Patients with Asian-type DEL can safely be transfused with RhD-positive blood.

Red blood cells (RBCs) of Asian-type DEL phenotype express few RhD proteins and are typed as serologic RhD-negative (D-) phenotype in routine testing. RhD-positive (D+) RBC transfusion for patients with Asian-type DEL has been proposed but has not been generally adopted because of a lack of direct evidence regarding its safety and the underlying mechanism. We performed a single-arm multicenter clinical trial to document the outcome of D+ RBC transfusion in patients with Asian-type DEL; none of the recipients (0/42; 95% confidence interval, 0-8.40) developed alloanti-D after a median follow-up of 226 days. We conducted a large retrospective study to detect alloanti-D immunization in 4045 serologic D- pregnant women throughout China; alloanti-D was found only in individuals with true D- (2.63%, 79/3009), but not in those with Asian-type DEL (0/1032). We further retrospectively examined 127 serologic D- pregnant women who had developed alloanti-D and found none with Asian-type DEL (0/127). Finally, we analyzed RHD transcripts from Asian-type DEL erythroblasts and examined antigen epitopes expressed by various RHD transcripts in vitro, finding a low abundance of full-length RHD transcripts (0.18% of the total) expressing RhD antigens carrying the entire repertoire of epitopes, which could explain the immune tolerance against D+ RBCs. Our results provide multiple lines of evidence that individuals with Asian-type DEL cannot produce alloanti-D when exposed to D+ RBCs after transfusion or pregnancy. Therefore, we recommend considering D+ RBC transfusion and discontinuing anti-D prophylaxis in patients with Asian-type DEL, including pregnant women. This clinical trial is registered at www.clinicaltrials.gov as #NCT03727230.

Serum 25-hydroxyvitamin D status of a large Chinese population from 30 provinces by LC-MS/MS measurement for consecutive 3 years: differences by age, sex, season and province.

PURPOSE: We aimed to describe the vitamin D status and its distribution in different age groups, sexes, seasons, and provinces of a large Chinese population. METHODS: This study retrospectively analyzed 1,528,685 results of serum 25-hydroxyvitamin D (25(OH)D) in the central laboratory of KingMed Diagnostics. The samples were from the individuals aged 0-119 years old in 30 provinces of China. Serum 25(OH)D was measured by an accurate commercial liquid chromatography-tandem mass spectrometry (LC-MS/MS) method from January 2017 to December 2019. The subjects were stratified by age, sex, the season of blood collection, and the province of residence. RESULTS: The median 25(OH)D concentration was 25.5 ng/mL (interquartile range (IQR) 18.7-32.7 ng/mL) in males and 20.8 ng/mL (IQR 14.4-28.2 ng/mL) in females. Overall, the median 25(OH)D concentration decreased with age in both males and females. Males had a 0.2-2.4 ng/mL higher median 25(OH)D concentration than females in different age groups. Vitamin D deficiency (25(OH)D < 15 ng/mL for the individuals under 14 years old; < 20 ng/mL for the individuals over 14 years old) was found in 21.3% of males and 43.6% of females. Significant seasonal variation of serum 25(OH)D concentrations was repeatedly observed in 3 years, with median concentration higher in summer (25.3 ng/mL (IQR 19.3-31.9 ng/mL)) and lower in winter (18.5 ng/mL (IQR 12.3-26.6 ng/mL)). Vitamin D status varied by province. The median 25(OH)D concentration was the highest in Hainan (31.0 ng/mL (IQR 24.9-39.2 ng/mL)) and the lowest in Qinghai (14.4 ng/mL (IQR 9.6-20.0 ng/mL)). 25(OH)D2 was detected in 12.2% of the results, and no significant seasonal variation was observed. CONCLUSION: In China, vitamin D deficiency is prevalent in the population participating in clinical vitamin D measurement. Age and sex differences in vitamin D levels were observed in our study. Seasonal variation and provincial differences are important aspects of serum vitamin D status. 25(OH)D2 cannot be ignored entirely in clinical measurement practice in China.

