Crosstalk between KCNK3-Mediated Ion Current and Adrenergic Signaling Regulates Adipose Thermogenesis and Obesity.

Adrenergic stimulation promotes lipid mobilization and oxidation in brown and beige adipocytes, where the harnessed energy is dissipated as heat in a process known as adaptive thermogenesis. The signaling cascades and energy-dissipating pathways that facilitate thermogenesis have been extensively described, yet little is known about the counterbalancing negative regulatory mechanisms. Here, we identify a two-pore-domain potassium channel, KCNK3, as a built-in rheostat negatively regulating thermogenesis. Kcnk3 is transcriptionally wired into the thermogenic program by PRDM16, a master regulator of thermogenesis. KCNK3 antagonizes norepinephrine-induced membrane depolarization by promoting potassium efflux in brown adipocytes. This limits calcium influx through voltage-dependent calcium channels and dampens adrenergic signaling, thereby attenuating lipolysis and thermogenic respiration. Adipose-specific Kcnk3 knockout mice display increased energy expenditure and are resistant to hypothermia and obesity. These findings uncover a critical K+-Ca2+-adrenergic signaling axis that acts to dampen thermogenesis, maintain tissue homeostasis, and reveal an electrophysiological regulatory mechanism of adipocyte function.

Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch.

A clear relationship exists between visceral obesity and type 2 diabetes, whereas subcutaneous obesity is comparatively benign. Here, we show that adipocyte-specific deletion of the coregulatory protein PRDM16 caused minimal effects on classical brown fat but markedly inhibited beige adipocyte function in subcutaneous fat following cold exposure or ß3-agonist treatment. These animals developed obesity on a high-fat diet, with severe insulin resistance and hepatic steatosis. They also showed altered fat distribution with markedly increased subcutaneous adiposity. Subcutaneous adipose tissue in mutant mice acquired many key properties of visceral fat, including decreased thermogenic and increased inflammatory gene expression and increased macrophage accumulation. Transplantation of subcutaneous fat into mice with diet-induced obesity showed a loss of metabolic benefit when tissues were derived from PRDM16 mutant animals. These findings indicate that PRDM16 and beige adipocytes are required for the "browning" of white fat and the healthful effects of subcutaneous adipose tissue.

Mitochondrial TNAP controls thermogenesis by hydrolysis of phosphocreatine.

Adaptive thermogenesis has attracted much attention because of its ability to increase systemic energy expenditure and to counter obesity and diabetes1-3. Recent data have indicated that thermogenic fat cells use creatine to stimulate futile substrate cycling, dissipating chemical energy as heat4,5. This model was based on the super-stoichiometric relationship between the amount of creatine added to mitochondria and the quantity of oxygen consumed. Here we provide direct evidence for the molecular basis of this futile creatine cycling activity in mice. Thermogenic fat cells have robust phosphocreatine phosphatase activity, which is attributed to tissue-nonspecific alkaline phosphatase (TNAP). TNAP hydrolyses phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation. Unlike in other cells, TNAP in thermogenic fat cells is localized to the mitochondria, where futile creatine cycling occurs. TNAP expression is powerfully induced when mice are exposed to cold conditions, and its inhibition in isolated mitochondria leads to a loss of futile creatine cycling. In addition, genetic ablation of TNAP in adipocytes reduces whole-body energy expenditure and leads to rapid-onset obesity in mice, with no change in movement or feeding behaviour. These data illustrate the critical role of TNAP as a phosphocreatine phosphatase in the futile creatine cycle.

γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis.

The sympathetic nervous system innervates peripheral organs to regulate their function and maintain homeostasis, whereas target cells also produce neurotrophic factors to promote sympathetic innervation1,2. The molecular basis of this bi-directional communication remains to be fully determined. Here we use thermogenic adipose tissue from mice as a model system to show that T cells, specifically γδ T cells, have a crucial role in promoting sympathetic innervation, at least in part by driving the expression of TGFß1 in parenchymal cells via the IL-17 receptor C (IL-17RC). Ablation of IL-17RC specifically in adipose tissue reduces expression of TGFß1 in adipocytes, impairs local sympathetic innervation and causes obesity and other metabolic phenotypes that are consistent with defective thermogenesis; innervation can be fully rescued by restoring TGFß1 expression. Ablating γδ Τ cells and the IL-17RC signalling pathway also impairs sympathetic innervation in other tissues such as salivary glands. These findings demonstrate coordination between T cells and parenchymal cells to regulate sympathetic innervation.

