bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced peroxisome proliferator-activated receptor-α and bile acid nuclear receptor NR1H4/FXR may affect the hepatic immune microenvironment of biliary atresia
Authors: Ma Yingxuan , Lu Li , Tan Kezhe , Li Zhi , Guo Ting , Wu Yibo , Wu Wei , Zheng Lulu , Fan Feilong , Mo Jiayu , Gong Zhenhua
Published: August 2022

Background

Biliary atresia (BA) is a childhood liver disease characterized by fibrous obstruction and obstruction of the extrahepatic biliary system and is one of the most common and serious biliary disorders in infants. Significant inflammation and fibrosis of the liver and biliary tract are the most prominent features, regardless of the initial damage to the BA. Abnormalities in innate or adaptive immunity have been found in human patients and mouse models of BA. We previously reported that children with BA had abnormal lipid metabolism, including free serum carnitine.

Objective

To study gene and protein expression levels of the hepatic peroxisome proliferator-activated receptor-α (PPARα) signaling pathway and farnesoid X receptor (FXR) in BA and BA fibrosis, and assess their clinical values.

Methods

Low expression of PPARα and NR1H4 (FXR) in BA were validated in the Gene Expression Omnibus database. Functional differences were determined by gene set enrichment analysis based on of PPARα and NR1H4 expression. BA patients from GSE46960 were divided into two clusters by using consensus clustering according to PPARα, NR1H4, and SMAD3 expression levels, and immunoinfiltration analysis was performed. Finally, 58 cases treated in our hospital were used for experimental verification. (IHC: 10 Biliary atresia, 10 choledochal cysts; PCR: 10 Biliary atresia, 14 choledochal cysts; WB: 10 Biliary atresia, 4 choledochal cysts).

Results

Bioinformatics analysis showed that the expression of PPARα, CYP7A1 and NR1H4 (FXR) in the biliary atresia group was significantly lower than in the control group. More BA-specific pathways, including TGFβ signaling pathway, P53 signaling pathway, PI3K-AKT-mTOR signaling pathway, etc., are enriched in BA patients with low PPARα and NR1H4 expression. In addition, low NR1H4 expression is abundant in inflammatory responses, IL6/STAT3 signaling pathways, early estrogen responses, IL2 STAT5 signaling pathways, and TGFβ signaling pathways. The TGFβ signaling pathway was significant in both groups. According to the expression of PPARα, NR1H4 and SMAD3, a key node in TGFβ pathway, BA patients were divided into two clusters using consensus clustering. In cluster 2, SMAD3 expression was high, and PPARα and NR1H4 expression were low. In contrast to cluster 1, immune cell infiltration was higher in cluster 2, which was confirmed by immunohistochemistry. The mRNA and protein levels of PPARα and NR1H4 in BA patients were lower than in the control group by immunohistochemistry, Western blot analysis and real-time PCR.

Conclusions

The downregulation of PPARα and NR1H4 (FXR) signaling pathway may be closely related to biliary atresia.
Taurine inhibits Streptococcus uberis-induced NADPH oxidase-dependent neutrophil extracellular traps via TAK1/MAPK signaling pathways
Authors: Li Ming , Gao Yabing , Wang Zhenglei , Wu Binfeng , Zhang Jinqiu , Xu Yuanyuan , Han Xiangan , Phouthapane Vanhnaseng , Miao Jinfeng
Published: August 2022

Neutrophil extracellular traps (NETs) are produced by neutrophil activation and usually have both anti-infective and pro-damage effects.Streptococcus uberis(S. uberis), one of the common causative organisms of mastitis, can lead to the production of NETs. Taurine, a free amino acid abundant in the organism, has been shown to have immunomodulatory effects. In this study, we investigated the molecular mechanisms ofS. uberis-induced NETs formation and the regulatory role of taurine. The results showed that NETs had a disruptive effect on mammary epithelial cells and barriers, but do not significantly inhibit the proliferation ofS. uberis.S. uberisinduced NADPH oxidase-dependent NETs. TLR2-mediated activation of the MAPK signaling pathway was involved in this process. Taurine could inhibit the activation of MAPK signaling pathway and NADPH oxidase by modulating the activity of TAK1, thereby inhibiting the production of ROS and NETs. The effects of taurine on NADPH oxidase and NETs inS. uberisinfection were also demonstratedin vivo. These results suggest that taurine can protect mammary epithelial cells and barriers from damage by reducingS. uberis-induced NETs. These data provide new insights and strategies for the prevention and control of mastitis.
CD4+CD8+ T follicular helper cells regulate humoral immunity in chronic inflammatory lesions
Authors: Murayama Kosuke , Ikegami Ippei , Kamekura Ryuta , Sakamoto Hiroshi , Yanagi Masahiro , Kamiya Shiori , Sato Taiki , Sato Akinori , Shigehara Katsunori , Yamamoto Motohisa , Takahashi Hiroki , Takano Ken-ichi , Ichimiya Shingo
Published: August 2022

