bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of a telomere-related gene signature to predict prognosis and immune landscape for glioma
Authors: Xie Qin , Liu Tingting , Zhang Xiaole , Ding Yanli , Fan Xiaoyan
Published: June 2023

Background

Glioma is one of the commonest malignant tumors of the brain. However, glioma present with a poor clinical prognosis. Therefore, specific detection markers and therapeutic targets need to be explored as a way to promote the survival rate of BC patients. Therefore, we need to search for quality immune checkpoints to support the efficacy of immunotherapy for glioma.

Methods

We first recognized differentially expressed telomere-related genes (TRGs) and accordingly developed a risk model by univariate and multivariate Cox analysis. The accuracy of the model is then verified. We evaluated the variations in immune function and looked at the expression levels of immune checkpoint genes. Finally, to assess the anti-tumor medications often used in the clinical treatment of glioma, we computed the half inhibitory concentration of pharmaceuticals.

Results

We finally identified nine TRGs and built a risk model. Through the validation of the model, we found good agreement between the predicted and observed values. Then, we found 633 differentially expressed genes between various risk groups to identify the various molecular pathways between different groups. The enrichment of CD4+ T cells, CD8+ T cells, fibroblasts, endothelial cells, macrophages M0, M1, and M2, mast cells, myeloid dendritic cells, and neutrophils was favorably correlated with the risk score, but the enrichment of B cells and NK cells was negatively correlated with the risk score. The expression of several immune checkpoint-related genes differed significantly across the risk groups. Finally, in order to create individualized treatment plans for diverse individuals, we searched for numerous chemotherapeutic medications for patients in various groups.

Conclusion

The findings of this research provide evidence that TRGs may predict a patient’s prognosis for glioma, assist in identifying efficient targets for glioma immunotherapy, and provide a foundation for an efficient, customized approach to treating glioma patients.
Transmission prevention behaviors in US households with SARS-CoV-2 cases in 2020
Authors: Rubinstein Rebecca J. , Mei Wenwen , Cassidy Caitlin A. , Streeter Gabrielle , Basham Christopher , Cerami Carla , Lin Feng-Chang , Lin Jessica T. , Mollan Katie R.
Published: June 2023

Introduction

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission frequently occurs within households, yet few studies describe which household contacts and household units are most likely to engage in transmission-interrupting behaviors.

Methods

We analyzed a COVID-19 prospective household transmission cohort in North Carolina (April to October 2020) to quantify changes in physical distancing behaviors among household contacts over 14 days. We evaluated which household contacts were most likely to ever mask at home and to ever share a bedroom with the index case between days 7–14.

Results

In the presence of a household COVID-19 infection, 24% of household contacts reported ever masking at home during the week before study entry. Masking in the home between days 7–14 was reported by 26% of household contacts and was more likely for participants who observed their household index case wearing a mask. Participants of color and participants in high-density households were more likely to mask at home. After adjusting for race/ethnicity, living density was not as clearly associated with masking. Symptomatic household contacts were more likely to share a bedroom with the index case. Working individuals and those with comorbidities avoided sharing a bedroom with the index case.

Discussion

In-home masking during household exposure to COVID-19 was infrequent in 2020. In light of the ongoing transmission of SARS-CoV-2, these findings underscore a need for health campaigns to increase the feasibility and social desirability of in-home masking among exposed household members. Joint messaging on social responsibility and prevention of breakthrough infections, reinfections, and long COVID-19 may help motivate transmission-interruption behaviors.
The pygidial gland secretion of Laemostenus punctatus (Coleoptera, Carabidae): a source of natural agents with antimicrobial, anti-adhesive, and anti-invasive activities
Authors: Nenadić Marija , Stojković Dejan , Soković Marina , Ćirić Ana , Dimkić Ivica , Janakiev Tamara , Vesović Nikola , Vujisić Ljubodrag , Todosijević Marina , Stanković Saša S. , Ćurčić Nina B. , Milinčić Uroš , Petrović Dragan , Milinčić Miroljub , Ćurčić Srećko
Published: June 2023

In the present study, we investigated in vitro the antimicrobial activity of the pygidial gland secretion of the guanophilic ground beetle Laemostenus (Pristonychus) punctatus (Dejean, 1828) and some of its chemicals against resistant and non-resistant bacteria and Candida species, the synergistic and additive potential of combinations of selected chemicals and antimicrobial drugs against resistant bacterial and fungal strains, anti-adhesive and anti-invasive potential of the secretion and formic acid alone and in selected combinations with antimicrobial drugs against methicillin-resistant Staphylococcus aureus (MRSA) toward spontaneously immortalized human keratinocyte cell line (HaCaT cells). In addition, we examined the antiproliferative activity of the secretion and formic acid in vitro. The tested secretion and the standards of formic and oleic acids possessed a significant level of antimicrobial potential against all tested strains (P < 0.05). The isolate from guano Pseudomonas monteilii showed the highest resistance to the secretion and formic acid, while MRSA achieved a significantly high level of susceptibility to all agents tested, particularly to the combinations of formic acid and antibiotics, but at the same time showed a certain level of resistance to the antibiotics tested individually. Candida albicans and C. tropicalis were found to be the most sensitive fungal strains to the secretion. Formic acid (MIC 0.0005 mg/mL) and gentamicin (MIC 0.0010 mg/mL) in the mixture achieved synergistic antibacterial activity against MRSA (FICI = 0.5, P < 0.05). The combination of formic acid, gentamicin and ampicillin accomplished an additive effect against this resistant bacterial strain (FICI = 1.5, P < 0.05). The secretion achieved a better inhibitory effect on the adhesion ability of MRSA toward HaCaT cells compared to formic acid alone, while formic acid showed better results regarding the invasion (P < 0.001). The combinations of gentamicin and ampicillin, as well as of formic acid and gentamicin and ampicillin achieved similar anti-adhesive and anti-invasive effects, with a slight advantage of formic acid and antibiotics in combination (P < 0.001). The secretion and formic acid were found to be non-toxic to HaCaT cells in vitro (IC50 ≥ 401 μg/mL).
The effect on the seasonal dynamics of soil N transformation resulting from biochar application in karst mountains
Authors: Wang Hankun , Liu Junping , Wu Yongbo , Xue Jianhui
Published: June 2023

