bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening, identification, and degradation characteristics of 3-methylindole degrading bacteria
Authors: Hu Hong , Li Lei , Gao Feng , Diao Wentao , Ma Huan , Feng Fei , Quan Shujing , Xiang Lingyun , Zhang Xiujiang
Published: November 2022

3-Methylindole is a major component of organic pollutants in livestock compost, which can contribute to the deterioration of the environment in livestock farms and their surrounding areas. This study demonstrates that using microorganisms to degrade 3-methylindole is an effective method for energy conservation and environmental protection. The microbe capable of efficiently degrading 3-methylindole was isolated and screened from fecal samples. The isolated bacteria were identified as Acinetobacter oleivorans after morphological characterization and 16S rRNA sequencing. This project demonstrated that 3-methylindole was completely degraded under optimal conditions (initial concentration of 3MI: 100 mg/L, 30°C, pH8.0, and shaking at 160 rpm for 48 h). N2-Acetyl-L-ornithine, Phenylacetaldehyde, Phenylacetic acid, Indole-3-carboxylic acid, and Indole-3-carboxaldehyde were the primary metabolites of this degradation process. This study provides a theoretical foundation for other microbe-mediated environmental remediation approaches as well as a basis for future work to apply bacteria that degrade 3-methylindole for the purification of polluted environments. It has a promising application in the control of malodorous gas pollution in the large-scale livestock and poultry breeding industries.
Comparisons of climate change characteristics in typical arid regions of the Northern Hemisphere
Authors: Yan Xinyang , Cheng Peng , Zhang Qiang , Li Xiaoqin , He Jinmei , Yan Xiaomin , Zhao Wenjing , Wang Lei
Published: November 2022

In recent years, with the frequent occurrence of severe drought events, climate change in arid regions has become one of the research hotspots. However, previous studies mainly focused on a specific arid region, and the correlations and differences of drought among various arid regions have not been clearly understood. In this study, based on the latest monthly gridded dataset of the CRU, we compare the characteristics of climate change and its relationship with large-scale oceanic oscillation indexes in the three typical arid regions of Pan-Central-Asia (PCA), North America (NAm) and North Africa (NAf) in multiple perspectives. The results show that the precipitation in the PCA and NAm has increased obviously over the past 80 years, while the NAf precipitation has decreased. After the 1980s, the climate in the PCA and NAm show warm-wet types. This type of the former continues to the present, but the latter’s has changed to a warm-dry type since the 21st century. The NAf climate remains the warm-dry type since the 1990s. Nonetheless, the arid and semi-arid climate patterns in the three typical arid regions remain unchanged. The NAm precipitation has an anti-phase variability pattern compared with the NAf precipitation on both interdecadal and multi-decadal time scales. The Pacific Decadal Oscillation (PDO) has a great influence on the precipitation of the PCA and NAm. The temperature of three arid regions is significantly related to the variations in the Arctic oscillation (AO). In the inland arid region, the contribution of strong warming effect during cold season to the whole year is much greater than that during warm season, while the contribution of the coastal arid regions in warm season is greater. The precipitation in the mid-latitude arid regions is dominated by cold-season precipitation regardless of whether these regions are near the sea or not. The precipitation in the low-latitude arid regions has little difference between cold and warm seasons.
Environmental drivers of the vital urban coastal zones: An explorative case study based on the data-driven multi-method approach
Authors: Yin Yuting , Shao Yuhan , Lu Huilin , Han Yun
Published: November 2022

Success in delivering dynamic urban coastal zones is considered essential, as it brings enormous opportunities to the social, economic, ecological, and cultural development of the cities in addition to benefitting the coastal zones. However, the environmental drivers contributing to urban coastal zone vitality remain uncertain due to unclarified spatial boundaries and the influences of diverse characteristics from surrounding contexts. This study aims at exploring environmental drivers that can vitalize urban coastal zones and can inform an effective way to instruct design procedures. It sets out from clarifying the spatial boundaries of urban coastal zones and emphasizing the mutual connections among its spatial components. A data-driven multi-method approach is used to analyze spatial forms, traffic organizations, land uses, landscape characteristics, and coastal functions of the eight typical coastal cases selected in different countries. Results suggested that six typical coastal zone types can be classified based on landscape characteristics and coastal functions, while the other vitality-related aspects, spatial forms, traffic organizations, and land uses are analyzed to imply design requirements for each type. It is found that requirements on vitality-related aspects of the six types evidently vary with the coastal functions, but there are similarities among the types with similar landscape characteristics.
Influence of single-cell RNA sequencing data integration on the performance of differential gene expression analysis
Authors: Kujawa Tomasz , Marczyk Michał , Polanska Joanna
Published: November 2022