T follicular helper (Tfh) cells drive humoral immunity by facilitating B cell responses at the initial and recall phases. Recent studies have indicated the possible involvement of Tfh cells in the process of chronic inflammation. However, the functional role of Tfh cells in persistent immune settings remains unclear. Here, we report that CD4+CD8+ (double-positive, DP; CD3+CD4+CD8+CXCR5hiPD-1hi) Tfh cells, a subset of germinal-center-type Tfh cells, were abundantly present in the fibroinflammatory lesions of patients with immunoglobulin G4-related disease (IgG4-RD). Transcriptome analyses showed that these DP-Tfh cells in the lesions of IgG4-RD preferentially expressed signature genes characteristic of cytotoxic CD8+ T cells, such as Eomes, CRTAM, GPR56, and granzymes, in addition to CD70. Scatter diagram analyses to examine the relationships between tissue-resident lymphocytes and various clinical parameters revealed that the levels of DP-Tfh cells were inversely correlated to the levels of serum IgG4 and local IgG4-expressing (IgG4+) memory B cells (CD19+CD27+IgD-) in patients with IgG4-RD. Cell culture experiments using autologous tonsillar lymphocytes further suggested that DP-Tfh cells possess a poor B-cell helper function and instead regulate memory B cells. Since CD4+ (single positive, SP; CD3+CD4+CD8-CXCR5hiPD-1hi) Tfh cells differentiated into DP-Tfh cells under stimulation with IL-2 and IL-7 as assessed by in vitro experiments, these data imply that SP-Tfh cells are a possible origin of DP-Tfh cells under persistent inflammation. These findings highlight the potential feedback loop mechanism of Tfh cells in immune tolerance under chronic inflammatory conditions. Further studies on DP-Tfh cells may facilitate control of unresolved humoral responses in IgG4-RD pathological inflammation.
Identify metabolism-related genes IDO1, ALDH2, NCOA2, SLC7A5, SLC3A2, LDHB, and HPRT1 as potential prognostic markers and correlate with immune infiltrates in head and neck squamous cell carcinoma
Authors: Li Ce , Chen Shuai , Jia Wenming , Li Wenming , Wei Dongmin , Cao Shengda , Qian Ye , Guan Rui , Liu Heng , Lei Dapeng
Published: August 2022

Hypopharyngeal squamous cell carcinoma (HSCC) is a kind of head and neck squamous cell carcinoma (HNSCC) with poor prognosis. Metabolic reprogramming may regulate the tumor microenvironment (TME) by adapting quickly to cellular stress and regulating immune response, but its role in HSCC has not been reported. We used the nCounter® Metabolic Pathways Panel to investigate metabolic reprogramming, cellular stress, and their relationship in HSCC tissues and adjacent normal tissues. Metabolism-related pathways nucleotide synthesis and glycolysis pathways were significantly upregulated, while amino acid synthesis and fatty acid oxidation pathways were significantly downregulated in HSCC tissues compared to adjacent normal tissues. There is a significant correlation between metabolism-related pathways and cellular stress pathways. Enrichment of immune cell and tumor infiltrating lymphocyte (TIL) analysis showed changes in immune responses between HSCC tissues and adjacent normal tissues. Overall survival analysis showed that upregulated genes CD276, LDHB, SLC3A2, EGFR, SLC7A5, and HPRT1 are potential unfavorable prognostic markers in HNSCC, while downregulated genes EEA1, IDO1, NCOA2, REST, CCL19, and ALDH2 are potential favorable prognostic markers in HNSCC. Moreover, metabolism-related genes IDO1, ALDH2, NCOA2, SLC7A5, SLC3A2, LDHB, and HPRT1 are correlated with immune infiltrates in HNSCC. These results suggest that metabolic reprogramming occurs and correlates with cellular stress and immune response in HSCC, which may help researchers understand mechanisms of metabolic reprogramming and develop effective immunotherapeutic strategies in HNSCC.
Influenza virus causes lung immunopathology through down-regulating PPARγ activity in macrophages
Authors: Zhang Hongbo , Alford Taylor , Liu Shuangquan , Zhou Dongming , Wang Jieru
Published: August 2022

Fatal influenza (flu) virus infection often activates excessive inflammatory signals, leading to multi-organ failure and death, also referred to as cytokine storm. PPARγ (Peroxisome proliferator-activated receptor gamma) agonists are well-known candidates for cytokine storm modulation. The present study identified that influenza infection reduced PPARγ expression and decreased PPARγ transcription activity in human alveolar macrophages (AMs) from different donors. Treatment with PPARγ agonist Troglitazone ameliorated virus-induced proinflammatory cytokine secretion but did not interfere with the IFN-induced antiviral pathway in human AMs. In contrast, PPARγ antagonist and knockdown of PPARγ in human AMs further enhanced virus-stimulated proinflammatory response. In a mouse model of influenza infection, flu virus dose-dependently reduced PPARγ transcriptional activity and decreased expression of PPARγ. Moreover, PPARγ agonist troglitazone significantly reduced high doses of influenza infection-induced lung pathology. In addition, flu infection reduced PPARγ expression in all mouse macrophages, including AMs, interstitial macrophages, and bone-marrow-derived macrophages but not in alveolar epithelial cells. Our results indicate that the influenza virus specifically targets the PPARγ pathway in macrophages to cause acute injury to the lung.
Suppression of FOXP3 expression by the AP-1 family transcription factor BATF3 requires partnering with IRF4
Authors: Arnold Preston R. , Wen Mou , Zhang Lei , Ying Yuanlin , Xiao Xiang , Chu Xiufeng , Wang Guangchuan , Zhang Xiaolong , Mao Zhuyun , Zhang Aijun , Hamilton Dale J. , Chen Wenhao , Li Xian C.
Published: August 2022

