Real-time diagnosis of intracerebral hemorrhage by generating dual-energy CT from single-energy CT.

Real-time diagnosis of intracerebral hemorrhage after thrombectomy is crucial for follow-up treatment. However, this is difficult to achieve with standard single-energy CT (SECT) due to similar CT values of blood and contrast agents under a single energy spectrum. In contrast, dual-energy CT (DECT) scanners employ two different energy spectra, which allows for real-time differentiation between hemorrhage and contrast extravasation based on energy-related attenuation characteristics. Unfortunately, DECT scanners are not as widely used as SECT scanners due to their high costs. To address this dilemma, in this paper, we generate pseudo DECT images from a SECT image for real-time diagnosis of hemorrhage. More specifically, we propose a SECT-to-DECT Transformer-based Generative Adversarial Network (SDTGAN), which is a 3D transformer-based multi-task learning framework equipped with a shared attention mechanism. In this way, SDTGAN can be guided to focus more on high-density areas (crucial for hemorrhage diagnosis) during the generation. Meanwhile, the introduced multi-task learning strategy and the shared attention mechanism also enable SDTGAN to model dependencies between interconnected generation tasks, improving generation performance while significantly reducing model parameters and computational complexity. In the experiments, we approximate real SECT images using mixed 120kV images from DECT data to address the issue of not being able to obtain the true paired DECT and SECT data. Extensive experiments demonstrate that SDTGAN can generate DECT images better than state-of-the-art methods. The code of our implementation is available at https://github.com/jiang-cw/SDTGAN.

Genetic Diversity and Natural Selection of Plasmodium vivax Merozoite Surface Protein 8 in Global Populations.

Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) is a promising candidate target for the development of multi-component vaccines. Therefore, determining the genetic variation pattern of Pvmsp8 is essential in providing a reference for the rational design of the P. vivax malaria vaccines. This study delves into the genetic characteristics of the Pvmsp8 gene, specifically focusing on samples from the China-Myanmar border (CMB) region, and contrasts these findings with broader global patterns. The study uncovers that Pvmsp8 exhibits a notable level of conservation across different populations, with limited polymorphisms and relatively low nucleotide diversity (0.00023-0.00120). This conservation contrasts starkly with the high polymorphisms found in other P. vivax antigens such as Pvmsp1. A total of 25 haplotypes and 14 amino acid mutation sites were identified in the global populations, and all mutation sites were confined to non-functional regions. The study also notes that most CMB Pvmsp8 haplotypes are shared among Burmese, Cambodian, Thai, and Vietnamese populations, indicating less geographical variance, but differ notably from those found in Pacific island regions or the Panama. The findings underscore the importance of considering regional genetic diversity in P. vivax when developing targeted malaria vaccines. Non departure from neutral evolution were found by Tajima's D test, however, statistically significant differences were observed between the kn/ks rates. The study's findings are crucial in understanding the evolution and population structure of the Pvmsp8 gene, particularly during regional malaria elimination efforts. The highly conserved nature of Pvmsp8, combined with the lack of mutations in its functional domain, presents it as a promising candidate for developing a broad and effective P. vivax vaccine. This research thus lays a foundation for the rational development of multivalent malaria vaccines targeting this genetically stable antigen.

Targeting Non-Alcoholic Fatty Liver Disease with Hawthorn Ethanol Extract (HEE): A Comprehensive Examination of Hepatic Lipid Reduction and Gut Microbiota Modulation.

Recent studies have highlighted the lipid-lowering ability of hawthorn ethanol extract (HEE) and the role played by gut flora in the efficacy of HEE. Our study sought to explore the effects of HEE on non-alcoholic fatty liver disease (NAFLD) in normal flora and pseudo germ-free mice. The results showed that HEE effectively diminished hepatic lipid accumulation, ameliorated liver function, reduced inflammatory cytokine levels and blood lipid profiles, and regulated blood glucose levels. HEE facilitated triglyceride breakdown, suppressed fatty acid synthesis, and enhanced intestinal health by modulating the diversity of the gut microbiota and the production of short-chain fatty acids in the gut. In addition, HEE apparently helps to increase the presence of beneficial genera of bacteria, thereby influencing the composition of the gut microbiota, and the absence of gut flora affects the efficacy of HEE. These findings reveal the potential of hawthorn for the prevention and treatment of NAFLD and provide new perspectives on the study of functional plants to improve liver health.

