H2O2 promotes trimming-induced tillering by regulating energy supply and redox status in bermudagrass.

Tillering/branching pattern plays a significant role in determining the structure and diversity of grass, and trimming has been found to induce tillering in turfgrass. Recently, it has been reported that hydrogen peroxide (H2O2) regulates axillary bud development. However, the role of H2O2 in trimming-induced tillering in bermudagrass, a kind of turfgrass, remains unclear. Our study unveils the significant impact of trimming on promoting the sprouting and growth of tiller buds in stolon nodes, along with an increase in the number of tillers in the main stem. This effect is accompanied by spatial-temporal changes in cytokinin and sucrose content, as well as relevant gene expression in axillary buds. In addition, the partial trimming of new-born tillers results in an increase in sucrose and starch reserves in their leaves, which can be attributed to the enhanced photosynthesis capacity. Importantly, trimming promotes a rapid H2O2 burst in the leaves of new-born tillers and axillary stolon buds. Furthermore, exogenous application of H2O2 significantly increases the number of tillers after trimming by affecting the expression of cytokinin-related genes, bolstering photosynthesis potential, energy reserves and antioxidant enzyme activity. Taken together, these results indicate that both endogenous production and exogenous addition of H2O2 enhance the inductive effects of trimming on the tillering process in bermudagrass, thus helping boost energy supply and maintain the redox state in newly formed tillers.

Electroacupuncture-Modulated MiR-106b-5p Expression Enhances Autophagy by Targeting Beclin-1 to Promote Motor Function Recovery After Spinal Cord Injury in Rats.

OBJECTIVE: Electroacupuncture (EA) has a definite effect on the treatment of spinal cord injuries (SCIs), but its underlying molecular mechanism remains unclear. Meanwhile, MiR106b-5p is an autophagy- and apoptosis-related microribonucleic acid, but whether it regulates the progression of autophagy and apoptosis in SCIs is yet undetermined. As such, this study aimed to elucidate the involvement of miR-106b-5p in the EA treatment of an SCI. METHODS: The miR-106b-5p level was detected by quantitative real-time polymerase chain reaction. In vitro, SH-SY5Y cells were transfected with miR-106b-5p mimics or inhibitors to regulate the miR-106b-5p expression, while in vivo, SCI rats were treated with EA for 7 days at the bilateral Zusanli (ST36) and Jiaji (EX-B2) acupoints. The motor function was evaluated using the Basso-Beattie-Bresnahan (BBB) criteria. Further, autophagic vacuoles, pathological damage, and neuronal cell morphology were observed by transmission electron microscopy, as well as by hematoxylin and eosin and Nissl staining, respectively. RESULTS: The miR-106b-5p level, which can interact directly with Beclin-1 by influencing its expression, as well as the expressions of P62, Caspase-3, and Bax, was upregulated after an SCI, but it decreased after EA. Moreover, the ratio of LC3-II to LC3-I was upregulated after EA. EA can enhance autophagy, reduce neuronal apoptosis, and minimize motor dysfunction and histopathological deficits after an SCI. More importantly, however, all the above effects induced by EA can be reversed after an injection of miR-106-5p agomir to produce an overexpression of miR-106b-5p. CONCLUSION: EA treatment could downregulate miR-106b-5p to alleviate SCI-mediated injuries by promoting autophagy and inhibiting apoptosis.

Size-fractionated ultrafine particles and their optical properties produced from heating edible oils in a kitchen laboratory.

