bluuebunny/crossref_metadata_2025 huggingface dataset:
Further Introduction of DNA Methylation (DNAm) Arrays in Regular Diagnostics
Authors: Mannens M. M. A. M. , Lombardi M. P. , Alders M. , Henneman P. , Bliek J.
Published: July 2022

Methylation tests have been used for decades in regular DNA diagnostics focusing primarily on Imprinting disorders or specific loci annotated to specific disease associated gene promotors. With the introduction of DNA methylation (DNAm) arrays such as the Illumina Infinium HumanMethylation450 Beadchip array or the Illumina Infinium Methylation EPIC Beadchip array (850 k), it has become feasible to study the epigenome in a timely and cost-effective way. This has led to new insights regarding the complexity of well-studied imprinting disorders such as the Beckwith Wiedemann syndrome, but it has also led to the introduction of tests such as EpiSign, implemented as a diagnostic test in which a single array experiment can be compared to databases with known episignatures of multiple genetic disorders, especially neurodevelopmental disorders. The successful use of such DNAm tests is rapidly expanding. More and more disorders are found to be associated with discrete episignatures which enables fast and definite diagnoses, as we have shown. The first examples of environmentally induced clinical disorders characterized by discrete aberrant DNAm are discussed underlining the broad application of DNAm testing in regular diagnostics. Here we discuss exemplary findings in our laboratory covering this broad range of applications and we discuss further use of DNAm tests in the near future.
Systematic Investigation of Immune-Related lncRNA Landscape Reveals a Potential Long Non-Coding RNA Signature for Predicting Prognosis in Renal Cell Carcinoma
Authors: Liu Kepu , Li Zhibin , Ruan Dongli , Wang Huilong , Wang Wei , Zhang Geng
Published: July 2022

Background: Renal cell carcinoma (RCC) is the predominant type of malignant tumor in kidney cancer. Finding effective biomarkers, particularly those based on the tumor immune microenvironments (TIME), is critical for the prognosis and diagnosis of RCC. Increasing evidence has revealed that long non-coding RNAs (lncRNAs) play a crucial role in cancer immunity. However, the comprehensive landscape of immune infiltration-associated lncRNAs and their potential roles in the prognosis and diagnosis of RCC remain largely unexplored.

Methods: Based on transcriptomic data of 261 RCC samples, novel lncRNAs were identified using a custom pipeline. RCC patients were classified into different immune groups using unsupervised clustering algorithms. Immune-related lncRNAs were obtained according to the immune status of RCC. Competing endogenous RNAs (ceRNA) regulation network was constructed to reveal their functions. Expression patterns and several tools such as miRanda, RNAhybrid, miRWalk were used to define lncRNAs-miRNAs-mRNAs interactions. Univariate Cox, LASSO, and multivariate Cox regression analyses were performed on the training set to construct a tumorigenesis-immune-infiltration-related (TIR)-lncRNA signature for predicting the prognosis of RCC. Independent datasets involving 531 RCC samples were used to validate the TIR-lncRNA signature.

Results: Tens of thousands of novel lncRNAs were identified in RCC samples. Comparing tumors with controls, 1,400 tumorigenesis-related (TR)-lncRNAs, 1269 TR-mRNAs, and 192 TR-miRNAs were obtained. Based on the infiltration of immune cells, RCC patients were classified into three immune clusters. By comparing immune-high with immune-low groups, 241 TIR-lncRNAs were identified, many of which were detected in urinary samples. Based on lncRNA-miRNA-mRNA interactions, we constructed a ceRNA network, which included 25 TR-miRNAs, 28 TIR-lncRNAs, and 66 TIR-mRNAs. Three TIR lncRNAs were identified as a prognostic signature for RCC. RCC patients in the high-risk group exhibited worse OS than those in the low-risk group in the training and testing sets (p < 0.01). The AUC was 0.9 in the training set. Univariate and multivariate Cox analyses confirmed that the TIR-lncRNA signature was an independent prognostic factor in the training and testing sets.

Conclusion: Based on the constructed immune-related lncRNA landscape, 241 TIR-lncRNAs were functionally characterized, three of which were identified as a novel TIR-lncRNA signature for predicting the prognosis of RCC.
Comprehensive Network-Based Analyses Reveal Novel Renal Function-Related Targets in Acute Kidney Injury
Authors: Zhang Yang , Cai Jieru , Lu Wei , Xu Sujuan , Qu Mengdi , Zhao Shuan , Ding Xiaoqiang
Published: July 2022

Background: Acute kidney injury (AKI) is a common clinical syndrome with limited methods of treatment and diagnosis. Although several molecules associated with AKI have been discovered, molecular mechanisms underlying AKI still remain unclear. Weighted gene co-expression network analysis (WGCNA) is a novel method to uncover the relationship between co-expression genes and clinical traits at the system level.

Methods: First, by employing WGCNA in transcriptional data on 30 patients with well/poor functioning kidney graft, we identified two co-expression modules that were significantly related to serum creatinine (SCr). Second, based on the modules, potential small molecular compound candidates for developing targeted therapeutics were obtained by connectivity map analysis. Furthermore, multiple validations of expression in space/time were carried out with two classical AKI models in vivo and other five databases of over 152 samples.

Results: Two of the 14 modules were found to be closely correlated with SCr. Function enrichment analysis illustrated that one module was enriched in the immune system, while the other was in the metabolic process. Six key renal function-related genes (RFRGs) were finally obtained. Such genes performed well in cisplatin-induced or cecal ligation and puncture-induced AKI mouse models.

