bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Hereditary transthyretin (ATTRv) amyloidosis: The p.G103R mutation of the transthyretin gene in a Han Chinese family is associated with vitreous hemorrhage
Authors: Shen Junhui , Yu Hao , Lin Jijian , Zhang Li , Pan Xiaohong , Chen Zhiqing
Published: September 2022

Hereditary transthyretin (ATTRv) amyloidosis is a rare disease caused by transthyretin gene (TTR) mutation. We identified that the p.G103R mutation of the TTR gene in a Han Chinese family was associated with vitreous hemorrhage. The proband was a 48-year-old woman who had progressive visual impairment in both eyes for 12 years. A Glass wool–like posterior vitreous cortex attached to the posterior retinal surface of both eyes was found using ocular coherence tomography. Visual acuity improved after the first vitrectomy. Two years later, the patient underwent two more vitrectomies because of vitreous opacity recrudescence. Four years later, she presented with vitreous hemorrhage in the right eye. The vitreous fluids acquired during the vitrectomy showed increased vascular endothelial growth factor, basic fibroblast growth factor, interleukin-6, interleukin-10, vascular cell adhesion molecule, and interleukin-8. Mutation sequencing revealed a heterozygous mutation in nucleotide c.307G > C (p.G103R) in exon 3 of the TTR gene in the proband (IV-13), her daughter (IV-9), and her fourth sister (III-11). To our knowledge, this is the first case of ATTRv amyloidosis caused by a p.G103R mutation of the TTR gene associated with vitreous hemorrhage in China.
Construction of a neural network diagnostic model and investigation of immune infiltration characteristics for Crohn’s disease
Authors: Yang Yufei , Xu Lijun , Qiao Yuqi , Wang Tianrong , Zheng Qing
Published: September 2022

Objective: Crohn’s disease (CD), a chronic recurrent illness, is a type of inflammatory bowel disease whose incidence and prevalence rates are gradually increasing. However, there is no universally accepted criterion for CD diagnosis. The aim of this study was to create a diagnostic prediction model for CD and identify immune cell infiltration features in CD.

Methods: In this study, gene expression microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Then, we identified differentially expressed genes (DEGs) between 178 CD and 38 control cases. Enrichment analysis of DEGs was also performed to explore the biological role of DEGs. Moreover, the “randomForest” package was applied to select core genes that were used to create a neural network model. Finally, in the training cohort, we used CIBERSORT to evaluate the immune landscape between the CD and normal groups.

Results: The results of enrichment analysis revealed that these DEGs may be involved in biological processes associated with immunity and inflammatory responses. Moreover, the top 3 hub genes in the protein-protein interaction network were IL-1β, CCL2, and CXCR2. The diagnostic model allowed significant discrimination with an area under the ROC curve of 0.984 [95% confidence interval: 0.971–0.993]. A validation cohort (GSE36807) was utilized to ensure the reliability and applicability of the model. In addition, the immune infiltration analysis indicated nine different immune cell types were significantly different between the CD and healthy control groups.

Conclusion: In summary, this study offers a novel insight into the diagnosis of CD and provides potential biomarkers for the precise treatment of CD.
Social differentiation of the perception and human tissues donation for research purposes
Authors: Majchrowska Anita , Wiechetek Michał , Domaradzki Jan , Pawlikowski Jakub
Published: September 2022

The willingness to donate human biological material for research purposes is shaped by socio-cultural factors; however, there is a lack of studies analysing the social perception of different human tissues, which may affect such willingness. This study aimed to distinguish different sociocultural categories of human tissues and types of potential donors based on their willingness to donate material. Quantitative research was conducted on a sample of 1,100 adult Poles representative in terms of sex, place of residence and education. According to the study, people were most willing to donate urine (73.9%), blood (69.7%), hair and tears (69.6%) and the least willing to donate post-mortem brain fragments (20%), sperm (males; 36.4%) and egg cells (females; 39.6%). A factor analysis revealed four sociocultural categories of donated tissues: irrelevant, redundant, ordinary and sensitive. Based on these sociocultural categories of tissues, four types of donors were identified: reluctant, highly cooperative, average cooperative and selectively cooperative. The willingness to donate human samples for research is shaped by the sociocultural perception of different body parts and tissues. The lower the sense of “personal relationship” with a specific type of tissue, organ or part of the body, the higher the motivation to donate such biological material for research purposes. Additionally, the willingness to donate is mostly shaped by social trust in physicians and scientists, and potential donors’ engagement in charity activities.
The DNA damage checkpoint: A tale from budding yeast
Authors: Pizzul Paolo , Casari Erika , Gnugnoli Marco , Rinaldi Carlo , Corallo Flavio , Longhese Maria Pia
Published: September 2022

Studies performed in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have led the way in defining the DNA damage checkpoint and in identifying most of the proteins involved in this regulatory network, which turned out to have structural and functional equivalents in humans. Subsequent experiments revealed that the checkpoint is an elaborate signal transduction pathway that has the ability to sense and signal the presence of damaged DNA and transduce this information to influence a multifaceted cellular response that is essential for cancer avoidance. This review focuses on the work that was done in Saccharomyces cerevisiae to articulate the checkpoint concept, to identify its players and the mechanisms of activation and deactivation.
Investigating CRISPR spacer targets and their impact on genomic diversification of Streptococcus mutans
Authors: Walker Alejandro R. , Shields Robert C.
Published: September 2022

