bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial growth stage determines the yields, protein composition, and periodontal pathogenicity of Porphyromonas gingivalis outer membrane vesicles
Authors: Mao Hongchen , Gong Ting , Sun Yuting , Yang Shiyao , Qiao Xin , Yang Deqin 
Published: October 2023

IntroductionP. gingivalis (W83), as the keystone pathogen in chronic periodontitis, has been found to be tightly bound to systemic diseases. Outer membrane vesicles (OMVs) produced by P. gingivalis (W83) are thought to serve key functions in bacterial virulence and pathogenicity. This study aims to comprehend the biological functions of P. gingivalis OMVs isolated from different growth stages by comparing their physicochemical properties and pathogenicity.MethodsProtein composition was analyzed via isotope-labeled relative and absolute quantification (iTRAQ). Macrophage polarization and the expression of IL-6 and IL-1β were detected. The proliferation, migration, osteogenic differentiation, and IL-1b/NLRP3 expression of periodontal ligament stem cells (PDLSCs) were evaluated. P. gingivalis/P. gingivalis OMVs-induced periodontal models were also constructed in Sprague Dawley rats.ResultsThe protein composition of P. gingivalis OMVs isolated from different growth stages demonstrated obvious differences ranging from 25 KDa to 75 KDa. In the results of flow cytometry, we found that in vitro experiments the M1 subtype of macrophages was more abundant in the late-log OMVs and stationary OMVs groups which boosted the production of inflammatory cytokines more than pre-log OMVs. Compared to pre-log OMVs, late-log OMVs and stationary OMVs had more pronounced inhibitory effects on proliferation, migration, and early osteogenesis of PDLSCs. The NLRP3 inflammasome was activated to a larger extent in the stationary OMVs group. Micro-computed tomography (Micro CT), hematoxylin-eosin staining (HE), and tartrate acid phosphatase (TRAP) results showed that the periodontal damage in the stationary OMVs group was worse than that in the pre-log OMVs and late-log OMVs group, but almost equal to that in the positive control group (P. gingivalis).DiscussionIn general, both in vivo and in vitro experiments showed that late-log OMVs and stationary OMVs have more significant pathogenicity in periodontal disease.
Late Quaternary glacier advances in the Andes of Santiago, central Chile, and paleoclimatic implications
Authors: Herrera-Ossandón Mariajosé , Easton Gabriel , Antinao José Luis , Forman Steven L. 
Published: October 2023

Andean mountain glaciers in central Chile are in a transitional zone between the seasonal influence of the mid-latitude westerlies and subtropical semiarid conditions to the north. Long-term glacial dynamics for these glaciers and their relationship with the paleoclimate during the late Quaternary are poorly known despite their relevancy. We estimate here the timing and extent of late Pleistocene–early Holocene glaciers in the Andes of Santiago (33°50′S) from geomorphological and geochronological analyses. Our observations evidence that a glacial stage occurred before the Last Glacial Maximum (ELGM) at the San Gabriel drift (1,300 m a.s.l.), dated as ∼46–36 ka. Glacial stages during the latest Pleistocene–early Holocene transition period, partially concomitant with the Antarctic Cold Reversal (ACR) and with the Younger Dryas (YD) chronozones, were identified and dated at La Engorda drift (2,450–2,570 m a.s.l.) at ∼15–10 ka. We propose that the San Gabriel drift represents a prolonged glacial advance driven by increased precipitation and cold conditions off central Chile during glacial times. In La Engorda drift, late glacial advances occurred associated with increased regional precipitation, in the context of a transition from humid to arid climate in central Chile, concomitantly with a general warming trend of sea surface temperatures offshore in the southeastern Pacific and with reduced austral summer insolation. The results support the sensitivity of the Andean mountain glaciers to precipitation and paleoclimate conditions, most possibly associated with periods of increased northward influence of the mid-latitude westerlies during glacial and late glacial times, in addition to the El Niño/Southern Oscillation (ENSO) impact since the mid-Holocene, driving late Quaternary glacier advances in central Chile. We estimate a maximum variation of ∼1,200 m in the position of the late Quaternary Equilibrium Line Altitude (ELA), inferred at ∼3,400 m and ∼3,600 m a.s.l. at the time of the San Gabriel and La Engorda drifts, respectively, with respect to its modern location close to 4,600 m a.s.l.
Association of sex hormones and sex hormone-binding globulin with liver fat in men and women: an observational and Mendelian randomization study
Authors: Cai Xinting , Thorand Barbara , Hohenester Simon , Prehn Cornelia , Cecil Alexander , Adamski Jerzy , Zeller Tanja , Dennis Andrea , Banerjee Rajarshi , Peters Annette , Yaghootkar Hanieh , Nano Jana 
Published: October 2023

