bluuebunny/crossref_metadata_2025 huggingface dataset:
Ancestral sequence reconstruction as a tool to study the evolution of wood decaying fungi
Authors: Ayuso-Fernández Iván , Molpeceres Gonzalo , Camarero Susana , Ruiz-Dueñas Francisco Javier , Martínez Angel T.
Published: October 2022

The study of evolution is limited by the techniques available to do so. Aside from the use of the fossil record, molecular phylogenetics can provide a detailed characterization of evolutionary histories using genes, genomes and proteins. However, these tools provide scarce biochemical information of the organisms and systems of interest and are therefore very limited when they come to explain protein evolution. In the past decade, this limitation has been overcome by the development of ancestral sequence reconstruction (ASR) methods. ASR allows the subsequent resurrection in the laboratory of inferred proteins from now extinct organisms, becoming an outstanding tool to study enzyme evolution. Here we review the recent advances in ASR methods and their application to study fungal evolution, with special focus on wood-decay fungi as essential organisms in the global carbon cycling.
Plant biomacromolecule delivery methods in the 21st century
Authors: Rustgi Sachin , Naveed Salman , Windham Jonathan , Zhang Huan , Demirer Gözde S.
Published: October 2022

The 21st century witnessed a boom in plant genomics and gene characterization studies through RNA interference and site-directed mutagenesis. Specifically, the last 15 years marked a rapid increase in discovering and implementing different genome editing techniques. Methods to deliver gene editing reagents have also attempted to keep pace with the discovery and implementation of gene editing tools in plants. As a result, various transient/stable, quick/lengthy, expensive (requiring specialized equipment)/inexpensive, and versatile/specific (species, developmental stage, or tissue) methods were developed. A brief account of these methods with emphasis on recent developments is provided in this review article. Additionally, the strengths and limitations of each method are listed to allow the reader to select the most appropriate method for their specific studies. Finally, a perspective for future developments and needs in this research area is presented.
Polycomb repressive complex 2 controls cardiac cell fate decision via interacting with RNA: Promiscuously or well-ordered
Authors: Wang Gang , Ye Heng , Wang Xuchao , Liu Binbin
Published: October 2022

The epigenetic landscape determines cell fate during heart development. Polycomb repressive complex 2 (PRC2) mediates histone methyltransferase activity during cardiac cell differentiation. The PRC2 complex contains the proteins embryonic ectoderm development (EED), suppressor of zeste (SUZ12), the chromatin assembly factor 1 (CAF1) histone-binding proteins RBBP4 and RBBP7, and the histone methyltransferase called enhancer of zeste (EZH2 or EZH1), which incorporates the Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain. Cardiac PRC2-deficient mice display lethal congenital heart malformations. The dynamic process of cardiac cell fate decisions is controlled by PRC2 and the PRC2-mediated epigenetic landscape. Although specific individual long noncoding RNAs (lncRNAs) including Braveheart were widely reported to regulate the recruitments of PRC2 to their specific targets, a promiscuous RNA binding profile by PRC2 was also identified to play an essential role in cardiac cell fate decision. In this review, we focus on RNA-mediated PRC2 recruitment machinery in the process of cardiac cell fate decisions. The roles of individual lncRNAs which recruit PRC2, as well as promiscuous RNA binding by PRC2 in heart development are summarized. Since the binding priority of RNAs with different primary and secondary structures differs in its affinity to PRC2, the competitive relationship between individual lncRNAs binding and promiscuous RNA binding by PRC2 may be important for understanding the machinery by which biding of individual lncRNA and promiscuous RNA by PRC2 coordinately control the well-ordered dynamic cardiac cell lineage differentiation process.
Identification of cuproptosis-related gene signature to predict prognosis in lung adenocarcinoma
Authors: Lv Yanju , Xiao Yajie , Cui Xiaoli , Luo Haitao , Xu Long
Published: October 2022

Background: Studies have reported that coppers are involved in the tumorigenesis and development of tumor. In herein, we aimed to construct a prognostic classification system for lung adenocarcinoma (LUAD) associated with cuproptosis.

Methods: Samples information of LUAD were acquired from The Cancer Genome Atlas (TCGA) and GSE31210 dataset. Cuproptosis-related genes were screened from previous research. ConsensusClusterPlus was applied to determine molecular subtypes, which evaluated by genome analysis, tumor immune microenvironment analysis, immunotherapy, functional enrichment analysis. Furthermore, univariate Cox analysis combined with Lasso analysis were employed to construct a cuproptosis-related risk model for LUAD.

Results: 14 genes related to cuproptosis phenotype were identified, and 2 clusters (C1 and C2) were determined. Among which, C1 had better survival outcome, less advanced stages, enhanced immune infiltration and enriched in TCA related pathways. A 7 cuproptosis-associated genes risk model was constructed, and the performance was verified in the GSE31210 dataset. A higher RiskScore was significantly correlated with worse overall survival, advanced stages. Cox survival analysis showed that RiskScore was an independent predictor. High-risk group patients had weakened immune infiltration, less likely to benefit from immunotherapy and was more sensitived to immunotherapy.