FOXP3 is the lineage-defining transcription factor for Tregs, a cell type critical to immune tolerance, but the mechanisms that control FOXP3 expression in Tregs remain incompletely defined, particularly as it relates to signals downstream of TCR and CD28 signaling. Herein, we studied the role of IRF4 and BATF3, two transcription factors upregulated upon T cell activation, to the conversion of conventional CD4+ T cells to FOXP3+ T cells (iTregs) in vitro. We found that IRF4 must partner with BATF3 to bind to a regulatory region in the Foxp3 locus where they cooperatively repress FOXP3 expression and iTreg induction. In addition, we found that interactions of these transcription factors are necessary for glycolytic reprogramming of activated T cells that is antagonistic to FOXP3 expression and stability. As a result, Irf4 KO iTregs show increased demethylation of the critical CNS2 region in the Foxp3 locus. Together, our findings provide important insights how BATF3 and IRF4 interactions integrate activating signals to control CD4+ cell fate decisions and govern Foxp3 expression.
An immunotherapy response prediction model derived from proliferative CD4+ T cells and antigen-presenting monocytes in ccRCC
Authors: Zheng Kun , Gao Lianchong , Hao Jie , Zou Xin , Hu Xiaoyong
Published: August 2022

Most patients with clear cell renal cell carcinoma (ccRCC) have an impaired response to immune checkpoint blockade (ICB) therapy. Few biomarkers can predict responsiveness, and there is insufficient evidence to extend them to ccRCC clinical use. To explore subtypes and signatures of immunocytes with good predictive performance for ICB outcomes in the ccRCC context, we reanalyzed two ccRCC single-cell RNA sequencing (scRNA-seq) datasets from patients receiving ICB treatment. A subtype of proliferative CD4+ T cells and regulatory T cells and a subtype of antigen-presenting monocytes that have good predictive capability and are correlated with ICB outcomes were identified. These findings were corroborated in independent ccRCC ICB pretreatment bulk RNA-seq datasets. By incorporating the cluster-specific marker genes of these three immunocyte subtypes, we developed a prediction model, which reached an AUC of 93% for the CheckMate cohort (172 samples). Our study shows that the ICB response prediction model can serve as a valuable clinical decision-making tool for guiding ICB treatment of ccRCC patients.
Preoperative prediction of glypican-3 positive expression in solitary hepatocellular carcinoma on gadoxetate-disodium enhanced magnetic resonance imaging
Authors: Chen Yidi , Qin Yun , Wu Yuanan , Wei Hong , Wei Yi , Zhang Zhen , Duan Ting , Jiang Hanyu , Song Bin
Published: August 2022

Purpose

As a coreceptor in Wnt and HGF signaling, glypican-3 (GPC-3) promotes the progression of tumor and is associated with a poor prognosis in hepatocellular carcinoma (HCC). GPC-3 has evolved as a target molecule in various immunotherapies, including chimeric antigen receptor T cell. However, its evaluation still relies on invasive histopathologic examination. Therefore, we aimed to develop an easy-to-use and noninvasive risk score integrating preoperative gadoxetic acid–enhanced magnetic resonance imaging (EOB-MRI) and clinical indicators to predict positive GPC-3 expression in HCC.

Methods and materials

Consecutive patients with surgically-confirmed solitary HCC who underwent preoperative EOB-MRI between January 2016 and November 2021 were retrospectively included. EOB-MRI features were independently evaluated by two masked abdominal radiologists and the expression of GPC-3 was determined by two liver pathologists. On the training dataset, a predictive scoring system for GPC-3 was developed against pathology via logistical regression analysis. Model performances were characterized by computing areas under the receiver operating characteristic curve (AUCs).

Results

A total of 278 patients (training set, n=156; internal validation set, n=39; external validation set, n=83) with solitary HCC (208 [75%] with positive GPC-3 expression) were included. Serum alpha-fetoprotein >10 ng/ml (AFP, odds ratio [OR]=2.3, four points) and five EOB-MR imaging features, including tumor size >3.0cm (OR=0.5, -3 points), nonperipheral “washout” (OR=3.0, five points), infiltrative appearance (OR=9.3, 10 points), marked diffusion restriction (OR=3.3, five points), and iron sparing in solid mass (OR=0.2, -7 points) were significantly associated with positive GPC-3 expression. The optimal threshold of scoring system for predicting GPC-3 positive expression was 5.5 points, with AUC 0.726 and 0.681 on the internal and external validation sets, respectively.

Conclusion

Based on serum AFP and five EOB-MRI features, we developed an easy-to-use and noninvasive risk score which could accurately predict positive GPC-3 HCC, which may help identify potential responders for GPC-3-targeted immunotherapy.
Assessing the reliability of species distribution models in the face of climate and ecosystem regime shifts: Small pelagic fishes in the California Current System
Authors: Asch Rebecca G. , Sobolewska Joanna , Chan Keo
Published: August 2022