Large-scale comprehensive single-cell experiments are often resource-intensive and require the involvement of many laboratories and/or taking measurements at various times. This inevitably leads to batch effects, and systematic variations in the data that might occur due to different technology platforms, reagent lots, or handling personnel. Such technical differences confound biological variations of interest and need to be corrected during the data integration process. Data integration is a challenging task due to the overlapping of biological and technical factors, which makes it difficult to distinguish their individual contribution to the overall observed effect. Moreover, the choice of integration method may impact the downstream analyses, including searching for differentially expressed genes. From the existing data integration methods, we selected only those that return the full expression matrix. We evaluated six methods in terms of their influence on the performance of differential gene expression analysis in two single-cell datasets with the same biological study design that differ only in the way the measurement was done: one dataset manifests strong batch effects due to the measurements of each sample at a different time. Integrated data were visualized using the UMAP method. The evaluation was done both on individual gene level using parametric and non-parametric approaches for finding differentially expressed genes and on gene set level using gene set enrichment analysis. As an evaluation metric, we used two correlation coefficients, Pearson and Spearman, of the obtained test statistics between reference, test, and corrected studies. Visual comparison of UMAP plots highlighted ComBat-seq, limma, and MNN, which reduced batch effects and preserved differences between biological conditions. Most of the tested methods changed the data distribution after integration, which negatively impacts the use of parametric methods for the analysis. Two algorithms, MNN and Scanorama, gave very poor results in terms of differential analysis on gene and gene set levels. Finally, we highlight ComBat-seq as it led to the highest correlation of test statistics between reference and corrected dataset among others. Moreover, it does not distort the original distribution of gene expression data, so it can be used in all types of downstream analyses.
Case report: Five-year periodontal management of a patient with two novel mutation sites in ELANE-induced cyclic neutropenia
Authors: Lao Zhentao , Fu Jiarun , Wu Zhiying , Zhu Lihong , Wu Shiwen , Lin Yongheng , Hu Chaoming , Duan Dingyu , Wang Panpan
Published: November 2022

Cyclic neutropenia (CyN) is a rare, ELANE-related neutropenia. Oral manifestations are among the initial signs of CyN and an important reason that leads patients to seek professional help. This case report describes a 12-year-old girl with recurrent oral ulcers, severe chronic periodontitis, and pathological tooth migration as the initial and main clinical symptoms of CyN. Two novel mutations in ELANE, c.180T>G (p.I60M) and c.182C>G (p.A61G) associated with CyN were observed. Bioinformatics research indicated lower stability and impaired molecular linkages of the mutant neutrophil elastase (NE) encoded by ELANE. However, the enzyme affinity to the classic substrate Suc–Ala–Ala–Ala–pNA was not substantially changed, suggesting that the impaired integrity and stability of the mutant NE, rather than catalytic deficiency, might be the pathogenic mechanism of ELANE mutation-induced neutropenia. The patient was prescribed scaling and root planing (SRP) and monthly periodontal maintenance without systemic management. Although the routine periodontal treatment was occasionally interrupted by the 2019 coronavirus pandemic, her periodontal devastation remained well-remitted in the 5-year follow-up assessment. The results of this study confirmed the importance of plaque control and proper diagnosis in the periodontal management of such patients and provide better clinical references. In addition, the novel mutations identified in this study expand the spectrum of known ELANE mutations in CyN and further contribute to knowledge regarding its pathogenic mechanism.
Establishment and analysis of a disease risk prediction model for the systemic lupus erythematosus with random forest
Authors: Chen Huajian , Huang Li , Jiang Xinyue , Wang Yue , Bian Yan , Ma Shumei , Liu Xiaodong
Published: November 2022

Systemic lupus erythematosus (SLE) is a latent, insidious autoimmune disease, and with the development of gene sequencing in recent years, our study aims to develop a gene-based predictive model to explore the identification of SLE at the genetic level. First, gene expression datasets of SLE whole blood samples were collected from the Gene Expression Omnibus (GEO) database. After the datasets were merged, they were divided into training and validation datasets in the ratio of 7:3, where the SLE samples and healthy samples of the training dataset were 334 and 71, respectively, and the SLE samples and healthy samples of the validation dataset were 143 and 30, respectively. The training dataset was used to build the disease risk prediction model, and the validation dataset was used to verify the model identification ability. We first analyzed differentially expressed genes (DEGs) and then used Lasso and random forest (RF) to screen out six key genes (OAS3, USP18, RTP4, SPATS2L, IFI27 and OAS1), which are essential to distinguish SLE from healthy samples. With six key genes incorporated and five iterations of 10-fold cross-validation performed into the RF model, we finally determined the RF model with optimal mtry. The mean values of area under the curve (AUC) and accuracy of the models were over 0.95. The validation dataset was then used to evaluate the AUC performance and our model had an AUC of 0.948. An external validation dataset (GSE99967) with an AUC of 0.810, an accuracy of 0.836, and a sensitivity of 0.921 was used to assess the model’s performance. The external validation dataset (GSE185047) of all SLE patients yielded an SLE sensitivity of up to 0.954. The final high-throughput RF model had a mean value of AUC over 0.9, again showing good results. In conclusion, we identified key genetic biomarkers and successfully developed a novel disease risk prediction model for SLE that can be used as a new SLE disease risk prediction aid and contribute to the identification of SLE.
The duration and breadth of antibody responses to 3-dose of inactivated COVID-19 vaccinations in healthy blood donors: An observational study
Authors: Ou Shanhai , Huang Zehong , Lan Miaoling , Ye Jianghui , Chen Jijin , Guo Huilin , Xiao Jin , Zhuang Shucheng , Wu Jiahuang , Yang Chuanlai , Fang Mujin , Su Yingying , Wu Ting , Ge Shengxiang , Cheng Tong , Zhang Yongchang , Lin Yongcai , Zhang Yali , Chen Guowei , Yuan Quan
Published: November 2022

Objectives

We aimed to evaluate the duration and breadth of antibodies elicited by inactivated COVID-19 vaccinations in healthy blood donors.