Single-cell RNA-seq profiling of individual Biomphalaria glabrata immune cells with a focus on immunologically relevant transcripts.

The immune cells of the snail Biomphalaria glabrata are classified into hyalinocyte and granulocyte subtypes. Both subtypes are essential for the proper functioning of the snail immune response, which we understand best within the context of how it responds to challenge with the human parasite Schistosoma mansoni. Granulocytes are adherent phagocytic cells that possess conspicuous granules within the cell cytoplasm. Hyalinocytes, on the other hand, are predominantly non-adherent and are known to produce a handful of anti-S. mansoni immune effectors. While our understanding of these cells has progressed, an in-depth comparison of the functional capabilities of each type of immune cell has yet to be undertaken. Here, we present the results of a single-cell RNA-seq study in which single granulocytes and hyalinocytes from S. mansoni-susceptible M-line B. glabrata and S. mansoni-resistant BS-90 B. glabrata are compared without immune stimulation. This transcriptomic analysis supports a role for the hyalinocytes as producers of immune effectors such as biomphalysin and thioester-containing proteins. It suggests that granulocytes are primarily responsible for producing fibrinogen-related proteins and are armed with various pattern-recognition receptors such as toll-like receptors with a confirmed role in the anti-S. mansoni immune response. This analysis also confirms that the granulocytes and hyalinocytes of BS-90 snails are generally more immunologically prepared than their M-line counterparts. As the first single-cell analysis of the transcriptional profiles of B. glabrata immune cells, this study provides crucial context for understanding the B. glabrata immune response. It sets the stage for future investigations into how each immune cell subtype differs in its response to various immunological threats.

Identification and functional characterization of complement regulatory protein CD59 in golden pompano (Trachinotus ovatus).

CD59, one of the essential inhibitors of the complement membrane attack complex (MAC), plays a crucial role in regulation of complement activation. In this study, we cloned and identified the CD59 gene (named ToCD59) of golden pompano (Trachinotus ovatus). The ORF sequence of ToCD59 is 357 bp long encoding 118 amino acids with a molecular weight of 13.09 kDa. Prediction of protein domains showed that ToCD59 contained an Lu domain and a C-terminal glycosylphosphatidylinositol (GPI) partial anchor. Homology comparisons indicated that ToCD59 shared the high sequence similarity with other fish CD59. RT-qPCR analysis showed that ToCD59 was expressed in all tested healthy tissues of golden pompano, with the highest level of expression in the brain. After stimulation with bacteria, ToCD59 expression levels were significantly up-regulated in head kidney, liver, gill and brain, but down-regulated in spleen. Subcellular localization results showed that ToCD59 localized to the cytoplasm of A549 cells. The hemolytic activity analysis showed that rToCD59 might have complement inhibitory activity through the alternative complement pathway. In addition, antibacterial test showed that rToCD59 had antibacterial ability against S. agalactiae and V. alginolyticus in vitro. These results suggest that ToCD59 might play an important role in the immune response against pathogens, which would provide basic information for elucidating the functional evolutionary history of complement system in teleost.

A novel C-type lectin from Crassostrea gigas involved in the innate defense against Vibrio alginolyticus.

C-type lectins (CTLs) are important immune molecules that participate in invertebrate defense response. In the present work, a novel structural CTL (CgLec-4E) was identified from Crassostrea gigas, which encodes 237 amino acids (aa) with an extra long chain of aa and in the C-type CRD domain with EPA, QPG and WHD mutated motifs respectively. rCgLec-4E could agglutinate and inhibit the growth of Vibrio alginolyticus, except Chlorella, which might be relevant to three mutated motifs. CgLec-4E was mainly expressed in digestive gland, and its expression level was significantly up-regulated post V. alginolyticus challenge, indicating that the high expression of CgLec-4E could provide necessary mucosal immune protections and might involve in food particle recognition for C. gigas. Moreover, the subcellular locations indicated that CgLec-4E might play different roles in the immune response. Taken together, our results enrich our understanding of the structures and function of CTLs in invertebrates.