CRISPR-Cas is a bacterial immune system that restricts the acquisition of mobile DNA elements. These systems provide immunity against foreign DNA by encoding CRISPR spacers that help target DNA if it re-enters the cell. In this way, CRISPR spacers are a type of molecular tape recorder of foreign DNA encountered by the host microorganism. Here, we extracted ∼8,000 CRISPR spacers from a collection of over three hundred Streptococcus mutans genomes. Phage DNA is a major target of S. mutans spacers. S. mutans strains have also generated immunity against mobile DNA elements such as plasmids and integrative and conjugative elements. There may also be considerable immunity generated against bacterial DNA, although the relative contribution of self-targeting versus bona fide intra- or inter-species targeting needs to be investigated further. While there was clear evidence that these systems have acquired immunity against foreign DNA, there appeared to be minimal impact on horizontal gene transfer (HGT) constraints on a species-level. There was little or no impact on genome size, GC content and ‘openness’ of the pangenome when comparing between S. mutans strains with low or high CRISPR spacer loads. In summary, while there is evidence of CRISPR spacer acquisition against self and foreign DNA, CRISPR-Cas does not act as a barrier on the expansion of the S. mutans accessory genome.
Healthcare resource utilization in Hepatitis C-infected patients completing eight versus twelve weeks of treatment: A retrospective cohort study
Authors: Valdez Katia E. , Javanbakht Marjan , Keith Kori , Archer Roxanne , Deng John Z. , Marx Steven E. , Kuznetsova Arina , Dylla Douglas E. , Klausner Jeffrey D.
Published: September 2022

Background

The objective of this study was to examine differences in healthcare utilization among patients receiving eight vs. 12-weeks of treatment for infection with the Hepatitis C Virus (HCV).

Methods

We conducted a retrospective cohort study among 282 treatment-naïve, HCV-infected patients. Those eligible were uninfected with the Human Immunodeficiency Virus, non-cirrhotic, and treated between 2016 and 2019 as part of an extensive, urban, university-affiliated healthcare system. Electronic medical data were abstracted starting from HCV treatment initiation and up to one year post-initiation or achievement of post-treatment sustained virologic response, whichever occurred first. The primary outcome of interest was healthcare utilization, defined by the number and type of healthcare encounters. Differences in healthcare utilization between those receiving eight vs. 12-weeks of treatment were examined using Student’s t-test, Fisher’s exact test, Pearson’s chi-square test, and the Wilcoxon rank-sum test.

Results

A total of 282 eligible patients were analyzed. At baseline, the average age was 59 years (standard deviation=12), and the majority were male (55%) and white/Caucasian (58%). There were no baseline demographic or clinical differences between those completing 8 (n=59) or 12 (n=223) weeks of treatment. While no overall difference in healthcare encounters was observed between those receiving the 8-weeks (median encounters 6; IQR 4-11) and 12-weeks of treatment (median encounters 8; IQR 5-12; P value=0.07), a notable difference was seen in the number of laboratory visits between the groups (median 1 vs. 2; P value=0.04).

Conclusions

Our findings indicate modest reductions in healthcare utilization among those receiving shorter treatment regimens for HCV infection, specifically regarding laboratory testing. These findings suggest that shorter treatment regimens may improve treatment expansion in settings that are otherwise too resource-constrained to deliver HCV care successfully.
Surface Display of porcine circovirus type 2 antigen protein cap on the spores of bacillus subtilis 168: An effective mucosal vaccine candidate
Authors: Li Weijie , Li Jianzhen , Dai Xixi , Liu Minggang , Khalique Abdul , Wang Zhenghua , Zeng Yan , Zhang Dongmei , Ni Xueqin , Zeng Dong , Jing Bo , Pan Kangcheng
Published: September 2022

The oral mucosal vaccine has great potential in preventing a series of diseases caused by porcine circovirus type 2 (PCV2) infection. This study constructed a recombinant Bacillus subtilis RB with PCV2 Capsid protein (Cap) on its spore surface and cotB as a fusion partner. The immune properties of the recombinant strain were evaluated in a mouse model. IgA in intestinal contents and IgG in serum were detected by enzyme-linked immunosorbent assay (ELISA). The results demonstrated that recombinant spores could activate strong specific mucosal and humoral immune responses. In addition, spores showed good mucosal immune adjuvant function, promoting the proliferation of CD3+, CD4+ and CD8+ T cells and other immune cells. We also found that the relative expression of inflammatory cytokines such as IL-1β, IL-6, IL-10, TNF-α and IFN in the small intestinal mucosa was significantly up-regulated under the stimulation of recombinant bacteriophage. These effects are important for the balance of Th1/Th2-like responses. In summary, our results suggest that recombinant B. subtilis RB as a feed additive provides a new strategy for the development of novel and safe PCV2 mucosal subunit vaccines.
The role of neuroimmune and inflammation in pediatric uremia-induced neuropathy
Authors: Zhu Linfeng , Tong Guoqin , Yang Fan , Zhao Yijun , Chen Guangjie
Published: September 2022

