bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of local and systemic immunity in ovarian cancer: Implications for immunotherapy
Authors: Rajtak Alicja , Ostrowska-Leśko Marta , Żak Klaudia , Tarkowski Rafał , Kotarski Jan , Okła Karolina
Published: November 2022

Cancer is a disease that induces many local and systemic changes in immunity. The difficult nature of ovarian cancer stems from the lack of characteristic symptoms that contributes to a delayed diagnosis and treatment. Despite the enormous progress in immunotherapy, its efficacy remains limited. The heterogeneity of tumors, lack of diagnostic biomarkers, and complex immune landscape are the main challenges in the treatment of ovarian cancer. Integrative approaches that combine the tumor microenvironment – local immunity – together with periphery – systemic immunity – are urgently needed to improve the understanding of the disease and the efficacy of treatment. In fact, multiparametric analyses are poised to improve our understanding of ovarian tumor immunology. We outline an integrative approach including local and systemic immunity in ovarian cancer. Understanding the nature of both localized and systemic immune responses will be crucial to boosting the efficacy of immunotherapies in ovarian cancer patients.
In silico analysis of alternative splicing events implicated in intracellular trafficking during B-lymphocyte differentiation
Authors: Ostwaldt Felix , Los Bruna , Heyd Florian
Published: November 2022

There are multiple regulatory layers that control intracellular trafficking and protein secretion, ranging from transcriptional to posttranslational mechanisms. Finely regulated trafficking and secretion is especially important for lymphocytes during activation and differentiation, as the quantity of secretory cargo increases once the activated cells start to produce and secrete large amounts of cytokines, cytotoxins, or antibodies. However, how the secretory machinery dynamically adapts its efficiency and specificity in general and specifically in lymphocytes remains incompletely understood. Here we present a systematic bioinformatics analysis to address RNA-based mechanisms that control intracellular trafficking and protein secretion during B-lymphocyte activation, and differentiation, with a focus on alternative splicing. Our in silico analyses suggest that alternative splicing has a substantial impact on the dynamic adaptation of intracellular traffic and protein secretion in different B cell subtypes, pointing to another regulatory layer to the control of lymphocyte function during activation and differentiation. Furthermore, we suggest that NERF/ELF2 controls the expression of some COPII-related genes in a cell type-specific manner. In addition, T cells and B cells appear to use different adaptive strategies to adjust their secretory machineries during the generation of effector and memory cells, with antibody secreting B cell specifically increasing the expression of components of the early secretory pathway. Together, our data provide hypotheses how cell type-specific regulation of the trafficking machinery during immune cell activation and differentiation is controlled that can now be tested in wet lab experiments.
Manipulation of the crosstalk between tumor angiogenesis and immunosuppression in the tumor microenvironment: Insight into the combination therapy of anti-angiogenesis and immune checkpoint blockade
Authors: Zheng Weiwei , Qian Cheng , Tang Yu , Yang Chunmei , Zhou Yueke , Shen Peiliang , Chen Wenxing , Yu Suyun , Wei Zhonghong , Wang Aiyun , Lu Yin , Zhao Yang
Published: November 2022

Immunotherapy has been recognized as an effective and important therapeutic modality for multiple types of cancer. Nevertheless, it has been increasing recognized that clinical benefits of immunotherapy are less than expected as evidenced by the fact that only a small population of cancer patients respond favorably to immunotherapy. The structurally and functionally abnormal tumor vasculature is a hallmark of most solid tumors and contributes to an immunosuppressive microenvironment, which poses a major challenge to immunotherapy. In turn, multiple immune cell subsets have profound consequences on promoting neovascularization. Vascular normalization, a promising anti-angiogenic strategy, can enhance vascular perfusion and promote the infiltration of immune effector cells into tumors via correcting aberrant tumor blood vessels, resulting in the potentiation of immunotherapy. More interestingly, immunotherapies are prone to boost the efficacy of various anti-angiogenic therapies and/or promote the morphological and functional alterations in tumor vasculature. Therefore, immune reprograming and vascular normalization appear to be reciprocally regulated. In this review, we mainly summarize how tumor vasculature propels an immunosuppressive phenotype and how innate and adaptive immune cells modulate angiogenesis during tumor progression. We further highlight recent advances of anti-angiogenic immunotherapies in preclinical and clinical settings to solidify the concept that targeting both tumor blood vessels and immune suppressive cells provides an efficacious approach for the treatment of cancer.
Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease
Authors: Ratnatunga Champa N. , Tungatt Katie , Proietti Carla , Halstrom Sam , Holt Michael R. , Lutzky Viviana P. , Price Patricia , Doolan Denise L. , Bell Scott C. , Field Matt A. , Kupz Andreas , Thomson Rachel M. , Miles John J.
Published: November 2022

