bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Bacillus subtilis strain Z-14 on microbial communities of wheat rhizospheric soil infested with Gaeumannomyces graminis var. tritici
Authors: Liu Zhaosha , Xiao Jiawen , Zhang Xuechao , Dou Shijuan , Gao Tongguo , Wang Dongmei , Zhang Dongdong
Published: September 2022

Wheat take-all disease caused by Gaeumannomyces graminis var. tritici (Ggt) spreads rapidly and is highly destructive, causing severe reductions in wheat yield. Bacillus subtilis strain Z-14 that significantly controlled wheat take-all disease effectively colonized the roots of wheat seedlings. Z-14 increased the metabolic activity and carbon source utilization of rhizospheric microorganisms, thus elevating average well-color development (AWCD) values and functional diversity indexes of soil microbial communities. Z-14 increased the abundance of Bacillus in the rhizosphere, which was positively correlated with AWCD and functional diversity indexes. The Z-14-treated samples acquired more linkages and relative connections between bacterial communities according to co-occurrence network analyses. After the application of Ggt, the number of linkages between fungal communities increased but later decreased, whereas Z-14 increased such interactions. Whole-genome sequencing uncovered 113 functional genes related to Z-14’s colonization ability and 10 secondary metabolite gene clusters in the strain, of which nine substances have antimicrobial activity. This study clarifies how bacterial agents like Z-14 act against phytopathogenic fungi and lays a foundation for the effective application of biocontrol agents.
Significant compositional and functional variation reveals the patterns of gut microbiota evolution among the widespread Asian honeybee populations
Authors: Su Qinzhi , Tang Min , Hu Jiahui , Tang Junbo , Zhang Xue , Li Xingan , Niu Qingsheng , Zhou Xuguo , Luo Shiqi , Zhou Xin
Published: September 2022

The gut microbiome is a crucial element that facilitates a host’s adaptation to a changing environment. Compared to the western honeybee Apis mellifera, the Asian honeybee, Apis cerana populations across its natural range remain mostly semi-feral and are less affected by bee management, which provides a good system to investigate how gut microbiota evolve under environmental heterogeneity on large geographic scales. We compared and analyzed the gut microbiomes of 99 Asian honeybees, from genetically diverged populations covering 13 provinces across China. Bacterial composition varied significantly across populations at phylotype, sequence-discrete population (SDP), and strain levels, but with extensive overlaps, indicating that the diversity of microbial community among A. cerana populations is driven by nestedness. Pollen diets were significantly correlated with both the composition and function of the gut microbiome. Core bacteria, Gilliamella and Lactobacillus Firm-5, showed antagonistic turnovers and contributed to the enrichment in carbohydrate transport and metabolism. By feeding and inoculation bioassays, we confirmed that the variations in pollen polysaccharide composition contributed to the trade-off of these core bacteria. Progressive change, i.e., nestedness, is the foundation of gut microbiome evolution among the Asian honeybee. Such a transition during the co-diversification of gut microbiomes is affected by environmental factors, diets in general, and pollen polysaccharides in particular.
Synthetic mimetics assigned a major role to IFNAR2 in type I interferon signaling
Authors: Zoellner Nele , Coesfeld Noémi , De Vos Frederik Henry , Denter Jennifer , Xu Haifeng C. , Zimmer Elena , Knebel Birgit , Al-Hasani Hadi , Mossner Sofie , Lang Philipp A. , Floss Doreen M. , Scheller Jürgen
Published: September 2022

Type I interferons (IFNs) are potent inhibitors of viral replication. Here, we reformatted the natural murine and human type I interferon-α/β receptors IFNAR1 and IFNAR2 into fully synthetic biological switches. The transmembrane and intracellular domains of natural IFNAR1 and IFNAR2 were conserved, whereas the extracellular domains were exchanged by nanobodies directed against the fluorescent proteins Green fluorescent protein (GFP) and mCherry. Using this approach, multimeric single-binding GFP-mCherry ligands induced synthetic IFNAR1/IFNAR2 receptor complexes and initiated STAT1/2 mediated signal transduction via Jak1 and Tyk2. Homodimeric GFP and mCherry ligands showed that IFNAR2 but not IFNAR1 homodimers were sufficient to induce STAT1/2 signaling. Transcriptome analysis revealed that synthetic murine type I IFN signaling was highly comparable to IFNα4 signaling. Moreover, replication of vesicular stomatitis virus (VSV) in a cell culture-based viral infection model using MC57 cells was significantly inhibited after stimulation with synthetic ligands. Using intracellular deletion variants and point mutations, Y510 and Y335 in murine IFNAR2 were verified as unique phosphorylation sites for STAT1/2 activation, whereas the other tyrosine residues in IFNAR1 and IFNAR2 were not involved in STAT1/2 phosphorylation. Comparative analysis of synthetic human IFNARs supports this finding. In summary, our data showed that synthetic type I IFN signal transduction is originating from IFNAR2 rather than IFNAR1.
Cultivation of gastrointestinal microbiota in a new growth system revealed dysbiosis and metabolic disruptions in carcinoma-bearing rats
Authors: Peña-Ocaña Betsy Anaid , Hoshiko Yuki , Silva-Flores Mayel , Maeda Toshinari , Pérez-Torres Israel , García-Contreras Rodolfo , Gutiérrez-Sarmiento Wilbert , Hernández-Esquivel Luz , Marín-Hernández Álvaro , Sánchez-Thomas Rosina , Saavedra Emma , Rodríguez-Zavala José Salud , Jasso-Chávez Ricardo
Published: September 2022

