One novel single nucleotide polymorphism c.424A>G on A1.02 allele in ABO glycosyltransferases leads to Aweak phenotype.

BACKGROUND: The dysfunction of the ABO glycosyltransferase (GT) enzyme, which is caused by mutations in the ABO gene, can lead to weak ABO phenotypes. In this study, we have discovered a novel weak ABO subgroup allele and investigated the underlying mechanism to causing its Aweak phenotype. MATERIALS AND METHODS: The ABO phenotyping and genotyping were performed by serological studies and direct DNA sequencing of ABO gene. The role of the novel single nucleotide polymorphism (SNP) was evaluated by 3D model, predicting protein structure changes, and in vitro expression assay. The total glycosyltransferase transfer capacity in supernatant of transfected cells was examined. RESULTS: The results of serological showed the subject was Aweak phenotype. A novel SNP c.424A > G (p. M142V) based on ABO*A1.02 was identified, and the genotype of the subject was AW-var/O.01 according to the gene analysis. In silico analysis showed that the SNP c.424A > G on the A allele may change the local conformation by damaging the hydrogen bonds and reduce the stability of GT. In vitro expression study showed that SNP p.M142V impaired H to A antigen conversion, although it did not affect the generation of A glycosyltransferase (GTA). CONCLUSIONS: One novel AW allele was identified and the SNP c.424A > G (p.M142V) can cause the Aweak phenotype through damaging the hydrogen bonds and reducing stability of the GTA.

Code Similarity Prediction Model for Industrial Management Features Based on Graph Neural Networks.

The code of industrial management software typically features few system API calls and a high number of customized variables and structures. This makes the similarity of such codes difficult to compute using text features or traditional neural network methods. In this paper, we propose an FSPS-GNN model, which is based on graph neural networks (GNNs), to address this problem. The model categorizes code features into two types, outer graph and inner graph, and conducts training and prediction with four stages-feature embedding, feature enhancement, feature fusion, and similarity prediction. Moreover, differently structured GNNs were used in the embedding and enhancement stages, respectively, to increase the interaction of code features. Experiments with code from three open-source projects demonstrate that the model achieves an average precision of 87.57% and an F0.5 Score of 89.12%. Compared to existing similarity-computation models based on GNNs, this model exhibits a Mean Squared Error (MSE) that is approximately 0.0041 to 0.0266 lower and an F0.5 Score that is 3.3259% to 6.4392% higher. It broadens the application scope of GNNs and offers additional insights for the study of code-similarity issues.

Halogen-Modulated 2D Coordination Polymers for Efficient Hydrogen Peroxide Photosynthesis under Air and Pure Water Conditions.

H2 O2 is a widely used eco-friendly oxidant and a potential energy carrier. Photocatalytic H2 O2 production from water and O2 is an ideal approach with the potential to address the current energy crisis and environmental issues. Three zig-zag two-dimensional coordination polymers (2D CPs), named CuX-dptz, were synthesized by a rapid and facile method at room temperature, showing preeminent H2 O2 photoproduction performance under pure water and open air without any additives. CuBr-dptz exhibits a H2 O2 production rate high up to 1874 µmol g-1 h-1 , exceeding most reported photocatalysts under this condition, even comparable to those supported by sacrificial agents and O2 . The coordination environment of Cu can be modulated by halogen atoms (X=Cl, Br, I), which in turn affects the electron transfer process and finally determines the reaction activity. This is the first time that 2D CPs have been used for photocatalytic H2 O2 production in such challenging conditions, which provides a new pathway for the development of portable in situ H2 O2 photosynthesis devices.

Identification of a novel variant c.761C>T on ABO*B.01 gene in ABO glycosyltransferases associated with Bweak phenotype.