Species distribution models (SDMs) are a commonly used tool, which when combined with earth system models (ESMs), can project changes in organismal occurrence, abundance, and phenology under climate change. An often untested assumption of SDMs is that relationships between organisms and the environment are stationary. To evaluate this assumption, we examined whether patterns of distribution among larvae of four small pelagic fishes (Pacific sardine Sardinops sagax, northern anchovy Engraulis mordax, jack mackerel Trachurus symmetricus, chub mackerel Scomber japonicus) in the California Current remained steady across time periods defined by climate regimes, changes in secondary productivity, and breakpoints in time series of spawning stock biomass (SSB). Generalized additive models (GAMs) were constructed separately for each period using temperature, salinity, dissolved oxygen (DO), and mesozooplankton volume as predictors of larval occurrence. We assessed non-stationarity based on changes in six metrics: 1) variables included in SDMs; 2) whether a variable exhibited a linear or non-linear form; 3) rank order of deviance explained by variables; 4) response curve shape; 5) degree of responsiveness of fishes to a variable; 6) range of environmental variables associated with maximum larval occurrence. Across all species and time periods, non-stationarity was ubiquitous, affecting at least one of the six indicators. Rank order of environmental variables, response curve shape, and oceanic conditions associated with peak larval occurrence were the indicators most subject to change. Non-stationarity was most common among regimes defined by changes in fish SSB. The relationships between larvae and DO were somewhat more likely to change across periods, whereas the relationships between fishes and temperature were more stable. Respectively, S. sagax, T. symmetricus, S. japonicus, and E. mordax exhibited non-stationarity across 89%, 67%, 50%, and 50% of indicators. For all species except E. mordax, inter-model variability had a larger impact on projected habitat suitability for larval fishes than differences between two climate change scenarios (SSP1-2.6 and SSP5-8.5), implying that subtle differences in model formulation could have amplified future effects. These results suggest that the widespread non-stationarity in how fishes utilize their environment could hamper our ability to reliably project how species will respond to climatic change.
Cost-effectiveness of using protons for breast irradiation aiming at minimizing cardiotoxicity: A risk-stratification analysis
Authors: Li Guo , Xia Yun-Fei , Huang Yi-Xiang , Okat Deniz , Qiu Bo , Doyen Jerome , Bondiau Pierre-Yves , Benezery Karen , Gao Jin , Qian Chao-Nan
Published: August 2022

Background

Incidental exposure of the heart to ionizing irradiation is associated with an increased risk of ischemic heart disease and subsequent fatality in patients with breast cancer after radiotherapy. Proton beam therapy can limit the heart dose in breast irradiation to a negligible level. However, compared with conventional photon modality, proton breast irradiation is more expensive. In this study, we performed cost-effectiveness analyses to identify the type of patients who would be more suitable for protons.

Methods

A Markov decision model was designed to evaluate the cost-effectiveness of protons vs. photons in reducing the risk of irradiation-related ischemic heart disease. A baseline evaluation was performed on a 50-year-old woman patient without the preexisting cardiac risk factor. Furthermore, risk-stratification analyses for photon mean heart dose and preexisting cardiac risk were conducted on 40-, 50-, and 60-year-old women patients under different proton cost and willingness-to-pay (WTP) settings.

Results

Using the baseline settings, the incremental effectiveness (protons vs. photons) increased from 0.043 quality-adjusted life-year (QALY) to 0.964 QALY when preexisting cardiac risk increased to 10 times its baseline level. At a proton cost of 50,000 US dollars ($), protons could be cost-effective for ≤ 60-year-old patients with diabetes and ≤50-year-old patients with grade II–III hypertension at the WTP of China ($37,653/QALY); for ≤ 60-year-old patients with diabetes and ≤ 50-year-old patients with grade II–III hypertension or ≥ 2 major cardiac risk factors at a WTP of $50,000/QALY; and for ≤ 60-year-old patients with diabetes, grade II–III hypertension or ≥ 2 major cardiac risk factors and ≤ 50-year-old patients with total cholesterol ≥ 240 mg/dL at a WTP of $100,000/QALY.

Conclusion

Patients' preexisting cardiac risk status was a key factor affecting the cardiac benefits gained from protons and should therefore be a major consideration for the clinical decision of using protons; cost-effective scenarios of protons exist in those patients with high risk of developing cardiac diseases.
The correlation between neutrophil-to-lymphocyte ratio, carcinoembryonic antigen, and carbohydrate antigen 153 levels with chemotherapy-related cognitive impairment in early-stage breast cancer patients
Authors: Yu Sheng , Zhao Jingjing , Wang Menglian , Cheng Guo , Li Wen , Tang Lingxue , Yao Senbang , Pang Lulian , Yin Xiangxiang , Jing Yanyan , Cheng Huaidong
Published: August 2022

Background

The changes in inflammation and tumor biomarkers are associated with the anti-tumor immunological processes. Early detection and intervention are of great significance to the clinical management of cancer-related diseases. Peripheral blood biomarkers [e.g., neutrophil-to-lymphocyte ratio (NLR), carcinoembryonic antigen (CEA), and carbohydrate antigen 153 (CA153)] are obtained in real-timely, conveniently, and less invasively, and proved to availably predicted the disease states and prognosis of various cancers, including breast cancer (BC). Inflammation and poor disease management promote cognitive impairment. Chemotherapy-related cognitive impairment (CRCI) hazard long-term survival and quality of life (QOL) of BC patients, but its correlation with NLR, CEA, and CA153 is not clear.

Purpose

This study aimed to investigate changes in NLR, CEA, and CA153 levels before and after chemotherapy and their correlation with CRCI in patients with early-stage BC.

Materials and methods

The 187 patients with BC who were measured for NLR, CEA, and CA153 values within the first 24 hours of admission, were assigned into two groups: the before/after chemotherapy group (BCG/ACG). The ACG was assigned into two subgroups based on the cognitive assessment results: the cognitive normal/impaired group (CNG/CIG). Patients’ self-perceived cognitive impairments were evaluated using a mini-mental state examination (MMSE), prospective and retrospective memory (PM and RM) questionnaire (PRMQ), and functional assessment of cancer therapy-cognitive function version 3 (FACT-Cog, version 3, including CogPCI, CogOth, CogPCA, and CogQOL). Their QOL was also evaluated.

