Using ChatGPT for Kidney Transplantation: Perceived Information Quality by Race and Education Levels.

BACKGROUND: Kidney transplantation is a complex process requiring extensive preparation and ongoing monitoring. Artificial intelligence (AI)-powered chatbots hold potential for providing accessible health information, but our understanding of their role in offering health advice for kidney transplantation and how individuals assess such advice remains limited. This study investigates how individuals evaluate ChatGPT's responses to kidney transplantation questions in terms of information quality and empathy, focusing on potential differences across race/ethnicity and educational backgrounds. METHODS: We collected Reddit posts (N = 4624) regarding kidney transplantation and selected 86 questions to represent typical clinician inquiries. These questions were used as input prompts for ChatGPT. A total of 565 participants assessed ChatGPT's responses through online surveys, rating information quality and empathy using Likert scales. RESULTS: Multilevel analyses (N = 2825) show that there is a significant interaction between race/ethnicity and education levels in various measures related to perceived information quality, but not perceived empathy of ChatGPT's responses: accuracy (p < 0.05); authenticity (p < 0.01); believability (p < 0.05); informativeness (p = 0.053); usefulness (p < 0.05); recognizing users' feelings (p = 0.70) and understanding feelings and situations (p = 0.65). Among non-White individuals, higher education levels predicted higher perceived quality of ChatGPT's responses across all information quality measures. Notably, this trend was reversed for White individuals, where higher education levels led to lower perceived information quality. CONCLUSIONS: Our results highlight the importance of developing AI tools sensitive to diverse communication styles and information needs.

Association between depressive symptoms and employment type of Korean workers: the Fifth Korean Working Conditions Survey.

BACKGROUND: This study analyzed the association between depressive symptoms and employment type, by considering both socioeconomic status and job stress factors. METHODS: We analyzed 27,369 participants (13,134 men and 14,235 women) using data from the fifth Korean Working Conditions Survey. The participants were divided into regular and precarious workers. Depressive symptoms were defined using the World Health Organization-5 Well-Being Index. A multivariate logistic regression analysis was performed to assess the association between depressive symptoms and employment type. RESULTS: Of the participants, 71.53% (N = 19578) were regular workers and 28.47% (N = 7791) were precarious workers. The weighted frequencies of participants with depressive symptoms (42.50%) were significantly higher than those of precarious workers (32.54%, p < 0.001). In the univariate and multivariate analyses, precarious workers had a significantly higher risk of depressive symptoms than regular workers (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.42-1.64; OR 1.16, 95% CI 1.07-1.26, respectively). The significant association between depressive symptoms and precarious workers has also been reflected in propensity score matched participants through crude and multivariate analysis (OR 1.54 [95% CI 1.43-1.66] and OR 1.15 [95% CI 1.04-1.26], respectively). CONCLUSIONS: The findings suggest that precarious workers may have a higher risk of depressive symptoms than regular workers. However, this is only a cross-sectional study. Therefore, further study is required to investigate the relevance association between depressive symptoms and employment types.

Anithiactin D, a Phenylthiazole Natural Product from Mudflat-Derived Streptomyces sp., Suppresses Motility of Cancer Cells.

Anithiactin D (1), a 2-phenylthiazole class of natural products, was isolated from marine mudflat-derived actinomycetes Streptomyces sp. 10A085. The chemical structure of 1 was elucidated based on the interpretation of NMR and MS data. The absolute configuration of 1 was determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectral data. Anithiactin D (1) significantly decreased cancer cell migration and invasion activities at a concentration of 5 µM via downregulation of the epithelial-to-mesenchymal transition (EMT) markers in A549, AGS, and Caco-2 cell lines. Moreover, 1 inhibited the activity of Rho GTPases, including Rac1 and RhoA in the A549 cell line, suppressed RhoA in AGS and Caco-2 cell lines, and decreased the mRNA expression levels of some matrix metalloproteinases (MMPs) in AGS and Caco-2 cell lines. Thus 1, which is a new entity of the 2-phenylthiazole class of natural products with a unique aniline-indole fused moiety, is a potent inhibitor of the motility of cancer cells.

The Extract of Gloiopeltis tenax Enhances Myogenesis and Alleviates Dexamethasone-Induced Muscle Atrophy.