Homozygous FUT1 Mutations Causing a Para-Bombay Phenotype: a Pedigree Investigation Report.

BACKGROUND: Para-Bombay phenotype is rare in ABO blood group. We describe FUT1 mutations in a Chinese woman with the para-Bombay phenotype, including her familial inheritance. METHODS: ABO grouping, H antigen detection, absorptionelution test, salivary antigen substance detection, deter-mination of titer of ABH antibody, ABO genotyping, gene sequencing (FUT1,2), blood transfusion compatibility test, and pedigree investigation were performed. RESULTS: The patient was confirmed as group A1 para-Bombay phenotype (Amh) in her family's investigation, revealing her FUT1 gene had c.658C>T (p.Arg220Cys) homozygous mutation and FUT2 gene had c.357C>T homozygous mutation. The patient was provided an appropriate transfusion solution. CONCLUSIONS: A combination of using classical serological methods, gene sequencing methods and pedigree investigation methods can effectively analyze the genetic inheritance of patients with para-Bombay phenotype, increasing their choices of blood transfusion.

A Case of AB Para-Bombay Phenotype with Weak A Antigen Expression.

BACKGROUND: The Para-Bombay phenotype is characterized by H antigen partially or totally deficient on red blood cells and the presence of ABH substances in body fluids. METHODS: A patient with discrepant results in forward and reverse ABO phenotyping was further investigated by serological and molecular methods. RESULTS: Ortho gel and tube results showed weak A antigen expression and weak antibody reacting with A and B cells. Absorption-elution assay detected B antigen, and saliva test confirmed substances H were present. The patient was confirmed as A102B101 and Le(a+b+) phenotype. CONCLUSIONS: These findings suggest that the case is AB Para-Bombay Phenotype (secretor).

Interference of Thalassemias on Hemoglobin A1c Measurement by Ion-Exchange High-Performance Liquid Chromatography Method Tosoh HLC-723 G8.

BACKGROUND: The presence of hemoglobinopathies could interfere with some assays for Hemoglobin A1c (HbA1c) measurement; therefore, the effect of thalassemia on ion-exchange high-performance liquid chromatography (IEHPLC) method Tosoh HLC-723 G8 (Tosoh G8) was evaluated. METHODS: A total of 43 normal controls and 101 thalassemia patients were quantified by Premier Hb9210 and Tosoh G8 (variant-mode) systems. At the same time, 7 normal controls and 8 thalassemia patients were confirmed by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference method for verification. RESULTS: For normal controls, the HbA1c values of Tosoh G8 system (y) showed great correlation and agreement with those from Premier Hb9210 (x) (y = 0.9688x + 0.2151, r = 0.9951; mean difference 0.02 ± 0.30%), and no significant relative bias above 7% was observed; the HbA1c values obtained by Tosoh G8 were consistent with the IFCC targets (relative bias < ± 6%) in all of the samples. However, for thalassemia, the correlation between Tosoh G8 (y) and Premier Hb9210 (x) became relatively low (y = 0.8079x + 1.2897, r = 0.7780); the HbA1c values of 91.1% of the samples (92/101) obtained by Tosoh G8 were higher than those by Premier Hb9210 (mean difference 0.33 ± 0.48%) and a significant positive bias above 7% was noticed in 43.3% (45/101) thalassemia patients; when compared with the IFCC targets, the 87.5% (7/8) relative bias was > ± 6%. CONCLUSIONS: Thalassemia could directly affect the measurement of HbA1c using the IE-HPLC method Tosoh G8 and the clinical laboratorial staff should pay close attention.

Clinical Correlates and Reference Intervals for Cystatin C in a Han Population from Southeast China.