Conclusion: The cuproptosis-related gene signature could serve as potential prognostic predictors for LUAD patients and may provide clues for the intervention of cuproptosis induced harm and targeted anti-tumor application.
Evolution of surrogate light chain in tetrapods and the relationship between lengths of CDR H3 and VpreB tails
Authors: Ott Jeannine A. , Haakenson Jeremy K. , Kelly Abigail R. , Christian Claire , Criscitiello Michael F. , Smider Vaughn V.
Published: October 2022

In the mammalian immune system, the surrogate light chain (SLC) shapes the antibody repertoire during B cell development by serving as a checkpoint for production of functional heavy chains (HC). Structural studies indicate that tail regions of VpreB contact and cover the third complementarity-determining region of the HC (CDR H3). However, some species, particularly bovines, have CDR H3 regions that may not be compatible with this HC-SLC interaction model. With immense structural and genetic diversity in antibody repertoires across species, we evaluated the genetic origins and sequence features of surrogate light chain components. We examined tetrapod genomes for evidence of conserved gene synteny to determine the evolutionary origin of VpreB1, VpreB2, and IGLL1, as well as VpreB3 and pre-T cell receptor alpha (PTCRA) genes. We found the genes for the SLC components (VpreB1, VpreB2, and IGLL1) only in eutherian mammals. However, genes for PTCRA occurred in all amniote groups and genes for VpreB3 occurred in all tetrapod groups, and these genes were highly conserved. Additionally, we found evidence of a new VpreB gene in non-mammalian tetrapods that is similar to the VpreB2 gene of eutherian mammals, suggesting VpreB2 may have appeared earlier in tetrapod evolution and may be a precursor to traditional VpreB2 genes in higher vertebrates. Among eutherian mammals, sequence conservation between VpreB1 and VpreB2 was low for all groups except rabbits and rodents, where VpreB2 was nearly identical to VpreB1 and did not share conserved synteny with VpreB2 of other species. VpreB2 of rabbits and rodents likely represents a duplicated variant of VpreB1 and is distinct from the VpreB2 of other mammals. Thus, rabbits and rodents have two variants of VpreB1 (VpreB1-1 and VpreB1-2) but no VpreB2. Sequence analysis of VpreB tail regions indicated differences in sequence content, charge, and length; where repertoire data was available, we observed a significant relationship between VpreB2 tail length and maximum DH length. We posit that SLC components co-evolved with immunoglobulin HC to accommodate the repertoire – particularly CDR H3 length and structure, and perhaps highly unusual HC (like ultralong HC of cattle) may bypass this developmental checkpoint altogether.
Association of dengue infection with anti-alpha-gal antibodies, IgM, IgG, IgG1, and IgG2
Authors: Olajiga Olayinka M. , Maldonado-Ruiz L. Paulina , Fatehi Soheila , Cardenas Jenny C. , Gonzalez Maria U. , Gutierrez-Silva Lady Y. , Londono-Renteria Berlin , Park Yoonseong
Published: October 2022

Dengue virus (DENV) transmitted by theAedesmosquitoes is the etiological agent of dengue fever, one of the fastest-growing reemerging mosquito-borne diseases on the planet with a 30-fold surge in the last five decades. Interestingly, many arthropod-borne pathogens, including DENV type 2, have been reported to contain an immunogenic glycan galactose-alpha1,3-galactose (alpha-Gal or aGal). The aGal molecule is a common oligosaccharide found in many microorganisms and in most mammals, except for humans and the Old-World primates. The loss of aGal in humans is considered to be an evolutionary innovation for enabling the production of specific antibodies against aGal that could be presented on the glycan of pathogens. The objective of this study was to evaluate different anti-aGal antibodies (IgM, IgG, IgG1, and IgG2) in people exposed to DENV. We observed a significant difference in anti-aGal IgG and IgG1 levels among dengue severity classifications. Furthermore, a significant positive correlation was observed between the anti-aGal IgG and the number of days with dengue symptoms in patients. Additionally, both anti-aGal IgM and IgG levels differ between the two geographical locations of patients. While the anti-aGal IgM and IgG2 levels were not significantly different according to the dengue severity levels, age was negatively correlated with anti-aGal IgM and positively correlated with anti-aGal IgG2. Significant involvement of aGal antibodies in Dengue infection processes is suggested based on the results. Our results open the need for further studies on the exact roles and the mechanisms of the aGal antibodies in Dengue infection.
Therapeutic effect on Alveolar echinococcosis by targeting EM-Leucine aminopeptidase
Authors: Zhou Zhen , Zhou Pei , Mu Yalin , Wang Lei , Cao Zhenjin , Dong Shizhong , Bao Haihua , Yang Baoliang , Xin Minyuan , Li Runle , Ge Ri-Li , Tang Feng
Published: October 2022

Alveolar echinococcosis (AE) is a parasitic disease caused by E. multilocularis metacestodes and it is highly prevalent in the northern hemisphere. We have previously found that vaccination with E. multilocularis Leucine aminopeptidase (EM-LAP) induced specific immune response and had an inhibiting effect on the parasites. In this study, the therapeutic effect of recombinant EM-LAP (rEM-LAP) on AE was evaluated and verified using Ubenimex, a broad-spectrum inhibitor of LAP. The results reveal that rEM-LAP could inhibit cyst growth and invasion and induce specific immunity response in BALB/c mice infected with E. multilocularis protoscoleces. The ultrasonic, MRI, and morphological results show that treatment with rEM-LAP inhibits E. multilocularis infection and reduces cyst weight, number, fibrosis and invasion. The same effect is observed for the treatment with Ubenimex by inhibiting LAP activity. The indirect ELISA shows that rEM-LAP could induce specific immunity response and produce high levels of IgG, IgG1, IgG2a, IgM, and IgA, and the serum levels of IFN-γ and IL-4 are significantly increased compared to the control groups, indicating that treatment with rEM-LAP leads to a Th1 and Th2 mixed-type immune response. This study suggests that EM-LAP could be a potential therapeutic target of E. multilocularis infection.
Gut microbiota composition reflects disease progression, severity and outcome, and dysfunctional immune responses in patients with hypertensive intracerebral hemorrhage
Authors: Luo Jielian , Chen Yang , Tang Guanghai , Li Zhuo , Yang Xiaobo , Shang Xiaoxiao , Huang Tao , Huang Gan , Wang Lixin , Han Yun , Zhou Yuexiang , Wang Chuyang , Wu Bin , Guo Qihua , Gong Baoying , Li Mengzhen , Wang Ruihua , Yang Jiecong , Cui Wanzhen , Zhong Jianbin , Zhong Linda Ld , Guo Jianwen
Published: October 2022