Conclusion: The analysis suggests that WGCNA is a proper method to connect clinical traits with genome data to find novel targets in AKI. The kidney tissue with worse renal function tended to develop a “high immune but low metabolic activity” expression pattern. Also, ACSM2A, GLYAT, CORO1A, DPEP1, ALDH7A1, and EPHX2 are potential targets of molecular diagnosis and treatment in AKI.
Trained Immunity in Primary Sjögren’s Syndrome: Linking Type I Interferons to a Pro-Atherogenic Phenotype
Authors: Huijser Erika , van Helden-Meeuwsen Cornelia G. , Grashof Dwin G. B. , Tarn Jessica R. , Brkic Zana , Huisman Josje M. A. , Wahadat M. Javad , van de Werken Harmen J. G. , Lopes Ana P. , van Roon Joel A. G. , van Daele Paul L. A. , Kamphuis Sylvia , Ng Wan-Fai , Bekkering Siroon , Joosten Leo A. B. , Dik Willem A. , Versnel Marjan A.
Published: July 2022

Background

Trained immunity – or innate immune memory – can be described as the long-term reprogramming of innate immune cells towards a hyperresponsive state which involves intracellular metabolic changes. Trained immunity has been linked to atherosclerosis. A subgroup of patients with primary Sjögren’s syndrome (pSS) exhibits systemic type I interferon (IFN) pathway activation, indicating innate immune hyperactivation. Here, we studied the link between type I IFNs and trained immunity in an in vitro monocytic cell model and peripheral blood mononuclear cells (PBMCs) from pSS patients.

Methods

The training stimuli heat killed Candida albicans, muramyl dipeptide, IFNβ, and patient serum were added to THP-1 cells for 24 hours, after which the cells were washed, rested for 48 hours and subsequently re-stimulated with LPS, Pam3Cys, poly I:C, IFNβ or oxLDL for 4-24 hours. PBMCs from pSS patients and healthy controls were stimulated with LPS, Pam3Cys, poly I:C or IFNβ for 0.5-24 hours.

Results

Training with IFNβ induced elevated production of pro-atherogenic cytokines IL-6, TNFα and CCL2, differential cholesterol- and glycolysis-related gene expression, and increased glucose consumption and oxLDL uptake upon re-stimulation. Type I IFN production was increased in Candida albicans- and IFNβ-trained cells after LPS re-stimulation, but was reduced after poly I:C re-stimulation. Training with muramyl dipeptide and IFNβ, but not Candida albicans, affected the IFN-stimulated gene expression response to IFNβ re-stimulation. PBMCs from pSS patients consumed more glucose compared with healthy control PBMCs and tended to produce more TNFα and type I IFNs upon LPS stimulation, but less type I IFNs upon poly I:C stimulation.

Conclusions

Type I IFN is a trainer inducing a trained immunity phenotype with pro-atherogenic properties in monocytes. Conversely, trained immunity also affects the production of type I IFNs and transcriptional response to type I IFN receptor re-stimulation. The phenotype of pSS PBMCs is consistent with trained immunity. This connection between type I IFN, trained immunity and cholesterol metabolism may have important implications for pSS and the pathogenesis of (subclinical) atherosclerosis in these patients.
Bifidobacterium infantis Promotes Foxp3 Expression in Colon Cells via PD-L1-Mediated Inhibition of the PI3K-Akt-mTOR Signaling Pathway
Authors: Zhou Linyan , Xie Ying , Li Yan
Published: July 2022

Aim

Our objective was to investigate whether Bifidobacterium infantis inhibits PI3K-Akt-mTOR signaling and upregulates Foxp3 expression through PD-L1 and to explore the possible mechanism of action of B. infantis in cellular immunosuppression.

Method

The effects of B. infantis supernatant on PD-L1, PD-1, Foxp3, and the PI3K-Akt-mTOR signaling pathway were observed by culturing HCT-116 cells. Simultaneously, the effects of blocking PD-L1 on PD-1, on Foxp3 protein and mRNA, and on the PI3K-Akt-mTOR signaling pathway protein were observed.

Results

B. infantis supernatant was able to upregulate the protein and mRNA expression of PD-L1 and Foxp3 and downregulate the phosphorylated protein expression of PI3K, Akt, and mTOR (P < 0.05); however, for PI3K, Akt, and mTOR, there was no change in the total protein expression. After the blocking of PD-L1, the stimulatory effect of B. infantis supernatant on Foxp3 and the inhibitory effect on the phosphorylated protein expression of PI3K, Akt, and mTOR were weakened.

Conclusion

B. infantis may inhibit the PI3K-Akt-mTOR signaling pathway and promote the expression of Foxp3 through PD-L1, which may be a target via which B. infantis exerts its immunosuppressive effect.
Chronic Inflammatory Demyelinating Polyradiculoneuropathy in Association With Concomitant Diseases: Identification and Management
Authors: Chen Yan , Tang Xiangqi
Published: July 2022

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare, heterogeneous, but treatable autoimmune-mediated peripheral neuropathy characterized by demyelination. CIDP can occur independently or simultaneously with a variety of diseases such as diabetes, monoclonal gammopathy of undetermined significance (MGUS), connective tissue disease, and HIV. It is important to identify CIDP and specific peripheral neuropathies caused by these diseases; this review aims to summarize the CIDP literatures related to diabetes, MGUS, SLE, and HIV, and to be helpful for the management of such patients.
Colchicine Impacts Leukocyte Trafficking in Atherosclerosis and Reduces Vascular Inflammation
Authors: Meyer-Lindemann Ulrike , Mauersberger Carina , Schmidt Anna-Christina , Moggio Aldo , Hinterdobler Julia , Li Xinghai , Khangholi David , Hettwer Jan , Gräßer Christian , Dutsch Alexander , Schunkert Heribert , Kessler Thorsten , Sager Hendrik B.
Published: July 2022

Background

Inflammation strongly contributes to atherosclerosis initiation and progression. Consequently, recent clinical trials pharmacologically targeted vascular inflammation to decrease the incidence of atherosclerosis-related complications. Colchicine, a microtubule inhibitor with anti-inflammatory properties, reduced cardiovascular events in patients with recent acute coronary syndrome and chronic coronary disease. However, the biological basis of these observations remains elusive. We sought to explore the mechanism by which colchicine beneficially alters the course of atherosclerosis.