BACKGROUND: Cystatin C (CysC) is an endogenous filtration marker for estimation of kidney function. This study aimed to define the reference interval (RI) for serum CysC in a southeast Chinese adult population and to explore the variables that affect serum CysC levels. METHODS: 532 reference individuals (259 male, 273 female, aged 18 - 79 years) were recruited from Guangzhou, China. Multiple regression analysis (MRA) was used to investigate the association between serum CysC levels and clinical factors including age, gender, body mass index, lifestyle, and biochemistry parameters. Reference values were defined using a parametric method according to Clinical and Laboratory Standards Institute guideline (C28A3). RESULTS: The mean serum CysC levels were significantly lower in females than in males (p < 0.001). Serum CysC levels increased with age (~0.047 mg/L increase per decade). MRA demonstrated that serum CysC levels correlated significantly with serum creatinine (Cr), high density lipoprotein (HDL-C), alkaline phosphatase (ALP), albumin (ALB), and uric acid (UA) concentrations, although their relationships were less prominent than those of gender or age. The RIs for serum CysC levels were calculated at 0.73 - 1.17 mg/L for subjects aged 18 - 49 years and at 0.73 - 1.49 mg/L for those aged 50 - 79 years. CONCLUSIONS: The RIs for serum CysC were established in a southeast Chinese population. In addition to gender and age, serum Cr, HDL-C, ALP, ALB, and UA also influenced serum CysC levels.

First characterization of three cyclophilin family proteins in the oyster, Crassostrea ariakensis Gould.

Cyclophilins (CyPs) are a family of proteins that bind the immunosuppressive agent cyclosporin A (CsA) with high-affinity and belong to one of the three superfamilies of peptidyl-prolyl cis-trans isomerases (PPIase). In this report, three cyclophilin genes (Ca-CyPs), including Ca-CyPA, Ca-CyPB and Ca-PPIL3, were identified from oyster, Crassostrea ariakensis Gould in which Ca-CyPA encodes a protein with 165 amino acid sequences, Ca-CyPB encodes a protein with 217 amino acid sequences and Ca-PPIL3 encodes a protein with 162 amino acid sequences. All of the three Ca-CyPs genes contain a typical CyP-PPIase domain with its signature sequences and Ca-CyPB contains an N-signal peptide sequences. Tissue distribution study revealed that Ca-CyPs were ubiquitously expressed in all examined tissues and the highest levels were observed in hemocytes. RLO incubation upregulated the mRNA expression levels of Ca-CyPs, indicating that three Ca-CyPs might be involved in oyster immune response against RLO infection.

Characterization and function of an E2-17 kDa (UBE2D) in an invertebrate Haliotis diversicolor supertexta.

Ubiquitin-conjugating enzymes (UBE2s or E2s) are characterized by the presence of a highly conserved ubiquitin-conjugating (UBC) domain, which predominantly determines the type of ubiquitin chains and directly controls the cellular fate of the substrate. In this study, an E2 homolog was identified and functionally characterized in abalone, which we named ab-UBE2D. The full-length cDNA consists of 1005 bp with an ORF encoding a protein of 147 amino acids. The deduced amino acid sequence shows ab-UBE2D shares conserved UBC domain with other E2 proteins and belongs to class I E2 enzyme family, which are further confirmed by phylogenetic tree analysis. Real-time PCR and western blot analyses showed that ab-UBE2D was ubiquitously expressed in abalone and the expression level of ab-UBE2d was significantly induced by LPS and Poly (I:C). Immunofluorescence microscopy staining demonstrated that native ab-UBE2D was mainly distributed in the cytoplast. Ubiquitination assay showed that ab-UBE2D had ubiquitin conjugating activity to form the enzyme-(Ub)n conjugates. Taken together, these results strongly suggest that ab-UBE2D is an E2 homolog and it may be involved in the immune response of abalone, Haliotis diversicolor supertexta.

Molecular characterization of a novel tetraspanin from the oyster, Crassostrea ariakensis: variation, localization and relationship to oyster host defense.

