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Background: Nanofluids are the most widely used materials in various engineering fields. They have different properties under different conditions, and predicting their properties requires several experiments. Artificial intelligence can predict the properties of nanofluids in the shortest time and cost. Methodology: This study aims to predict the viscosity and share rate of MWCNT-TiO2 (40–60)-oil SAE50 nano-lubricant (NL). Machine learning algorithms and neural networks can respond best to this important matter. For this purpose, the Group Method of Data Handling (GMDH) neural network is combined with the meta-heuristic algorithm Multi-Objective Gray Wolf Optimizer (MOGWO). This way, the experimental data is first given to the artificial neural network (ANN). Then, the meta-heuristic algorithm optimizes the hyperparameters of the ANN to bring the predicted results closer to the experimental data and minimize the error. The MOGWO algorithm's regulators are the number of iterations and the number of wolves investigated in this study to better select this algorithm. Then, these modes are measured using two criteria, correlation coefficient (R) and rote mean squared error (RMSE), to choose the best mode. Finally, by using the extracted equations by the GMDH neural network, the best models or the Pareto front can be obtained using the MOGWO meta-heuristic algorithm. Results: The error histogram diagram shows the excellent performance of the combination of the GMDH neural network and the MOGWO meta-heuristic algorithm. The values of R and RMSE for viscosity and shear rate are equal to 0.99217, 15.8749, and 0.99031, 68.7723, respectively. The optimization results showed that the best conditions to meet viscosity and cutting rate are when φ, T, and γ equal 1.21∗e−5, 46.71, and 50.11.

Abstract Background Ribosomal RNA processing protein 15 (RRP15) has been found to regulate the progression of hepatocellular carcinoma (HCC). Nevertheless, the extent to which it contributes to the spread of HCC cells remains uncertain. Thus, the objective of this research was to assess the biological function of RRP15 in the migration of HCC. Methods The expression of RRP15 in HCC tissue microarray (TMA), tumor tissues and cell lines were determined. In vitro, the effects of RRP15 knockdown on the migration, invasion and adhesion ability of HCC cells were assessed by wound healing assay, transwell and adhesion assay, respectively. The effect of RRP15 knockdown on HCC migration was also evaluated in vivo in a mouse model. Results Bioinformatics analysis showed that high expression of RRP15 was significantly associated with low survival rate of HCC. The expression level of RRP15 was strikingly upregulated in HCC tissues and cell lines compared with the corresponding controls, and TMA data also indicated that RRP15 was a pivotal prognostic factor for HCC. RRP15 knockdown in HCC cells reduced epithelial-to-mesenchymal transition (EMT) and inhibited migration in vitro and in vivo, independent of P53 expression. Mechanistically, blockade of RRP15 reduced the protein level of the transcription factor POZ/BTB and AT hook containing zinc finger 1 (PATZ1), resulting in decreased expression of the downstream genes encoding laminin 5 subunits, LAMC2 and LAMB3, eventually suppressing the integrin β4 (ITGB4)/focal adhesion kinase (FAK)/nuclear factor κB kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Conclusions RRP15 promotes HCC migration by activating the LAMC2/ITGB4/FAK pathway, providing a new target for future HCC treatment.

As inorganic rigid waterproof materials with excellent substrate compatibility, non-toxicity, harmless, and deep penetration depth, cementitious capillary crystalline waterproof materials (CCCW) hold great potential for application in concrete structures. However, the formulations of commercially available CCCW are currently undisclosed, hindering the mechanism study of CCCW, which is not conducive to the development of more efficient and cost-effective CCCW materials. In this study, a new formulation of CCCW active chemicals was developed, consisting of calcium carbonate, sodium silicate, glycine, EDTA-4Na, and sodium acetate. The effectiveness of sodium acetate as a high-quality impermeable admixture to CCCW was explored to enhance the impermeability of the substrate. Subsequently, the fundamental performance of the coatings was subjected to further examination. After application of the coating, the impermeability and strength of the substrate were enhanced, and the fist impermeability strength reached 1.5 MPa. Micro characteristics testing indicated that the coated sample had a denser microstructure, resulting in an increase of calcium carbonate crystals and hydrated calcium silicate in the pores. The harmful pores (100–3000 nm) were transformed into less harmful or harmless pores (< 100 nm). The durability tests indicated a 12.37 % drop in carbonation area over 14 days, with an approximately 30 % drop in the Coulomb electric flux of chloride ions.