Uremic neuropathy in children encompasses a wide range of central nervous system (CNS), peripheral nervous system (PNS), autonomic nervous system (ANS), and psychological abnormalities, which is associated with progressive renal dysfunction. Clinically, the diagnosis of uremic neuropathy in children is often made retrospectively when symptoms improve after dialysis or transplantation, due to there is no defining signs or laboratory and imaging findings. These neurological disorders consequently result in increased morbidity and mortality among children population, making uremia an urgent public health problem worldwide. In this review, we discuss the epidemiology, potential mechanisms, possible treatments, and the shortcomings of current research of uremic neuropathy in children. Mechanistically, the uremic neuropathy may be caused by retention of uremic solutes, increased oxidative stress, neurotransmitter imbalance, and disturbance of the blood-brain barrier (BBB). Neuroimmune, including the change of inflammatory factors and immune cells, may also play a crucial role in the progression of uremic neuropathy. Different from the invasive treatment of dialysis and kidney transplantation, intervention in neuroimmune and targeted anti-inflammatory therapy may provide a new insight for the treatment of uremia.
Mechanisms of tumor resistance to immune checkpoint blockade and combination strategies to overcome resistance
Authors: Zhou Xiaoting , Ni Yanghong , Liang Xiao , Lin Yi , An Biao , He Xiang , Zhao Xia
Published: September 2022

Immune checkpoint blockade (ICB) has rapidly transformed the treatment paradigm for various cancer types. Multiple single or combinations of ICB treatments have been approved by the US Food and Drug Administration, providing more options for patients with advanced cancer. However, most patients could not benefit from these immunotherapies due to primary and acquired drug resistance. Thus, a better understanding of the mechanisms of ICB resistance is urgently needed to improve clinical outcomes. Here, we focused on the changes in the biological functions of CD8+ T cells to elucidate the underlying resistance mechanisms of ICB therapies and summarized the advanced coping strategies to increase ICB efficacy. Combinational ICB approaches and individualized immunotherapies require further in-depth investigation to facilitate longer-lasting efficacy and a more excellent safety of ICB in a broader range of patients.
The role of mucosal-associated invariant T cells in visceral leishmaniasis
Authors: Moreira Marcela de Lima , Borges-Fernandes Luana Oliveira , Pascoal-Xavier Marcelo Antônio , Ribeiro Ágata Lopes , Pereira Victória Hellena Silva , Pediongco Troi , Araújo Márcio Sobreira da Silva , Teixeira-Carvalho Andréa , de Carvalho Andrea Lucchesi , Mourão Maria Vitória Assumpção , Campos Flávia Alves , Borges Marineide , Carneiro Mariângela , Chen Zhenjun , Saunders Eleanor , McConville Malcolm , Tsuji Moriya , McCluskey James , Martins-Filho Olindo Assis , Eckle Sidonia Barbara Guiomar , Coelho-dos-Reis Jordana Grazziela Alves , Peruhype-Magalhães Vanessa
Published: September 2022

Mucosal-associated invariant T (MAIT) cells are restricted by MR1 and are known to protect against bacterial and viral infections. Our understanding of the role of MAIT cells in parasitic infections, such as visceral leishmaniasis (VL) caused by protozoan parasites ofLeishmania donovani, is limited. This study showed that in response toL. infantum, human peripheral blood MAIT cells from children with leishmaniasis produced TNF and IFN-γ in an MR1-dependent manner. The overall frequency of MAIT cells was inversely correlated with alanine aminotransferase levels, a specific marker of liver damage strongly associated with severe hepatic involvement in VL. In addition, there was a positive correlation between total protein levels and the frequency of IL-17A+CD8+MAIT cells, whereby reduced total protein levels are a marker of liver and kidney damage. Furthermore, the frequencies of IFN-γ+and IL-10+MAIT cells were inversely correlated with hemoglobin levels, a marker of severe anemia. In asymptomatic individuals and VL patients after treatment, MAIT cells also produced IL-17A, a cytokine signature associated with resistance to visceral leishmaniasis, suggesting that MAIT cells play important role in protecting against VL. In summary, these results broaden our understanding of MAIT-cell immunity to include protection against parasitic infections, with implications for MAIT-cell-based therapeutics and vaccines. At last, this study paves the way for the investigation of putative MAIT cell antigens that could exist in the context ofLeishmaniainfection.
Aging-related features predict prognosis and immunotherapy efficacy in hepatocellular carcinoma
Authors: Hong Ting , Su Wei , Pan Yitong , Tian Chenxi , Lei Guang
Published: September 2022

The aging microenvironment serves important roles in cancers. However, most studies focus on circumscribed hot spots such as immunity and metabolism. Thus, it is well ignored that the aging microenvironment contributes to the proliferation of tumor. Herein, we established three prognosis-distinctive aging microenvironment subtypes, including AME1, AME2, and AME3, based on aging-related genes and characterized them with “Immune Exclusion,” “Immune Infiltration,” and “Immune Intermediate” features separately. AME2-subtype tumors were characterized by specific activation of immune cells and were most likely to be sensitive to immunotherapy. AME1-subtype tumors were characterized by inhibition of immune cells with high proportion of Catenin Beta 1 (CTNNB1) mutation, which was more likely to be insensitive to immunotherapy. Furthermore, we found that CTNNB1 may inhibit the expression of C-C Motif Chemokine Ligand 19 (CCL19), thus restraining immune cells and attenuating the sensitivity to immunotherapy. Finally, we also established a robust aging prognostic model to predict the prognosis of patients with hepatocellular carcinoma. Overall, this research promotes a comprehensive understanding about the aging microenvironment and immunity in hepatocellular carcinoma and may provide potential therapeutic targets for immunotherapy.
Serine protease PRSS23 drives gastric cancer by enhancing tumor associated macrophage infiltration via FGF2
Authors: Qin Shanshan , Wang Zidi , Huang Congcong , Huang Pan , Li Dandan
Published: September 2022

