Top of tide: Nexus between organization agility, digital capability and top management support in SME digital transformation.

In the swiftly evolving business landscape, digital transformation (DT) has emerged as a crucial strategy for firms to gain a competitive edge. Despite the abundance of literature on DT in firms, there remains a dearth of empirical research that defines and analyzes crucial antecedents of small and medium-sized enterprises' (SMEs) DT from an internal perspective. To fill this research gap, this study examines the correlation between organizational agility and digital capability in cultivating SMEs' DT while also evaluating top management support as a moderating variable through the lens of internal factors of SMEs. The results indicate that both organizational agility and digital capability have a positive impact on SMEs' DT, with organizational agility significantly influencing digital capability. Furthermore, the findings highlight that digital capability serves as a mediator between organizational agility and SMEs' DT. In addition, top management support plays a moderating role in these relationships to a certain extent. Additionally, we explicate the concept of digital capabilities from the perspective of dynamic capability. Our study contributes to an enhanced understanding of the effect of organizational agility and digital capability on SMEs' DT, as well as the role of top management support. We provide recommendations for managers to enhance organizational agility and suggest that SMEs should improve their digital thinking to better perceive digital technology changes, enhance digital operation capabilities, and better integrate digital resources.

Myeloid cell-expressed MNDA enhances M2 polarization to facilitate the metastasis of hepatocellular carcinoma.

Stable infiltration of myeloid cells, especially tumor-associated M2 macrophages, acts as one of the essential features of the tumor immune microenvironment by promoting the malignant progression of hepatocellular carcinoma (HCC). However, the factors affecting the infiltration of M2 macrophages are not fully understood. In this study, we found the molecular subtypes of HCC with the worst prognosis are characterized by immune disorders dominated by myeloid cell infiltration. Myeloid cell nuclear differentiation antigen (MNDA) was significantly elevated in the most aggressive subtype and exhibited a positively correlation with M2 infiltration and HCC metastasis. Moreover, MNDA functioned as an independent prognostic predictor and has a good synergistic effect with some existing prognostic clinical indicators. We further confirmed that MNDA was primarily expressed in tumor M2 macrophages and contributed to the enhancement of its polarization by upregulating the expression of the M2 polarization enhancers. Furthermore, MNDA could drive the secretion of M2 macrophage-derived pro-metastasis proteins to accelerate HCC cells metastasis both in vivo and in vitro. In summary, MNDA exerts a protumor role by promoting M2 macrophages polarization and HCC metastasis, and can serve as a potential biomarker and therapeutic target for HCC.

An Enzymatically Activated and Catalytic Hairpin Assembly-Driven Intelligent AND-Gated DNA Network for Tumor Molecular Imaging.

Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, and tFNA-H2, were rationally engineered to form a polymeric tFNA network, termed an intelligent DNA network, in an AND-gated manner. The intelligent DNA network was designed for tumor-specific molecular imaging by leveraging the elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cytoplasm instead of normal cells and the high expression of miRNA-21 in tumor cytoplasm. The activation of tFNA-H1AP can be achieved through specific recognition and cleavage by APE1, targeting the apurinic/apyrimidinic site (AP site) modified within the stem region of hairpin 1 (H1AP). Subsequently, miRNA-21 facilitates the hybridization of activated H1AP on tFNA-H1AP with hairpin 2 (H2) on tFNA-H2, triggering a catalytic hairpin assembly (CHA) reaction that opens the H1AP at the vertices of tFNA-H1AP to bind with H2 at the vertices of tFNA-H2 and generate fluorescence signals. Upon completion of hybridization, miRNA-21 is released, initiating the subsequent cycle of the CHA reaction. The AND-gated intelligent DNA network can achieve specific tumor molecular imaging in vivo and also enables risk stratification of neuroblastoma patients.