Nitrogen (N) is frequently a limiting element for primary productivity in karst ecosystems due to its low availability. N mineralization drives N availability and is important for improving N use efficiency in soils. While the use of biochar in agricultural and forest ecosystems has attracted great attention recently, little has been reported on the seasonal dynamics of soil N transformation in karst and its response to biochar application. Therefore, we conducted a pot experiment over 1 year using two types of biochar (rice husk biochar and wood biochar) as soil amendments. The results demonstrated that in the karst mountain region, the soil had the highest content of mineral N (19.41 mg/kg) during summer and the lowest content of mineral nitrogen (3.74 mg/kg) during winter. There was a significant positive correlation (p < 0.01) between soil mineral N content and temperature, and between soil temperature and urease activity. Thus, the higher temperatures during summer enhance soil urease activity, making it easier for soil N mineralization to occur, and increasing soil mineral N content. The soil mineral N content of the CK treatment was 2.61–209.42% higher than the other treatments, indicating that the biochar application reduced the soil mineral N content, which was supported by the negative net N mineralization. This may be due to biochar facilitating the adsorption and immobilization of nitrogen. The soil mineral N content of rice husk biochar was significantly higher than that of woody biochar by 109.55%, indicating that woody biochar would adsorb more N or more readily stimulate N immobilization than rice husk biochar. Furthermore, soil N immobilization (negative net N mineralization) after biochar application varied according to the season. The higher temperatures during summer promoted soil N immobilization more with biochar application. These results are crucial to understanding soil N transformation in karst mountains and guiding effective soil management.
Responses of fine-root biomass and production to drying depend on wetness and site nutrient regime in boreal forested peatland
Authors: Lampela Maija , Minkkinen Kari , Straková Petra , Bhuiyan Rabbil , He Wei , Mäkiranta Päivi , Ojanen Paavo , Penttilä Timo , Laiho Raija
Published: June 2023

Introduction

Peatlands are terrestrial-carbon hotspots, where changes in carbon pools and fluxes potentially caused by drying or warming may have significant feedbacks to climate change. In forested peatlands, fine-root biomass (FRB), and production (FRP) are important carbon pools and fluxes, but they and their depth distribution and plant functional type (PFT) composition are poorly known.

Methods

We studied the effects of persistent water-table level (WTL) drawdown on these characteristics in four forested boreal peatland site types that varied in soil nutrient and WTL regimes, ground vegetation and tree stand characteristics. Each site type was represented by a pair of one undrained and one drained site. Two pairs were nutrient-poor, Scots pine dominated sites, one very wet and one relatively dry in their undrained condition. The other two pairs were nutrient-rich, Norway spruce dominated sites, again one wetter and one drier in the undrained condition. FRB was estimated by separating and visually identifying roots from soil cores extending down to 50 cm depth. FRP was estimated using ingrowth cores covering the same depth, and the separated roots were identified using infrared spectroscopy.

Results and discussion

Both FRB and FRP varied widely both within and among the different types of boreal forested peatland. In FRB, the clearest differences were seen in the two originally wettest sites, nutrient-poor tall-sedge pine fen and nutrient-rich herb-rich spruce swamp: FRB was smaller in the drained site compared to the undrained site in the pine fen, but the opposite was true in the spruce swamp. FRP was generally higher in the nutrient-poor, pine-dominated sites than the nutrient-rich, spruce-dominates sites. The depth distribution of FRB was more superficial than that of FRP, except for the most nutrient-rich spruce swamp. Tree and shrub roots dominated both FRB and FRP, except for the undrained pine fen, where graminoids and forbs dominated. Even there, these PFTs were replaced by trees and shrubs at the drained site. Site wetness and nutrient regime both thus clearly regulated FRB and FRP of the forested peatland site types studied, and both need to be considered when making any generalizations.
An amino acid metabolism-based seventeen-gene signature correlates with the clinical outcome and immune features in pancreatic cancer
Authors: Hao Jie , Zhou Cancan , Wang Zheng , Ma Zhenhua , Wu Zheng , Lv Yi , Wu Rongqian
Published: June 2023

Background: Pancreatic cancer is an aggressive tumor with a low 5-year survival rate and primary resistance to most therapy. Amino acid (AA) metabolism is highly correlated with tumor growth, crucial to the aggressive biological behavior of pancreatic cancer; nevertheless, the comprehensive predictive significance of genes that regulate AA metabolism in pancreatic cancer remains unknown.