Serine proteases has been considered to be closely associated with the inflammatory response and tumor progression. As a novel serine protease, the biological function of PRSS23 is rarely studied in cancers. In this study, the prognostic significance of PRSS23 was analyzed in two-independent gastric cancer (GC) cohorts. PRSS23 overexpression was clinically correlated with poor prognosis and macrophage infiltration of GC patients. Loss-of-function study verified that PRSS23 plays oncogenic role in GC. RNA-seq, qRT-PCR, western blotting and ELISA assay confirmed that serine protease PRSS23 positively regulated FGF2 expression and secretion. Single-cell analysis and gene expression correlation analysis showed that PRSS23 and FGF2 were high expressed in fibroblasts, and highly co-expressed with the biomarkers of tumor associated macrophages (TAMs), cancer-associated fibroblasts (CAFs) and mesenchymal cells. Functional analysis confirmed PRSS23/FGF2 was required for TAM infiltration. Rescue assay further verified that PRSS23 promotes GC progression and TAM infiltration through FGF2. Survival analysis showed that high infiltration of M1-macrophage predicted favorable prognosis, while high infiltration level of M2-macrophage predicted poor prognosis in GC. Our finding highlights that PRSS23 promotes TAM infiltration through regulating FGF2 expression and secretion, thereby resulting in a poor prognosis.
Tissue-specific pathway activities: A retrospective analysis in COVID-19 patients
Authors: Pham Nhung , Hu Finterly , Evelo Chris T. , Kutmon Martina
Published: September 2022

The ACE2 receptors essential for SARS-CoV-2 infections are expressed not only in the lung but also in many other tissues in the human body. To better understand the disease mechanisms and progression, it is essential to understand how the virus affects and alters molecular pathways in the different affected tissues. In this study, we mapped the proteomics data obtained from Nie X. et al. (2021) to the pathway models of the COVID-19 Disease Map project and WikiPathways. The differences in pathway activities between COVID-19 and non-COVID-19 patients were calculated using the Wilcoxon test. As a result, 46% (5,235) of the detected proteins were found to be present in at least one pathway. Only a few pathways were altered in multiple tissues. As an example, the Kinin-Kallikrein pathway, an important inflammation regulatory pathway, was found to be less active in the lung, spleen, testis, and thyroid. We can confirm previously reported changes in COVID-19 patients such as the change in cholesterol, linolenic acid, and arachidonic acid metabolism, complement, and coagulation pathways in most tissues. Of all the tissues, we found the thyroid to be the organ with the most changed pathways. In this tissue, lipid pathways, energy pathways, and many COVID-19 specific pathways such as RAS and bradykinin pathways, thrombosis, and anticoagulation have altered activities in COVID-19 patients. Concluding, our results highlight the systemic nature of COVID-19 and the effect on other tissues besides the lung.
Cardiovascular risk factors: The effects of ageing and smoking on the immune system, an observational clinical study
Authors: Grievink H. W. , Smit V. , Huisman B. W. , Gal P. , Yavuz Y. , Klerks C. , Binder C. J. , Bot I. , Kuiper J. , Foks A. C. , Moerland M.
Published: September 2022

Currently immunomodulatory compounds are under investigation for use in patients with cardiovascular disease, caused by atherosclerosis. These trials, using recurrent cardiovascular events as endpoint, require enrollment of large patient groups. We investigated the effect of key risk factors for atherosclerosis development, ageing and smoking, on the immune system, with the objective to identify biomarkers differentiating between human populations, and potentially serving as endpoints for future phase 1B trials with immunomodulatory compounds. Blood was collected from young healthy volunteers (aged 18-25 years, n=30), young smokers (18-25 years, n=20), elderly healthy volunteers (>60 years, n=20), heavy smokers (>45 years, 15 packyears, n=11) and patients with stable coronary artery disease (CAD) (>60 years, n=27). Circulating immune cell subsets were characterized by flow cytometry, and collected plasma was evaluated by proteomics (Olink). Clear ageing effects were observed, mostly illustrated by a lower level in CD8+ and naïve CD4+ and CD8+ T cells, with an increase in CD4+ and CD8+ effector memory T cells in elderly healthy volunteers compared to young healthy volunteers. Heavy smokers showed a more inflammatory cellular phenotype, especially a shift in Th1/Th2 ratio: higher Th1 and lower Th2 percentages compared to young healthy volunteers. A significant decrease in circulating atheroprotective oxLDL-specific IgM was found in patients with CAD compared to young healthy volunteers. Elevated pro-inflammatory and chemotactic proteins TREM1 and CCL11 were observed in elderly volunteers compared to young volunteers. In addition, heavy smokers had an increase in pro-inflammatory cytokine IL-6 and lysosomal protein LAMP3. These data show that ageing and smoking are associated with an inflammatory immunophenotype, and that heavy smokers or aged individuals may serve as potential populations for future clinical trials investigating immunomodulatory drugs targeted for cardiovascular disease.
A novel genomic instability-derived lncRNA signature to predict prognosis and immune characteristics of pancreatic ductal adenocarcinoma
Authors: Yang Huijie , Zhang Weiwen , Ding Jin , Hu Jingyi , Sun Yi , Peng Weijun , Chu Yi , Xie Lingxiang , Mei Zubing , Shao Zhuo , Xiao Yang
Published: September 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor of the digestive system. Its grim prognosis is mainly attributed to the lack of means for early diagnosis and poor response to treatments. Genomic instability is shown to be an important cancer feature and prognostic factor, and its pattern and extent may be associated with poor treatment outcomes in PDAC. Recently, it has been reported that long non-coding RNAs (lncRNAs) play a key role in maintaining genomic instability. However, the identification and clinical significance of genomic instability-related lncRNAs in PDAC have not been fully elucidated.