The decline in the function and mass of skeletal muscle during aging or other pathological conditions increases the incidence of aging-related secondary diseases, ultimately contributing to a decreased lifespan and quality of life. Much effort has been made to surmise the molecular mechanisms underlying muscle atrophy and develop tools for improving muscle function. Enhancing mitochondrial function is considered critical for increasing muscle function and health. This study is aimed at evaluating the effect of an aqueous extract of Gloiopeltis tenax (GTAE) on myogenesis and muscle atrophy caused by dexamethasone (DEX). The GTAE promoted myogenic differentiation, accompanied by an increase in peroxisome proliferator-activated receptor γ coactivator α (PGC-1α) expression and mitochondrial content in myoblast cell culture. In addition, the GTAE alleviated the DEX-mediated myotube atrophy that is attributable to the Akt-mediated inhibition of the Atrogin/MuRF1 pathway. Furthermore, an in vivo study using a DEX-induced muscle atrophy mouse model demonstrated the efficacy of GTAE in protecting muscles from atrophy and enhancing mitochondrial biogenesis and function, even under conditions of atrophy. Taken together, this study suggests that the GTAE shows propitious potential as a nutraceutical for enhancing muscle function and preventing muscle wasting.

Lithium and exercise ameliorate insulin-deficient hyperglycemia by independently attenuating pancreatic α-cell mass and hepatic gluconeogenesis.

As in type 1 diabetes, the loss of pancreatic ß-cells leads to insulin deficiency and the subsequent development of hyperglycemia. Exercise has been proposed as a viable remedy for hyperglycemia. Lithium, which has been used as a treatment for bipolar disorder, has also been shown to improve glucose homeostasis under the conditions of obesity and type 2 diabetes by enhancing the effects of exercise on the skeletal muscles. In this study, we demonstrated that unlike in obesity and type 2 diabetic conditions, under the condition of insulin-deficient type 1 diabetes, lithium administration attenuated pancreatic a-cell mass without altering insulin-secreting ß-cell mass, implying a selective impact on glucagon production. Additionally, we also documented that lithium downregulated the hepatic gluconeogenic program by decreasing G6Pase protein levels and upregulating AMPK activity. These findings suggest that lithium's effect on glucose metabolism in type 1 diabetes is mediated through a different mechanism than those associated with exerciseinduced metabolic changes in the muscle. Therefore, our research presents the novel therapeutic potential of lithium in the treatment of type 1 diabetes, which can be utilized along with insulin and independently of exercise.

Endoplasmic reticulum stress in pancreatic ß cells induces incretin desensitization and ß-cell dysfunction via ATF4-mediated PDE4D expression.

Pancreatic ß-cell dysfunction and eventual loss are key steps in the progression of type 2 diabetes (T2D). Endoplasmic reticulum (ER) stress responses, especially those mediated by the protein kinase RNA-like ER kinase and activating transcription factor 4 (PERK-ATF4) pathway, have been implicated in promoting these ß-cell pathologies. However, the exact molecular events surrounding the role of the PERK-ATF4 pathway in ß-cell dysfunction remain unknown. Here, we report our discovery that ATF4 promotes the expression of PDE4D, which disrupts ß-cell function via a downregulation of cAMP signaling. We found that ß-cell-specific transgenic expression of ATF4 led to early ß-cell dysfunction and loss, a phenotype that resembles accelerated T2D. Expression of ATF4, rather than C/EBP homologous protein (CHOP), promoted PDE4D expression, reduced cAMP signaling, and attenuated responses to incretins and elevated glucose. Furthermore, we found that ß-cells of leptin receptor-deficient diabetic (db/db) mice had elevated nuclear localization of ATF4 and PDE4D expression, accompanied by impaired ß-cell function. Accordingly, pharmacological inhibition of the ATF4 pathway attenuated PDE4D expression in the islets and promoted incretin-simulated glucose tolerance and insulin secretion in db/db mice. Finally, we found that inhibiting PDE4 activity with selective pharmacological inhibitors improved ß-cell function in both db/db mice and ß-cell-specific ATF4 transgenic mice. In summary, our results indicate that ER stress causes ß-cell failure via ATF4-mediated PDE4D production, suggesting the ATF4-PDE4D pathway could be a therapeutic target for protecting ß-cell function during the progression of T2D.NEW & NOTEWORTHY Endoplasmic reticulum stress has been implied to cause multiple ß-cell pathologies during the progression of type 2 diabetes (T2D). However, the precise molecular events underlying this remain unknown. Here, we discovered that elevated ATF4 activity, which was seen in T2D ß cells, attenuated ß-cell proliferation and impaired insulin secretion via PDE4D-mediated downregulation of cAMP signaling. Additionally, we demonstrated that pharmacological inhibition of the ATF4 pathway or PDE4D activity alleviated ß-cell dysfunction, suggesting its therapeutic usefulness against T2D.