A challenge in the study of gastrointestinal microbiota (GITm) is the validation of the genomic data with metabolic studies of the microbial communities to understand how the microbial networks work during health and sickness. To gain insights into the metabolism of the GITm, feces from healthy and sick rats with cancer were inoculated in a defined synthetic medium directed for anaerobic prokaryote growth (INC-07 medium). Significant differences between cultures of healthy and sick individuals were found: 1) the consumption of the carbon source and the enzyme activity involved in their catabolism (e.g., sucrase, lactase, lipases, aminotransferases, and dehydrogenases); 2) higher excretion of acetic, propionic, isobutyric, butyric, valeric, and isovaleric acids; 3) methane production; 4) ability to form biofilms; and 5) up to 500 amplicon sequencing variants (ASVs) identified showed different diversity and abundance. Moreover, the bowel inflammation induced by cancer triggered oxidative stress, which correlated with deficient antioxidant machinery (e.g., NADPH-producing enzymes) determined in the GITm cultures from sick individuals in comparison with those from control individuals. Altogether, the data suggested that to preserve the microbial network between bacteria and methanogenic archaea, a complete oxidation of the carbon source may be essential for healthy microbiota. The correlation of 16S rRNA gene metabarcoding between cultures and feces, as well as metabolomic data found in cultures, suggest that INC-07 medium may be a useful tool to understand the metabolism of microbiota under gut conditions.
The species-level microbiota of healthy eyes revealed by the integration of metataxonomics with culturomics and genome analysis
Authors: Dong Kui , Pu Ji , Yang Jing , Zhou Guohong , Ji Xuan , Kang Zhiming , Li Juan , Yuan Min , Ning Xiaoling , Zhang Zhaoxia , Ma XingYu , Cheng Yanpeng , Li Hong , Ma Qin , Li Hong , Zhao Lijun , Lei Wenjing , Sun Bin , Xu Jianguo
Published: September 2022

Objectives

To characterize the healthy ocular surface microbiota at the species level, including cultured and uncultured taxa.

Methods

We integrated the metataxonomic method with culturomics and genome sequencing analysis of selected isolated strains to better illustrate the taxonomic structure of the ocular surface microbiota. The metataxonomics used the full-length 16S rRNA gene sequences and the operational phylogenetic unit strategy, which can precisely identify the cultured and uncultured or potentially new taxa to species level based on the phylogenetic tree constructed.

Results

We detected 1,731 operational phylogenetic units (OPUs) in 196 healthy eyes from 128 people, affiliated to 796 cultured species, 784 potentially new species, and 151 potentially new higher taxa. The microbiota for each eye had 49.17 ± 35.66 OPUs. Of the 796 cultured species, 170 (21.36%) had previously caused clinical infections. Based on where they were initially isolated, the ocular surface microbiota mainly came from human body sites (34.55%), the environment (36.93%), plants (9.05%), animals (4.90%), and others; 428 strains were isolated from 20 eyes, affiliated to 42 species, and had come from the environment (33.33%) and the skin (16.67%). Of these, 47.62% had previously caused clinical infections. Genome analysis of 73 isolators revealed that 68.5% of them carried antibiotic resistance genes. The most frequently isolated genera, namely Staphylococcus, Streptococcus, and Moraxella, had an average of 5.30, four, and three resistance genes per strain, respectively.

Discussion

The study found that the ocular surface microbiota mainly came from the environment, plants, animals, food, and human body sites such as the skin, oral cavity, upper respiratory tract, etc. No core member of ocular surface microbiota was detected at the species level. The human eyes were invaded and colonized by bacteria from the exposed environment, some of which were capable of causing infections in humans and carried antibiotic resistance genes. Preventive measures should be developed to protect our eyes from danger.
Responses of soil fungal communities and functional guilds to ~160 years of natural revegetation in the Loess Plateau of China
Authors: Yang Wen , Diao Longfei , Wang Yaqi , Yang Xitong , Zhang Huan , Wang Jinsong , Luo Yiqi , An Shuqing , Cheng Xiaoli
Published: September 2022