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic, progressive, and growing worldwide health burden associated with mounting morbidity, mortality, and economic costs. Improvements in NTM-PD management are urgently needed, which requires a better understanding of fundamental immunopathology. Here, we examine temporal dynamics of the immune compartment during NTM-PD caused by Mycobacterium avium complex (MAC) and Mycobactereoides abscessus complex (MABS). We show that active MAC infection is characterized by elevated T cell immunoglobulin and mucin-domain containing-3 expression across multiple T cell subsets. In contrast, active MABS infection was characterized by increased expression of cytotoxic T-lymphocyte-associated protein 4. Patients who failed therapy closely mirrored the healthy individual immune phenotype, with circulating immune network appearing to ‘ignore’ infection in the lung. Interestingly, immune biosignatures were identified that could inform disease stage and infecting species with high accuracy. Additionally, programmed cell death protein 1 blockade rescued antigen-specific IFN-γ secretion in all disease stages except persistent infection, suggesting the potential to redeploy checkpoint blockade inhibitors for NTM-PD. Collectively, our results provide new insight into species-specific ‘immune chatter’ occurring during NTM-PD and provide new targets, processes and pathways for diagnostics, prognostics, and treatments needed for this emerging and difficult to treat disease.
Impact of ATP-citrate lyase catalytic activity and serine 455 phosphorylation on histone acetylation and inflammatory responses in human monocytic THP-1 cells
Authors: Dominguez Monica , Truemper Verena , Mota Ana Carolina , Brüne Bernhard , Namgaladze Dmitry
Published: November 2022

ATP-citrate lyase (ACLY) is a key enzyme provoking metabolic and epigenetic gene regulation. Molecularly, these functions are exerted by the provision of acetyl-coenzyme A, which is then used as a substrate for de novo lipogenesis or as an acetyl-group donor in acetylation reactions. It has been demonstrated that ACLY activity can be positively regulated via phosphorylation at serine 455 by Akt and protein kinase A. Nonetheless, the impact of phosphorylation on ACLY function in human myeloid cells is poorly understood. In this study we reconstituted ACLY knockout human monocytic THP-1 cells with a wild type ACLY as well as catalytically inactive H760A, and phosphorylation-deficient S455A mutants. Using these cell lines, we determined the impact of ACLY activity and phosphorylation on histone acetylation and pro-inflammatory gene expression in response to lipopolysaccharide (LPS). Our results show that ACLY serine 455 phosphorylation does not influence the proper enzymatic function of ACLY, since both, wild type ACLY and phosphorylation-deficient mutant, exhibited increased cell growth and histone acetylation as compared to cells with a loss of ACLY activity. Transcriptome analysis revealed enhanced expression of pro-inflammatory and interferon response genes in ACLY knockout and H760A THP-1 cells under unstimulated or LPS-treated conditions. At the same time, S455A ACLY-expressing cells showed a phenotype very similar to wild type cells. Contrary to ACLY knockout, pharmacological inhibition of ACLY in THP-1 cells or in primary human macrophages does not enhance LPS-triggered pro-inflammatory gene expression. Our data thus suggest that ACLY retains functionality in the absence of Akt/PKA-mediated phosphorylation in human myeloid cells. Furthermore, loss of ACLY activity may elicit long-term adaptive mechanisms, increasing inflammatory responses.
Central nervous system commitment in Chagas disease
Authors: Useche Yerly , Pérez Ana Rosa , de Meis Juliana , Bonomo Adriana , Savino Wilson
Published: November 2022

The involvement of the central nervous system (CNS) during human acute and chronic Chagas disease (CD) has been largely reported. Meningoencephalitis is a frequent finding during the acute infection, while during chronic phase the CNS involvement is often accompanied by behavioral and cognitive impairments. In the same vein, several studies have shown that rodents infected with Trypanosoma cruzi (T. cruzi) display behavior abnormalities, accompanied by brain inflammation, in situ production of pro-inflammatory cytokines and parasitism in diverse cerebral areas, with involvement of microglia, macrophages, astrocytes, and neurons. However, the mechanisms used by the parasite to reach the brain remain now largely unknown. Herein we discuss the evidence unravelling the CNS involvement and complexity of neuroimmune interactions that take place in acute and chronic CD. Also, we provide some clues to hypothesize brain infections routes in human and experimental acute CD following oral infection by T. cruzi, an infection route that became a major CD related public health issue in Brazil.
Barcode clonal tracking of tissue-resident immune cells in rhesus macaque highlights distinct clonal distribution pattern of tissue NK cells
Authors: Wu Chuanfeng , Liang Jialiu A. , Brenchley Jason M. , Shin Taehoon , Fan Xing , Mortlock Ryland D. , Abraham Diana M. , Allan David S.J. , Thomas Marvin L. , Hong So Gun , Dunbar Cynthia E.
Published: November 2022

