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Biological wastewater treatment processes usually occur under dynamic conditions involving a dynamic regime with respect to carbon substrate, which results in different microbial internal storage processes. These storage processes play important roles in pollutant removal (e.g., chemical oxygen demand, nitrogen and phosphate removal) and resource recovery (e.g., anaerobic digestion for methane production). This review focuses on two different internal storage processes: microbial storage for shock loading of electron donor and another for separate electron donor and acceptor. The review gives the up-to-date status on several essential microbial internal storage issues: their formation and consumption, the kinetics of these processes, the key factors governing microbial storage, their relationship to microbial growth and other important microbial products, their role in nitrous oxides emissions, and their implications in biological wastewater treatment systems. Although previous research in microbial internal storage has undoubtedly improved our level of understanding, it is clear that much remains to be learned about the processes, as many unanswered questions still remain; some of these important future research areas are then outlined. One of the challenges appears to be the competitions for carbon substrate by these microbial internal storage groups when they encounter the same dynamic regimes. [ABSTRACT FROM PUBLISHER]

Activated sludge is subjected to transient conditions, resulting in the enhanced production of microbial products (i.e., extracellular polymeric substances, soluble microbial products, and internal storage products). The authors review the status of the microbial products formed by activated sludge in wastewater treatment systems. They outline the fundamental facets of their formation and metabolism, define their key characteristics and important roles, and identify the interrelationships between the microbial products and activated sludge processes as well as discuss their implications. In addition, they appraise present understanding about their conversion kinetics. Finally, the authors also summarize modeling works on the microbial products formation processes and discuss a model incorporating their formation and utilization in activated sludge systems. [ABSTRACT FROM AUTHOR]

Bioconversion of medium-chain carboxylic acids (MCCAs) from biowastes through anaerobic mixed-culture fermentation is undergoing a revolution in terms of mitigating the lower fossil fuels requirement and increasing biowaste treatment capacity. Benefiting from hydrophobicity and high energy density of MCCA, this high-valuable biofuel exhibits easier separation and wider application than traditional volatile fatty acid products. The biggest bottleneck for efficiently and simultaneously producing MCCAs by mixed-culture fermentation is complicated or even entangled microbial interaction. Therefore, this review aimed to supply guidelines to understand and steer these microbiomes toward the controllable ones. The metabolic pathway of chain elongation and associated cooperating and competing pathways were firstly discussed to understand the primary microbial interaction in mixed-culture fermentation. In an attempt to inspect the overall performance of mixed-culture CE reactor, the typical microbial community and its variation influenced by reactor parameters were also identified. The methods of in-line extraction of MCCAs for relieving toxicity inhibition on microbiome were also summarized regarding the difficulties lied in continuous MCCAs production. Finally, the future research directions of MCCAs production via mixed-culture fermentation would be proposed to help steer these novel bioproduction processes toward full-scale applications. [ABSTRACT FROM AUTHOR]

T helper 17 (Th17) cells constitute a unique T-cell lineage that plays a crucial role in inflammatory diseases. A decade ago, retinoic acid receptor-related orphan receptor-γt (RORγt) was identified as the specific transcription factor required for Th17-cell lineage commitment. However, the underlying mechanisms involved in the regulation of the RORγt expression remain largely unclear and therefore preclude the accurate identification and manipulation of Th17 cells. In this review, we summarize the recent advances to obtain an understanding of how RORγt expression is controlled at the molecular level, highlighting the importance of signal transduction pathways and epigenetic regulations in the control of RORγt expression in Th17 cells. [ABSTRACT FROM AUTHOR]

Familial amyotrophic lateral sclerosis (FALS) accounts for about 5% of cases of the neurodegenerative disorder ALS. At least 100 Cu/Zn superoxide dismutase (SOD1) genetic mutations have been associated with FALS. We identified a FALS family in China with an atypical clinical phenotype. To investigate the SOD1 gene mutations in this family, five exons of the SOD1 gene from each living patient were amplified by PCR and screened by SSCP and direct DNA sequencing. SSCP analysis demonstrated a mutation in exon 2 of SOD1, and DNA sequencing demonstrated the presence of an insertion mutation in exon 2 that has not been reported previously. The mutant SOD1 gene encodes a truncated protein of 35 amino acid residues compared to the normal SOD1 protein of 153 amino acids. In conclusion, The SOD1 exon 2 mutation is likely to be the etiological factor of ALS in this family. [ABSTRACT FROM AUTHOR]