Methods and Results

In mice with early atherosclerosis (Apoe-/- mice on a high cholesterol diet for 8 weeks), we found that colchicine treatment (0.25 mg/kg bodyweight once daily over four weeks) reduced numbers of neutrophils, inflammatory monocytes and macrophages inside atherosclerotic aortas using flow cytometry and immunohistochemistry. Consequently, colchicine treatment resulted in a less inflammatory plaque composition and reduced plaque size. We next investigated how colchicine prevented plaque leukocyte expansion and found that colchicine treatment mitigated recruitment of blood neutrophils and inflammatory monocytes to plaques as revealed by adoptive transfer experiments. Causally, we found that colchicine reduced levels of both leukocyte adhesion molecules and receptors for leukocyte chemoattractants on blood neutrophils and monocytes. Further experiments showed that colchicine treatment reduced vascular inflammation also in post-myocardial infarction accelerated atherosclerosis through similar mechanisms as documented in early atherosclerosis. When we examined whether colchicine also decreased numbers of macrophages inside atherosclerotic plaques by impacting monocyte/macrophage transitioning or in-situ proliferation of macrophages, we report that colchicine treatment did not influence macrophage precursor differentiation or macrophage proliferation using cell culture experiments with bone marrow derived macrophages.

Conclusions

Our data reveal that colchicine prevents expansion of plaque inflammatory leukocytes through lowering recruitment of blood myeloid cells to plaques. These data provide novel mechanistic clues on the beneficial effects of colchicine in the treatment of atherosclerosis and may inform future anti-inflammatory interventions in patients at risk.
Alterations of NK Cell Phenotype During Pregnancy in Multiple Sclerosis
Authors: Wisgalla Anne , Ramien Caren , Streitz Mathias , Schlickeiser Stephan , Lupu Andreea-Roxana , Diemert Anke , Tolosa Eva , Arck Petra C. , Bellmann-Strobl Judith , Siebert Nadja , Heesen Christoph , Paul Friedemann , Friese Manuel A. , Infante-Duarte Carmen , Gold Stefan M.
Published: July 2022

In multiple sclerosis (MS), relapse rate is decreased by 70-80% in the third trimester of pregnancy. However, the underlying mechanisms driving this effect are poorly understood. Evidence suggests that CD56bright NK cell frequencies increase during pregnancy. Here, we analyze pregnancy-related NK cell shifts in a large longitudinal cohort of pregnant women with and without MS, and provide in-depth phenotyping of NK cells. In healthy pregnancy and pregnancy in MS, peripheral blood NK cells showed significant frequency shifts, notably an increase of CD56bright NK cells and a decrease of CD56dim NK cells toward the third trimester, indicating a general rather than an MS-specific phenomenon of pregnancy. Additional follow-ups in women with MS showed a reversal of NK cell changes postpartum. Moreover, high-dimensional profiling revealed a specific CD56bright subset with receptor expression related to cytotoxicity and cell activity (e.g., CD16+ NKp46high NKG2Dhigh NKG2Ahigh phenotype) that may drive the expansion of CD56bright NK cells during pregnancy in MS. Our data confirm that pregnancy promotes pronounced shifts of NK cells toward the regulatory CD56bright population. Although exploratory results on in-depth CD56bright phenotype need to be confirmed in larger studies, our findings suggest an increased regulatory NK activity, thereby potentially contributing to disease amelioration of MS during pregnancy.
Transcription Factor RUNX3 Mediates Plasticity of ThGM Cells Toward Th1 Phenotype
Authors: Rasouli Javad , Casella Giacomo , Zhang Weifeng , Xiao Dan , Kumar Gaurav , Fortina Paolo , Zhang Guang-Xian , Ciric Bogoljub , Rostami Abdolmohamad
Published: July 2022

GM-CSF-producing T helper (Th) cells play a crucial role in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). Recent studies have identified a distinct population of GM-CSF-producing Th cells, named ThGM cells, that also express cytokines TNF, IL-2, and IL-3, but lack expression of master transcription factors (TF) and signature cytokines of commonly recognized Th cell lineages. ThGM cells are highly encephalitogenic in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Similar to Th17 cells, in response to IL-12, ThGM cells upregulate expression of T-bet and IFN-γ and switch their phenotype to Th1. Here we show that in addition to T-bet, TF RUNX3 also contributes to the Th1 switch of ThGM cells. T-bet-deficient ThGM cells in the CNS of mice with EAE had low expression of RUNX3, and knockdown of RUNX3 expression in ThGM cells abrogated the Th1-inducing effect of IL-12. Comparison of ThGM and Th1 cell transcriptomes showed that ThGM cells expressed a set of TFs known to inhibit the development of other Th lineages. Lack of expression of lineage-specific cytokines and TFs by ThGM cells, together with expression of TFs that inhibit the development of other Th lineages, suggests that ThGM cells are a non-polarized subset of Th cells with lineage characteristics.
Characteristics of Fatty Acid Metabolism in Lung Adenocarcinoma to Guide Clinical Treatment
Authors: Huang Dejing , Tang Enyu , Zhang Tianze , Xu Guangquan
Published: July 2022

Background

Lung adenocarcinoma (LUAD) has a very high morbidity and mortality rate, and its pathogenesis and treatment are still in the exploratory stage. Fatty acid metabolism plays a significant role in tumorigenesis, progression, and immune regulation. However, the gene expression of fatty acid metabolism in patients with LUAD and its relationship with prognosis remain unclear.

