods to eliminate bacterial biofilms as an alternative to clinical debridement techniques. Herein, we develop a dissolving microneedle system containing Ag nanoparticles (AgNPs)-decorated silk fibroin microspheres (SFM-AgNPs) and antibiotics for synergistic treatment of bacterial biofilm infection. Silk fibroin microspheres (SFM) are controllably prepared in an incompatible system formed by a mixture of protein and carbohydrate solutions by using a mild all-aqueous phase method and serve as biological templates for the synthesis of AgNPs. The SFM-AgNPs exert dose- and time-dependent broad-spectrum antibacterial effects by inducing bacterial adhesion. The combination of SFM-AgNPs with antibiotics breaks the limitation of the antibacterial spectrum and achieves better efficacy with reduced antibiotic dosage. Using hyaluronic acid (HA) as the soluble matrix, the microneedle system containing SFM-AgNPs and anti-Gram-positive coccus drug (Mupirocin) inserts into the bacterial biofilms with sufficient strength, thereby effectively delivering the antibacterial agents and realizing good antibiofilm effect on Staphylococcus aureus-infected wounds. This work demonstrates the great potential for the development of novel therapeutic systems for eradicating bacterial biofilm infections.

A qualitative study on the willingness and influencing factors of master of geriatric nursing specialist postgraduates to volunteer for home respite care for disabled elderly families.

BACKGROUND: As China's population ages, the demand for care for the disabled elderly is increasing, and family caregivers find it challenging to meet the comprehensive care needs of the disabled elderly. Through home respite services, families of the disabled elderly can receive help and support from specialized nursing professionals to ease the burden on family caregivers and provide high-quality services. This study explores the willingness and influencing factors of Master of Geriatric Nursing Specialist postgraduates in China to volunteer to provide home respite services for disabled elderly individuals. METHODS: A qualitative study based on Grounded Theory used Strauss and Corbin's programmatic version. A purposive sampling method was employed to conduct semi-structured interviews with 12 Master of Geriatric Nursing Specialist postgraduates from a tertiary hospital in Changsha, Hunan Province, China. RESULTS: The willingness of Master of Geriatric Nursing Specialist postgraduates to volunteer to provide home respite services for the disabled elderly was established as a core category, which was influenced by three main categories: personal factors, service object factors, and social factors, and nine categories formed from 39 initial concepts were included under the main category. CONCLUSIONS: Influenced by China's traditional cultural background, Master of Geriatric Nursing Specialist postgraduates in China have shown high motivation in volunteering to provide home respite services for the families of the disabled elderly but have been challenged by several challenges from China's healthcare environment and education system. Relevant departments need to adopt a series of policies and measures to increase volunteers' willingness to participate in respite care and promote its development.

Genome-wide screen reveals cellular functions that counteract rifampicin lethality in Escherichia coli.

IMPORTANCE: Rifamycins are a group of antibiotics with a wide antibacterial spectrum. Although the binding target of rifamycin has been well characterized, the mechanisms underlying the discrepant killing efficacy between gram-negative and gram-positive bacteria remain poorly understood. Using a high-throughput screen combined with targeted gene knockouts in the gram-negative model organism Escherichia coli, we established that rifampicin efficacy is strongly dependent on several cellular pathways, including iron acquisition, DNA repair, aerobic respiration, and carbon metabolism. In addition, we provide evidence that these pathways modulate rifampicin efficacy in a manner distinct from redox-related killing. Our findings provide insights into the mechanism of rifamycin efficacy and may aid in the development of new antimicrobial adjuvants.

Polyaniline-metal oxide coatings for biocidal applications: Mechanisms of activation and deactivation.

Metal oxide (MO) coatings (e.g. TiO2, ZnO, and CuO) have shown great promise to inactivate pathogenic bacteria, maintain self-cleaning surfaces, and prevent infectious diseases spread via surface contact. Under light illumination, the antibacterial performance of photoactive MO coatings is determined by reactive oxygen species (ROS) generation. However, several drawbacks, such as photo-corrosion and rapid electron-hole recombination, hinder the ROS production of MO coatings and diminish their antibacterial efficiency. In this study, we employed polyaniline (PANI), an inexpensive and easy-to-synthesize conductive polymer, to fabricate polyaniline-metal oxide composite (PMC) films. The antibacterial performance of PMC films was tested using E. coli as the model bacterium and Lake Michigan water (LMW) as the background medium and revealed enhanced antibacterial performance relative to MO coatings alone (approximately 75-90 % kill of E. coli by PMC coatings in comparison to 20-40 % kill by MO coatings), which is explained by an increase in the ROS yields of PMC. However, with repeated use, the antibacterial performance of the PMC coatings is diminished due to deprotonation of the PANI in the neutral/slightly basic aqueous environment of LMW. Overall, PANI can enhance the antibacterial performance of MO coatings, but efforts need to be directed to preserve or regenerate PMC stability under environmental conditions and applications.