Methods: The mRNA expression data downloaded from The Cancer Genome Atlas (TCGA) were derived as the training cohort, and the GSE57495 cohort from Gene Expression Omnibus (GEO) database was applied as the validation cohort. Random survival forest (RSF) and the least absolute shrinkage and selection operator (LASSO) regression analysis were employed to screen genes and construct an AA metabolism-related risk signature (AMRS). Kaplan-Meier analysis and receiver operating characteristic (ROC) curve were performed to assess the prognostic value of AMRS. We performed genomic alteration analysis and explored the difference in tumor microenvironment (TME) landscape associated with KRAS and TP53 mutation in both high- and low-AMRS groups. Subsequently, the relationships between AMRS and immunotherapy and chemotherapy sensitivity were evaluated.

Results: A 17-gene AA metabolism-related risk model in the TCGA cohort was constructed according to RSF and LASSO. After stratifying patients into high- and low-AMRS groups based on the optimal cut-off value, we found that high-AMRS patients had worse overall survival (OS) in the training cohort (a median OS: 13.1 months vs. 50.1 months, p < 0.0001) and validation cohort (a median OS: 16.2 vs. 30.5 months, p = 1e-04). Genetic mutation analysis revealed that KRAS and TP53 were significantly more mutated in high-AMRS group, and patients with KRAS and TP53 alterations had significantly higher risk scores than those without. Based on the analysis of TME, low-AMRS group displayed significantly higher immune score and more enrichment of T Cell CD8+ cells. In addition, high-AMRS-group exhibited higher TMB and significantly lower tumor immune dysfunction and exclusion (TIDE) score and T Cells dysfunction score, which suggested a higher sensitive to immunotherapy. Moreover, high-AMRS group was also more sensitive to paclitaxel, cisplatin, and docetaxel.

Conclusion: Overall, we constructed an AA-metabolism prognostic model, which provided a powerful prognostic predictor for the clinical treatment of pancreatic cancer.
Virus tracking technologies and their applications in viral life cycle: research advances and future perspectives
Authors: Liu Di , Pan Li , Zhai Huanjie , Qiu Hua-Ji , Sun Yuan
Published: June 2023

Viruses are simple yet highly pathogenic microorganisms that parasitize within cells and pose serious threats to the health, economic development, and social stability of both humans and animals. Therefore, it is crucial to understand the dynamic mechanism of virus infection in hosts. One effective way to achieve this is through virus tracking technology, which utilizes fluorescence imaging to track the life processes of virus particles in living cells in real-time, providing a comprehensively and detailed spatiotemporal dynamic process and mechanism of virus infection. This paper provides a broad overview of virus tracking technology, including the selection of fluorescent labels and virus labeling components, the development of imaging microscopes, and its applications in various virus studies. Additionally, we discuss the possibilities and challenges of its future development, offering theoretical guidance and technical support for effective prevention and control of the viral disease outbreaks and epidemics.
The UK kidney donor risk index poorly predicts long-term transplant survival in paediatric kidney transplant recipients
Authors: Kim Jon Jin , Curtis Rebecca M. K. , Reynolds Ben , Marks Stephen D. , Drage Martin , Kosmoliaptsis Vasilis , Dudley Jan , Williams Alun
Published: June 2023

Background

The UK kidney offering scheme introduced a kidney donor risk index (UK-KDRI) to improve the utility of deceased-donor kidney allocations. The UK-KDRI was derived using adult donor and recipient data. We assessed this in a paediatric cohort from the UK transplant registry.

Methods

We performed Cox survival analysis on first kidney-only deceased brain-dead transplants in paediatric (<18 years) recipients from 2000-2014. The primary outcome was death-censored allograft survival >30 days post-transplant. The main study variable was UK-KDRI derived from seven donor risk-factors, categorised into four groups (D1-low risk, D2, D3 and D4-highest risk). Follow-up ended on 31-December-2021.

Results

319/908 patients experienced transplant loss with rejection as the main cause (55%). The majority of paediatric patients received donors from D1 donors (64%). There was an increase in D2-4 donors during the study period, whilst the level of HLA mismatching improved. The KDRI was not associated with allograft failure. In multi-variate analysis, increasing recipient age [adjusted HR and 95%CI: 1.05(1.03-1.08) per-year, p<0.001], recipient minority ethnic group [1.28(1.01-1.63), p<0.05), dialysis before transplant [1.38(1.04-1.81), p<0.005], donor height [0.99 (0.98-1.00) per centimetre, p<0.05] and level of HLA mismatch [Level 3: 1.92(1.19-3.11); Level 4: 2.40(1.26-4.58) versus Level 1, p<0.01] were associated with worse outcomes. Patients with Level 1 and 2 HLA mismatches (0 DR +0/1 B mismatch) had median graft survival >17 years regardless of UK-KDRI groups. Increasing donor age was marginally associated with worse allograft survival [1.01 (1.00-1.01) per year, p=0.05].