CD4++ T helper (Th) cells act as important regulators of the mammalian adaptive immune response. CD4++ Th cells were originally characterized as either Th1 or Th2 types, based on the cytokines they produce. Over the past two decades, however, we have attained a much more detailed understanding of CD4++ T-cell differentiation, functions, and gene expression profiles, which led to the identification of additional types, such as the Th17 and induced regulatory T cells. Recently, researchers have characterized yet another novel and distinct population that exists among these immune-modulatory cells. The ''Th9'' cells were first identified as a Th2 subpopulation that produced exceptionally large quantities of the Th2-specific cytokine interleukin 9. However, experimental analysis revealed that Th9 cells had divergent regulatory capabilities and were critically involved in different immune processes. In particular, we now know that Th9 acts as a major contributor to the onset and progression of allergies, especially asthma. Here, we will review the heterogeneity and biology of CD4++ Th cells and summarize the characteristics known to date of interleukin 9 and Th9 cells to build a framework for better understanding of their roles in disease processes, especially in allergy-induced asthma. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) represent a newly identified class of non-coding RNAs that have been shown to be involved in several diseases, including autoimmune diseases. Two studies have revealed the aberrant circRNA expression profiles in the peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA) by microarrays. However, due to the intrinsic defects of microarrays, such as their inability to detect unidentified circRNAs, we examined the circRNA expression profiles in the PBMCs from four RA patients and three healthy controls by RNA sequencing (RNA-seq) and further explored the value of circRNAs in diagnosing RA. The results showed 71 markedly dysregulated circRNAs, including 41 upregulated and 30 downregulated circRNAs; these data included several previously unidentified candidate circRNAs. Gene Ontology and pathway annotation revealed that the most altered pathways and genes were associated with inflammation and transcriptional activity, such as the TNF pathway. The selected dysregulated circRNAs were verified by qRT-PCR in the PBMCs of 32 RA patients and 20 healthy controls, and the results indicated that hsa_circ_0000396 and hsa_circ_0130438 were downregulated in the RA group versus the healthy group, consistent with the RNA-seq data. The area under the receiver operating characteristic curve indicated the diagnostic value of both circRNAs for RA. Our results identified aberrant dysregulated circRNAs in RA patients, including several identified circRNAs, and the diagnostic value of circRNAs for RA, suggesting the superiority of RNA-seq versus microarrays for screening differentially expressed circRNAs and further strengthening the potential diagnostic value of circRNAs for the diagnosis of RA. [ABSTRACT FROM AUTHOR]

Programmed death-1 (PD-1), a key immune checkpoint molecule, has been developed as an oncotherapy target for various carcinomas. However, treatment with anti-PD-1 elicited only a minimal effect in pancreatic ductal adenocarcinoma (PDAC). Subsequent studies revealed the existence of a subset of PD-1+ T cells coexpressing CD38 and CD101, representing a fixed dysfunctional subpopulation that are not able to be rescued by anti-PD-1 immunotherapy. However, whether this subpopulation of PD-1 expressing CD8+ T cells could be useful in predicting PDAC stage or prognosing survival is unknown. In this study, we used flow cytometry and immunofluorescence assay to analyze the expression of CD38 and CD101 in 183 clinical PDAC samples, including 84 of peripheral blood and 99 of surgical tissues. High coexpression of CD38/CD101 on peripheral PD-1+CD8+ T cells or tumor-infiltrating lymphocytes (TILs) was found to be most significantly correlated with Tumor/Node/Metastasis (T/N/M) classification and clinical stage, in contrast PD-1+CD8+ T cells could not correlate with T classification. CD38/CD101 co-repression on TILs also correlated with the poor survival in these PDAC patient samples. Our data suggest that CD38/CD101 might represent a more helpful biomarker than PD-1 alone for diagnosis and prognosis of PDAC. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a typical autoimmune disease. Genome-wide analyses have revealed that interleukin-1 receptor-associated kinase 1 (IRAK1) is associated with susceptibility to SLE. Our previous study investigated the role of IRAK1 in nuclear factor-κB (NF-κB)-related pathways in a mouse model of lupus. In this study, we aimed to further explore the etiological role of IRAK1. The gene expression and phosphorylation of IRAK1 in CD4+ T cells from lupus patients and healthy controls were examined by quantitative reverse transcription-polymerase chain reaction and western blotting, respectively. The percentage of circulating Th17 cells and plasma IL-17A levels were evaluated by flow cytometry and enzyme-linked immunosorbent assay, respectively. The influence of IRAK1 suppression on Th17 development was assessed using an IRAK1 inhibitor and small interfering RNA. We found that IRAK1 transcript levels in CD4+ T cells were significantly upregulated in SLE patients in comparison to controls and were positively correlated with disease activity. In vitro experiments showed that lupus CD4+ T cells had more pronounced IRAK1 phosphorylation at threonine-209 upon IL-1β stimulation than did control cells. Moreover, IRAK1 expression was positively associated with Th17/IL-17A in patients. When naïve CD4+ T cells were polarized toward the Th17 subset, IRAK1 inhibition significantly repressed IL-17A production and the gene expression of Th17 markers, namely, retinoic acid receptor-related orphan receptor c, IL-23 receptor and IL-17A. In summary, IRAK1 is overexpressed and hyperactivated in CD4+ T cells from SLE patients. IRAK1 inhibition attenuates Th17 differentiation in the context of human SLE, suggesting a therapeutic opportunity. [ABSTRACT FROM AUTHOR]