Preventive effect and mechanism of compound Danshen dripping pills on contrast-induced nephropathy after percutaneous coronary interventional.

Background: Contrast-induced nephropathy (CIN) is one of the most common complications after coronary stent implantation due to the extensive development of coronary catheterization technology. Compound Danshen dripping pills (CDDP) are clinically used as cardiovascular drugs, relieving systemic inflammatory response. Previous studies have observed that CDDP can decrease CIN incidence after coronary stent implantation with uncertain effectiveness. Methods: We conducted a prospective, randomized, single-center, single-blind, controlled trial. We enrolled patients 18 years and older with unstable angina pectoris and NSTEMI who underwent PCI at the Tianjin Chest Hospital between November 1, 2021, and November 31, 2022, and followed for 30 days. Patients were randomized to CDDP and hydration therapy (10 capsules three times/day; N = 411) or hydration only (N = 411). The primary outcome was the contrast nephropathy incidence, defined as an elevation in serum creatinine by more than 25% or 44 µmol/L from baseline within 48-72 h of contrast exposure. Secondary outcomes included major adverse cardiovascular events post-surgery and during follow-up. Results: After 48 h of operation, the two groups had statistical significance in Scr and BUN values (80.0 ± 12.59 vs. 84.43 ± 13.49, P < 0.05; 6.22 ± 1.01 vs. 6.40 ± 0.93, P < 0.05). The difference in Scr in 72 h between the two groups was statistically significant (76.42 ± 10.92 vs. 79.06 ± 11.58, P < 0.05). The CIN incidence was significantly lower in the CDDP group than in the hydration group. The CIN risk was significantly elevated in patients with LVEF <50%, contrast volume ≥160 ml, and hypertension, after 48 and 72 h of operation. The serum inflammation index levels NGAL, TNF-α, oxidative stress indexes SOD, and MDA significantly differed between the two groups. However, there was no significant difference in serum apoptosis indexes Bax, Bcl-2, and Casepase-9. Conclusions: CDDP pre-treatment could prevent contrast-induced nephropathy. Inflammatory response and oxidative stress could be significant in the CDDP mechanism.

Mycobacterial DnaQ is an Alternative Proofreader Ensuring DNA Replication Fidelity.

Remove of mis-incorporated nucleotides ensures replicative fidelity. Although the ε-exonuclease DnaQ is a well-established proofreader in the model organism Escherichia coli, proofreading in mycobacteria relies on the polymerase and histidinol phosphatase (PHP) domain of replicative polymerase despite the presence of an alternative DnaQ homolog. Here, we show that depletion of DnaQ in Mycolicibacterium smegmatis results in increased mutation rate, leading to AT-biased mutagenesis and elevated insertions/deletions in homopolymer tract. We demonstrated that mycobacterial DnaQ binds to the b-clamp and functions synergistically with the PHP domain to correct replication errors. Further, we found that the mycobacterial DnaQ sustains replicative fidelity upon chromosome topological stress. Intriguingly, we showed that a naturally evolved DnaQ variant prevalent in clinical Mycobacterium tuberculosis isolates enables hypermutability and is associated with extensive drug resistance. These results collectively establish that the alternative DnaQ functions in proofreading, and thus reveal that mycobacteria deploy two proofreaders to maintain replicative fidelity.

Impact and cost-effectiveness of measles vaccination through microarray patches in 70 low-income and middle-income countries: mathematical modelling and early-stage economic evaluation.