Alkali-activated slag cement (AASC) has shown immense potential for application as a low-carbon and eco-friendly cementitious material. It’s crucial to modify the AASC with superhydrophobic property to obtain excellent durability performance. In this paper, low-cost and non-toxic stearic acid (SA) is selected as a hydrophobic agent to impart integral hydrophobic property to the alkali-activated Portland slag cement mortar (AAPSCM). The SA-modified AAPSCM (M-AAPSCM) shows superhydrophobicity with a contact angle of 150.6° and a sliding angle of 9.5°, even when hammered to reveal its broken inner structure. The characterization analysis indicates that stearic acid not only successfully grafts onto the mortar surface but also forms calcium stearate, which successfully reduces the surface energy of the material. Combined with the porous rough structure constructed by medium sand and ethanol volatilization, the originally hydrophilic material achieves hydrophobic modification under the dual synergistic effect. The M-AAPSCM reached a compressive strength of 20.8 MPa after 28 days of curing, satisfying the requirements for hydraulic engineering applications. And the M-AAPSCM not only exhibits an excellent self-cleaning ability against contaminants like sand particles and chalk powder, but also demonstrates remarkable mechanical robustness, even after being subjected to blade scratching or mechanical fracture. Concurrently, the initial and final setting times of M-AAPSCM were determined to be 32 minutes and 41 minutes respectively, demonstrating its rapid-setting characteristic. Additionally, following the hydrophobic modification, AAPSCM effectively overcomes its inherent issues of severe autogenous shrinkage and poor carbonation resistance. Furthermore, when compared with the ordinary AAPSCM (O-AAPSCM), the durability of the M-AAPSCM against dry-wet cycles, icing, and freeze-thaw cycles is significantly enhanced.

To further guide the exploration and development of shale oil in the Da'anzhai Member of the Jurassic Ziliujing Formation in the Sichuan Basin, it is urgent to clarify the favorable lithofacies of shale oil. In this study, core observation, thin section authentication, high pressure mercury injection, NMR, rock pyrolysis analysis and other experiments were used to analyze the reservoir space types, pore structure characteristics and oil-bearing properties of different lithofacies of shale series in the Da'anzhai Member. The results show that mainly six types of lithofacies are developed in the Da'anzhai Member: massive (argillaceous) shell limestone, layered argillaceous shell limestone, layered shell shale, laminar shell-bearing shale, massive shell-bearing clay shale and foliated siltstone-bearing clay shale. The physical properties of shale in the Da'anzhai Member are much better than those of shell limestone, and with the increase of calcareous content, the pore size of the shale gradually increases, but the total pore volume and total connected volume gradually decrease. The average free oil value (S1) of the shale series in the Da'anzhai Member is 1.31 mg/g, with moderate oil-bearing property. The S1 values of the foliated siltstone-bearing clay shale and the laminar shell-bearing shale are relatively higher, which are 2.37 mg/g and 1.82 mg/g, respectively. In summary, it is believed that the foliated siltstone-bearing clay shale and the laminar shell-bearing shale have good reservoir properties and high oil-bearing properties. The lithofacies combination of the two can be a key exploration target for shale oil in the Da'anzhai Member.

Salt accumulation in bare strips under film-mulched drip irrigation is a global concern as it adversely affects soil quality and hinders sustainable agricultural development in arid and semi-arid regions. This study aims to investigate the spatial distribution of soil moisture and salt under various planting patterns and assess the lateral salt accumulation effect in bare strips. Seven treatments were implemented based on the local cotton planting pattern, including the local classical planting pattern (LTP), mulch width of 220 cm (WFM-220), spacing of 90 cm (SFM-90), mulch width of 40 cm (WFM-40), spacing of 10 cm (SFM-10), ridge tillage (TFM-RT), and ditching (TFM-D), varying in mulch width, spacing, and tillage method in bare strips. Additionally, the performance of the HYDRUS-2D model was evaluated by comparing simulated and observed values using field data. The results revealed that (I) the WFM-220 cm treatment exhibited the best water content retention under mulched film, with lower salt accumulation in the surface bare strip (0–20 cm soil layer); (II) all treatments with narrow rows showed desalination effects in the 0–40 cm soil layer, with salt content reductions ranging from approximately 13% to 38% compared to the initial values; (III) under the LTP treatment, the lateral salt discharge effect in the bare strip of the 0–40 cm soil layer was the best, regardless of mulch width and spacing, with a salt accumulation rate up to three times higher than the initial value, and even up to four times higher in the 0–10 cm layer; (IV) the TFM-RT treatment exhibited the best salt accumulation ability on the surface bare strip; and (V) the HYDRUS-2D model proved to be an effective tool for studying the dynamic regulation mechanism of water and salt with root mean square error values ranging from 0.079 to 0.106 cm3·cm−3 for soil water content and from 0.044 to 0.079 dS·m−1 for electrical conductivity, indicating good agreement between simulations and observations.