Adult donor risk scores were not associated with long-term allograft survival in paediatric patients. The level of HLA mismatch had the most profound effect on survival. Risk models based on adult data alone may not have the same validity for paediatric patients and therefore all age-groups should be included in future risk prediction models.
Trophic redundancy in benthic fish food webs increases with scarcity of prey items, in the Southern Baltic Sea
Authors: de la Vega Camille , Paar Martin , Köhler Linda , von Dorrien Christian , Kriegl Michael , Oesterwind Daniel , Schubert Hendrik
Published: June 2023

Bottom trawling is one of the main pressures on benthic ecosystems, directly impacting the targeted species and physically disturbing the seabed and the benthic invertebrate communities, in turn indirectly impacting benthivorous fish and the entire benthic food web structure and functioning. To predict the cascading effect of bottom trawling on benthic and demersal fish communities, it is crucial to understand the trophic interactions between benthic and demersal fish and benthic invertebrates. Here, we assessed the diet of benthic and demersal fish and the structure and functioning of the benthic food web in two areas in the German Baltic Sea, the Fehmarnbelt and the Odra Bank. The Fehmarnbelt benthic invertebrate community is characterized by a high number of species and biomass, contrary to the one on the Odra Bank which is species poor with high individual abundance but low biomass. We used mixing models based on stable isotopes of carbon and nitrogen combined with stomach content analyses to estimate the fish diet at both sites, and we used community-wide trophic indices, derived from stable isotopes to compare the structure and functioning of the fish benthic food webs. We show that fish in the Fehmarnbelt can chose preferential prey items, resulting in higher trophic diversity, contrary to fish on the Odra Bank, which feed on all available prey species, resulting in higher trophic redundancy. We found that the generalist behavior of fish on the Odra Bank is likely the result of scarcity in prey items, the benthic invertebrate community being species poor with high abundance of small individuals. We demonstrate that the differences in structure and functioning of the benthic fish food web between the two sites was mainly driven by differences in the characteristics of the benthic prey communities.
Early diagenesis and benthic fluxes of redox-sensitive metals in eastern China shelf sediments
Authors: Wang Xiaojing , Li Li , Ren Yijun , Cao Peng , Zhu Aimei , Liu Jihua , Shi Xuefa
Published: June 2023

Thirteen Short sediment cores (30-50 cm) were collected from Bohai Sea, Yellow Sea and Changjiang Estuary in China, and the early diagenesis of several redox sensitive metals (Fe, Mn, Mo, U and V, referring to as RSMs) in sediment were studied. The recycling process of Mo and Mn was closely correlated with each other, generating benthic fluxes diffusing upward from sediment to overlying water column, and the flux rates are related to the organic carbon oxidation rates. The recycling of U and V were more tightly coupled with Fe oxides, generating benthic fluxes going downward into the sediment in most cores. Significant authigenic accumulation of U, in contrary to little to no accumulation of Mo and V, were found in the study region, even in Changjiang Estuary where hypoxic condition was often found during summer. Benthic diffusive fluxes were compared with authigenic mass accumulate rates (MAR), which indicated that, besides the benthic diffusion process, there are other processes controlling the authigenic accumulation of the RSMs. The close relationships between authigenic accumulation of RSMs with OCburial and OCburial with Sburial, indicating the authigenic accumulation of RSMs is a consequence of redox environment in shelf sediment, which directly influencing the organic carbon degradation process. Compared with other continental margin, moderate enrichment of U was found in China continental sediment. The authigenic U accumulation in BS and NYS sediments accounted for 20 - 68% of the Yellow River input, whilst in SYS sediments accounted for ~ 64% of the Yellow River and Changjiang River input, which acting as important U sinks that cannot be ignored.
Bivalves and microbes: a mini-review of their relationship and potential implications for human health in a rapidly warming ocean
Authors: Masanja Fortunatus , Yang Ke , Xu Yang , He Guixiang , Liu Xiaolong , Xu Xin , Jiang Xiaoyan , Luo Xin , Mkuye Robert , Deng Yuewen , Zhao Liqiang
Published: June 2023

Heatwaves have become increasingly frequent and intense, posing a significant threat to the survival and health of marine bivalves. The temperature fluctuations associated with heatwaves can cause significant alterations in the composition and quantity of microbial communities in bivalves, resulting in changes to their immunological responses, gut microbiome, oxidative stress levels, and other physiological processes and eventually making them more susceptible to diseases and mass mortalities. This is particularly concerning because some of these bivalves are consumed raw, which could represent a risk to human health. This paper provides an overview of the current state of knowledge regarding the impact of marine heatwaves on bivalves and their microbial communities, demonstrating the intricate relationship between heatwaves, microbial ecosystems, and bivalve health. Our analysis highlights the need for additional research to establish the underlying mechanisms of these reactions and to develop appropriate conservation and management strategies to limit the impact of heatwaves on bivalves and their microbial ecosystems.
Efficacy of acupuncture for pain relief in patients receiving extracorporeal shock wave lithotripsy: a meta-analysis of randomized controlled studies
Authors: Chen Hsiao-Tien , Hung Kuo-Chuan , Hsu Yao-Chin , Kuo Jinn-Rung , Chang Ying-Jen , Chen I-Wen , Sun Cheuk-Kwan
Published: June 2023

Background

This meta-analysis aimed at investigating the efficacy of acupuncture for pain relief in patients receiving extracorporeal shock wave lithotripsy (ESWL).

Methods

Randomized controlled trials comparing the efficacy of acupuncture with conventional treatments were retrieved from major electronic databases (e.g., MEDLINE, EMBASE, and Cochrane Library) until August 28, 2022. The primary outcome was the response rate (i.e., rate of pain relief), while secondary outcomes included stone-free rate, satisfaction rate, duration of ESWL, peri-/post-procedural pain score, and risk of adverse events.