Objective

In this study, we aimed to explore the alterations in gut microbiota composition and cytokine responses related to disease progression, severity, and outcomes in patients with hypertensive intracerebral hemorrhage (ICH).

Methods

Fecal microbiota communities of 64 patients with ICH, 46 coronary heart disease controls, and 23 healthy controls were measured by sequencing the V3-V4 region of the 16S ribosomal RNA (16S rRNA) gene. Serum concentrations of a broad spectrum of cytokines were examined by liquid chips and ELISA. Relationships between clinical phenotypes, microbiotas, and cytokine responses were analyzed in the group with ICH and stroke-associated pneumonia (SAP), the major complication of ICH.

Results

In comparison with the control groups, the gut microbiota of the patients with ICH had increased microbial richness and diversity, an expanded spectrum of facultative anaerobes and opportunistic pathogens, and depletion of anaerobes. Enterococcus enrichment and Prevotella depletion were more significant in the ICH group and were associated with the severity and functional outcome of ICH. Furthermore, Enterococcus enrichment and Prevotella depletion were also noted in the SAP group in contrast to the non-SAP group. Enterococci were also promising factors in the prognosis of ICH. The onset of ICH induced massive, rapid activation of the peripheral immune system. There were 12 cytokines (Eotaxin, GM-CSF, IL-8, IL-9, IL-10, IL-12p70, IL-15, IL-23, IL-1RA, IP-10, RANTES, and TNF-α) changed significantly with prolongation of ICH, and the Th2 responses correlated with the 90-day outcomes. Cytokines TNF-α, IP-10, IL-1RA, IL-8, IL-18, and MIP-1β in SAP group significantly differed from non-SAP group. Among these cytokines, only IP-10 levels decreased in the SAP group. Enterococcus was positively associated with IL-1RA and negatively associated with IP-10, while Prevotella was inversely associated in both the ICH and SAP groups.

Conclusion

This study revealed that gut dysbiosis with enriched Enterococcus and depleted Prevotella increased the risk of ICH and subsequently SAP. The altered gut microbiota composition and serum cytokine profiles are potential biomarkers that reflect the inciting physiologic insult/stress involved with ICH.
Performance of the clinical assessment scale for autoimmune encephalitis in a pediatric autoimmune encephalitis cohort
Authors: Zhou Hao , Deng Qun , Yang Zailan , Tai Zhaoqing , Liu Kaiyu , Ping Yue , Chen Yun , Mao Zhifeng , Hu Xiao , Wang Yi
Published: October 2022

Background

The Clinical Assessment Scale for Autoimmune Encephalitis (CASE), a new scale used for rating the severity of autoimmune encephalitis (AE), has demonstrated good validity and reliability in adults with AE, but there is a shortage of data on its performance in children with AE. This study aimed to assess the reliability and validity of the CASE in a cohort of children with AE.

Methods

Forty-seven pediatric inpatients with AE who visited Guizhou Provincial People’s Hospital between January 1, 2017, and October 31, 2021, were enrolled in the study. The CASE and mRS scores were obtained through a review of detailed medical records from the Health Information System by two pediatric neurologists. Finally, the performance of the CASE in this pediatric AE cohort was analyzed.

Results

The results showed that anti-NMDA receptor encephalitis was the most common (61.70%) type of AE in children. The most common clinical manifestations were language problems (85.1%), psychiatric symptoms (80.9%), and dyskinesia/dystonia (78.7%). The CASE had good item reliability and interevaluator reliability; the Cronbach’s alpha value of the total score was 0.825, and the intraclass correlation (ICC) was 0.980. The Cronbach’s alpha value by item ranged from 0.16 to 0.406; items 1 and 9 had the lowest and highest Cronbach’s alpha values, respectively. The criterion validity between CASE and mRS total scores, as quantified by Pearson correlation, was 0.459, indicating slight to good criterion validity. The area under the curve (AUC) was 0.992 (95% confidence interval: 0.974-1.00). A cutoff value of 14 was selected to determine whether a patient needed admission to the ICU; this cutoff had a sensitivity of 100% and a specificity of 92%. The changes in EEG, MRI, and antibody titers were not related to the severity of AE. A CASE score cutoff of 9 was selected to indicate whether second-line treatment would be needed.

Conclusion

The CASE has good reliability and validity in children with AE; however, some items of the CASE may not apply to this population. Thus, an in-depth study of the CASE is needed in children with AE.
A comprehensive investigation discovered the novel methyltransferase METTL24 as one presumably prognostic gene for kidney renal clear cell carcinoma potentially modulating tumor immune microenvironment
Authors: Jiang Zhongji , Zhang Wei , Zeng Zhipeng , Tang Donge , Li Chujiao , Cai Wanxia , Chen Yumei , Li Ya , Jin Qiu , Zhang Xinzhou , Yin Lianghong , Liu Xueyan , Xu Yong , Dai Yong
Published: October 2022

Background

Recently, an increasing number of studies have uncovered the aberrant expression of methyltransferase-like family (METTL) plays an important role in tumorigenesis, such as METTL3 (an m6A writer). In our recent work, we discovered METTL24 expression was highly associated with the hazard ratio (HR) of kidney renal clear cell carcinoma (KIRC) compared to other tumors, implying a special function of METTL24 in KIRC carcinogenesis. Until now, the functions and mechanisms of METTL24 in KIRC have remained mostly unknown.