Methods

We collected 309 fatty acid metabolism-related genes, established a LUAD risk model based on The Cancer Genome Atlas (TCGA) using Least Absolute Shrinkage Selection Operator (LASSO) regression analysis, and divided LUAD patients into high-risk and low-risk groups, which were further validated using the Gene Expression Omnibus (GEO) database. The nomogram, principal component analysis (PCA), and receiver operating characteristic (ROC) curves showed that the model had the best predictive performance. The ROC curves and calibration plots confirmed that the nomogram had good predictive power. We further analyzed the differences in clinical characteristics, immune cell infiltration, immune-related functions, chemotherapy drug sensitivity, and immunotherapy efficacy between the high-risk and low-risk groups. We also analyzed the enrichment pathways and protein–protein interaction (PPI) networks of different genes in the high-risk and low-risk groups to screen for target genes and further explored the correlation between target genes and differences in survival prognosis, clinical characteristics, gene mutations, and immune cells.

Results

Risk score and staging are independent prognostic factors for patients with LUAD. The high-risk group had lower immune cell infiltration, was more sensitive to chemotherapeutic agents, and had a poorer survival prognosis. We also obtained three pivotal genes with poor survival prognosis in the high expression group, which were strongly associated with clinical symptoms and immune cells.

Conclusion

Risk score and staging are independent prognostic factors for patients with LUAD. The high-risk group had lower immune cell infiltration, was more sensitive to chemotherapeutic agents, and had a poorer survival prognosis. We also obtained three survival prognosis-associated target genes that are closely associated with clinical symptoms and immune cells and may be potential targets for immune-targeted therapy in LUAD.
ETV1 Positively Correlated With Immune Infiltration and Poor Clinical Prognosis in Colorectal Cancer
Authors: Shen Xiaonan , Zhou Chunhua , Feng Haoran , Li Jialu , Xia Tianxue , Cheng Xi , Zhao Ren , Zou Duowu
Published: July 2022

Objective

Numerous studies recently suggested that the immune microenvironment could influence the development of colorectal cancer (CRC). These findings implied that the infiltration of immune cells could be a promising prognostic biomarker for CRC.

Methods

Furthermore, the Oncomine database and R2 platform analysis were applied in our research to validate CRC clinical prognosis via expression levels of polyoma enhancer activator 3 (PEA3) members. We explored the correlation of ETV1, ETV4, and ETV5 with tumor-infiltrating immune cells (TIICs) in CRC tumor microenvironments via the Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). Immunohistochemistry (IHC) was used to validate our CRC clinical data.

Results

Our findings indicated that the upregulation of PEA3 members including ETV1 and ETV5 was positively associated with poor prognosis in CRC patients. Meanwhile, ETV1 and ETV5 may play significant roles in the development progress of CRC. Furthermore, ETV1 tends to be associated with immune infiltration of CRC, especially with cancer-associated fibroblasts and M2 macrophages.

Conclusion

These findings revealed that ETV1 and ETV5 played significant roles in the development of CRC. Moreover, ETV1 was significantly associated with the infiltration of cancer-associated fibroblasts and M2 macrophages in CRC. Targeting ETV1 can be a potential auspicious approach for CRC treatment.
High-Throughput Identification of Antihypertensive Peptides (AHTPs) and Characterization of AHTP-Derived Genes in the Lined Seahorse (Hippocampus erectus)
Authors: Huang Yu , Chen Xiyang , Shu Haoyue , Xiao Panpan , Lin Xueqiang , Xu Junmin , Bian Chao , You Xinxin , Yang Jian , Shi Qiong
Published: July 2022

Recently, the prevalence of hypertension has become a global challenge. Therefore, tremendous efforts have been made to identify and purify antihypertensive peptides (AHTPs) from food-derived proteins to aid the discovery of new hypotensive drugs with fewer side effects. In this study, we performed high-throughput prediction of AHTPs based on multi-omics data, providing an overview of AHTPs in the lined seahorse proteins and suggesting their potential application as bioactive agents to lower blood pressure. We identified 14,695 AHTP-derived genes in the lined seahorse, and most of them were supported by transcriptomic evidence, whereas only 495 genes were further detected by proteome sequencing. Among these predicted AHTP-derived genes, the longest titin had the most hits with 104 AHTPs, some of which were clustered in exon 158, 194, and 204. Another AHTP-rich group was in the collagen family, and four AHTP-rich collagens exhibited much higher transcription in the pouch than in other examined tissues, including brain, testis, and embryos. Additionally, antihypertensive triplets, comprised of the permutations of Gly, Pro, and Lys, prevailed in all collagen sequences due to the representative XaaYaaGly repeat units. In summary, our present findings provide a solid basis for understanding the abundance of various AHTPs in the lined seahorse as well as shed light on the development of antihypertensive products and drugs using seahorses as an important resource.
Improving Extreme Anchor Tension Prediction of a 10-MW Floating Semi-Submersible Type Wind Turbine, Using Highly Correlated Surge Motion Record
Authors: Gaidai Oleg , Xing Yihan , Wang Fang , Wang Shuaishuai , Yan Ping , Naess Arvid
Published: July 2022