BACKGROUND AND OBJECTIVES: ABO antigens are produced from H antigen by the activity of glycosyltransferase enzyme encoded by the ABO gene. Variants in the ABO gene can produce a weak ABO phenotype. In this study, we identify a novel ABO*BW allele and investigate the underlying mechanism leading to the Bweak phenotype. MATERIALS AND METHODS: The ABO phenotype and genotype of the sample were determined using serological and direct DNA sequencing methods. We assessed the impact of the novel variant by three-dimensional modelling to predict protein stability changes (ΔΔG), and carried out an in vitro expression assay. The total glycosyltransferase transfer capacity in the supernatant of transfected cells was also examined. RESULTS: Serological analysis confirmed the Bweak phenotype in the subject, and gene sequencing identified a novel variant c.761C>T (p.A254V) on the ABO*B.01 allele, resulting in a BW-var/O.01.02 genotype. In silico analysis suggested that the p.A254V variant on the B allele may reduce the stability of glycosyltransferase B (GTB), as indicated by the ΔΔG values. In vitro expression studies showed that the variant p.A254V impaired H to B antigen conversion, although it did not affect the expression of GTB. CONCLUSION: We identified a novel BW allele and demonstrated that the variant c.761C>T (p.A254V) can cause the Bweak phenotype by reducing the stability of GTB.

Point CNN:3D Face Recognition with Local Feature Descriptor and Feature Enhancement Mechanism.

Three-dimensional face recognition is an important part of the field of computer vision. Point clouds are widely used in the field of 3D vision due to the simple mathematical expression. However, the disorder of the points makes it difficult for them to have ordered indexes in convolutional neural networks. In addition, the point clouds lack detailed textures, which makes the facial features easily affected by expression or head pose changes. To solve the above problems, this paper constructs a new face recognition network, which mainly consists of two parts. The first part is a novel operator based on a local feature descriptor to realize the fine-grained features extraction and the permutation invariance of point clouds. The second part is a feature enhancement mechanism to enhance the discrimination of facial features. In order to verify the performance of our method, we conducted experiments on three public datasets: CASIA-3D, Bosphorus, and Lock3Dface. The results show that the accuracy of our method is improved by 0.7%, 0.4%, and 0.8% compared with the latest methods on these three datasets, respectively.

Molecular biology analysis of ABO blood group variants caused by natural chimaerism.

BACKGROUND AND OBJECTIVES: The chimaerism phenomenon constitutes a significant mechanism underlying ABO phenotype discrepancies; however, its detection has technical challenges. In the current study, we explored different techniques to establish the chimaeric status of ABO blood types. MATERIALS AND METHODS: Fifteen individuals with possible chimaeric ABO blood type, as suggested by standard tube or column agglutination method and RBC adsorption-elution test, were enrolled in the study. The red blood cells from 11 investigated subjects showed mix-field agglutination with anti-A or anti-B in blood typing; weak A or B antigens on the other four individuals' RBCs were detected by adsorption-elution tests. The genetic study was conducted with PCR-SSP genotype, DNA sequencing of the ABO gene, STR analysis and ddPCR. RESULTS: The genetic chimaeric status was confirmed in four (27%) individuals by SSP test alone. The ABO gene sequencing identified an additional ABO allele and enabled chimaerism detection in 10 (67%) subjects. The STR analyses established the chimaerism status in 13 (87%) individuals. In the two cases where neither of the tests mentioned above had positive findings, the ddPCR was adopted, and microchimaerism, with an extremely low degree of chimaerism (0.77% and 0.12%), was revealed. The ddPCR revealed the unequal haplotypes (29.5% B vs. 70.5% O) in one subject and distinguished this B/O-O/O chimaera from certain B subgroups (B/O genotype without any mutation) like B3 . CONCLUSION: The ABO blood type chimaerism can be genetically established by comprehensive molecular methods, including PCR-SSP/DNA sequencing, STR and ddPCR, which is particularly sensitive for the detection of microchimaerism.

The landscape of long noncoding RNA-involved and tumor-specific fusions across various cancers.

The majority of the human genome encodes long noncoding RNA (lncRNA) genes, critical regulators of various cellular processes, which largely outnumber protein-coding genes. However, lncRNA-involved fusions have not been surveyed and characterized yet. Here, we present a systematic study of the lncRNA fusion landscape across cancer types and identify >30 000 high-confidence tumor-specific lncRNA fusions (using 8284 tumor and 6946 normal samples). Fusions positively correlated with DNA damage and cancer stemness and were specifically low in microsatellite instable (MSI)-High or virus-infected tumors. Moreover, fusions distribute differently among cancer molecular subtypes, but with shared enrichment in tumors that are microsatellite stable (MSS), with high somatic copy number alterations (SCNA), and with poor survival. Importantly, we find a potentially new mechanism, mediated by enhancer RNAs (eRNA), which generates secondary fusions that form densely connected fusion networks with many fusion hubs targeted by FDA-approved drugs. Finally, we experimentally validate functions of two tumor-promoting chimeric proteins derived from mRNA-lncRNA fusions, KDM4B-G039927 and EPS15L1-lncOR7C2-1. The EPS15L1 fusion protein may regulate (Gasdermin E) GSDME, critical in pyroptosis and anti-tumor immunity. Our study completes the fusion landscape in cancers, sheds light on fusion mechanisms, and enriches lncRNA functions in tumorigenesis and cancer progression.