Methods

The mRNA expression of METTL24 in KIRC was analyzed using the TIMER 2.0, GEPIA, and UALCAN databases. The immunohistochemical assay was performed to validate METTL24 expression in our self-built Chinese cohort (n tumor = 88, n normal = 85). The gene set enrichment analysis (GSEA) was used to investigate the biological processes in which METTL24 might be engaged. The Spearman analysis was used to evaluate the expression correlations between METTL24 and a range of immunological variables, and the effects of METTL24 on the infiltration levels of multiple immune cells were explored using TCGA data. The upstream transcription factors of METTL24 were screened through a multi-omics analysis.

Results

METTL24 expression in KIRC tissues was significantly decreased compared to normal adjacent kidney tissues, which was associated with the lower survival rate of KIRC patients. METTL24 potentially participated in the immune-relevant biological processes such as cytokine binding, NF-kappa B binding, MHC protein complex, and interleukin-12 action. Besides, METTL24 expression was linked to a number of immune checkpoints, cytokines, chemokines, and chemokine receptors, and also correlated with the infiltration levels of 10 types of immune cells in KIRC. Meanwhile, METTL24 expression differently affected the overall survival rates (OS) of KIRC patients with high or low levels of immune infiltration. Finally, CTCF and EP300 were discovered to be the probable transcription factors of METTL24 in KIRC.

Conclusion

This study revealed that METTL24 might serve as a prognostic marker in KIRC and as one immune-relevant target for clinical treatment.
mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model
Authors: Sittplangkoon Chutamath , Alameh Mohamad-Gabriel , Weissman Drew , Lin Paulo J. C. , Tam Ying K. , Prompetchara Eakachai , Palaga Tanapat
Published: October 2022

An mRNA with unmodified nucleosides induces type I interferons (IFN-I) through the stimulation of innate immune sensors. Whether IFN-I induced by mRNA vaccine is crucial for anti-tumor immune response remains to be elucidated. In this study, we investigated the immunogenicity and anti-tumor responses of mRNA encoding tumor antigens with different degrees of N1-methylpseudouridine (m1Ψ) modification in B16 melanoma model. Our results demonstrated that ovalbumin (OVA) encoding mRNA formulated in a lipid nanoparticle (OVA-LNP) induced substantial IFN-I production and the maturation of dendritic cells (DCs) with negative correlation with increasing percentages of m1Ψ modification. In B16-OVA murine melanoma model, unmodified OVA-LNP significantly reduced tumor growth and prolonged survival, compared to OVA-LNP with m1Ψ modification. This robust anti-tumor effect correlated with the increase in intratumoral CD40+ DCs and the frequency of granzyme B+/IFN-γ+/TNF-α+ polyfunctional OVA peptide-specific CD8+ T cells. Blocking type I IFN receptor completely reversed the anti-tumor immunity of unmodified mRNA-OVA reflected in a significant decrease in OVA-specific IFN-γ secreting T cells and enrichment of PD-1+ tumor-infiltrating T cells. The robust anti-tumor effect of unmodified OVA-LNP was also observed in the lung metastatic tumor model. Finally, this mRNA vaccine was tested using B16 melanoma neoantigens (Pbk-Actn4) which resulted in delayed tumor growth. Taken together, our findings demonstrated that an unmodified mRNA vaccine induces IFN-I production or the downstream signaling cascades which plays a crucial role in inducing robust anti-tumor T cell response for controlling tumor growth and metastasis.
A perspective on the expansion of the genetic technologies to support the control of neglected vector-borne diseases and conservation
Authors: Raban Robyn , Gendron William A. C. , Akbari Omar S.
Published: October 2022

Genetic-based technologies are emerging as promising tools to support vector population control. Vectors of human malaria and dengue have been the main focus of these development efforts, but in recent years these technologies have become more flexible and adaptable and may therefore have more wide-ranging applications. Culex quinquefasciatus, for example, is the primary vector of avian malaria in Hawaii and other tropical islands. Avian malaria has led to the extinction of numerous native bird species and many native bird species continue to be threatened as climate change is expanding the range of this mosquito. Genetic-based technologies would be ideal to support avian malaria control as they would offer alternatives to interventions that are difficult to implement in natural areas, such as larval source reduction, and limit the need for chemical insecticides, which can harm beneficial species in these natural areas. This mosquito is also an important vector of human diseases, such as West Nile and Saint Louis encephalitis viruses, so genetic-based control efforts for this species could also have a direct impact on human health. This commentary will discuss the current state of development and future needs for genetic-based technologies in lesser studied, but important disease vectors, such as C. quinquefasciatus, and make comparisons to technologies available in more studied vectors. While most current genetic control focuses on human disease, we will address the impact that these technologies could have on both disease and conservation focused vector control efforts and what is needed to prepare these technologies for evaluation in the field. The versatility of genetic-based technologies may result in the development of many important tools to control a variety of vectors that impact human, animal, and ecosystem health.
Coastal vulnerability modelling and social vulnerability assessment under anthropogenic impacts
Authors: Lu Jingfang , Zhang Yibo , Shi Honghua , Lv Xianqing
Published: October 2022