Results

The NLR and CA153 levels were elevated after chemotherapy (BCG vs ACG: Z = −1.996 and −1.615, P = 0.046 and 0.106, respectively), and significantly elevated in patients with CRCI (BCG vs CIG: Z = −2.444 and -2.293, P = 0.015 and 0.022; respectively). However, there was not reach significant difference in CEA levels between the four groups. In addition, there was a weak to moderate correlation between peripheral blood biomarkers (NLR, CEA, and CA153) levels and CRCI (r = −0.404, −0.205, −0.322; respectively; P < 0.001). Cognitive impairment scores (MMSE, PM, RM, and FACT-Cog) had a strong correlation with QOL in patients with early-stage BC (r = −0.786, 0.851, 0.849, and 0.938; respectively; P < 0.001).

Conclusion

NLR and CA153 m be valuable diagnostic adjuncts of CRCI, and CRCI has a strong correlation with QOL in patients with early-stage BC.
LNG-IUS vs. medical treatments for women with heavy menstrual bleeding: A systematic review and meta-analysis
Authors: Chen Sijing , Liu Jianhong , Peng Shiyi , Zheng Ying
Published: August 2022

Introduction

To compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with medical treatments for women with heavy menstrual bleeding.

Materials and methods

We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), and Wanfang databases for relevant randomized controlled trials (RCTs) in November 2021. All meta-analyses were performed using the random-effects model. PROSPERO registration number: CRD42021295379.

Results

A total of trials (with 14 references) reporting on 1,677 women were included in this systematic review. The majority of the included RCTs were rated with low-to-unclear risk of bias in selection, detection, attrition, reporting, and other bias. All RCTs were rated as high risk in performance bias because blinding was difficult to ensure in the compared groups. Results of meta-analyses revealed that the number of clinical responders was greater in the LNG-IUS group than that in the medical treatments group at both 6-month (steroidal: five RCTs; n = 490; risk ratio [RR]: 1.72 [1.13, 2.62]; I2 = 92%; nonsteroidal: one RCT; n = 42; RR: 2.34 [1.31, 4.19]) and 12-month (steroidal: three RCTs; n = 261; RR: 1.31 [1.01, 1.71]; I2 = 74%) endpoints, with no clear differences on number of dropouts, and the incidence of adverse events.

Conclusion

Evidence indicates that LNG-IUS is superior to the medical treatments in short-term and medium-term clinical responses, blood loss control, compliance, and satisfaction. Meanwhile, frequency of adverse events related to LNG-IUS is acceptable.

Systematic review registration

PROSPERO, identifier CRD42021259335, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021295379.
Combined intensive management of fertilization, tillage, and organic material mulching regulate soil bacterial communities and functional capacities by altering soil potassium and pH in a Moso bamboo forest
Authors: Zheng Ying , Liu Xinzhu , Cai Yanjiang , Shao Qingsong , Zhu Wei , Lin Xinchun
Published: August 2022

Intensive management is a common practice in agricultural and forestry ecosystems to improve soil quality and crop yield by influencing nutrient supply and soil microbiota; however, the linkage between soil nutrients and bacterial community and functional capacities in intensively managed economic forests has not been well studied. In this study, we investigated the soil properties such as available potassium (AK), available nitrogen (AN), available phosphorus (AP), ammonium (NH4+), nitrate (NO3-), organic matter (OM), total nitrogen (TN), total phosphorus (TP), bacterial diversity and community composition, potential functions of rhizome roots, and soil microbiota across a chronosequence of intensively managed Moso bamboo (Phyllostachys edulis) forests. Our results demonstrated that the combined intensive management (deep tillage, fertilization, and organic material mulching) in this study caused a significant increase in the concentrations of AK, AN, AP, NH4+, NO3-, OM, TN, and TP (P < 0.05). However, they led to a remarkable decrease in pH (P < 0.05). Such changes lowered the Shannon diversity of the soil and rhizome root microbiota but did not significantly affect the community composition and functional capacity. Soil bacterial community variation was predominantly mediated by soil total potassium (TK) (15.02%), followed by pH (11.29%) and AK (11.13%). We further observed that Nitrospirae accounted for approximately 50% of the variation in soil pH, NO3-, NH4+, and AK, indicating its importance in soil nutrient cycling, especially nitrogen cycling. Accordingly, we propose that the management-induced changes in soil parameters reshaped the bacterial community structure and keystone bacterial assemblage, leading to the differentiation of microbial functions.
Neonatal microbiota-epithelial interactions that impact infection
Authors: Negi Shikha , Hashimoto-Hill Seika , Alenghat Theresa
Published: August 2022

Despite modern therapeutic developments and prophylactic use of antibiotics during birth or in the first few months of life, enteric infections continue to be a major cause of neonatal mortality and morbidity globally. The neonatal period is characterized by initial intestinal colonization with microbiota and concurrent immune system development. It is also a sensitive window during which perturbations to the environment or host can significantly impact colonization by commensal microbes. Extensive research has demonstrated that these early life alterations to the microbiota can lead to enhanced susceptibility to enteric infections and increased systemic dissemination in newborns. Various contributing factors continue to pose challenges in prevention and control of neonatal enteric infections. These include alterations in the gut microbiota composition, impaired immune response, and effects of maternal factors. In addition, there remains limited understanding for how commensal microbes impact host-pathogen interactions in newborns. In this review, we discuss the recent recognition of initial microbiota-epithelial interactions that occur in neonates and can regulate susceptibility to intestinal infection. These studies suggest the development of neonatal prophylactic or therapeutic regimens that include boosting epithelial defense through microbiota-directed interventions.
Analysis of the composition of culturable airborne microorganisms in the archaeological excavation protection site of the Nanhai No. 1 Ancient Shipwreck
Authors: Ma Kaixuan , Wang Yu , Yang Xinyu , Wang Cen , Han Yeqing , Huang Xinduo , Guo Peifeng , Du Jing , Chen Yue , Pan Jiao
Published: August 2022

