Human noroviruses (HuNoVs) are the leading etiological agent causing the worldwide outbreaks of acute epidemic non-bacterial gastroenteritis. Histo-blood group antigens (HBGAs) are commonly acknowledged as cellular receptors or co-receptors for HuNoVs. However, certain genotypes of HuNoVs cannot bind with any HBGAs, suggesting potential additional co-factors and attachment receptors have not been identified yet. In addition, food items, such as oysters and lettuce, play an important role in the transmission of HuNoVs. In the past decade, a couple of attachment factors other than HBGAs have been identified and analyzed from foods and microbiomes. Attachment factors exhibit potential as inhibitors of viral binding to receptors on host cells. Therefore, it is imperative to further characterize the attachment factors for HuNoVs present in foods to effectively control the spread of HuNoVs within the food chain. This review summarizes the potential attachment factors/receptors of HuNoVs in humans, foods, and microbiome.

The dimeric architecture of tandem-repeat type galectins, such as galectin-4 (Gal-4), modulates their biological activities, although the underlying molecular mechanisms have remained elusive. Emerging evidence show that tandem-repeat galectins play an important role in innate immunity by recognizing carbohydrate antigens present on the surface of certain pathogens, which very often mimic the structures of the human self-glycan antigens. Herein, we have analyzed the binding preferences of the C-domain of Gal-4 (Gal-4C) toward the ABH-carbohydrate histo-blood antigens with different core presentations and their recognition features have been rationalized by using a combined experimental approach including NMR, solid-phase and hemagglutination assays, and molecular modeling. The data show that Gal-4C prefers A over B antigens (two-fold in affinity), contrary to the N-domain (Gal-4N), although both domains share the same preference for the type-6 presentations. The behavior of the full-length Gal-4 (Gal-4FL) tandem-repeat form has been additionally scrutinized. Isothermal titration calorimetry and NMR data demonstrate that both domains within full-length Gal-4 bind to the histo-blood antigens independently of each other, with no communication between them. In this context, the heterodimeric architecture does not play any major role, apart from the complementary A and B antigen binding preferences. However, upon binding to a bacterial lipopolysaccharide containing a multivalent version of an H-antigen mimetic as O-antigen, the significance of the galectin architecture was revealed. Indeed, our data point to the linker peptide domain and the F-face of the C-domain as key elements that provide Gal-4 with the ability to cross-link multivalent ligands, beyond the glycan binding capacity of the dimer.

暂无摘要。

Galectins (Gals), a family of multifunctional glycan-binding proteins, have been traditionally defined as β-galactoside binding lectins. However, certain members of this family have shown selective affinity toward specific glycan structures including human milk oligosaccharides (HMOs) and blood group antigens. In this work, we explored the affinity of human galectins (particularly Gal-1, -3, -4, -7, and -12) toward a panel of oligosaccharides including HMOs and blood group antigens using a complementary approach based on both experimental and computational techniques. While prototype Gal-1 and Gal-7 exhibited differential affinity for type I versus type II Lac/LacNAc residues and recognized fucosylated neutral glycans, chimera-type Gal-3 showed high binding affinity toward poly-LacNAc structures including LNnH and LNnO. Notably, the tandem-repeat human Gal-12 showed preferential recognition of 3-fucosylated glycans, a unique feature among members of the galectin family. Finally, Gal-4 presented a distinctive glycan-binding activity characterized by preferential recognition of specific blood group antigens, also validated by saturation transfer difference nuclear magnetic resonance experiments. Particularly, we identified oligosaccharide blood group A antigen tetraose 6 (BGA6) as a biologically relevant Gal-4 ligand, which specifically inhibited interleukin-6 secretion induced by this lectin on human peripheral blood mononuclear cells. These findings highlight unique determinants underlying specific recognition of HMOs and blood group antigens by human galectins, emphasizing the biological relevance of Gal-4-BGA6 interactions, with critical implications in the development and regulation of inflammatory responses.

BACKGROUND: This study aimed to identify the blood transfusion rates for several surgical procedures in a single district general hospital and assess the value of preoperative blood type and antibody screen across all relevant surgical procedures. We hypothesized that there was an overuse of blood type and antibody screen in our general surgical population.
METHODS: A database containing transfusions of patients who underwent elective- or emergency surgery from January 2015 to September 2020 was matched to a database of preoperative type-and-screen performed in the same period. Registered procedures where the incidence of transfusion is deemed low were excluded. The included procedures were assessed for the intraoperative usefulness of type- and-screen testing.
RESULTS: In the included 68.892 surgeries, 36.134 (52.0%) blood samples were preoperatively tested for the blood type and screened for antibodies according to the hospital\'s routine. Overall 3.517 (5.1%) of surgeries had patients that received a transfusion in the perioperative period and 1.2% (n = 850) during the surgery.
CONCLUSIONS: Most surgeries had a very low incidence of transfusion. Despite this, type-and-screen tests were widely used. This suggests the need for a more focused pre-surgery type-and-screen approach, and a more data driven approach to local guidelines in collaboration with surgical specialties.