VBlock: A Blockchain-Based Tamper-Proofing Data Protection Model for Internet of Vehicle Networks.

The rapid advancement of the Internet of Vehicles (IoV) has led to a massive growth in data received from IoV networks. The cloud storage has been a timely service that provides a vast range of data storage for IoV networks. However, existing data storage and access models used to manage and protect data in IoV networks have proven to be insufficient. They are centralized and usually accompanied by a lack of trust, transparency, security, immutability, and provenance. In this paper, we propose VBlock, a blockchain-based system that addresses the issues of illegal modification of outsourced vehicular data for smart city management and improvement. We introduce a novel collusion-resistant model for outsourcing data to cloud storage that ensures the network remains tamper-proof, has good data provenance and auditing, and solves the centralized problems prone to the single point of failure. We introduced a key revocation mechanism to secure the network from malicious nodes. We formally define the system model of VBlock in the setting of a consortium blockchain. Our simulation results and security analysis show that the proposed model provides a strong security guarantee with high efficiency and is practicable in the IoV environment.

METTL3 regulates skeletal muscle specific miRNAs at both transcriptional and post-transcriptional levels.

METTL3 increasing the mature miRNA levels via N6-Methyladenosine (m6A) modification of primary miRNA (pri-miRNA) transcripts has emerged as an important post-transcriptional regulation of miRNA biogenesis. Our previous studies and others have showed that muscle specific miRNAs are essential for skeletal muscle differentiation. Whether these miRNAs are also regulated by METTL3 is still unclear. Here, we found that m6A motifs were present around most of these miRNAs, which were indeed m6A modified as confirmed by m6A-modified RNA immunoprecipitation (m6A RIP). However, we surprisingly found that these muscle specific miRNAs were repressed instead of increased by METTL3 in C2C12 in vitro differentiation and mouse skeletal muscle regeneration after injury in vivo model. To elucidate the underlined mechanism, we performed reporter assays in 293T cells and validated METTL3 increasing these miRNAs at post-transcriptional level as expected. Furthermore, in myogenic C2C12 cells, we found that METTL3 not only repressed the expression of myogenic transcription factors (TFs) which can enhance the muscle specific miRNAs, but also increased the expression of epigenetic regulators which can repress these miRNAs. Thus, METTL3 could repress the muscle specific miRNAs at transcriptional level indirectly. Taken together, our results demonstrated that skeletal muscle specific miRNAs were repressed by METTL3 and such repression is likely synthesized transcriptional and post-transcriptional regulations.

A Para-Bombay Blood Group Case Associated with a Novel FUT1 Mutation c.361G>A.

BACKGROUND: Here we report a case of para-Bombay phenotype due to a novel mutation FUT1 c.361G>A p.(Ala121Thr) and a nonfunctional allele FUT1*01N.13(c.881_882delTT) which showed a discrepancy in the routine ABO blood group typing. MATERIALS AND METHODS: The ABO phenotype and the Lewis blood group were typed with serological methods. The ABH antigens in saliva were determined by a hemagglutination inhibition test. The CDS region of ABO, FUT1and FUT2 were amplified with polymerase chain reaction and then directly sequenced. The novel mutation was confirmed by cloning and sequencing. Three-dimensional (3-D) structural analysis of the mutant and wild-type Fut1 were performed by the Chimera software. RESULTS: A, B and H antigens were not detected on the surface of red blood cells (RBCs) by the serological technique, and the B and H blood group substances were detected in the saliva, while the Lewis phenotype was Le(a-b+). Sequencing and cloning analysis showed the presence of a novel FUT1 mutation c.361G>A and a nonfunctional allele FUT1*01N.13(c.881_882delTT). The ABO genotype was ABO*B.01/ABO*O.01.01. The in silico analysis showed that the mutation p.(Ala121Thr) of FUT1did not change the 3-D structure of the whole enzyme but caused a certain amplitude of turnover in the loop region where Ala121 was located. CONCLUSIONS: A novel FUT1 allele (FUT1*c.361G>A) was identified in a Chinese individual with para-Bombay B phenotype. The FUT1c.361G>A mutation may significantly downregulate the expression of H antigens on RBCs by damaging the enzyme conformation.