Crystalline nanosheets of three-dimensional supramolecular frameworks with uniform thickness and high stability.

Fabricating three dimensional (3D) supramolecular frameworks (SMFs) into stable crystalline nanosheets remains a great challenge due to the homogeneous and weak inter-building block interactions along 3D directions. Herein, crystalline nanosheets of a 3D SMF with a uniform thickness of 4.8 ± 0.1 nm immobilized with Pt nanocrystals on the surface (Q[8]/Pt NSs) were fabricated via the solid-liquid reaction between cucurbit[8]uril/H2PtCl6 single crystals and hydrazine hydrate with the help of gas and heat yielded during the reaction process. A series of experiments and theoretical calculations reveal the ultrahigh stability of Q[8]/Pt NSs due to the high density hydrogen bonding interaction among neighboring Q[8] molecules. This in turn endows Q[8]/Pt NSs with excellent photocatalytic and continuous thermocatalytic CO oxidation performance, representing the thus-far reported best Pt nano-material-based catalysts.

IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis.

Cellular sensitivity to ferroptosis is primarily regulated by mechanisms mediating lipid hydroperoxide detoxification. We show that inositol-requiring enzyme 1 (IRE1α), an endoplasmic reticulum (ER) resident protein critical for the unfolded protein response (UPR), also determines cellular sensitivity to ferroptosis. Cancer and normal cells depleted of IRE1α gain resistance to ferroptosis, while enhanced IRE1α expression promotes sensitivity to ferroptosis. Mechanistically, IRE1α's endoribonuclease activity cleaves and down-regulates the mRNA of key glutathione biosynthesis regulators glutamate-cysteine ligase catalytic subunit (GCLC) and solute carrier family 7 member 11 (SLC7A11). This activity of IRE1α is independent of its role in regulating the UPR and is evolutionarily conserved. Genetic deficiency and pharmacological inhibition of IRE1α have similar effects in inhibiting ferroptosis and reducing renal ischemia-reperfusion injury in mice. Our findings reveal a previously unidentified role of IRE1α to regulate ferroptosis and suggests inhibition of IRE1α as a promising therapeutic strategy to mitigate ferroptosis-associated pathological conditions.

SIRT5 exacerbates eosinophilic chronic rhinosinusitis through promoting polarization of M2 macrophage.

BACKGROUND: Previous study implied that local M2 polarization of macrophage promoted mucosal edema and exacerbates Th2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We thought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: RT-qPCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5 knockout mice were used to establish nasal polyp model with Th2 inflammation and investigate the effects of SIRT5 in macrophages on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophages markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5 deficiency mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages through promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting the alternative polarization of macrophage and thus provides a potential target for CRSwNP interventions.

Seedling root system adaptation to water availability during maize domestication and global expansion.

The maize root system has been reshaped by indirect selection during global adaptation to new agricultural environments. In this study, we characterized the root systems of more than 9,000 global maize accessions and its wild relatives, defining the geographical signature and genomic basis of variation in seminal root number. We demonstrate that seminal root number has increased during maize domestication followed by a decrease in response to limited water availability in locally adapted varieties. By combining environmental and phenotypic association analyses with linkage mapping, we identified genes linking environmental variation and seminal root number. Functional characterization of the transcription factor ZmHb77 and in silico root modeling provides evidence that reshaping root system architecture by reducing the number of seminal roots and promoting lateral root density is beneficial for the resilience of maize seedlings to drought.