Methods

We performed serological tests on 1,417 samples from 658 blood donors who received two (n=357), or three (n=301) doses of COVID-19 inactivated vaccine. We also accessed the change in antibody response before and after booster vaccination in 94 participants and their neutralization breadth to the current variants after the booster.

Results

Following vaccination, for either the 2- or 3-dose, the neutralizing antibodies (nAbs) peaked with about 97% seropositivity approximately within one month but subsequently decreased over time. Of plasmas collected 6-8 months after the last immunization, the nAb seropositivities were 37% and 85% in populations with 2-dose and 3-dose vaccinations, respectively. The nAbs of plasma samples (collected between 2-6 weeks after the 3rd dose) from triple-vaccinated donors (n=94) showed a geometric mean titer of 145.3 (95% CI: 117.2 to 180.1) against the ancestral B.1, slightly reduced by 1.7-fold against Delta variant, but markedly decreased by 4-6 fold in neutralizing Omicron variants, including the sub-lineages of BA.1 (5.6-fold), BA.1.1 (6.0-fold), BA.2 (4.2-fold), B.2.12.1 (6.2-fold) and BA.4/5 (6.5-fold).

Conclusion

These findings suggested that the 3rd dose of inactivated COVID-19 vaccine prolongs the antibody duration in healthy populations, but the elicited-nAbs are less efficient in neutralizing circulating Omicron variants.
IL-1β promotes IL-9-producing Th cell differentiation in IL-2-limiting conditions through the inhibition of BCL6
Authors: Canaria D. Alejandro , Clare Maia G. , Yan Bingyu , Campbell Charlotte B. , Ismaio Zachariah A. , Anderson Nicole L. , Park Sungtae , Dent Alexander L. , Kazemian Majid , Olson Matthew R.
Published: November 2022

IL-9-producing CD4+ T helper cells, termed Th9 cells, differentiate from naïve precursor cells in response to a combination of cytokine and cell surface receptor signals that are elevated in inflamed tissues. After differentiation, Th9 cells accumulate in these tissues where they exacerbate allergic and intestinal disease or enhance anti-parasite and anti-tumor immunity. Previous work indicates that the differentiation of Th9 cells requires the inflammatory cytokines IL-4 and TGF-β and is also dependent of the T cell growth factor IL-2. While the roles of IL-4 and TGF-β-mediated signaling are relatively well understood, how IL-2 signaling contributes to Th9 cell differentiation outside of directly inducing the Il9 locus remains less clear. We show here that murine Th9 cells that differentiate in IL-2-limiting conditions exhibit reduced IL-9 production, diminished NF-kB activation and a reduced NF-kB-associated transcriptional signature, suggesting that IL-2 signaling is required for optimal NF-kB activation in Th9 cells. Interestingly, both IL-9 production and the NF-kB transcriptional signature could be rescued by addition of the NF-kB-activating cytokine IL-1β to IL-2-limiting cultures. IL-1β was unique among NF-kB-activating factors in its ability to rescue Th9 differentiation as IL-2 deprived Th9 cells selectively induced IL-1R expression and IL-1β/IL-1R1 signaling enhanced the sensitivity of Th9 cells to limiting amounts of IL-2 by suppressing expression of the Th9 inhibitory factor BCL6. These data shed new light on the intertwined nature of IL-2 and NF-kB signaling pathways in differentiating Th cells and elucidate the potential mechanisms that promote Th9 inflammatory function in IL-2-limiting conditions.
The neonatal Fc receptor expression during macrophage differentiation is related to autophagy
Authors: Lamamy Juliette , Larue Anthony , Mariot Julie , Dhommée Christine , Demattei Marie-Véronique , Delneste Yves , Gouilleux-Gruart Valérie
Published: November 2022

The neonatal Fc receptor (FcRn) plays a central role in recycling and biodistributing immunoglobulin G. FcRn is also involved in many physiological immune functions as well as pathological immune responses in cancer or autoimmune diseases. Low levels of FcRn in tumor cells and the microenvironment is associated with poor prognosis in non-small cell lung cancers. Among cells that are present in the tumor microenvironment, macrophages express high levels of FcRn. Macrophages are involved in these pathophysiological contexts by their dual differentiation states of pro- or anti-inflammatory macrophages. However, variations in FcRn protein expression have not been described in macrophage subtypes. In this work, we studied FcRn expression in an in vitro model of pro- and anti-inflammatory macrophage differentiation. We demonstrated an inverse relation between FcRn protein and mRNA expression in macrophage populations. Autophagy, which is involved in protein degradation and acquisition of phagocytic function in macrophages, participated in regulating FcRn levels. Intravenous immunoglobulin protected FcRn against autophagosome degradation in anti-inflammatory macrophages. Our data demonstrate that autophagy participates in regulating FcRn expression in pro- and anti-inflammatory macrophages. This finding raises new questions concerning the regulation of FcRn in immune functions.
Single-cell atlas of murine adrenal glands reveals immune-adrenal crosstalk during systemic Candida albicans infection
Authors: Zhang Kai , Hu Yuzhe , Li Ruoyu , Li Ting
Published: November 2022