Results

Thirteen eligible studies involving 1,220 participants published between 1993 and 2022 were analyzed. Pooled results indicated that acupuncture had a better response rate compared to conventional treatments (RR = 1.17, 95% CI: 1.06–1.3, p = 0.003, seven trials, n = 832). Despite no difference in ESWL duration (MD = 0.02 min, 95% CI: −1.53 to 1.57, p = 0.98, three trials, n = 141), stone-free rate (RR = 1.11, 95% CI: 1–1.25, p = 0.06, six trials, n = 498), and satisfaction rate (RR = 1.51, 95% CI: 0.92–2.47, p = 0.1, three trials, n = 334) between the two groups, the acupuncture group had a lower risk of adverse events (RR = 0.51, 95% CI: 0.33–0.79, p = 0.003, five trials, n = 327), peri- (MD = −1.91 points, 94% CI: −3.53 to −0.28, p = 0.02, four trials, n = 258 patient) and post-procedural (MD = −1.07, 95% CI: −1.77 to −0.36, p = 0.003, four trials, n = 335) pain score.

Conclusion

The results of this meta-analysis showed that the use of acupuncture in patients receiving ESWL was associated with a higher pain relief rate and a lower risk of adverse events, suggesting feasibility of its use in this clinical setting.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42022356327.
Historical eye on IPF: a cohort study redefining the mortality scenario
Authors: Tomassetti Sara , Ravaglia Claudia , Piciucchi Sara , Ryu Jay , Wells Athol , Donati Luca , Dubini Alessandra , Klersy Catherine , Luzzi Valentina , Gori Leonardo , Rosi Elisabetta , Lavorini Federico , Poletti Venerino
Published: June 2023

Rationale

Therapies that slow idiopathic pulmonary fibrosis (IPF) progression are now available and recent studies suggest that the use of antifibrotic therapy may reduce IPF mortality.

Objectives

The aim of the study was to evaluate whether, to what extent, and for which factors the survival of IPF in a real-life setting has changed in the last 15 years.

Methods

Historical eye is an observational study of a large cohort of consecutive IPF patients diagnosed and treated in a referral center for ILDs with prospective intention. We recruited all consecutive IPF patients seen at GB Morgagni Hospital, Forlì, Italy between January 2002 and December 2016 (15 years). We used survival analysis methods to describe and model the time to death or lung transplant and Cox regression to model prevalent and incident patient characteristics (time-dependent Cox models were fitted).

Measurements and main results

The study comprised 634 patients. The year 2012 identifies the time point of mortality shift (HR 0.58, CI 0.46–0.63, p < 0.001). In the more recent cohort, more patients had better preserved lung function, underwent cryobiopsy instead of surgery, and were treated with antifibrotics. Highly significant negative prognostic factors were lung cancer (HR 4.46, 95% CI 3.3–6, p < 0.001), hospitalizations (HR 8.37, 95% CI 6.5–10.7, p < 0.001), and acute exacerbations (HR 8.37, 95% CI 6.52–10.7, p < 0.001). The average antifibrotic treatment effect estimated using propensity score matching showed a significant effect in the reduction of all-cause mortality (ATE coeff −0.23, SE 0.04, p < 0.001), acute exacerbations (ATE coeff −0.15, SE 0.04, p < 0.001), and hospitalizations (ATE coeff −0.15, SE 0.04, p < 0.001) but no effect on lung cancer risk (ATE coeff −0.03, SE 0.03, p = 0.4).

Conclusion

Antifibrotic drugs significantly impact hospitalizations, acute exacerbations, and IPF survival. After the introduction of cryobiopsy and antifibrotic drugs, the prognosis of IPF patients has significantly improved together with our ability to detect IPF at an earlier stage.
Nebulized mesenchymal stem cell derived conditioned medium ameliorates Escherichia coli induced pneumonia in a rat model
Authors: González Héctor E. , McCarthy Sean D. , Masterson Claire , Laffey John G. , MacLoughlin Ronan , O’Toole Daniel
Published: June 2023

Background

Mesenchymal stem cells (MSC) have shown immense therapeutic promise in a range of inflammatory diseases, including acute respiratory distress syndrome (ARDS), and are rapidly advancing through clinical trials. Among their multimodal mechanisms of action, MSCs exert strong immunomodulatory effects via their secretome, which contains cytokines, small molecules, extracellular vesicles, and a range of other factors. Recent studies have shown that the MSC secretome can recapitulate many of the beneficial effects of the MSC itself. We aimed to determine the therapeutic capacity of the MSC secretome in a rat bacterial pneumonia model, especially when delivered directly to the lung by nebulization which is a technique more appropriate for the ventilated patient.

Methods

Conditioned medium (CM) was generated from human bone marrow derived MSCs in the absence of antibiotics and serum supplements. Post-nebulization lung penetration was estimated through nebulization of CM to a cascade impactor and simulated lung and quantification of collected total protein and IL-8 cytokine. Control and nebulized CM was added to a variety of lung cell culture models and injury resolution assessed. In a rat E. coli pneumonia model, CM was instilled or administered by nebulization and lung injury and inflammation assessed at 48 h.

Results

MSC-CM was predicted to have good distal lung penetration and delivery when administered by nebulizer. Both control and nebulized CM reduced NF-κB activation and inflammatory cytokine production in lung cell culture, while promoting cell viability and would closure in oxidative stress and scratch wound models. In a rat bacterial pneumonia model, both instilled and nebulizer delivered CM improved lung function, increasing blood oxygenation and reducing carbon dioxide levels compared to unconditioned medium controls. A reduction in bacterial load was also observed in both treatment groups. Inflammatory cytokines were reduced significantly by both liquid and aerosol CM administration, with less IL-1β, IL-6, and CINC1 in these groups compared to controls.

