Association of HLA-E single nucleotide polymorphisms with human myeloid leukemia.

Single nucleotide polymorphisms (SNPs) of HLA-E are related to the occurrence of many diseases, but their functions remain unclear. In this study, the function of SNPs at HLA-E rs76971248 and rs1264457 on the myeloid leukemia cells was analyzed by a progressive procedure, included genotyping, mRNA transcription, regulatory element, protein expression, and anti-tumor effect. The frequencies of rs76971248 G and rs1264457 G were found higher in myeloid leukemia patients than those in healthy blood donors (p < 0.05). For myeloid leukemia, rs76971248 T was protective, while rs1264457 G was susceptible. We also found that rs76971248 affected HLA-E mRNA transcription and membrane HLA-E (mHLA-E) expression in K562 cells through differently binding to transcription factor HOXA5 (p < 0.0001), while rs1264457 affected mHLA-E expression by changing mRNA transcription and an encoding amino acid (p < 0.01). In contrast, the expression of soluble HLA-E (sHLA-E) was not influenced by both rs1264457 and rs76971248. The higher HLA-E expression was detected among myeloid leukemia patients, and the K562 cells with higher HLA-E molecules played a significant inhibitory effect on the killing activity of NK-92MI cells (p < 0.05). In conclusion, the higher HLA-E expression of myeloid leukemia cells is promoted by rs76971248 G and rs1264457 G, which helps escape from NK-92MI cells' killing.

HP promotes neutrophil inflammatory activation by regulating PFKFB2 in the glycolytic metabolism of sepsis.

BACKGROUND: Sepsis, described as an inflammatory reaction to an infection, is a very social health problem with high mortality. This study aims to explore the new mechanism in the progression of sepsis. METHODS: We downloaded the GSE69528 dataset to screen differentially expressed genes (DEGs) for WGCNA, in which the key module was identified and analyzed by DMNC algorithm, expression verification and ROC curve analysis to identify the hub gene. Furthermore, the hub gene was analyzed by immunoassay, and the potential mechanism of hub gene in neutrophils was investigated by in vitro experiments. RESULTS: The turquoise module was the key module for sepsis in WGCNA on 94 DEGs. The top 20 genes of DMNC network were verified in GSE69528 and GSE9960, and 10 significant genes were obtained for ROC analysis. Based on the ROC curves, HP was considered the hub gene in sepsis, and its expression difference in sepsis and control groups was substantially significant. Further, it was demonstrated the knockdown of HP and PFKFB3 could suppress glycolysis and inflammatory cytokine levels in dHL-60 cell treated with LPS. CONCLUSION: In conclusion, HP is identified as a potential diagnostic indicator for sepsis patients, and HP promotes neutrophil inflammatory activation by regulating PFKFB2 in the glycolytic metabolism of sepsis confirmed by in vitro experiments. These will help us deepen the molecular mechanism of sepsis.

Bavachin ameliorates neuroinflammation and depressive-like behaviors in streptozotocin-induced diabetic mice through the inhibition of PKCδ.

Depression and diabetes are closely linked; however, the pathogenesis of depression associated with diabetes is unclear, and there are no clinically effective antidepressant drugs for diabetic patients with depression. Bavachin is an important active ingredient in Fructus Psoraleae. In this study, we evaluated the anti-neuroinflammatory and antidepressant effects associated with diabetes and the molecular mechanisms of bavachin in a streptozotocin-induced diabetes mouse model. We found that bavachin clearly decreased streptozotocin (STZ)-induced depressive-like behaviors in mice. It was further found that bavachin significantly inhibited microglia activation and the phosphorylation level of PKCδ and inhibited the activation of the NF-κB pathway in vivo and in vitro. Knockdown of PKCδ with siRNA-PKCδ partially reversed the inhibitory effect of bavachin on the NF-κB pathway and the level of pro-inflammatory factors. We further found that PKCδ directly bound to bavachin based on molecular docking and pull-down assays. We also found that bavachin improved neuroinflammation-induced neuronal survival and functional impairment and that this effect may be related to activation of the ERK and Akt pathways mediated by the BDNF pathway. Taken together, these data suggested that bavachin, by targeting inhibition PKCδ to inhibit the NF-κB pathway, further reduced the inflammatory response and oxidative stress and subsequently improved diabetic neuronal survival and function and finally ameliorated diabetes-induced depressive-like behaviors in mice. For the first time, we found that bavachin is a potential agent for the treatment of diabetes-associated neuroinflammation and depression and that PKCδ is a potential target for the treatment of diabetes-associated neuroinflammation, including depression.