A fresh-cut papaya freshness prediction model based on partial least squares regression and support vector machine regression.

This study investigated the physicochemical and flavor quality changes in fresh-cut papaya that was stored at 4 °C. Multivariate statistical analysis was used to evaluate the freshness of fresh-cut papaya. Aerobic plate counts were selected as a predictor of freshness of fresh-cut papaya, and a prediction model for freshness was established using partial least squares regression (PLSR), and support vector machine regression (SVMR) algorithms. Freshness of fresh-cut papaya could be well distinguished based on physicochemical and flavor quality analyses. The aerobic plate counts, as a predictor of freshness of fresh-cut papaya, significantly correlated with storage time. The SVMR model had a higher prediction accuracy than the PLSR model. Combining flavor quality with multivariate statistical analysis can be effectively used for evaluating the freshness of fresh-cut papaya.

Genome Analysis of Plasmodium falciparum: A Preliminary Observation - Sierra Leone, 2022-2023.

What is already known about this topic?: Sierra Leone, with a gross domestic product (GDP) per capita below $300 and significant poverty, ranks among the world's least developed countries (LDCs). Despite its modest population of 8.6 million, the nation reports approximately 2.6 million malaria cases annually. Previously, there has been no reporting on the malaria genome data from this country. What is added by this report?: In this study, we present the first reported whole-genome sequence analysis of 19 high parasite-density Plasmodium falciparum isolates from Sierra Leone, providing insights into the genomic epidemiology of this high-prevalence area. We found a high degree of relatedness among infections and substantial genetic diversity, consistent with the gradual reduction in overall case numbers. Moreover, our whole-genome analysis revealed that, beyond drug-resistance genes, gene families related to blood cell invasion, immune evasion, and others are undergoing directional selection. This suggests that the population in Sierra Leone has developed a relatively strong acquired immunity. What are the implications for public health practice?: The genomic data not only facilitate the creation of single nucleotide polymorphism barcodes for case tracking but also enable the analysis of evolving transmission dynamics and selection pressures. Additionally, the samples from Sierra Leone exhibited higher selective pressures on resistance genes compared to those from Asia, a trend not commonly observed in other African samples. This suggests that less stringent healthcare systems and inconsistent treatment strategies can subject parasites to increased drug pressure, thereby accelerating the development of resistant strains.

Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of cardiovascular mortality and is increasingly prevalent in our population. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can safely and effectively lower glucose levels while concurrently managing the full spectrum of ASCVD risk factors and improving patients' long-term prognosis. Several cardiovascular outcome trials (CVOTs) have been carried out to further investigate the cardiovascular benefits of GLP-1RAs. Analyzing data from CVOTs can provide insights into the pathophysiologic mechanisms by which GLP-1RAs are linked to ASCVD and define the use of GLP-1RAs in clinical practice. Here, we discussed various mechanisms hypothesized in previous animal and preclinical human studies, including blockade of the production of adhesion molecules and inflammatory factors, induction of endothelial cells' synthesis of nitric oxide, protection of mitochondrial function and restriction of oxidative stress, suppression of NOD-like receptor thermal protein domain associated protein three inflammasome, reduction of foam cell formation and macrophage inflammation, and amelioration of vascular smooth muscle cell dysfunction, to help explain the cardiovascular benefits of GLP-1RAs in CVOTs. This paper provides an overview of the clinical research, molecular processes, and possible therapeutic applications of GLP-1RAs in ASCVD, while also addressing current limitations in the literature and suggesting future research directions.

Qualitative classification of waste garments for textile recycling based on machine vision and attention mechanisms.