Novel 3D Nanoporous Zn-Cu Alloy as Long-Life Anode toward High-Voltage Double Electrolyte Aqueous Zinc-Ion Batteries.

The recharge ability of zinc metal-based aqueous batteries is greatly limited by the zinc anode. The poor cycling durability of Zn anodes is attributed to the dendrite growth, shape change and passivation, but this issue has been ignored by using an excessive amount of Zn in the past. Herein, a 3D nanoporous (3D NP) Zn-Cu alloy is fabricated by a sample electrochemical-assisted annealing thermal method combined, which can be used directly as self-supported electrodes applied for renewable zinc-ion devices. The 3D NP architectures electrode offers high electron and ion transport paths and increased material loading per unit substrate area, which can uniformly deposit/strip Zn and improve charge storage ability. Benefiting from the intrinsic materials and architectures features, the 3D NP Zn-Cu alloy anode exhibits high areal capacity and excellent cycling stability. Further, the fabricated high-voltage double electrolyte aqueous Zn-Br2 battery can deliver maximum areal specific capacity of ≈1.56 mAh cm-2 , which is close to the level of typical commercial Li-ion batteries. The excellent performance makes it an ideal candidate for next-generation aqueous zinc-ion batteries.

Mannosylated structures of mycobacterial lipoarabinomannans facilitate the maturation and activation of dendritic cells.

Lipoarabinomannan (LAM) is an important virulent factor secreted by mycobacteria, which generally elicit a strong immune response in the host. In this study, the structural difference of LAMs from three mycobacterial strains, Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc2155 and a newly discovered clinical isolate, M. sp. QGD101, was analyzed and further evaluated whether these LAMs can induce DC maturation and promote the immunomodulatory properties. The results reveal that the major structural difference of these LAMs is the amount of mannosyl residues, especially at the terminal end of LAM, which play a key role in determining the divergent response of DCs after mycobacterial infection. Also, this study indicates an important relevance between the glycosylated structure of LAM and its immunomodulatory property, which is helpful to develop a potential approach for identification of different mycobacteria and also lays a foundation for the development of a novel polysaccharide immunological strategy against tuberculosis.

An exonic missense mutation c.28G>A is associated with weak B blood group by affecting RNA splicing of the ABO gene.

BACKGROUND: The amino acid substitutions caused by ABO gene mutations are usually predicted to impact glycosyltransferase's function or its biosynthesis. Here we report an ABO exonic missense mutation that affects B-antigen expression by decreasing the mRNA level of the ABO gene rather than the amino acid change. STUDY DESIGN AND METHODS: Serologic studies including plasma total GTB transfer capacity were performed. The exon sequences of the ABO gene were analyzed by Sanger sequencing. B310 cDNA with c.28G>A (p.G10R) mutation was expressed in HeLa cells and total GTB transfer capacity in cell supernatant was measured. Flow cytometry was performed on these HeLa cells after transfection, and agglutination of Hela-Bweak cells was also examined. The mRNA of the ABO gene was analyzed by direct sequencing and real-time reverse transcriptase-polymerase chain reaction. A minigene construct was prepared to evaluate the potential of splicing. RESULTS: While plasma total GTB transfer capacity was undetectable in this B3 -like individual, the relative percentage of antigen-expressing cells and mean fluorescence index of the Bweak red blood cells (RBCs) were 19 and 14% of normal B RBCs, respectively. There was no significant difference of total GTB transfer capacity in cell supernatant and B-antigen expression on cell surfaces between HeLa cells transfected with B310 cDNA and B cDNA. The mRNA expression level of B310 in peripheral whole blood was significantly reduced. The amount of splicing is significantly lower in c.28G>A construct compared to that in wild-type construct after transfection in K562 cells. CONCLUSION: ABO c.28G>A mutation may cause B3 -like subgroup by affecting RNA splicing of the ABO gene.

Intensified dust storm activity and Valley fever infection in the southwestern United States.