ADAM9 deubiquitination induced by USP22 suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition of trophoblast cells in preeclampsia.

INTRODUCTION: The dysregulation of deubiquitination has been shown to affect the development of pre-eclampsia (PE). A disintegrin and metalloprotease 9 (ADAM9) plays roles in diverse physiological contexts, including PE. Here, this study aimed to investigate whether ADAM9 regulated trophoblast cell dysfunction through ubiquitin-specific protease 22 (USP22) deubiquitinase-mediated deubiquitination during PE. METHODS: Levels of genes and proteins were tested via qRT-PCR and western blotting assays. Cell proliferation, migration, and invasion were detected using cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell and wound healing assays, respectively. Epithelial-mesenchymal transition related markers were assayed using western blotting. Proteins between USP22 and ADAM9 were identified by co-immunoprecipitation assay. RESULTS: ADAM9 was highly expressed in PE patients, functionally, ADAM9 overexpression weakened the proliferation, migration, invasion, and EMT progression in trophoblast cells. Mechanistically, the deubiquitinase USP22 removed ubiquitination on ADAM9 and maintained its stability. Forced expression of USP22 also suppressed the proliferation and mobility in trophoblast cells. Moreover, the regulatory effects of USP22 on trophoblast cells were reversed by ADAM9 silencing. In addition, USP22 interacted with ADAM9 to regulate the activation of Wnt/ß-catenin pathway. DISCUSSION: ADAM9 was deubiquitinated and stabilized by USP22 and then suppressed the proliferation, migration, invasion, and EMT progression in trophoblast cells, indicating a new pathway of USP10/RUNX1 axis in PE process.

Towards Better Generalization Using Synthetic Data: A Domain Adaptation Framework for T2 Mapping via Multiple Overlapping-Echo Acquisition.

The generation of synthetic data using physics-based modeling provides a solution to limited or lacking real-world training samples in deep learning methods for rapid quantitative magnetic resonance imaging (qMRI). However, synthetic data distribution differs from real-world data, especially under complex imaging conditions, resulting in gaps between domains and limited generalization performance in real scenarios. Recently, a single-shot qMRI method, multiple overlapping-echo detachment imaging (MOLED), was proposed, quantifying tissue transverse relaxation time (T2) in the order of milliseconds with the help of a trained network. Previous works leveraged a Bloch-based simulator to generate synthetic data for network training, which leaves the domain gap between synthetic and real-world scenarios and results in limited generalization. In this study, we proposed a T2 mapping method via MOLED from the perspective of domain adaptation, which obtained accurate mapping performance without real-label training and reduced the cost of sequence research at the same time. Experiments demonstrate that our method outshined in the restoration of MR anatomical structures.

Sociodemographic Factors Related to Adverse Donor Reactions in Shenzhen.

Background: The adverse donor reaction (ADR) means the uncomfortable feeling felt by blood donors during the whole process of blood donation, which can affect the blood donation behavior of blood donors. So, it is very necessary for blood centers to monitor and prevent it. Methods: Data about ADRs in Shenzhen Blood Center from January 2018 to December 2022 were collected, and correlation analysis was conducted using SPSS 24.0 software. Results: From January 2018 to December 2022, a total of 1265 ADRs occurred in 642,767 blood donations in Shenzhen Blood Center, with an incidence of 0.20%. Most of the ADRs were mild and occurred during blood collections (>90%). The ADR rate of young individuals aged 18-29 years old was the highest (p<0.0001). In addition, a higher ADR rate was observed in first-time blood donors, whole blood donors, and blood donors who donated in the mobile sites (p<0.05). Conclusion: The occurrence of ADRs is related to the sociodemographic factors of blood donors, including age, donation type, donation history, and donation sites. Shenzhen Blood Centers should pay special attention to the process of blood donation among young blood donors aged 18-29 years old, first-time blood donors, whole-blood donors, and blood donors who donate at mobile sites to further reduce the occurrence of ADRs.