Curcumin Inhibits α-Synuclein Aggregation by Acting on Liquid-Liquid Phase Transition.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is linked to α-synuclein (α-Syn) aggregation. Despite no specific drug being available for its treatment, curcumin, from the spice turmeric, shows promise. However, its application in PD is limited by a lack of understanding of its anti-amyloidogenic mechanisms. In this study, we first reconstructed the liquid-liquid phase separation (LLPS) of α-Syn in vitro under different conditions, which may be an initial step in entraining the pathogenic aggregation. Subsequently, we evaluated the effects of curcumin on the formation of droplets, oligomers, and aggregated fibers during the LLPS of α-synuclein, as well as its impact on the toxicity of aggregated α-synuclein to cultured cells. Importantly, we found that curcumin can inhibit amyloid formation by inhibiting the occurrence of LLPS and the subsequent formation of oligomers of α-Syn in the early stages of aggregation. Finally, the molecular dynamic simulations of interactions between α-Syn decamer fibrils and curcumin showed that van der Waal's interactions make the largest contribution to the anti-aggregation effect of curcumin. These results may help to clarify the mechanism by which curcumin inhibits the formation of α-Syn aggregates during the development of PD.

Functionalizing tetrahedral framework nucleic acids-based nanostructures for tumor in situ imaging and treatment.

Timely in situ imaging and effective treatment are efficient strategies in improving the therapeutic effect and survival rate of tumor patients. In recent years, there has been rapid progress in the development of DNA nanomaterials for tumor in situ imaging and treatment, due to their unsurpassed structural stability, excellent material editability, excellent biocompatibility and individual endocytic pathway. Tetrahedral framework nucleic acids (tFNAs), are a typical example of DNA nanostructures demonstrating superior stability, biocompatibility, cell-entry performance, and flexible drug-loading ability. tFNAs have been shown to be effective in achieving timely tumor in situ imaging and precise treatment. Therefore, the progress in the fabrication, characterization, modification and cellular internalization pathway of tFNAs-based functional systems and their potential in tumor in situ imaging and treatment applications were systematically reviewed in this article. In addition, challenges and future prospects of tFNAs in tumor in situ imaging and treatment as well as potential clinical applications were discussed.

Preparation and Performance of a Novel ZnO/TM/PET Composite Negative Ion Functional Fiber.

Using zinc oxide (ZnO), tourmaline (TM), and polyethylene terephthalate (PET) as main raw materials, a novel ZnO/TM/PET negative ion functional fiber was created. The rheological properties of a ZnO/TM/PET masterbatch were investigated; the morphology, XRD, and FT-IR of the fibers were observed; and the mechanical properties, thermal properties, and negative ion release properties of the new fiber were tested. The results showed that the average particle size of the ZnO/TM composite is nearly 365 nm, with an increase in negative ion emission efficiency by nearly 50% compared to the original TM. The apparent viscosity of fiber masterbatch decreases with the increase in the addition of the ZnO/TM composite, and the rheological properties of the PET fiber masterbatch are not significantly effected, still showing shear thinning characteristics when the amount of addition reaches 10%. The ZnO/TM composite disperses well in the interior and surface of the ZnO/TM/PET fiber matrix. The prepared ZnO/TM/PET fiber has excellent properties, such as fineness of 1.54 dtex, glass transition temperature of 122.4 °C, fracture strength of 3.31 cN/dtex, and negative ion release of 1640/cm3, which shows great industrialization potential.

An APE1 gated signal amplified biosensor driven by catalytic hairpin assembly for the specific imaging of microRNA in situ.

In situ imaging of microRNA (miRNA) content and distribution is valuable for monitoring tumor progression. However, tumor specific in situ imaging remains a challenge due to low miRNA abundance, lack of biological compatibility, and poor specificity. In this study, we designed a DNA tetrahedral framework complex with hairpins (DTF-HPAP) consisting of an apurinic/apyrimidinic site (AP site) that could be specifically recognized and cleaved by apurinic/apyrimidinic endonuclease 1 (APE1). Efficient and specific in situ imaging of miR-21 in tumors was thus achieved through catalytic hairpin assembly (CHA) reaction. In this study, DTF-HPAP was successfully constructed to trigger the cumulative amplification of fluorescence signal in situ. The specificity, sensitivity and serum stability of DTF-HPAP were verified in vitro, and DTF-HPAP could be easily taken up by cells, acting as a biosensor to detect tumors in mice. Furthermore, we verified the ability of DTF-HPAP to specifically image miR-21 in tumors, and demonstrated its capability for tumor-specific imaging in clinical samples.

Comparison of robotic versus thoracoscopic repair for congenital esophageal atresia: a propensity score matching analysis.

