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.

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。.

Unlike pandemic GII.4 norovirus, GII.6 norovirus shows limited sequence variation in its major capsid protein VP1. In this study, we investigated the VP1 expression profiles, binding abilities, and cross-blocking effects of three GII.6 norovirus strains derived from three distinct variants. Norovirus VP1 was expressed using a recombinant baculovirus expression system and characterized by transmission electron microscopy, mass spectrometry, salivary histo-blood group antigen (HBGA)-virus like particles (VLPs) binding and binding blockade assays. Mass spectrometry revealed the expected molecular weight (MW) of full-length proteins and degraded or cleaved fragments of all three VP1 proteins. Peptide mapping showed loss of 2 and 3 amino acids from the N- and C-terminus, respectively. Further, the co-expression of VP1 and VP2 proteins did not lead to extra fragmentation during mass spectrometry. Salivary HBGA-VLP binding assay revealed similar binding patterns of the three GII.6 VP1 proteins. Salivary HBGA-VLP binding blockade assay induced cross-blocking effects. Our results demonstrate similar binding abilities against salivary HBGAs and specific cross-blocking effects for GII.6 norovirus strains derived from distinct variants, suggesting that fewer GII.6 strains from different evolutionary variants are needed for the development of norovirus vaccines.

Augustine is a newly identified blood group system comprising four antigens, one of which is the high-frequency antigen Ata in the original \"series\". Four antigens are located on a multipass membrane glycoprotein equilibrative nucleoside transporter 1 (ENT1), and equilibrative nucleoside transporter is encoded by SLC29A1. In 2016, the International Society of Blood Transfusion (ISBT) recognised Augustine as a blood group system and numbered it as 036. The glycoprotein ENT1 transports nucleotides into cells to participate in the synthesis of DNA and RNA, and this is an important link for chemotherapeutic glycosides to enter tumour cells. Augustine antibodies are clinically relevant in blood transfusion and pregnancy.

BACKGROUND: Numerous observational studies have investigated on the correlation of whole, semi-skimmed, and skimmed milk with coronary artery disease (CAD) and myocardial infarction (MI) risk; However, no consensus has been reached and evidence on any causal links between these exposures and outcomes remains unclear. This study aimed to conduct univariate and multivariate Mendelian randomization (MR) analyses, using publicly released genome-wide association study summary statistics (GWAS) from the IEU GWAS database, to ascertain the causal association of milk with various fat content with CAD and MI risk.
METHODS: For the exposure data, 29, 15, and 30 single-nucleotide polymorphisms for whole milk, semi-skimmed milk, and skimmed milk, respectively, obtained from 360,806 Europeans, were used as instrumental variables. CAD and MI comprised 141,217 and 395,795 samples, respectively. We used inverse variance weighted (IVW), weighted median, MR-Egger regression, and MR Pleiotropy Residual Sum and Outlier analyses to determine whether pleiotropy and heterogeneity could skew the MR results. Sensitivity tests were conducted to verify the robustness of the results.
RESULTS: After adjusting for false discovery rates (FDR), we discovered proof that skimmed milk intake is a genetically predicted risk factor for CAD (odds ratio [OR] = 5.302; 95% confidence interval [CI] 2.261-12.432; P < 0.001; FDR-corrected P < 0.001) and MI (OR = 2.287; 95% CI 1.218-4.300; P = 0.010; FDR-corrected P = 0.009). Most sensitivity assessments yielded valid results. Multivariable MR for CAD and MI produced results consistent with those obtained using the IVW method. There was no causal relationship between whole or semi-skimmed milk, and CAD or MI.
CONCLUSIONS: Our findings indicate that the consumption of skimmed milk may increase the risk of CAD and MI. This evidence may help inform dietary recommendations for preventing cardiovascular disease. Further studies are required to elucidate the underlying mechanisms.