Coastal regions are highly vulnerable to the impacts of human activities, land cover change, sea level rise (SLR), and climate extremes. In this study, we attempt to address this issue by simulating the spatial interactions among natural hazards, ever-increasing human activities, and social vulnerability in the south coast of the Bohai Sea, China. It is found that the activities occurring on land, especially within coastal environments, such as agricultural pond and ports, and those in the ocean (tide and residual current) both impose disaster risks on the marine environment. In 2020, 25.2% of the total study area is highly vulnerable, which is 21% larger than that in 1997. The socially vulnerable areas are mainly distributed in the southeast coast of the Laizhou Bay. These areas should be strengthened to reduce and prevent the storm surge and flood disasters. Ultimately, we emphasize the urgent needs to implement effective policy measures for reducing tomorrow’s risks from natural hazards.
Underwater Raman microscopy—a novel in situ tool for deep-sea microscale target studies
Authors: Liu Qingsheng , Guo Jinjia , Lu Yuan , Wei Zihao , Liu Shuang , Wu Lulu , Ye Wangquan , Zheng Ronger , Zhang Xilin
Published: October 2022

Microscale processes and interactions in the ocean are pervasive. They play a fundamental role in global biogeochemical cycles and have a significant impact on benthic marine ecosystems. However, our understanding of microscale processes and interactions that appeared in the benthic environment is still very limited, particularly for the deep ocean, due to a lack of appropriate in situ observation and detection methods. To address this challenge, we have developed an in situ observation and detection system for microscopic targets suitable for the deep sea and have successfully deployed the instrument on a remotely operated vehicle (ROV) to achieve in situ microscopic Raman detection of targets on the seabed over a depth of 770 m. This is a combined system that integrated microscopic imaging and Raman detection techniques for in situ observation and analysis of underwater microscale targets. The complete system consists of an electronics chamber, a detection probe, and a precision external positioning device. Power supply and real-time data transmission are achieved via ROV tethers. This allows researchers to operate the instrument in real time to perform microscopic imaging capture and Raman spectroscopy acquisition of interesting targets on the seafloor. The first sea trial of the system was conducted in the South China Sea in 2020, and during the cruise, microscopic image acquisition and in situ compositional analysis of shell fragments, seabed rock samples, and live sea stars were successively performed. The system has solved the key technical challenges of deep-sea microscopic imaging, demonstrated the feasibility of deep-sea microscopic imaging, and illustrated the great potential of combining Raman spectroscopy and microscopic imaging in marine research. In this paper, we present the unique design of the instrument and the deep-sea results. With further optimization, the system promises to be a versatile instrument providing a unique perspective for deep-sea geochemical and biochemical studies.
Comparative transcriptome analysis of Portunus trituberculatus in response to Vibrio parahaemolyticus and low salinity
Authors: Li Yukun , Lv Jianjian , Wu Jie , Liu Ping , Gao Baoquan
Published: October 2022

Vibrio parahaemolyticus is a common pathogen of marine crustaceans and is responsible for large losses in aquaculture. Salinity is an important environmental factor, and abrupt changes in salinity can affect the immunity of crustaceans. In this study, we carried out a transcriptomic analysis under pathogenic infection and low salt stress, and conducted a comparative analysis of the differentially expressed genes (DEGs) after stimulation by the two factors. Illumina sequencing technology was used for the transcriptome sequencing of 27 hepatopancreas samples, and 178.77 G sequencing data and an average of 44,142,119 clean reads per sample were obtained. A total of 3,047 and 3,710 DEGs were found after V. parahaemolyticus infection and low salt stress, which included a number of innate immunity genes, such as Toll-like receptor (TLR), anti-lipopolysaccharide factor (ALF), lectin, and hemocyanin. In addition, 2,016 common DEGs were found, accounting for 42.52% of the total DEGs. Among these, 169 DEGs were up-regulated after pathogenic infection and down-regulated after low salt stress, and were mainly enriched in starch and sucrose metabolism, nitrogen metabolism, amino sugar and nucleotide sugar processes, and other pathways. Collectively, these results provide data support for the analysis of the immune mechanism of crabs against V. parahaemolyticus and will also help to clarify the molecular mechanism by which salinity affects immunity.
Antibiofilm activity of secondary metabolites of sponge-associated bacterium Alcanivorax sp. from the Red Sea
Authors: Jamal Mamdoh T. , Satheesh Sathianeson
Published: October 2022

Sponge-associated bacteria are a well-known source of unique and diverse natural products with potential biological activities. In this study, a rarely occurring sponge-associated bacterium from the genus Alcanivorax was isolated from the sponge Siphonochalina siphonella and subjected to extraction of metabolites. Metabolites were extracted from the culture supernatant and biomass of the bacterium using the solvent extraction method. Extracts were evaluated for antibacterial and antibiofilm activities against five different biofilm-forming bacteria isolated from the microfouling assemblage. The crude extracts were subjected to chemical profiling to identify their composition using gas chromatography-coupled mass spectrometry (GC-MS). The results obtained show mild to strong antibacterial activity of the extracts against the biofilm-forming bacteria with the minimum inhibitory concentration (MIC) of 3.125 mg ml-1. The percentage inhibition of biofilm formation ranged from 46% to 71%. Compounds detected in GC-MS analysis are mostly fatty acids and their derivatives that include compounds with known antibiofilm activity such as tetradecanoic acid, dodecanoic acid, and hexadecanol from the culture supernatant extract. Eicosane; hexadecanoic acid, methyl ester; and hexadecanoic acid, ethyl ester were detected from the biomass extract. Molecular docking analysis of the compounds from the bacterial extracts confirms their potential antibiofilm properties. The result indicated that Alcanivorax sp. associated with the sponge possess relevant antibiofilm activity and may serve as a novel source of secondary metabolites with the application as antibiofilm agents.
Immuno-PET: Design options and clinical proof-of-concept
Authors: Lugat Alexandre , Bailly Clément , Chérel Michel , Rousseau Caroline , Kraeber-Bodéré Françoise , Bodet-Milin Caroline , Bourgeois Mickaël
Published: October 2022