Extreme value prediction of the load-effect responses of complex offshore structures such as the floating wind turbine (FWT) is crucial in ultimate limit state (ULS) design. This paper considers two cases to understand the feasibility of the bivariate correction on the extreme load and motion responses of a 10-MW semi-submersible type FWT. The empirical anchor tension force and surge motion used in this study are obtained from the FAST simulation tool (developed by the National Renewable Energy Laboratory) with the load cases stimulated at under-rated, rated and above rated speeds. Then, the bivariate correction method is applied to model FWT extreme response for a 5-years return period prediction with a 95% confidence interval (CI), based on just 2 min short response record. The proposed methodology permits accurate correction of the bivariate extreme value in case of, for example, corrupted measurement sensor data. Based on the proposed novel method’s performance, it is concluded that the bivariate correction method can offer better robust and precise bivariate predictions of coupled surge motion and anchor tension of the FWT.
Subfoveal Choroidal Thickness After Femtosecond Laser-Assisted Cataract Surgery for Age-Related Cataracts
Authors: Chen Wan , Chen Hui , Mi Lan , Li Jing , Lin Haotian , Chen Weirong
Published: July 2022

Purpose

To compare the effects of femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification surgery (CPS) on subfoveal choroidal thickness (SFCT) in patients with age-related cataracts.

Methods

In this prospective consecutive study, 26 patients (26 eyes) with age-related cataracts without previous ocular surgery or other ocular diseases who had FLACS were included as the study group. Twenty-six age-matched patients (26 eyes) who underwent CPS in the same period were also included as the control group. The SFCT and the foveal retinal thickness (FRT) were measured at baseline and at 1 day (D1), 7 days (D7), 1 month (M1), and 3 months (M3) postoperatively by spectral-domain optical coherence tomography. Aqueous flare was also measured with a laser flare meter.

Results

The mean SFCTs of the FLACS group at baseline and at D1, D7, M1, and M3 were 185.2, 174.3, 184.2, 180.8, and 184.1 μm, respectively. A Bonferroni posttest showed that the choroid became thinner on postoperative D1 (P = 0.006). The measurements at 1 week, 1 month, and 3 months postoperatively showed no significant differences in the SFCTs compared with that at baseline (P = 0.66, P = 0.22, and P = 0.53, respectively). A different trend was observed in the CPS group. The choroid became thicker by the 3-month postoperative measurement, as follows: 1 day (P = 0.28), 1 week (P = 0.016), 1 month (P = 0.020), and 3 months (P < 0.001).

Conclusion

The mean SFCT significantly and temporarily decreased following FLACS. In contrast, an increased SFCT was observed following CPS.
The Impact of Low-Level Viraemia on Virological Failure—Results From a Multicenter HIV Antiretroviral Therapy Cohort Study in Yunnan, China
Authors: An Jing , Lao Yunfei , Tang Songyuan , Lou Jincheng , Li Tianshu , Dong Xingqi
Published: July 2022

Background

HIV viral load (VL) is an important indicator to monitor treatment response in antiretroviral therapy (ART). Patients on ART may experience viral blips, with low-level elevations of VL between 50 and 999 copies/mL known as low-level viraemia (LLV), but not reaching the threshold for virological failure (≥1,000 copies/mL) defined by WHO guidelines. The objective was to investigate the long-term impact of LLV on virological failure.

Methods

We analyzed adults who were ART naïve at baseline. LLV was defined as having an VL of 51–999 copies/mL at least once. The subjects with LLV were grouped into three categories: 51–199, 200–399, and 400–999 copies/mL. Patients with multiple episodes of LLV were classified based on the highest VL result. The subjects with LLV were also grouped by the frequency of LLV, i.e., a single episode, two consecutive episodes, two intermittent episodes, more than two consecutive episodes, and more than two intermittent episodes. Multivariable Cox models were used to predict the association of LLV with virological failure.

Results

A total of 93,944 subjects were included. The median number of VL tests performed was 3. There were 21,203 LLV cases, with an overall incidence of 22.6%. Most of the LLV cases were found in subjects with LVs of 50–199 copies/mL, followed by 400–999 and 200–399 copies/mL. Most of the LLV cases experienced single episodes, and the numbers of LLV with two consecutive episodes, two intermittent episodes, more than two consecutive episodes and more than two intermittent episodes were decreased successively. The risk factors associated with virological failure include: intermediate-level (200–399 copies/mL) and high-level (400–999 copies/mL) LLV, single episodes of LLV and two or more than two consecutive episodes of LLV, which may put the subjects at a 1.28–2.26-fold higher risk for virological failure.

Conclusion

Strengthened immediate medical attention should be placed on patients with VL of 200–999 copies/mL. The patients having experienced LLV once should be targeted for case management and repeat VL testing within 24 weeks to determine persistent LLV and monitor virological failure.
Microbiome Research as an Effective Driver of Success Stories in Agrifood Systems – A Selection of Case Studies
Authors: Olmo Rocío , Wetzels Stefanie Urimare , Armanhi Jaderson Silveira Leite , Arruda Paulo , Berg Gabriele , Cernava Tomislav , Cotter Paul D. , Araujo Solon Cordeiro , de Souza Rafael Soares Correa , Ferrocino Ilario , Frisvad Jens C. , Georgalaki Marina , Hansen Hanne Helene , Kazou Maria , Kiran George Seghal , Kostic Tanja , Krauss-Etschmann Susanne , Kriaa Aicha , Lange Lene , Maguin Emmanuelle , Mitter Birgit , Nielsen Mette Olaf , Olivares Marta , Quijada Narciso Martín , Romaní-Pérez Marina , Sanz Yolanda , Schloter Michael , Schmitt-Kopplin Philippe , Seaton Sarah Craven , Selvin Joseph , Sessitsch Angela , Wang Mengcen , Zwirzitz Benjamin , Selberherr Evelyne , Wagner Martin
Published: July 2022

