Cluster of Differentiation 36 (CD36) Preferentially Mediates Intestinal Absorption of Dietary Z-Astaxanthin and Especially 9-Z-Isomer via Higher Binding Affinity.

Variances in the biological functions of astaxanthin geometric isomers (i.e., all-E, Z) are related to their intestinal absorption, but the mechanism of isomer absorption mediated by transporters remains unclear. Here, models of in vitro cell overexpression, in situ intestinal perfusion, and in vivo mouse inhibition were employed to investigate the impact of cluster of differentiation 36 (CD36) on the absorption of astaxanthin isomers. Cells overexpressing CD36 notably enhanced the uptake of Z-astaxanthin, particularly the 9-Z-isomer (47.76%). The absorption rate and permeability of Z-astaxanthin surpassed that of the all-E-isomer by the in situ model. Furthermore, the addition of the CD36-specific inhibitor sulfo-N-succinimidyl oleate significantly reduced the absorption of Z-astaxanthin in the mouse duodenum and jejunum, especially the 9-Z-isomer (57.66%). Molecular docking and surface plasmon resonance techniques further validated that 9-Z-astaxanthin binds to more amino acids of CD36 with higher affinity and in a fast-binding, fast-dissociating mode, thus favoring transport. Our findings elucidate, for the first time, the mechanism of the CD36-mediated transmembrane transport of astaxanthin geometric isomers.

ZmSPL10, ZmSPL14 and ZmSPL26 act together to promote stigmatic papilla formation in maize through regulating auxin signaling and ZmWOX3A expression.

Maize silk is a specialized type of stigma, covered with numerous papillae for pollen grain capture. However, the developmental process of stigmatic papillae and the underlying regulatory mechanisms have remained largely unknown. Here, we combined the cytological, genetic and molecular studies to demonstrate that three homologous genes ZmSPL10, ZmSPL14 and ZmSPL26 play a central role in promoting stigmatic papilla formation in maize. We show that their triple knockout mutants are nearly complete lack of stigmatic papilla, resulting in a severe reduction in kernel setting. Cellular examination reveals that stigmatic papilla is developed from a precursor cell, which is the smaller daughter cell resulting from asymmetric cell division of a silk epidermal cell. In situ hybridization shows that ZmSPL10, ZmSPL14 and their target genes SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A are preferentially expressed in the precursor cells of stigmatic papillae. Moreover, ZmSPL10, ZmSPL14 and ZmSPL26 directly bind to the promoters of SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A and promote their expression. Further, Zmwox3a knockout mutants display severe defects in stigmatic papilla formation and reduced seed setting. Collectively, our results demonstrate that ZmSPL10, ZmSPL14 and ZmSPL26 act together to promote stigmatic papilla development through regulating auxin signaling and ZmWOX3A expression.

Emerging Nanotechnology in Preclinical Pancreatic Cancer Immunotherapy: Driving Towards Clinical Applications.

The high malignant degree and poor prognosis of pancreatic cancer (PC) pose severe challenges to the basic research and clinical translation of next-generation therapies. The rise of immunotherapy has improved the treatment of a variety of solid tumors, while the application in PC is highly restricted by the challenge of immunosuppressive tumor microenvironment. The latest progress of nanotechnology as drug delivery platform and immune adjuvant has improved drug delivery in a variety of disease backgrounds and enhanced tumor therapy based on immunotherapy. Based on the immune loop of PC and the status quo of clinical immunotherapy of tumors, this article discussed and critically analyzed the key transformation difficulties of immunotherapy adaptation to the treatment of PC, and then proposed the rational design strategies of new nanocarriers for drug delivery and immune regulation, especially the design of combined immunotherapy. This review also put forward prospective views on future research directions, so as to provide information for the new means of clinical treatment of PC combined with the next generation of nanotechnology and immunotherapy.

A proof-of-concept study of ultrasound-guided continuous parasacral ischial plane block for postoperative pain control in patients undergoing total knee arthroplasty.