We identified a tetraspanin family member gene, named Ca-TSP, in the oyster Crassostrea ariakensis and found that the transcription profiles of Ca-TSP were variable in the oyster hemocytes. Three distinct patterns of variation of Ca-TSP were observed. Using immunofluorescence and immunoelectron microscopy, we show that Ca-TSP was present in granules and in vesicular structures of the oyster hemocyte. Sequence analysis, structural features and immunogold electron microscopy showed that Ca-TSP is an integral membrane glycoprotein of granules of hemocyte and may be a novel CD63-like gene of the tetraspanin family of molluscs. The gene expression analysis of Ca-TSP using isolated oyster hemocytes, was done following challenge of the oysters with LPS and Poly I:C. The Ca-TSP mRNA levels increased in hemocytes in the first 12 h after LPS and Poly I:C stimulation, and decreased after the addition of H(2)O(2). Western blot analysis using anti-Ca-TSP antibody indicated that gene expression and protein levels were similar. The recombinant Ca-TSP was found to significantly inhibit hemocytes aggregation. Our results suggested that Ca-TSP participates in the innate immunity of the oyster.

Identification of expressed genes in cDNA library of hemocytes from the RLO-challenged oyster, Crassostrea ariakensis Gould with special functional implication of three complement-related fragments (CaC1q1, CaC1q2 and CaC3).

A SMARTer™ cDNA library of hemocyte from Rickettsia-like organism (RLO) challenged oyster, Crassostrea ariakensis Gould was constructed. Random clones (400) were selected and single-pass sequenced, resulted in 200 unique sequences containing 96 known genes and 104 unknown genes. The 96 known genes were categorized into 11 groups based on their biological process. Furthermore, we identified and characterized three complement-related fragments (CaC1q1, CaC1q2 and CaC3). Tissue distribution analysis revealed that all of three fragments were ubiquitously expressed in all tissues studied including hemocyte, gills, mantle, digestive glands, gonads and adductor muscle, while the highest level was seen in the hemocyte. Temporal expression profile in the hemocyte monolayers reveled that the mRNA expression levels of three fragments presented huge increase after the RLO incubation at 3 h and 6 h in post-challenge, respectively. And the maximal expression levels at 3 h in post-challenge are about 256, 104 and 64 times higher than the values detected in the control of CaC1q1, CaC1q2 and CaC3, respectively.

A novel toll-like receptor from Crassostrea gigas is involved in innate immune response to Vibrio alginolyticus.

Based on previous reports，toll-like receptors (TLRs) are recognition molecules common in various aquatic animals and play a vital role in innate immunity. In this study, a novel TLR CgToll-3 with leucine-rich repeats (LRRs) and a TIR (Toll-interleukin 1-resistance) domain was cloned in Crassostrea gigas. CgToll-3 with sixteen potential extracellular N-linked glycosylation sites and shares the closest phylogenic relationship with molluscan TLRs. Alignment of LRRs and TIR domains indicated that CgToll-3 was highly conserved compared to other LRRs of mollusks which could respond against Vibrio or other bacterial molecules, and contained three conserved functionally important motifs (Box 1, Box 2, and Box 3). The Hex Molecular Docking result showed that CgToll-3 could interact with CgMyd88 via the TIR domain. Subcellular Co-localization and BiFC Assay confirmed this interaction, and they could induce NF-κB activation. CgToll-3 was moderately expressed in the digestive gland, and its expression level was significantly up-regulated after Vibrio alginolyticus challenge. Taken together, CgToll-3 might be involved in the innate immune response to V. alginolyticus for C. gigas through a MyD88-dependent TLR mediated signaling pathway.

Identification and expression localization of a Ran homologue in mollusc abalone, Haliotis diversicolor supertexta.