Tissue resident (TR) immune cells play important roles in facilitating tissue homeostasis, coordinating immune responses against infections and tumors, and maintaining immunological memory. While studies have shown these cells are distinct phenotypically and functionally from cells found in the peripheral blood (PB), the clonal relationship between these populations across tissues has not been comprehensively studied in primates or humans. We utilized autologous transplantation of rhesus macaque hematopoietic stem and progenitor cells containing high diversity barcodes to track the clonal distribution of T, B, myeloid and natural killer (NK) cell populations across tissues, including liver, spleen, lung, and gastrointestinal (GI) tract, in comparison with PB longitudinally post-transplantation, in particular we focused on NK cells which do not contain endogenous clonal markers and have not been previously studied in this context. T cells demonstrated tissue-specific clonal expansions as expected, both overlapping and distinct from blood T cells. In contrast, B and myeloid cells showed a much more homogeneous clonal pattern across various tissues and the blood. The clonal distribution of TR NK was more heterogenous between individual animals. In some animals, as we have previously reported, we observed large PB clonal expansions in mature CD56-CD16+ NK cells. Notably, we found a separate set of highly expanded PB clones in CD16-CD56- (DN) NK subset that were also contributing to TR NK cells in all tissues examined, both in TR CD56-CD16+ and DN populations but absent in CD56+16- TR NK across all tissues analyzed. Additionally, we observed sets of TR NK clones specific to individual tissues such as lung or GI tract and sets of TR NK clones shared across liver and spleen, distinct from other tissues. Combined with prior functional data that suggests NK memory is restricted to liver or other TR NK cells, these clonally expanded TR NK cells may be of interest for future investigation into NK cell tissue immunological memory, with implications for development of NK based immunotherapies and an understanding of NK memory.
Dorsal switch protein 1 as a damage signal in insect gut immunity to activate dual oxidase via an eicosanoid, PGE2
Authors: Roy Miltan Chandra , Ahmed Shabbir , Kim Yonggyun
Published: November 2022

Various microbiota including beneficial symbionts reside in the insect gut. Infections of pathogens cause dysregulation of the microflora and threaten insect survival. Reactive oxygen species (ROS) have been used in the gut immune responses, in which its production is tightly regulated by controlling dual oxidase (Duox) activity via Ca2+ signal to protect beneficial microflora and gut epithelium due to its high cytotoxicity. However, it was not clear how the insects discriminate the pathogens from the various microbes in the gut lumen to trigger ROS production. An entomopathogenic nematode (Steinernema feltiae) infection elevated ROS level in the gut lumen of a lepidopteran insect, Spodoptera exigua. Dorsal switch protein 1 (DSP1) localized in the nucleus in the midgut epithelium was released into plasma upon the nematode infection and activated phospholipase A2 (PLA2). The activated PLA2 led to an increase of PGE2 level in the midgut epithelium, in which rising Ca2+ signal up-regulated ROS production. Inhibiting DSP1 release by its specific RNA interference (RNAi) or specific inhibitor, 3-ethoxy-4-methoxyphenol, treatment failed to increase the intracellular Ca2+ level and subsequently prevented ROS production upon the nematode infection. A specific PLA2 inhibitor treatment also prevented the up-regulation of Ca2+ and subsequent ROS production upon the nematode infection. However, the addition of PGE2 to the inhibitor treatment rescued the gut immunity. DSP1 release was not observed at infection with non-pathogenic pathogens but detected in plasma with pathogenic infections that would lead to damage to the gut epithelium. These results indicate that DSP1 acts as a damage-associated molecular pattern in gut immunity through DSP1/PLA2/Ca2+/Duox.
Light response of Vibrio parahaemolyticus
Authors: Kuroyanagi Yunato , Tsuchiya Jiro , Jiang Chunqi , Mino Sayaka , Kasai Hisae , Motooka Daisuke , Iida Tetsuya , Satomi Masataka , Sawabe Tomoo
Published: November 2022

Light is one of the most critical stimuli in the majority of living organisms. In the last two decades, blue light (BL) has become a major subject of attention because of developments in light-emitting diodes (LED). The effects of BL on eukaryotic organisms and phototrophic prokaryotes have been well studied, but the knowledge of its effects on non-phototrophic prokaryotes remains unclear. Since BL can penetrate seawater, it is expected that most prokaryotes living in the ocean possess molecular mechanisms which protect against BL. The aim of this study is to assess the molecular mechanisms ofVibrio parahaemolyticuscells against BL as a marine bacterial model compared to other wavelength light exposures. Physiological and transcriptomic analyses of BL-exposed cells compared to other light treated cells revealed the highest ROS fold change, the highest number of differentially expressed genes (DEGs), and up-regulation in the gene responsible to not only compatible solute such as glycine betaine and ectoine but also iron-sulfur biosynthesis related to ROS formation. Furthermore, red light (RL) up-regulated the expression of cryptochrome DASH, a protein known to be excited by BL, and orange light (OL) decreased the expression of thermostable direct hemolysin (TDH), suggesting that OL attenuates the virulence ofV. parahaemolyticus. In addition, the expression of VtrA (V. parahaemolyticustype III secretion system 2 (T3SS2) regulator A) but not VtrB (V. parahaemolyticusT3SS2 regulator B) increased under both light treatments, indicating that light exposure is unlikely to be involved in T3SS2-mediated pathogenicity. These results expand our knowledge on unique light responses in non-phototrophic marine prokaryotes.
The clinical efficacy of pure-grind acellular dermal matrix without gelatin in lower extremity skin defect treatment: A prospective randomized study
Authors: Kim Min Ji , Jeong Yon Soo , Kim Tae Wook , Park Dong Ha , Lee Il Jae
Published: November 2022

Background: Acellular dermal matrix (ADM) is currently considered as a replacement for lost extracellular matrix. Trials have been conducted on dressing materials with high contents of ADM without any impurities, such as gelatin, which only undergo the grinding process. In this study, we aimed to investigate the clinical application and wound healing effect of pure-grind ADM in lower extremity skin defect treatment.