Increasing knowledge of the microbiome has led to significant advancements in the agrifood system. Case studies based on microbiome applications have been reported worldwide and, in this review, we have selected 14 success stories that showcase the importance of microbiome research in advancing the agrifood system. The selected case studies describe products, methodologies, applications, tools, and processes that created an economic and societal impact. Additionally, they cover a broad range of fields within the agrifood chain: the management of diseases and putative pathogens; the use of microorganism as soil fertilizers and plant strengtheners; the investigation of the microbial dynamics occurring during food fermentation; the presence of microorganisms and/or genes associated with hazards for animal and human health (e.g., mycotoxins, spoilage agents, or pathogens) in feeds, foods, and their processing environments; applications to improve HACCP systems; and the identification of novel probiotics and prebiotics to improve the animal gut microbiome or to prevent chronic non-communicable diseases in humans (e.g., obesity complications). The microbiomes of soil, plants, and animals are pivotal for ensuring human and environmental health and this review highlights the impact that microbiome applications have with this regard.
Optimization of Antibacterial Activity in Tibetan Swine α-Helix Peptide TP by Site-Directed Mutagenesis
Authors: Li Guoyu , Yuan Xiaojie , Chen Hongyu , Li Bowen , Shao Changxuan , Zhu Yongjie , Lai Zhenheng , Shan Anshan
Published: July 2022

Antimicrobial peptides (AMPs) have attracted extensive attention because of their broad-spectrum antibacterial activity and low level of induced bacterial resistance. However, the development of some natural AMPs does not consider the perfect balance of structural characteristics, resulting in some empirical and controversial practices still existing. To further explore and complete the relationship between parameters and function of α-helix peptide, in this study, the natural antimicrobial peptide TP secreted from Bacillus strain of Tibetan pigs was selected as a template to investigate the effect of systematic mutations in the hydrogen bond formation site of the α-helical antimicrobial peptide on the activity and cell selectivity of the antimicrobial peptide. The target peptide TP(i+4) 1&2&5 with modification of two pairs of positively charged amino acids and a pair of hydrophobic amino acids showed excellent antibacterial ability and the best selectivity index (SI = 64) in vitro. At the same time, TP(i+4) 1&2&5 remained active in the presence of physiological salts and serum. The results of fluorescence, flow cytometry, and electron microscopy showed that the optimized sequences showed good antibacterial activity by membrane infiltration and membrane destruction. The potential of TP(i+4) 1&2&5 in vivo was tested in a mouse peritonitis model. Organ bacterial loads in the liver, kidney, spleen, and lungs of mice treated with TP(i+4) 1&2&5 were significantly lower compared to the infected group (p < 0.05). Overall, these findings contribute to the design and optimization of antimicrobial peptides with high activity and low toxicity and may accelerate the clinical application of antimicrobial peptides.
Comparative Genomics of Thaumarchaeota From Deep-Sea Sponges Reveal Their Niche Adaptation
Authors: Wang Peng , Li Minchun , Dong Liang , Zhang Cheng , Xie Wei
Published: July 2022

Thaumarchaeota account for a large portion of microbial symbionts in deep-sea sponges and are even dominant in some cases. In this study, we investigated three new sponge-associated Thaumarchaeota from the deep West Pacific Ocean. Thaumarchaeota were found to be the most dominant phylum in this sponge by both prokaryotic 16S rRNA amplicons and metagenomic sequencing. Fifty-seven published Thaumarchaeota genomes from sponges and other habitats were included for genomic comparison. Similar to shallow sponge-associated Thaumarchaeota, those Thaumarchaeota in deep-sea sponges have extended genome sizes and lower coding density compared with their free-living lineages. Thaumarchaeota in deep-sea sponges were specifically enriched in genes related to stress adapting, symbiotic adhesion and stability, host–microbe interaction and protein transportation. The genes involved in defense mechanisms, such as the restriction-modification system, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system, and toxin-antitoxin system were commonly enriched in both shallow and deep sponge-associated Thaumarchaeota. Our study demonstrates the significant effects of both depth and symbiosis on forming genomic characteristics of Thaumarchaeota, and provides novel insights into their niche adaptation in deep-sea sponges.
Seasonal and Soil Microbiota Effects on the Adaptive Strategies of Wild Goitered Gazelles Based on the Gut Microbiota
Authors: Qin Wen , Song Pengfei , Zhang Shoudong
Published: July 2022