BackgroundSex hormones and sex hormone-binding globulin (SHBG) may play a role in fatty liver development. We sought to examine the association of various endogenous sex hormones, including testosterone (T), and SHBG with liver fat using complementary observational and Mendelian randomization (MR) analyses.MethodsThe observational analysis included a total of 2,239 participants (mean age 60 years; 35% postmenopausal women) from the population-based KORA study (average follow-up time: 6.5 years). We conducted linear regression analysis to investigate the sex-specific associations of sex hormones and SHBG with liver fat, estimated by fatty liver index (FLI). For MR analyses, we selected genetic variants associated with sex hormones and SHBG and extracted their associations with magnetic resonance imaging measured liver fat from the largest up to date European genome-wide associations studies.ResultsIn the observational analysis, T, dihydrotestosterone (DHT), progesterone and 17α-hydroxyprogesterone (17-OHP) were inversely associated with FLI in men, with beta estimates ranging from -4.23 to -2.30 [p-value &lt;0.001 to 0.003]. Whereas in women, a positive association of free T with FLI (β = 4.17, 95%CI: 1.35, 6.98) was observed. SHBG was inversely associated with FLI across sexes [men: -3.45 (-5.13, -1.78); women: -9.23 (-12.19, -6.28)]. No causal association was found between genetically determined sex hormones and liver fat, but higher genetically determined SHBG was associated with lower liver fat in women (β = -0.36, 95% CI: -0.61, -0.12).ConclusionOur results provide suggestive evidence for a causal association between SHBG and liver fat in women, implicating the protective role of SHBG against liver fat accumulation.
Temporal and spatial dynamics in emission of water-soluble ions in fine particulate matter during forest fires in Southwest China
Authors: Zhan Xiaoyu , Ma Yuanfan , Huang Ziyan , Zheng Chenyue , Lin Haichuan , Tigabu Mulualem , Guo Futao 
Published: October 2023

AimsThe aim of this study was to analyze changes in emission of water-soluble ions in fine particulate matter over time and in different southwest forest areas in China based on China’s Forestry Statistical Yearbook and MODIS satellite fire point data.MethodsWe took 6 dominant tree species samples in the southwestern forest region of China and simulated combustion using controllable biomass combustion devices. Based on the spatial analysis method of ArcGIS, combining satellite fire point data and official statistical yearbooks, we analyzed the spatial and temporal dynamics of emissions of water-soluble ions in PM2.5 released by forest fires in southwestern forest areas from 2004 to 2021.ResultsThe total amount of forest biomass combusted in southwest forest areas was 64.43 kt. Among the different forest types, the proportion of burnt subtropical evergreen broad-leaved forest was the largest (60.49%) followed by subtropical mixed coniferous and broad-leaved forest (22.78%) and subtropical evergreen coniferous forest (16.72%). During the study period, 61.19 t of water-soluble ions were released in PM2.5 from forest fires, and the emissions of Li+, Na+, NH4+, K+, Mg2+, Ca2+, F−, Cl−, Br−, NO3−, PO43− and SO42− were 0.48 t, 11.54 t, 2.51 t, 19.44 t, 2.12 t, 2.92 t, 1.94 t, 12.70 t, 1.12 t, 1.18 t, 1.17 t and 4.07 t, respectively. Yunnan was the province with the highest emissions of water-soluble ions in PM2.5 in the southwest forest areas, and the concentration K+ was the highest. Emission of water-soluble ions in Yunnan and Sichuan all showed a significant downward trend, while the overall decrease in Tibet, Chongqing and Guizhou was not significant. The peak emission of water-soluble ions in PM2.5 during forest fires appeared in spring and winter, which accounted for 87.66% of the total emission.DiscussionThis study reveals the spatiotemporal changes in water-soluble ion emissions from forest fires, by studying the spatiotemporal dynamics of water-soluble ions in PM2.5, we can better understand the sources, distribution, and change patterns of these ions, as well as their impact on the atmospheric environment, ecosystems, and climate change. This information is crucial for predicting and managing air pollution, as well as developing effective forest management and environmental protection policies to respond to fires; and hence concerted fire prevention efforts should be made in each province, taking into account the season with higher probability of fire occurrence to reduce the potential impact of fire-related pollutions.
Sulindac sulfide as a non-immune suppressive γ-secretase modulator to target triple-negative breast cancer
Authors: Hossain Fokhrul , Ucar Deniz A. , Monticone Giulia , Ran Yong , Majumder Samarpan , Larter Kristina , Luu Hanh , Wyczechowska Dorota , Heidari Soroor , Xu Keli , Shanthalingam Sudarvili , Matossian Margarite , Xi Yaguang , Burow Matthew , Collins-Burow Bridgette , Del Valle Luis , Hicks Chindo , Zabaleta Jovanny , Golde Todd , Osborne Barbara , Miele Lucio 
Published: October 2023