Methods: Patients with skin defects in the lower extremities who did not achieve wound healing within 4 weeks with conservative treatment were enrolled in this study from March 2021 to July 2021. We randomized the patients into two groups. The patients in the experimental group were treated with pure-grind ADM and conventional negative-pressure wound therapy (NPWT), whereas the patients in the control group were only treated with NPWT. Every wound was followed-up for 7 weeks, and complete wound healing was confirmed when the skin defect was fully covered with epithelized tissue.

Results: A total of 41 patients were enrolled in this study. Complete wound healing was observed in 73.2% of patients, and 26.8% had an unhealed status until the end of the follow-up. The pure-grind ADM did not promote complete healing (p = 0.796) and was not associated with epithelization time but promoted the velocity of epithelization (experimental 5.58 vs. 3.50 cm2/day, p = 0.020). Considering the time of healing, the decrease in wound depth was more extensive (p = 0.021), the speed of granulation tissue formation was higher, and this difference was more evident after 5 weeks of treatment in the experimental group.

Conclusion: We demonstrated the clinical efficacy of pure-grind ADM in treatment of lower extremity skin defects. This new type of ADM, without any impurities, is important in wound healing. Its depth filling effect is powerful, and it can promote epithelization velocity and speed of granulation tissue formation.
Transition of electrochemical measurement to machine learning in the perspective of two-dimensional materials
Authors: Jitapunkul Kulpavee , Chenwittayakhachon Apiphu , Iamprasertkun Pawin
Published: November 2022

Two-dimensional materials (e.g. graphene, and transition metal dichalcogenides) have become ubiquitous in electrochemical contexts including energy storage, electrocatalyst, and ion-selective membranes. This is due to its superior electrochemical properties, specifically “capacitance”, which can be referred to the storage ions at the electrolyte/materials interfaces. Experimental work and computational chemistry were carried out in the past decade for solving and improving the understanding of two-dimensional materials; however, these techniques are relatively expensive, complex, and time-consuming. Therefore, we accentuate the future trend of two-dimensional material study with machine learning as the modest alternative. In this perspective, the intrinsic capacitance properties of the two dimension materials were described from an atomic level, explaining the heteroatom doping to a nanoscopic level, showing (basal vs edge capacitance). The studies also extended to the macroscopic level i.e., the flake size of the two-dimensional materials. We then shed more light on the applicability of machine learning coupled with the “fundamental measurement” for solving electrochemistry of two-dimensional materials. The shallow artificial neural network was demonstrated for the prediction of CV curves using the data from size-dependent graphene. In addition, the application of deep neural networks with complicated architecture has also been explored through the prediction of capacitance for heteroatom-doped graphene. This perspective provides a clear background and creates the connection between fundamental measurement and machine learning for understanding the capacitance properties of two-dimensional materials.
Poly (ADP-ribose) polymerases as PET imaging targets for central nervous system diseases
Authors: Tong Jie , Chen Baosheng , Tan Peng Wen , Kurpiewski Stephen , Cai Zhengxin
Published: November 2022

Poly (ADP-ribose) polymerases (PARPs) constitute of 17 members that are associated with divergent cellular processes and play a crucial role in DNA repair, chromatin organization, genome integrity, apoptosis, and inflammation. Multiple lines of evidence have shown that activated PARP1 is associated with intense DNA damage and irritating inflammatory responses, which are in turn related to etiologies of various neurological disorders. PARP1/2 as plausible therapeutic targets have attracted considerable interests, and multitudes of PARP1/2 inhibitors have emerged for treating cancer, metabolic, inflammatory, and neurological disorders. Furthermore, PARP1/2 as imaging targets have been shown to detect, delineate, and predict therapeutic responses in many diseases by locating and quantifying the expression levels of PARP1/2. PARP1/2-directed noninvasive positron emission tomography (PET) has potential in diagnosing and prognosing neurological diseases. However, quantitative PARP PET imaging in the central nervous system (CNS) has evaded us due to the challenges of developing blood-brain barrier (BBB) penetrable PARP radioligands. Here, we review PARP1/2's relevance in CNS diseases, summarize the recent progress on PARP PET and discuss the possibilities of developing novel PARP radiotracers for CNS diseases.
The diagnostic value of interleukin 35 as a septic biomarker: A meta-analysis
Authors: Hu Yuanhui , Tang Dongling , Zhang Pingan
Published: November 2022

Background

There is growing evidence that interleukin 35 (IL-35) represents a potential diagnostic biomarker for sepsis. The purpose of this meta-analysis was to evaluate the overall diagnostic accuracy of IL-35 in sepsis.

Materials and methods

From October 1998 to May 2022, set retrieval standards were used to search literature Databases. Each included study was assessed diagnostic accuracy study quality assessment tool. Two researchers independently extracted the data and research features. If there are differences, the issue will be resolved by mutual agreement. Meta-disc and Stata software were utilized to calculate combined sensitivity, specificity, and summary diagnostic odds ratio (SDOR), I2, or Cochrane Q in order to detection for heterogeneity, and meta-regression was performed to figure out the cause of heterogeneity. Utilizing funnel plots, we tested for publication bias.