Methods

Genomic instability-derived lncRNA signature (GILncSig) was constructed based on the results of multiple regression analysis combined with genomic instability-associated lncRNAs and its predictive power was verified by the Kaplan-Meier method. And real-time quantitative polymerase chain reaction (qRT-PCR) was used for simple validation in human cancers and their adjacent non-cancerous tissues. In addition, the correlation between GILncSig and tumor microenvironment (TME) and epithelial-mesenchymal transition (EMT) was investigated by Pearson correlation analysis.

Results

The computational framework identified 206 lncRNAs associated with genomic instability in PDAC and was subsequently used to construct a genome instability-derived five lncRNA-based gene signature. Afterwards, we successfully validated its prognostic capacity in The Cancer Genome Atlas (TCGA) cohort. In addition, via careful examination of the transcriptome expression profile of PDAC patients, we discovered that GILncSig is associated with EMT and an adaptive immunity deficient immune profile within TME.

Conclusions

Our study established a genomic instability-associated lncRNAs-derived model (GILncSig) for prognosis prediction in patients with PDAC, and revealed the potential functional regulatory role of GILncSig.
Case report: Refractory intestinal Behçet’s syndrome successfully treated with tofacitinib: A report of four cases
Authors: Zhao Na , Tang Yanchun , Wang Shaokun , Cui Liping , Sun Xuehui , Wang Zhihua , Liu Ying
Published: September 2022

Behçet’s syndrome (BS) is a chronic form of relapsing multisystem vasculitis, characterized by recurrent oral and genital ulcers. Intestinal BS is a special type of BS. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BS, and punched-out ulcers can be observed in the intestine or esophagus. At present, there is no recognized radical treatment for intestinal BS. Glucocorticoids and immunosuppressants are currently the main drugs used to improve the condition. Although it has been reported that monoclonal anti-TNF antibodies may be effective for some refractory intestinal BS, further randomized, prospective trials are necessary to confirm these findings. Some patients are restricted from using biological agents because of serious allergic reactions of drugs, inconvenient drug injections or the impact of the novel coronavirus epidemic. If endoscopic remission (endoscopic healing) is not achieved for a prolonged period of time, serious complications, such as perforation, fistula formation, and gastrointestinal bleeding can be induced. Therefore, it is necessary to develop new treatment methods for controlling disease progression. We reviewed the relevant literature, combined with the analysis of the correlation between the pathogenesis of BS and the mechanism of Janus kinase (JAK) inhibition, and considered that tofacitinib (TOF) may be effective for managing refractory intestinal BS. We report for the first time that four patients with severe refractory intestinal BS were successfully treated with TOF. We hope to provide valuable information on JAK inhibitors as potential therapeutic targets for the treatment of severe refractory intestinal BS.
Largemouth bass (Micropterus salmoides) exhibited better growth potential after adaptation to dietary cottonseed protein concentrate inclusion but experienced higher inflammatory risk during bacterial infection
Authors: Wang Mengya , Chen Zhenwei , Wang Yunhua , Zou Jiahong , Li Shuaitong , Guo Xiaolong , Gao Jian , Wang Qingchao
Published: September 2022

Cottonseed protein concentrate (CPC) has been proven to partially replace fishmeal without adverse effects on fish growth performance, while little information is known about the effects on liver health during bacterial infection. In the present study, 15% CPC was included into the diet of juvenile largemouth bass (32.12 ± 0.09g) to replace fishmeal for 8 weeks, with fish growth potential and hepatic inflammatory responses during Nocardia seriolae (N. seriolae) infection systemically evaluated. After adaptation to dietary CPC inclusion, largemouth bass even exhibited better growth potential with higher SGR and WGR during the last three weeks of whole feeding trial, which was accompanied with higher phosphorylation level of TOR signaling and higher mRNA expression level of myogenin (myog). At the end of 8-weeks feeding trial, the histological structure of largemouth bass liver was not significantly affected by dietary CPC inclusion, accompanied with the similar expression level of genes involved in innate and adaptive immunity and comparable abundance of T cells in bass liver. N.seriolae infection induced the pathological changes of bass liver, while such hepatic changes were more serious in CPC group than that in FM group. Additionally, RT-qPCR results also suggested that largemouth bass fed with CPC experienced much higher inflammatory potential both in liver and gill during N. seriolae infection, which was accompanied with higher expression level of genes involved in pyroptosis. Therefore, this study demonstrated that the application of CPC in largemouth bass diet should be careful, which may induce higher inflammatory potential during N. seriolae infection.
Phylogeny and adaptative evolution to chemosynthetic habitat in barnacle (Cirripedia: Thoracica) revealed by mitogenomes
Authors: Gan Zhibin , Jones Diana S. , Liu Xinming , Sui Jixing , Dong Dong , Li Xinzheng
Published: September 2022