IntroductionTriple-negative breast cancer (TNBC) comprises a heterogeneous group of clinically aggressive tumors with high risk of recurrence and metastasis. Current pharmacological treatment options remain largely limited to chemotherapy. Despite promising results, the efficacy of immunotherapy and chemo-immunotherapy in TNBC remains limited. There is strong evidence supporting the involvement of Notch signaling in TNBC progression. Expression of Notch1 and its ligand Jagged1 correlate with poor prognosis. Notch inhibitors, including g-secretase inhibitors (GSIs), are quite effective in preclinical models of TNBC. However, the success of GSIs in clinical trials has been limited by their intestinal toxicity and potential for adverse immunological effects, since Notch plays key roles in T-cell activation, including CD8 T-cells in tumors. Our overarching goal is to replace GSIs with agents that lack their systemic toxicity and ideally, do not affect tumor immunity. We identified sulindac sulfide (SS), the active metabolite of FDA-approved NSAID sulindac, as a potential candidate to replace GSIs.MethodsWe investigated the pharmacological and immunotherapeutic properties of SS in TNBC models in vitro, ex-vivo and in vivo.ResultsWe confirmed that SS, a known γ-secretase modulator (GSM), inhibits Notch1 cleavage in TNBC cells. SS significantly inhibited mammosphere growth in all human and murine TNBC models tested. In a transplantable mouse TNBC tumor model (C0321), SS had remarkable single-agent anti-tumor activity and eliminated Notch1 protein expression in tumors. Importantly, SS did not inhibit Notch cleavage in T- cells, and the anti-tumor effects of SS were significantly enhanced when combined with a-PD1 immunotherapy in our TNBC organoids and in vivo.DiscussionOur data support further investigation of SS for the treatment of TNBC, in conjunction with chemo- or -chemo-immunotherapy. Repurposing an FDA-approved, safe agent for the treatment of TNBC may be a cost-effective, rapidly deployable therapeutic option for a patient population in need of more effective therapies.
Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma
Authors: Qualiotto Aline Nery , Baldavira Camila Machado , Balancin Marcelo , Ab’Saber Alexandre , Takagaki Teresa , Capelozzi Vera Luiza 
Published: October 2023