The increasing volume of garment waste underscores the need for advanced sorting and recycling strategies. As a critical procedure in the secondary usage of waste clothes, qualitative classification of garments categorizes post-consumer clothes based on types and styles. However, this process currently relies on manual labor, which is inefficient, labor-intensive, and poses risks to workers. Despite efforts to implement automatic clothes classification systems, challenges persist due to visual complexities such as similar colors, deformations, and occlusions. In response to these challenges, this study introduces an enhanced intelligent machine vision system with attention mechanisms designed to automate the laborious and skill-demanding task of garment classification. Initially, a waste garment dataset comprising approximately 27,000 garments was curated using a self-developed automatic classification platform. Subsequently, the proposed attention method parameters were selected, and a series of benchmarks were conducted against state-of-the-art methods. Finally, the proposed system underwent a two-week online deployment to evaluate its running stability and sensitivity to similar colors, deformation, and occlusion in industrial production settings. The benchmarks indicate that the proposed method significantly improves classification accuracy across various models. The visualization interpretation of Grad-CAM reveals that the proposed method effectively handles complex environments by directing its focus toward garment-related pixels. Notably, the proposed system elevates classification accuracy from 68.28 % to human-level performance (>90 %) while ensuring greater running stability. This advancement holds promise for automating the classification process and potentially alleviating workers from labor-intensive and hazardous tasks associated with clothes recycling.

Improved random forest classification model combined with C5.0 algorithm for vegetation feature analysis in non-agricultural environments.

In response to the challenges posed by the high computational complexity and suboptimal classification performance of traditional random forest algorithms when dealing with high-dimensional and noisy non-agricultural vegetation satellite data, this paper proposes an enhanced random forest algorithm based on the C5.0 algorithm. The paper focuses on the Liaohe Plain, selecting two distinct non-agricultural landscape patterns in Shenbei New District and Changtu County as research objects. High-resolution satellite data from GF-2 serves as the experimental dataset. This paper introduces an ensemble feature method based on the bagging concept to improve the original random forest classification model. This method enhances the likelihood of selecting features beneficial to classifying positive class samples, avoiding excessive removal of useful features from negative samples. This approach ensures feature importance and model diversity. The C5.0 algorithm is then employed for feature selection, and the enhanced vegetation index (EVI) is utilized for vegetation coverage estimation. Results indicate that employing a multi-scale parameter selection tool, combined with limited field-measured data, facilitates the identification and classification of plant species in forest landscapes. The C5.0 algorithm effectively selects classification features, minimizing information redundancy. The established object-oriented random forest classification model achieves an impressive accuracy of 94.02% on the aerial imagery for forest classification dataset, with EVI-based vegetation coverage estimation demonstrating high accuracy. In experiments on the same test set, the proposed algorithm attains an average accuracy of 90.20%, outperforming common model algorithms such as bidirectional encoder representation from transformer, FastText, and convolutional neural network, which achieve average accuracies ranging from 84.41 to 88.33% in identifying non-agricultural artificial habitat vegetation features. The proposed algorithm exhibits a competitive edge compared to other algorithms. These research findings contribute scientific evidence for protecting agricultural ecosystems and restoring agricultural ecosystem biodiversity.

Toll-interacting protein is activated by the transcription factor GATA1 and Sp1 to negatively regulate NF-κB and MAPK pathways in the Japanese eel (Anguilla japonica).

Toll-interacting protein (Tollip) serves as a crucial inhibitory factor in the modulation of Toll-like receptor (TLR)-mediated innate immunological responses. The structure and function of Tollip have been well documented in mammals, yet the information in teleost remained limited. This work employed in vitro overexpression and RNA interference in vivo and in vitro to comprehensively examine the regulatory effects of AjTollip on NF-κB and MAPK signaling pathways. The levels of p65, c-Fos, c-Jun, IL-1, IL-6, and TNF-α were dramatically reduced following overexpression of AjTollip, whereas knocking down AjTollip in vivo and in vitro enhanced those genes' expression. Protein molecular docking simulations showed AjTollip interacts with AjTLR2, AjIRAK4a, and AjIRAK4b. A better understanding of the transcriptional regulation of AjTollip is crucial to elucidating the role of Tollip in fish antibacterial response. Herein, we cloned and characterized a 2.2 kb AjTollip gene promoter sequence. The transcription factors GATA1 and Sp1 were determined to be associated with the activation of AjTollip expression by using promoter truncation and targeted mutagenesis techniques. Collectively, our results indicate that AjTollip suppresses the NF-κB and MAPK signaling pathways, leading to the decreased expression of the downstream inflammatory factors, and GATA1 and Sp1 play a vital role in regulating AjTollip expression.