BACKGROUND: Microarray patches (MAPs) are a promising technology being developed to reduce barriers to vaccine delivery based on needles and syringes (N&S). To address the evidence gap on the public health value of applying this potential technology to immunisation programmes, we evaluated the health impact on measles burden and cost-effectiveness of introducing measles-rubella MAPs (MR-MAPs) in 70 low-income and middle-income countries (LMICs). METHODS: We used an age-structured dynamic model of measles transmission and vaccination to project measles cases, deaths and disability-adjusted life-years during 2030-2040. Compared with the baseline scenarios with continuing current N&S-based practice, we evaluated the introduction of MR-MAPs under different measles vaccine coverage projections and MR-MAP introduction strategies. Costs were calculated based on the ingredients approach, including direct cost of measles treatment, vaccine procurement and vaccine delivery. Model-based burden and cost estimates were derived for individual countries and country income groups. We compared the incremental cost-effectiveness ratios of introducing MR-MAPs to health opportunity costs. RESULTS: MR-MAP introduction could prevent 27%-37% of measles burden between 2030 and 2040 in 70 LMICs, compared with the N&S-only immunisation strategy. The largest health impact could be achieved under lower coverage projection and accelerated introduction strategy, with 39 million measles cases averted. Measles treatment cost is a key driver of the net cost of introduction. In countries with a relatively higher income, introducing MR-MAPs could be a cost-saving intervention due to reduced treatment costs. Compared with country-specific health opportunity costs, introducing MR-MAPs would be cost-effective in 16%-81% of LMICs, depending on the MR-MAPs procurement prices and vaccine coverage projections. CONCLUSIONS: Introducing MR-MAPs in LMICs can be a cost-effective strategy to revitalise measles immunisation programmes with stagnant uptake and reach undervaccinated children. Sustainable introduction and uptake of MR-MAPs has the potential to improve vaccine equity within and between countries and accelerate progress towards measles elimination.

MiR-122 knockdown regulates vascular smooth muscle cells phenotypic switching through enhanced FOXO3 expression.

Vascular smooth muscle cells (VSMCs) phenotypic switching is identified as enhanced dedifferentiation, proliferation, and migration ability of VSMCs, in which microRNAs have been identified as important regulators of the process. The present study is aimed to explore the pathophysiological effect of miR-122 on VSMC phenotypic modulation. Here, the result showed that the decreased miR-122 expression was found in VSMCs subjected to platelet-derived growth factor-BB (PDGF-BB) treatment. Next, we investigated the response of miR-122 knockdown in VSMCs with PDGF-BB stimulation. MiR-122 silencing showed increased proliferation and migration capability, whereas attenuated the differentiation markers expression. The above results were reversed by miR-122 overexpression. Finally, we further demonstrated that FOXO3 was an important target for miR-122. Collectively, we demonstrated that miR-122 silencing promoted VSMC phenotypic modulation partially through upregulated FOXO3 expression that indicated miR-122 may be a novel therapeutic target for neointimal formation.

Protocol of a multicenter, single-blind, randomized, parallel controlled trial evaluating the effect of microbiological rapid on-site evaluation (M-ROSE) guiding anti-infection treatment in patients with severe hospital-acquired pneumonia.

INTRODUCTION: The mortality rate of hospitalized patients with severe hospital-acquired pneumonia (SHAP) remains high. Empirical broad-spectrum antibiotic coverage and the misuse of high-grade antibiotics could lead to the emergence of multi-drug and even pandrug-resistant bacteria. In addition to metagenomic next-generation sequencing (mNGS), microbiological rapid on-site evaluation (M-ROSE) might be a useful technique to identify the pathogens in the early stage; however, the effect of M-ROSE guiding anti-infection treatment on prognostic outcomes of SHAP patients is still unclear. METHODS/DESIGN: This is a multicenter, single-blind, prospective, randomized controlled trial to evaluate the effect of M-ROSE guiding anti-infection treatment in SHAP patients, which will provide new strategies for the prevention and control of clinical multi-drug resistance bacteria. A total of 166 patients with SHAP, aged 18 years and over, will be recruited from seven centers in Beijing and randomly assigned to the intervention group (M-ROSE combined with mNGS) or the control group (mNGS only) in a 1:1 ratio using the central randomization system. Patients in the intervention group will accept M-ROSE and mNGS analysis, and the control group will accept mNGS analysis. Individualized anti-infective treatment and routine treatment will be selected according to the analysis results. The primary outcome is the ICU outcome (mortality). The safety of the intervention measures will be evaluated during the entire trial period. This trial will be the first randomized controlled trial to evaluate the effect of M-ROSE guiding treatment on mortality in patients with SHAP and may change the prevalence of multi-drug resistant bacteria. ETHICS AND DISSEMINATION: This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Chinese PLA General Hospital (Approval Number: 20220322001). TRIAL REGISTRATION: ClinicalTrials.gov NCT05300776. Registered on 25 March 2022.