BACKGROUND: Continuous peripheral nerve blocks are widely used for anesthesia and postoperative analgesia in lower limb surgeries. The authors aimed to develop a novel continuous sacral plexus block procedure for analgesia during total knee arthroplasty. METHODS: The study comprised two stages. In Stage I, the authors built upon previous theories and technological innovations to develop a novel continuous sacral plexus block method, ultrasound-guided continuous parasacral ischial plane block (UGCPIPB) and subsequently conducted a proof-of-concept study to assess its effectiveness and feasibility. Stage II involved a historical control study to compare clinical outcomes between patients undergoing this new procedure and those receiving the conventional procedure. RESULTS: The study observed a 90% success rate in catheter placement. On postoperative day (POD) 1, POD2, and POD3, the median visual analog scale (VAS) scores were 3 (range, 1.5-3.5), 2.5 (1.6-3.2), and 2.7 (1.3-3.4), respectively. Furthermore, 96.3% of the catheters remained in place until POD3, as confirmed by ultrasound. The study revealed a significant increase in skin temperature and peak systolic velocity of the anterior tibial artery on the blocked side compared with those on the non-blocked side. Complications included catheter clogging in one patient and leakage at the insertion site in two patients. In Stage II, the novel technique was found to be more successful than conventional techniques, with a lower catheter displacement rate than the conventional procedure for continuous sciatic nerve block. CONCLUSION: UGCPIPB proved to be an effective procedure and safe for analgesia in total knee arthroplasty. CHINESE CLINICAL TRIAL REGISTRY NUMBER: ChiCTR2300068902.

Combining metabolomics with network pharmacology to reveal the therapeutic mechanism of Dingchuan Decoction in rats with OVA-induced allergic asthma.

Dingchuan Decoction (DCD) is a traditional Chinese medicine prescription commonly used in the treatment of asthma, but the mechanism of DCD in treating asthma has not yet been determined. In this study, we employed a combination of metabolomics and network pharmacology to investigate the mechanism of DCD in treating asthma. An allergic asthma rat model was induced by ovalbumin (OVA). Metabolomics based on 1H NMR and UHPLC-MS was used to identify differential metabolites and obtain the major metabolic pathways and potential targets. Network pharmacology was utilized to explore potential targets of DCD for asthma treatment. Finally, the results of metabolomics and network pharmacology were integrated to obtain the key targets and metabolic pathways of DCD for the therapy of asthma, and molecular docking was utilized to validate the key targets. A total of 76 important metabolites and 231 potential targets were identified through metabolomics. Using network pharmacology, 184 potential therapeutic targets were obtained. These 184 targets were overlaid with the 231 potential targets obtained through metabolomics and were analyzed in conjunction with metabolic pathways. Ultimately, the key targets were identified as aldehyde dehydrogenase 2 (ALDH2) and amine oxidase copper-containing 3 (AOC3), and the relevant metabolic pathways affected were glycolysis and gluconeogenesis as well as arginine and proline metabolism. Molecular docking showed that the key targets had high affinity with the relevant active ingredients in DCD, which further demonstrated that DCD may exert therapeutic effects by acting on the key targets. The present study demonstrated that DCD can alleviate OVA-induced allergic asthma and that DCD may have a therapeutic effect by regulating intestinal flora and polyamine metabolism through its effects on ALDH2 and AOC3.

Normothermic Ex Vivo Heart Perfusion With Exosomes From Human Umbilical Cord Mesenchymal Stem Cells Improves Graft Function in Donation After Circulatory Death Hearts.

BACKGROUND: This study aimed to investigate the cardioprotective effect of exosomes derived from human umbilical cord mesenchymal stem cells on donation after circulatory death (DCD) hearts preserved with normothermic ex vivo heart perfusion (EVHP) in a rat heart transplantation model. METHODS: Thirty-two male Lewis rats were divided into 2 groups: the control group and the exosome group. The donor-heart rats were subjected to the DCD procedure by suffering a 15-min warm ischemia injury, subsequently preserved with EVHP for 90 min, and then transplanted into recipients via abdominal heterotopic heart transplantation. Vehicle or exosome was added into the perfusate of normothermic EVHP in the control or exosome group. We evaluated left ventricular graft function, myocardial inflammation, and myocardial apoptosis of the donor heart 1.5 h after heart transplantation. Furthermore, we investigate the alternation of myocardial gene expression in the donor hearts between both groups by transcriptome sequencing. RESULTS: The treatment with exosome significantly enhanced cardiac function through increasing left ventricular developed pressure, dp/dtmax, and dp/dtmin of DCD hearts at 90 min after heart transplantation compared with the control group. The myocardial cells in the exosome group exhibited an orderly arrangement without obvious edema. Furthermore, exosome added into perfusate in the exosome group significantly attenuated the level of inflammatory response and apoptosis. Transcriptome sequencing and RT-qPCR showed the phosphoinositide 3-kinase/protein kinase B pathway was activated after exosome treatment. CONCLUSIONS: Normothermic EVHP combined with exosome can be a promising and novel DCD heart preservation strategy, alleviating myocardial ischemia-reperfusion injury in the DCD heart.