The Rh blood grouping system is a critical standardized test in transfusion medicine, especially for the cases related to haemolytic transfusion reactions and neonatal haemolytic disease caused by clinical RhD blood group incompatibility. In the present case report, we presented two cases with the uncommon RHD gene variation RHD*DEL37. The blood samples of the two subjects were mistakenly identified as RhD-negative through conventional serological testing. Firstly, both blood samples were tested negative for the RhD antigen using traditional tube test and gel microcolumn methods. The phenotyping of RhCE were identified as ccEe and ccee for each sample, respectively. Secondly, genetic analysis was performed using polymerase chain reaction-sequence specific prime (PCR-SSP) which revealed that neither sample belonging to the several common RHD gene variants which was found in Asia. Moreover, they turned out to be positive for the RHD haplotype, which indicated that exons 1-10 on one of the RHD alleles were entirely absent. In addition, a T>C mutation was observed at bases 1154-31 in intron 8 of the other allele, which was located at the intron 8 breakpoint. This result was obtained after further Sanger sequencing of exons 1-10 of the RHD gene. The mutant allele was designated as RHD*DEL37 by the International Society of Blood Transfusion (ISBT) and was identified as D-elute(Del) by phenotype ana-lysis. Both samples were genotyped as RHD*DEL37 and showed positive results. In summary, the true genotype of the two blood samples, of which the screening results only using serological testing method was negative, were RHD*DEL37 /RHD-(RHD*01N.01). Notably, this kind of genotype was reported for the first time in Chinese population. Moreover, the two individuals did not have ties of consanguinity, indicating that some of the Chinese individuals could be carriers of the genetic mutation. Therefore, it might be necessary to further confirm the frequency of this mutation in the Chinese population and the possibility of homozygosity for this mutation. This report identifies infrequent RHD gene mutation samples by coupling molecular biology and serological methods to prevent misclassification of blood groups. Combining serological and molecular biology test results to determine blood group is critical in protecting patients during clinical transfusion procedures.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree and a sporadic case with Neurofibromatosis type 1 (NF1).
METHODS: Clinical data of the pedigree and the sporadic case were collected. Genomic DNA was extracted from peripheral venous blood samples and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis.
RESULTS: All patients from the pedigree were found to harbor a c.3251delC variant in exon 25 of the NF1 gene, whilst a c.4312_4314delGAA variant was found in exon 32 of the NF1 gene in the sporadic case.
CONCLUSIONS: Variants of the NF1 gene may account for the occurrence of NF1 in this pedigree and sporadic case.

BACKGROUND: Krüppel-like factor 1 (KLF1), a crucial erythroid transcription factor, plays a significant role in various erythroid changes and haemolytic diseases. The rare erythrocyte Lutheran inhibitor (In(Lu)) blood group phenotype serves as an effective model for identifying KLF1 hypomorphic and loss-of-function variants. In this study, we aimed to analyse the genetic background of the In(Lu) phenotype in a population-based sample group by high-throughput technologies to find potentially clinically significant KLF1 variants.
RESULTS: We included 62 samples with In(Lu) phenotype, screened from over 300,000 Chinese blood donors. Among them, 36 samples were sequenced using targeted Next Generation Sequencing (NGS), whereas 19 samples were sequenced using High Fidelity (HiFi) technology. In addition, seven samples were simply sequenced using Sanger sequencing. A total of 29 hypomorphic or loss-of-function variants of KLF1 were identified, 21 of which were newly discovered. All new variants discovered by targeted NGS or HiFi sequencing were validated through Sanger sequencing, and the obtained results were found to be consistent. The KLF1 haplotypes of all new variants were further confirmed using clone sequencing or HiFi sequencing. The lack of functional KLF1 variants detected in the four samples indicates the presence of additional regulatory mechanisms. In addition, some samples exhibited BCAM polymorphisms, which encodes antigens of the Lutheran (LU) blood group system. However, no BCAM mutations which leads to the absence of LU proteins were detected.
CONCLUSIONS: High-throughput sequencing methods, particularly HiFi sequencing, were introduced for the first time into genetic analysis of the In(Lu) phenotype. Targeted NGS and HiFi sequencing demonstrated the accuracy of the results, providing additional advantages such as simultaneous analysis of other blood group genes and clarification of haplotypes. Using the In(Lu) phenotype, a powerful model for identifying hypomorphic or loss-of-function KLF1 variants, numerous novel variants have been detected, which have contributed to the comprehensive understanding of KLF1. These clinically significant KLF1 mutations can serve as a valuable reference for the diagnosis of related blood cell diseases.