Health effects of routine measles vaccination and supplementary immunisation activities in 14 high-burden countries: a Dynamic Measles Immunization Calculation Engine (DynaMICE) modelling study.

BACKGROUND: WHO recommends at least 95% population coverage with two doses of measles-containing vaccine (MCV). Most countries worldwide use routine services to offer a first dose of measles-containing vaccine (MCV1) and later, a second dose of measles-containing vaccine (MCV2). Many countries worldwide conduct supplementary immunisation activities (SIAs), offering vaccination to all people in a specific age range irrespective of previous vaccination history. We aimed to estimate the relative effects of each dose and delivery route in 14 countries with high measles burden. METHODS: We used an age-structured compartmental dynamic model, the Dynamic Measles Immunization Calculation Engine (DynaMICE), to assess the effects of different vaccination strategies on measles susceptibility and burden during 2000-20 in 14 countries with high measles incidence (containing 53% of the global birth cohort and 78% of the global measles burden). Country-specific routine MCV1 and MCV2 coverage data during 1980-2020 were obtained from the WHO and UNICEF Estimates of National Immunization Coverage database for all modelled countries and SIA data were obtained from the WHO summary of measles and rubella SIAs. We estimated the incremental health effects of different vaccination strategies using prevented cases of measles and deaths from measles and their efficiency using the incremental number needed to vaccinate (NNV) to prevent an additional measles case. FINDINGS: Compared with no vaccination, MCV1 implementation was estimated to have prevented 824 million cases of measles and 9·6 million deaths from measles, with a median NNV of 1·41 (IQR 1·35-1·44). Adding routine MCV2 to MCV1 was estimated to have prevented 108 million cases and 404 270 deaths, whereas adding SIAs to MCV1 was estimated to have prevented 256 million cases and 4·4 million deaths. Despite larger incremental effects, adding SIAs to MCV1 (median incremental NNV 6·02, 5·30-7·68) showed reduced efficiency compared with adding routine MCV2 (5·41, 4·76-6·11). INTERPRETATION: Vaccination strategies, including non-selective SIAs, reach a greater proportion of children who are unvaccinated and reduce measles burden more than MCV2 alone, but efficiency is lower because of the wide age range targeted by SIAs. This analysis provides information to help improve the health effects and efficiency of measles vaccination strategies. The interplay between MCV1, MCV2, and SIAs should be considered when planning future measles vaccination strategies. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Defibrotide modulates pulmonary endothelial cell activation and protects against lung inflammation in pre-clinical models of LPS-induced lung injury and idiopathic pneumonia syndrome.

Introduction: A multiple organ dysfunction syndrome (MODS) workshop convened by the National Institute of Child Health and Human Development in 2015 identified acute respiratory distress syndrome (ARDS) and complications of allogeneic blood and marrow transplantation (allo-BMT) as contributors to MODS in pediatric patients. Pulmonary dysfunction also remains a significant complication of allo-BMT. Idiopathic pneumonia syndrome (IPS) defines non-infectious, acute, lung injury that occurs post-transplant. Injury and activation to endothelial cells (ECs) contribute to each form of lung inflammation. Methods: Two murine models were employed. In an ARDS model, naïve B6 mice receive an intravenous (i.v.) injection of lipopolysaccharide (LPS). In the established model of IPS, naïve B6D2F1 mice receive lethal total body irradiation followed by BMT from either allogeneic (B6) or syngeneic (B6D2F1) donors. Lung inflammation was subsequently assessed in each scenario. Results: Intravenous injection of LPS to B6 mice resulted in enhanced mRNA expression of TNFα, IL-6, Ang-2, E-, and P-selectin in whole lung homogenates. The expression of Ang-2 in this context is regulated in part by TNFα. Additionally, EC activation was associated with increased total protein and cellularity in broncho-alveolar lavage fluid (BALF). Similar findings were noted during the development of experimental IPS. We hypothesized that interventions maintaining EC integrity would reduce the severity of ARDS and IPS. Defibrotide (DF) is FDA approved for the treatment of BMT patients with sinusoidal obstruction syndrome and renal or pulmonary dysfunction. DF stabilizes activated ECs and protect them from further injury. Intravenous administration of DF before and after LPS injection significantly reduced mRNA expression of TNFα, IL6, Ang-2, E-, and P-selectin compared to controls. BALF showed decreased cellularity, reflecting less EC damage and leak. Allogeneic BMT mice were treated from day -1 through day 14 with DF intraperitoneally, and lungs were harvested at 3 weeks. Compared to controls, DF treatment reduced mRNA expression of TNFα, IL6, Ang-2, E-, and P- selectin, BALF cellularity, and lung histopathology. Conclusion: The administration of DF modulates EC injury in models of ARDS and IPS. Cytokine inhibition in combination with agents that stabilize EC integrity may be an attractive strategy for patients in each setting.