Results

In this meta-analysis, eight publications were included. The combined sensitivity, specificity, and DOR were 0.87 (95% CI, 0.77–0.93), 0.73 (95% CI, 0.60–0.83), and 18.26 (95% CI, 9.70–34.37), respectively. In addition, 0.88 (95% CI, 0.84–0.90) was the area under the summary receiver operating characteristic curve. In the heterogeneity analysis, the sensitivity of comprehensive I2 statistic was 84.38, and the specificity was 87.82. Deeks’ funnel plot showed no publication bias in this meta-analysis (P = 0.17). A meta-analysis revealed that IL-35 has a modest sensitivity (AUC = 0.88) for diagnosing sepsis. We also compared the diagnostic accuracy of IL-35 and procalcitonin (PCT), and our results showed that the diagnostic accuracy parameters for IL-35 were significantly higher than those for PCT.

Conclusion

Interleukin 35 is a valuable biomarker for the early detection of sepsis. However, the data should be combined with clinical symptoms, signs, and laboratory and microbiological findings.
Elevational changes in the bacterial community composition and potential functions in a Tibetan grassland
Authors: Li Yaoming , Fang Zhen , Yang Fan , Ji Baoming , Li Xiangzhen , Wang Shiping
Published: November 2022

In the Tibetan grasslands, the distribution patterns of the microbial community structure and function along elevation gradients have attracted considerable attention due to the wide distribution of mountain slopes, but the controlling factors of these patterns are still unclear. Here we investigated the taxonomy and potential functions of soil bacteria along an elevation gradient in a Tibetan mountainous grassland in 2 years, aiming to explore the elevation patterns of the bacterial structure and function and the underlying drivers. High-throughput sequencing and environment attribute measurements were conducted to survey the bacterial and environment characters. Furthermore, PICRUSt2 for prediction of bacterial functions, iCAMP for unraveling the drivers controlling community assembly, and HMSC for variance partitioning of bacterial community composition were used. Elevation did not significantly affect the bacterial diversity but changed their composition, driven by both deterministic and stochastic processes. In addition, elevation did not significantly affect the relative importance of deterministic and stochastic processes. Soil carbon, nitrogen, and temperature were important deterministic factors in driving bacterial community structure. The genus Solirubrobacter in Actinobacteriota was identified as most elevation discriminatory. Based on these observations, the bacterial community in the Tibetan mountainous grasslands was more controlled by edaphic factors than temperature, indicating their relative stability under climate change scenarios.
Roux-en-Y gastric bypass-induced perturbative changes in microbial communities and metabolic pathways in rats
Authors: Yang Jing , Chen Lei , Shang Xue-Ying , Chen Yi-Lin , Zhao Shan-Shan , Jin Shi , Yang Jing , Liu Hui-Xin , Du Jian
Published: November 2022

Background

Obesity has become a global health and socioeconomic problem because of an inadequate balance between energy intake and energy expenditure. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the two most commonly used strategies for weight loss, which have been proven to benefit from gut microbiota restoration.

Methods

Rats received SG, RYGB, and sham operations for 10 weeks. At the end of the experiment, the fecal microbiota was analyzed using 16s rRNA gene sequencing. In addition, the shift in the plasma metabolism of rats that underwent RYGB surgery was analyzed using untargeted metabolomics. The crosstalk between microbiome and metabolites was revealed using metabolic pathway enrichment and integrated analysis.

Result

The SG surgery induced a modest shift in the gut microbiota relative to the RYGB. RYGB significantly decreased the alpha diversity and Firmicutes/Bacteroides (F/B) ratio and increased the proportion of Escherichia, Bacteroides, and Akkermansia genera compared to sham and SG operations. The predicted function of gut microbiota revealed that the RYGB surgery uniquely enhanced the capability of linoleic acid and sphingolipid metabolism. Furthermore, the circulating serine, phosphatidylcholine (PC) 20:5/22:5, riboflavin, L–carnitine, and linoleic acid were evaluated after RYGB surgery. In addition, the metabolic pathway enrichment and integrated analysis suggest that the RYGB induced Escherichia, Bacteroides, and Akkermansia might inhibit the sphingonine and phytosphingosine metabolisms from serine and promote the PC (20:5/22:5) metabolism to produce linoleic acid.

Conclusion

This comprehensive analysis not only revealed the difference in the gut microbiota shifts after SG and RYGB but also discovered the perturbative changes in microbial communities and metabolic pathways after RYGB surgery, which provided clues for improving the beneficial effect of RYGB in metabolic disease intervention via regulating bacterial-metabolite crosstalk.
Global trends in Akkermansia muciniphila research: A bibliometric visualization
Authors: Li Zitong , Ke Haoran , Wang Ying , Chen Shuze , Liu Xiuying , Lin Qianyun , Wang Pu , Chen Ye
Published: November 2022

Background

Akkermansia muciniphila is a member of the gut microbiome, using mucin as sources of carbon, nitrogen, and energy. Since the first discovery of this unique bacterium in 2004, A. muciniphila has been extensively studied. It is considered a promising “next-generation beneficial microbe.” The purpose of this paper is to sort out the research status and summarize the hotspots through bibliometric analysis of the publications of A. muciniphila.

Methods

The publications about A. muciniphila from January 2004 to February 2022 were obtained from the Web of Science Core Collection. Visualization analyses were performed using three bibliometric tools and GraphPad Prism.