Fungal sepsis remains a major health threat with high mortality, where the adrenal gland stress response has been rarely reported. Candida albicans (C.albicans) is the most common opportunistic fungal pathogen of life-threatening disseminated candidiasis and fungal sepsis. In the present study, we performed single-cell RNA sequencing (scRNA-Seq) using the 10x Genomics platform to analyze the changes in murine adrenal transcriptome following systemic C.albicans infection. A total of 16 021 cells were categorized into 18 transcriptionally distinct clusters, representing adrenocortical cells, endothelial cells, various immune cells, mesenchymal cells, smooth muscle cells, adrenal capsule, chromaffin cells, neurons and glials. As the main cell component in the adrenal gland responsible for steroidogenesis, the adrenocortical cells dramatically diminished and were further grouped into 10 subclusters, which differently distributed in the infected and uninfected samples. Pseudo-time analysis revealed transitions of the adrenocortical cells from the initial normal states to active or dysfunctional states following systemic C.albicans infection via two trajectory paths. Endothelial cells in the highly vascularized organ of adrenal gland further proliferated following infection, with the upregulation of genes positively regulating angiogenesis and downregulation of protective genes of endothelial cells. Immune cells were also excessively infiltrated in adrenal glands of C.albicans-infected mice. Macrophages dominated the immune microenvironments in murine adrenal glands both before and after C.albicans infection, mediating the crosstalk among the steroid-producing cells, endothelial cells and immune cells within the adrenal gland. NLR family, pyrin domain containing 3 (NLRP3, encoded by Nlrp3) and complement receptor 3 (CR3, encoded by Itgam) were found to be significantly upregulated on the adrenal macrophages upon systemic C.albicans infection and might play critical roles in mediating the myeloid response. Meanwhile, the number and strength of the interactions between the infiltrating immune cells and adrenal resident cells were unveiled by cell-cell communication analysis to be dramatically increased after systemic C.albicans infection, indicating that the immune-adrenal crosstalk might contribute to the compromised functions of adrenal cells. Overall, our comprehensive picture of the murine adrenal gland microenvironment in systemic C.albicans infection provides deeper insights into the immune-adrenal cell communications during fungal sepsis.
Selective targeting of MD2 attenuates intestinal inflammation and prevents neonatal necrotizing enterocolitis by suppressing TLR4 signaling
Authors: Huang Dabin , Wang Ping , Chen Juncao , Li Yanbin , Zhu Mingwei , Tang Yaping , Zhou Wei
Published: November 2022

Neonatal necrotizing enterocolitis (NEC) is an inflammatory disease that occurs in premature infants and has a high mortality rate; however, the mechanisms behind this disease remain unclear. The TLR4 signaling pathway in intestinal epithelial cells, mediated by TLR4, is important for the activation of the inflammatory storm in NEC infants. Myeloid differentiation protein 2 (MD2) is a key auxiliary component of the TLR4 signaling pathway. In this study, MD2 was found to be significantly increased in intestinal tissues of NEC patients at the acute stage. We further confirmed that MD2 was upregulated in NEC rats. MD2 inhibitor (MI) pretreatment reduced the occurrence and severity of NEC in neonatal rats, inhibited the activation of NF-κB and the release of inflammatory molecules (TNF-α and IL-6), and reduced the severity of intestinal injury. MI pretreatment significantly reduced enterocyte apoptosis while also maintaining tight junction proteins, including occludin and claudin-1, and protecting intestinal mucosal permeability in NEC rats. In addition, an NEC in vitro model was established by stimulating IEC-6 enterocytes with LPS. MD2 overexpression in IEC-6 enterocytes significantly activated NF-κB. Further, both MD2 silencing and MI pretreatment inhibited the inflammatory response. Overexpression of MD2 increased damage to the IEC-6 monolayer cell barrier, while both MD2 silencing and MI pretreatment played a protective role. In conclusion, MD2 triggers an inflammatory response through the TLR4 signaling pathway, leading to intestinal mucosal injury in NEC. In addition, MI alleviates inflammation and reduces intestinal mucosal injury caused by the inflammatory response by blocking the TLR4-MD2/NF-κB signaling axis. These results suggest that inhibiting MD2 may be an important way to prevent NEC.
Increased monocyte abundance as a marker for relapse after discontinuation of biologics in inflammatory bowel disease with deep remission
Authors: Kwon Yiyoung , Kim Yoon Zi , Choe Yon Ho , Kim Mi Jin
Published: November 2022

Monocytes are involved in the upstream inflammatory process in the immune reaction in inflammatory bowel disease (IBD). Patients with IBD who discontinued biologics have been found to relapse, even after checking for deep remission. This study investigated whether monocytes could act as a predictor of relapse in patients who experienced relapse after the discontinuation of biologics. To this end, pediatric patients (<19 years old, n = 727) diagnosed with IBD from January 2003 to December 2021 were retrospectively reviewed. Clinical features, monocytes, and disease activity at the time of discontinuing biologics were evaluated by dividing patients into a relapsed group and a non-relapsed group after discontinuing biologics. The percentage of monocytes (8.65% vs. 6.42%, P < 0.001), the absolute monocyte count (614.79 cells/μL vs. 381.70 cells/μL, P < 0.001), and the monocyte/polymorphonuclear leukocyte (PMN) ratio (0.18 vs. 0.11, P < 0.001) at the time of discontinuation were significantly higher in patients who experienced relapse. As a result of multivariate analysis, the monocyte percentage (odds ratio: 2.012, P < 0.001) and monocyte/PMN ratio (odds ratio: 4.320E+14, P = 0.002) were evaluated as risk factors for relapse. Diagnostic capability was confirmed using area under operating characteristic curve (0.782) of the monocyte percentage for assessing the relapse within 6 months with cutoff value of 8.15% (P < 0.001). The findings presented in this study indicate that the patients with high monocyte counts experienced relapse after the discontinuation of biologics. A monocyte percentage of over 8.15% in the blood at the time of discontinuation was found to be associated with a high probability of relapse within 6 months, even in deep remission.
The impact of genetic modified Ma bamboo on soil microbiome
Authors: Wang Kai , Liu Mengxia , Cai Changyang , Cai Shifeng , Ma Xiangqing , Lin Chentao , Zhu Qiang
Published: November 2022