Exploring personalization via federated representation Learning on non-IID data.

Federated Learning (FL) can learn a global model across decentralized data over different clients. However, it is susceptible to statistical heterogeneity of client-specific data. Clients focus on optimizing for their individual target distributions, which would yield divergence of the global model due to inconsistent data distributions. Moreover, federated learning approaches adhere to the scheme of collaboratively learning representations and classifiers, further exacerbating such inconsistency and resulting in imbalanced features and biased classifiers. Hence, in this paper, we propose an independent two-stage personalized FL framework, i.e., Fed-RepPer, to separate representation learning from classification in federated learning. First, the client-side feature representation models are learned using supervised contrastive loss, which enables local objectives consistently, i.e., learning robust representations on distinct data distributions. Local representation models are aggregated into the common global representation model. Then, in the second stage, personalization is studied by learning different classifiers for each client based on the global representation model. The proposed two-stage learning scheme is examined in lightweight edge computing that involves devices with constrained computation resources. Experiments on various datasets (CIFAR-10/100, CINIC-10) and heterogeneous data setups show that Fed-RepPer outperforms alternatives by utilizing flexibility and personalization on non-IID data.

Demographic Factors Among HIV Confirmed Blood Donors from 2013 to 2021 in Shenzhen.

Background: New HIV (Human immune deficiency virus) infections are continuously increasing in China and it remains a huge challenge to blood donation. As access to health services has affected by COVID-19 (Corona virus disease 2019) pandemic, a drop in new diagnoses (especially HIV) was observed worldwide. Methods: During 2013-2021, 735,247 specimens from unpaid blood donors collected by Shenzhen Blood Center underwent ELISA (Enzyme -linked immunosorbent assay) and NAT (Nucleic acid test). Samples with reactivity results were sent to the Shenzhen Center for Disease Control and Prevention for WB (Western blot). All data were statistically analyzed by the Chi-Square test. Results: From 2013 to 2021, the prevalence of HIV among male blood donors was higher than in females (P < 0.01). During the COVID-19 pandemic, the prevalence of HIV among repeat blood donors decreased significantly compared to 2019 (P < 0.05), and the characteristics of blood donors changed in 2020 compared to 2019 and 2021. Conclusion: The high proportion of female blood donors would help prevent HIV from getting into the blood supply. The COVID-19 pandemic affected the demographics of blood donors as well as the prevalence of HIV among repeat blood donors. An increased number of repeat blood donors can help decrease the risk of HIV transfusion transmission during the epidemic.

Enhanced Deep Blind Hyperspectral Image Fusion.

The goal of hyperspectral image fusion (HIF) is to reconstruct high spatial resolution hyperspectral images (HR-HSI) via fusing low spatial resolution hyperspectral images (LR-HSI) and high spatial resolution multispectral images (HR-MSI) without loss of spatial and spectral information. Most existing HIF methods are designed based on the assumption that the observation models are known, which is unrealistic in many scenarios. To address this blind HIF problem, we propose a deep learning-based method that optimizes the observation model and fusion processes iteratively and alternatively during the reconstruction to enforce bidirectional data consistency, which leads to better spatial and spectral accuracy. However, general deep neural network inherently suffers from information loss, preventing us to achieve this bidirectional data consistency. To settle this problem, we enhance the blind HIF algorithm by making part of the deep neural network invertible via applying a slightly modified spectral normalization to the weights of the network. Furthermore, in order to reduce spatial distortion and feature redundancy, we introduce a Content-Aware ReAssembly of FEatures module and an SE-ResBlock model to our network. The former module helps to boost the fusion performance, while the latter make our model more compact. Experiments demonstrate that our model performs favorably against compared methods in terms of both nonblind HIF fusion and semiblind HIF fusion.

ISG15 is associated with cervical cancer development.