A Vis/NIR spectra-based approach for identifying bananas infected with Colletotrichum musae.

Introduction: Anthracnose of banana caused by Colletotrichum species is one of the most serious post-harvest diseases, which can cause significant yield losses. Clarifying the infection mechanism of the fungi using non-destructive methods is crucial for timely discriminating infected bananas and taking preventive and control measures. Methods: This study presented an approach for tracking growth and identifying different infection stages of the C. musae in bananas using Vis/NIR spectroscopy. A total of 330 banana reflectance spectra were collected over ten consecutive days after inoculation, with a sampling rate of 24 h. The four-class and five-class discriminant patterns were designed to examine the capability of NIR spectra in discriminating bananas infected at different levels (control, acceptable, moldy, and highly moldy), and different time at early stage (control and days 1-4). Three traditional feature extraction methods, i.e. PC loading coefficient (PCA), competitive adaptive reweighted sampling (CARS) and successive projections algorithm (SPA), combining with two machine learning methods, i.e. partial least squares discriminant analysis (PLSDA) and support vector machine (SVM), were employed to build discriminant models. One-dimensional convolutional neural network (1D-CNN) without manually extracted feature parameters was also introduced for comparison. Results: The PCA-SVM and·SPA-SVM models had good performance with identification accuracies of 93.98% and 91.57%, 94.47% and 89.47% in validation sets for the four- and five-class patterns, respectively. While the 1D-CNN models performed the best, achieving an accuracy of 95.18% and 97.37% for identifying infected bananas at different levels and time, respectively. Discussion: These results indicate the feasibility of identifying banana fruit infected with C. musae using Vis/NIR spectra, and the resolution can be accurate to one day.

Ascorbate peroxidase plays an important role in photoacclimation in the extremophilic red alga Cyanidiococcus yangmingshanensis.

Introduction: Acidothermophilic cyanidiophytes in natural habitats can survive under a wide variety of light regimes, and the exploration and elucidation of their long-term photoacclimation mechanisms promises great potential for further biotechnological applications. Ascorbic acid was previously identified as an important protectant against high light stress in Galdieria partita under mixotrophic conditions, yet whether ascorbic acid and its related enzymatic reactive oxygen species (ROS) scavenging system was crucial in photoacclimation for photoautotrophic cyanidiophytes was unclear. Methods: The significance of ascorbic acid and related ROS scavenging and antioxidant regenerating enzymes in photoacclimation in the extremophilic red alga Cyanidiococcus yangmingshanensis was investigated by measuring the cellular content of ascorbic acid and the activities of ascorbate-related enzymes. Results and discussion: Accumulation of ascorbic acid and activation of the ascorbate-related enzymatic ROS scavenging system characterized the photoacclimation response after cells were transferred from a low light condition at 20 µmol photons m-2 s-1 to various light conditions in the range from 0 to 1000 µmol photons m-2 s-1. The activity of ascorbate peroxidase (APX) was most remarkably enhanced with increasing light intensities and illumination periods among the enzymatic activities being measured. Light-dependent regulation of the APX activity was associated with transcriptional regulation of the chloroplast-targeted APX gene. The important role of the APX activity in photoacclimation was evidenced by the effect of the APX inhibitors on the photosystem II activity and the chlorophyll a content under the high light condition at 1000 µmol photons m-2 s-1. Our findings provide a mechanistic explanation for the acclimation of C. yangmingshanensis to a wide range of light regimes in natural habitats.

Anticancer mechanisms on pyroptosis induced by Oridonin: New potential targeted therapeutic strategies.