Blockade of a novel MAP4K4-LATS2-SASH1-YAP1 cascade inhibits tumorigenesis and metastasis in luminal breast cancer.

Novel components in the noncanonical Hippo pathway that mediate the growth, metastasis, and drug resistance of breast cancer (BC) cells need to be identified. Here, we showed that expression of SAM and SH3 domain-containing protein 1 (SASH1) is negatively correlated with expression of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) in a subpopulation of patients with luminal-subtype BC. Downregulated SASH1 and upregulated MAP4K4 synergistically regulated the proliferation, migration, and invasion of luminal-subtype BC cells. The expression of LATS2, SASH1, and YAP1 and the phosphorylation of YAP1 were negatively regulated by MAP4K4, and LATS2 then phosphorylated SASH1 to form a novel MAP4K4-LATS2-SASH1-YAP1 cascade. Dephosphorylation of Yes1 associated transcriptional regulator (YAP1), YAP1/TAZ nuclear translocation, and downstream transcriptional regulation of YAP1 were promoted by the combined effects of ectopic MAP4K4 expression and SASH1 silencing. Targeted inhibition of MAP4K4 blocked proliferation, cell migration, and ER signaling both in vitro and in vivo. Our findings reveal a novel MAP4K4-LATS2-SASH1-YAP1 phosphorylation cascade, a noncanonical Hippo pathway that mediates ER signaling, tumorigenesis, and metastasis in breast cancer. Targeted intervention with this noncanonical Hippo pathway may constitute a novel alternative therapeutic approach for endocrine-resistant BC.

Innervation of thermogenic adipose tissue via a calsyntenin 3ß-S100b axis.

The sympathetic nervous system drives brown and beige adipocyte thermogenesis through the release of noradrenaline from local axons. However, the molecular basis of higher levels of sympathetic innervation of thermogenic fat, compared to white fat, has remained unknown. Here we show that thermogenic adipocytes express a previously unknown, mammal-specific protein of the endoplasmic reticulum that we term calsyntenin 3ß. Genetic loss or gain of expression of calsyntenin 3ß in adipocytes reduces or enhances functional sympathetic innervation, respectively, in adipose tissue. Ablation of calsyntenin 3ß predisposes mice on a high-fat diet to obesity. Mechanistically, calsyntenin 3ß promotes endoplasmic-reticulum localization and secretion of S100b-a protein that lacks a signal peptide-from brown adipocytes. S100b stimulates neurite outgrowth from sympathetic neurons in vitro. A deficiency of S100b phenocopies deficiency of calsyntenin 3ß, and forced expression of S100b in brown adipocytes rescues the defective sympathetic innervation that is caused by ablation of calsyntenin 3ß. Our data reveal a mammal-specific mechanism of communication between thermogenic adipocytes and sympathetic neurons.

Publisher Correction: Innervation of thermogenic adipose tissue via a calsyntenin 3ß-S100b axis.

In Fig. 6a of this Article, the two dots corresponding to Cidea and S100b were erroneously moved to the top left of the volcano plot; this figure has been corrected online.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Auxiliary-cavity-enhanced quantum estimation of optorotational-coupling strength.

A scheme is proposed to achieve significantly enhanced quantum estimation of optorotational-coupling (ORC) strength by coupling a driven auxiliary cavity to a Laguerre-Gaussian (L-G) rotational cavity, where the ORC originates from the exchange of orbital angular momentum between a L-G light and rotational mirror. The results indicate that, by appropriately designing the auxiliary-cavity mechanism, the estimation error of the ORC parameter is significantly reduced, and revealing the estimation precision has a much stronger thermal noise and dissipation robustness in comparison with the unassisted case. Our study paves the way toward achieving high-precision quantum sensors.

Lysine-specific demethylase 1 promotes brown adipose tissue thermogenesis via repressing glucocorticoid activation.