Cervical cancer (CC) is a complex disease. Numerous factors contribute to the tumourigenesis and progression of CC neoplasms. The present study analysed transcriptomic differences and simulated tumour progression to explore the pathogenesis of CC. RNA sequencing was performed to analyse the transcriptomic differences among normal tissue (NC), paracarcinoma tissue (TP), and primary tumour tissue (TT). Pseudo-time analysis was performed to simulate tumour progression. Reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) were used to analyse the expression levels of ISG15 ubiquitin-like modifier (ISG15). Cell proliferation wound healing and Transwell assays were used to examine the effect of ISG15 inhibition and overexpression on HeLa cells. The RT-qPCR and IHC results indicated that ISG15 expression was significantly upregulated in TT. An increasing trend of ISG15 expression from NC to TP to TT was observed, which suggested that elevated ISG15 expression was closely associated with malignant evolution in CC tissues. HeLa cell experiments revealed that ISG15-small interfering RNA inhibited cell proliferation and invasion. The present study demonstrated that ISG15 was upregulated in CC and positively associated with the development of CC. ISG15 may act as an oncogene in the tumourigenesis of CC.

Comprehensive Evaluation of Deep Coal Miners' Unsafe Behavior Based on HFACS-CM-SEM-SD.

The unsafe behavior of miners seriously affects the safety of deep mining. A comprehensive evaluation of miners' unsafe behavior in deep coal mines can prevent coal mine accidents. This study combines HFACS-CM, SEM, and SD models to evaluate miners' unsafe behaviors in deep coal mining. First, the HFACS-CM model identifies the risk factors affecting miners' unsafe behavior in deep coal mines. Second, SEM was used to analyze the interaction between risk factors and miners' unsafe behavior. Finally, the SD model was used to simulate the sensitivity of each risk factor to miners' unsafe behavior to explore the best prevention and control strategies for unsafe behavior. The results showed that (1) environmental factors, organizational influence, unsafe supervision, and unsafe state of miners are the four main risk factors affecting the unsafe behavior of miners in deep coal mines. Among them, the unsafe state of miners is the most critical risk factor. (2) Environmental factors, organizational influence, unsafe supervision, and the unsafe state of miners have both direct and indirect impacts on unsafe behaviors, and their immediate effects are far more significant than their indirect influence. (3) Environmental factors, organizational influence, and unsafe supervision positively impact miners' unsafe behavior through the mediating effect of miners' unsafe states. (4) Mental state, physiological state, business abilities, resource management, and organizational climate were the top five risk factors affecting miners' unsafe behaviors. Taking measures to improve the adverse environmental factors, strengthening the organization's supervision and management, and improving the unsafe state of miners can effectively reduce the risk of miners' unsafe behavior in deep coal mines. This study provides a new idea and method for preventing and controlling the unsafe behavior of miners in deep coal mines.

Hot topics and frontier evolution in college flipped classrooms based on mapping knowledge domains.

With the outbreak of COVID-19 and the development of online teaching, the online flipping teaching mode has attracted increasing attention. Systematic analysis of the research status and development trend of the flipped classrooms is significant for guiding the improvement of the quality of online flipped teaching. This study used the metrology software CiteSpace to draw a scientific knowledge map of relevant research in the web of science database from 2013 to 2021. It performed visual analysis of research authors, research institutions and countries, keyword clustering, keywords co-occurrence, and keyword time zone distribution. The results showed that: (1) The flipped classrooms research has attracted increasing attention from the social and educational circles, however, the relationship between relevant research authors, institutions, and countries is not close enough, and there is little cooperation. We need to strengthen cooperation further and realize the sharing of high-quality resources; (2) Based on keyword co-occurrence cluster analysis, this study identified three hot topics, namely, preparation before class, classroom activities and consolidation after class; (3) According to the keyword time zone map, this study divided three frontier evolution trends: exploration period, adaptation period, and growth period; (4) Finally, with the spread of novel coronavirus, it is suggested to promote the online flipped classroom teaching mode, and put forward reasonable suggestions from the perspective of teachers, students and researchers, and look forward to the future digital development direction of the flipped classroom.

[Establishment of sequence-based typing assay for KIR2DS4 gene and identification of a new allele KIR2DS4*016].

