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The Flavian reforms had put an end to the purely legal Romanization of Spain but the depth and intensity of the process seem to have varied in different regions of the country. Like in the late Republican times, in the first and second centuries A.D. Spain had three zones of Romanization - a wholly (or almost wholly) Romanized zone, a Romanizing zone and a non- Romanized region but unlike the previous period the boundaries of them were absolutely different. The former covered practically the whole of Baetics and East Tarraconensis (except the Balearic Islands).

Abstract Ischemic stroke poses significant challenges in terms of mortality and disability rates globally. A key obstacle to the successful treatment of ischemic stroke lies in the limited efficacy of administering therapeutic agents. Leveraging the unique properties of nanoparticles for brain targeting and crossing the blood–brain barrier, researchers have engineered diverse nanoparticle-based drug delivery systems to improve the therapeutic outcomes of ischemic stroke. This review provides a concise overview of the pathophysiological mechanisms implicated in ischemic stroke, encompassing oxidative stress, glutamate excitotoxicity, neuroinflammation, and cell death, to elucidate potential targets for nanoparticle-based drug delivery systems. Furthermore, the review outlines the classification of nanoparticle-based drug delivery systems according to these distinct physiological processes. This categorization aids in identifying the attributes and commonalities of nanoparticles that target specific pathophysiological pathways in ischemic stroke, thereby facilitating the advancement of nanomedicine development. The review discusses the potential benefits and existing challenges associated with employing nanoparticles in the treatment of ischemic stroke, offering new perspectives on designing efficacious nanoparticles to enhance ischemic stroke treatment outcomes. Graphical Abstract

Abstract To investigate alteration of outer nuclear layer (ONL) and choroidal vascularity index (CVI) in different status of central serous chorioretinopathy (CSC). A retrospective review of 65 CSC eyes with subretinal fluid (manifest CSC) and 40 control eyes was conducted in a single tertiary university hospital. Differences in best-corrected visual acuity (BCVA), ONL, and CVI were compared. CVI was assessed both in the entire choroid (CVI-EC) and around the 1500 μm leakage area (CVI-1500). Measurements were repeated after the subretinal fluid resorption (quiescent CSC), and compared. CSC eyes showed worse BCVA, thinner ONL and greater CVI than controls. Quiescent CSC showed a recovery of ONL compared to the manifest CSC, along with the BCVA improvement. The resolution of the CSC revealed a decrease across all three choroidal areas (total, stromal and luminal), with a more pronounced reduction in the stromal than in the luminal choroidal area, leading to an increase in the CVI. This phenomenon was shown in both CVI-EC and CVI-1500. Conclusively, ONL thickness can be used as a quantitative biomarker for photoreceptor function in CSC. Increased CVI may reflect a disease activity. The stromal choroidal area is particularly sensitive in illustrating leakage from the choroidal vasculature.

Abstract Growth differentiation factor 15 (GDF15) as a stress response cytokine is involved in the development and progression of several diseases associated with metabolic disorders. However, the regulatory role and the underlying mechanisms of GDF15 in sepsis remain poorly defined. Our study analyzed the levels of GDF15 and its correlations with the clinical prognosis of patients with sepsis. In vivo and in vitro models of sepsis were applied to elucidate the role and mechanisms of GDF15 in sepsis-associated lung injury. We observed strong correlations of plasma GDF15 levels with the levels of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and lactate as well as Sequential Organ Failure Assessment (SOFA) scores in patients with sepsis. In the mouse model of lipopolysaccharide-induced sepsis, recombinant GDF15 inhibited the proinflammatory responses and alleviated lung tissue injury. In addition, GDF15 decreased the levels of cytokines produced by alveolar macrophages (AMs). The anti-inflammatory effect of glycolysis inhibitor 2-DG on AMs during sepsis was mediated by GDF15 via inducing the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α) and the expression of activating transcription factor 4 (ATF4). Furthermore, we explored the mechanism underlying the beneficial effects of GDF15 and found that GDF15 inhibited glycolysis and mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) signaling via promoting AMPK phosphorylation. This study demonstrated that GDF15 inhibited glycolysis and NF-κB/MAPKs signaling via activating AMP-activated protein kinase (AMPK), thereby alleviating the inflammatory responses of AMs and sepsis-associated lung injury. Our findings provided new insights into novel therapeutic strategies for treating sepsis.