Higher Dietary Quercetin Intake Is Associated with Lower Risk of Adverse Outcomes among Individuals with Inflammatory Bowel Disease in a Prospective Cohort Study.

BACKGROUND: Cumulative preclinical evidence reported quercetin, a major flavonoid, can attenuate the disease activity of inflammatory bowel diseases (IBD). However, there is limited evidence that supports the benefits of quercetin for patients with IBD. OBJECTIVES: To investigate whether dietary quercetin intake is associated with adverse outcomes among individuals with IBD in a prospective cohort study. METHODS: We included 2293 participants with IBD (764 Crohn's disease [CD] and 1529 ulcerative colitis [UC]) from the UK Biobank. Dietary information was collected using validated 24-h dietary assessments, and quercetin intake was estimated based on national nutrient databases. Two outcomes, enterotomy and all-cause mortality, were obtained based on the national data. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a mean (standard deviation) follow-up of 9.6 (1.8) y, we documented 193 enterotomy events and 176 deaths. Compared with participants with the lowest quartile intake of quercetin, those in the highest quartiles were associated with lower risk of enterotomy (HR: 0.46; 95% CI: 0.28, 0.76) and all-cause mortality (HR: 0.53; 95% CI: 0.33, 0.83) in IBD. The inverse associations between quercetin and enterotomy were consistent in CD (HR: 0.30; 95% CI: 0.12, 0.78) but not UC (HR: 0.58; 95% CI: 0.32, 1.07), while the inverse associations between quercetin and mortality were consistent both in CD (HR: 0.37; 95% CI: 0.15, 0.92) and UC (HR: 0.55; 95% CI: 0.31, 0.95). CONCLUSIONS: Higher dietary intake of quercetin was associated with lower risk of enterotomy and all-cause mortality in IBD. Our study provides novel evidence that further suggests the benefits of quercetin for patients with IBD, while also calling for further validation in other cohorts and clinical trials.

Iron deficiency: prevalence, mortality risk, and dietary relationships in general and heart failure populations.

Background: Iron deficiency (ID) is the most common nutritional deficiency, with little research on its prevalence and long-term outcomes in the general population and those with heart failure (HF). Both the relationships between dietary iron and ID, as well as dietary folate and ID, are understudied. Methods: We used data from the National Health and Nutrition Examination Survey from 1999 to 2002 to investigate the prevalence, prognosis, and relationship between dietary and ID defined by different criteria in the general population (n = 6,660) and those with HF (n = 182). Results: There was no significant difference in the prevalence of ID between HF patients and the general population after propensity score matching. Transferrin saturation (TSAT) <20% was associated with higher 5-year all-cause mortality (HR: 3.49, CI: 1.40-8.72, P = 0.007), while ferritin <30 ng/ml was associated with higher 10-year (HR: 2.70, CI: 1.10-6.67, P = 0.031) and 15-year all-cause mortality (HR: 2.64, CI: 1.40-5.00, P = 0.003) in HF patients. Higher dietary total folate but dietary iron reduced the risk of ID (defined as ferritin <100 ng/ml) in HF patients (OR: 0.80; 95% CI: 0.65-1.00; P = 0.047). Conclusions: The prevalence of ID was identical in HF and non-HF individuals. Ferritin <30 ng/ml was associated with long-term outcomes whereas TSAT <20% was associated with short-term prognosis in both the general population and HF patients. A diet rich in folate might have the potential for prevention and treatment of ID in HF patients.

