[Genetic analysis of an individual with A3 phenotype due to variant of A-glycosyltransferase enzyme gene].

OBJECTIVE: To explore the serological characteristics and molecular mechanism underlying an individual with A3 phenotype. METHODS: A 27-year-old ethnic Han Chinese woman presented at the Fourth Affiliated Hospital of China Medical University on May 12, 2022 was selected as the study subject. ABO blood type was determined with standard serological techniques. The ABO gene was subjected to direct sequencing of PCR products. Exons 6 and 7 of the ABO gene were sequenced using specific primers to determine the haplotypes. Bioinformatic software was used to analyze the structure of the mutant protein. RESULTS: Serological typing of the ABO blood group has suggested a rare A3 phenotype. The proband was found to harbor heterozygous c.261delG, c.467C>T and c.745C>T variants by direct sequencing. Single strand sequencing revealed that she has harbored ABO*A3.07 and ABO*O.01.01 alleles. The ABO*A3.07 allele has contained a c.745C>T (p.R249W) variant on the background of an ABO*A1.02 allele. The p.R249W substitution was predicted to be probably damaging by the PolyPhen2 software. The free energy change (ΔΔG) value predicted it to have a destabilizing effect on the GTA protein. Meanwhile, modeling of the 3D structure has predicted that the p.R249W amino acid substitution may alter the hydrogen bond network of the GTA protein. CONCLUSION: The p.R249W substitution of the α-1,3-N-acetylgalactosaminyltransferase gene may reduce the antigen expression owing to a great destabilizing effect on the structure and function of the GTA protein.

Molecular-Level Interfacial Chemistry Regulation of MXene Enables Energy Storage beyond Theoretical Limit.

Ti3C2Tx MXene often suffers from poor lithium storage behaviors due to its electrochemically unfavorable OH terminations. Herein, we propose molecular-level interfacial chemistry regulation of Ti3C2Tx MXene with phytic acid (PA) to directly activate its OH terminations. Through constructing hydrogen bonds (H-bonds) between oxygen atoms of PA and OH terminations on Ti3C2Tx surface, interfacial charge distribution of Ti3C2Tx has been effectively regulated, thereby enabling sufficient ion-storage sites and expediting ion transport kinetics for high-performance energy storage. The results show that Li ions preferably bind to H-bond acceptors (oxygen atoms from PA), and the flexibility of H-bonds therefore renders their interactions with adsorbed Li ions chemically "tunable", thus alleviating undesirable localized geometric changes of the OH terminations. Meanwhile the H-bond-induced microscopic dipoles can act as directional Li-ion pumps to expedite ion diffusion kinetics with lower energy barrier. As a result, the as-designed Ti3C2Tx/PA achieves a 2.4-fold capacity enhancement compared with pristine Ti3C2Tx (even beyond theoretical capacity), superior long-term cyclability (220.0 mAh g-1 after 2000 cycles at 2.0 A g-1), and broad temperature adaptability (-20 to 50 °C). This work offers a promising interface engineering strategy to regulate microenvironments of inherent terminations for breaking through the energy storage performance of MXenes.

Conductive Ti3C2Tx networks to optimize Na3V2O2(PO4)2F cathodes for improved rate capability and low-temperature operation.

Na3V2O2(PO4)2F (NVOPF) is gaining attention as a high-energy cathode candidate for sodium-ion batteries owing to its wide operating voltage, high energy density and excellent thermal stability. However, its intrinsic poor electrical conductivity results in its current sodium-storage performance being far below expectations. Herein, two-dimensional Ti3C2Tx MXene nanosheets with excellent electrical conductivity are introduced to construct an interconnected conductive framework to tightly encapsulate NVOPF nanoparticles. The Ti3C2Tx nanosheets ensure superior electronic contacts, along with inhibiting the agglomeration of NVOPF nanoparticles, thus accelerating electron and ion transfer during sodium-ion de/intercalation and maximizing the storage capacity. As a result, the optimized NVOPF/Ti3C2Tx cathode exhibits high rate capabilities (111 mA h g-1 at 0.2 C and 78 mA h g-1 at 20 C), with an impressively high capacity retention of 74.8% over a wide temperature range (from -20 to 20 °C). Additionally, the assembled sodium-ion full cell provides a highly reversible capacity of 116 mA h g-1 at 1 C, with a capacity retention of 67.2% after 100 cycles. These inspiring results provide new insights for improving the charge-transfer kinetics of the NVOPF cathode and this methodology may be extended to other cathode materials.

A novel HLA allele, HLA-B*07:248, detected in a Chinese hematopoietic stem cell donor and platelet donor.

HLA-B*07:248 has one nucleotide change from HLA-B*07:18:01 where Tyrosine (Y) is changed to Serine (S).

Label-free and sensitive microRNA detection method based on the locked nucleic acid assisted fishing amplification strategy.