Abstract Background Erythroid and myeloid differentiation disorders are commonly occurred in leukemia. Given that the relationship between erythroid and myeloid lineages is still unclear. To find the co-regulators in erythroid and myeloid differentiation might help to find new target for therapy of myeloid leukemia. In hematopoiesis, ALA (alpha lipoic acid) is reported to inhibit neutrophil lineage determination by targeting transcription factor ELK1 in granulocyte-monocyte progenitors via splicing factor SF3B1. However, further exploration is needed to determine whether ELK1 is a common regulatory factor for erythroid and myeloid differentiation. Methods In vitro culture of isolated CD34+, CMPs (common myeloid progenitors) and CD34+ CD371– HSPCs (hematopoietic stem progenitor cells) were performed to assay the differentiation potential of monocytes, neutrophils, and erythrocytes. Overexpression lentivirus of long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 transduced CD34+ HSPCs were transplanted into NSG mice to assay the human lymphocyte and myeloid differentiation differences 3 months after transplantation. Knocking down of SRSF11, which was high expressed in CD371+GMPs (granulocyte-monocyte progenitors), upregulated by ALA and binding to ELK1-RNA splicing site, was performed to analyze the function in erythroid differentiation derived from CD34+ CD123mid CD38+ CD371– HPCs (hematopoietic progenitor cells). RNA sequencing of L-ELK1 and S-ELK1 overexpressed CD34+ CD123mid CD38+ CD371– HPCs were performed to assay the signals changed by ELK1. Results Here, we presented new evidence that ALA promoted erythroid differentiation by targeting the transcription factor ELK1 in CD34+ CD371– hematopoietic stem progenitor cells (HSPCs). Overexpression of either the long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 inhibited erythroid-cell differentiation, but knockdown of ELK1 did not affect erythroid-cell differentiation. RNAseq analysis of CD34+ CD123mid CD38+ CD371– HPCs showed that L-ELK1 upregulated the expression of genes related to neutrophil activity, phosphorylation, and hypoxia signals, while S-ELK1 mainly regulated hypoxia-related signals. However, most of the genes that were upregulated by L-ELK1 were only moderately upregulated by S-ELK1, which might be due to a lack of serum response factor interaction and regulation domains in S-ELK1 compared to L-ELK1. In summary, the differentiation of neutrophils and erythrocytes might need to rely on the dose of L-ELK1 and S-ELK1 to achieve precise regulation via RNA splicing signals at early lineage commitment. Conclusions ALA and ELK1 are found to regulate both human granulopoiesis and erythropoiesis via RNA spliceosome, and ALA-ELK1 signal might be the target of human leukemia therapy.

BackgroundMultiple myeloma (MM) exhibits considerable heterogeneity in treatment responses and survival rates, even when standardized care is administered. Ongoing efforts are focused on developing prognostic models to predict these outcomes more accurately. Recently, neutrophil extracellular traps (NETs) have emerged as a potential factor in MM progression, sparking investigation into their role in prognostication.MethodsIn this study, a multi-gene risk scoring model was constructed using the intersection of NTEs and differentially expressed genes (DEGs), applying the least absolute shrinkage and selection operator (LASSO) Cox regression model. A nomogram was established, and the prognostic model’s effectiveness was determined via Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The ESTIMATE algorithm and immune-related single-sample gene set enrichment analysis (ssGSEA) were employed to evaluate the level of immune infiltration. The sensitivity of chemotherapy drugs was assessed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. Ultimately, the presence of the detected genes was confirmed through quantitative real-time polymerase chain reaction (qRT-PCR) analysis in MM cell specimens.Results64 NETs-DEGs were yielded, and through univariate Cox regression and LASSO regression analysis, we constructed a risk score composed of six genes: CTSG, HSPE1, LDHA, MPO, PINK1, and VCAM1. MM patients in three independent datasets were classified into high- and low-risk groups according to the risk score. The overall survival (OS) of patients in the high-risk group was significantly reduced compared to the low-risk group. Furthermore, the risk score was an independent predictive factor for OS. In addition, interactions between the risk score, immune score, and immune cell infiltration were investigated. Further analysis indicated that patients in the high-risk group were more sensitive to a variety of chemotherapy and targeted drugs, including bortezomib. Moreover, the six genes provided insights into the progression of plasma cell disorders.ConclusionThis study offers novel insights into the roles of NETs in prognostic prediction, immune status, and drug sensitivity in MM, serving as a valuable supplement and enhancement to existing grading systems.