Results

A total of 1,478 published documents were analyzed. Annual publication number grew from 1 in 2004 to 336 in 2021, with China being the leading producer (33.36%). De Vos, Willem M was the most productive author with the highest H-index (documents = 56, H-index = 37), followed by Cani, Patrice D (documents = 35, H-index = 25). And Scientific Reports published the most papers. PNAS was the keystone taxa in this field, with high betweenness centrality (0.11) and high frequency. The keywords with high frequency in recent years include: oxidative stress, diet, metformin, fecal microbiota transplantation, short-chain fatty acids, polyphenols, microbiota metabolites and so on. The keyword “oxidative stress” was observed to be increasing in frequency recently.

Conclusion

Over time, the scope of the research on the clinical uses of A. muciniphila has gradually increased, and was gradually deepened and developed toward a more precise level. A. muciniphila is likely to remain a research hotspot in the foreseeable future and may contribute to human health.
Experimental warming increases fungal alpha diversity in an oligotrophic maritime Antarctic soil
Authors: Newsham Kevin K. , Misiak Marta , Goodall-Copestake William P. , Dahl Malin Stapnes , Boddy Lynne , Hopkins David W. , Davey Marie L.
Published: November 2022

The climate of maritime Antarctica has altered since the 1950s. However, the effects of increased temperature, precipitation and organic carbon and nitrogen availability on the fungal communities inhabiting the barren and oligotrophic fellfield soils that are widespread across the region are poorly understood. Here, we test how warming with open top chambers (OTCs), irrigation and the organic substrates glucose, glycine and tryptone soy broth (TSB) influence a fungal community inhabiting an oligotrophic maritime Antarctic fellfield soil. In contrast with studies in vegetated soils at lower latitudes, OTCs increased fungal community alpha diversity (Simpson’s index and evenness) by 102–142% in unamended soil after 5 years. Conversely, OTCs had few effects on diversity in substrate-amended soils, with their only main effects, in glycine-amended soils, being attributable to an abundance ofPseudogymnoascus. The substrates reduced alpha and beta diversity metrics by 18–63%, altered community composition and elevated soil fungal DNA concentrations by 1–2 orders of magnitude after 5 years. In glycine-amended soil, OTCs decreased DNA concentrations by 57% and increased the relative abundance of the yeastVishniacozymaby 45-fold. The relative abundance of the yeastGelidatremadeclined by 78% in chambered soil and increased by 1.9-fold in irrigated soil. Fungal DNA concentrations were also halved by irrigation in TSB-amended soils. In support of regional- and continental-scale studies across climatic gradients, the observations indicate that soil fungal alpha diversity in maritime Antarctica will increase as the region warms, but suggest that the accumulation of organic carbon and nitrogen compounds in fellfield soils arising from expanding plant populations are likely, in time, to attenuate the positive effects of warming on diversity.
Disrupted gut microbiota aggravates working memory dysfunction induced by high-altitude exposure in mice
Authors: Zhao Zhifang , Cui Dejun , Wu Guosong , Ren Hong , Zhu Ximei , Xie Wenting , Zhang Yuming , Yang Liu , Peng Weiqi , Lai Chunxiao , Huang Yongmei , Li Hao
Published: November 2022

Background

The widely accepted microbiome-gut-brain axis (MGBA) hypothesis may be essential for explaining the impact of high-altitude exposure on the human body, especially brain function. However, studies on this topic are limited, and the underlying mechanism remains unclear. Therefore, this study aimed to determine whether high-altitude-induced working memory dysfunction could be exacerbated with gut microbiota disruption.

Methods and results

C57BL/6 mice were randomly divided into three groups: control, high-altitude exposed (HAE), and high-altitude exposed with antibiotic treatment (HAE-A). The HAE and HAE-A groups were exposed to a low-pressure oxygen chamber (60–65 kPa) simulating the altitude of 3,500–4,000 m for 14 days, The air pressure level for the control group was maintained at 94.5 kPa. Antibiotic water (mixed with 0.2 g/L of ciprofloxacin and 1 g/L of metronidazole) was provided to the HAE-A group. Based on the results of the novel object test and P300 in the oddball behavioral paradigm training test, working memory dysfunction was aggravated by antibiotic treatment. We determined the antioxidant capacity in the prefrontal cortex and found a significant negative influence (p < 0.05) of disturbed gut microbiota on the total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content, as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The same trend was also observed in the apoptosis-related functional protein content and mRNA expression levels in the prefrontal cortex, especially the levels of bcl-2, Bax, and caspase-3. The high-altitude environment and antibiotic treatment substantially affected the richness and diversity of the colonic microbiota and reorganized the composition and structure of the microbial community. S24-7, Lachnospiraceae, and Lactobacillaceae were the three microbial taxa with the most pronounced differences under the stimulation by external factors in this study. In addition, correlation analysis between colonic microbiota and cognitive function in mice demonstrated that Helicobacteraceae may be closely related to behavioral results.