Cooking oil fume (COF) is an important source of indoor and outdoor air pollutants. COF generates a large number of organic compounds through volatilization and thermal oxidation, mainly including acids, alcohols, aldehydes and polycyclic aromatic hydrocarbons (PAHs), which can contribute 10 %-35 % to airborne organic particles in urban areas. COF not only affects human health owning to their small sizes, but also may absorb incident light due to the presence of brown carbon (BrC) chromophores in organic components. Therefore, we investigated size distributions and light absorption properties of particles produced from heating four types of edible oil. Results showed over 75 % of COF particles belonged to ultrafine particles (UFPs) and capable of absorbing light. The particle number size distributions for heating all edible oils were bimodal lognormal distribution, and the two mode diameters were within 27.9-32.2 nm and 187.7-299.6 nm. Both real-time monitoring and offline analyzing results show the average absorption coefficients of particles generated from heating soybean oil were much greater compare to those of heating other three edible oils. The mean AAE370/520 for heating soybean oil, olive oil, corn oil and peanut oil were 1.877, 1.669, 1.745 and 1.288, respectively, indicating the presence of BrC chromophores. A large proportion of BrC identified by HPLC-DAD-Q-TOF-MS only contain carbon, hydrogen and oxygen, which are CnH2nO2, CnH2n-2O2, CnH2n-4O2 and CnH2n-6O2 (9

Quantitative and Fiber-Selective Evaluation for Central Poststroke Pain.

The electrophysiological recording can be used to quantify the clinical features of central poststroke pain (CPSP) caused by different lesion locations. We aimed to explore the relationship between clinical features and lesion location in patients with CPSP using the current perception threshold (CPT) approach. Here, patients underwent the standardized CPT measure at five detection sites on both the contralesional and ipsilesional sides, using a constant alternating-current sinusoid waveform stimulus at three frequencies: 2000 Hz, 250 Hz, and 5 Hz. 57 CPSP patients were recruited in this cross-sectional study, including 13 patients with thalamic lesions and 44 patients with internal capsule lesions. Patients with a thalamic lesion had more frequent abnormal Aδ and C fibers than those with an internal capsule lesion (69.2% versus 36.4%, p value = 0.038; 53.8% versus 63.6%, p value = 0.038). The patients with internal capsule lesions had more frequent abnormal Aß fibers than those with thalamic lesions (53.8% versus 63.6%, p value < 0.001). The sensory dysfunction in the patients with thalamic lesions was more likely to occur in the upper limbs (i.e., the shoulder (p value = 0.027) and the finger (p value = 0.040)). The lower limbs (i.e., the knee (p value = 0.040) and the toe (p value = 0.005)) were more likely to experience sensory dysfunction in the patients with internal capsule lesions. Hyperesthesia was more likely to occur in the thalamic patients, and hypoesthesia was more likely to occur in the patients with internal capsule lesions (p value < 0.001). In patients with thalamic lesions, Visual Analogue Scale (VAS) had a positive correlation with 5 Hz CPT on the shoulder (r = 0.010, p value = 0.005), 250 Hz CPT on the finger (r = 0.690, p value = 0.009) from the contralesional side, and 2000 Hz CPT on the knee (r = 0.690, p value = 0.009). In patients with internal capsule lesions, VAS had a positive correlation with 2000 Hz CPT on the knee (r = 0.312, p value = 0.039) and foot (r = 0.538, p value < 0.001). In conclusion, the abnormal fiber types, sensory dysfunction territory, and clinical signs of CPSP in thalamic stroke differ from those in internal capsule stroke. Implementation of the portable and convenient CPT protocol may help clarify the locations of different stroke lesions in various clinical settings.

From concept to action: a united, holistic and One Health approach to respond to the climate change crisis.

It is unequivocal that human influence has warmed the planet, which is seriously affecting the planetary health including human health. Adapting climate change should not only be a slogan, but requires a united, holistic action and a paradigm shift from crisis response to an ambitious and integrated approach immediately. Recognizing the urgent needs to tackle the risk connection between climate change and One Health, the four key messages and recommendations that with the intent to guide further research and to promote international cooperation to achieve a more climate-resilient world are provided.

Asymmetric Synthesis and Biological Screening of Quinoxaline-Containing Synthetic Lipoxin A4 Mimetics (QNX-sLXms).