BACKGROUND: Despite the rapid advancement of robotic surgery across various surgical domains, only cases of robotic repair (RR) for neonates with esophageal atresia (EA) have been reported. Comprehensive studies comparing RR and thoracoscopic repair (TR) are lacking. The authors aimed to compare the safety and efficacy of RR and TR for EA. METHODS: A retrospective multicenter study was conducted on 155 EA neonates undergoing RR (79 patients) or TR (76 patients) between August 2020 and February 2023 using propensity score matching. Asymmetric port distribution and step-trocar insertion techniques were applied during RR. Demographics and surgical outcomes were compared. RESULTS: After matching, 63 patients (out of 79) in RR group and 63 patients (out of 76) in TR group were included. There were no significant differences in short-term outcomes between two groups, except for longer total operative time (173.81 vs. 160.54 min; P <0.001) and shorter anastomotic time (29.52 vs. 40.21 min; P <0.001) in RR group. Compared with TR group, the RR group had older age at surgery (8.00 vs. 3.00 days; P <0.001), but a comparable pneumonia rate. More importantly, the incidence of anastomotic leakage (4.76 vs. 19.05%, P =0.013), anastomotic stricture (15.87 vs. 31.74%, P =0.036) within 1 year postoperatively, and unplanned readmission (32.26 vs. 60.00%, P =0.030) within 2 years postoperatively were lower in RR group than in TR group. CONCLUSIONS: RR is a technically safe and effective option for EA patients. This approach delays the age of surgery without increasing respiratory complication rates while reducing the incidence of postoperative anastomotic complications and unplanned readmission.

STOP1 attenuates the auxin response to maintain root stem cell niche identity.

In plant roots, the identity of the stem cell niche (SCN) is maintained by an auxin gradient with its maximum in the quiescent center (QC). Optimal levels of auxin signaling are essential for root SCN identity, but the regulatory mechanisms that control this pathway in root are largely unknown. Here, we find that the zinc finger transcription factor sensitive to proton rhizotoxicity 1 (STOP1) regulates root SCN identity by negative feedback of auxin signaling in root tips. Mutation and overexpression of STOP1 both affect QC cell division and distal stem cell differentiation in the root. We find that auxin treatment stabilizes STOP1 via MPK3/6-dependent phosphorylation. Accumulating STOP1 can compete with AUX/IAAs to interact with, and enhance the repressive activity of, auxin-repressive response factor ARF2. Overall, we show that the MPK3/6-STOP1-ARF2 module prevents excessive auxin signaling in the presence of auxin to maintain root SCN identity.

Density Functional Theory Investigation of the Sulfur-Iron Compound Formation Mechanism in Petrochemical Facilities.

In order to investigate the formation mechanism of hydrogen sulfide corrosion products in petroleum and petrochemical facilities, the interaction mechanism between iron oxides and H2S was studied by density functional theory (DFT). First, the adsorption of H2S on Fe2O3 clusters and Fe3O4 clusters was studied. The results indicated that H2S was more inclined to adsorb on the Fe site. After adsorption, the S-H bond changed from 1.356 to 1.360 Å in the gas phase, which was the main reason for the decomposition of H2S. On this basis, the reaction paths of Fe2O3 clusters and Fe3O4 clusters with H2S and the rate-determining steps of different reaction paths were calculated. The thermodynamic parameters and kinetic parameters of the rate-determining step of each path are analyzed. The results indicated that reaction path 1 of H2S and Fe2O3 clusters is the best reaction channel. The reaction will gradually form products such as S, H2O, and Fe2S2, which can release a total of 622.23 kJ/mol heat. The reaction path 2 of H2S and Fe3O4 clusters is the best reaction channel. The reaction will gradually form products such as S, H2O, and Fe3S2, which can release a total of 260.40 kJ/mol heat. Finally, the reaction paths of Fe2S2, Fe3S2, and S2 were further calculated, and it was observed that the products formed by hydrogen sulfide corrosion were easy to react with S2 to form sulfur-iron compounds with different iron-sulfur ratios. This is consistent with the corrosion products including FeS, FeS2, and Fe3S4 observed in the experiment. It lays a theoretical foundation for the subsequent study of the effect of associated elemental sulfur on the spontaneous combustion of sulfur-iron compounds.

Engineering extracellular vesicles with macrophage membrane fusion for ameliorating imiquimod-induced psoriatic skin inflammation.