Radioimmunoconjugates have been used for over 30 years in nuclear medicine applications. In the last few years, advances in cancer biology knowledge have led to the identification of new molecular targets specific to certain patient subgroups. The use of these targets in targeted therapies approaches has allowed the developments of specifically tailored therapeutics for patients. As consequence of the PET-imaging progresses, nuclear medicine has developed powerful imaging tools, based on monoclonal antibodies, to in vivo characterization of these tumor biomarkers. This imaging modality known as immuno-positron emission tomography (immuno-PET) is currently in fastest-growing and its medical value lies in its ability to give a non-invasive method to assess the in vivo target expression and distribution and provide key-information on the tumor targeting. Currently, immuno-PET presents promising probes for different nuclear medicine topics as staging/stratification tool, theranostic approaches or predictive/prognostic biomarkers. To develop a radiopharmaceutical drug that can be used in immuno-PET approach, it is necessary to find the best compromise between the isotope choice and the immunologic structure (full monoclonal antibody or derivatives). Through some clinical applications, this paper review aims to discuss the most important aspects of the isotope choice and the usable proteic structure that can be used to meet the clinical needs.
Caffeine intake improves the cognitive performance of patients with chronic kidney disease
Authors: Jia Linpei , Zhao Hanxue , Hao Lixiao , Jia Lin-Hui , Jia Rufu , Zhang Hong-Liang
Published: October 2022

Objective

Cognitive impairment is a common complication of chronic kidney disease (CKD). Caffeine intake has been reported to improve cognitive performance in several studies. However, whether the benefits of caffeine intake on cognitive function apply to patients with CKD remains unknown.

Methods

We performed a retrospective cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). The data of CKD subjects and non-CKD subjects from NHANES 2011−2014 were analyzed. Propensity score matching (PSM) was performed based on age, sex, diabetes, cancer, educational level, energy intake and protein intake to select subjects. The Consortium to Establish a Registry for Alzheimer’s Disease Word Learning Test (CERAD-WL), the CERAD Word List Recall Test (CERAD-DR), the Animal Fluency Test (AF) and the Digit Symbol Substitution Test (DSST) were used, whereby the occurrence of cognitive impairment was identified. Logistic regression models were performed to evaluate the association between caffeine intake and cognitive performance in CKD and non-CKD participants. Stratified analyses according to the stage of CKD and the urinary albumin/creatinine ratio levels were performed. Plot curves were then generalized to present a non-linear relationship, and the inflection point for each non-linear model was obtained by using a recursive algorithm.

Results

Cognitive impairment was more prevalent in CKD patients than in non-CKD subjects. For CKD patients, caffeine intake was associated with higher CERAD-WL, CERAD-DR, AF and DSST scores. For non-CKD subjects, caffeine intake was associated with higher DSST scores only. Subgroup analysis revealed that caffeine only benefited the cognitive function of patients with CKD stages 2 and 3. The analysis showed non-linear relationships of caffeine intake and cognitive function for both CKD and non-CKD subjects. The inflection point of caffeine intake for CKD patients was 279 mg/day.

Conclusion

The recommended dose of caffeine intake to improve the cognitive function of CKD patients is ≤279 mg/day.
Synthetic antibody-derived immunopeptide provides neuroprotection in glaucoma through molecular interaction with retinal protein histone H3.1
Authors: Fomo Kristian Nzogang , Schmelter Carsten , Atta Joshua , Beutgen Vanessa M. , Schwarz Rebecca , Perumal Natarajan , Govind Gokul , Speck Thomas , Pfeiffer Norbert , Grus Franz H.
Published: October 2022

Glaucoma is a group of optic neuropathies characterized by the progressive degeneration of retinal ganglion cells (RGCs) as well as their axons leading to irreversible loss of sight. Medical management of the intraocular pressure (IOP) still represents the gold standard in glaucoma therapy, which only manages a single risk factor and does not directly address the neurodegenerative component of this eye disease. Recently, our group showed that antibody-derived immunopeptides (encoding complementarity-determining regions, CDRs) provide attractive glaucoma medication candidates and directly interfere its pathogenic mechanisms by different modes of action. In accordance with these findings, the present study showed the synthetic complementary-determining region 2 (CDR2) peptide (INSDGSSTSYADSVK) significantly increased RGC viability in vitro in a concentration-dependent manner (p < 0.05 using a CDR2 concentration of 50 μg/mL). Employing state-of the-art immunoprecipitation experiments, we confirmed that synthetic CDR2 exhibited a high affinity toward the retinal target protein histone H3.1 (HIST1H3A) (p < 0.001 and log2-fold change > 3). Furthermore, molecular dynamics (MD) simulations along with virtual docking analyses predicted potential CDR2-specific binding regions of HIST1H3A, which might represent essential post-translational modification (PTM) sites for epigenetic regulations. Quantitative mass spectrometry (MS) analysis of retinas demonstrated 39 proteins significantly affected by CDR2 treatment (p < 0.05). An up-regulation of proteins involved in the energy production (e.g., ATP5F1B and MT-CO2) as well as the regulatory ubiquitin proteasome system (e.g., PSMC5) was induced by the synthetic CDR2 peptide. On the other hand, CDR2 reduced metabolic key enzymes (e.g., DDAH1 and MAOB) as well as ER stress-related proteins (e.g., SEC22B and VCP) and these data were partially confirmed by microarray technology. Our outcome measurements indicate that specific protein-peptide interactions influence the regulatory epigenetic function of HIST1H3A promoting the neuroprotective mechanism on RGCs in vitro. In addition to IOP management, such synthetic peptides as CDR2 might serve as a synergistic immunotherapy for glaucoma in the future.
First report of Klebsiella pneumoniae co-producing OXA-181, CTX-M-55, and MCR-8 isolated from the patient with bacteremia
Authors: Ge Haoyu , Qiao Jie , Xu Hao , Liu Ruishan , Chen Ruyan , Li Chenyu , Hu Xinjun , Zhou Jiawei , Guo Xiaobing , Zheng Beiwen
Published: October 2022