Failure to resolve inflammation underlies many prevalent pathologies. Recent insights have identified lipid mediators, typified by lipoxins (LXs), as drivers of inflammation resolution, suggesting potential therapeutic benefit. We report the asymmetric preparation of novel quinoxaline-containing synthetic-LXA4-mimetics (QNX-sLXms). Eight novel compounds were screened for their impact on inflammatory responses. Structure-activity relationship (SAR) studies showed that (R)-6 (also referred to as AT-02-CT) was the most efficacious and potent anti-inflammatory compound of those tested. (R)-6 significantly attenuated lipopolysaccharide (LPS)- and tumor-necrosis-factor-α (TNF-α)-induced NF-κB activity in monocytes and vascular smooth muscle cells. The molecular target of (R)-6 was investigated. (R)-6 activated the endogenous LX receptor formyl peptide receptor 2 (ALX/FPR2). The anti-inflammatory properties of (R)-6 were further investigated in vivo in murine models of acute inflammation. Consistent with in vitro observations, (R)-6 attenuated inflammatory responses. These results support the therapeutic potential of the lead QNX-sLXm (R)-6 in the context of novel inflammatory regulators.

Chemical Fingerprinting of HULIS in Particulate Matters Emitted from Residential Coal and Biomass Combustion.

Identification of humic-like substances (HULIS) structures and components is still a major challenge owing to their chemical complexity. This study first employed a complementary method with the combination of two-dimensional gas chromatography-time-of-flight mass spectrometry and liquid chromatography-quadrupole-time-of-flight mass spectrometry to address low-polarity and polar components of HULIS in PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 µm), respectively. The combination method showed a significant correlation in identifying overlapping species and performed well in uncovering the chemical complexity of HULIS. A total of 1246 compound species in HULIS (65.6-81.0% for each sample), approximately 1 order of magnitude more compounds than that reported in previous studies, were addressed in PM2.5 collected in real-world household biomass and coal combustion. Aromatics were the most abundant compounds (37.4-64.1% in biomass and 34.5-70.0% in coal samples) of the total mass in all HULIS samples according to carbon skeleton determination, while the major components included phenols (2.6-21.1%), ketones (6.0-17.1%), aldehydes (1.1-6.8%), esters (2.9-20.0%), amines/amides (3.2-8.5%), alcohols (3.8-17.0%), and acids (4.7-15.1%). Among the identified HULIS species, 11-36% mass in biomass and 11-41% in coal were chromophores, while another 22-35 and 23-29% mass were chromophore precursors, respectively. The combination method shows promise for uncovering HULIS fingerprinting.

Assessing the Effect of Reactive Oxygen Species and Volatile Organic Compound Profiles Coming from Certain Types of Chinese Cooking on the Toxicity of Human Bronchial Epithelial Cells.

The International Agency of Research on Cancer identifies high-temperature frying, which features prominently in Chinese cooking, as producing group 2A carcinogens. This study simultaneously characterized particulate and gaseous-phase cooking emissions, monitored their reactive oxygen species (ROS) concentrations, and evaluated their impact on genetic damage and expression in exposed human bronchial epithelial cells. Five types of edible oil, three kinds of seasonings, and two dishes were assessed. Among tested edible oils, heating of soybean oil released the largest particle number concentration (2.09 × 1013 particles/(g cooking material and oil)·h) and volatile organic compounds (VOCs) emissions (12103.42 µg/(g cooking material and oil)·h). Heating of lard produced the greatest particle mass concentration (0.75 mg/(g cooking material and oil)·h). The main finding was that sunflower and rapeseed oils produced the highest ROS concentrations (80.48 and 71.75 nmol/(g cooking material and oil)·h, respectively). ROS formation most likely occurred during the autoxidation of both polyunsaturated and monounsaturated fatty acids. Among all the tested parameters, only ROS concentrations exhibited consistency with cell viability and showed significant correlations with the expression levels of CYP1A1, HIF-1a, and especially with IL-8 (the marker for oxidative stress within the cell). These findings indicate that ROS concentration is potentially a suitable metric for direct assessment of exposure levels and potential toxicity.

Ultrastructure of sensilla on the maxillary and labial palps of the adult Xylotrechus grayii (Coleoptera: Cerambycidae).