Evaluating the potential alteration of microbial communities is a vital step for biosafety of genetic modified plants. Recently, we have produced genetic modified Ma bamboo with increased cold and drought tolerance by anthocyanin accumulation. In this work, we aim to study the potential effects on microbial communities in rhizosphere soils during the cultivation of genetic modified bamboo. Rhizosphere and surrounding soil were collected at 3-month post-transplant. The amplicon (16S rDNA and ITS1) were sequenced for analysis of bacterial and fungal communities. Multiple software and database (Picrust2, FAPROTAX and FUNGulid) were applied to predict and compare the microbial functions involving basic metabolisms, nitrogen usage and presence of plant pathogens. There were no substantial change of the structure and abundance of rhizosphere soil microbial communities between genetic modified and wild type bamboo. For the surrounding soil, the bacterial biota α-diversity increased (chao1: 1,001 ± 80–1,276 ± 84, observed species: 787 ± 52–1,194 ± 137, PD whole tree: 75 ± 4–117 ± 18) and fungal biota α-diversity decreased (chao1: 187 ± 18–145 ± 10) in samples of genetic modified bamboo compared to those of wild type bamboo. The microbiota predicted functions did not change or had no negative alteration between genetic modified and wild type bamboo, in both rhizosphere and surrounding soils. As a conclusion, the growth of genetic modified bamboo had no substantial change on rhizosphere soil microbial communities, while minor alteration on bamboo surrounding soil microbial communities with no harmful effects. Moreover, the genetic modified bamboo had no negative effect on the predicted functions of microbiota in soil.
Antimicrobial activity, chemical composition and mechanism of action of Chinese chive (Allium tuberosum Rottler) extracts
Authors: Chen Cun , Cai Jing , Ren Ying-hong , Xu Yue , Liu Hong-ling , Zhao Yu-yang , Chen Xing-fu , Liu Zhi-bin
Published: November 2022

Chinese chive (Allium tuberosum Rottler) is a popular food from Allium species in East and Southeast Asia. Most Allium species possess characteristic aromas and have antimicrobial activity. In this study, the antimicrobial activities of root, leaf, and scape extracts of Chinese chive at different pH levels (3.0, 5.0, 7.0, 9.0, and 10.7) were compared. The most pronounced activity was produced by the scape extract, and the greatest activity was obtained at pH 5.0. HPLC and GC–MS analysis showed that the major active ingredient was 2-amino-5-methylbenzoic acid. The mechanism of action of Chinese chive scape extracts may involve the depression or disruption of cell membrane integrity, according to our results of the leakage of electrolytes and protein, as well as scanning electron microscopy and transmission electron microscopy observations.
Exploring the active ingredients and pharmacological mechanisms of the oral intake formula Huoxiang Suling Shuanghua Decoction on influenza virus type A based on network pharmacology and experimental exploration
Authors: Tang Ruying , Wang Linyuan , Zhang Jianjun , Li Xinyu , Tan Lingyun , He Wei , Han Hui , Liu Yuan , Wang Keyu , Wang Mengyao
Published: November 2022

Objective

To investigate the active ingredients, underlying anti-influenza virus effects, and mechanisms of Huoxiang Suling Shuanghua Decoction (HSSD).

Materials and methods

The therapeutic effect of HSSD were confirmed through the survival rate experiment of H1N1-infected mice. Then, the HSSD solution and the ingredients absorbed into the blood after treatment with HSSD in rats were identified by UPLC/Q-TOF MS, while the main contents of ingredients were detected by high performance liquid chromatography (HPLC). Next, a systems pharmacology approach incorporating target prediction, gene ontology (GO) enrichment, kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and molecular docking were performed to screen out the active compounds and critical pathways of HSSD in treating influenza. According to prediction results, real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry assay were used to detect the mRNA and protein expression levels of critical targets in H1N1-infected mice lungs.

Results

Huoxiang Suling Shuanghua Decoction improved the survival rate of H1N1-infected mice and prolonged the mice’s lifespan. Besides, HSSD exerts an antivirus effect by decreasing the levels of hemagglutinin (HA) and nucleoprotein (NP) to inhibit the replication and proliferation of H1N1, reducing the lung pathological state, inhibiting the cell apoptosis in the lung, and regulating the abnormal responses of peripheral blood, including GRA, LYM, white blood cell (WBC), PLT, and hemoglobin (HGB). Then, 87 compounds in the HSSD solution and 20 ingredients absorbed into the blood after treatment with HSSD were identified. Based on this, combined with the network analysis and previous research on antivirus, 16 compounds were screened out as the active components. Moreover, 16 potential targets were predicted by network pharmacology analysis. Next, molecular docking results showed stable binding modes between compounds and targets. Furthermore, experimental validation results indicated that HSSD regulates the contents of Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) in serum, modulating the levels of IFN-γ, IL-6, IL-10, MCP-1, MIP-1α, and IP-10 in the lung tissue, and significantly decreasing the mRNA and protein expressions of TLR4, CD14, MyD88, NF-κB p65, HIF1 α, VEGF, IL17A, and IL6 in the lung tissue.