INTRODUCTION: Herein, we developed an engineered extracellular vehicle (EV)-based method for ameliorating inflammatory responses in psoriasis. METHODS: EVs, derived from annexin A1 (ANXA1) overexpressing T cells, were co-extruded with M2 macrophage membrane to obtain engineered EVs. In vitro, the effect of engineered EVs on macrophage polarization was evaluated by real-time PCR. In imiquimod (IMQ)-induced psoriasis-like mouse model, the efficacy of engineered EVs in ameliorating psoriatic inflammation was evaluated by Psoriasis Area and Severity Index (PASI) score and immunohistochemistry staining after subcutaneous injection of EVs. RESULTS: The engineered EVs not only preserved the high stability of M2 macrophage membrane but also retained the macrophage reprogramming potential of ANXA1 overexpressed in T cells. In the psoriasis-like mouse model, subcutaneous injection of engineered EVs successfully reduced the PASI score and the levels of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Along with high biosafety, the administration of EVs also rescued the histomorphological changes of spleen, liver, and kidney. CONCLUSIONS: The engineered EVs exhibited the potential to alleviate inflammation of psoriasis, providing new insights and potential strategies for the immunotherapies of psoriasis.

Robotic-Assisted Proctosigmoidectomy vs. Laparoscopic-Assisted Soave Pull-Through for Hirschsprung's Disease: Medium-Term Outcomes From a Prospective Multicenter Study.

OBJECTIVE: To compare the surgical outcomes of robotic-assisted proctosigmoidectomy (RAP) and laparoscopic-assisted Soave pull-through (LAP) for children with Hirschsprung's disease (HD). SUMMARY BACKGROUND DATA: LAP and RAP have been developed for minimally invasive pull-through of HD, but the clinical benefits of robotic-assisted versus laparoscopic-assisted approaches have yet to be proven in a multicenter prospective study. METHODS: This study was a prospective multicenter clinical trial conducted on children with rectosigmoid/descending HD from July 2015 to June 2022, with registration in the Chinese Clinical Trial Registry (ChiCTR2000035220). The primary outcome was the medium-term functional outcomes in children aged ≥4 years based on bowel functional scores, which were assessed and compared between LAP and RAP. RESULTS: A total of 328 consecutive patients (RAP=165, LAP=163) were approached who were considered eligible for elective minimally invasive endorectal pull-through, and 219 patients aged ≥4 years of age completed follow-up (RAP=109, LAP=110). The transanal dissection length and anal traction time were significantly shorter in RAP than those in LAP (0.30 cm vs. 3.70 cm, P <0.001; 45 min vs. 62 min, P <0.001). The RAP group had significantly lower urinary retention rate (0% vs. 5.52%, P=0.006), while other short-term results between two groups were not significantly different. The medium-term overall BFS scores were comparable between two groups; however, among the subgroup of children aged ≤ 3 months at surgery, the RAP group had better anal canal resting pressure at one year postoperatively and amounted to better annual POFC scores at 4-7 years old postoperatively (all P <0.05). CONCLUSIONS: RAP and LAP should have similar medium-term bowel functional outcomes in HD children, but RAP may be associated with a slight functional benefit in infants operated on below age 3 months, requiring further investigation in larger case cohorts.

Laparoscopic lateral duodenojejunostomy for pediatric superior mesenteric artery compression syndrome: a cohort retrospective study.

PURPOSE: There are only a few case reports of laparoscopic lateral duodenojejunostomy (LLDJ) in children with Wilkie's syndrome, also known as superior mesenteric artery compression syndrome (SMAS). We aimed to describe our laparoscopic technique and evaluate its outcomes for SMAS in children. METHODS: From January 2013 to May 2021, SMAS children who received LLDJ were included. The procedure was carried out utilizing the four-trocar technique. The elevation of the transverse colon allows good exposure of the dilated and bulging second and third sections of the duodenum. Using a linear stapler, we established a lateral anastomosis connecting the proximal jejunum with the third part of the duodenum. Following that, a running suture was used to intracorporeally close the common enterotomy. Clinical data on patients was collected for analysis. The demographics, diagnostic findings, and postoperative outcomes were analyzed retrospectively. RESULTS: We retrospectively analyzed 9 SMAS patients (6 females and 3 males) who underwent LLDJ, aged between 7 and 17 years old. The mean operative time was 118.4 ± 16.5 min and the mean estimated blood loss was 5.6 ± 1.4 ml. There were no conversion, intraoperative complications or immediate postoperative complications. The mean postoperative hospital stay was 6.8 ± 1.9 days and the mean follow-up time was 5.4 ± 3.0 years. During follow-up, seven patients (77.8%) experienced complete recovery of symptoms prior to surgery. One patient (11.1%) still had mild vomiting, which resolved with medication. Another patient (11.1%) developed psychological-induced nausea, which significantly improved after treatment with education, training and diet management. CONCLUSIONS: LLDJ represents a feasible and safe treatment option for SMAS in well-selected children. Further evaluation with more cases and case-control studies is required for the real benefits.