The longhorn beetle, Xylotrechus grayii (White, 1855), is a serious woodborer pest of many economic and medicinal plants. The maxillary and labial palps of X. grayii adults are strongly involved in mating and host selection behaviors. To further develop control strategies of the pest, sensilla on the palps were studied with scanning and transmission electron microscopy. Five types of sensilla (nine subtypes) were identified: sensilla styloconica (four subtypes, Sty1-4), sensilla chaetica (2 subtypes, SC1-2), sensilla digitiformia (Di), sensilla basiconica (Ba), and Böhm sensilla (Bm). Sty and Ba have dendrites and wall pores. SC2 has a tubular body. Di exist only on the terminal segment of the maxillary palp. Sty numbers are the highest in both palps, followed by SC. The number of sensilla in the maxillary palp is significantly higher than that in the labial palp. There are no significant sexual differences in sensilla types, characteristics, distribution, and quantity in the maxillary or labial palps, except for the number of SC sensilla on the maxillary palp. Sensilla functions were compared with correlative sensilla in previous studies. Sty may be sense gustation and olfaction stimulation, while SC are mechanoreceptors. Ba are likely thermo- and hygroreceptors. The phylliform depression area formed by Di may exert multiple functions. Bm may sense palp position and movement. These results contribute to the study of the electrophysiology and behavior mechanisms of X. grayii.

YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway.

Pancreatic ductal adenocarcinoma (PDAC) is one of the malignant lethal tumors. It has been reported that the transcriptional regulator Yin Yang-1 (YY1) suppressed the invasion and metastasis of PDAC. However, the function of YY1 on proliferation and migration of pancreatic cancer remains to be clarified. In this study, we found that YY1 overexpression or knockdown can inhibit or promote the proliferation and migration of pancreatic cancer cells. Digital gene expression sequencing indicates that cyclin-dependent kinase inhibitor 3 (CDKN3) may be the candidate target gene of YY1. Then we found that YY1 can downregulate the expression of CDKN3 by directly binding to the promoter region of CDKN3. Silencing CDKN3 expression could inhibit the ability of cell proliferation and migration and overexpression of CDKN3 could restore the effects induced by YY1 overexpression in pancreatic cancer cells. The expression levels of YY1 and CDKN3 were negatively correlated in pancreatic cancer tissues and PDAC patients with higher levels of CDKN3 have poor prognosis. Vitro and vivo study show that CDKN3 can form a complex with MdM2-P53, thus leading to inhibiting the expression of P21, which is the target gene of P53, and finally facilitates the cell cycle to promote the proliferation of pancreatic cancer cells. Hence, YY1 can directly regulate the expression of CDKN3 and participate in the cycle of pancreatic cancer cells, which can inhibit the progression of pancreatic cancer. These results reveal that YY1-CDKN3-MDM2/P53-P21 axis is involved in pancreatic tumorigenesis, which may develop new methods for human pancreatic cancer therapy.

Hydrothermal liquefaction of agricultural and forestry wastes: state-of-the-art review and future prospects.

Hydrothermal liquefaction has been widely applied to obtain bioenergy and high-value chemicals from biomass in the presence of a solvent at moderate to high temperature (200-550°C) and pressure (5-25MPa). This article summarizes and discusses the conversion of agricultural and forestry wastes by hydrothermal liquefaction. The history and development of hydrothermal liquefaction technology for lignocellulosic biomass are briefly introduced. The research status in hydrothermal liquefaction of agricultural and forestry wastes is critically reviewed, particularly for the effects of liquefaction conditions on bio-oil yield and the decomposition mechanisms of main components in biomass. The limitations of hydrothermal liquefaction of agricultural and forestry wastes are discussed, and future research priorities are proposed.

Maternal Dietary Vitamin D Does Not Program Systemic Inflammation and Bone Health in Adult Female Mice Fed an Obesogenic Diet.