Ciliates are able to form resting cysts as a survival strategy in response to stressful environmental factors. Studies on the characteristics of cellular structure during encystment may provide useful information for further understanding of the regulatory mechanism of cellular patterns and supply new clues regarding the phylogeny of ciliates. Scanning and transmission electron microscopies were used to observe the ultrastructure of cells during encystment of the soil ciliateAustralocirruscf.australis. The dedifferentiation of ciliature was revealed for the first time. Ciliary shafts first shortened, and the remaining ciliature, including basal bodies and the fibrillar cirral basket, retracted into the cytoplasm and was surrounded by the autophagic vacuoles and then gradually digested. A large number of autophagic vacuoles were observed in mature resting cysts. Autophagy might not only be necessary for the differentiation of cellular structures during encystment but might also be important to sustain the basic life activities in the resting stage.Australocirruscf.australisformed a kinetosome-resorbing cyst and contained four layers in the cyst wall: the ectocyst, mesocyst, endocyst and granular layer. The ciliature resorbing state and the number of layers in the cyst wall were consistent with those found in other oxytrichous ciliates. However, the phenomenon wherein the two macronuclear nodules are not fused during encystment is not commonly observed among oxytrichids. Additionally, the octahedral granules in the mesocyst of this species exhibit different morphology from the congeners. [ABSTRACT FROM PUBLISHER]

Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are mainly localize to epithelial surfaces, have been characterized as regulators of chronic inflammation and tissue remodeling, representing a functional bridge between the innate and adaptive immunity. Moreover, recent research has implicated ILCs as potential contributing factors to several kinds of fibrosis diseases, such as hepatic fibrosis and pulmonary fibrosis. Here, we will summarize and discuss the key roles of ILCs and their related factors in fibrotic diseases and their potential for translation to the clinic. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with the English Course for International Academic Conferences, an international strategy to train graduate students in English communication for international academic conferences.

Innate lymphoid cells (ILCs) are involved in the development of mucosal-associated lymphoid tissues and serve as a rapid and early source of the effector cytokines that are typically associated with the T helper cell subsets in response to pathogen-induced changes in the microenvironment. Recent research has implicated ILCs as potential contributing factors to the spectrum of inflammation-related hepatic diseases, particularly hepatitis, fibrosis and carcinoma. In this review, we summarize the current knowledge on the roles of ILCs in these hepatic pathogeneses, providing insights into the underlying cellular and signaling mechanisms to help guide the future research to elucidate the ILCs’ characters under normal and diseased conditions and provide interventional targets with therapeutic potential. [ABSTRACT FROM PUBLISHER]

T helper 17 (Th17) cells have been identified as a distinct T helper lineage that mediates tissue inflammation. Retinoic acid receptor-related orphan receptor (ROR) γt has been identified as the master transcription factor (TF) required for Th17 cell lineage commitment. There is an established consensus that TFs never function alone. Thus, RORγt is considered to form protein complexes that mediate Th17 cell differentiation. Given the importance of RORγt complexes in Th17 cell development and function, here, we summarize recent progress in research investigating the interaction of RORγt with potential partners, highlighting detailed mechanisms that direct Th17 cell differentiation and potential therapeutic targets in inflammatory diseases. [ABSTRACT FROM AUTHOR]