BACKGROUND: In Al-Ahsa, Saudi Arabia, the high consanguinity rates contribute to the prevalence of inherited hemoglobinopathies such as sickle cell disease and thalassemia, which frequently require blood transfusions. These transfusions carry the risk of alloimmunization, necessitating a precise blood component matching to mitigate health risks. Local antigen frequency data is vital for optimizing transfusion practices and enhancing the safety of these medical procedures for the Al-Ahsa population.
METHODS: This study investigated the distribution of Duffy, Kidd, Lewis, and Rh blood group antigens in 1,549 individuals from the region; comparing the frequencies with global data.
RESULTS: Serological analyses revealed a high prevalence of the Fy(a+b-) and Jk(a+b+) phenotypes in the Duffy and Kidd blood groups, respectively, with Jk(a-b-) being notably scarce. The Lewis blood group exhibited a significant presence of Le(a-b+) and Le(a+b-) phenotypes, whereas Le(a+b+) was less common. In the Rh system, the D antigen was most prevalent, with other antigens following in descending order of frequency.
CONCLUSIONS: The study underscores the regional variation in antigen frequencies, emphasizing the need for local blood banks to adapt their screening and matching practices to mitigate the risk of alloimmunization and enhance transfusion safety. These findings are pivotal for refining transfusion strategies and understanding the immunohematology landscape in Al-Ahsa.

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Human norovirus was discovered more than five decades ago and is a widespread cause of outbreaks of acute gastroenteritis. There are no approved vaccines or antivirals currently available. However, norovirus inhibitors, including capsid-specific monoclonal antibodies (Mabs) and nanobodies, have recently shown promising results. Several Mabs and nanobodies were found to inhibit norovirus replication using a human intestinal enteroid (HIE) culture system and/or could block norovirus attachment to histo-blood group antigen (HBGA) co-factors. In our pursuit to develop a single broad-spectrum norovirus therapeutic, we continued our analysis and development of a cross-reactive and HBGA interfering nanobody (NB26). To improve NB26 binding capacity and therapeutic potential, we conjugated NB26 onto a human IgG Fc domain (Fc-NB26). We confirmed that Fc-NB26 cross-reacts with genetically diverse GII genotype capsid protruding (P) domains (GII.8, GII.14, GII.17, GII.24, GII.26, and GII.NA1) using a direct enzyme-linked immunosorbent assay. Furthermore, X-ray crystallography structures of these P domains and structures of other GII genotypes reveal that the NB26 binding site is largely conserved, validating its broad reactivity. We showed that Fc-NB26 has ~100-fold higher affinity toward the norovirus P domain compared to native NB26. We also found that both NB26 and Fc-NB26 neutralize human norovirus replication in the HIE culture system. Furthermore, the mode of inhibition confirmed that like NB26, Fc-NB26 caused norovirus particle disassembly and aggregation. Overall, these new findings demonstrate that structural modifications to nanobodies can improve their therapeutic potential.IMPORTANCEDeveloping vaccines and antivirals against norovirus remains a challenge, mainly due to the constant genetic and antigenic evolution. Moreover, re-infection with genetically related and/or antigenic variants is not uncommon. We further developed our leading norovirus nanobody (NB26) that indirectly interfered with norovirus binding to HBGAs, by converting NB26 into a dimeric Fc-linked Nanobody (Fc-NB26). We found that Fc-NB26 had improved binding affinity and neutralization capacity compared with native NB26. Using X-ray crystallography, we showed this nanobody engaged highly conserved capsid residues among genetically diverse noroviruses. Development of such broadly reactive potent therapeutic nanobodies delivered as a slow-releasing prophylactic could be of exceptional value for norovirus outbreaks, especially for the prevention or treatment of severe acute gastroenteritis in high-risk groups such as the young, elderly, and immunocompromised.