After the recovery of the ship from the sea on 2007, the Nanhai No. 1 Ancient Shipwreck is currently exposed to the air. Air microorganisms settle on wooden shipwrecks, and they can use wood matrix to grow and multiply, causing biocorrosion and biodegradation. In this study, a systematical survey of the composition of culturable airborne microorganisms was performed at the conservation site of the Nanhai No. 1 Ancient Shipwreck. Airborne microorganisms were collected from seven sites in the preservation Nanhai No. 1 area over five periods. Molecular identification of the culturable microorganisms isolated from the air was done by sequencing both 16S rRNA (bacteria) and ITS (fungi) gene regions. The biodegradability of these strains was evaluated by degradation experiments with cellulose and lignin as substrate. The results showed that the composition of the isolated microbial communities was different in each period, and microbial spatial distribution was dissimilar in the same period. In the recent 2020, the dominant bacterial genus was Acinetobacter, and the dominant fungal genera were Penicillium, Aspergillus, and Cerrena. Acinetobacter spp. can degrade cellulose and lignin. Penicillium spp., Aspergillus spp., and Cerrena spp. degraded cellulose but only Cerrena spp. could utilize lignin. These dominant strains may have a harmful effect on the Nanhai No. 1 Ancient Shipwreck. This study provides data on the airborne microbial community found inside the protective chamber where Nanhai No. 1 Shipereck is placed, which can be used as a reference basis for the future conservation of the ship.
Effects of dietary palygorskite supplementation on the growth performance, oxidative status, immune function, intestinal barrier and cecal microbial community of broilers
Authors: Du Mingfang , Chen Yueping , Wang Shiqi , Zhao Haoran , Wen Chao , Zhou Yanmin
Published: August 2022

The present study aimed to investigate the effects of palygorskite (PAL) as an alternative to antibiotic on the growth performance, oxidative status, immune function, intestinal barrier and cecal microbial community of broilers. A total of 360 1-day-old male Ross-308 broilers were randomly allotted to three treatments with eight replicates. Broilers in the three groups were designated as follows: basal diet (CON group), basal diet+50 mg/kg chlorotetracycline (ANT group), and basal diet+ 10 g/kg PAL (PAL group). Supplementing PAL reduced feed to gain ratio in broilers during 22 to 42 days of age (P < 0.05), with its value being similar to that of the ANT group (P > 0.05). Broilers fed a PAL-supplemented diet exerted decreased contents of interferon-γ (IFN-γ) and interleukin-1β in serum, and the same reduction was found in jejunal IFN-γ level, when compared to the CON group (P < 0.05). Moreover, compared with the CON group, broilers after PAL treatment had a lower malondialdehyde content in jejunal mucosa (P < 0.05). Supplementing PAL elevated jejunal villus height (VH) and ratio of VH to crypt depth compared with the ANT group (P < 0.05). Cecal microbiota communities among the three groups were significant different, as demonstrated by distinct clusters from partial least squares discriminant analysis, although dietary treatments had no significant effects on the bacterial richness and diversity indices (P > 0.05). At genus level, the addition of PAL increased the relative abundance of norank_f__Barnesiellaceae and decreased that of unclassified_f__Oscillospiraceae in cecal digesta compared with those in the CON group (P < 0.05); the proportion of genus norank_f__Barnesiellaceae was increased by PAL treatment when compared with the ANT group (P < 0.05). Moreover, spearman's correlations showed that the modulation of cecal microflora composition by PAL supplementation was closely correlated with the promotion of growth performance (feed to gain ratio) and intestinal health-related (contents of malondialdehyde and IFN-γ, and VH value in jejunum) variables of broilers (P < 0.05). Taken together, dietary PAL could improve the growth performance, antioxidant capacity, and immune status, as well as intestinal barrier function in broilers, which might be partially associated with the alteration of cecal microbiota. Moreover, dietary PAL may be a promising alternative to antibiotic growth promoter for broilers.
Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model
Authors: Carneiro Tatiana J. , Pinto Joana , Serrao Eva M. , Barros António S. , Brindle Kevin M. , Gil Ana M.
Published: August 2022

Untargeted Nuclear Magnetic Resonance (NMR) metabolomics of polar extracts from the pancreata of a caerulin-induced mouse model of pancreatitis (Pt) and of a transgenic mouse model of pancreatic cancer (PCa) were used to find metabolic markers of Pt and to characterize the metabolic changes accompanying PCa progression. Using multivariate analysis a 10-metabolite metabolic signature specific to Pt tissue was found to distinguish the benign condition from both normal tissue and precancerous tissue (low grade pancreatic intraepithelial neoplasia, PanIN, lesions). The mice pancreata showed significant changes in the progression from normal tissue, through low-grade and high-grade PanIN lesions to pancreatic ductal adenocarcinoma (PDA). These included increased lactate production, amino acid changes consistent with enhanced anaplerosis, decreased concentrations of intermediates in membrane biosynthesis (phosphocholine and phosphoethanolamine) and decreased glycosylated uridine phosphates, reflecting activation of the hexosamine biosynthesis pathway and protein glycosylation.
Individual differences in slow wave sleep architecture relate to variation in white matter microstructure across adulthood
Authors: Gudberg Christel , Stevelink Remi , Douaud Gwenaëlle , Wulff Katharina , Lazari Alberto , Fleming Melanie K. , Johansen-Berg Heidi
Published: August 2022