CD8+CD62L+ T cells have been shown to play pivotal roles in anti-viral immunity, chronic myeloid leukemia and renal cell carcinoma. Recently, CD8+CD62L+ T cells from naïve mice (nCD8+CD62L+ T cells) have shown superior anti-tumor properties in melanoma-bearing mice. Considering that antigen-specific memory T cells have shown to possess more potent immunity than non-specific memory T cells, we hypothesized that CD8+CD62L+ T cells from tumor-bearing individuals (mCD8+CD62L+ T cells) might have superior anti-tumor effect than nCD8+CD62L+ T cells. Therefore, we investigated phenotypes, functions and the in vivo distribution of mCD8+CD62L+ T cells in tumor-bearing mice. We found that, while keeping the features of central memory T cells, the frequency of mCD8+CD62L+ T cell in the spleen of tumor-bearing mice was significantly higher than that the one of nCD8+CD62L+ T cell in naive mice. Moreover, we demonstrated that mCD8+CD62L+ T cells had higher proliferation rate and IFN-γ production than nCD8+CD62L+ T cells, in vitro. We performed adoptive transfer of mCD8+CD62L+ T cells into melanoma-bearing mice and tracked them in spleen, lymph nodes and in melanoma tissues. Our results show that mCD8+CD62L+ T cells had stronger in vivo anti-tumoral activity than nCD8+CD62L+ T cells. This study highlights the therapeutic potential of mCD8+CD62L+ T cells in the immunotherapy of melanoma and possibly other tumors. [ABSTRACT FROM AUTHOR]

Extrusomes of different categories in ciliates have been suggested to have different structures and functions. To investigate the characteristics of extrusomes in the hypotrichous ciliate, we examinedArchitricha indicausing scanning and transmission electron microscopy and electron microscopic enzymo-cytochemistry. The results showed that the mature extrusomes were ellipsoidal vesicles with structureless cavities on their anterior parts and arranged in rows beneath the pellicle; the extruded structures of extrusomes were cyathiform and can remain outside of the cell surface after extrusion. These findings differ distinctly from that of previously reported extrusomes in other ciliates and thus suggest a new type of extrusomes. These organelles originated from endoplasmic reticulum in the deeper part of the cytoplasm, underwent a serious of development, gradually migrated to the cortical cytoplasm and finally positioned in their functional areas. In contrast with lower forms of ciliates, density, arrangement, and localization of extrusomes inA. indicashowed obvious differences between the ventral and dorsal surface of cells. This may be in some way related to the differentiation of the dorsoventral cortex, and functional ciliature happened to the hypotrichous ciliates. In addition, the extrusomes may perform protective or defensive function, which associates with the activity of mitochondria and contributes to the pellicle retrieval or renewal. [ABSTRACT FROM PUBLISHER]

Hepatocellular carcinoma (HCC) remains one of the most prevalent malignant diseases worldwide, and the majority of cases are related to hepatitis B virus (HBV) infection. Interactions between the HBV-encoded X (HBx) protein and host factors are known to play major roles in the onset and progression of HBV-related HCC. These dynamic molecular mechanisms are extremely complex and lead to prominent changes in the host genetic and epigenetic architecture. This review summarizes the current knowledge about HBx-induced epigenetic changes, including aberrations in DNA methylation, histone modifications, and microRNA expression, and their roles in HBV-infected liver cells and HBV-related HCC. Moreover, the HBx-mediated epigenetic control of HBV covalently closed circular DNA (cccDNA) is also discussed. Although this field of study is relatively new, the accumulated evidence has indicated that the epigenetic events induced by HBx play important roles in the development of HBV-related HCC. Ongoing research will help to identify practical applications of the HBV-related epigenetic signatures as biomarkers for early HCC detection or as potential targets to prevent and treat HBV-related HCC. [ABSTRACT FROM AUTHOR]

The follicle stimulating hormone (FSH) is of great importance in reproduction modulation of both sexes. The extracellular domain (ECD) of its receptor (FSHR) is crucial for FSH binding and subsequent signal transduction; therefore, it is the potential target for fertility control. To avoid unwanted side-effect when used as immunocontraceptive agent, the ECD was analysed by online prediction combined with molecular docking to identify the candidate B-cell epitopes. Four potential B-cell epitopes were identified and synthesised in tandem with Pan DR epitope. Then the epitope-based peptides were used to boost adult male mice following rhFSHR protein priming, thus to determine their immune responses and fertility inhibition capacity. Three of the four peptides showed suppressed fertility accompanied with small testis and lower serum testosterone level, which was consistent with absolutely lower sperm quantity and poor quality. Among the four epitope peptides, Pep2 displayed the lowest fertility rate of 26.67%, which was similar to that of rhFSHR homologously prime/boost mice (23.30 and 25.00%). Thus, we identified a novel immunodominant B-cell epitope by molecular docking and protein prime/peptide boost strategy. [ABSTRACT FROM AUTHOR]