A Rare Case of Synchronous Fumarate Hydratase-Deficient Renal Cell Carcinoma and Clear Cell Renal Cell Carcinoma With Fumarate Hydratase and von Hippel-Lindau Gene Mutations: A Clinicopathologic and Molecular Study.

Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and aggressive tumor characterized by pathogenic alterations in the fumarate hydratase (FH) gene. Clear cell renal cell carcinoma (clear cell RCC) is a common renal cell carcinoma (RCC) associated with von Hippel-Lindau (VHL) gene variations. Here, we reported a case of bilateral RCCs. A 60-year-old man was admitted to hospital with a 3.6 cm × 3.3 cm mass in the right kidney and a 2.8 cm × 2.3 cm nodule in the left kidney. Pathologically, the right tumor showed a nested growth pattern of cells with clear cytoplasm and was FH positive and 2-succinylcysteine (2SC) negative. The left tumor demonstrated a high-grade papillary pattern and was FH negative and 2SC positive. Whole-exome sequencing and Sanger sequencing identified a germline FH c.563A > T mutation in both the tumors and an additional somatic VHL c.479_480insA mutation in the right tumor, confirming the diagnosis of clear cell RCC and FH-deficient RCC in the right and left kidneys, respectively. We reported a rare case of synchronous bilateral clear cell RCC (right) and FH-deficient RCC (left) likely driven by somatic VHL mutation and germline FH mutation, respectively.

AKR1B10 Is a New Sensitive and Specific Marker for Fumarate Hydratase-Deficient Renal Cell Carcinoma.

Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare and distinct subtype of renal cancer caused by FH gene mutations. FH negativity and s-2-succinocysteine (2SC) positivity on immunohistochemistry can be used to screen for FH-deficient RCC, but their sensitivity and specificity are not perfect. The expression of AKR1B10, an aldo-keto reductase that catalyzes cofactor-dependent oxidation-reduction reactions, in RCC is unclear. We compared AKR1B10, 2SC, and FH as diagnostic biomarkers for FH-deficient RCC. We included genetically confirmed FH-deficient RCCs (n = 58), genetically confirmed TFE3 translocation RCCs (TFE3-tRCC) (n = 83), clear cell RCCs (n = 188), chromophobe RCCs (n = 128), and papillary RCCs (pRCC) (n = 97). AKR1B10, 2SC, and FH were informative diagnostic markers. AKR1B10 had 100% sensitivity and 91.4% specificity for FH-deficient RCC. The nonspecificity of AKR1B10 was shown in 26.5% of TFE3-tRCCs and 21.6% of pRCCs. 2SC showed 100% sensitivity and 88.9% specificity. However, nonspecificity for 2SC was evident in multiple RCCs, including pRCC, TFE3-tRCC, clear cell RCCs, and chromophobe RCCs. FH was 100% specific but 84.5% sensitive. AKR1B10 served as a highly sensitive and specific diagnostic biomarker. Our findings suggest the value of combining AKR1B10 and 2SC to screen for FH-deficient RCC. AKR1B10+/2SC+/FH- cases can be diagnosed as FH-deficient RCC. Patients with AKR1B10+/2SC+/FH+ are highly suspicious of FH-deficient RCC and should be referred for FH genetic tests.

Robotic-assisted proctosigmoidectomy for Hirschsprung's disease: A multicenter prospective study.