Climate models have consistently projected a drying trend in the southwestern United States, aiding speculation of increasing dust storms in this region. Long-term climatology is essential to documenting the dust trend and its response to climate variability. We have reconstructed long-term dust climatology in the western United States, based on a comprehensive dust identification method and continuous aerosol observations from the Interagency Monitoring of Protected Visual Environments (IMPROVE) network. We report here direct evidence of rapid intensification of dust storm activity over American deserts in the past decades (1988-2011), in contrast to reported decreasing trends in Asia and Africa. The frequency of windblown dust storms has increased 240% from 1990s to 2000s. This dust trend is associated with large-scale variations of sea surface temperature in the Pacific Ocean, with the strongest correlation with the Pacific Decadal Oscillation. We further investigate the relationship between dust and Valley fever, a fast-rising infectious disease caused by inhaling soil-dwelling fungus (Coccidioides immitis and C. posadasii) in the southwestern United States. The frequency of dust storms is found to be correlated with Valley fever incidences, with a coefficient (r) comparable to or stronger than that with other factors believed to control the disease in two endemic centers (Maricopa and Pima County, Arizona).

The novel HLA-B*46:01:42 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*46:01:42 differs from HLA-B*46:01:01:01 by one nucleotide in exon 5.

Case report: Decreased hemoglobin and multiple organ failure caused by ceftizoxime-induced immune hemolytic anemia in a Chinese patient with malignant rectal cancer.

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious condition, with an estimated incidence of one in 100,000 cases, associated with various antibiotics. This study reports on a case of ceftizoxime-induced hemolysis observed in a patient in China. Case description: A Chinese patient diagnosed with malignant rectal cancer underwent antimicrobial therapy after laparoscopic partial recto-sigmoid resection (L-Dixon). After receiving four doses of ceftizoxime, the patient developed symptoms including rash, itchy skin, and chest distress, followed by a rapid decline in hemoglobin levels, the presence of hemoglobin in the urine (hemoglobinuria), renal failure, and disseminated intravascular coagulation. Laboratory analysis revealed high-titer antibodies against ceftizoxime and red blood cells (RBCs) in the patient's serum, including immunoglobulin M (IgM) (1:128) antibodies and immunoglobulin G (IgG) (1:8) antibodies, with noted crossreactivity to ceftriaxone. Significant improvement in the patient's hemolytic symptoms was observed following immediate discontinuation of the drug, two plasma exchanges, and extensive RBC transfusion. Conclusion: This case, together with previous reports, underscores the importance of considering DIIHA in patients who exhibit unexplained decreases in hemoglobin levels following antibiotic therapy. A thorough examination of the patient's medical history can provide crucial insights for diagnosing DIIHA. The effective management of DIIHA includes immediate cessation of the implicated drug, plasma exchange, and transfusion support based on the identification of specific drug-dependent antibodies through serological testing.

Frailty and psychiatric disorders: A bidirectional Mendelian randomization study.

BACKGROUND: The association between frailty and psychiatric disorders has been reported in observational studies. However, it is unclear whether frailty facilitates the appearance of psychiatric disorders or vice versa. Therefore, we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causality. METHODS: Independent genetic variants associated with frailty index (FI) and psychiatric disorders were obtained from large genome-wide association studies (GWAS). The inverse variance weighted method was utilized as the primary method to estimate causal effects, followed by various sensitivity analyses. Multivariable analyses were performed to further adjust for potential confounders. RESULTS: The present MR study revealed that genetically predicted FI was significantly and positively associated with the risk of major depressive disorder (MDD) (odds ratio [OR] 1.79, 95 % confidence interval [CI] 1.48-2.15, P = 1.06 × 10-9), anxiety disorder (OR 1.61, 95 % CI 1.19-2.18, P = 0.002) and neuroticism (OR 1.38, 95 % CI 1.18-1.61, P = 3.73 × 10-5). In the reverse MR test, genetic liability to MDD (beta 0.232, 95 % CI 0.189-0.274, P = 1.00 × 10-26) and neuroticism (beta 0.128, 95 % CI 0.081-0.175, P = 8.61 × 10-8) were significantly associated with higher FI. Multivariable analyses results supported the causal association between FI and MDD and neuroticism. LIMITATIONS: Restriction to European populations, and sample selection bias. CONCLUSIONS: Our study suggested a bidirectional causal association between frailty and MDD neuroticism, and a positive correlation of genetically predicted frailty on the risk of anxiety disorder. Developing a deeper understanding of these associations is essential to effectively manage frailty and optimize mental health in older adults.