Natural revegetation has been widely confirmed to be an effective strategy for the restoration of degraded lands, particularly in terms of rehabilitating ecosystem productivity and soil nutrients. Yet the mechanisms of how natural revegetation influences the variabilities and drivers of soil residing fungal communities, and its downstream effects on ecosystem nutrient cycling are not well understood. For this study, we investigated changes in soil fungal communities along with ~160 years of natural revegetation in the Loess Plateau of China, employing Illumina MiSeq DNA sequencing analyses. Our results revealed that the soil fungal abundance was greatly enhanced during the later stages of revegetation. As revegetation progresses, soil fungal richness appeared first to rise and then decline at the climax Quercus liaotungensis forest stage. The fungal Shannon and Simpson diversity indexes were the lowest and highest at the climax forest stage among revegetation stages, respectively. Principal component analysis, Bray–Curtis similarity indices, and FUNGuild function prediction suggested that the composition, trophic modes, and functional groups for soil fungal communities gradually shifted along with natural revegetation. Specifically, the relative abundances of Basidiomycota, Agaricomycetes, Eurotiomycetes, and ectomycorrhizal fungi progressively increased, while that of Ascomycota, Sordariomycetes, Dothideomycetes, Tremellomycetes, saprotrophic, pathotrophic, arbuscular mycorrhizal fungi, and endophyte fungi gradually decreased along with natural revegetation, respectively. The most enriched members of Basidiomycota (e.g., Agaricomycetes, Agaricales, Cortinariaceae, Cortinarius, Sebacinales, Sebacinaceae, Tricholomataceae, Tricholoma, Russulales, and Russulaceae) were found at the climax forest stage. As important carbon (C) sources, the most enriched symbiotic fungi (particularly ectomycorrhizal fungi containing more recalcitrant compounds) can promote organic C and nitrogen (N) accumulation in soils of climax forest. However, the most abundant of saprotrophic fungi in the early stages of revegetation decreased soil organic C and N accumulation by expediting the decomposition of soil organic matter. Our results suggest that natural revegetation can effectively restore soil fungal abundance, and modify soil fungal diversity, community composition, trophic modes, and functional groups by altering plant properties (e.g., plant species richness, diversity, evenness, litter quantity and quality), quantity and quality of soil nutrient substrates, soil moisture and pH. These changes in soil fungal communities, particularly their trophic modes and functional groups along with natural revegetation, impact the accumulation and decomposition of soil C and N and potentially affect ecosystem C and N cycling in the Loess Plateau of China.
Inhibitors targeting the autophosphorylation of serine/threonine kinase of Streptococcus suis show potent antimicrobial activity
Authors: Li Haotian , Li Tingting , Hu Qiao , Yao Zhiming , Li Lu , Huang Qi , Zhou Rui
Published: September 2022

Antimicrobial resistance (AMR) is a global concern threatening public health. Developing novel antibiotics is one of the effective strategies to tackle AMR. Serine/threonine kinases (STKs) have been recently shown to play critical roles in the physiology and pathogenesis of several important bacterial pathogens which are regarded as a promising antimicrobial drug target. We previously reported the roles of STK in the regulation of bacterial cell division, metabolism, and pathogenesis in Streptococcus suis, an important zoonotic bacterial pathogen. In this study, we firstly identified the Thr167 and Ser175 residues in the activation loop of S. suis STK (ssSTK) as the kinase autophosphorylation sites. Phenotyping results demonstrated that the autophosphorylation deficient strain resembled the stk deletion strain showing essentiality for bacterial growth in minimal medium, abnormal morphology, and decreased virulence when compared with the wild-type S. suis SC19 strain. Based on these findings, we established an ssSTK inhibitor screening approach by measuring the growth of S. suis in a minimal medium and testing the autophosphorylation inhibition by measuring the consumption of ATP in an enzymatic reaction by ssSTK. A series of inhibitors against ssSTK are identified from a commercial kinase inhibitors library, including Staurosporine, K252a, AT9283, and APY29. These inhibitors showed antimicrobial activity in vitro. Moreover, by using Galleria mellonella larvae infection assay, compound APY29 displayed in vivo efficacy against S. suis infection. Additionally, it was predicted by molecular docking that these inhibitors could interact with ssSTK. Collectively, our data illustrated the essential roles of ssSTK autophosphorylation in the physiology and pathogenicity of S. suis and consider these inhibitors as promising antimicrobial lead compounds.
Exploration on neurobiological mechanisms of the central–peripheral–central closed-loop rehabilitation
Authors: Jia Jie
Published: September 2022

Central and peripheral interventions for brain injury rehabilitation have been widely employed. However, as patients’ requirements and expectations for stroke rehabilitation have gradually increased, the limitations of simple central intervention or peripheral intervention in the rehabilitation application of stroke patients’ function have gradually emerged. Studies have suggested that central intervention promotes the activation of functional brain regions and improves neural plasticity, whereas peripheral intervention enhances the positive feedback and input of sensory and motor control modes to the central nervous system, thereby promoting the remodeling of brain function. Based on the model of a central–peripheral–central (CPC) closed loop, the integration of center and peripheral interventions was effectively completed to form “closed-loop” information feedback, which could be applied to specific brain areas or function-related brain regions of patients. Notably, the closed loop can also be extended to central and peripheral immune systems as well as central and peripheral organs such as the brain–gut axis and lung–brain axis. In this review article, the model of CPC closed-loop rehabilitation and the potential neuroimmunological mechanisms of a closed-loop approach will be discussed. Further, we highlight critical questions about the neuroimmunological aspects of the closed-loop technique that merit future research attention.
The art of pain: A quantitative color analysis of the self-portraits of Frida Kahlo
Authors: Turkheimer Federico E. , Liu Jingyi , Fagerholm Erik D. , Dazzan Paola , Loggia Marco L. , Bettelheim Eric
Published: September 2022

Frida Kahlo (1907–1954) was a Mexican artist who is remembered for her self-portraits, pain and passion, and bold, vibrant colors. This work aims to use her life story and her artistic production in a longitudinal study to examine with quantitative tools the effects of physical and emotional pain (rage) on artistic expression. Kahlo suffered from polio as a child, was involved in a bus accident as a teenager where she suffered multiple fractures of her spine and had 30 operations throughout her lifetime. She also had a tempestuous relationship with her painter husband, Diego Rivera. Her physical and personal troubles however became the texture of her vivid visual vocabulary—usually expressed through the depiction of Mexican and indigenous culture or the female experience and form. We applied color analysis to a series of Frida's self-portraits and revealed a very strong association of physical pain and emotional rage with low wavelength colors (red and yellow), indicating that the expression of her ailments was, consciously or not, achieved by increasing the perceived luminance of the canvas. Further quantitative analysis that used the fractal dimension identified “The broken column” as the portrait with higher compositional complexity, which matches previous critical acclaim of this portrait as the climax of her art. These results confirm the ability of color analysis to extract emotional and cognitive features from artistic work. We suggest that these tools could be used as markers to support artistic and creative interventions in mental health.
Regional impairment of deep gray matter perfusion in neonates with congenital heart disease revealed by arterial spin labeling MRI
Authors: Sun Yan , Liu Yujie , Yu Wenwen , Zhong Yumin
Published: September 2022