The authors Маша и Ю met in 2022 at the PostOst Kongress in a small town in Germany, Гёттинген, where a bunch of people, queer and non-queer, with cultural connections to the former European East оттуда were trying to figure out what connects us beyond the usual migrant identity concepts (if anything). Masha has cultural ties to Ukraine and lives in Berlin, Germany. Ju has cultural ties to Kazakhstan and Germany and lives in Sydney, Australia, on Gadigal Land. At the Kongress the question of queerness presented itself as the most fragile and the least important one: in the context of the intergenerational migrant trauma on one hand, and the Russian invasion of Ukraine on the other. Nonetheless, the authors are interested exactly in this queerness, when developing out of 1368 text messages, 56 photos, 6 videos and 8 voice messages, 30 links and one gif over multiple time zones sent to each other in the months after the Kongress the experimental text, here called В этом смысле да. an intersectional Play.

The inadequacy of tactile perception systems in humanoid robotic manipulators limits the breadth of available robotic applications. Here, we designed a multifunctional flexible tactile sensor for robotic fingers that provides capabilities similar to those of human skin sensing modalities. This sensor utilizes a novel PI-MXene/SrTiO3 hybrid aerogel developed as a sensing unit with the additional abilities of electromagnetic transmission and thermal insulation to adapt to certain complex environments. Moreover, polyimide (PI) provides a high-strength skeleton, MXene realizes a pressure-sensing function, and MXene/SrTiO3 achieves both thermoelectric and infrared radiation response behaviors. Furthermore, via the pressure response mechanism and unsteady-state heat transfer, these aerogel-derived flexible sensors realize multimodal sensing and recognition capabilities with minimal cross-coupling. They can differentiate among 13 types of hardness and four types of material from objects with accuracies of 94% and 85%, respectively, using a decision tree algorithm. In addition, based on the infrared radiation-sensing function, a sensory array was assembled, and different shapes of objects were successfully recognized. These findings demonstrate that this PI-MXene/SrTiO3 aerogel provides a new concept for expanding the multifunctionality of flexible sensors such that the manipulator can more closely reach the tactile level of the human hand. This advancement reduces the difficulty of integrating humanoid robots and provides a new breadth of application scenarios for their possibility.

Long-term overfertilization not only aggravates environmental costs, but reduces the quality and yield of fruit in dryland apple orchard, and this issue is closely associated with post-germination fertilization management. On the basis of multi-year observations, we developed a targeted fertigation strategy of FORD, i.e. formula fertilization (rational fertilizer scheme), on-demand fertilization in the sensitive period, reduced fertilization and delayed fertilization. Two-year field investigations were conducted with conventional furrow application (CK), integrated furrow and injection application (FI) and the optimized injection application under the FORD principle in a semiarid apple orchard. The data indicated that FI and FORD had a similar fruit yield of 57.2 Mg ha-1, significantly greater (by 4.5%) than CK. Yet, fruit quality (nutrition, flavor and appearance) was substantially improved under FORD, relative to FI and CK (P