Brown adipocytes display phenotypic plasticity, as they can switch between the active states of fatty acid oxidation and energy dissipation versus a more dormant state. Cold exposure or ß-adrenergic stimulation favors the active thermogenic state, whereas sympathetic denervation or glucocorticoid administration promotes more lipid accumulation. Our understanding of the molecular mechanisms underlying these switches is incomplete. Here we found that LSD1 (lysine-specific demethylase 1), a histone demethylase, regulates brown adipocyte metabolism in two ways. On the one hand, LSD1 associates with PRDM16 to repress expression of white fat-selective genes. On the other hand, LSD1 represses HSD11B1 (hydroxysteroid 11-ß-dehydrogenase isozyme 1), a key glucocorticoid-activating enzyme, independently from PRDM16. Adipose-specific ablation of LSD1 impaired mitochondrial fatty acid oxidation capacity of the brown adipose tissue, reduced whole-body energy expenditure, and increased fat deposition, which can be significantly alleviated by simultaneously deleting HSD11B1. These findings establish a novel regulatory pathway connecting histone modification and hormone activation with mitochondrial oxidative capacity and whole-body energy homeostasis.

Homogeneous Polyporus polysaccharide exerts anti-bladder cancer effects via autophagy induction.

CONTEXT: Polyporus polysaccharide (PPS), the leading bioactive ingredient extracted from Polyporus umbellatus (Pers.) Fr. (Polyporaceae), has been demonstrated to exert anti-bladder cancer and immunomodulatory functions in macrophages. OBJECTIVE: To explore the effects of homogeneous Polyporus polysaccharide (HPP) on the proliferation and autophagy of bladder cancer cells co-cultured with macrophages. MATERIALS AND METHODS: MB49 bladder cancer cells and RAW264.7 macrophages were co-cultured with or without HPP intervention (50, 100, or 200 µg/mL) for 24 h. The cell counting kit-8 (CCK-8) assay and 5-ethynyl-2″-deoxyuridine (EdU) staining evaluated MB49 cell proliferation. Monodansylcadaverine (MDC) staining and transmission electron microscopy (TEM) observed autophagosomes. Western blotting detected the expression levels of autophagy-related proteins and PI3K/Akt/mTOR pathway proteins. RESULTS: HPP inhibited the proliferation of MB49 cells co-cultured with RAW264.7 cells but not MB49 cells alone. HPP altered the expression of autophagy-related proteins and promoted the formation of autophagosomes in MB49 cells in the co-culture system. Autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) not only antagonized HPP-induced autophagy but also attenuated the inhibitory effects of HPP on MB49 cell proliferation in the co-culture system. HPP or RAW264.7 alone was not sufficient to induce autophagy in MB49 cells. In addition, HPP suppressed the protein expression of the PI3K/Akt/mTOR pathway in MB49 cells in the co-culture system. DISCUSSION AND CONCLUSIONS: HPP induced bladder cancer cell autophagy by regulating macrophages in the co-culture system, resulting in the inhibition of cancer cell proliferation. The PI3K/Akt/mTOR pathway was involved in HPP-induced autophagy in the co-culture system.

Metabolic classifications of renal cell carcinoma reveal intrinsic connections with clinical and immune characteristics.

BACKGROUND: Kidney cancer undergoes a dramatic metabolic shift and has demonstrated responsiveness to immunotherapeutic intervention. However, metabolic classification and the associations between metabolic alterations and immune infiltration in Renal cell carcinoma still remain elucidative. METHODS: Unsupervised consensus clustering was conducted on the TCGA cohorts for metabolic classification. GESA, mRNAsi, prognosis, clinical features, mutation load, immune infiltration and differentially expressed gene differences among different clusters were compared. The prognosis model and nomograms were constructed based on metabolic gene signatures and verified using external ICGC datasets. Immunohistochemical results from Human Protein Atlas database and Tongji hospital were used to validate gene expression levels in normal tissues and tumor samples. CCK8, apoptosis analysis, qPCR, subcutaneously implanted murine models and flowcytometry analysis were applied to investigate the roles of ACAA2 in tumor progression and anti-tumor immunity. RESULTS: Renal cell carcinoma was classified into 3 metabolic subclusters and the subcluster with low metabolic profiles displayed the poorest prognosis, highest invasiveness and AJCC grade, enhanced immune infiltration but suppressive immunophenotypes. ACAA2, ACAT1, ASRGL1, AKR1B10, ABCC2, ANGPTL4 were identified to construct the 6 gene-signature prognosis model and verified both internally and externally with ICGC cohorts. ACAA2 was demonstrated as a tumor suppressor and was associated with higher immune infiltration and elevated PD-1 expression of CD8+ T cells. CONCLUSIONS: Our research proposed a new metabolic classification method for RCC and revealed intrinsic associations between metabolic phenotypes and immune profiles. The identified gene signatures might serve as key factors bridging tumor metabolism and tumor immunity and warrant further in-depth investigations.