The present study examined deep gray matter perfusion in neonates with congenital heart disease (CHD) with arterial spin labeling magnetic resonance imaging preoperatively. We found that neonates with cyanotic CHD showed lower right thalamus compared with controls and lower right basal ganglia perfusion compared with acyanotic CHD. When the CHD group was assessed as a whole, it showed slightly decreased left thalamus perfusion compared with controls. The results suggest that cardiac physiology plays a crucial part in changes in regional cerebral perfusion. Perfusion with arterial spin labeling may be a useful marker of high risk for impaired cerebral blood flow auto-regulation and cerebral hypoperfusion in neonates with CHD.
Visual cortical γ−aminobutyric acid and perceptual suppression in amblyopia
Authors: Mukerji Arjun , Byrne Kelly N. , Yang Eunice , Levi Dennis M. , Silver Michael A.
Published: September 2022

In amblyopia, abnormal visual experience during development leads to an enduring loss of visual acuity in adulthood. Physiological studies in animal models suggest that intracortical GABAergic inhibition may mediate visual deficits in amblyopia. To better understand the relationship between visual cortical γ-aminobutyric acid (GABA) and perceptual suppression in persons with amblyopia (PWA), we employed magnetic resonance spectroscopy (MRS) to quantify GABA levels in both PWA and normally-sighted persons (NSP). In the same individuals, we obtained psychophysical measures of perceptual suppression for a variety of ocular configurations. In PWA, we found a robust negative correlation between the depth of amblyopia (the difference in visual acuity between the amblyopic and non-amblyopic eyes) and GABA concentration that was specific to visual cortex and was not observed in a sensorimotor cortical control region. Moreover, lower levels of visual cortical GABA were associated with weaker perceptual suppression of the fellow eye by the amblyopic eye and stronger suppression of the amblyopic eye by the fellow eye. Taken together, our findings provide evidence that intracortical GABAergic inhibition is an important component of the pathology of human amblyopia and suggest possible therapeutic interventions to restore vision in the amblyopic eye through enhancement of visual cortical GABAergic signaling in PWA.
Expected affine: A registration method for damaged section in serial sections electron microscopy
Authors: Xin Tong , Shen Lijun , Li Linlin , Chen Xi , Han Hua
Published: September 2022

Registration is essential for the volume reconstruction of biological tissues using serial section electron microscope (ssEM) images. However, due to environmental disturbance in section preparation, damage in long serial sections is inevitable. It is difficult to register the damaged sections with the common serial section registration method, creating significant challenges in subsequent neuron tracking and reconstruction. This paper proposes a general registration method that can be used to register damaged sections. This method first extracts the key points and descriptors of the sections to be registered and matches them via a mutual nearest neighbor matcher. K-means and Random Sample Consensus (RANSAC) are used to cluster the key points and approximate the local affine matrices of those clusters. Then, K-nearest neighbor (KNN) is used to estimate the probability density of each cluster and calculate the expected affine matrix for each coordinate point. In clustering and probability density calculations, instead of the Euclidean distance, the path distance is used to measure the correlation between sampling points. The experimental results on real test images show that this method solves the problem of registering damaged sections and contributes to the 3D reconstruction of electronic microscopic images of biological tissues. The code of this paper is available at https://github.com/TongXin-CASIA/Excepted_Affine.
Investigating changes in blood-cerebrospinal fluid barrier function in a rat model of chronic hypertension using non-invasive magnetic resonance imaging
Authors: Perera Charith , Tolomeo Daniele , Baker Rebecca R. , Ohene Yolanda , Korsak Alla , Lythgoe Mark F. , Thomas David L. , Wells Jack A.
Published: September 2022

Chronic hypertension is a major risk factor for the development of neurodegenerative disease, yet the etiology of hypertension-driven neurodegeneration remains poorly understood. Forming a unique interface between the systemic circulation and the brain, the blood-cerebrospinal fluid barrier (BCSFB) at the choroid plexus (CP) has been proposed as a key site of vulnerability to hypertension that may initiate downstream neurodegenerative processes. However, our ability to understand BCSFB’s role in pathological processes has, to date, been restricted by a lack of non-invasive functional measurement techniques. In this work, we apply a novel Blood-Cerebrospinal Fluid Barrier Arterial Spin Labeling (BCSFB-ASL) Magnetic resonance imaging (MRI) approach with the aim of detecting possible derangement of BCSFB function in the Spontaneous Hypertensive Rat (SHR) model using a non-invasive, translational technique. SHRs displayed a 36% reduction in BCSFB-mediated labeled arterial water delivery into ventricular cerebrospinal fluid (CSF), relative to normotensive controls, indicative of down-regulated choroid plexus function. This was concomitant with additional changes in brain fluid biomarkers, namely ventriculomegaly and changes in CSF composition, as measured by T1 lengthening. However, cortical cerebral blood flow (CBF) measurements, an imaging biomarker of cerebrovascular health, revealed no measurable change between the groups. Here, we provide the first demonstration of BCSFB-ASL in the rat brain, enabling non-invasive assessment of BCSFB function in healthy and hypertensive rats. Our data highlights the potential for BCSFB-ASL to serve as a sensitive early biomarker for hypertension-driven neurodegeneration, in addition to investigating the mechanisms relating hypertension to neurodegenerative outcomes.
Role of lipidomics in assessing the functional lipid composition in breast milk
Authors: Ganeshalingam Moganatharsa , Enstad Samantha , Sen Sarbattama , Cheema Sukhinder , Esposito Flavia , Thomas Raymond
Published: September 2022