Folate receptor 4 (FR4) is recently found as a lymphoid tissue specific protein. In this study, we have identified an alternative splicing variant of the FR4 gene from murine splenocytes, termed FR4v, which is almost identical to FR4 cDNA sequence except with the retained 108 bp intron 3 between exon 3 and 4 of FR4 gene. FR4v mRNA encodes a larger protein than FR4 and is constitutively expressed on CD4+CD25+ regulatory T cell (Treg) membrane via a GPI anchor mechanism. Whether FR4v plays a redundant or unique functional role in Tregs should be investigated further in the future. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B was characterized by fluctuant immune response to infected hepatocytes resulting in hepatic inflammation and virus persistence. Recently, Programmed Death-1 (PD-1) and its ligand PD-L1 have been demonstrated to play an essential role in balancing antiviral immunity and inflammation in the livers of acute hepatitis B patients, significantly influencing disease outcome. PD-1 up-regulation in peripheral T cells is associated with immune dysfunction in chronic hepatitis B patients. However, the effect of PD-1/PD-L1 on hepatic damage and chronic infective status is still unknown in patients with chronic HBV infection. Here, we report up-regulation of PD-1 and PD-L1 in liver biopsies from 32 chronic HBV patients compared to 4 healthy donors. PD-1/PD-L1 up-regulation was significantly associated with hepatic inflammation and ALT elevation. Moreover, appropriate up-regulation but not overexpression of PD-L1 in the active phase of chronic hepatitis B as well as lower expression of PD-L1 in the inactive phase in liver residential antigen presenting cells (including Kupffer cells and sinusoidal endothelial cells) may contribute to viral inhibition. Our data suggest that the intrahepatic interaction of PD-1 and PD-L1 might play an important role in balancing the immune response to HBV and immune-mediated liver damage in chronic HBV infection. [ABSTRACT FROM AUTHOR]

Expanded CD4+CD28null T cells have not been described in the circulation of patients with chronic hepatitis B (CHB). The aim of the present was to detect and characterize the surface phenotype and functional capacity of these cells in CHB patients. Expanded CD4+CD28null T cells were detected in the circulation of CHB patients with high viral load and elevated aminotransferase levels. Most CD4+CD28null T cells showed a CD27-CD45RA-CD45RO+ surface phenotype. The markers CD56, CD57 and killer immunoglobulin-like receptor (KIR) were detected on CD4+CD28null T cells, but the majority were positive for CD57. Functionally, CD4+CD28null T cells were found to be potent cytotoxic T lymphocytes with perforin and granzyme B secretion profiles. These findings indicate that the expanded CD4+CD28null T cells are cytotoxic memory T cells and display a distinct functional phenotype in comparison with CD4+CD28+ T cells. The presence of these cells appears to be associated with inflammatory conditions, suggesting that these elevated CD4+CD28null T cells might be involved in the pathogenesis of CHB. [ABSTRACT FROM AUTHOR]

Optimal approaches to differentiate tumor antigen-specific cytotoxic T lymphocytes (CTLs) from pluripotent stem cells (PSCs) remain elusive. In the current study, we showed that combination ofin vitropriming through Notch ligands andin vivodevelopment facilitated the generation of tumor Ag-specific CTLs that effectively inhibited tumor growth. We co-cultured the murine induced PSCs (iPSCs) genetically modified with tyrosinase-related protein 2 (TRP2)-specific T cell receptors with OP9 cell line expressing both Notch ligands Delta-like 1 and 4 (OP9-DL1/DL4) for a week before adoptively transferred into recipient C67BL/6 mice. Three weeks later, B16 melanoma cells were inoculated subcutaneously, and the antitumor activity of the iPSC-derived T cells was assessed. We observed the development of the TRP2-specific iPSC-CD8+T cells that responded to Ag stimulation and infiltrated into melanoma tissues, significantly inhibited the tumor growth, and improved the survival of the tumor-bearing mice. Thus, this approach may provide a novel effective strategy to treatment of malignant tumors. [ABSTRACT FROM PUBLISHER]