Thoracican barnacles represent a unique group that has evolved in parallel identical somatotype s (sessile, stalked and asymmetric) in both normal and chemosynthetic environments. Hydrothermal vents and methane seeps are typical extreme deep-sea chemosynthetic habitats for marine macrobenthos. Characterizing the evolutionary history and adaptive strategy of barnacles is fundamentally important for understanding their origin, speciation, and diversification. Herein, we performed a series of phylogenetic analyses focusing on the mitochondrial genomes of the main extant barnacle lineages. Phylogenetic inferences and topology tests contradict the view of the sister relationship between verrucomorphs and balanomorphs, instead revealing that pollicipedids, calanticids and balanomorphs share common ancestor. Selective pressure analyses indicate that the two barnacle lineages of chemosynthetic ecosystems exhibit similar patterns in their evolution of adaptive characters, but have diverse and specific positive substitution sites of mitogenomes. Divergence times suggest that chemosynthetic barnacles originated in the Cenozoic, coinciding with the origins of other metazoan animals in chemosynthetic habitats as well as the Paleogene mass extinction and oceanic anoxic events. It is reasonable to suppose that ecological niche vacancy, sitotaxis, gene specificity in adaptive stress responses, and the subdivision of the ecological niche contributed to the origin and diversification of barnacles in chemosynthetic ecosystems.
Occurrence and driving mechanism of antibiotic resistance genes in marine recreational water around Qinhuangdao, China
Authors: Han Ying , Hu Yikai , Wen Hexin , Wu Jiayue , Liu Yuanwang , Zhang Yingchao , Wu Hao
Published: September 2022

Rapid urbanization and other human activities have exacerbated the global human health risks associated with antibiotic resistance genes (ARGs). Swimming in contaminated waters is one of important pathways by which humans can be exposed to ARGs. However, little is currently known about the overall levels of ARGs in recreational waters and the forces driving their occurrence. In this study, we analyzed the ARGs and bacterial communities in water samples taken from five recreational coastal waters (RCWs) and their adjacent estuaries in the Qinhuangdao area of Bohai Bay, China, using high-throughput quantitative PCR and 16S rRNA gene amplicon sequencing technique. The relative abundances of ARGs in RCWs varied greatly, and occurred at levels close to, or even higher than, those in the neighboring estuaries, ranging from 9.4×10-2 to 2.5 copies/16S rRNA gene. A total of 159 different ARGs able to express resistance to almost all antibiotics were detected in all of the water samples. β-lactamase resistance genes (blaTEM gene) were the most abundance of all ARGs. Patterns of ARG occurrence were significantly correlated with those of bacterial communities (Mantel test, P < 0.05). A partial redundancy analysis showed that differences in bacterial communities accounted for 50.3% of the total ARG variations, which was much higher than the sum of the contribution of mobile genetic elements (18.1%) and the other selected environmental factors (8.3%). Principal coordinate analysis based on Bray-Curtis distance revealed the similarities between ARG profiles in the RCWs and in their adjacent estuaries. To our knowledge, this is the first study to report the ARG profiles in RCWs using high throughput qPCR technology. These results implied that it is necessary to develop proper regulations and monitoring strategies of RCWs for reducing risks of ARGs on human health.
Response of benthic foraminifera to environmental successions of cold seeps from Vestnesa Ridge, Svalbard: Implications for interpretations of paleo-seepage environments
Authors: Melaniuk Katarzyna , Sztybor Kamila , Treude Tina , Sommer Stefan , Zajączkowski Marek , Rasmussen Tine L.
Published: September 2022

This paper presents the results of a study on the response of living benthic foraminifera to progressing environmental successions in a cold-seep ecosystem. Sediment samples were collected from Vestnesa Ridge (79°N, Fram Strait) at ~1200 m water depth. The distribution of live (Rose Bengal-stained) foraminifera were analyzed in the upper sediment layers in relation to pore water biogeochemical data together with the distribution of sulfur-bacterial mats and Siboglinidae tubeworms. At methane cold seeps, the process of environmental succession is strongly connected to the duration and strength of methane seepage and the intensity of methane-related biological processes, e.g, aerobic and anaerobic oxidation of methane (MOx and AOM, respectively). The results show that the distribution patterns of benthic foraminifera change according to the progressing environmental succession. The benthic foraminifera seemed to thrive in sediments with a moderate activity of seepage, dominated by MOx, i.e, at an early stage of seepage or when seepage decreases at a late stage of the succession. Species composition of the foraminiferal fauna under these conditions was similar to the control sites (outside of pockmarks with no seepage); the dominant species being Melonis barleeanus and Cassidulina neoteretis. In sediments with strong seepage and high AOM activity, the hostile environmental conditions due to the presence of toxic sulfide caused a reduction in the foraminiferal population, and samples were almost barren of foraminifera. In environments of moderate methane seepage, the presence of chemosynthetic Siboglinidae tube worms potentially support communities of the epibenthic species Cibicidoides wuellerstorfi. Despite the very different environmental conditions, the foraminiferal assemblages were very similar (or nearly absent). Therefore, the foraminiferal faunas cannot be used as exclusive indicators of past strength of methane seepage in palaeoceanographic interpretations.
Identification of a prognostic index system and tumor immune infiltration characterization for lung adenocarcinoma based on mRNA molecular of pyroptosis
Authors: Li Huawei , Chang Xiaoyan , Wang Haiyan , Peng Bo , Wang Jun , Zhang Pengfei , Zhang Linyou
Published: September 2022