OBJECTIVE: To establish a reliable sequence-based typing method for KIR2DS4 and study its allele polymorphism in Chinese Han population. METHODS: Using PCR-SSP method to detect the positive or negative of KIR2DS4 gene in 222 random Chinese Han individuals, and then using the method of high fidelity and long-fragment PCR-SBT to amplify, sequence and genotype the exons 4 and 5 of KIR2DS4 positive individuals. RESULTS: We successfully amplified the fragment with 3.2 kb length contains exons 4 and 5 of KIR2DS4 and detected the KIR2DS4 allele frequency in Chinese Han population. 209 KIR2DS4 positive individuals were detected, and the positive rate is 94.1%. By sequence-based typing, we identified 12 genotypes and 7 alleles of KIR2DS4. The 6 known alleles and their detection frequency is as follows: KIR2DS4* 00101/011 (180, 81.1%), KIR2DS4* 010 (53, 23.9%), KIR2DS4* 004 (34, 15.3%), KIR2DS4* 003 (15 and 6.8%), KIR2DS4* 006 (2, 0.9%) and KIR2DS4* 015 (1, 0.5%). In this study, we found a new allele, KIR2DS4* 016, with the difference in exon 5 comparing its most similar allele KIR2DS4* 010. In the exon 5 of KIR2DS4* 010, there is a 22bp-deletion, while the exon 5 of KIR2DS4* 016 is normal. This is not a rare allele because it was detected 3 times in studied population and with the frequency of 1.4%. The sequence of the new allele sequence has been submitted to GenBank (accession no.: KC414890) and the IPD -KIR database (submission no.: IWS40001804), and was nominated by WHO nomenclature committee for HLA system. CONCLUSION: In this study, a sequence-based typing method for KIR2DS4 was established, and the polymorphism data of KIR2DS4 in Chinese Han population was enriched by studying the allele polymorphism and new allele.

A New Method for Calculating the Relative Permeability Curve of Polymer Flooding Based on the Viscosity Variation Law of Polymer Transporting in Porous Media.

Relative permeability of polymer flooding plays a very important role in oil field development. This paper aimed to measure and calculate the relative permeability curves of polymer flooding more accurately. First, viscosity variation law of polymer in porous media was studied. Rock particles of different diameters and cementing agent were used to make artificial cores and hydrophobically associating polymer solutions were prepared for experiments. Polymer solutions were injected into the cores filled with crude oil and irreducible water. In the process of polymer flooding, produced fluid was collected at different water saturations and locations of the core. Polymer solutions were separated and their viscosities were measured. With the experimental data, the viscosity variation rule of polymer transporting in porous media was explored. The result indicates that the viscosity retention rate of polymer solutions transporting in porous media has power function relationship with the water saturation and the dimensionless distance from the core inlet. Finally, the relative permeability curves of polymer flooding were measured by unsteady state method and the viscosity variation rule was applied to the calculation of the relative permeability curves.

Neuroprotective Mechanisms of Ginsenoside Rb1 in Central Nervous System Diseases.

Panax ginseng and Panax notoginseng, two well-known herbs with enormous medical value in Asian countries, have a long usage history in China for the therapy of some diseases, such as stroke. Ginsenoside Rb1 is one of most important active ingredients in Panax ginseng and Panax notoginseng. In the last two decades, more attention has focused on ginsenoside Rb1 as an antioxidative, anti-apoptotic and anti-inflammatory agent that can protect the nervous system. In the review, we summarize the neuroprotective roles of ginsenoside Rb1 and its potential mechanisms in central nervous system diseases (CNSDs), including neurodegenerative diseases, cerebral ischemia injury, depression and spinal cord injury. In conclusion, ginsenoside Rb1 has a potential neuroprotection due to its inhibition of oxidative stress, apoptosis, neuroinflammation and autophagy in CNSDs and may be a promising candidate agent for clinical therapy of CNSDs in the future.

Comparative efficacy of targeted structural patterns of electroencephalography neurofeedback in children with inattentive or combined attention deficit hyperactivity disorder.