A surge in the number of anthropogenic pollutants has been caused by increasing industrial activities. Nanoplastics are spotlighted as a new aquatic pollutant that are a threat to microbes and larger organisms. Our previous study showed that the subinhibitory concentrations of aquatic pollutants such as phenol and formalin act as signaling molecules and modulate global gene expression and metabolism. In this study, we aimed to investigate the impact of a new type of anthropogenic contaminant, polystyrene (PS) nanoplastics, on the expression of key virulence factors in zoonotic pathogen Edwardsiella piscicida and the assessment of potential changes in the susceptibility of zebrafish as a model host. The TEM data indicated a noticeable change in the cell membrane indicating that PS particles were possibly entering the bacterial cells. Transcriptome analyses performed to identify the differentially expressed genes upon PS exposure revealed that the genes involved in major virulence factor type VI secretion system (T6SS) were down-regulated. However, the expression of T6SS-related genes was recovered from the PS adapted E. piscicida when nanoplastics are free. This demonstrated the hypervirulence of pathogen in infection assays with both cell lines and in vivo zebrafish model. Therefore, this study provides experimental evidence elucidating the direct regulatory impact of nanoplastics influx into aquatic ecosystems on fish pathogenic bacteria, notably influencing the expression of virulence factors.

Abstract To investigate the changes in outer nuclear layer (ONL) thickness during anti-vascular endothelial growth factor (VEGF) treatment in type 1 choroidal neovascularization (CNV) and its impact on vision. Type 1 CNV eyes (n = 94) were retrospectively compared to normal control eyes (n = 35). Along with best-corrected visual acuity (BCVA), the location of CNV, foveal ONL thickness, and subretinal fluid height were measured using optical coherence tomography (OCT) and analyzed. Visual outcome and OCT biomarkers were compared. As a result, the CNV group had thinner foveal ONL and worse BCVA compared to the control group. ONL thickness recovered partially along with visual improvement following 3 monthly initial loading doses of aflibercept injections, and it correlated with the final BCVA during the 1-year follow-up. Eyes achieved foveal ONL recovery over + 10 µm had lower subfoveal CNV (45.5%) and showed better visual outcomes than eyes with stationary ONL or suboptimal ONL recovery (76.0%, p = 0.012). In conclusion, type 1 CNV eyes that recovered foveal ONL thickness at initial loading of anti-VEGF demonstrated good final visual outcome during the 1-year follow-up. Monitoring the foveal ONL thickness during early anti-VEGF treatment can give information about the visual outcomes in type 1 CNV.

Abstract Background Multiple myeloma remains incurable despite treatment advancements over the last 20 years. LCAR-B38M Cells in Treating Relapsed/Refractory Multiple Myeloma was a phase 1, first-in-human, investigator-initiated study in relapsed/refractory multiple myeloma conducted at four sites in China. The study used LCAR-B38M chimeric antigen receptor-T cells expressing two B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity, and a CD3ζ signaling domain with a 4-1BB costimulatory domain to optimize T-cell activation and proliferation. This chimeric antigen receptor construct is identical to ciltacabtagene autoleucel. In the LEGEND-2 study (n = 57, Xi’an site), overall response rate was 88%; median (95% CI) progression-free survival and overall survival were 19.9 (9.6–31.0) and 36.1 (26.4–not evaluable) months, respectively; and median follow-up was 25 months. This case study reports on a patient with relapsed/refractory multiple myeloma (λ light chain type) who was treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study (Xi’an site); he had received five prior lines of treatment and had extensive extramedullary lesions. Case presentation The patient, a 56-year-old Asian male, received cyclophosphamide (500 mg daily × 3 days) as lymphodepletion therapy and a total dose of 0.5 × 106 chimeric antigen receptor + T cells/kg split into three infusions (days 1, 24, and 84 from June to August 2016). He experienced grade 2 cytokine release syndrome after the first infusion; all symptoms resolved with treatment. No cytokine release syndrome occurred following the second and third infusions. His λ light chain levels decreased and normalized 20 days after the first infusion, and extramedullary lesions were healed as of January 2018. He has sustained remission for 5 years and received no other multiple myeloma treatments after LCAR-B38M chimeric antigen receptor T cell infusion. As of 30 October 2020, the patient is still progression-free and has maintained minimal residual disease-negative (10–4) complete response status for 52 months. Conclusions This case provides support that treatment with LCAR-B38M chimeric antigen receptor T cells can result in long-term disease remission of 5 or more years without disease progression in a heavily pretreated patient with extensive extramedullary disease and no other treatment options.