OBJECTIVE: To understand the serological characteristics of irregular antibodies in pregnant women and explore their clinical significance.
METHODS: From January 2017 to March 2022, 151 471 pregnant women in Women and Children\'s Hospital of Chongqing Medical University were enrolled in this study, microcolumn gel card test was used for irregular antibody screening, and antibody specificity identification was further performed in some antibody-positive subjects.
RESULTS: The positive rate of irregular antibody screening in the enrolled pregnant women was 0.91% (1 375/151 471), 0.23% (355/151 471) was detected in the first trimester, 0.05% (71/151 471) in the second trimester, and 0.63% (949/151 471) in the third trimester. The positive rate of irregular antibody screening in the third trimester was significantly higher than that in the first and second trimester, and a significant increase in the number of positive cases was found in the third trimester than that in the second trimester. The analysis of agglutination intensity of 1 375 irregular antibody screening positive results showed that the weakly positive agglutination intensity accounted for 50.11% (689/ 1 375), which was the highest, the suspicious positive was 18.69% (257/1 375), and the positive was 31.20% (429/1 375). The significant difference in distribution of agglutination intensity was not observed between the first trimester group and the second trimester group, however, in the third trimester, the proportion of suspicious positive and weakly positive was lower than the first trimester, while, the proportion of positive was higher than the first trimester, and the difference was statistically significant (P < 0.001). Among the irregular antibody screening positive pregnant women, the proportion of pregnant women with pregnancy number ≥ 2 was significantly higher than that with pregnancy ≤ 1. Among 60 pregnant women who underwent antibody identification, the distributions of the antibodies were as follows: Rh blood group system accounted for 23.33% (14/60), Lewis system 43.33% (26/60), Kidd system 3.33% (2/60), MNS system 16.67% (10/60), P1PK system 1.67% (1/60), autoantibodies 1.67% (1/60), and 4 cases was unable to identify (6.67%, 4/60). Among specific antibodies, the anti-Lea was the most common (30.00%), followed by anti-E (16.67%) and anti-M (16.67%).
CONCLUSIONS: The differences of irregular antibody serological characteristics exist in pregnant women from different regions with different genetic backgrounds, understanding the characteristics of irregular antibody in local pregnant women is of great significance for ensuring transfusion safety in pregnant women and preventing hemolytic disease of newborn.
UNASSIGNED: 孕产妇不规则抗体血清学特征和临床意义分析.
UNASSIGNED: 明确不规则抗体在孕产妇人群中的血清学特征，探讨其临床意义。.
UNASSIGNED: 选取2017年1月-2022年3月于重庆医科大学附属妇女儿童医院就诊的孕产妇151 471例，采用微柱凝胶抗人球蛋白法进行不规则抗体筛查，对部分抗体筛查阳性标本进一步做抗体特异性鉴定。.
UNASSIGNED: 孕产妇不规则抗体筛查阳性率为0.91%（1 375/151 471），其中0.23%（355/151 471）在孕早期检出，0.05%（71/151 471）在孕中期检出，0.63%（949/151 471）在孕晚期检出，孕晚期抗体阳性率明显高于孕早期和孕中期，且孕晚期新增阳性例数明显高于孕中期新增例数；分析1 375例不规则抗体阳性结果的凝集强度，其中凝集强度为弱阳性占比最高，为50.11%（689/1 375），可疑阳性占18.69%（257/1 375），阳性占31.20%（429/1 375），孕中期凝集强度分布与孕早期相比差异无统计学意义，但孕晚期可疑阳性和弱阳性的比例低于孕早期，阳性比例高于孕早期，比较差异有统计学意义（P <0.001）。不规则抗体阳性孕产妇中，妊娠≥2次孕产妇的占比明显高于≤1次者；进行抗体鉴定的60例孕产妇中，Rh系统占25.00%（15/60），Lewis系统占43.33%（26/60），Kidd系统占3.33%（2/60），MNS系统抗体占16.67%（10/60），P1PK系统抗体占1.67%（1/60），自身抗体占1.67%（1/60），4例无法确认特异性占6.67%（4/60）；特异性抗体中以抗-Lea（30.00%）最为常见，其次是抗-E （16.67%）和抗-M（16.67%）。.
UNASSIGNED: 不同地区、具有不同遗传背景的孕产妇人群的不规则抗体血清学特征存在差异，掌握本地区孕产妇不规则抗体的特征，对保证孕产妇输血安全、防治新生儿溶血病具有十分重要的意义。.

The aggregation of α-Synuclein (α-Syn) into amyloid fibrils is the hallmark of Parkinson\'s disease. Under stress or other pathological conditions, the accumulation of α-Syn oligomers is the main contributor to the cytotoxicity. A potential approach for treating Parkinson\'s disease involves preventing the accumulation of these α-Syn oligomers. In this study, we present a novel mechanism involving a conserved group of disorderly proteins known as small EDRK-rich factor (SERF), which promotes the aggregation of α-Syn through a cophase separation process. Using diverse methods like confocal microscopy, fluorescence recovery after photobleaching assays, solution-state NMR spectroscopy, and Western blot, we determined that the N-terminal domain of SERF1a plays a role in the interactions that occur during cophase separation. Within these droplets, α-Syn undergoes a gradual transformation from solid condensates to amyloid fibrils, while SERF1a is excluded from the condensates and dissolves into the solution. Notably, in vivo experiments show that SERF1a cophase separation with α-Syn significantly reduces the deposition of α-Syn oligomers and decreases its cellular toxicity under stress. These findings suggest that SERF1a accelerates the conversion of α-Syn from highly toxic oligomers to less toxic fibrils through cophase separation, thereby mitigating the biological damage of α-Syn aggregation.