Development of a Perioperative Enteral Nutrition Program for Gastric Cancer Surgery.

Objective: This study aimed to summarize the current evidence-based approach to perioperative enteral nutritional (EN) program for gastric cancer (GC) surgery and to develop a staged and operable EN management scheme based on the evidence to provide clinical guidance for improving perioperative EN management in patients with GC.Methods: First, we synthesized expert consensuses, systematic reviews, and guidelines related to GC patients who had undergone surgery, based on a review of the literature and expert meetings. Subsequently, after carefully evaluating and selecting relevant EN management data, we created a preliminary draft of a perioperative EN program. Following Delphi expert consultations, the final version of the perioperative EN program was constructed after revision.Results: After two rounds of consultation, the expert opinions tended to be consistent. The expert positive coefficient was 1.00, and the expert authority coefficient was 0.90. After the second round of consultation, the coefficient of variation of the importance score ranged from 0.05 to 0.20, and the coefficient of variation of the feasibility score ranged from 0.09 to 0.23. The Kendall harmony coefficients were 0.338 and 0.392, and the difference between them was statistically significant (p < 0.001). The final practice plan includes 4 first-level, 16 s-level, and 64 third-level items.Conclusions: The perioperative EN program constructed in this study is comprehensive in content, feasible, and evidence-based, and can provide insights for clinical improvement.

Construction of Chiral Cyclobutanone-Fused 4-Aminoquinolines via Sequential Chiral Phosphoric Acid and Palladium Catalysis.

A one-pot catalytic asymmetric route to novel chiral quaternary-carbon-containing cyclobutanone-fused 4-aminoquinoline derivatives in good to high yields and enantioselectivities is described. This process consists of a chiral phosphoric acid-catalyzed desymmetric carbonyl-amine condensation of prochiral cyclobutane-1,3-diones with 2-halogenated anilines and a Pd-catalyzed coupling reaction of the chiral enaminone intermediates with isocyanides.

Synthesis of α-allenic aldehydes/ketones from homopropargylic alcohols using a visible-light irradiation system.

A visible-light irradiation tandem oxidative aryl migration/carbonyl formation reaction, mediated by K2S2O8 and visible-light photoredox catalysis, has been discovered. The presented transformation provides a straightforward access to important α-allenic aldehyde/ketone derivatives from readily available homopropargylic alcohol derivatives in a regioselective manner of 1,4-aryl shift concomitant with carbonyl formation. The operational simplicity and broad substrate scope demonstrate the great potential of this method for the synthesis of highly functional α-allenic aldehyde/ketone derivatives.

The Transcription Factor ZmNAC89 Gene Is Involved in Salt Tolerance in Maize (Zea mays L.).

The NAC gene family has transcription factors specific to plants, which are involved in development and stress response and adaptation. In this study, ZmNAC89, an NAC gene in maize that plays a role in saline-alkaline tolerance, was isolated and characterized. ZmNAC89 was localized in the nucleus and had transcriptional activation activity during in vitro experiments. The expression of ZmNAC89 was strongly upregulated under saline-alkaline, drought and ABA treatments. Overexpression of the ZmNAC89 gene in transgenic Arabidopsis and maize enhanced salt tolerance at the seedling stage. Differentially expressed genes (DEGs) were then confirmed via RNA-sequencing analysis with the transgenic maize line. GO analyses showed that oxidation-reduction process-regulated genes were involved in ZmNAC89-mediated salt-alkaline stress. ZmNAC89 may regulate maize saline-alkali tolerance through the REDOX pathway and ABA signal transduction pathway. From 140 inbred maize lines, 20 haplotypes and 16 SNPs were found in the coding region of the ZmNAC89 gene, including the excellent haplotype HAP20. These results contribute to a better understanding of the response mechanism of maize to salt-alkali stress and marker-assisted selection during maize breeding.

Gu-Ben-Hua-Shi (AESS) formula ameliorates atopic dermatitis via regulating NLRP3 signaling pathways.