Exploring the Mechanism of KLF15 on the Biological Activity and Autophagy of Gastric Cancer Cells based on PI3K/Akt/Mtor Signaling Pathway.

OBJECTIVE: To explore the mechanism of KLF15 on the biological activity and autophagy of gastric cancer cells based on the PI3K/Akt/mTOR signaling pathway. MATERIAL AND METHODS: The gastric cancer AGS cells were divided into the Con group, pcDNANC group, pcDNA-KLF15 group, LY294002 group and IGF-1 group. RT-PCR was used to detect the expression of KLF15 in human gastric mucosal cells and gastric cancer cells; MTT method to detect cell proliferation; Transwell method to detect cell invasion; flow cytometry to detect cell apoptosis; Western blotting to detect PI3K, Akt, mTOR in cells, LC3, Beclin1, p62 protein expression.P<0.05 was used to indicate statistical significance. RESULTS: Compared with the human gastric mucosal cell line GES-1 cells, the expression of KLF15 in human gastric cancer cell lines MKN-28, MFC, SCG-7901 and AGS cells was significantly decreased, And the expression of KLF15 in AGS cells, was the lowest (P=0.006). Compared with the Con group, The expression of KLF15 in the cells of the PCDNA-KLF15 group was significantly increased (P=0.018); There was no significant difference in the expression of KLF15 between the Con group and the PCDNA-NC group (P=0.225). Compared with the Con group, the proliferation and invasion abilities of the cells in the pcDNA-KLF15 group were significantly reduced, And the apoptosis ability was significantly increased (P=0.019). The ratio of LC3II/LC31 and the expression of Beclin1 Protein in the control group were significantly higher than those in the Con group (P=0.017). CONCLUSION: Overexpression of KLF15 can inhibit the proliferation and invasion of Gastric cancer cells and promote cell apoptosis and autophagy, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR signaling pathway.

Cancer immunometabolism: advent, challenges, and perspective.

For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role.

Yin Yang 1 regulates cohesin complex protein SMC3 in mouse hematopoietic stem cells.

ABSTRACT: Yin Yang 1 (YY1) and structural maintenance of chromosomes 3 (SMC3) are 2 critical chromatin structural factors that mediate long-distance enhancer-promoter interactions and promote developmentally regulated changes in chromatin architecture in hematopoietic stem/progenitor cells (HSPCs). Although YY1 has critical functions in promoting hematopoietic stem cell (HSC) self-renewal and maintaining HSC quiescence, SMC3 is required for proper myeloid lineage differentiation. However, many questions remain unanswered regarding how YY1 and SMC3 interact with each other and affect hematopoiesis. We found that YY1 physically interacts with SMC3 and cooccupies with SMC3 at a large cohort of promoters genome wide, and YY1 deficiency deregulates the genetic network governing cell metabolism. YY1 occupies the Smc3 promoter and represses SMC3 expression in HSPCs. Although deletion of 1 Smc3 allele partially restores HSC numbers and quiescence in YY1 knockout mice, Yy1-/-Smc3+/- HSCs fail to reconstitute blood after bone marrow transplant. YY1 regulates HSC metabolic pathways and maintains proper intracellular reactive oxygen species levels in HSCs, and this regulation is independent of the YY1-SMC3 axis. Our results establish a distinct YY1-SMC3 axis and its impact on HSC quiescence and metabolism.

The GPR40 novel agonist SZZ15-11 improves non-alcoholic fatty liver disease by activating the AMPK pathway and restores metabolic homeostasis in diet-induced obese mice.