In the past tens of years, the power conversion efficiency of Cu(In,Ga)Se2 (CIGS) has continuously improved and been one of the fastest growing photovoltaic technologies that can also help us achieve the goal of carbon emissions reduction. Among several key advances, the alkali element post-deposition treatment (AlK PDT) is regarded as the most important finding in the last 10 years, which has led to the improvement of CIGS solar cell efficiency from 20.4% to 23.35%. A profound understanding of the influence of alkali element on the chemical and electrical properties of the CIGS absorber along with the underlying mechanisms is of great importance. In this review, we summarize the strategies of the alkali element doping in CIGS solar cell, the problems to be noted in the PDT process, the effects on the CdS buffer layer, the effects of different alkali elements on the structure and morphology of the CIGS absorber layer, and retrospect the progress in the CIGS solar cell with emphasis on the alkali element post deposition treatment.

The western region of Mongolia is characterized by an arid climate and a fragile ecological environment. It is a sensitive zone in response to global climate change and one of the major sources of dust globally. This region is home to numerous lakes, and their dynamic changes not only reflect global climate variations but also have implications for the global ecological environment quality. In this study, Landsat images were used as the data source, and Google Earth Engine (GEE) was employed to extract lakes with an area larger than 1 km2 from 1992 to 2021. The spatiotemporal characteristics of lake water area (LWA) changes were analyzed, and a structural equation model was applied to attribute the lake changes. The results indicate an overall trend of increasing lake area followed by a decrease in the study area. Specifically, lakes in the provinces of Khovd and Gobi-Altai exhibited a decreasing trend followed by an increasing trend, while lakes in the provinces of Uvs and Zavkhan showed an increasing trend followed by a decreasing trend. Three typical types of lakes, namely, alpine lakes, throughflow lakes, and terminal lakes, all exhibited a trend of increasing area followed by a decrease. The analysis of driving forces behind lake area changes reveals that climate change and human activities primarily exert indirect influences on the lake area changes in each province. Specifically, climate change and human activities lead to changes in soil moisture, which have a significant explanatory power for lake area changes. Regarding the typical types of lakes, climate change serves as the primary driving force for alpine lakes, while human activities are the main driving forces for throughflow lakes and terminal lakes.

Reconstructing karst palaeogeomorphology is a useful approach to identifying target areas for oil and gas exploration. This study used the elevation method to reconstruct the karst palaeogeomorphology at the top of the 4th member (Z 2 dn 4 ) of the Dengying Formation (Z 2 dn) in the Central Sichuan Basin based on 2D and 3D seismic and drilling data. The bottom of the Longwangmiao Formation and the top of the 2nd member (Z 2 dn 2 ) of the Z 2 dn were optimized as the upper and lower base levels, respectively. The reconstructed palaeogeomorphology was divided into five types – slopes, erosional peneplains, monadnocks, domes and depressions – according to their morphology, scope and gradient, allowing inference of the palaeohydrological conditions. Slopes were subdivided into gentle (