Polytetrafluoroethylene (PTFE) with good resistance can be used under extreme conditions, however, its surface hydrophobicity greatly limits its wide application in water treatment field. In this work, the hydrophobic PTFE microfiltration (MF) membrane was innovatively modified into a hydrophilic loose nanofiltration (NF) via synergic effect of the deposited polyethyleneimine (PEI) and poly(vinylpyrrolidone) (PVP) with assistance of fluorocarbon surfactant (FCS), and then crosslinked by glutaraldehyde (GA). The surface morphology, porosity and aperture size of the obtained cPEI-PVP-FCS/PTFE (cPPF) membrane were characterized in detail. The resultant membrane showed good dye desalination performance with high Evans blue rejection of 98.5%, NaCl rejection of 13.4%, along with permeance of 192.1 L m−2 h−1·MPa−1. In addition, the membrane showed long-term stability and good acid resistance.

Abstract Background LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years. Methods LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 106 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy. Results As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer. Conclusions The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285.

A survey of C2H N = 1 − 0 and N2H+J = 1 − 0 toward Planck Galactic cold clumps (PGCCs) was performed using the Purple Mountain Observatory's 13.7 m telescope. C2H and N2H+ were chosen to study the chemical evolutionary states of PGCCs. Among 121 observed molecular cores associated with PGCCs, 71 and 58 are detected with C2H N = 1 − 0 and N2H+J = 1 − 0, respectively. The detected lines of most sources can be fitted with a single component with compatible VLSR and line widths, which confirms that these PGCC cores are very cold (with gas temperatures 9–21 K) and quiescent while still dominanted by turbulence. The ratio between the column densities of C2H and N2H+ (N(C2H)/N(N2H+)) is found to be a good tracer for the evolutionary states of PGCC cores. Gas-grain chemical model can reproduce the decreasing trend of N(C2H)/N(N2H+) as a function of time. The cores with the lowest abundances of N2H+ (X[N2H+] < 10−10) are the youngest, and have nearly constant abundances of C2H. In evolved cores with X[N2H+] ~10−9, abundances of C2H drop quickly as the exhaustion of carbon atoms. Although these PGCC cores are in different evolutionary states, they are all quite young (< 5 × 105 yr) with N(C2H) > N(N2H+). Mapping observations are carried out toward 20 PGCC cores. The PGCC cores in Cepheus have lower N(C2H)/N(N2H+) and larger line widths compared with those in Taurus. This implies that PGCC cores in Taurus are less chemically evolved than those in Cepheus. [ABSTRACT FROM AUTHOR]

Abstract The insulated gate bipolar transistor (IGBT) is one of the most fragile components in power electronics converters. In order to improve the reliability of IGBTs, various measurements are taken according to the condition monitoring (CM) technique. Traditional CM techniques include the measurement and estimation of the device operation conditions. Recently, emerging techniques have been developed, not only for the detection and estimation but also for the prognostics of IGBTs with the condition data. In this paper, a review is performed on the recent progress in the CM techniques for IGBTs. First, some emerging electrical and thermal measurements are reviewed. Based on the sensed data, the health indicator estimation techniques are summarised. Moreover, for the emerging prognostics and health management applications, some remaining using lifetime (RUL) prediction methods are reviewed. Finally, the research gaps and directions are discussed for the CM in IGBT applications.