Conclusion

Disrupted gut microbiota could aggravate working memory dysfunction induced by high-altitude exposure in mice, indicating the existence of a link between high-altitude exposure and MGBA.
Screening and fermentation medium optimization of a strain favorable to Rice–fish Coculture
Authors: Xia Banghua , Zou Haobo , Li Linyuan , Zhang Bitao , Xiang Yifang , Zou Yuning , Shen Zhentao , Xue Shuqun , Han Ying
Published: November 2022

Rice–fish coculture (RF) is a small ecosystem in which microorganisms are widely distributed in the fish, water environment, soil, and plants. In order to study the positive effects of microorganisms on common carp and rice in the RF ecosystem, a total of 18 strains with growth-promoting ability were screened from common carp (Cyprinus carpio) gut contents, among which three strains had the ability to produce both DDP-IV inhibitors and IAA. The strain with the strongest combined ability, FYN-22, was identified physiologically, biochemically, and by 16S rRNA, and it was initially identified as Bacillus licheniformis. As the number of metabolites secreted by the strain under natural conditions is not sufficient for production, the FYN-22 fermentation medium formulation was optimized by means of one-factor-at-a-time (OFAT) experiments and response surface methodology (RSM). The results showed that, under the conditions of a soluble starch concentration of 10.961 g/l, yeast concentration of 2.366 g/l, NH4Cl concentration of 1.881 g/l, and FeCl3 concentration of 0.850 g/l, the actual measured number of FYN-22 spores in the fermentation broth was 1.913 × 109 CFU/ml, which was 2.575-fold improvement over the pre-optimization value. The optimized fermentation solution was used for the immersion operation of rice seeds, and, after 14 days of incubation in hydroponic boxes, the FYN-22 strain was found to have a highly significant enhancement of 48.31% (p < 0.01) on the above-ground part of rice, and different degrees of effect on root length, fresh weight, and dry weight (16.73, 17.80, and 21.97%, respectively; p < 0.05). This study may provide new insights into the fermentation process of Bacillus licheniformis FYN-22 and its further utilization in RF systems.
Antibiofilm effect and mechanism of protocatechuic aldehyde against Vibrio parahaemolyticus
Authors: Liu Yawen , Wang Li
Published: November 2022

This study investigated the effect of protocatechuic aldehyde (PCA) on Vibrio parahaemolyticus biofilm formation and its effects on gene expression. Crystal violet assay, metabolic activity assay, and fluorescence experiments were used to evaluate the antibiofilm activities of PCA and to reveal its possible antibiofilm mechanisms using transcriptomic analysis. The results indicated that the minimum antibacterial concentration of PCA against V. parahaemolyticus was 300 μg/mL. PCA (9.375 μg/mL) inhibited biofilm generation and adhesion of the mature biofilm. PCA (75 μg/mL) significantly reduced the metabolic viability of V. parahaemolyticus, reduced polysaccharide production, and inhibited cell surface flagella-mediated swimming and aggregation phenotypes. Meanwhile, transcriptome analysis showed that the key genes of V. parahaemolyticus expressed under PCA (75 μg/mL) inhibition were mainly related to biofilm formation (pfkA, galE, narL, and oppA), polysaccharide production and adhesion (IF, fbpA, and yxeM), and motility (cheY, flrC, and fliA). By regulating these key genes, PCA reduced biofilm formation, suppressed polysaccharide production and transport, and prevented the adhesion of V. parahaemolyticus, thereby reducing the virulence of V. parahaemolyticus. This study demonstrated that protocatechuic aldehyde can be used to control V. parahaemolyticus biofilm to ensure food safety.
Improved tolerance of apple plants to drought stress and nitrogen utilization by modulating the rhizosphere microbiome via melatonin and dopamine
Authors: Du Peihua , Cao Yang , Yin Baoying , Zhou Shasha , Li Zhongyong , Zhang Xueying , Xu Jizhong , Liang Bowen
Published: November 2022

This study explored the contributions of melatonin and dopamine to the uptake and utilization of nitrogen and the formation of rhizosphere microbial communities in ‘Tianhong 2’/M. hupehensis, with the goal improving plant resistance to drought stress. Drought stress was formed by artificially controlling soil moisture content. And melatonin or dopamine solutions were applied to the soil at regular intervals for experimental treatment. After 60 days of treatment, plant indices were determined and the structure of the rhizosphere microbial community was evaluated using high-throughput sequencing technology. The findings revealed two ways through which melatonin and dopamine alleviate the inhibition of growth and development caused by drought stress by promoting nitrogen uptake and utilization in plants. First, melatonin and dopamine promote the absorption and utilization of nitrogen under drought stress by directly activating nitrogen transporters and nitrogen metabolism-related enzymes in the plant. Second, they promote the absorption of nitrogen by regulating the abundances of specific microbial populations, thereby accelerating the transformation of the soil nitrogen pool to available nitrogen that can be absorbed directly by plant roots and utilized by plants. These findings provide a new framework for understanding how melatonin and dopamine regulate the uptake and utilization of nitrogen in plants and improve their ability to cope with environmental disturbances.
Combining p-values from various statistical methods for microbiome data
Authors: Ham Hyeonjung , Park Taesung
Published: November 2022

Motivation

In the field of microbiome analysis, there exist various statistical methods that have been developed for identifying differentially expressed features, that account for the overdispersion and the high sparsity of microbiome data. However, due to the differences in statistical models or test formulations, it is quite often to have inconsistent significance results across statistical methods, that makes it difficult to determine the importance of microbiome taxa. Thus, it is practically important to have the integration of the result from all statistical methods to determine the importance of microbiome taxa. A standard meta-analysis is a powerful tool for integrative analysis and it provides a summary measure by combining p-values from various statistical methods. While there are many meta-analyses available, it is not easy to choose the best meta-analysis that is the most suitable for microbiome data.