The Jurassic Da’anzhai Member in Sichuan Basin is an important target for shale oil exploration. Whole rock X-ray diffraction analysis, thin section, SEM and TOC testing, as well as major and trace element analysis are used to analyze the relationship of lithofacies and pore types with the sedimentary environment of the Da’anzhai Member in the Central Sichuan Basin. The results show the Da’anzhai Member in the Well Ren’an 1 (RA1) is divided into six types of lithofacies, based on a three-level division method of mineral composition-TOC-mineral structure— namely, massive mud-bearing shell limestone lithofacies (F), thick argillaceous shell limestone lithofacies (E), laminated clay silt shale lithofacies (D), thin shell calcareous shale lithofacies (C), laminated shell-bearing shale lithofacies (B), and thick clay shale lithofacies (A). The pore spaces include intergranular pores, intergranular dissolution pores, authigenic calcite intergranular pores, authigenic quartz intercrystalline pores, intergranular pores of clay minerals or pyrite nodules, as well as organic pores. The Da’anzhai Member was deposited in a semi-deep to shallow lake sedimentary environment, with relatively low salinity. This strata experienced moderate-to-strong chemical weathering as a result of the semi-arid, warm and humid paleoclimate environmental conditions that persisted during its deposition; low weathering and dry paleoclimate conditions occurred periodically. Paleoenvironment is an important influence on the lithofacies and pore types of the Da’anzhai Member. The persistence of arid climate conditions contributed to a decline in water depth, relatively high salinity, low organic productivity, and the deposition of carbonate rocks that characterize lithofacies E and F; mostly intercrystalline pores formed in these lithofacies in response to the prevailing arid climate conditions. Conversely, warm, and humid climate conditions increased the inflow of fresh water, terrigenous debris, and nutrients into the lacustrine basin that led to the deposition of fine-grained sedimentary rocks of lithofacies A, B, and C. These lithofacies are characterized by abundant nano pores, such as clay intercrystalline pores and organic pores.

Based on drilling data of JT1 and CS1, outcrop profiles and seismic data, the sedimentary pattern, space configuration of source-reservoir-cap combinations and paleouplift evolution characteristics of the Cambrian Lower Canglangpu Member in the central Sichuan paleouplift have been investigated to determine the favorable exploration zones. Controlled by Deyang-Anyue rift, the Lower Canglangpu Member features differential characteristics from east to west in sedimentary framework. In the west side of the Deyang-Anyue rift, this member is composed of clastic sediments, while in the east side of the Deyang-Anyue rift, it is fresh water shelf sediments, with grain beaches occurring along edges of the depressions, shelf and lagoon. Among the beaches, the dolomitic ones are mainly distributed around the depression edge and in the north of the lagoon. The beach sediments could become high quality reservoirs under the effect of karstification. Underlying the Lower Canglangpu Member is the widespread source rock of the Qiongzhusi Formation, so oil and gas generated by the Qiongzhusi Formation source rock can directly charge into the beach reservoirs. The sandy mudstone of the Upper Canglangpu Member can serve as the caprock of the Lower Canglangpu Member reservoir. The dolomitic beaches are located at the higher part of the paleo-uplift during the main accumulation period, with good hydrocarbon accumulation elements. Blocks PT1-CS1, HT1-GT2 and east GT2 are favorable exploration zones.

Objective: To examine the psychometric properties of four common hamstring muscle flexibility tests involving the straight leg raise (SLR), passive knee extension (PKE), sit and reach test (SRT) and toe touch test (TTT) in young adults.Methods: Forty-three young healthy adults (mean age 27.4 years) were recruited for 3 repeated sessions of hamstring flexibility assessments using the 4 tests mentioned above and the subsequent isokinetic examinations. The first two sessions (S1 and S2) were conducted by two different raters randomly on the first day (D1), and the third session (S3) was conducted by the same rater as S1 3 days later (D4). The next day (D5), the isokinetic performances of knee extensors and flexors of the dominant leg were assessed. To evaluate the interrater (S1 vs. S2) and test-retest (S1 vs. S3) reliability of hamstring flexibility tests, intraclass correlation coefficients (ICCs), standard errors of measurement, and the minimum detectable differences were calculated. Correlation analyses were performed to study the association of each hamstring flexibility test with the isokinetic muscle function of the knee flexors (H) and extensors (Q), including the peak torque (PT), total amount of work (TW) and average power (AP).Results: Excellent interrater and test-retest reliability of hamstring flexibility tests involving the SLR, PKE, SRT and TTT were confirmed with ICCs ranging from 0.923 to 0.986. Fair correlations were found between the 4 hamstring flexibility tests and the H/Q for the PT at angular speeds of 180°/s (Pearson’s r at 0.330–0.449). In addition, the PKE was fairly correlated with the AP of the hamstring (Pearson’s r = 0.320) and the H/Q for the TW (Pearson’s r = 0.345) and AP (Pearson’s r = 0.386) at angular speeds of 180°/s.Conclusions: This study confirmed that the SLR, PKE, SRT and TTT were reliable flexibility tests for hamstring muscles in young healthy adults, and the PKE might be a more valid outcome measure to predict hamstring injury.