Pyroptosis is a type of inflammatory cell death that is triggered by the formation of pores on the cell membrane by gasdermin (GSDM) family proteins. This process activates inflammasomes and leads to the maturation and release of proinflammatory cytokines such as interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). Pyroptosis, a form of programmed cell death, has been found to be associated with various biomolecules such as caspases, granzymes, non-coding RNA (lncRNA), reactive oxygen species (ROS), and NOD-like receptor protein 3 (NLRP3). These biomolecules have been shown to play a dual role in cancer by affecting cell proliferation, metastasis, and the tumor microenvironment (TME), resulting in both tumor promotion and anti-tumor effects. Recent studies have found that Oridonin (Ori) has anti-tumor effects by regulating pyroptosis through various pathways. Ori can inhibit pyroptosis by inhibiting caspase-1, which is responsible for activating pyroptosis of the canonical pathway. Additionally, Ori can inhibit pyroptosis by inhibiting NLRP3, which is responsible for activating pyroptosis of the noncanonical pathway. Interestingly, Ori can also activate pyroptosis by activating caspase-3 and caspase-8, which are responsible for activating pyroptosis of the emerging pathway; Ori has been found to be effective in inhibiting pyroptosis by blocking the action of perforin, which is responsible for facilitating the entry of granzyme into cells and activating pyroptosis. Additionally, Ori plays a crucial role in regulating pyroptosis by promoting the accumulation of ROS while inhibiting the ncRNA and NLRP3 pathways. It is worth noting that all of these pathways ultimately regulate pyroptosis by influencing the cleavage of GSDM, which is a key factor in the process. These studies concludes that Ori has extensive anti-cancer effects that are related to its potential regulatory function on pyroptosis. The paper summarizes several potential ways in which Ori participates in the regulation of pyroptosis, providing a reference for further study on the relationship between Ori, pyroptosis, and cancer.

Effect of molecular structure on the adsorption behavior of sulfanilamide antibiotics on crumpled graphene balls.

Since the 1930s, sulfonamide(SA)-based antibiotics have served as important pharmaceuticals, but their widespread detection in water systems threatens aquatic organisms and human health. Adsorption via graphene, its modified form (graphene oxide, GO), and related nanocomposites is a promising method to remove SAs, owing to the strong and selective surface affinity of graphene/GO with aromatic compounds. However, a deeper understanding of the mechanisms of interaction between the chemical structure of SAs and the GO surface is required to predict the performance of GO-based nanostructured materials to adsorb the individual chemicals making up this large class of pharmaceuticals. In this research, we studied the adsorptive performance of 3D crumpled graphene balls (CGBs) to remove 10 SAs and 13 structural analogs from water. The maximum adsorption capacity qm of SAs on CGB increased with the number of (1) aromatic rings; (2) electron-donating functional groups; (3) hydrogen bonding acceptor sites. Furthermore, the CGB surface displayed a preference for homocyclic relative to heterocyclic aromatic structures. A leading mechanism, π-π electron-donor-acceptor interaction, combined with hydrogen bonding, explains these trends. We developed a multiple linear regression model capable of predicting the qm as a function of SA chemical structure and properties and the oxidation level of CGB. The model predicted the adsorptive behaviors of SAs well with the exception of a chlorinated/fluorinated SA. The insights afforded by these experiments and modeling will aid in tailoring graphene-based adsorbents to remove micropollutants from water and reduce the growing public health threats associated with antibiotic resistance and endocrine-disrupting chemicals.

Comparing dual heat pulse methods with Péclet's number as universal switch to measure sap flow across a wide range.

Accurate determination of sap flow over a wide measurement range is important for assessing tree transpiration. However, this is difficult to achieve by using a single heat pulse method. Recent attempts have been made to combine multiple heat pulse methods and have successfully increased the sap flow measurement range. However, relative performance of different dual methods has not yet been addressed, and selection of the numerical threshold used to switch between methods has not been verified among different dual methods. This paper evaluates three different dual methods with respect to measurement range, precision and sources of uncertainty: (method 1) the heat ratio (HR) and compensation heat pulse method; (method 2) the HR and T-max method; and (method 3) the HR and double ratio method. Field experiments showed that methods 1, 2 with three needles and 3 compare well with the benchmark Sapflow+ method, having root mean square deviations of 4.7 cm h-1, 3.0 cm h-1 and 2.4 cm h-1, respectively. The three dual methods are equivalent in accuracy (P > 0.05). Moreover, all dual methods can satisfactorily measure reverse, low and medium heat pulse velocities. However, for high velocities (>100 cm h-1), the HR + T-max (method 2) performed better than the other methods. Another advantage is that this method has a three- instead of four-needle probe configuration, making it less error prone to probe misalignment and plant wounding. All dual methods in this study use the HR method for calculating low to medium flow and a different method for calculating high flow. The optimal threshold for switching from HR to another method is HR's maximum flow, which can be accurately determined from the Péclet number. This study therefore provides guidance for an optimal selection of methods for quantification of sap flow over a wide measurement range.