Ran protein is a central molecular in several key nuclear functions, including nucleocytoplasmic transport, cell-cycle progression and nuclear envelope assembly. In this study, we have isolated and characterized a Ran homologue from a gastropod abalone which we named ab-Ran. The full-length cDNA consists of 1239 bp with an ORF encoding a 220 amino acid protein. The deduced amino acid sequence of ab-Ran shows highly similar to that of other Ran members (84-88%). Moreover, the ab-Ran contains five conserved regions and four carboxy-terminal residues CAAX-box. RT-PCR analysis showed that the ab-Ran was ubiquitously expressed in abalone tissues. The intracellular localization examined by immunofluorescence and immunohistochemistry staining displayed that ab-Ran was largely concentrated in the nuclei and partially in the cytoplasm. To the best of our knowledge, this is the first identification and characterization of a Ran homologue in mollusk.

Expression, purification and characterization of yellow grouper Epinephelus awoara regulator of G protein signaling 16 protein.

Regulators of G-protein signaling (RGS) proteins are a family of proteins, which accelerate GTPase-activity intrinsic to the alpha subunits of heterotrimeric G-proteins and play crucial roles in the physiological control of G-protein signaling. Here, yellow grouper RGS16 protein was expressed in Escherichia coli and purified by Ni-NTA affinity chromatography. The expression level of the fusion protein was up to 30% of the total cellular protein.Western blotting analysis showed that a band with the molecular mass of about 21 Kda was detected. The purified recombinant protein was used to prepare polyclonal antibody, and antiserum obtained was highly specific with the titer of over 1:32,000. Additionally, RGS16 protein was expressed in the Tn-5B1-4 insect cells. Western blotting analysis revealed that the expressed protein had immunoreactivity.

Identification and functional characterization of the transcription factor coding Dp1 gene in large yellow croaker Pseudosciaena crocea.

The transcription factor Dp1, as a binding partner, often forms a dimerization complex with typical E2F to play a central role in regulating gene expression during G1/S cell cycle progression. In this study, a full-length dp1 cDNA (Pcdp1) was successfully cloned and characterized from the large yellow croaker Pseudosciaena crocea. The nucleotidic sequence of Pcdp1 is 1,427 bp long with an open reading frame (ORF) of 1,239 bp encoding a putative protein of 412 amino acids, a 5'-untranslated region of 116 bp and a 3'-untranslated region of 70 bp. Prediction of protein domains showed that PcDp1 contains a DNA-binding domain (DBD) with a DEF box, a dimerization domain and an acidic region at C terminus with transcription activity. Homology comparisons indicated that PcDp1 shared the highest sequence identity of 98.55% with Oreochromis niloticus dp1, followed by 88.72% identity with Danio rerio dp1 and a relatively low identity of 78.91-80.55% with its mammalian and amphibian counterparts. The mRNA of Pcdp1 showed ubiquitously expression in all analyzed tissues, with the highest level of expression in the body kidney. Moderate expression levels of Pcdp1 was found in several immune-related tissues including the gills, head kidney and liver, indicating that PcDp1 might play an important role in osmotic pressure regulation and immune response of the large yellow croaker. The subcellular localization of PcDp1 revealed that it is mainly distributed in the cytoplasm both in COS-7 and parenchymal cells of the spleen, head kidney and kidney tissues. Furthermore, the recombinant PcDp1 exhibited DNA-binding activity to E2F site in vitro. In conclusion, these results indicated that PcDp1 may participate in immune regulation and provide a foundation for further study of the regulatory mechanism of Dp1 in teleosts.

Establishment of the reference intervals of lymphocyte subsets for healthy Chinese Han adults and its influencing factors.