Obesity is associated with systemic inflammation and impaired bone health. Vitamin D regulates bone metabolism, and has anti-inflammatory properties and epigenetic effects. We showed that exposure to high dietary vitamin D during pregnancy and lactation beneficially programs serum concentration of lipopolysaccharide (LPS) and bone structure in male offspring fed an obesogenic diet. Here we assessed if this effect is also apparent in females. C57BL/6J dams were fed AIN93G diet with high (5000 IU/kg diet) or low (25 IU/kg diet) vitamin D during pregnancy and lactation. Post-weaning, female offspring remained on their respective vitamin D level or were switched and fed a high fat and sucrose diet (44.2% fat, 19.8% sucrose) until age seven months when glucose response, adiposity, serum LPS, and bone mineral, trabecular and cortical structure, and biomechanical strength properties of femur and vertebra were assessed. There was no evidence for a programming effect of vitamin D for any outcomes. However, females exposed to a high vitamin D diet post-weaning had higher bone mineral content (p = 0.037) and density (p = 0.015) of lumbar vertebra. This post-weaning benefit suggests that in females, bone mineral accrual but not bone structure is compromised with low vitamin D status in utero until weaning in an obesogenic context.

The impact of glutamine supplementation on the symptoms of ataxia-telangiectasia: a preclinical assessment.

BACKGROUND: Our previous studies of Alzheimer's disease (AD) suggested that glutamine broadly improves cellular readiness to respond to stress and acts as a neuroprotectant both in vitro and in AD mouse models. We now expand our studies to a second neurodegenerative disease, ataxia-telangiectasia (A-T). Unlike AD, where clinically significant cognitive decline does not typically occur before age 65, A-T symptoms appear in early childhood and are caused exclusively by mutations in the ATM (A-T mutated) gene. RESULTS: Genetically ATM-deficient mice and wild type littermates were maintained with or without 4 % glutamine in their drinking water for several weeks. In ATM mutants, glutamine supplementation restored serum glutamine and glucose levels and reduced body weight loss. Lost neurophysiological function assessed through the magnitude of hippocampal long term potentiation was significantly restored. Glutamine supplemented mice also showed reduced thymus pathology and, remarkably, a full one-third extension of lifespan. In vitro assays revealed that ATM-deficient cells are more sensitive to glutamine deprivation, while supra-molar glutamine (8 mM) partially rescued the reduction of BDNF expression and HDAC4 nuclear translocation of genetically mutant Atm(-/-) neurons. Analysis of microarray data suggested that glutamine metabolism is significantly altered in human A-T brains as well. CONCLUSION: Glutamine is a powerful part of an organism's internal environment. Changes in its concentrations can have a huge impact on the function of all organ systems, especially the brain. Glutamine supplementation thus bears consideration as a therapeutic strategy for the treatment of human A-T and perhaps other neurodegenerative diseases.

Evaluation of GC-ICP-MS/MS as a New Strategy for Specific Heteroatom Detection of Phosphorus, Sulfur, and Chlorine Determination in Foods.

For the first time in the literature, application of a GC-ICP-MS/MS method for the selective and sensitive detection of specific heteroatoms of phosphorus, sulfur, and chlorine has been accomplished. As a proof of concept, organophosphorus, organosulfur, and organochlorine pesticides in various food matrices have been studied. For the detection of organophosphorus and organosulfur pesticides, oxygen was used in the collision reaction cell (CRC) to convert P (m/z 31) to PO(+) (m/z 47) and S (m/z 32) to SO(+) (m/z 48). Similarly, ClH2(+) (m/z 37) was monitored after the reaction of Cl (m/z 35) with hydrogen in the CRC for the determination of organochlorine pesticides. Real food samples (baby food purees, fresh vegetables, loose tea) were screened for their pesticide content, following preparation of triplicate extracts using QuEChERS (quick, easy, cheap, effective, rugged, and safe). Excellent linearity with correlation coefficients R ≥ 0.997 was achieved, and the lowest detection limits obtained for the organophosphorus, organosulfur, and organochlorine pesticides were 0.0005, 0.675, and 0.144 µg/kg, respectively.

Flaxseed oil enhances the effectiveness of trastuzumab in reducing the growth of HER2-overexpressing human breast tumors (BT-474).