The worldwide spread of carbapenem-resistant Enterobacteriaceae (CRE) has led to a major challenge to human health. In this case, colistin is often used to treat the infection caused by CRE. However, the coexistence of genes conferring resistance to carbapenem and colistin is of great concern. In this work, we reported the coexistence of blaOXA-181, blaCTX-M-55, and mcr-8 in an ST273 Klebsiella pneumoniae isolate for the first time. The species identification was performed using MALDI-TOF MS, and the presence of various antimicrobial resistance genes (ARGs) and virulence genes were detected by PCR and whole-genome sequencing. Antimicrobial susceptibility testing showed that K. pneumoniae 5589 was resistant to aztreonam, imipenem, meropenem, ceftriaxone, cefotaxime, ceftazidime, levofloxacin, ciprofloxacin, gentamicin, piperacillin-tazobactam, cefepime, and polymyxin B, but sensitive to amikacin. S1-pulsed-field gel electrophoresis (PFGE) and Southern blotting revealed the mcr-8 gene was carried on a ~ 138 kb plasmid with a conserved structure (IS903B-ymoA-inhA-mcr-8-copR-baeS-dgkA-ampC). In addition, blaOXA-181 was found on another ~51 kb plasmid with a composite transposon flanked by insertion sequence IS26. The in vitro conjugation experiments and plasmid sequence probe indicated that the plasmid p5589-OXA-181 and the p5589-mcr-8 were conjugative, which may contribute to the propagation of ARGs. Relevant detection and investigation measures should be taken to control the prevalence of pathogens coharboring blaOXA-181, blaCTX-M-55 and mcr-8.
Taxifolin increased semen quality of Duroc boars by improving gut microbes and blood metabolites
Authors: Zhou Yexun , Chen Liang , Han Hui , Xiong Bohui , Zhong Ruqing , Jiang Yue , Liu Lei , Sun Haiqing , Tan Jiajian , Cheng Xiaowei , Schroyen Martine , Gao Yang , Zhao Yong , Zhang Hongfu
Published: October 2022

Taxifolin (TAX), as a natural flavonoid, has been widely focused on due to its strong anti-oxidation, anti-inflammation, anti-virus, and even anti-tumor activity. However, the effect of TAX on semen quality was unknown. The purpose of this study was to analyze the beneficial influences of adding feed additive TAX to boar semen in terms of its quality and potential mechanisms. We discovered that TAX increased sperm motility significantly in Duroc boars by the elevation of the protein levels such as ZAG, PKA, CatSper, and p-ERK for sperm quality. TAX increased the blood concentration of testosterone derivatives, antioxidants such as melatonin and betaine, unsaturated fatty acids such as DHA, and beneficial amino acids such as proline. Conversely, TAX decreased 10 different kinds of bile acids in the plasma. Moreover, TAX increased “beneficial” microbes such as Intestinimonas, Coprococcus, Butyrivibrio, and Clostridium_XlVa at the Genus level. However, TAX reduced the “harmful” intestinal bacteria such as Prevotella, Howardella, Mogibacterium, and Enterococcus. There was a very close correlation between fecal microbes, plasma metabolites, and semen parameters by the spearman correlation analysis. Therefore, the data suggest that TAX increases the semen quality of Duroc boars by benefiting the gut microbes and blood metabolites. It is supposed that TAX could be used as a kind of feed additive to increase the semen quality of boars to enhance production performance.
The negative effect of Akkermansia muciniphila-mediated post-antibiotic reconstitution of the gut microbiota on the development of colitis-associated colorectal cancer in mice
Authors: Wang Kaicen , Wu Wenrui , Wang Qing , Yang Liya , Bian Xiaoyuan , Jiang Xianwan , Lv Longxian , Yan Ren , Xia Jiafeng , Han Shengyi , Li Lanjuan
Published: October 2022