Background: Gu-ben-hua-shi (AESS) formula is a clinical experienced prescription from Guangdong Hospital of Traditional Chinese Medicine (TCM), which is used to treat atopic dermatitis (AD). Our previous work has shown that AESS has therapeutic effect on AD by regulating yes-associated protein (YAP). AESS formula has multi-component and multi-target characteristic, and need to be analyzed by systematic chemical profiling and network pharmacology technology, as well as verification of key signaling pathways. Therefore, this study aimed at investigating the efficacy and effect of AESS formula in the treatment of AD and its effect on NLRP3 signaling pathway. Methods: The components of AESS formula were analyzed and identified by ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC- MS/MS), and the potential mechanism of AESS formula in the treatment of AD was predicted by network pharmacology approach, with detected main components, and the potential components targeted NOD-like receptor thermal protein domain associated protein (NLRP3) signaling pathway [Direct binding with NLRP3, apoptosis-associated speck-like protein (ASC) and Caspase-1] were assessed using molecular docking. AD-like symptoms were constructed by DNCB induced BALB/c mice. The effect of AESS formula on dorsal skin structure in AD-like mice was observed using H&E staining. Furthermore, the western blotting experiment explored the expression of the NLRP3 pathway protein. Results: By UHPLC-MS/MS analysis, 91 compounds were detected in AESS formula, and 76 of them were identified, while by network pharmacological analysis, 1500 component targets were obtained, and 257 of them were obtained by intersection with eczema targets. Then one of the key pathways, nucleotide-binding oligomerization domain (NOD)-like signaling pathway was obtained by KEGG enrichment analysis. Molecular docking results showed 24 main components could effectively combine with ASC and Caspase-1 (≤-7 kcal/mol). The animal experiment results further showed that AESS formula alleviates symptoms in AD-like mice. ELISA kit results showed that the expression of IL-1ß and IL-18 in serum was inhibited after AESS treatment. Additionally, western blotting analysis showed that the expressions of ASC, Caspase-1 and NLRP3 protein expression in the skin tissue of mice were down-regulated after AESS treatment. The experimental results show that AESS formula inhibited the expression of NLRP3 signaling pathway for the treatment of AD. Conclusions: AESS formula can improve AD symptoms in mice by inhibiting the activation of NLRP3 inflammasome and the expression of the related downstream inflammatory cytokines.

Development and Validation of Multiparametric MRI-based Radiomics Models for Preoperative Risk Stratification of Endometrial Cancer.

Background Stratifying high-risk histopathologic features in endometrial carcinoma is important for treatment planning. Radiomics analysis at preoperative MRI holds potential to identify high-risk phenotypes. Purpose To evaluate the performance of multiparametric MRI three-dimensional radiomics-based machine learning models for differentiating low- from high-risk histopathologic markers-deep myometrial invasion (MI), lymphovascular space invasion (LVSI), and high-grade status-and advanced-stage endometrial carcinoma. Materials and Methods This dual-center retrospective study included women with histologically proven endometrial carcinoma who underwent 1.5-T MRI before hysterectomy between January 2011 and July 2015. Exclusion criteria were tumor diameter less than 1 cm, missing MRI sequences or histopathology reports, neoadjuvant therapy, and malignant neoplasms other than endometrial carcinoma. Three-dimensional radiomics features were extracted after tumor segmentation at MRI (T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI). Predictive features were selected in the training set with use of random forest (RF) models for each end point, and trained RF models were applied to the external test set. Five board-certified radiologists conducted MRI-based staging and deep MI assessment in the training set. Areas under the receiver operating characteristic curve (AUCs) were reported with balanced accuracies, and radiologists' readings were compared with radiomics with use of McNemar tests. Results In total, 157 women were included: 94 at the first institution (training set; mean age, 66 years ± 11 [SD]) and 63 at the second institution (test set; 67 years ± 12). RF models dichotomizing deep MI, LVSI, high grade, and International Federation of Gynecology and Obstetrics (FIGO) stage led to AUCs of 0.81 (95% CI: 0.68, 0.88), 0.80 (95% CI: 0.67, 0.93), 0.74 (95% CI: 0.61, 0.86), and 0.84 (95% CI: 0.72, 0.92), respectively, in the test set. In the training set, radiomics provided increased performance compared with radiologists' readings for identifying deep MI (balanced accuracy, 86% vs 79%; P = .03), while no evidence of a difference was observed in performance for advanced FIGO stage (80% vs 78%; P = .27). Conclusion Three-dimensional radiomics can stratify patients by using preoperative MRI according to high-risk histopathologic end points in endometrial carcinoma and provide nonsignificantly different or higher performance than radiologists in identifying advanced stage and deep myometrial invasion, respectively. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kido and Nishio in this issue.