Flaxseed oil (FSO) reduces breast tumorigenesis and HER2 expression in animal models of luminal breast cancer. The primary treatment for HER2-overexpressing tumors is trastuzumab (TRAS). We aimed to determine the effect of 4% FSO alone and combined with TRAS on HER2-overexpressing tumor (BT-474) growth and to explore potential mechanisms with a specific focus on HER2, mitogen-activated protein kinase (MAPK) and Akt signaling and fatty acid profile. Athymic mice with established tumors were fed the basal diet (control) or 4% FSO diet, with or without TRAS (1 or 2.5 mg/kg) treatment for 4 weeks. Tumor growth, HER2 signaling biomarkers (mRNA and protein) and fatty acid profile were measured. Tumors treated with FSO alone showed no difference in tumor growth compared to control; however, compared to TRAS2.5 and other groups, FSO+TRAS2.5 caused significantly lower tumor growth and cell proliferation and higher apoptosis and the greatest lowering of signaling biomarker expressions (MAPK2, HER2 mRNA; pHER2 protein). Both TRAS and FSO had main effects of reducing the phosphorylated/total expression of Akt and MAPK protein expression. Dietary FSO altered the tumor fatty acid profile. In conclusion, 4% dietary FSO alone does not affect BT-474 tumor growth but enhances the tumor-reducing effect of TRAS (2.5 mg/kg). FSO×TRAS interactive effect may be modulated by their combined reductions of HER2 signaling through the Akt and MAPK pathways leading to reduced cell proliferation and increased apoptosis. FSO alters tumor fatty acid profile that likely contributes to effects on signaling pathways. This supports FSO as a complementary treatment for HER2+ breast cancer treated with TRAS.

Long-term vitamin D3 supplementation does not prevent colonic inflammation or modulate bone health in IL-10 knockout mice at young adulthood.

Inflammatory bowel disease (IBD) is an idiopathic disease that can impair bone metabolism. Low vitamin D status has been implicated in its progress. This study used interleukin (IL)-10 knockout (KO) mice, that develop an intestinal inflammation when housed in a non-sterile environment, to determine if supplementation with vitamin D3 throughout life could mitigate inflammation and attenuate the lower bone mineral content (BMC) and density (BMD), and bone strength. Female IL-10 KO mice were randomized 25 or 5000 IU vitamin D3/kg diet throughout pregnancy and lactation. At weaning, offspring received the same or opposite diet as their mother until age three months. Body weight growth was similar among groups within a sex. At three months of age, there were no differences in inflammation and gene expression in the colon of offspring. Male offspring exposed to continuous 25 IU vitamin D3/kg diet had lower (p < 0.001) colonic VDR expression and those exposed only to low vitamin D3 until weaning had higher serum IL-6. There were no differences in femur or vertebral BMC, BMD or bone strength. In summary, long-term exposure to vitamin D3 did not attenuate intestinal inflammation or preserve bone mineral or bone strength. Thus, supplementation with vitamin D3 does not exert anti-inflammatory effects in this mouse model that mimics human inflammatory bowel disease.

17ß-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17ß-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status.

MAP3K10 promotes the proliferation and decreases the sensitivity of pancreatic cancer cells to gemcitabine by upregulating Gli-1 and Gli-2.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal human malignancies and is regulated by Sonic Hedgehog (Shh) signaling. Recently, MAP3K10 has been shown to regulate Shh signaling, suggesting a role for MAP3K10 in the tumorigenesis of PDAC. We determined the expression status of MAP3K10 in PDAC tissues and cell lines, and analyzed the viability and cell proliferation of PDAC cells with an overexpression or knockdown of MAP3K10 in vitro. MAP3K10 was upregulated in PDAC tissues and cell lines. Overexpression of MAP3K10 promoted the proliferation and decreased the gemcitabine sensitivity of pancreatic cancer cells. In contrast, knockdown of MAP3K10 significantly decreased cell proliferation and sensitized cells to gemcitabine. However, neither overexpression nor knockdown of MAP3K10 affected cell migration. Moreover, overexpression of MAP3K10 resulted in upregulation of Gli-1 and Gli-2 in PDAC cells. Our results indicate a novel and important role for MAP3K10 in the proliferation and chemoresistance of PDAC. Our study suggests that targeting MAP3K10 is a potential strategy for the development of alternative therapies for pancreatic cancers.