BACKGROUND: Robotic surgery is a cutting-edge minimally invasive technique that overcomes many shortcomings of laparoscopic techniques, yet few studies have evaluated the use of robotic surgery to treat Hirschsprung's disease (HSCR). AIM: To analyze the feasibility and medium-term outcomes of robotic-assisted proctosigmoidectomy (RAPS) with sphincter- and nerve-sparing surgery in HSCR patients. METHODS: From July 2015 to January 2022, 156 rectosigmoid HSCR patients were enrolled in this multicenter prospective study. Their sphincters and nerves were spared by dissecting the rectum completely from the pelvic cavity outside the longitudinal muscle of the rectum and then performing transanal Soave pull-through procedures. Surgical outcomes and continence function were analyzed. RESULTS: No conversions or intraoperative complications occurred. The median age at surgery was 9.50 months, and the length of the removed bowel was 15.50 ± 5.23 cm. The total operation time, console time, and anal traction time were 155.22 ± 16.77, 58.01 ± 7.71, and 45.28 ± 8.15 min. There were 25 complications within 30 d and 48 post-30-d complications. For children aged ≥ 4 years, the bowel function score (BFS) was 17.32 ± 2.63, and 90.91% of patients showed moderate-to-good bowel function. The postoperative fecal continence (POFC) score was 10.95 ± 1.04 at 4 years of age, 11.48 ± 0.72 at 5 years of age, and 11.94 ± 0.81 at 6 years of age, showing a promising annual trend. There were no significant differences in postoperative complications, BFS, and POFC scores related to age at surgery being ≤ 3 mo or > 3 mo. CONCLUSION: RAPS is a safe and effective alternative for treating HSCR in children of all ages; it offers the advantage of further minimizing damage to sphincters and perirectal nerves and thus providing better continence function.

The interplay of common genetic variants NRG1 rs2439302 and RET rs2435357 increases the risk of developing Hirschsprung's disease.

Introduction: As a congenital and genetically related disease, many single nucleotide polymorphisms (SNPs) have been reported to be associated with the risk of HSCR. Our previous research showed that SNP rs2439302 (NRG1) interacted with rs2435357 (RET) to increase the risk of HSCR development. However, the underlying molecular mechanism is still not well understood. Methods: SNP rs2439302 (NRG1) and rs2435357 (RET) were genotyped in 470 HSCR cases. The expression of NRG1 and RET was investigated in the colon of HSCR patients. Knockdown of the NRG1 and RET homologs was performed in zebrafish to investigate their synergistic effect on ENS development. The effect of SNP rs2439302 and rs2435357 polymorphism on neuron proliferation, migration, and differentiation were investigated in SHSY-5Y cells and IPSCs. Results: Significant downregulation of NRG1 and RET expression was noticed in the aganglionic segment of HSCR patients and SHSY-5Y cells with rs2439302 GG/rs2435357 TT genotype. NRG1 and RET double mutants caused the most severe reduction in enteric neuron numbers than NRG1 single mutant or RET single mutant in the hindgut of zebrafish. SHSY-5Y cells and IPSCs with rs2439302 GG/rs2435357 TT genotype exhibited a decreased proliferative, migration, and differentiative capacity. CTCF showed a considerably higher binding ability to SNP rs2439302 CC than GG. NRG1 reduction caused a further decrease in SOX10 expression via the PI3K/Akt pathway, which regulates RET expression by directly binding to rs2435357. Discussion: SNP rs2439302 (NRG1) GG increases the risk of developing HSCR by affecting the binding of transcription factor CTCF and interacting with rs2435357 (RET) to regulate RET expression via the PI3K/Akt/SOX10 pathway.

Auxin promotes hypocotyl elongation by enhancing BZR1 nuclear accumulation in Arabidopsis.

Auxin and brassinosteroids (BRs) are two major growth-promoting phytohormones that shape hypocotyl elongation; however, the cross-talk between auxin and BR in this process is not fully understood. In this study, we found that auxin-induced hypocotyl elongation is dependent on brassinazole-resistant 1 (BZR1), a core BR signaling component. Auxin promotes BZR1 nuclear accumulation in hypocotyl cells, a process dependent on mitogen-activated protein kinase 3 (MPK3) and MPK6, which are both activated by auxin and whose encoding genes are highly expressed in hypocotyls. We determined that MPK3/MPK6 phosphorylate and reduce the protein stability of general regulatory factor 4 (GRF4), a member of the 14-3-3 family of proteins that retain BZR1 in the cytoplasm. In summary, this study reveals the molecular mechanism by which auxin promotes hypocotyl elongation by enhancing BZR1 nuclear accumulation via MPK3/MPK6-regulated GRF4 protein stability.