Netrin-1 induces the anti-apoptotic and pro-survival effects of B-ALL cells through the Unc5b-MAPK axis.

BACKGROUND: B-cell acute lymphoblastic leukemia (B-ALL) comprises over 85% of all acute lymphoblastic leukemia (ALL) cases and is the most common childhood malignancy. Although the 5 year overall survival of patients with B-ALL exceeds 90%, patients with relapsed or refractory B-ALL may suffer from poor prognosis and adverse events. The axon guidance factor netrin-1 has been reported to be involved in the tumorigenesis of many types of cancers. However, the impact of netrin-1 on B-ALL remains unknown. METHODS: The expression level of netrin-1 in peripheral blood samples of children with B-ALL and children without neoplasia was measured by enzyme-linked immunosorbent assay (ELISA) kits. Then, CCK-8 cell proliferation assays and flow cytometric analysis were performed to detect the viability and apoptosis of B-ALL cells (Reh and Sup B15) treated with exogenous recombinant netrin-1 at concentrations of 0, 25, 50, and 100 ng/ml. Furthermore, co-immunoprecipitation(co-IP) was performed to detect the receptor of netrin-1. UNC5B expression interference was induced in B-ALL cells with recombinant lentivirus, and then CCK-8 assays, flow cytometry assays and western blotting assays were performed to verify that netrin-1 might act on B-ALL cells via the receptor Unc5b. Finally, western blotting and kinase inhibitor treatment were applied to detect the downstream signaling pathway. RESULTS: Netrin-1 expression was increased in B-ALL, and netrin-1 expression was upregulated in patients with high- and intermediate-risk stratification group of patients. Then, we found that netrin-1 induced an anti-apoptotic effect in B-ALL cells, implying that netrin-1 plays an oncogenic role in B-ALL. co-IP results showed that netrin-1 interacted with the receptor Unc5b in B-ALL cells. Interference with UNC5B was performed in B-ALL cells and abolished the antiapoptotic effects of netrin-1. Further western blotting was applied to detect the phosphorylation levels of key molecules in common signaling transduction pathways in B-ALL cells treated with recombinant netrin-1, and the FAK-MAPK signaling pathway was found to be activated. The anti-apoptotic effect of netrin-1 and FAK-MAPK phosphorylation was abrogated by UNC5B interference. FAK inhibitor treatment and ERK inhibitor treatment were applied and verified that the FAK-MAPK pathway may be downstream of Unc5b. CONCLUSION: Taken together, our findings suggested that netrin-1 induced the anti-apoptotic effect of B-ALL cells through activation of the FAK-MAPK signaling pathway by binding to the receptor Unc5b. Video Abstract.

Combined QTL mapping and RNA-Seq pro-filing reveal candidate genes related to low-temperature tolerance in maize.

Maize (Zea mays L.) is the most important food crop in the world, with significant acreage and production across the globe. However, it is affected by low temperatures throughout its growth process, especially during germination. Therefore, it is important to identify more QTLs or genes associated with germination under low-temperature conditions. For the QTL analysis of traits related to low-temperature germination, we used a high-res genetic map of 213 lines of the intermated B73 × Mo17 (IBM) Syn10 doubled haploid (DH) population, which had 6618 bin markers. We detected 28 QTLs of eight phenotypic characteristics associated with low-temperature germination, while they explained the phenotypic contribution rate of 5.4 ~ 13.34%. Additionally, 14 overlapping QTLs produced six QTL clusters on every chromosome, except for 8 and 10. RNA-Seq found six genes related to low-temperature tolerance in these QTLs, while qRT-PCR analysis demonstrated that the expression trends of the Zm00001d045568 gene in the LT_BvsLT_M group and the CK_BvsCK_M group were highly significantly different at all four-time points (P < 0.01), and encoded the RING zinc finger protein. It was located on qRTL9-2 and qRSVI9-1 and is related to the total length and simple vitality index. These results provided potential candidate genes for further gene cloning and improving the low-temperature tolerance of maize. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01297-6.