AIM: Non-alcoholic fatty liver is the most common cause of chronic liver disease. GPR40 is a potential therapeutic target for energy metabolic disorders. GPR40 is a potential therapeutic target for energy metabolic disorders. SZZ15-11 is a newly synthesized GPR40 agonist. In this study, we estimate the potency of SZZ15-11 in fatty liver treatment. METHODS: In vivo, diet-induced obese (DIO) mice received SZZ15-11 (50 mg/kg) and TAK875 (50 mg/kg) for 6 weeks. Blood glucose and lipid, hepatocyte lipid and liver morphology were analysed. In vitro, HepG2 cells and GPR40-knockdown HepG2 cells induced with 0.3 mM oleic acid were treated with SZZ15-11. Triglyceride and total cholesterol of cells were measured. At the same time, the AMPK pathway regulating triglycerides and cholesterol esters synthesis was investigated via western blot and quantitative polymerase chain reaction in both liver tissue and HepG2 cells. RESULTS: SZZ15-11 was found to not only attenuate hyperglycaemia and hyperlipidaemia but also ameliorate fatty liver disease in DIO mice. At the same time, SZZ15-11 decreased triglyceride and total cholesterol content in HepG2 cells. Whether examined in the liver of DIO mice or in HepG2 cells, SZZ15-11 upregulated AMPKα phosphorylation and then downregulated the expression of the cholesterogenic key enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase and inhibited acetyl-CoA carboxylase activity. Furthermore, SZZ15-11 promotes AMPK activity via [cAMP]i accumulation. CONCLUSION: This study confirmed that SZZ15-11, a novel GPR40 agonist, improves hyperlipidaemia and fatty liver, partially via Gs signalling and the AMPK pathway in hepatocytes.

Effect of different starting doses of FSH on laboratory and clinical outcomes in patients with moderate AMH level.

BACKGROUND: IVF and ICSI-ET are widely used ART for addressing infertility which have been developed and improved over the last four decades. COS is a crucial step in IVF/ICSI-ET, whereby medications stimulate the ovaries to produce multiple eggs. The success of the procedure depends on the number of eggs retrieved, and individualized ovarian stimulation protocols based on factors like age and ovarian reserve can optimize the chances of obtaining mature oocytes. The optimal starting dose of FSH at moderate AMH levels remains a topic of debate., tThis study aims to compare different starting doses of FSH in clinical outcomes by analyzing data from a single center. METHODS: This retrospective study collected clinical material from patients with moderate AMH levels at 1.2 ~ 4.5 ng/mL who received IVF/ICSI-ET under a follicular phase long protocol from July 2018 to December 2021 at Guiyang Maternal and Child Health Care Hospital, China. The patients' clinical data were retrieved from the hospital's software database and divided into two groups based on FSH starting dose, as follows: lower starting dose group: FSH ≤ 150 IU; and higher starting dose group: FSH > 150 IU. Multiple laboratory and clinical outcomes were compared between the two groups. RESULTS: A total of 1784 patients with moderate serum AMH levels who received IVF/ICSI-ET under a follicular phase long protocol were enrolled based on eligibility criteria. In the population with moderate AMH levels, a lower starting dose of FSH might have more benefit than a higher starting dose in numbers of follicles with diameters ≥ 14 mm and < 16 mm, ≥ 16 mm and < 18 mm, and ≥ 18 mm; numbers of retrieved oocytes, 2PNs, transferable embryos, high-quality embryos, and cleavage stage embryos transferred; and clinical pregnancy rate, intrauterine pregnancy rate, and parturition rate. Moreover, rFSH had a statistically significantly higher number of oocytes retrieved, number of 2PNs, and number of transferable embryos than that of patients who received uFSH. CONCLUSIONS: The starting dose of FSH in the moderate AMH population remains controversial and a higher starting dose may not lead to more benefit in laboratory and clinical outcomes.

Investigation of the therapeutic effect of Hedan tablets on high-fat diet-induced obesity in rats by GC-MS technology and 16S ribosomal RNA gene sequencing.