Herein, a label free and sensitive miRNA detection method with enhanced practical applicability was developed based on the locked nucleic acid (LNA) assisted repeated fishing amplification strategy. The working mechanism of the proposed method is as follows: 1) a DNA probe (i.e, L-DNA) with LNA bases is immobilized onto the surface of a gold foil. The L-DNA hybridizes with the 3' terminus of the first strands of complementary deoxyribonucleic acid (cDNA) of the target miRNA in the test samples; 2) The protruding 5' terminus of the cDNA serves as a 'fishhook' to repeatedly fish the products of a hybridization chain reaction (HCR) out from a 'reaction tube'; 3) The HCR products can be unloaded from the gold foil into a 'product tube' through temperature-controlled dehybridization; 4) The concentration of the target miRNA is determined based on the fluorescence intensity generated by the addition of SYBR-Green I (SG) into the 'product tube'. The proposed platform was applied to the detection of miRNA-122 in cell lysate samples and obtained quantitative results with accuracy comparable to the quantitative reverse transcription PCR method (qRT-PCR). It is worth pointing out that the proposed platform achieved a limit of detection value of 2.9 fM for miRNA-122 by a simple but effective LNA-assisted repeated fishing amplification strategy instead of complicated enzyme-based amplification techniques. It is reasonable to expect that the proposed method provides a competitive alternative for designing practically applicable, cost-effective and label-free miRNA detection methods.

A spatiotemporal steroidogenic regulatory network in human fetal adrenal glands and gonads.

Human fetal adrenal glands produce substantial amounts of dehydroepiandrosterone (DHEA), which is one of the most important precursors of sex hormones. However, the underlying biological mechanism remains largely unknown. Herein, we sequenced human fetal adrenal glands and gonads from 7 to 14 gestational weeks (GW) via 10× Genomics single-cell transcriptome techniques, reconstructed their location information by spatial transcriptomics. Relative to gonads, adrenal glands begin to synthesize steroids early. The coordination among steroidogenic cells and multiple non-steroidogenic cells promotes adrenal cortex construction and steroid synthesis. Notably, during the window of sexual differentiation (8-12 GW), key enzyme gene expression shifts to accelerate DHEA synthesis in males and cortisol synthesis in females. Our research highlights the robustness of the action of fetal adrenal glands on gonads to modify the process of sexual differentiation.

An assumption-free quantitative polymerase chain reaction method with internal standard.

In real-time quantitative polymerase chain reaction (PCR), the standard curve between threshold cycle and logarithm of template concentration is currently the gold standard for template quantification. The efficacy of this approach is limited by the necessary assumption that all samples are amplified with the same efficiency. To overcome this limitation, a new method has been proposed in this contribution for quantitative PCR with internal standard. Unlike existing methods based upon analysis of amplification profile position, the new method tries to determine the initial quantity of the target template in a sample from the fluorescence spectrum measured at a certain point during its PCR reaction. There is no unrealistic prerequisite (e.g., constant amplification efficiency) for the successful application of the new method. The performance of the new method was evaluated by the quantification of KRAS gene in HepG2 samples. Quantitative results with recovery rates in the range of 91.2-118% were achieved by the new method. It is reasonable to expect that the new method would have a place in real-time quantitative PCR, thanks to its features of no unrealistic prerequisite, sound theoretical basis, good performance, and implementation simplicity.

Underlying renal insufficiency: the pivotal risk factor for Pneumocystis jirovecii pneumonia in immunosuppressed patients with non-transplant glomerular disease.

PURPOSES: Data on PCP in patients with glomerular disease are rare. The aim of this study was to assess the predictors of PCP development, the risk factors for mortality and the incidence of acute kidney injury (AKI) when high-dose trimethoprim-sulphamethoxazole (TMP-SMX) was used in patients with non-transplant glomerular disease. METHODS: Forty-seven patients with PCP, as confirmed by positive results for Pneumocystis jirovecii DNA or Pneumocystis jirovecii cysts tested by a methenamine silver stain between January 1, 2003, and December 30, 2012, were retrospectively investigated. The baseline characteristics of glomerular disease, clinical findings of PCP and renal parameters after treatment were collected. Predictors for PCP development and risk factors for mortality were determined using a multivariate logistic regression analysis. RESULTS: All PCP patients exclusively received immunosuppressants. Baseline renal insufficiency [estimated glomerular filtration rate (eGFR) <60 mL/min·1.73 m2] was present in 87.23 % of patients. The overall mortality rate was 29.79 %. A pulmonary coinfection and the need for mechanical ventilation were independently associated with PCP mortality. A lower eGFR, lower serum albumin level and a higher percentage of global glomerulosclerosis were independent predictors of PCP in patients with IgA nephropathy receiving immunosuppressants. AKI occurred in 60.47 % of patients who received TMP-SMX. After treatment cessation, 93.75 % of surviving patients showed a recovery of renal function to baseline values. CONCLUSIONS: PCP is a fatal complication in patients with glomerular disease, and the use of immunosuppressants may be a basic risk factor for this infection. Underlying renal insufficiency and high renal pathology chronicity are the key risk factors for PCP in IgA nephropathy. TMP-SMX therapy remains an ideal choice because of high treatment response and frequently reversible kidney injury.