Seasonal variation in extreme environments is a threat to endangered species. The gut microbiota is important in the adaptive strategies of wild herbivores, and herbivores will contact the soil microbiota when they are feeding. However, there are no studies about the effects of soil microbiota on the gut microbiota of wild herbivores. Understanding the seasonal adaptive strategies of wild herbivores based on their gut microbiota and the effects of soil microbiota on the herbivorous gut microbiota is indispensable for making optimal conservation recommendations. To address those issues, we compared the diversity and functions of gut microbiota in goitered gazelles between winter and summer with a non-invasive fecal sampling method from the Qaidam Basin based on 16S rRNA V3–V4 regions. The data showed that seasonal variations caused the significant changes in gut microbiota at α-and β-diversity levels. The main gut microbial function was “Metabolism.” It showed significant seasonal changes. The goitered gazelles adapted to the seasonal changes by increasing the relative abundance of Firmicutes, Christensenellaceae, Bacteroides and the function about “Metabolism” in the winter to improve the adaptability. We also compared the effects of soil microbiota on the gut microbiota between winter and summer, covering source tracking analysis and the seasonal differences in ecological assembly processes. The contribution of soil microbiota on the gut microbiota of goitered gazelles was 5.3095% and 15.6347% in winter and summer, respectively, which was greater than on species of animals living underground. Seasonal variation also influenced the ecological processes of microbiota both in the gut and soil. Due to the differences in environments, the ecological processes between fecal microbiota and soil microbiota showed significant differences, and they were dominated by stochastic processes and deterministic processes, respectively. The soil microbiota has contributed to the gut microbiota, but not a decisive factor. Our research laid the foundation on the seasonal and soil microbiota effects on the adaptive strategies of goitered gazelles, and is the first study to explain the soil microbiota influence on the gut microbiota of wild herbivores.
A New Muscarine-Containing Inosperma (Inocybaceae, Agaricales) Species Discovered From One Poisoning Incident Occurring in Tropical China
Authors: Deng Lun-Sha , Yu Wen-Jie , Zeng Nian-Kai , Zhang Yi-Zhe , Wu Xiao-Peng , Li Hai-Jiao , Xu Fei , Fan Yu-Guang
Published: July 2022

Currently, mushroom poisoning still poses a huge problem to humans' health and life globally. Poisoning incidents caused by Inosperma spp. were reported continuously in tropical China in recent years. In this study, a new poisonous Inosperma species, discovered from a poisoning incident, was described in tropical China based on morphological, molecular, and toxin detection evidence; detailed descriptions, photographs, and comparisons to closely related species were provided. For qualitative analysis, through targeted screening using ultra-high liquid chromatography triple quadrupole mass spectrometry (UPLC-MS/MS), the new species contains muscarine and no other toxins (two isoxazole derivatives, two tryptamine alkaloids, three amatoxins, and three phallotoxins). For quantitative analysis, muscarine contents in the pileus and the stipe were 2.08 ± 0.05 and 6.53 ± 1.88 g/kg, respectively.
Fallow Land Enhances Carbon Sequestration in Glomalin and Soil Aggregates Through Regulating Diversity and Network Complexity of Arbuscular Mycorrhizal Fungi Under Climate Change in Relatively High-Latitude Regions
Authors: Yang Yurong , Luo Wenbo , Xu Jiazheng , Guan Pingting , Chang Liang , Wu Xuefeng , Wu Donghui
Published: July 2022

Soil aggregation and aggregate-associated carbon (C) play an essential function in soil health and C sequestration. Arbuscular mycorrhizal fungi (AMF) are considered to be primary soil aggregators due to the combined effect of extraradical hyphae and glomalin-related soil proteins (GRSPs). However, the effects of diversity and network complexity of AMF community on stability of soil aggregates and their associated C under long-term climate change (CC) and land-use conversion (LUC) in relatively high-latitude regions are largely unexplored. Therefore, an 8-year soil plot (with a 30-year cropping history) transplantation experiment was conducted to simulate CC and LUC from cropland to fallow land. The results showed that Glomus, Paraglomus, and Archaeospora were the most abundant genera. The diversity of AMF community in fallow land was higher than cropland and increased with increasing of mean annual temperature (MAT) and mean annual precipitation (MAP). Fallow land enhanced the network complexity of AMF community. The abundance families (Glomeraceae and Paraglomeraceae) exhibited higher values of topological features and were more often located in central ecological positions. Long-term fallow land had a significantly higher hyphal length density, GRSP, mean weight diameter (MWD), geometric mean diameter (GMD), and C concentration of GRSP (C-GRSP) than the cropland. The soil aggregate associated soil organic carbon (SOC) was 16.8, 18.6, and 13.8% higher under fallow land compared to that under cropland at HLJ, JL, and LN study sites, respectively. The structural equation model and random forest regression revealed that AMF diversity, network complexity, and their secreted GRSP mediate the effects of CC and LUC on C-GRSP and aggregate-associated SOC. This study elucidates the climate sensitivity of C within GRSP and soil aggregates which response symmetry to LUC and highlights the potential importance of AMF in C sequestration and climate change mitigation.
Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material
Authors: Matejtschuk Paul , Bird Christopher , Ezeajughi Ernest , MacLellan-Gibson Kirsty , Wadhwa Meenu
Published: July 2022

Formulation is critical to successful delivery of lyophilized biologics. We have compared the impact of buffer choice and the addition of sodium chloride (a formulant often viewed as unfavorable for freeze-drying applications) on the outcome of trial lyophilization of an interleukin-6 reference material. While phosphate buffer was a preferred choice and yielded well-formed cakes associated with fair recovery of biological activity, the resultant residual moisture content was high (2–4% w/w). By inclusion of isotonic levels of NaCl, the freeze-dried appearance and process were not impaired, but the residual moisture delivered was considerably reduced to levels <1% w/w. We postulate that this is due to the presence of a more open-cake structure and support this with evidence from thermal analysis and scanning electron microscopy. This work illustrates the importance of wide ranging empirical investigation of formulation options in order to optimize freeze-drying outcomes for biologics.
Development of Molecular Mechanisms and Their Application on Oncolytic Newcastle Disease Virus in Cancer Therapy
Authors: Huang Fang , Dai Chuanjing , Zhang Youni , Zhao Yuqi , Wang Yigang , Ru Guoqing
Published: July 2022