Abstract To investigate the visual/anatomical outcome of diabetic macular edema (DME) patients lost to follow-up (LTFU) for more than 1 year during intravitreal anti-VEGF treatment. A retrospective review of 182 treatment-naïve DME patients was performed. Among them, we identified patients LTFU for more than 1 year during anti-VEGF treatment. Visual acuity and anatomic outcomes at the first visit, last visit before being LTFU, return visit, and after re-treatment were analyzed and compared with those of DME patients with regular follow-up. Patients who had continuous follow-up visits were assigned to the control group. Sixty patients (33%) with DME were LTFU for more than 1 year during anti-VEGF treatment. Multivariate analysis revealed that the ratio of male (p = 0.004), diabetes mellitus (DM) duration less than 5 years (p = 0.015), and poor early anatomic response (p = 0.012) were higher compared to the control group. Eighteen patients returned to the clinic and received re-treatment. After re-treatment with anti-VEGF, central subfield thickness (CST) was significantly improved to the CST of before LTFU. However, visual acuity did not recover to the level before LTFU (0.63 ± 0.26 vs. 0.45 ± 0.28, p = 0.003). About thirty percent of DME patients were LTFU for more than 1 year. Permanent visual loss was observed in these LTFU patients. Patients with a high risk of LTFU such as male, early DM, and poor response after initial injections should be treated more aggressively to improve the visual outcomes.

Abstract Background To analyze the long-term effects of persistent subretinal fluid (SRF) on visual/anatomic outcomes according to the type of macular neovascularization (MNV) during relaxed treat-and-extend regimen with anti-vascular endothelial growth factor (anti-VEGF) agents in age-related macular degeneration (AMD) patients. Methods Patients with fovea-involving type 1 or type 2 MNV, treated with a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. Eyes with SRF observed more than three times per year were defined as the ‘persistent SRF (+) group’. To exclude the effects of IRF as much as possible, the eyes with persistent IRF were excluded. The effects of persistent SRF on the best-corrected visual acuity (BCVA), central subfield retinal thickness (CST), and changes in the photoreceptor layer (PRL) thickness and outer retinal bands (external limiting membrane, ellipsoid zone, and cone outer segment tip line) after anti-VEGF injection were analyzed for each MNV type. Results Seventy-seven eyes with type 1 MNV (44 eyes with persistent SRF) and 53 eyes with type 2 MNV (18 eyes with persistent SRF) were enrolled. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST improved for each MNV type. In comparison between persistent SRF (+) and persistent SRF (−) group, there were no differences in the amount of change in BCVA and CST between the two groups for each MNV type during 2-year follow-up periods. In addition, there were no differences in the amount of reduction in PRL thickness and state of the outer retinal bands between the two groups for each MNV type. Conclusions Using a relaxed treat-and-extend regimen with anti-VEGF agents, persistent SRF did not have additional effects on visual and anatomic outcomes by 2 years, regardless of the MNV type.

Granulocyte-monocyte progenitors (GMPs) differentiate into both neutrophils and monocytes. Recently, uni-potential neutrophil progenitors have been identified both in mice and humans using an array of surface markers. However, how human GMPs commit to neutrophil progenitors and the regulatory mechanisms of fate determination remain incompletely understood. In the present study, we established a human neutrophil deficiency model using the small molecule alpha-lipoic acid. Using this neutrophil deficiency model, we determined that the neutrophil progenitor commitment process from CD371+ CD115– GMPs defined by CD34 and CD15 and discovered that critical signals generated by RNA splicing and rRNA biogenesis regulate the process of early commitment for human early neutrophil progenitors derived from CD371+ CD115– GMPs. These processes were elucidated by single-cell RNA sequencing both in vitro and in vivo derived cells. Sequentially, we identified that the transcription factor ELK1 is essential for human neutrophil lineage commitment using the alpha-lipoic acid (ALA)-inducing neutrophil deficiency model. Finally, we also revealed differential roles for long-ELK1 and short-ELK1, balanced by SF3B1, in the commitment process of neutrophil progenitors. Taken together, we discovered a novel function of ALA in regulating neutrophil lineage specification and identified that the SF3B1-ELK axis regulates the commitment of human neutrophil progenitors from CD371+ CD115– GMPs.