Background and purpose

Pyroptosis is a form of programmed cell death, which plays an important role in tumorigenesis, progression, and regulation of the tumor microenvironment. It can affect lung adenocarcinoma (LUAD) progression. This study aimed to construct a pyroptosis-related mRNA prognostic index (PRMPI) for LUAD and clarify the tumor microenvironment infiltration characterization of LUAD.

Materials and methods

We performed a univariate Cox regression analysis for pyroptosis-related mRNAs in the TCGA cohort. Then, we used LASSO Cox regression to establish a PRMPI. The quantitative real time polymerase chain reaction (qRT-PCR) was used to quantify the relative expression of pyroptosis-related mRNAs. The CPTAC cohort was used to confirm the stability and wide applicability of the PRMPI. The single-sample gene set enrichment analysis (ssGSEA) was performed to assess the tumor microenvironment infiltration characterization.

Results

A total of 36 pyroptosis-related mRNAs were identified. The PRMPI was established based on five pyroptosis-related mRNAs. The expression patterns of these mRNAs were verified in LUAD samples from our medical center by qRT-PCR. High-PRMPI patients had worse overall survival than low-PRMPI patients. The result was validated in the CPTAC cohort. The comprehensive analysis indicated that the high-PRMPI patients exhibited lower immune activity, more aggressive immunophenotype, lower expression of immune checkpoint molecule, higher TP53 mutation rate, and higher tumor stemness than low-PRMPI patients. Low-PRMPI patients may be more sensitive to immunotherapy, while high-PRMPI patients may benefit more from chemotherapy and targeted therapy.

Conclusions

The PRMPI may be a promising biomarker to predict the prognosis, tumor microenvironment infiltration characterization, and the response to adjuvant therapy in LUAD.
Building and implementing a contactless clinical trial protocol for patients with COVID-19: A Korean perspective
Authors: Bae Ye Seul , Sung Sumi , Lee Jungeun , Lee Hyeonji , Chie Eui Kyu
Published: September 2022

Introduction

To effectively manage patients with coronavirus disease 2019 (COVID-19) while minimizing contact between medical staff, clinical trial protocol that facilitates contactless patient management was designed to predict deterioration of disease condition and monitor mental health status.

Methods

Through consultation with infectious disease specialists and psychiatrists, this study identified main clinical indicators related to respiratory and non-respiratory outcomes, and mental health. Telehealth devices that could collect relevant data indicators were explored. The following three modes were identified: wearable devices, video calls, and online questionnaires. Clinical trial protocol was implemented to patients confirmed with COVID-19 infection and admitted to Seongnam residential treatment centers between September 1, 2021 and December 30, 2021. Data were collected from wearable devices, video calls, online questionnaires, and from electronic health records. Participant satisfaction was assessed through an online survey at the time of discharge.

Results

In total, 120 asymptomatic and mildly symptomatic COVID-19 patients participated in this trial. Seven types of physiological and life log data were collected from 87 patients using wearable devices, video and audio recordings, and online mental health-related questionnaire. Most participants were satisfied with the overall trial process, but perceived difficulties in using telehealth devices.

Conclusion

This trial collected simultaneously generated multimodal patient data using various telehealth devices in a contactless setting for COVID-19 patients. Data collected in this study will be used to build a remote patient management system based on the prediction algorithms.
Identification, characterization, and expression profiling of the putative U-box E3 ubiquitin ligase gene family in Sorghum bicolor
Authors: Fang Yuanpeng , Du Qiaoli , Yang Qian , Jiang Junmei , Hou Xiaolong , Yang Zaifu , Zhao Degang , Li Xiangyang , Xie Xin
Published: September 2022

The U-box family is one of the main E3 ubiquitin ligase families in plants. The U-box family has been characterized in several species. However, genome-wide gene identification and expression profiling of the U-box family in response to abiotic stress in Sorghum bicolor remain unclear. In this study, we broadly identified 68 U-box genes in the sorghum genome, including 2 CHIP genes, and 1 typical UFD2 (Ub fusion degradation 2) gene. The U-box gene family was divided into eight subclasses based on homology and conserved domain characteristics. Evolutionary analysis identified 14, 66, and 82 U-box collinear gene pairs in sorghum compared with arabidopsis, rice, and maize, respectively, and a unique tandem repeat pair (SbPUB26/SbPUB27) is present in the sorghum genome. Gene Ontology (GO) enrichment analysis showed that U-box proteins were mainly related to ubiquitination and modification, and various stress responses. Comprehensive analysis of promoters, expression profiling, and gene co-regulation networks also revealed that many sorghum U-box genes may be correlated with multiple stress responses. In summary, our results showed that sorghum contains 68 U-box genes, which may be involved in multiple abiotic stress responses. The findings will support future gene functional studies related to ubiquitination in sorghum.
The red thread between methylation and mutation in bacterial antibiotic resistance: How third-generation sequencing can help to unravel this relationship
Authors: Papaleo Stella , Alvaro Alessandro , Nodari Riccardo , Panelli Simona , Bitar Ibrahim , Comandatore Francesco
Published: September 2022