Cancer is caused by the destruction or mutation of cellular genetic materials induced by environmental or genetic factors. It is defined by uncontrolled cell proliferation and abnormality of the apoptotic pathways. The majority of human malignancies are characterized by distant metastasis and dissemination. Currently, the most common means of cancer treatment include surgery, radiotherapy, and chemotherapy, which usually damage healthy cells and cause toxicity in patients. Targeted therapy is an effective tumor treatment method with few side effects. At present, some targeted therapeutic drugs have achieved encouraging results in clinical studies, but finding an effective solution to improve the targeting and delivery efficiency of these drugs remains a challenge. In recent years, oncolytic viruses (OVs) have been used to direct the tumor-targeted therapy or immunotherapy. Newcastle disease virus (NDV) is a solid oncolytic agent capable of directly killing tumor cells and increasing tumor antigen exposure. Simultaneously, NDV can trigger the proliferation of tumor-specific immune cells and thus improve the therapeutic efficacy of NDV in cancer. Based on NDV’s inherent oncolytic activity and the stimulation of antitumor immune responses, the combination of NDV and other tumor therapy approaches can improve the antitumor efficacy while reducing drug toxicity, indicating a broad application potential. We discussed the biological properties of NDV, the antitumor molecular mechanisms of oncolytic NDV, and its application in the field of tumor therapy in this review. Furthermore, we presented new insights into the challenges that NDV will confront and suggestions for increasing NDV’s therapeutic efficacy in cancer.
Retinal Neurovascular Changes in Patients With Ischemic Stroke Investigated by Optical Coherence Tomography Angiography
Authors: Liang Yingying , Liu Baoyi , Xiao Yu , Zeng Xiaomin , Wu Guanrong , Du Zijing , Fang Ying , Hu Yijun , Yang Xiaohong , Yu Honghua
Published: July 2022

Background

To investigate retinal neurovascular structural changes in patients with ischemic stroke (IS) using optical coherence tomography angiography (OCTA).

Materials and Methods

The cross-sectional study was conducted in Guangdong Provincial People’s Hospital, China, consisting of 159 eyes from IS patients and 109 eyes from age-matched control subjects. Retinal microvascular parameters including the vessel density (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillary (RPC), and neural parameters such as ganglion cell complex thickness (GCCt) and retinal nerve fibre layer thickness (RNFLt) were measured by OCTA.

Results

The VD of SCP and DCP in the macular area were significantly reduced in IS patients compared to the control group (all p < 0.001). The VD of RPC at the optic disc was also significantly reduced in IS patients (all p < 0.05). IS patients showed reduced GCCt and RNFLt and increased GCC focal loss volume and global loss volume compared with the controls (all p < 0.05). Among patients with IS, the parafovea SCP VD was positively correlated with GCCt (r = 0.346–0.408, all p < 0.001) but not with DCP VD (all p > 0.1). In the optic disc region, the whole image RPC VD was positively correlated with mean RNFLt (r = 0.467–0.548, all p < 0.001).

Conclusion

Reduction of retinal VD, GCCt and RNFLt was observed in patients with IS. The parafovea SCP VD and RPC VD were positively correlated with GCCt and RNFLt, respectively.
Pre-clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson's Disease: A Systematic Review
Authors: Fathi Mobina , Vakili Kimia , Yaghoobpoor Shirin , Qadirifard Mohammad Sadegh , Kosari Mohammadreza , Naghsh Navid , Asgari taei Afsaneh , Klegeris Andis , Dehghani Mina , Bahrami Ashkan , Taheri Hamed , Mohamadkhani Ashraf , Hajibeygi Ramtin , Rezaei Tavirani Mostafa , Sayehmiri Fatemeh
Published: July 2022

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by neuroinflammation, formation of Lewy bodies, and progressive loss of dopaminergic neurons in the substantia nigra of the brain. In this review, we summarize evidence obtained by animal studies demonstrating neuroinflammation as one of the central pathogenetic mechanisms of PD. We also focus on the protein factors that initiate the development of PD and other neurodegenerative diseases. Our targeted literature search identified 40 pre-clinicalin vivoandin vitrostudies written in English. Nuclear factorkappaB (NF-kB) pathway is demonstrated as a common mechanism engaged by neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), as well as the bacterial lipopolysaccharide (LPS). The α-synuclein protein, which plays a prominent role in PD neuropathology, may also contribute to neuroinflammation by activating mast cells. Meanwhile, 6-OHDA models of PD identify microsomal prostaglandin E synthase-1 (mPGES-1) as one of the contributors to neuroinflammatory processes in this model. Immune responses are used by the central nervous system to fight and remove pathogens; however, hyperactivated and prolonged immune responses can lead to a harmful neuroinflammatory state, which is one of the key mechanisms in the pathogenesis of PD.
Emerging Memristive Devices for Brain-Inspired Computing and Artificial Perception
Authors: Wang Jingyu , Zhu Ying , Zhu Li , Chen Chunsheng , Wan Qing
Published: July 2022

Brain-inspired computing is an emerging field that aims at building a compact and massively parallel architecture, to reduce power consumption in conventional Von Neumann Architecture. Recently, memristive devices have gained great attention due to their immense potential in implementing brain-inspired computing and perception. The conductance of a memristor can be modulated by a voltage pulse, enabling emulations of both essential synaptic and neuronal functions, which are considered as the important building blocks for artificial neural networks. As a result, it is critical to review recent developments of memristive devices in terms of neuromorphic computing and perception applications, waiting for new thoughts and breakthroughs. The device structures, operation mechanisms, and materials are introduced sequentially in this review; additionally, late advances in emergent neuromorphic computing and perception based on memristive devices are summed up. Finally, the challenges that memristive devices toward high-performance brain-inspired computing and perception are also briefly discussed. We believe that the advances and challenges will lead to significant advancements in artificial neural networks and intelligent humanoid robots.