BACKGROUND: Cellular immune monitoring is becoming more critical in the clinic, but its application has not yet become sufficiently widespread. One reason may be the different reference intervals among clinical laboratories due to several factors. Percentage and number of lymphocyte subsets are standard indicators of cellular immune detection. The present study aimed to establish standardized reference intervals of lymphocyte subsets in the healthy Chinese Han adult population and examine such influencing factors as age, gender, region, and measurement instruments. METHODS: A total of 496 healthy Chinese Han people aged 18-59 years from 3 China Mainland regions (north, east, and south) were enrolled. The sample of each center was simultaneously examined by three flow cytometers (FACSCantoTMII, FACSLyricTM, and FACSCaliburTM). A single-platform flow cytometry-based absolute count technique was used to quantify the percentage and number of each lymphocyte subset. The flow cytometry results were analyzed by variance analysis and Z test to determine the influence of age, gender, and instruments on lymphocyte subsets. RESULTS: Multi-center, age-specific, and gender-specific reference intervals of healthy Chinese Han adults' lymphocyte subsets were established. There was no statistical difference in the results from the three flow cytometers. Gender affected the results of CD4+ (%) and the absolute count of CD3-CD16+CD56+, where CD4+ (%) was higher in women, and the absolute count of CD3-CD16+CD56+ was higher in men. Age mainly affected the CD4+/CD8+ ratio, which was statistically higher in groups aged over 40 years; the percentage and number of CD3-CD19+ were more elevated in age groups below 30 years; however, the difference was not statistically significant. CONCLUSIONS: This study established the reference intervals of lymphocyte subsets for healthy Chinese Han adult populations under the standardized methods. This study was the first nationwide study in China to use a flow cytometry-based single-platform method to establish the reference intervals of lymphocyte subsets of the healthy Chinese Han adult population. Gender and age were shown to influence the results of lymphocyte subsets.

Inflammation Pharmacological Reaction and YMDD Mutational Patterns in Lamivudine Therapeutics Hepatitis B Virus.

Background/Aims: Emergence of tyrosine-methionine-aspartate-aspartate (YMDD) motif in reverse transcriptase is a serious problem in chronic hepatitis B(CHB) patients after Lamivudine (LAM) therapy. However, the relationship between inflammation pharmacological reaction and YMDD mutational patterns of CHB has not been well-characterized. The aim of this study was to investigate the inflammation pharmacological reaction and different YMDD mutants patterns of CHB patients. Methods: We investigated the inflammation pharmacological reaction and YMDD mutational patterns through biochemical, serological and virological detection among 83 CHB patients, including 25 YMDD mutants, 25 under detection, and 33 control patients without YMDD mutants. Results: Prevalence of YMDD mutation patterns is different. Among 25 YMDD mutants patients, YIDD was the dominant mutation (72%), followed YVDD (16%) and the hybrid YIDD + YVDD (12%). The time course during the YMDD mutations was also different. 52.4% patients developed the mutation less than 12 months after the LAM therapy. Serum hepatitis B virus (HBV) DNA level in patients with YMDD mutants were significantly higher than that in control and negative groups. Serum HbsAg and HbeAg in patients with YMDD mutants were also higher than those in control and negative groups, despite no significant difference was found forserum HbeAb. ALT and AST levels were also significantly higher in mutants group. Conclusions: Illuminating inflammation pharmacological reaction and YMDD mutational patterns of CHB during pathological process may have implications for future therapy in YMDD mutation patients. This may have impact on the choice of treatment strategies for lamivudine-resistant HBV.

Coordination of humoral immune factors dictates compatibility between Schistosoma mansoni and Biomphalaria glabrata.

Immune factors in snails of the genus Biomphalaria are critical for combating Schistosoma mansoni, the predominant cause of human intestinal schistosomiasis. Independently, many of these factors play an important role in, but do not fully define, the compatibility between the model snail B. glabrata, and S. mansoni. Here, we demonstrate association between four previously characterized humoral immune molecules; BgFREP3, BgTEP1, BgFREP2 and Biomphalysin. We also identify unique immune determinants in the plasma of S. mansoni-resistant B. glabrata that associate with the incompatible phenotype. These factors coordinate to initiate haemocyte-mediated destruction of S. mansoni sporocysts via production of reactive oxygen species. The inclusion of BgFREP2 in a BgFREP3-initiated complex that also includes BgTEP1 almost completely explains resistance to S. mansoni in this model. Our study unifies many independent lines of investigation to provide a more comprehensive understanding of the snail immune system in the context of infection by this important human parasite.