The therapeutic strategy of Ewing sarcoma (EWS) remains largely unchanged over the past few decades. Hypoxia is reported to have an impact on tumor cell progression and is regarded as a novel potential therapeutic target in tumor treatment. This study aimed at developing a prognostic gene signature based on hypoxia-related genes (HRGs). EWS patients from GSE17674 in the GEO database were analyzed as a training cohort, and differently expressed HRGs between tumor and normal samples were identified. The univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analyses were used in this study. A total of 57 EWS patients from the International Cancer Genome Consortium (ICGC) database were set as the validation cohort. A total of 506 differently expressed HRGs between tumor and normal tissues were identified, among which 52 were associated with the prognoses of EWS patients. Based on 52 HRGs, EWS patients were divided into two molecular subgroups with different survival statuses. In addition, a prognostic signature based on 4 HRGs (WSB1, RXYLT1, GLCE and RORA) was constructed, dividing EWS patients into low- and high-risk groups. The 2-, 3- and 5-years area under the receiver operator characteristic curve of this signature was 0.913, 0.97 and 0.985, respectively. It was found that the survival rates of patients in the high-risk group were significantly lower than those in the low-risk group (p < 0.001). The risk level based on the risk score could serve as an independent clinical factor for predicting the survival probabilities of EWS patients. Additionally, antigen-presenting cell (APC) related pathways and T cell co-inhibition were differently activated in two risk groups, which may result in different prognoses. CTLA4 may be an effective immune checkpoint inhibitor to treat EWS patients. All results were verified in the validation cohort. This study constructed 4-HRGs as a novel prognostic marker for predicting survival in EWS patients.

The study of extraordinarily high organic matter content (EHOMC) is beneficial to promote the fine evaluation of shale oil and gas, but so far, there have been few studies on its mechanism. This paper carried out a comprehensive lithological and geochemical analysis of the black shales of the Wujiaping Formation in the Kaijiang-Liangping Trough. The results showed that the black shales of the Wujiaping Formation can be divided into two units (the upper and lower parts), and EHOMC occurs in its upper part. The redox-sensitive trace elements (RSTEs), MoEF-UEF covariation, and Ni/Co correlation showed that the lower part of Wujiaping Formation was a weakly restricted oxidation environment, while the upper part evolved into a sulfidation reducing environment. The productivity indicator elements (BaXS, NiXS, CuXS, P, and Mo) indicated that the upper Wujiaping Formation had higher primary productivity than the lower part. However, rare earth elements ((La/Yb)N) indicated that the deposition rate in the lower part of the Wujiaping Formation was higher than that in the upper part. In general, although the oxygenated water in the lower part of the Wujiaping Formation is not conducive to the preservation of organic matter, the high input of nutrients from land sources and the high deposition rate inhibit the decomposition of organic matter, so the lower part has a certain degree of organic matter accumulation. The sulfidation reducing environment and high paleoproductivity are the main reasons for the enrichment of organic matter in the upper part of the Wujiaping Formation. In addition, the sulfidation reducing environment and high paleoproductivity occurred during the violent upwelling at the end of Guadeloupe, a period of high sea level, these factors have jointly contributed to the enrichment of OM in the upper the Wujiaping Formation.

Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been demonstrated to exhibit promising anti-tumor properties in multiple cancer types. However, the effects of CBD on hepatocellular carcinoma (HCC) cells remain unknown. We have shown that CBD effectively suppresses HCC cell growth in vivo and in vitro, and induced HCC cell pyroptosis in a caspase-3/GSDME-dependent manner. We further demonstrated that accumulation of integrative stress response (ISR) and mitochondrial stress may contribute to the initiation of pyroptotic signaling by CBD. Simultaneously, CBD can repress aerobic glycolysis through modulation of the ATF4–IGFBP1–Akt axis, due to the depletion of ATP and crucial intermediate metabolites. Collectively, these observations indicate that CBD could be considered as a potential compound for HCC therapy.

Dimethyl fumarate (DMF) is an approved drug used in the treatment of multiple sclerosis (MS) and psoriasis therapy. Multiple studies have demonstrated other pharmacological activities of DMF such as an anti-cancer agent. In particular, studies have shown that DMF can modulate the NRF2/HO1/NQO1 antioxidant signal pathway and inactivate NF-κB to suppress the growth of colon and breast cancer cells, and induce cell death. In this study, we aimed to evaluate the anti-tumor activities of DMF in pancreatic cancer (PC) focusing on cell death as the predominant mechanism of response. We showed that both mitochondrial respiration and aerobic glycolysis were severely depressed following treatment with DMF and the effects could be abrogated by treatment with L-cysteine and N-acetyl-L-cysteine (NAC). Importantly, we verified that DMF induced metabolic crisis and that cell death was not related to alterations in ROS. Our data implied that MTHFD1 could be a potential downstream target of DMF identified by molecular docking analysis. Finally, we confirmed that MTHFD1 is up-regulated in PC and overexpression of MTHFD1 was negatively related to outcomes of PC patients. Our data indicate that DMF induces metabolic crisie to suppress cell growth and could be a potential novel therapy in the treatment of PC.