Breast milk is the ideal source of nutrients for infants in early life. Lipids represent 2–5% of the total breast milk composition and are a major energy source providing 50% of an infant’s energy intake. Functional lipids are an emerging class of lipids in breast milk mediating several different biological functions, health, and developmental outcome. Lipidomics is an emerging field that studies the structure and function of lipidome. It provides the ability to identify new signaling molecules, mechanisms underlying physiological activities, and possible biomarkers for early diagnosis and prognosis of diseases, thus laying the foundation for individualized, targeted, and precise nutritional management strategies. This emerging technique can be useful to study the major role of functional lipids in breast milk in several dimensions. Functional lipids are consumed with daily food intake; however, they have physiological benefits reported to reduce the risk of disease. Functional lipids are a new area of interest in lipidomics, but very little is known of the functional lipidome in human breast milk. In this review, we focus on the role of lipidomics in assessing functional lipid composition in breast milk and how lipid bioinformatics, a newly emerging branch in this field, can help to determine the mechanisms by which breast milk affects newborn health.
The mitigative effect of ovotransferrin-derived peptide IQW on DSS-induced colitis via alleviating intestinal injury and reprogramming intestinal microbes
Authors: Chai Yajuan , Ding Sujuan , Jiang Lihong , Wang Shuangshuang , Yuan Xiangnan , Jiang Hongmei , Fang Jun
Published: September 2022

Inflammatory bowel disease (IBD) is a chronic disease with multiple complications during its development, and it is difficult to cure. The aim of this study was to evaluate the alleviating effect of different concentrations of the bioactive peptide IQW (Ile-Gln-Trp) on dextran sodium sulfate (DSS)-induced colitis in mice. For this study, we randomly divided 56 ICR mice into seven groups: the (I) control (CON), (II) dextran sodium sulfate treatment (2.5% DSS), (III) IQW-DSS (20 μg/ml) treatment, (IV) IQW-DSS (40 μg/ml) treatment, (V) IQW-DSS (60 μg/ml) treatment, (VI) IQW-DSS (80 μg/ml) treatment, and (VII) IQW-DSS (100 μg/ml) groups. The results showed that IQW at 60 μg/ml alleviated body weight loss, improved the liver index (p < 0.05), and improved histomorphological and pathological changes in the colon compared to the DSS-treated group. IQW at 60 μg/ml and IQW at 80 μg/ml modified intestinal microbial disorders. In addition, IQW at 60 μg/ml significantly increased butyric acid levels and decreased valeric acid levels, while IQW at 80 μg/ml significantly increased isobutyric acid and isovaleric acid levels. Hence, IQW at a concentration of 60 μg/ml alleviates DSS-induced colitis by enhancing the body's anti-inflammatory ability and regulating intestinal flora and metabolic changes. In the above context, IQW at 60 μg/ml could be a potential candidate for IBD prevention and treatment.
Serum creatinine/cystatin C ratio is a systemic marker of sarcopenia in patients with gastrointestinal stromal tumours
Authors: Ding Ping’an , Guo Honghai , Sun Chenyu , Chen Shuya , Yang Peigang , Tian Yuan , Lowe Scott , Zhao Qun
Published: September 2022

Background

It is well known that sarcopenia is a common risk factor in patients with gastrointestinal tumours, which may negatively affect the clinical outcome and prognosis. Recent studies suggest that serum creatinine-cystatin C (Cr/CysC) ratio may be associated with sarcopenia, but this association lacks sufficient evidence in patients with gastrointestinal stromal tumours (GIST). Therefore, this study aimed to investigate whether the Cr/CysC ratio was associated with sarcopenia and recurrence-free survival (RFS) in patients with GIST.

Materials and methods

The study retrospectively analysed 413 patients with GIST who underwent surgical resection from January 2016 to January 2020. The serum Cr/CysC ratio was determined as a proxy for sarcopenia by comparing it with various biomarkers and Cox multifactorial analysis was used to determine the relationship between Cr/CysC ratio and prognosis.

Results

Serum Cr/CysC was positively correlated with skeletal muscle area (SMA) (r = 0.256, p < 0.001), skeletal muscle index (SMI) (r = 0.300, p < 0.001), and hand grip strength (HGS) (r = 0.251, p < 0.001). The area under the receiver operator characteristic curve for sarcopenic subjects with serum Cr/CysC ratio was significantly greater than other biomarkers (Cr/CysC: 0.840, CysC: 0.732, Cr: 0.518). The optimal cut-off value for Cr/CysC was 0.65, and patients in the high Cr/CysC group had a higher 3-year recurrence-free survival (RFS) than those in the low Cr/CysC group (92.72 vs. 72.46%, p < 0.001). Cox multifactorial analysis found that the Cr/CysC ratio was an independent risk factor for RFS in GIST patients (HR = 2.143, 95% CI: 1.431–5.459, p = 0.011).