BackgroundThe combination of immunobiological agents with immune checkpoint proteins is a promising treatment for malignant pleural mesothelioma (MPM). Mesothelin and anti-PD-L1 antibody-drug conjugates specifically target malignant neoplastic cells, inhibit the migration and invasion of neoplastic cells, and restore the immune landscape. In this study, we confirmed the importance of mesothelin and examined the relationship between mesothelin and the immune landscape of the tumor microenvironment (TME) in two MPM cohorts.MethodsThe discovery cohort included 82 MPM cases. Tissue microarray slides were generated, and samples were processed for hematoxylin &amp; eosin staining, immunohistochemistry, and immunofluorescence assays. The relationship between mesothelin, biomarkers of histogenesis, histological aggressiveness, PD-L1, immune cells (CD4, CD8, CD20, CD68), and collagen type I and type V fibers was evaluated by quantitative digital analyses. The outcome was the survival time until death from disease recurrence. The exploratory cohort included 87 malignant mesothelioma (MESO) patients from The Cancer Genome Atlas database.ResultsMost patients were male (70.7%) with a history of asbestos exposure (53.7%) and with the epithelioid subtype (89%). Surgical resection was performed in 85.4% of patients, and 14.6% received chemotherapy; 59.8% of patients died from disease extension to the mediastinum. Low tumor mesothelin expression was associated with tumor necrosis and nuclear grade 1, whereas high mesothelin expression was significantly associated with the epithelioid histotype and high density of T cells CD8+, macrophages CD68+, and collagen type I fibers. Cox multivariate analysis showed a high risk of death for non-operated patients [hazard ratio (HR), 3.42 (1.15–10.16)] with low tumor mesothelin levels [HR, 2.58 (1.09–6.10)] and high PD-L1 and low infiltration of T cells CD4+ [HR, 3.81 (1.58–9.18)]. In the exploratory cohort, low mesothelin and high COL1A1 and COL5A1 expression were associated with poor overall survival.ConclusionTumor mesothelin expression associated with the TME immune landscape predicts the risk of death for patients with MPM and could be a new target for immunotherapy in MPM.
The effect of multiple outgrowths from bronchial tissue explants on progenitor/stem cell number in primary bronchial epithelial cell cultures from smokers and patients with COPD
Authors: Bostancieri Nuray , Bakir Kemal , Kul Seval , Eralp Ayhan , Kayalar Ozgecan , Konyalilar Nur , Rajabi Hadi , Yuncu Mehmet , Yildirim Ali Önder , Bayram Hasan 
Published: October 2023

BackgroundAlthough studies suggest a deficiency in stem cell numbers in chronic airway diseases such as chronic obstructive pulmonary disease (COPD), the role of bronchial epithelial progenitor/stem (P/S) cells is not clear. The objectives of this study were to investigate expression of progenitor/stem (P/S) cell markers, cytokeratin (CK) 5, CK14 and p63 in bronchial epithelial explants and cell cultures obtained from smokers with and without COPD following multiple outgrowths, and to study this effect on bronchial epithelial cell (BEC) proliferation.MethodsBronchial epithelial explants were dissected from lung explants and cultured on coverslips. Confluent cultures were obtained after 3–4 weeks’ (transfer, Tr1), explants were then transferred and cultured for a second (Tr2) and third (Tr3) time, respectively. At each stage, expression of CK5, CK14 and p63 in explants and BEC were determined by immunostaining. In parallel experiments, outgrowing cells from explants were counted after 4wks, and explants subsequently transferred to obtain new cultures for a further 3 times.ResultsAs the transfer number advanced, CK5, CK14 and p63 expression was decreased in both explants and BEC from both smokers without COPD and patients with COPD, with a more pronounced decrease in BEC numbers in the COPD group. Total cell numbers cultured from explants were decreased with advancing outgrowth number in both groups. Smoking status and lung function parameters were correlated with reduced P/S marker expression and cell numbers.ConclusionOur findings suggest that the number of P/S cells in airway epithelium may play a role in the pathogenesis of COPD, as well as a role in the proliferation of airway epithelial cells, in vitro.
Interaction between intratumoral microbiota and tumor mediates the response of neoadjuvant therapy for rectal cancer
Authors: Sun Lejia , Qu Jiangming , Ke Xindi , Zhang Yue , Xu Hengyi , Lv Ning , Leng Jingze , Zhang Yanbin , Guan Ai , Feng Yifei , Sun Yueming 
Published: October 2023

BackgroundPrevious observations have demonstrated that the response to neoadjuvant chemoradiotherapy (nCRT) is highly variable in patients with locally advanced rectal cancer (LARC). Recent studies focusing on the intratumoral microbiota of colorectal cancer have revealed its role in oncogenesis and tumor progression. However, limited research has focused on the influence of intratumoral microbiota on the nCRT of LARC.MethodsWe explored the microbial profiles in the tumor microenvironment of LARC using RNA-seq data from a published European cohort. Microbial signatures were characterized in pathological complete response (pCR) and non-pCR groups. Multi-omics analysis was performed between intratumor microbiomes and transcriptomes.ResultsMicrobial α and β diversity were significantly different in pCR and non-pCR groups. Twelve differential microbes were discovered between the pCR and non-pCR groups, six of which were related to subclusters of cancer-associated fibroblasts (CAFs) associated with extracellular matrix formation. A microbial risk score based on the relative abundance of seven differential microbes had predictive value for the nCRT response (AUC = 0.820, p &lt; 0.001).ConclusionOur study presents intratumoral microbes as potential independent predictive markers for the response of nCRT to LARC and demonstrates the underlying mechanism by which the interaction between intratumoral microbes and CAFs mediates the response to nCRT.
Host genetic background rather than diet-induced gut microbiota shifts of sympatric black-necked crane, common crane and bar-headed goose
Authors: Wang Yeying , Long Zhengmin , Zhang Yu , Li Xianyu , Zhang Xu , Su Haijun 
Published: October 2023