DNA methylation is an important mechanism involved in bacteria limiting foreign DNA acquisition, maintenance of mobile genetic elements, DNA mismatch repair, and gene expression. Changes in DNA methylation pattern are observed in bacteria under stress conditions, including exposure to antimicrobial compounds. These changes can result in transient and fast-appearing adaptive antibiotic resistance (AdR) phenotypes, e.g., strain overexpressing efflux pumps. DNA methylation can be related to DNA mutation rate, because it is involved in DNA mismatch repair systems and because methylated bases are well-known mutational hotspots. The AdR process can be the first important step in the selection of antibiotic-resistant strains, allowing the survival of the bacterial population until more efficient resistant mutants emerge. Epigenetic modifications can be investigated by third-generation sequencing platforms that allow us to simultaneously detect all the methylated bases along with the DNA sequencing. In this scenario, this sequencing technology enables the study of epigenetic modifications in link with antibiotic resistance and will help to investigate the relationship between methylation and mutation in the development of stable mechanisms of resistance.
Drug development concerning metallo-β-lactamases in gram-negative bacteria
Authors: Li Xiuyun , Zhao Jing , Zhang Bin , Duan Xuexia , Jiao Jin , Wu Weiwei , Zhou Yuxia , Wang Hefeng
Published: September 2022

β-Lactams have been a clinical focus since their emergence and indeed act as a powerful tool to combat severe bacterial infections, but their effectiveness is threatened by drug resistance in bacteria, primarily by the production of serine- and metallo-β-lactamases. Although once of less clinical relevance, metallo-β-lactamases are now increasingly threatening. The rapid dissemination of resistance mediated by metallo-β-lactamases poses an increasing challenge to public health worldwide and comprises most existing antibacterial chemotherapies. Regrettably, there have been no clinically available inhibitors of metallo-β-lactamases until now. To cope with this unique challenge, researchers are exploring multidimensional strategies to combat metallo-β-lactamases. Several studies have been conducted to develop new drug candidates or calibrate already available drugs against metallo-β-lactamases. To provide an overview of this field and inspire more researchers to explore it further, we outline some promising candidates targeting metallo-β-lactamase producers, with a focus on Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Promising candidates in this review are composed of new antibacterial drugs, non-antibacterial drugs, antimicrobial peptides, natural products, and zinc chelators, as well as their combinations with existing antibiotics. This review may provide ideas and insight for others to explore candidate metallo-β-lactamases as well as promote the improvement of existing data to obtain further convincing evidence.
Reconciling concepts of black queen and tragedy of the commons in simulated bulk soil and rhizosphere prokaryote communities
Authors: Finn Damien Robert , App Mario , Hertzog Lionel , Tebbe Christoph C.
Published: September 2022

The Black Queen hypothesis describes the evolutionary strategy to lose costly functions in favour of improving growth efficiency. This results in mutants (cheaters) becoming obligately dependent upon a provider (black queen) to produce a necessary resource. Previous analyses demonstrate black queens and cheaters reach a state of equilibrium in pair-wise systems. However, in complex communities, accumulation of cheaters likely poses a serious burden on shared resources. This should result in a Tragedy of the Commons (ToC), whereby over-utilisation of public resources risks making them growth-limiting. With a collection of differential equations, microbial communities composed of twenty prokaryote ‘species’ either from rhizosphere, characterised by abundant carbon and energy sources, or bulk soil, with limited carbon and energy supply, were simulated. Functional trait groups differed based on combinations of cellulase and amino acid production, growth and resource uptake. Randomly generated communities were thus composed of species that acted as cellulolytic prototrophic black queens, groups that were either cellulolytic or prototrophic, or non-cellulolytic auxotrophic cheaters. Groups could evolve to lose functions over time. Biomass production and biodiversity were tracked in 8,000 Monte Carlo simulations over 500 generations. Bulk soil favoured oligotrophic co-operative communities where biodiversity was positively associated with growth. Rhizosphere favoured copiotrophic cheaters. The most successful functional group across both environments was neither black queens nor cheaters, but those that balanced providing an essential growth-limiting function at a relatively low maintenance cost. Accumulation of loss of function mutants in bulk soil risked resulting in loss of cumulative growth by ToC, while cumulative growth increased in the rhizosphere. In the bulk soil, oligotrophic adaptations assisted species in avoiding extinction. This demonstrated that loss of function by mutation is a successful evolutionary strategy in host-associated and/or resource-rich environments, but poses a risk to communities that must co-operate with each other for mutual co-existence. It was concluded that microbial communities must follow different evolutionary and community assembly strategies in bulk soil versus rhizosphere, with bulk soil communities more dependent on traits that promote co-operative interactions between microbial species.