OBJECTIVE: This study was aimed to provide ideas for identifying the antibodies to high-frequency antigens by analyzing a female case of high-frequency antigen antibody (anti-Ku) using serological and sequencing method.
METHODS: The methods for identification of blood group, erythrocyte antigen, screening and identification of antibody were used to detect the blood type and antibody in the proband. The proband\'s serum and reagent screening cells treated with Sulfhydryl reagent were applied to judge the type and characteristics of this antibodies when reacted with the regaent screening cells or proband\'s serum respectively. Gene sequencing was used to determine the genotype of the proband\'s blood group.
RESULTS: The proband\'s red blood cells were determined as O type RhD positive, whose serum showed strong positive reaction to antibody-screening cells and antibody identification cells with the same intensity in saline and IAT medium, however, the self-cells showed negative effect. The Direct Antihuman Globulin of proband\'s red blood cells also showed weak positive reaction, and the other blood types were CcEe, Jk(a+b-), P1-, Le(a-b -), Lu (a-b +), K-, k-, Kp(a-b-). Serum of the proband treated with 2-ME still react with three groups of screening cells in IAT medium. The reaction intensity of proband\'s serum was also unchanged with the cells modified with papain and bromelain, but showed negative effect when the cells were treated with sulfhydryl agents including DTT and 2-ME. Gene sequencing revealed that the KEL genotype of the patient was KEL*02N.24 . This patient had a rare K0 phenotype.
CONCLUSIONS: The rare Kell-null blood group (also known as K0) were identified by serological and molecular tests in the proband who produced both IgG and IgM type of antibody to high-frequency antigen (anti-Ku). These two methods are of great significance in the identification of this rare blood group as well as the antibody to high frequency antigen.
UNASSIGNED: 抗Ku及其他高频抗原抗体的鉴定思路.
UNASSIGNED: 通过对一例女性高频抗原抗体（抗-Ku）病例进行血清学鉴定及血型基因测序分析，为高频抗原抗体的鉴定提供一定思路。.
UNASSIGNED: 运用血型鉴定、患者红细胞抗原鉴定、抗体筛选、抗体鉴定等方式检测该患者的血型及抗体。以巯基试剂处理后的血清与筛选细胞反应、患者血清与酶或巯基试剂处理的筛选细胞反应的方式来判断该抗体的类型及特点，采用基因测序的方法确定患者血型的基因型。.
UNASSIGNED: 该患者血型为O型RhD+，其血清与抗体筛选细胞及抗体鉴定细胞在间接抗人球及盐水介质中的反应呈强反应性，且强度一致，自身阴性，直接抗人球蛋白弱阳性；其他血型为CcEe、Jk(a+b-)、P1-、Le(a-b-)、Lu（a-b+）、K-、k-、Kp(a-b-)。血清经2-ME处理后，在间接抗人球介质中仍与3组筛选细胞反应；血清与经木瓜酶、菠萝酶修饰后的筛选细胞反应强度不变，与巯基试剂DTT、2-ME处理后的筛选细胞反应为阴性。基因测序显示该患者KEL 基因型为KEL*02N.24 ，为罕见的K0表型。.
UNASSIGNED: 血清学试验和分子生物学实验鉴定出该患者为罕见的Kel-null血型（又称K0），该患者体内产生了IgG及IgM性质的高频抗原抗体抗-Ku。血清学方法及分子生物学方法在此类稀有血型及高频抗原抗体的鉴定中具有重要意义。.

Our group generated two induced pluripotent stem cell (iPSC) lines for in vitro red blood cell (RBC) production from blood donors with extensively known erythrocyte antigen profiles. One line was intended to give rise to RBCs for transfusions in patients with sickle cell disease (SCD), while the other was developed to create RBC panel reagents. Two blood donors were selected based on their RBC phenotypes, further complemented by high-throughput DNA array analysis to obtain a more comprehensive erythrocyte antigen profile. Enriched erythroblast populations from the donors\' peripheral blood mononuclear cells were reprogrammed into iPSCs using nonintegrative plasmid vectors. The iPSC lines were characterized and subsequently subjected to hematopoietic differentiation. iPSC PB02 and iPSC PB12 demonstrated in vitro and in vivo iPSC features and retained the genotype of each blood donor\'s RBC antigen profile. Colony-forming cell assays confirmed that iPSC PB02 and iPSC PB12 generated hematopoietic progenitors. These two iPSC lines were generated with defined erythrocyte antigen profiles, self-renewal capacity, and hematopoietic differentiation potential. With improvements in hematopoietic differentiation, these cells could potentially be more efficiently differentiated into RBCs in the future. They could serve as a complementary approach for obtaining donor-independent RBCs and addressing specific demands for blood transfusions.