Conclusion

Serum Cr/CysC ratio has satisfactory and comparable diagnostic accuracy, and prognostic value for sarcopenia in patients with GIST. Therefore, it can be a simple and practical clinical tool to screen sarcopenia in GIST patients. However, further studies are required to validate these findings.
IP6 reduces colorectal cancer metastasis by mediating the interaction of gut microbiota with host genes
Authors: Lan Tong-Tong , Song Yang , Liu Xiao-Han , Liu Cui-Ping , Zhao Hui-Chao , Han Yi-Sa , Wang Chu-Hui , Yang Ning , Xu Zhen , Tao Meng , Li Hui
Published: September 2022

Inositol hexaphosphate (IP6) is a phytochemical widely found in grains and legumes that plays an anti-cancer role. However, the mechanism underlying the inhibition of colorectal cancer metastasis by IP6 through host genes, gut microbiota, and their interactions remain elusive. In this study, 16S rRNA sequencing was used to study the effect of IP6 on gut microbiota in an orthotopic transplantation model of colorectal cancer mice. The transcriptome was used to study the changes of host genes in metastasis and the relationship with gut microbiota. The results showed that the gut microbiota composition of model mice was significantly different from that of normal mice. The beta diversity partly tended to return to the normal level after IP6 intervention. Especially, Lactobacillus helveticus and Lactococcus lactis were recovered after IP6-treated. Enrichment analysis showed that the enrichment score of the Cytokine-Cytokine receptor interaction signal pathway decreased after IP6 treatment compared to the model group. Further analysis of differentially expressed genes (DEGs) in this pathway showed that IP6 reduced the expression of the Tnfrsf1b gene related to the area of liver metastasis, and the Tnfrsf1b gene was negatively correlated with the relative abundance of Lactobacillus helveticus. Our results presented that host gene, microbiome and their interaction may serve as promising targets for the mechanism of IP6 intervention in colorectal cancer metastasis.
A high preoperative serum IL-25 level is a negative prognosis predictor after liver resection for HBV-HCC
Authors: Chen Shao-hua , Wang Xu
Published: September 2022

Objective

The aim of this study was to evaluate the association between preoperative IL-25 levels and HBV-HCC patient outcomes following liver surgery.

Methods

This study enrolled consecutive HCC patients that had undergone liver surgery from 2008 to 2015. Baseline patient clinical properties were assessed to establish predictors of postoperative overall survival and recurrence-free survival (OS and RFS, respectively) following liver resection. In addition, serum IL-25 levels were assessed via ELISA.

Results

Cox regression analyses revealed IL-25 levels to be independently related to the OS and RFS of 896 HBV-associated HCC patients. An optimal IL-25 cutoff level of 14.9 μg/ml was identified, with 206 patients in this cohort having IL-25 levels above this threshold. Both the OS and RFS of patients with an IL-25 level <14.9 μg/ml were significantly better after liver resection as compared to those of patients with higher preoperative levels of this cytokine (p < 0.05). Cox multivariate regression analyses revealed an IL-25 level ≥ 14.9 μg/L to be an independent predictor of poorer RFS and OS. A combination of IL-25 levels and tumor diameter may be an even more reliable predictor of OS.

Conclusions

IL-25 levels are independent predictors of postoperative survival within HCC patients undergoing liver resection.
Association of the TGFβ gene family with microenvironmental features of gastric cancer and prediction of response to immunotherapy
Authors: Han Bangling , Fang Tianyi , Zhang Yao , Zhang Yongle , Gao Jialiang , Xue Yingwei
Published: September 2022

In the complex tumor microenvironment, TGFβ is a pleiotropic cytokine involved in regulating cellular processes such as cancer cell proliferation, apoptosis and metastasis. TGFβ defines three subtypes (TGFβ1, TGFβ2, and TGFβ3), of which TGFβ is highly expressed in many cancers, especially those showing high dissemination potential. In addition, increased expression of TGFβ in multiple cancers is usually positively correlated with epithelial mesenchymal transition (EMT) and coordinated with the expression of genes driving EMT-related genes. TGFβ signaling in the tumor microenvironment inhibits the antitumor function of multiple immune cell populations, including T cells and natural killer cells, and the resulting immunosuppression severely limits the efficacy of immune checkpoint inhibitors and other immunotherapeutic approaches. As a major pathway to enhance the efficacy of cancer immunotherapy effects, the role of TGFβ signaling inhibitors have been evaluated in many clinical trials. However, the potential functions and mechanisms of TGFβ1, TGFβ2 and TGFβ3 in gastric cancer progression and tumor immunology are unclear. In this study, we comprehensively analyzed TGFβ1, TGFβ2 and TGFβ3 and gastric cancer microenvironmental features, including immune cell infiltration, EMT, hypoxia, mutation, immunotherapy and drug treatment, based on HMUCH sequencing data (GSE184336) and public databases. We also validated the protein expression levels of TGFβ in gastric cancer tissues as well as the role of TGFβ factor in cytology experiments. This report reveals the important role of the TGFβ gene family in gastric cancer and provides possible relationships and potential mechanisms of TGFβ in gastric cancer.
The epidemic of thyroid cancer in China: Current trends and future prediction
Authors: Wu Jiayuan , Zhao Xiaoyan , Sun Jianzhong , Cheng Chong , Yin Chunyu , Bai Ruhai
Published: September 2022

Background

Thyroid cancer (TC) is one of the most common cancers in China. The aim of this study was to identify the potential age, period, and cohort effect under the long-term trends in TC incidence and mortality, making projections up to 2030.