Conclusion

Huoxiang Suling Shuanghua Decoction exerts an anti-influenza effect by affecting the expressions of mRNA and protein including TLR4, CD14, MyD88, NF-kB p65, HIF-1α, VEGF, IL17A, IL6, and inhibiting the accumulation of inflammation. Our study provided experimental pieces of evidence about the practical application of HSSD in treating influenza.
Effect of exogenous microorganisms on the fermentation quality, nitrate degradation and bacterial community of sorghum-sudangrass silage
Authors: Zhao Meirong , Zhang Hongyu , Pan Gang , Yin Hang , Sun Juanjuan , Yu Zhu , Bai Chunsheng , Xue Yanlin
Published: November 2022

This study aims to investigate the effects of adding Lactobacillus buchneri (LB), Lactobacillus brevis (LBR) and Bacillus subtilis (BS) on the fermentation quality, nitrate degradation and bacterial community of sorghum-sudangrass silage. The results showed that the addition of LB significantly increased the pH and acetic acid content (p < 0.05), but high-quality silage was obtained. The addition of LBR and BS improved the fermentation quality of sorghum-sudangrass silage. The use of additives reduced the nitrate content in sorghum-sudangrass silage. The LB group increased the release of N2O at 3–7 days of ensiling (p < 0.05), and LBR and BS increased the release of N2O at 1–40 days of ensiling (p < 0.05). On the first day of ensiling, all silages were dominated by Weisslla, over 3 days of ensiling all silages were dominated by Lactobacillus. Acinetobacter, Serratia, Aquabacterium, and unclassified_f_enterobacteriaceae showed significant negative correlations with nitrate degradation during sorghum-sudangrass ensiling (p < 0.05). The BS and LBR groups increased the metabolic abundance of denitrification, dissimilatory nitrate reduction, and assimilatory nitrate reduction (p < 0.05). Overall, the additive ensures the fermentation quality of sorghum-sudangrass silage and promotes the degradation of nitrate by altering the bacterial community.
Strategies to improve safety profile of AAV vectors
Authors: Suoranta Tuisku , Laham-Karam Nihay , Ylä-Herttuala Seppo
Published: November 2022

Adeno-associated virus (AAV) vectors are currently used in four approved gene therapies for Leber congenital amaurosis (Luxturna), spinal muscular atrophy (Zolgensma), aromatic L-amino acid decarboxylase deficiency (Upstaza) and Haemophilia A (Roctavian), with several more therapies being investigated in clinical trials. AAV gene therapy has long been considered extremely safe both in the context of immunotoxicity and genotoxicity, but recent tragic deaths in the clinical trials for X-linked myotubular myopathy and Duchenne’s muscular dystrophy, together with increasing reports of potential hepatic oncogenicity in animal models have prompted re-evaluation of how much trust we can place on the safety of AAV gene therapy, especially at high doses. In this review we cover genome and capsid engineering strategies that can be used to improve safety of the next generation AAV vectors both in the context of immunogenicity and genotoxicity and discuss the gaps that need filling in our current knowledge about AAV vectors.
Neurofilaments contribution in clinic: state of the art
Authors: Delaby Constance , Bousiges Olivier , Bouvier Damien , Fillée Catherine , Fourier Anthony , Mondésert Etienne , Nezry Nicolas , Omar Souheil , Quadrio Isabelle , Rucheton Benoit , Schraen-Maschke Susanna , van Pesch Vincent , Vicca Stéphanie , Lehmann Sylvain , Bedel Aurelie
Published: November 2022

Neurological biomarkers are particularly valuable to clinicians as they can be used for diagnosis, prognosis, or response to treatment. This field of neurology has evolved considerably in recent years with the improvement of analytical methods, allowing the detection of biomarkers not only in cerebrospinal fluid (CSF) but also in less invasive fluids like blood. These advances greatly facilitate the repeated quantification of biomarkers, including at asymptomatic stages of the disease. Among the various informative biomarkers of neurological disorders, neurofilaments (NfL) have proven to be of particular interest in many contexts, such as neurodegenerative diseases, traumatic brain injury, multiple sclerosis, stroke, and cancer. Here we discuss these different pathologies and the potential value of NfL assay in the management of these patients, both for diagnosis and prognosis. We also describe the added value of NfL compared to other biomarkers currently used to monitor the diseases described in this review.
The role of microglial autophagy in Parkinson’s disease
Authors: Zhu Rui , Luo Yuyi , Li Shangang , Wang Zhengbo
Published: November 2022

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Studies have shown that abnormal accumulation of α-synuclein (α-Syn) in the substantia nigra is a specific pathological characteristic of PD. Abnormal accumulation of α-Syn in PD induces the activation of microglia. Microglia, which are immune cells in the central nervous system, are involved in the function and regulation of inflammation in PD by autophagy. The role of microglial autophagy in the pathophysiology of PD has become a hot-pot issue. This review outlines the pathways of microglial autophagy, and explores the key factor of microglial autophagy in the mechanism of PD and the possibility of microglial autophagy as a potential therapeutic target for PD.
Utility of serum nuclear factor erythroid 2-related factor 2 as a potential prognostic biomarker of severe traumatic brain injury in adults: A prospective cohort study
Authors: Yan Xin-Jiang , Zhan Cheng-Peng , Lv Yao , Mao Dan-Dan , Zhou Ri-Cheng , Xv Yong-Min , Yu Guo-Feng
Published: November 2022

Objective

Nuclear factor erythroid 2-related factor 2 (Nrf2) may harbor endogenous neuroprotective role. We strived to ascertain the prognostic significance of serum Nrf2 in severe traumatic brain injury (sTBI).