ObjectivesCytokine activation and low complement levels are common in depression patients. This study is aimed at investigating the clinical significance of changes in serum concentrations of melatonin (MT), interleukin-6 (IL-6), homocysteine (hcy), and complement C3 and C4 in depression patients and relationships of them with depression activity.MethodsA total of 95 depression patients, including first-episode group (n = 43) and recurrent group (n = 52), and 45 age- and gender-matched healthy controls (HC) were recruited. Serum levels of MT, IL-6, hcy, C3, and C4 in all samples were measured by using enzyme-linked immunosorbent assay (ELISA), chemiluminescence method, enzyme circulation method, and immuno-scatter turbidimetric assay, respectively.ResultsThe serum MT, IL-6, and hcy levels in the first-episode group (113.08 ± 5.06 pg/ml, 2.06 ± 0.12 ng/L, and 13.87 ± 0.45 μmol/L), and recurrent group (117.63 ± 4.63 pg/ml, 2.20 ± 0.12 ng/L, and 13.61 ± 0.46 μmol/L) were significantly higher than those in the control group (89.50 ± 5.10 pg/ml, 1.57 ± 0.06 ng/L, and 11.34 ± 0.40 μmol/L). The serum levels of C3 in the first-episode group (0.95 ± 0.02 ng/L) were significantly lower than those in the recurrent group (1.05 ± 0.03 ng/L) and control group (1.12 ± 0.03 ng/L). There was no significant difference in serum C4 level between each group.ConclusionThese results suggest that higher serum MT, IL-6, and hcy levels were correlated with pathogenesis of depression.

Snowmelt from the Tianshan Mountains (TS) is a major contributor to the water resources of the Central Asian region. Thus, changes in snow phenology over the TS have significant implications for regional water supplies and ecosystem services. However, the characteristics of changes in snow phenology and their influences on the climate are poorly understood throughout the entire TS due to the lack of in situ observations, limitations of optical remote sensing due to clouds, and decentralized political landscapes. Using passive microwave remote sensing snow data from 1979 to 2016 across the TS, this study investigates the spatiotemporal variations of snow phenology and their attributes and implications. The results show that the mean snow onset day (Do), snow end day (De), snow cover duration days (Dd), and maximum snow depth (SDmax) from 1979 to 2016 were the 78.2nd day of hydrological year (DOY), 222.4th DOY, 146.2 days, and 16.1 cm over the TS, respectively. Dd exhibited a spatial distribution of days with a temperature of

This study expanded upon a previous study in mice reporting a link between exenatide treatment and exocrine pancreatic injury by demonstrating temporal and dose responses and providing an initial mechanistic hypothesis. The design of the present study included varying lengths of exenatide exposure (3, 6 weeks to 12 weeks) at multiple concentrations (3, 10, or 30 µg/kg) with multiple endpoints (histopathology evaluations, immunoassay for cytokines, immunostaining of the pancreas, serum chemistries and measurement of trypsin, amylase, and, lipase, and gene expression profiles). Time- and dose-dependent exocrine pancreatic injury was observed in mice on a high fat diet treated with exenatide. The morphological changes identified in the pancreas involved acinar cell injury and death (autophagy, apoptosis, necrosis, and atrophy), cell adaptations (hypertrophy and hyperplasia), and cell survival (proliferation/regeneration) accompanied by varying degrees of inflammatory response leading to secondary injury in pancreatic blood vessels, ducts, and adipose tissues. Gene expression profiles indicated increased signaling for cell survival and altered lipid metabolism in exenatide treated mice. Immunohistochemistry supported gene expression findings that exenatide caused and/or exacerbated pancreatic injury in a high fat diet environment potentially by further increasing high fat diet exacerbated lipid metabolism and resulting oxidative stress. Further investigation is required to confirm these findings and determine their relevance to human disease.