Results

In this study, we investigated which meta-analysis method most adequately represents the importance of microbiome taxa. We considered Fisher’s method, minimum value of p method, Simes method, Stouffer’s method, Kost method, and Cauchy combination test. Through simulation studies, we showed that Cauchy combination test provides the best combined value of p in the sense that it performed the best among the examined methods while controlling the type 1 error rates. Furthermore, it produced high rank similarity with the true ranks. Through the real data application of colorectal cancer microbiome data, we demonstrated that the most highly ranked microbiome taxa by Cauchy combination test have been reported to be associated with colorectal cancer.
Comparative genomics of Myxococcus and Pyxidicoccus, including the description of four novel species: Myxococcus guangdongensis sp. nov., Myxococcus qinghaiensis sp. nov., Myxococcus dinghuensis sp. nov., and Pyxidicoccus xibeiensis sp. nov.
Authors: Wang Chunling , Lv Yingying , Zhou Lian , Zhang Yulian , Yao Qing , Zhu Honghui
Published: November 2022

Myxobacteria are recognized for fascinating social behaviors and producing diverse extracellular active substances. Isolating novel myxobacteria is of great interest in the exploitation of new antibiotics and extracellular enzymes. Herein, four novel strains were isolated from Dinghu Mountain Biosphere Reserve, Guangdong province, and Qinghai virgin forest soils, Qinghai province, China. The phylogenetic analysis based on 16S rRNA gene and genomic sequences indicated that the four strains belong to the genera Myxococcus and Pyxidicoccus, sharing the highly similarities of 16S rRNA gene with the genera Myxococcus and Pyxidicoccus (99.3–99.6%, respectively). The four strains had average nucleotide identity (ANI) values of 82.8–94.5%, digital DNA–DNA hybridization (dDDH) values of 22.2–56.6%, average amino acid identity (AAI) values of 75.8–79.1% and percentage of conserved protein (POCP) values of 66.4–74.9% to members of the genera Myxococcus and Pyxidicoccus. Based on phylogenetic analyses, physiological and biochemical characteristics, and comparative genomic analyses, we propose four novel species of the genera Myxococcus and Pyxidicoccus and further supported the two genera above represented the same genus. Description of the four novel species is Myxococcus guangdongensis sp. nov. (K38C18041901T = GDMCC 1.2320T = JCM 39260T), Myxococcus qinghaiensis sp. nov. (QH3KD-4-1T = GDMCC 1.2316T = JCM 39262T), Myxococcus dinghuensis sp. nov. (K15C18031901T = GDMCC 1.2319T = JCM 39259T), and Pyxidicoccus xibeiensis sp. nov. (QH1ED-7-1T = GDMCC 1.2315T = JCM 39261T), respectively. Furthermore, comparative genomics of all 15 species of the genera Myxococcus and Pyxidicoccus revealed extensive genetic diversity. Core genomes enriched more genes associated with housekeeping functional classes while accessory genomes enriched more genes related to environmental interactions, indicating the former is relatively indispensable compared to signaling pathway genes. The 15 species of Myxococcus and Pyxidicoccus also exhibited great gene diversity of carbohydrate-active enzymes (CAZymes) and secondary metabolite biosynthesis gene clusters (BGCs), especially related to glycosyl transferases (GT2 and GT4), glycoside hydrolases (GH13 and GH23), non-ribosomal peptide synthetases (NRPS), and Type I polyketide synthase (PKS)/NRPS hybrids.
Association of walking speed with cognitive function in Chinese older adults: A nationally representative cohort study
Authors: Liu Jianping , Cui Kaiwang , Chen Qian , Li Zhiteng , Fu Jing , Gong Xiangwen , Xu Hui
Published: November 2022

Background

Slow walking speed has been shown to predict cognitive decline in older individuals, but studies conducted among Chinese older adults are scarce. We examined the association of walking speed with cognitive function and the trajectory of cognitive decline among Chinese adults aged 60 years and older.

Methods

Data was from the China Health and Retirement Longitudinal Study (CHARLS), an ongoing nationally representative prospective cohort study. Walking speed was evaluated over a straight 2.5-meter flat course at baseline and categorized into tertiles (the lowest, middle, and highest). Cognitive function was assessed at each wave in three domains: episodic memory, mental status, and global cognition. Data were analyzed using linear mixed-effects models.

Results

A total of 3,954 older adults (48.6% female; mean age: 67.6 ± 5.55 years) were followed for up to 7 years. Participants with lowest walking speed have poorer episodic memory (β = −0.37; 95% CI: −0.46, −0.28), mental status (β = −0.45; 95% CI: −0.60, −0.29), and global cognition (β = −0.81; 95% CI: −1.03, −0.60) over the follow-up. Compared with the highest tertile of walking speed, the lowest walking speed was associated with a faster decline in episodic memory (β = −0.04; 95% CI: −0.07, −0.02), mental status (β = −0.04; 95% CI: −0.07, −0.01), and global cognition (β = −0.06; 95% CI: −0.11, −0.01).

Conclusion

Slower walking speed is associated with subsequent risk of poorer cognitive function and faster cognitive decline in older Chinese adults.