Obesity is a persistent metabolic condition resulting from the excessive accumulation or abnormal distribution of body fat. This study aimed to establish an experimental rat model of obesity. The efficacy of treating obesity with Hedan tablets (HDT) was assessed by monitoring changes in weight, blood lipid levels, analyzing inflammatory factors, evaluating organ indices, and observing liver tissue pathology. Furthermore, we utilized 16S ribosomal RNA gene sequencing technology to explore changes in intestinal flora. In addition, GC-MS was used to measure fecal short-chain fatty acid (SCFA) content. The onset of obesity led to a significant decrease in the relative abundance of beneficial bacteria. Conversely, the administration of HDT demonstrated a substantial ability to increase the relative abundance of beneficial bacteria. Obesity resulted in a noteworthy reduction in total SCFAs, a trend significantly reversed in the HDT group. Through correlation analysis, it was determined that HDT mitigated the inflammatory response and improved blood lipid levels by augmenting the abundance of Lactobacillus, Limosilactobacillus, Ruminococcus, and Enterococcus. These particular intestinal flora were identified as regulators of SCFA metabolism, thereby ameliorating metabolic abnormalities associated with obesity. Moreover, HDT intervention elevated the overall fecal concentration of SCFAs, thereby improving metabolic disorders induced by obesity. The anti-obesity effects of HDT are likely attributable to their capacity to influence the composition of intestinal flora and boost SCFA levels in the intestine.

Construction of a prognosis model of head and neck squamous cell carcinoma pyroptosis and an analysis of immuno-phenotyping based on bioinformatics.

Background: Head and neck squamous cell carcinoma (HNSCC) is currently the sixth most common cancer worldwide, and its prevalence and recurrence rates are gradually increasing. To study the relationship between HNSCC and cell pyroptosis and provide new treatment options for HNSCC, a prognostic model of pyroptosis-related genes (PRGs) was established to predict the prognosis of patients with HNSCC, and an immune correlation analysis was performed. Methods: A total of 53 PRGs were selected. We comprehensively analyzed the role of these PRGs in HNSCC through multiple omics data-set integration. We then identified two different molecular subtypes and found that changes in multi-layer PRGs were associated with clinicopathological characteristics, prognosis, and tumor microenvironment cell-infiltration characteristics in patients. Next, prognostic models were generated for nine PRGs; that is, cytotoxic T lymphocyte antigen 4 (CTLA4), V-set and immunoglobulin domain containing 4 (VSIG4), heparin-binding-epidermal growth factor (HBEGF), aquaporin-1 (AQP1), sodium channel epithelial 1 subunit delta (SCNN1D), argininosuccinate synthase 1 (ASS1), family with sequence similarity 83 member (FAM83), cyclin dependent kinase inhibitor 2A (CDKN2A), and serine protease inhibitor Kazal 6 (SPINK6). Finally, a risk-score model was constructed, and the Kaplan-Meier method was used to evaluate overall survival. In addition, the immune environment and drug sensitivity were analyzed. Results: This study showed that pyroptosis is closely related to HNSCC. The scores generated by the risk markers based on the new nine PRGs were identified as independent risk factors for predicting HNSCC. The differentially expressed genes between the low- and high-risk groups were further found to be related to the tumor immune cells and pathways. In addition, the risk score was found to be significantly correlated with chemosensitivity. Conclusions: Our comprehensive analysis of PRGs revealed their potential role in the tumor immune microenvironment, clinicopathological characteristics, and prognosis. These findings may improve our understanding of pyroptosis in HNSCC and may provide new ideas for evaluating prognosis and developing more effective immunotherapy strategies.

Analyzing public demands on China's online government inquiry platform: A BERTopic-Based topic modeling study.

This study aims to enhance governmental decision-making by leveraging advanced topic modeling algorithms to analyze public letters on the "People Call Me" online government inquiry platform in Zhejiang Province, China. Employing advanced web scraping techniques, we collected publicly available letter data from Hangzhou City between June 2022 and May 2023. Initial descriptive statistical analyses and text mining were conducted, followed by topic modeling using the BERTopic algorithm. Our findings indicate that public demands are chiefly focused on livelihood security and rights protection, and these demands exhibit a diversity of characteristics. Furthermore, the public's response to significant emergency events demonstrates both sensitivity and deep concern, underlining its pivotal role in government emergency management. This research not only provides a comprehensive landscape of public demands but also validates the efficacy of the BERTopic algorithm for extracting such demands, thereby offering valuable insights to bolster the government's agility and resilience in emergency responses, enhance public services, and modernize social governance.

Biopolymer separators from polydopamine-functionalized bacterial cellulose for lithium-sulfur batteries.