Methods

This prospective cohort study included 105 controls and 105 sTBI patients, whose serum Nrf2 levels were quantified. Its relations to traumatic severity and 180-day overall survival, mortality, and poor prognosis (extended Glasgow Outcome Scale score 1–4) were discerned using multivariate analysis.

Results

There was a substantial enhancement of serum Nrf1 levels of patients (median, 10.9 vs. 3.3 ng/ml; P < 0.001), as compared to controls. Serum Nrf2 levels were independently correlative to Rotterdam computed tomography (CT) scores (ρ = 0.549, P < 0.001; t = 2.671, P = 0.009) and Glasgow Coma Scale (GCS) scores (ρ = −0.625, P < 0.001; t = −3.821, P < 0.001). Serum Nrf2 levels were significantly higher in non-survivors than in survivors (median, 12.9 vs. 10.3 ng/ml; P < 0.001) and in poor prognosis patients than in good prognosis patients (median, 12.5 vs. 9.4 ng/ml; P < 0.001). Patients with serum Nrf2 levels > median value (10.9 ng/ml) had markedly shorter 180-day overall survival time than the other remainders (mean, 129.3 vs. 161.3 days; P = 0.002). Serum Nrf2 levels were independently predictive of 180-day mortality (odds ratio, 1.361; P = 0.024), overall survival (hazard ratio, 1.214; P = 0.013), and poor prognosis (odds ratio, 1.329; P = 0.023). Serum Nrf2 levels distinguished the risks of 180-day mortality and poor prognosis with areas under receiver operating characteristic curve (AUCs) at 0.768 and 0.793, respectively. Serum Nrf2 levels > 10.3 ng/ml and 10.8 ng/ml discriminated patients at risk of 180-day mortality and poor prognosis with the maximum Youden indices of 0.404 and 0.455, respectively. Serum Nrf2 levels combined with GCS scores and Rotterdam CT scores for death prediction (AUC, 0.897; 95% CI, 0.837–0.957) had significantly higher AUC than GCS scores (P = 0.028), Rotterdam CT scores (P = 0.007), or serum Nrf2 levels (P = 0.006) alone, and the combination for poor outcome prediction (AUC, 0.889; 95% CI, 0.831–0.948) displayed significantly higher AUC than GCS scores (P = 0.035), Rotterdam CT scores (P = 0.006), or serum Nrf2 levels (P = 0.008) alone.

Conclusion

Increased serum Nrf2 levels are tightly associated with traumatic severity and prognosis, supporting the considerable prognostic role of serum Nrf2 in sTBI.
Dexmedetomidine-mediated sleep phase modulation ameliorates motor and cognitive performance in a chronic blast-injured mouse model
Authors: Bibineyshvili Yelena , Schiff Nicholas D. , Calderon Diany P.
Published: November 2022

Multiple studies have shown that blast injury is followed by sleep disruption linked to functional sequelae. It is well established that improving sleep ameliorates such functional deficits. However, little is known about longitudinal brain activity changes after blast injury. In addition, the effects of directly modulating the sleep/wake cycle on learning task performance after blast injury remain unclear. We hypothesized that modulation of the sleep phase cycle in our injured mice would improve post-injury task performance. Here, we have demonstrated that excessive sleep electroencephalographic (EEG) patterns are accompanied by prominent motor and cognitive impairment during acute stage after secondary blast injury (SBI) in a mouse model. Over time we observed a transition to more moderate and prolonged sleep/wake cycle disturbances, including changes in theta and alpha power. However, persistent disruptions of the non-rapid eye movement (NREM) spindle amplitude and intra-spindle frequency were associated with lasting motor and cognitive deficits. We, therefore, modulated the sleep phase of injured mice using subcutaneous (SC) dexmedetomidine (Dex), a common, clinically used sedative. Dex acutely improved intra-spindle frequency, theta and alpha power, and motor task execution in chronically injured mice. Moreover, dexmedetomidine ameliorated cognitive deficits a week after injection. Our results suggest that SC Dex might potentially improve impaired motor and cognitive behavior during daily tasks in patients that are chronically impaired by blast-induced injuries.
Characteristics of sleep structure in Parkinson's disease patients with hallucinations based on polysomnography
Authors: Gu Ruxin , Zhu Jun , Zhong Min , Jiang Yinyin , Zhu Sha , Wang Yaxi , Jiang Xu , Shen Bo , Yan Jun , Zhang Li , Pan Yang
Published: November 2022