Methods

Incidence and mortality data on TC were obtained from the Global Burden of Disease Study 2019. The population predictions were obtained from the United Nations World Population Prospects 2019. An age–period–cohort model was used for the analysis.

Results

From 1990 to 2019, the net drift (the overall annual percentage change of TC over time adjusted for age groups) of the TC incidence was 5.01% (95% confidence interval [CI]: 4.72%, 5.29%) for men and 1.48% (95% CI: 1.14%, 1.82%) for women. The net drift of TC mortality was 1.64% (95% CI: 1.38%, 1.91%) for men and –2.51% (95% CI: –2.77%, –2.26%) for women. Regarding the incidence of TC, both the period and the cohort relative risks (RRs) in men and women showed an overall increasing trend. As to the mortality rate of TC, both the period and cohort RRs in women showed a monotonic declining trend. The period RRs for men decreased after 2015, but the cohort RRs revealed a fluctuating upward pattern. From 2019 to 2030, the TC incidence was projected to rise by 32.4% in men and 13.1% in women, the mortality declining by 13.0% in men and 17.3% in women. The elderly was projected to have an increasing proportion of TC occurrence and deaths.

Conclusions

Over the past 30 years, the incidence rate of TC in China has continually increased, and this trend was projected to continue. Although male mortality has increased in the past, it is expected to decline in the future. The proportion of older people among TC occurrence and death was projected to gradually increase, and the difficulties elderly with TC lrequire more attention.
Deep learning analysis to predict EGFR mutation status in lung adenocarcinoma manifesting as pure ground-glass opacity nodules on CT
Authors: Yoon Hyun Jung , Choi Jieun , Kim Eunjin , Um Sang-Won , Kang Noeul , Kim Wook , Kim Geena , Park Hyunjin , Lee Ho Yun
Published: September 2022

Background

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) showed potency as a non-invasive therapeutic approach in pure ground-glass opacity nodule (pGGN) lung adenocarcinoma. However, optimal methods of extracting information about EGFR mutation from pGGN lung adenocarcinoma images remain uncertain. We aimed to develop, validate, and evaluate the clinical utility of a deep learning model for predicting EGFR mutation status in lung adenocarcinoma manifesting as pGGN on computed tomography (CT).

Methods

We included 185 resected pGGN lung adenocarcinomas in the primary cohort. The patients were divided into training (n = 125), validation (n = 23), and test sets (n = 37). A preoperative CT-based deep learning model with clinical factors as well as clinical and radiomics models was constructed and applied to the test set. We evaluated the clinical utility of the deep learning model by applying it to 83 GGNs that received EGFR-TKI from an independent cohort (clinical validation set), and treatment response was regarded as the reference standard.

Results

The prediction efficiencies of each model were compared in terms of area under the curve (AUC). Among the 185 pGGN lung adenocarcinomas, 122 (65.9%) were EGFR-mutant and 63 (34.1%) were EGFR-wild type. The AUC of the clinical, radiomics, and deep learning with clinical models to predict EGFR mutations were 0.50, 0.64, and 0.85, respectively, for the test set. The AUC of deep learning with the clinical model in the validation set was 0.72.

Conclusions

Deep learning approach of CT images combined with clinical factors can predict EGFR mutations in patients with lung adenocarcinomas manifesting as pGGN, and its clinical utility was demonstrated in a real-world sample.
Development and validation of a nomogram for predicting pelvic lymph node metastasis and prognosis in patients with cervical cancer
Authors: Wang Mengting , Ma Min , Yang Liju , Liang Chengtong
Published: September 2022

Objective

Cervical cancer (CC) is one of the main causes of death among gynecological malignancies. Patients with CC with lymph node metastasis (LNM) have poor prognoses. We investigated the risk factors and prognosis of LNM in patients with CC patients using data from the SEER database.

Methods

We collected the information of cervical cancer patients registered in SEER database from 2010 to 2015. The dataset was divided into a training set and a validation set at a 7:3 ratio. LASSO regression analysis was used to evaluate risk factors for LNM in patients with CC. Using the results, we established a nomogram prediction model. C-index, ROC curves, calibration curves, decision curve analysis, and clinical impact curves were used to evaluate the prediction performance of the model.

Results

We included 14,356 patients with CC in the analysis. Among these, 3997 patients were diagnosed with LNM. A training set (10,050 cases) and a validation set (4306 cases) were used for the following analysis. We established nomogram LNM prediction models for the patients with T1-2-stage CC. The C-indices for the internal and external validations of the prediction models were 0.758 and 0.744, respectively. In addition, we established a prognostic nomogram for all CC patients with LNM, and the internal and external validation C-indices were 0.763 and 0.737.