The advancement of the lithium-sulfur (Li-S) batteries is immensely impeded by two main challenges: polysulfide shuttling between the electrodes and Li dendrite formation associated with the Li-metal anode. To tackle these challenges, we synthesized a polydopamine coated bacterial cellulose (PDA@BC) separator in a way to create physical and chemical traps for the shuttling polysulfides and to control the Li+ flux. While nanocellulose offers its dense network as a physical trap, the presence of polydopamine in the separator offers polar functional groups which not only has a high binding energy towards the polysulfides but also helps in redistribution of the Li+ ions across it. The electrochemical and physiochemical results suggest that the synthesized separator can have practical applicability owing to its superior performance compared to a commercial separator. The Li-S batteries assembled with this separator showed a specific discharge capacity of 1449 mAh/g at 0.1C and 877 mAh/g at 1C, and a capacity fade of 0.03 % per cycle over 650 cycles at 1C. Using a PDA@BC separator, a practical Li-S battery cell with S loading of 7.5 mg cm-2 (and E/S ratio of 10 µLmg-1, 82 % S ratio) was also tested at 1C, which delivered a capacity of âˆ¼ 6 mAh cm-2 for 500 cycles.

Parallel perception of visual motion using light-tunable memory matrix.

Parallel perception of visual motion is of crucial significance to the development of an intelligent machine vision system. However, implementing in-sensor parallel visual motion perception using conventional complementary metal-oxide semiconductor technology is challenging, because the temporal and spatial information embedded in motion cannot be simultaneously encoded and perceived at the sensory level. Here, we demonstrate the parallel perception of diverse motion modes at the sensor level by exploiting light-tunable memory matrix in a van der Waals (vdW) heterostructure array. The optoelectronic characteristics of gate-tunable photoconductivity and light-tunable memory matrix enable devices in the array to realize simultaneous encoding and processing of incoming spatiotemporal light pattern. Furthermore, we implement a visual motion perceptron with the array capable of deciphering multiple motion parameters in parallel, including direction, velocity, acceleration, and angular velocity. Our work opens up a promising venue for the realization of an intelligent machine vision system based on in-sensor motion perception.

Impact of patterns of language use and socio-economic status on a constructed response Situational Judgment Test (SJT).

The study explored the impacts of patterns of language use (PLU) and socio-economic status (SES) on Casper, a constructed-response situational judgment test (SJT). 10,266 applicants from two U.S. medical schools were grouped into self-reported balanced bilinguals, unbalanced bilinguals, English monolinguals, and English as a Second Language (ESL) students. A multicomponent SES composite was used to assess the degree of socioeconomic disadvantage (DSD). Results from a hierarchical regression analysis showed that after accounting for demographic variables, both PLU and DED were significant factors on applicants' Casper performance. Bilingualism was associated with better Casper performance compared to English monolinguals and ESL students. No significant effect of speaking English as a native language was found on applicants' Casper performance. English monolinguals and ESL students performed equivalently on Casper. Finally, high DSD was associated with better Casper performance than low DSD, and the impact of DSD on Casper held the same across all four language groups. These findings provide evidence that socio-cultural factors, such as PLU and DSD have important impacts on SJT performance. Further research is needed to understand the role of differences in language construction across socio-cultural factors on constructed-response SJT performance.

WOX-ARF modules initiate different types of roots.

Seed plants have evolved a complex root system consisting of at least three root types, i.e., adventitious roots, lateral roots, and the primary root. Auxin is the key hormone that controls the initiation of different root types. Here, we show that protein complexes with different combinations of intermediate-clade WUSCHEL-RELATED HOMEOBOXs (IC-WOXs) and class-A AUXIN RESPONSE FACTORs (A-ARFs) initiate the three root types in Arabidopsis thaliana. In adventitious root founder cells from detached leaves, the WOX11-ARF6/8 complex activates RGF1 INSENSITIVEs (RGIs) and LATERAL ORGAN BOUNDARIES DOMAIN 16 (LBD16) to initiate the adventitious root primordium. In lateral root founder cells, ARF7/19 activate RGIs and LBD16 without IC-WOX to initiate the lateral root primordium. In the primary root founder cell (i.e., hypophysis of an embryo), the WOX9-ARF5 complex initiates the primary root by activation of RGIs. Overall, the WOX-ARF modules show a division of labor to initiate different type of roots.