Conclusion

MSC-CM is a potential therapeutic for pneumonia ARDS, and administration is compatible with vibrating mesh nebulization.
Serum metabolic signatures for acute pulmonary embolism identified by untargeted metabolomics
Authors: Xie Ming , Liu Yu , Zheng Hui , Gao Xiaoli , Liu Ran
Published: June 2023

Background and aims

The important metabolic features of acute pulmonary embolism (APE) risk stratification and their underlying biological basis remain elusive. Our study aims to develop early diagnostic models and classification models by analyzing the plasma metabolic profile of patients with APE.

Materials and methods

Serum samples were collected from 68 subjects, including 19 patients with confirmed APE, 35 patients with confirmed NSTEMI, and 14 healthy individuals. A comprehensive metabolic assessment was performed using ultra-performance liquid chromatography-mass spectrometry based on an untargeted metabolomics approach. In addition, an integrated machine learning strategy based on LASSO and logistic regression was used for feature selection and model building.

Results

The metabolic profiles of patients with acute pulmonary embolism and NSTEMI is significantly altered relative to that of healthy individuals. KEGG pathway enrichment analysis revealed differential metabolites between acute pulmonary embolism and healthy individuals mainly involving glycerophosphate shuttle, riboflavin metabolism, and glycerolipid metabolism. A panel of biomarkers was defined to distinguish acute pulmonary embolism, NSTEMI, and healthy individuals with an area under the receiver operating characteristic curve exceeding 0.9 and higher than that of D-dimers.

Conclusion

This study contributes to a better understanding of the pathogenesis of APE and facilitates the discovery of new therapeutic targets. The metabolite panel can be used as a potential non-invasive diagnostic and risk stratification tool for APE.
Collagen co-localized with macrovesicular steatosis better differentiates fibrosis progression in non-alcoholic fatty liver disease mouse models
Authors: Wang Xiao-Xiao , Jin Rui , Li Xiao-He , Yang Qiang , Teng Xiao , Liu Fang-Fang , Wu Nan , Rao Hui-Ying , Liu Feng
Published: June 2023

Background

Non-alcoholic fatty liver disease (NAFLD) is a global commonly occurring liver disease. However, its exact pathogenesis is not fully understood. The purpose of this study was to quantitatively evaluate the progression of steatosis and fibrosis by examining their distribution, morphology, and co-localization in NAFLD animal models.

Methods

Six mouse NAFLD groups were established: (1) western diet (WD) group; (2) WD with fructose in drinking water (WDF) group; (3) WDF + carbon tetrachloride (CCl4) group, WDF plus intraperitoneal injection of CCl4; (4) high-fat diet (HFD) group, (5) HFD with fructose (HFDF) group; and (6) HFDF + CCl4 group, HFDF plus intraperitoneal injection of CCl4. Liver tissue specimens from NAFLD model mice were collected at different time points. All the tissues were serially sectioned for histological staining and second-harmonic generation (SHG)/two-photon excitation fluorescence imaging (TPEF) imaging. The progression of steatosis and fibrosis was analyzed using SHG/TPEF quantitative parameters with respect to the non-alcoholic steatohepatitis Clinical Research Network scoring system.

Results

qSteatosis showed a good correlation with steatosis grade (R: 0.823–0.953, p < 0.05) and demonstrated high performance (area under the curve [AUC]: 0.617-1) in six mouse models. Based on their high correlation with histological scoring, qFibrosis containing four shared parameters (#LongStrPS, #ThinStrPS, #ThinStrPSAgg, and #LongStrPSDis) were selected to create a linear model that could accurately identify differences among fibrosis stages (AUC: 0.725-1). qFibrosis co-localized with macrosteatosis generally correlated better with histological scoring and had a higher AUC in six animal models (AUC: 0.846-1).

Conclusion

Quantitative assessment using SHG/TPEF technology can be used to monitor different types of steatosis and fibrosis progression in NAFLD models. The collagen co-localized with macrosteatosis could better differentiate fibrosis progression and might aid in developing a more reliable and translatable fibrosis evaluation tool for animal models of NAFLD.
Establishment of a novel cytokine-related 8-gene signature for distinguishing and predicting the prognosis of triple-negative breast cancer
Authors: Liu Xiaojun , Zhang Liang , Chen Liang
Published: June 2023

Background

Triple-negative breast cancer (TNBC) is a common carcinoma in women, and the prognosis of TNBC is the worst. Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the functional roles of cytokine-related genes in TNBC.

Methods

The clinical and transcriptome data of TNBC patients were downloaded from TCGA database. A systematical analyses of the data from TCGA database were conducted to screen the prognostic genes and identify the main cytokine-related pathways related to TNBC.

Results

We identified 499 prognostic genes in TNBC patients from TCGA database and the cytokine-related pathways closely related to TNBC. TCGA-TNBC patients were divided into the high-risk cluster (C1) group and the low-risk cluster (C2) group based on the cytokine-related genes. The C1 group patients exhibited tumor metastasis and an advanced tumor stage. The functional analysis revealed that the upregulated differentially expressed genes (DEGs) in the C1 group were mainly associated with the extracellular matrix (ECM)-receptor interaction, stem cell proliferation, focal adhesion, and cyclic adenosine monophosphate (cAMP) signaling pathway, while the downregulated DEGs in the C1 group were mainly associated with cytokine and cytokine receptors, T-helper 17 (Th17) cell differentiation, and primary immunodeficiency. The immune activity of C1 group was lower than that of C2 group, and the identified half-maximal inhibitory concentration scores of 3 chemotherapy drugs (i.e., doxorubicin, methotrexate, and paclitaxel) were lower in C2 group than C1 group. More importantly, we constructed a novel prognostic signature and identified the following 8 genes: CCL25, CXCL13, IL12RB2, IL21, TNFRSF13C, TNFRSF8, CCL7 and GDF5.