Hallucination is a common non-motor symptom in patients with Parkinson's disease (PD). Additionally, sleep disorders are associated with an increased risk of hallucinations in PD patients. This study aimed to examine the association between hallucination and objective sleep parameters in PD patients. We retrospectively recruited 278 PD patients who underwent polysomnography and clinical assessments and classified them into non-hallucination and hallucination groups. Hallucinations were observed in 77 older PD patients who had more severe motor symptoms and higher scores on the Non-Motor Symptoms Questionnaire (NMSQ), Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) but lower scores on the Montreal Cognitive Assessment (MOCA) and PD Sleep Scale (PDSS) than PD patients without hallucinations. Analysis of the polysomnographic variables in patients with hallucinations showed that they exhibited a decrease in total sleep time, sleep efficiency (SE), rapid eye movement (REM) sleep time and slow wave sleep (SWS, N3) time and percentage but a significant increase in wake time after sleep onset (WASO), periodic limb movement index (PLMI) scores, and stage 2 NREM (N2)percentage. Logistic regression analysis revealed that higher NMSQ scores, lower MOCA scores, lower SE, and a lower percentage of N3 sleep were associated with hallucinations in PD patients. Our results suggested that PD patients with hallucinations had worse sleep quality and differences in sleep architecture (measured by polysomnography).
RETRACTED: CSF p-tau as a potential cognition impairment biomarker in ALS
Authors: Gong Zhongying , Gao Lina , Lu Yi , Wang Zhiyun
Published: November 2022

Background

Cerebrospinal fluid (CSF) and serum tau (t-tau, p-tau) are potential biomarkers for neurodegeneration in Alzheimer disease (AD), but their role in amyotrophic lateral sclerosis (ALS) is unclear.

Objectives

The aim of our study was to evaluate CSF and serum p-tau and t-tau in patients with ALS and to analyze the correlation and clinical parameters between them.

Methods

CSF and serum samples were obtained from 90 patients with ALS, 48 other neurological disease (OND), and 20 with AM (ALS mimic, AM) diseases. The levels of p-tau and t-tau in the CSF and serum were assessed with an enzyme-linked immunosorbent assay, and disease progression parameters, including the duration, the ALSFRS-R score, disease progression rate (DPR), the upper motor neuron (UMN) score, the Mini-mental State Examination (MMSE) score, the Montreal Cognitive Assessment (MoCA) score, and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) results, were analyzed by registered neurologists. Statistical analyses were performed using Prism software.

Results

Compared with controls, patients with ALS displayed significantly lower levels of CSF p-tau and p-tau:t-tau ratio. The CSF p-tau level in patients with ALS and cognition impairment was higher than that in patients with ALS who did not have cognition impairment. CSF p-tau level was negatively correlated with MMSE, MoCA, and ECAS total score and the specific score of ECAS in patients with ALS and cognition impairment.

Conclusions

The CSF p-tau level and p-tau:t-tau ratio were lower in patients with ALS than patients with OND and AM. Results suggest that CSF p-tau may be used as an index of cognition impairment in patients with ALS.
Visual P2p component responds to perceived numerosity
Authors: Grasso Paolo A. , Petrizzo Irene , Caponi Camilla , Anobile Giovanni , Arrighi Roberto
Published: November 2022

Numerosity perception is a key ability for human and non-human species, probably mediated by dedicated brain mechanisms. Electrophysiological studies revealed the existence of both early and mid-latency components of the Electrophysiological (EEG) signal sensitive to numerosity changes. However, it is still unknown whether these components respond to physical or perceived variation in numerical attributes. We here tackled this point by recording electrophysiological signal while participants performed a numerosity adaptation task, a robust psychophysical method yielding changes in perceived numerosity judgments despite physical numerosity invariance. Behavioral measures confirmed that the test stimulus was consistently underestimated when presented after a high numerous adaptor while perceived as veridical when presented after a neutral adaptor. Congruently, EEG results revealed a potential at around 200 ms (P2p) which was reduced when the test stimulus was presented after the high numerous adaptor. This result was much prominent over the left posterior cluster of electrodes and correlated significantly with the amount of adaptation. No earlier modulations were retrievable when changes in numerosity were illusory while both early and mid-latency modulations occurred for physical changes. Taken together, our results reveal that mid-latency P2p mainly reflects perceived changes in numerical attributes, while earlier components are likely to be bounded to the physical characteristics of the stimuli. These results suggest that short-term plastic mechanisms induced by numerosity adaptation may involve a relatively late processing stage of the visual hierarchy likely engaging cortical areas beyond the primary visual cortex. Furthermore, these results also indicate mid-latency electrophysiological correlates as a signature of the internal representation of numerical information.
Monitoring improvements in the nutritional quality of new packaged foods launched between 2016 and 2020
Authors: Tassy Marie , Rytz Andréas , Drewnowski Adam , Lecat Alec , Jacquier Emma F. , Charles Véronique Rheiner
Published: November 2022

Food and beverage companies reformulate packaged foods and to better align their products with public health policies and evolving consumer needs. The nutritional quality of packaged foodscan be tracked using nutrient profiling methods. The present study compared the nutritional quality of packaged foods launched globally between 2016 and 2018 and those launched in 2018–2020, as reported in the Mintel Global New Products Database. Nutrient profiling analyses showed that the nutrient composition of product categories shifted for almost 40% of newly launched products between 2016–2018 and 2018–2020. For example, pizzas that had been assigned to one nutritionally homogenous category in 2016–2018 separated in two nutritionally distinct subgroups in 2018–2020. The new products that were reduced in protein, saturated fat, and sodium were now nutritionally distinct from the traditional pizza offer. By 2018–2020 “best of category” products were significantly lower in sugar and sodium than before; however, no clear trend was observed for saturated fats, proteins, or fibers. The relative speed of product reformulation was category specific. This analysis of the Mintel Global New Products Database suggests that the WHO nutritional recommendations focusing on sugar and sodium reduction did have a positive impact on the composition of new packaged foods, whether through reformulation of existing products, launches of line extensions or new product development.