Sleep plays a key role in supporting brain function and resilience to brain decline. It is well known that sleep changes substantially with aging and that aging is associated with deterioration of brain structure. In this study, we sought to characterize the relationship between slow wave slope (SWslope)—a key marker of sleep architecture and an indirect proxy of sleep quality—and microstructure of white matter pathways in healthy adults with no sleep complaints. Participants were 12 young (24–27 years) and 12 older (50–79 years) adults. Sleep was assessed with nocturnal electroencephalography (EEG) and the Pittsburgh Sleep Quality Index (PSQI). White matter integrity was assessed using tract-based spatial statistics (TBSS) on tensor-based metrics such as Fractional Anisotropy (FA) and Mean Diffusivity (MD). Global PSQI score did not differ between younger (n = 11) and older (n = 11) adults (U = 50, p = 0.505), but EEG revealed that younger adults had a steeper SWslope at both frontal electrode sites (F3: U = 2, p < 0.001, F4: U = 4, p < 0.001, n = 12 younger, 10 older). There were widespread correlations between various diffusion tensor-based metrics of white matter integrity and sleep SWslope, over and above effects of age (n = 11 younger, 9 older). This was particularly evident for the corpus callosum, corona radiata, superior longitudinal fasciculus, internal and external capsule. This indicates that reduced sleep slow waves may be associated with widespread white matter deterioration. Future studies should investigate whether interventions targeted at improving sleep architecture also impact on decline in white matter microstructure in older adults.
Relationships Among Temporal Fine Structure Sensitivity, Transient Storage Capacity, and Ultra-High Frequency Hearing Thresholds in Tinnitus Patients and Normal Adults of Different Ages
Authors: Ding Yu , Liang Yibo , Cao Chunmei , Zhang Yueqi , Hu Ming
Published: August 2022

Background

Elderlies and tinnitus patients often find it challenging to process acoustic signals in noisy environments. The sensitivity to temporal fine structure (TFS), the transient storage capacity for TFS, and the ultra-high frequency (UHF) thresholds are all associated with aging-related damage, evidenced by speech-in-noise perception deficits. In the present study, we aimed to investigate the relationships among TFS sensitivity, transient storage capacity, and UHF thresholds in tinnitus patients and normal adults of different ages.

Methods

In the present study, 38 tinnitus patients (age ranging from 21 to 65) and 23 non-tinnitus adults (age ranging from 22 to 56) were enrolled, and some of their auditory indicators were examined, including the TFS-adaptive frequency (TFS-AF), break in interaural correlation (BIAC) delay threshold, and UHF thresholds.

Results

We found no significant difference in TFS-AF thresholds and BIAC delay thresholds between the tinnitus group and normal group, while their relationships with age were more evident in the tinnitus group. Moreover, these two tests were only significantly correlated in the tinnitus group. UHF thresholds were significantly correlated with TFS-AF thresholds only in the tinnitus group, suggesting that the UHF hearing was positively associated with the TFS sensitivity.

Conclusion

These findings indicated that the influencing factors, such as tinnitus and UHF thresholds, should be fully considered when examining age-related hearing decline, because the combination of tinnitus and poor UHF hearing might play a role in affecting hearing ability, such as TFS sensitivity.
Epigenetic clock indicates accelerated aging in glial cells of progressive multiple sclerosis patients
Authors: Kular Lara , Klose Dennis , Urdánoz-Casado Amaya , Ewing Ewoud , Planell Nuria , Gomez-Cabrero David , Needhamsen Maria , Jagodic Maja
Published: August 2022

Background

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by irreversible disability at later progressive stages. A growing body of evidence suggests that disease progression depends on age and inflammation within the CNS. We aimed to investigate epigenetic aging in bulk brain tissue and sorted nuclei from MS patients using DNA methylation-based epigenetic clocks.

Methods

We applied Horvath’s multi-tissue and Shireby’s brain-specific Cortical clock on bulk brain tissue (n = 46), sorted neuronal (n = 54), and glial nuclei (n = 66) from post-mortem brain tissue of progressive MS patients and controls.

Results

We found a significant increase in age acceleration residuals, corresponding to 3.6 years, in glial cells of MS patients compared to controls (P = 0.0024) using the Cortical clock, which held after adjustment for covariates (Padj = 0.0263). The 4.8-year age acceleration found in MS neurons (P = 0.0054) did not withstand adjustment for covariates and no significant difference in age acceleration residuals was observed in bulk brain tissue between MS patients and controls.