OBJECTIVE: To evaluate and compare the effects of three courses of different structural patterns of electroencephalography neurofeedback on predominantly inattentive attention deficit hyperactivity disorder (ADHD-PI) and combined ADHD (ADHD-CT). METHODS: Thirty-eight ADHD-PI and ADHD-CT children were selected and completed three courses of different structural patterns of electroencephalography neurofeedback according to their ADHD type. Before and after each course, relative power value of electroencephalography, including θ, ß, α, SMR and their ratios (θ/ß, θ/α), and eighteen integrated visual and auditory continuous performance test (IVA/CPT) quotients were obtained and compared. Data were analyzed by SPSS software, and p < .05 was considered statistically significant. RESULTS: After one course, θ, three IVA/CPT quotients in both types and two comprehensive quotients in ADHD-CT changed significantly (all p < .05). After two courses, θ/α, θ/ß and five IVA/CPT quotients in both types, θ and α in ADHD-PI, four comprehensive quotients, and four respond control quotients in ADHD-CT varied significantly compared to before treatment and after one course (all p < .05). After three courses, α, ß, θ, θ/α, θ/ß and ten IVA/CPT quotients in both types changed significantly compared to before treatment and after one course (all p < .05). In addition, six IVA/CPT quotients in both types after three courses were significantly higher than those after two courses (all p < .05). CONCLUSION: Different structural patterns of electroencephalography neurofeedback targeted for ADHD-CT and ADHD-PI were both effective and feasible. Three courses of EEG neurofeedback were most effective.

[Study on the Relationship between the Level of Soluble HLA-E Molecules in Plasma and Gene Polymorphism and Leukemia].

OBJECTIVE: To explore the relationship between the level of soluble HLA-E (sHLA-E) molecules in plasma and gene polymorphism and leukemia in Shenzhen of China. METHODS: Enzyme-linked immunosorbent assay was used to detect sHLA-E level in plasma of 103 leukemia patients and 113 healthy blood donors. PCR-SBT was used to identify the HLA-E genotype of 73 leukemia patients and 76 healthy blood donors. RESULTS: The level of plasma sHLA-E of 103 leukemia patients was significantly higher than that of 113 healthy blood donors (P<0.001); And the level of plasma sHLA-E in 77 myeloid leukemia patients was also significantly higher (P<0.001). The percentage of patients with plasma sHLA-E concentration of 0-199 ng/ml in leukemia and myeloid leukemia patients was 37.86% and 32.47%, respectively, which was significantly lower than 53.98% of healthy donors, the difference was statistically significant (P<0.05, P<0.01); While, when the plasma sHLA-E concentration was more than 400 ng/ml, the percentage was 33.01% and 36.36%, respectively, which was significantly higher than 13.28% of healthy donors, the difference was also statistically significant (P=0.001, P<0.001). There was no significant difference in the level of plasma sHLA-E among different HLA-E genotypes (P>0.05), whether healthy blood donors or leukemia patients. CONCLUSION: The level of plasma sHLA-E in patients with leukemia (especially myeloid leukemia) is significantly higher than that of healthy blood donors, but different HLA-E genotypes do not affect the level of plasma sHLA-E. A cut-off value for the concentration of plasma sHLA-E (recommended risk value >400 ng/ml) can be set to assess the risk of certain pre-leukemia patients.

Harmonizing Pathological and Normal Pixels for Pseudo-Healthy Synthesis.

Synthesizing a subject-specific pathology-free image from a pathological image is valuable for algorithm development and clinical practice. In recent years, several approaches based on the Generative Adversarial Network (GAN) have achieved promising results in pseudo-healthy synthesis. However, the discriminator (i.e., a classifier) in the GAN cannot accurately identify lesions and further hampers from generating admirable pseudo-healthy images. To address this problem, we present a new type of discriminator, the segmentor, to accurately locate the lesions and improve the visual quality of pseudo-healthy images. Then, we apply the generated images into medical image enhancement and utilize the enhanced results to cope with the low contrast problem existing in medical image segmentation. Furthermore, a reliable metric is proposed by utilizing two attributes of label noise to measure the health of synthetic images. Comprehensive experiments on the T2 modality of BraTS demonstrate that the proposed method substantially outperforms the state-of-the-art methods. The method achieves better performance than the existing methods with only 30% of the training data. The effectiveness of the proposed method is also demonstrated on the LiTS and the T1 modality of BraTS. The code and the pre-trained model of this study are publicly available at https://github.com/Au3C2/Generator-Versus-Segmentor.