Conclusion

The status of the cytokine-related pathway was closely related to tumor classification and immune activity in the TNBC patients. The gene signature of the cytokine-related genes showed an good performance in predicting the prognosis of TNBC patients, and could predict the prognosis of TNBC patients.
All tangled up: interactions of the fibrinolytic and innate immune systems
Authors: Whyte Claire S.
Published: June 2023

The hemostatic and innate immune system are intertwined processes. Inflammation within the vasculature promotes thrombus development, whilst fibrin forms part of the innate immune response to trap invading pathogens. The awareness of these interlinked process has resulted in the coining of the terms “thromboinflammation” and “immunothrombosis.” Once a thrombus is formed it is up to the fibrinolytic system to resolve these clots and remove them from the vasculature. Immune cells contain an arsenal of fibrinolytic regulators and plasmin, the central fibrinolytic enzyme. The fibrinolytic proteins in turn have diverse roles in immunoregulation. Here, the intricate relationship between the fibrinolytic and innate immune system will be discussed.
A three-species synthetic community model whose rapid response to antagonism allows the study of higher-order dynamics and emergent properties in minutes
Authors: Aguilar-Salinas Bernardo , Olmedo-Álvarez Gabriela
Published: June 2023

Microbial communities can be considered complex adaptive systems. Understanding how these systems arise from different components and how the dynamics of microbial interactions allow for species coexistence are fundamental questions in ecology. To address these questions, we built a three-species synthetic community, called BARS (Bacillota A + S + R). Each species in this community exhibits one of three ecological roles: Antagonistic, Sensitive, or Resistant, assigned in the context of a sediment community. We show that the BARS community reproduces features of complex communities and exhibits higher-order interaction (HOI) dynamics. In paired interactions, the majority of the S species (Sutcliffiella horikoshii 20a) population dies within 5 min when paired with the A species (Bacillus pumilus 145). However, an emergent property appears upon adding the third interactor, as antagonism of species A over S is not observed in the presence of the R species (Bacillus cereus 111). For the paired interaction, within the first 5 min, the surviving population of the S species acquires tolerance to species A, and species A ceases antagonism. This qualitative change reflects endogenous dynamics leading to the expression for tolerance to an antagonistic substance. The stability reached in the triple interaction exhibits a nonlinear response, highly sensitive to the density of the R species. In summary, our HOI model allows the study of the assembly dynamics of a three-species community and evaluating the immediate outcome within a 30 min frame. The BARS has features of a complex system where the paired interactions do not predict the community dynamics. The model is amenable to mechanistic dissection and to modeling how the parts integrate to achieve collective properties.
Coordination and divergence in community assembly processes across co-occurring microbial groups separated by cell size
Authors: Li Xinghao , Stegen James C. , Yu Yuhe , Huang Jie
Published: June 2023

Setting the pace of life and constraining the role of members in food webs, body size can affect the structure and dynamics of communities across multiple scales of biological organization (e.g., from the individual to the ecosystem). However, its effects on shaping microbial communities, as well as underlying assembly processes, remain poorly known. Here, we analyzed microbial diversity in the largest urban lake in China and disentangled the ecological processes governing microbial eukaryotes and prokaryotes using 16S and 18S amplicon sequencing. We found that pico/nano-eukaryotes (0.22−20 μm) and micro-eukaryotes (20−200 μm) showed significant differences in terms of both community composition and assembly processes even though they were characterized by similar phylotype diversity. We also found scale dependencies whereby micro-eukaryotes were strongly governed by environmental selection at the local scale and dispersal limitation at the regional scale. Interestingly, it was the micro-eukaryotes, rather than the pico/nano-eukaryotes, that shared similar distribution and community assembly patterns with the prokaryotes. This indicated that assembly processes of eukaryotes may be coupled or decoupled from prokaryotes’ assembly processes based on eukaryote cell size. While the results support the important influence of cell size, there may be other factors leading to different levels of assembly process coupling across size classes. Additional studies are needed to quantitatively parse the influence of cell size versus other factors as drivers of coordinated and divergent community assembly processes across microbial groups. Regardless of the governing mechanisms, our results show that there are clear patterns in how assembly processes are coupled across sub-communities defined by cell size. These size-structured patterns could be used to help predict shifts in microbial food webs in response to future disturbance.
Multi-strain probiotics alleviate loperamide-induced constipation by adjusting the microbiome, serotonin, and short-chain fatty acids in rats
Authors: Jeong Jin-Ju , Ganesan Raja , Jin Yoo-Jeong , Park Hee Jin , Min Byeong Hyun , Jeong Min Kyo , Yoon Sang Jun , Choi Mi Ran , Choi Jieun , Moon Ji Hyun , Min Uigi , Lim Jong-Hyun , Lee Do Yup , Han Sang Hak , Ham Young Lim , Kim Byung-Yong , Suk Ki Tae
Published: June 2023