Conclusion

We constructed a quantitative and visual predictive nomogram that predicted prognosis of patients with LNM in CC to provide clinicians with a reference for diagnosis and treatment.
Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment
Authors: Li Yuying , Li Tianfu , Zhai Duanyang , Xie Chuanbo , Kuang Xiaying , Lin Ying , Shao Nan
Published: September 2022

Clinical significance and biological functions of the ferroptosis pathway were addressed in all aspect of cancer regarding multi-omics level; however, the overall status of ferroptosis pathway alteration was hard to evaluate. The aim of this study is to comprehensively analyze the putative biological, pathological, and clinical functions of the ferroptosis pathway in breast cancer on a pathway level. By adopting the bioinformatic algorithm “pathifier”, we quantified five programmed cell death (PCD) pathways (KO04210 Apoptosis; KO04216 Ferroptosis; KO04217 Necroptosis; GO:0070269 Pyroptosis; GO:0048102 Autophagic cell death) in breast cancer patients, and we featured the clinical characteristics and prognostic value of each pathway in breast cancer and found significantly activated PCD in cancer patients, among which ferroptosis demonstrated a significant correlation with the prognosis of breast cancer. Correlation analysis between PCD pathways identified intra-tumor heterogeneity of breast cancer. Therefore, clustering of patients based on the status of PCD pathways was done. Comparisons between subgroups highlighted specifically activated ferroptosis in cluster 2 patients, which showed the distinct status of tumor immunity and microenvironment from other clusters, indicating putative correlations with ferroptosis. NDUFA13 was identified and selected as a putative biomarker for cluster 2 patients. Experimental validations were executed on cellular level and NDUFA13 showed an important role in regulating ferroptosis activation and can work as a biomarker for ferroptosis pathway status. In conclusion, the status of the ferroptosis pathway significantly correlated with the clinical outcomes and intra-tumor heterogeneity of breast cancer, and NDUFA13 expression was identified as a positive biomarker for ferroptosis pathway activation in breast cancer patients.
Exercise as cancer treatment: A clinical oncology framework for exercise oncology research
Authors: Courneya Kerry S. , Booth Christopher M.
Published: September 2022

Exercise has been proposed as a possible cancer treatment; however, there are an infinite number of clinical oncology settings involving diverse cancer types and treatment protocols in which exercise could be tested as a cancer treatment. The primary purpose of this paper is to propose a conceptual framework to organize and guide research on exercise as a cancer treatment across distinct clinical oncology settings. A secondary purpose is to provide an overview of existing exercise research using the proposed framework. The Exercise as Cancer Treatment (EXACT) framework proposes nine distinct clinical oncology scenarios based on tumor/disease status and treatment status at the time of the proposed exercise treatment. In terms of tumor/disease status, the primary tumor has either been surgically removed (primary goal to treat micrometastases), not surgically removed (primary goal to treat the primary tumor), or metastatic disease is present (primary goal to treat metastatic disease). In terms of treatment status, the extant disease has either not been treated yet (treatment naïve), is currently being treated (active treatment), or has previously been treated. These two key clinical oncology variables—tumor/disease status and treatment status—result in nine distinct clinical oncology scenarios in which exercise could be tested as a new cancer treatment: (a) treatment naïve micrometastases, (b) actively treated micrometastases, (c) previously treated micrometastases, (d) treatment naïve primary tumors, (e) actively treated primary tumors, (f) previously treated primary tumors, (g) treatment naïve metastatic disease, (h) actively treated metastatic disease, and (i) previously treated metastatic disease. To date, most preclinical animal studies have examined the effects of exercise on treatment naïve and actively treated primary tumors. Conversely, most observational human studies have examined the associations between exercise and cancer recurrence/survival in patients actively treated or previously treated for micrometastases. Few clinical trials have been conducted in any of these scenarios. For exercise to be integrated into clinical oncology practice as a cancer treatment, it will need to demonstrate benefit in a specific clinical setting. The EXACT framework provides a simple taxonomy for systematically evaluating exercise as a potential cancer treatment across a diverse range of cancer types and treatment protocols.
CRISPR/Cas9-3NLS/sgHMGA2@PDA nanosystem is the potential efficient gene editing therapy for gastric cancer with HMGA2 high expression
Authors: Wu Zhouying , Huo Xue , Yang Tingyu , Liu Kun , Wu Ting , Feng Zongqi , Wang Min , Li Feng , Jia Jianchao , Zhang Xiaoran , Gao Wenming , Yu Lan
Published: September 2022

Gene therapy is one of the target therapies with promising clinical use for gastric cancer (GC). However, the delivery of the CRISPR/Cas9/sgRNA (RNP) gene editing tool severely limits the practical therapeutic effect of GC. Therefore, it is a great challenge to develop an RNP delivery system that is simple to prepare and can rapidly encapsulate RNP while achieving high delivery and gene editing efficiency. We developed, for the first time, the CRISPR/Cas9@PDA nano-delivery system that can achieve high-efficiency delivery (95%) of CRISPR/Cas9-3NLS/sgHMGA2 and high-efficient HMGA2 gene editing (82%) of GC cells. In particular, the experiment’s weak alkaline environment can not only protect the activity of CRISPR/Cas9-3NLS/sgHMGA2 but also trigger the self-polymerization of polydopamine (PDA). Meanwhile, the presence of KE in the CRISPR/Cas9 amino acid sequence can achieve the directional growth of PDA, thus forming a core–shell structure that protects CRISPR/Cas9-3NLS/sgHMGA2. This efficient CRISPR/Cas9-3NLS/sgHMGA2 delivery and HMGA2 gene editing ability has also been verified in mice, which can significantly inhibit tumor growth in mice. The success of building the delivery system and its ideal treating effect give hope to the efficacious treatment for the GC patients with HMGA2 high expression.