The bidirectional relationship between colorectal cancer (CRC) and the gut microbiome has been well-documented. Here, we investigated the impact of Akkermansia muciniphila-mediated post-antibiotic gut microbial reconstitution on the development of colitis-associated CRC (CAC). The results showed that post-antibiotic replenishment of A. muciniphila worsened the tumorigenesis of CAC as indicated by increased number of large (>2 mm in diameter) tumors and both average and total tumor diameters. Measures of intestinal barrier function showed that post-antibiotic A. muciniphila gavage damaged the intestinal barrier as reflected by lower transcriptional levels of Tjp1, Ocln, Cdh1, and MUC2. Impaired gut barrier was followed by lipopolysaccharides (LPS) translocation as indicated by higher level of serum LPS-binding protein (LBP). The increased colonic mRNA levels of Il1b, Il6, and Tnfa and serum levels of IL-1β, IL-6, and TNF-α indicated that post-antibiotic A. muciniphila replenishment resulted in overactivated inflammatory environment in CAC. The analysis of the evolution of the microbial community during the progression of CAC showed that post-antibiotic supplementation of A. muciniphila led to a distinct microbial configuration when compared with other treatments characterized by enriched Firmicutes, Lachnospiraceae, and Ruminococcaceae, and depleted Bacteroidetes, which was accompanied by higher Firmicutes/Bacteroidetes (F/B) ratio. Furthermore, post-antibiotic A. muciniphila administration changed the bile acid (BA) metabolic profile as indicated by decreased concentrations of secondary BA (SBA), ω–murocholic acid (ωMCA), and murocholic acid (muroCA). In addition, the A. muciniphila supplementation after antibiotic pretreatment also impacted the metabolism of short-chain fatty acids (SCFAs) as evidenced by increased concentrations of acetic acid, propionic acid, butyric acid, and valeric acid. Our study surprisingly observed that A. muciniphila-mediated post-antibiotic reconstitution of the gut microbiota aggravated the CAC in mice. It might exert its effect by damaging the gut barrier, exacerbating inflammatory responses, disrupting the post-antibiotic recovery of the microbial community, and further influencing the metabolism of BA and SCFAs. These findings indicated that maintaining the homeostasis of intestinal microorganisms is more crucial to health than replenishing a single beneficial microbe, and probiotics should be used with caution after antibiotic treatment.
A discussion of RNA virus taxonomy based on the 2020 International Committee on Taxonomy of Viruses report
Authors: Yuan Wen-Guang , Liu Guang-Feng , Shi Ying-Hui , Xie Ke-Ming , Jiang Jing-Zhe , Yuan Li-Hong
Published: October 2022

RNA viruses have a higher mutation rate than DNA viruses; however, RNA viruses are insufficiently studied outside disease settings. The International Committee on Taxonomy of Viruses (ICTV) is an organization set up by virologists to standardize virus classification. To better understand ICTV taxonomy and the characteristics and rules of different RNA virus families, we analyzed the 3,529 RNA viruses included in the 2020 ICTV report using five widely used metrics: length, host, GC content, number of predicted ORFs, and sequence similarity. The results show that host type has a significant influence on viral genome length and GC content. The genome lengths of virus members within the same genus are quite similar: 98.28% of the genome length differences within any particular genus are less than 20%. The species within those genera containing segmented viruses also have a similar length and number of segments. The number of predicted ORFs in the RNA viral genomes also shows a strong, statistically significant correlation with genome length. We suggest that due to the high mutation rate of RNA virus genomes, current RNA virus classification should mainly rely on protein similarities rather than nucleic acid similarities.
Whole genome sequencing and characteristics of extended-spectrum beta-lactamase producing Escherichia coli isolated from poultry farms in Banaskantha, India
Authors: Patel Mitul A. , Pandey Aparna , Patel A. C. , Patel S. S. , Chauhan H. C. , Shrimali M. D. , Patel Pankaj A. , Mohapatra S. K. , Chandel B. S.
Published: October 2022

Worldwide dissemination of extended-spectrum -lactamase (ESBL)-producing Escherichia coli constitutes an emerging global health issue, with animal food products contributing as potential reservoirs. ESBL E. coli infection is associated with the high mortality and mobility rate in developing countries due to less susceptibility to antibiotics. The present study aimed to elucidate the molecular characteristics and sequence-based analysis of ESBL E. coli in the Gujarat state of India. This study included 108 E. coli strains were isolated from different poultry farms (broiler and layer) in the Banaskantha District. PCR was employed to identify genotypic ESBL-producing antimicrobial resistance genes. Overall, a high occurrence of ESBL genes was found in poultry farms due to the high usage of antimicrobials. The PCR analysis revealed that 79.62% of isolates were detected positive with one or more ESBL genes. Among them, blaTEM (63.88%) was found to be the predominant genotype, followed by blaSHV (30.55%) and blaOXA (28.70%). In the blaCTX-M group, a higher occurrence was observed in blaCTX-M-9 (23.14%), followed by blaCTX-M-2 (24.07%) and blaCTX-M-1 (22.22%). We used the whole-genome sequencing (WGS) method to evaluate the antimicrobial resistance genes, virulence factors, single nucleotide polymorphisms (SNPs), plasmid replicons, and plasmid-mediated AMR genes of one ESBL E. coli isolated. We examined the genetic relatedness of a human pathogenic E. coli strain by comparing its sequence with the broad geographical reference E. coli sequences. Escherichia coli ST 681 was determined using multi-locus sequence typing. We compared our findings to the reference sequence of Escherichia coli str. K- 12 substr. MG1655. We found 24,937 SNPs with 21,792 in the genic region, 3,145 in the intergenic region, and six InDels across the genome. The WGS analysis revealed 46 antimicrobial resistance genes and seven plasmid-mediated AMR genes viz., tetA, qnrS1, dfrA14, sul2, aph(3”)-lb, aph(6)-ld, and Aph(3’)-la. The ST 681 was found to have Cib, traT, and terC virulence factors and two plasmid replicons, IncFII(pHN7A8) and IncI1-I(Alpha). This study revealed a higher occurrence of ESBL E. coli detected in poultry.