The effect of distal locking mode on postoperative mechanical complications in intertrochanteric fractures: a retrospective cohort study of five hundred and seven patients.

PURPOSE: The optimal choice of distal locking modes remains a subject due to limited available data, and therefore, this study aims to investigate the relationship between distal locking mode and postoperative mechanical complications in an intertrochanteric fracture (ITF) population who underwent closed reduction and intramedullary fixation with a PFNA-II. METHODS: Patients aged 65 years or older who underwent surgery with PFNA-II fixation in a university teaching hospital between January 2020 and December 2021 were potentially eligible. Based on the distal locking mode, patients were classified into static, dynamic, and limited dynamic groups, among which the differences were tested using univariate analysis. Multivariate logistic regression was used to examine whether the distal locking mode was independently associated with the risk of postoperative one year mechanical complications, adjusting for covariates and potential confounders. Subgroup analyses were performed to evaluate the robustness of the findings. RESULT: Among 507 eligible patients, 33 (6.5%) developed postoperative mechanical complications. In the univariate analysis, sex (P = 0.007), fracture type (P = 0.020), LAT Parker ratio (P = 0.023), and lateral femoral (P = 0.003) wall showed that the differences were significant. Compared to the static group, the limited dynamic group and the dynamic group showed higher odds of postoperative mechanical complications (OR = 3.314, 95% CI: 1.215-9.041; and OR = 3.652, 95% CI: 1.451-9.191, respectively). These associations were robust across a series of analyses, including adjusting for confounders and subgroup analyses. CONCLUSION: Using a distal non-static locking mode significantly increases the risk of postoperative mechanical complications, and static locking could be a preferable option when treating an intertrochanteric fracture.

System-level time computation and representation in the suprachiasmatic nucleus revealed by large-scale calcium imaging and machine learning.

The suprachiasmatic nucleus (SCN) is the mammalian central circadian pacemaker with heterogeneous neurons acting in concert while each neuron harbors a self-sustained molecular clockwork. Nevertheless, how system-level SCN signals encode time of the day remains enigmatic. Here we show that population-level Ca2+ signals predict hourly time, via a group decision-making mechanism coupled with a spatially modular time feature representation in the SCN. Specifically, we developed a high-speed dual-view two-photon microscope for volumetric Ca2+ imaging of up to 9000 GABAergic neurons in adult SCN slices, and leveraged machine learning methods to capture emergent properties from multiscale Ca2+ signals as a whole. We achieved hourly time prediction by polling random cohorts of SCN neurons, reaching 99.0% accuracy at a cohort size of 900. Further, we revealed that functional neuron subtypes identified by contrastive learning tend to aggregate separately in the SCN space, giving rise to bilaterally symmetrical ripple-like modular patterns. Individual modules represent distinctive time features, such that a module-specifically learned time predictor can also accurately decode hourly time from random polling of the same module. These findings open a new paradigm in deciphering the design principle of the biological clock at the system level.

Origami metamaterials for ultra-wideband and large-depth reflection modulation.

The dynamic control of electromagnetic waves is a persistent pursuit in modern industrial development. The state-of-the-art dynamic devices suffer from limitations such as narrow bandwidth, limited modulation range, and expensive features. To address these issues, we fuse origami techniques with metamaterial design to achieve ultra-wideband and large-depth reflection modulation. Through a folding process, our proposed metamaterial achieves over 10-dB modulation depth over 4.96 - 38.8 GHz, with a fractional bandwidth of 155% and tolerance to incident angles and polarizations. Its ultra-wideband and large-depth reflection modulation performance is verified through experiments and analyzed through multipole decomposition theory. To enhance its practical applicability, transparent conductive films are introduced to the metamaterial, achieving high optical transparency (>87%) from visible to near-infrared light while maintaining cost-effectiveness. Benefiting from lightweight, foldability, and low-cost properties, our design shows promise for extensive satellite communication and optical window mobile communication management.

Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny.

Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.