IntroductionGut microbiota of wild birds are affected by many factors, and host genetic background and diet are considered to be two important factors affecting their structure and function.MethodsIn order to clarify how these two factors influence the gut microbiota, this study selected the sympatric and closely related and similar-sized Black-necked Crane (Grus nigricollis) and Common Crane (Grus grus), as well as the distantly related and significantly different-sized Bar-headed Goose (Anser indicus). The fecal samples identified using sanger sequencing as the above three bird species were subjected to high-throughput sequencing of rbcL gene and 16S rRNA gene to identify the feeding types phytophagous food and gut microbiota.ResultsThe results showed significant differences in food diversity between black-necked cranes and Common Cranes, but no significant differences in gut microbiota, Potatoes accounted for approximately 50% of their diets. Bar-headed Geese mainly feed on medicinal plants such as Angelica sinensis, Alternanthera philoxeroides, and Ranunculus repens. Black-necked cranes and Common Cranes, which have a high-starch diet, have a similar degree of enrichment in metabolism and synthesis functions, which is significantly different from Bar-headed Geese with a high-fiber diet. The differences in metabolic pathways among the three bird species are driven by food. The feeding of medicinal plants promotes the health of Bar-headed Geese, indicating that food influences the functional pathways of gut microbiota. Spearman analysis showed that there were few gut microbiota related to food, but almost all metabolic pathways were related to food.ConclusionThe host genetic background is the dominant factor determining the composition of the microbiota. Monitoring the changes in gut microbiota and feeding types of wild birds through bird feces is of great reference value for the conservation of other endangered species.
Unraveling the functional instability of bacterial consortia in crude oil degradation via integrated co-occurrence networks
Authors: Li Ping , Liang Xiaolong , Shi Rongjiu , Wang Yongfeng , Han Siqin , Zhang Ying 
Published: October 2023

IntroductionSoil ecosystems are threatened by crude oil contamination, requiring effective microbial remediation. However, our understanding of the key microbial taxa within the community, their interactions impacting crude oil degradation, and the stability of microbial functionality in oil degradation remain limited.MethodsTo better understand these key points, we enriched a crude oil-degrading bacterial consortium generation 1 (G1) from contaminated soil and conducted three successive transfer passages (G2, G3, and G4). Integrated Co-occurrence Networks method was used to analyze microbial species correlation with crude oil components across G1-G4.Results and discussionIn this study, G1 achieved a total petroleum hydrocarbon (TPH) degradation rate of 32.29% within 10 days. Through three successive transfer passages, G2-G4 consortia were established, resulting in a gradual decrease in TPH degradation to 23.14% at the same time. Specifically, saturated hydrocarbon degradation rates ranged from 18.32% to 14.17% among G1-G4, and only G1 exhibited significant aromatic hydrocarbon degradation (15.59%). Functional annotation based on PICRUSt2 and FAPROTAX showed that functional potential of hydrocarbons degradation diminished across generations. These results demonstrated the functional instability of the bacterial consortium in crude oil degradation. The relative abundance of the Dietzia genus showed the highest positive correlation with the degradation efficiency of TPH and saturated hydrocarbons (19.48, 18.38, p &lt; 0.05, respectively), Bacillus genus demonstrated the highest positive correlation (21.94, p &lt; 0.05) with the efficiency of aromatic hydrocarbon degradation. The key scores of Dietzia genus decreased in successive generations. A significant positive correlation (16.56, p &lt; 0.05) was observed between the Bacillus and Mycetocola genera exclusively in the G1 generation. The decline in crude oil degradation function during transfers was closely related to changes in the relative abundance of key genera such as Dietzia and Bacillus as well as their interactions with other genera including Mycetocola genus. Our study identified key bacterial genera involved in crude oil remediation microbiome construction, providing a theoretical basis for the next step in the construction of the oil pollution remediation microbiome.