Conclusion

While the findings warrant replication in larger cohorts, our study suggests that glial cells of progressive MS patients exhibit accelerated biological aging.
An examination of the relationship among plasma brain derived neurotropic factor, peripheral vascular function, and body composition with cognition in midlife African Americans/Black individuals
Authors: Traylor Miranda K. , Bauman Allison J. , Saiyasit Napatsorn , Frizell Carl A. , Hill Benjamin D. , Nelson Amy R. , Keller Joshua L.
Published: August 2022

African American/Black individuals have been excluded from several lines of prominent neuroscience research, despite exhibiting disproportionately higher risk factors associated with the onset and magnitude of neurodegeneration. Therefore, the objective of the current investigation was to examine potential relationships among brain derived neurotropic factor (BDNF), peripheral vascular function, and body composition with cognition in a sample of midlife, African American/Black individuals. Midlife adults (men: n = 3, 60 ± 4 years; women: n = 9, 58 ± 5 years) were invited to complete two baseline visits separated by 4 weeks. Peripheral vascular function was determined by venous occlusion plethysmography, a dual-energy X-ray absorptiometry was used to determine body composition, and plasma was collected to quantify BDNF levels. The CNS Vital Signs computer-based test was used to provide scores on numerous cognitive domains. The principal results included that complex attention (r = 0.629) and processing speed (r = 0.734) were significantly (p < 0.05) related to the plasma BDNF values. However, there was no significant (p > 0.05) relationship between any vascular measure and any cognitive domain or BDNF value. Secondary findings included the relationship between lean mass and peak hyperemia (r = 0.758) as well as total hyperemia (r = 0.855). The major conclusion derived from these results was that there is rationale for future clinical trials to use interventions targeting increasing BDNF to potentially improve cognition. Additionally, these results strongly suggest that clinicians aiming to improve cognitive health via improvements in the known risk factor of vascular function should consider interventions capable of promoting the size and function of skeletal muscle, especially in the African American/Black population.
The impact of age and electrode position on amplitude-integrated EEGs in children from 1 month to 17 years of age
Authors: Greve Sandra , Löffelhardt Verena Tamara , Della Marina Adela , Felderhoff-Müser Ursula , Dohna-Schwake Christian , Bruns Nora
Published: August 2022

Aim

Amplitude-integrated electroencephalography (aEEG) is used to monitor electrocortical activity in critically ill children but age-specific reference values are lacking. We aimed to assess the impact of age and electrode position on aEEG amplitudes and derive normal values for pediatric aEEGs from neurologically healthy children.

Methods

Normal EEGs from awake children aged 1 month to 17 years (213 female, 237 male) without neurological disease or neuroactive medication were retrospectively converted into aEEGs. Two observers manually measured the upper and lower amplitude borders of the C3 – P3, C4 – P4, C3 – C4, P3 – P4, and Fp1 – Fp2 channels of the 10–20 system. Percentiles (10th, 25th, 50th, 75th, 90th) were calculated for each age group (<1 year, 1 year, 2–5 years, 6–9 years, 10–13 years, 14–17 years).

Results

Amplitude heights and curves differed between channels without sex-specific differences. During the first 2 years of life, upper and lower amplitudes of all but the Fp1–Fp2 channel increased and then declined until 17 years. The decline of the upper Fp1–Fp2 amplitude began at 4 years, while the lower amplitude declined from the 1st year of life.

Conclusions

aEEG interpretation must account for age and electrode positions but not for sex in infants and children.
Food cue reactivity in successful laparoscopic gastric banding: A sham-deflation-controlled pilot study
Authors: Koenis Marinka M. G. , Ng Janet , Anderson Beth , Stevens Michael C. , Tishler Darren S. , Papasavas Pavlos K. , Stone Andrea , McLaughlin Tara , Verhaak Allison , Domakonda Mirjana J. , Pearlson Godfrey D.
Published: August 2022

Laparoscopic adjustable gastric banding (LAGB) offers a unique opportunity to examine the underlying neuronal mechanisms of surgically assisted weight loss due to its instant, non-invasive, adjustable nature. Six participants with stable excess weight loss (%EWL ≥ 45) completed 2 days of fMRI scanning 1.5–5 years after LAGB surgery. In a within-subject randomized sham-controlled design, participants underwent (sham) removal of ∼ 50% of the band’s fluid. Compared to sham-deflation (i.e., normal band constriction) of the band, in the deflation condition (i.e., decreasing restriction) participants showed significantly lower activation in the anterior (para)cingulate, angular gyrus, lateral occipital cortex, and frontal cortex in response to food images (p < 0.05, whole brain TFCE-based FWE corrected). Higher activation in the deflation condition was seen in the fusiform gyrus, inferior temporal gyrus, lingual gyrus, lateral occipital cortex. The findings of this within-subject randomized controlled pilot study suggest that constriction of the stomach through LAGB may indirectly alter brain activation in response to food cues. These neuronal changes may underlie changes in food craving and food preference that support sustained post-surgical weight-loss. Despite the small sample size, this is in agreement with and adds to the growing literature of post-bariatric surgery changes in behavior and control regions.
EEG brain signals to detect the sleep health of a driver: An automated framework system based on deep learning
Authors: Ettahiri Halima , Ferrández Vicente José Manuel , Fechtali Taoufiq
Published: August 2022

Mental fatigue is complex disorganization that affects the human being's efficiency in work and daily activities (e.g., driving, exercising). Encephalography is routinely used to discern this fatigue. Several automatic procedures have deployed conventional approaches to support neurologists in mental fatigue detection episodes (e.g., sleepy vs. normal). In all of the traditional procedures (e.g., support vector machine, discrimination fisher, K-nearest neighbor, and Bayesian classification), only a low accuracy is achieved when a binary classification task (e.g., tired vs. normal) is applied. The convolutional neural network model identifies the correct mathematical manipulation to turn the input into the output. In this study, a convolutional neural network is trained to recognize brain signals recorded by a wearable encephalographic cap. Unfortunately, the convolutional neural network works with large datasets. To overcome this problem, an augmentation scheme for a convolutional neural network model is essential because it can achieve higher accuracy than the traditional classifiers. The results show that our model achieved 97.3% compared to the state-of-the-art traditional methods (e.g., SVM and LDA).