Constipation is one of the most common gastrointestinal (GI) disorders worldwide. The use of probiotics to improve constipation is well known. In this study, the effect on loperamide-induced constipation by intragastric administration of probiotics Consti-Biome mixed with SynBalance® SmilinGut (Lactobacillus plantarum PBS067, Lactobacillus rhamnosus LRH020, Bifidobacterium animalis subsp. lactis BL050; Roelmi HPC), L. plantarum UALp-05 (Chr. Hansen), Lactobacillus acidophilus DDS-1 (Chr. Hansen), and Streptococcus thermophilus CKDB027 (Chong Kun Dang Bio) to rats was evaluated. To induce constipation, 5 mg/kg loperamide was intraperitoneally administered twice a day for 7 days to all groups except the normal control group. After inducing constipation, Dulcolax-S tablets and multi-strain probiotics Consti-Biome were orally administered once a day for 14 days. The probiotics were administered 0.5 mL at concentrations of 2 × 108 CFU/mL (G1), 2 × 109 CFU/mL (G2), and 2 × 1010 CFU/mL (G3). Compared to the loperamide administration group (LOP), the multi-strain probiotics not only significantly increased the number of fecal pellets but also improved the GI transit rate. The mRNA expression levels of serotonin- and mucin-related genes in the colons that were treated with the probiotics were also significantly increased compared to levels in the LOP group. In addition, an increase in serotonin was observed in the colon. The cecum metabolites showed a different pattern between the probiotics-treated groups and the LOP group, and an increase in short-chain fatty acids was observed in the probiotic-treated groups. The abundances of the phylum Verrucomicrobia, the family Erysipelotrichaceae and the genus Akkermansia were increased in fecal samples of the probiotic-treated groups. Therefore, the multi-strain probiotics used in this experiment were thought to help alleviate LOP-induced constipation by altering the levels of short-chain fatty acids, serotonin, and mucin through improvement in the intestinal microflora.
Complete genome sequence of biocontrol strain Bacillus velezensis YC89 and its biocontrol potential against sugarcane red rot
Authors: Xie Linyan , Liu Lufeng , Luo Yanju , Rao Xibing , Di Yining , Liu Han , Qian Zhenfeng , Shen Qingqing , He Lilian , Li Fusheng
Published: June 2023

Introduction

Sugarcane is one of the most important sugar crops worldwide, however, sugarcane production is seriously limited by sugarcane red rot, a soil-borne disease caused by Colletotrichum falcatum. Bacillus velezensis YC89 was isolated from sugarcane leaves and can significantly inhibited red rot disease caused by C. falcatum.

Methods

In this study, the genome of YC89 strain was sequenced, its genome structure and function were analyzed using various bioinformatics software, and its genome was compared with those of other homologous strains. In addition, the effectiveness of YC89 against sugarcane red rot and the evaluation of sugarcane plant growth promotion were also investigated by pot experiments.

Results

Here, we present the complete genome sequence of YC89, which consists of a 3.95 Mb circular chromosome with an average GC content of 46.62%. The phylogenetic tree indicated that YC89 is closely related to B. velezensis GS-1. Comparative genome analysis of YC89 with other published strains (B. velezensis FZB42, B. velezensis CC09, B. velezensis SQR9, B. velezensis GS-1, and B. amyloliquefaciens DSM7) revealed that the strains had a part common coding sequences (CDS) in whereas 42 coding were unique of strain YC89. Whole-genome sequencing revealed 547 carbohydrate-active enzymes and identified 12 gene clusters encoding secondary metabolites. Additionally, functional analysis of the genome revealed numerous gene/gene clusters involved in plant growth promotion, antibiotic resistance, and resistance inducer synthesis. In vitro pot tests indicated that YC89 strain controlled sugarcane red rot and promoted the growth of sugarcane plants. Additionally, it increased the activity of enzymes involved in plant defense, such as superoxide dismutase, peroxidase, polyphenol oxidase, chitinase, and β-1,3-glucanase.

Discussion

These findings will be helpful for further studies on the mechanisms of plant growth promotion and biocontrol by B. velezensis and provide an effective strategy for controlling red rot in sugarcane plants.
The combined effect of a novel formula of herbal extracts on bacterial infection and immune response in Micropterus salmoides
Authors: Guo Huanyu , Chen Jing , Yuan Xuemei , Zhang Jian , Wang Jiayang , Yao Jiayun , Ge Haixia
Published: June 2023

Herbal extracts have been considered as ideal alternative to antibiotics in aquaculture and application of combinatory effective extracts always can exhibit the enhanced bioactivity with high efficiency. In our study, a novel herbal extract combination GF-7, which is composed of Galla Chinensis, Mangosteen Shell extracts as well as the effective parts of Pomegranate peel and Scutellaria baicalensis Georgi extracts, was prepared and applied for the therapy of bacterial infection in aquaculture. The HPLC analysis of GF-7 was also investigated for quality control and chemical identification. In the bioassay, GF-7 had excellent antibacterial activity against various aquatic pathogenic bacteria in vitro, and the related MIC values were between 0.045 and 0.36 mg/mL. After feeding Micropterus salmoide with GF-7 (0.1, 0.3, and 0.6%, respectively) for 28 days, the activities of ACP, AKP, LZM, SOD, and CAT of the liver in each treatment group were significantly increased and the content of MDA was significantly decreased. Meanwhile, the hepatic expression of the immune regulators including IL-1β, TNF-α, and Myd88 at different times was up-regulated in varying degrees. The challenge results exhibited a good dose-dependent protective effect on M. salmoides infected with A. hydrophila, which was further confirmed by liver histopathology. Our results imply that the novel combination GF-7 is a potential natural medicine for the prevention and treatment of numerous aquatic pathogenic infectious diseases in aquaculture.