Transcytosis-Inducing Multifunctional Albumin Nanomedicines with Deep Penetration Ability for Image-Guided Solid Tumor Treatment.

Transcytosis is an active transcellular transportation pathway that has garnered interest for overcoming the limited deep penetration of nanomedicines in solid tumors. In this study, a charge-convertible nanomedicine that facilitates deep penetration into solid tumors via transcytosis is designed. It is an albumin-based calcium phosphate nanomedicine loaded with IR820 (mAlb-820@CaP) for high-resolution photoacoustic imaging and enhanced photothermal therapy. Biomineralization on the surface stabilizes the albumin-IR820 complex during circulation and provides calcium ions (Ca2+ ) for tissue penetration on degradation in an acidic environment. pH-triggered transcytosis of the nanomedicine enabled by caveolae-mediated endocytosis and calcium ion-induced exocytosis in 2D cellular, 3D spheroid, and in vivo tumor models is demonstrated. Notably, the extravasation and penetration ability of the nanomedicine is observed in vivo using a high-resolution photoacoustic system, and nanomedicine shows the most potent photothermal antitumor effect in vivo. Overall, the strategy provides a versatile theragnosis platform for both noninvasive photoacoustic imaging and high therapeutic efficiency resulting from deep penetration of nanomedicine.

CGV: Cancer Genome Viewer, a web service for integrative cancer genome and pharmacogenomic data analysis.

MOTIVATION: Multi-omic profiling data, such as The Cancer Genome Atlas and pharmacogenomic data, facilitate research into cancer mechanisms and drug development. However, it is not easy for researchers to connect, integrate and analyze huge and heterogeneous data, which is a major obstacle to the utilization of cancer genomic data. RESULTS: We developed Cancer Genome Viewer (CGV), a user-friendly web service that provides functions to integrate and visualize cancer genome data and pharmacogenomic data. Users can easily select and customize the samples to be analyzed with the pre-defined selection options for patients' clinic-pathological features from multiple datasets. Using the customized dataset, users can perform subsequent data analyses comprehensively, including gene set analysis, clustering or survival analysis. CGV also provides pre-calculated drug response scores from pharmacogenomic data, which may facilitate the discovery of new cancer targets and therapeutics. AVAILABILITY AND IMPLEMENTATION: CGV web service is implemented with the R Shiny application at http://cgv.sysmed.kr and the source code is freely available at https://git.sysmed.kr/sysmed_public/cgv. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Circadian timing, melatonin and hippocampal volume in later-life adults.

Hippocampal atrophy is a prominent neurodegenerative feature of Alzheimer's disease and related dementias. Alterations in circadian rhythms can exacerbate cognitive aging and neurodegeneration. This study aimed to examine how dim light melatonin onset and melatonin levels are associated with hippocampal volume in cognitively healthy individuals. We studied data from 52 later-life adults (mean age ± SD = 70.0 ± 6.3 years). T1-weighted anatomical images from 3.0 T magnetic resonance imaging data were collected and processed using the BRAINSTools toolbox. Dim light melatonin onset was used to assess circadian timing. The area under the curve was calculated to quantify melatonin concentration levels 6 hr before bedtime, and 14-day wrist actigraphy data were used to assess habitual bedtime. Multiple linear regression modelling with hippocampal volume as the dependent variable was used to analyse the data adjusting for age and sex. The average dim light melatonin onset was 19:45 hours (SD = 84 min), and area under the curve of melatonin levels 6 hr before habitual bedtime was 38.4 pg ml-1 × hr (SD = 29.3). We found that later dim light melatonin onset time (b = 0.16, p = 0.005) and greater area under the curve of melatonin levels 6 hr before habitual bedtime (b = 0.05, p = 0.046) were associated with greater adjusted hippocampal volume. The time between dim light melatonin onset and the midpoint of sleep timing was not associated with hippocampal volume. The findings suggest that earlier circadian timing (dim light melatonin onset) and reduced melatonin may be associated with reduced hippocampal volume in older adults. Future research will help researchers utilize circadian rhythm information to delay brain aging.

A Programmable Crypto-Processor for National Institute of Standards and Technology Post-Quantum Cryptography Standardization Based on the RISC-V Architecture.

The advancement of quantum computing threatens the security of conventional public-key cryptosystems. Post-quantum cryptography (PQC) was introduced to ensure data confidentiality in communication channels, and various algorithms are being developed. The National Institute of Standards and Technology (NIST) has initiated PQC standardization, and the selected algorithms for standardization and round 4 candidates were announced in 2022. Due to the large memory footprint and highly repetitive operations, there have been numerous attempts to accelerate PQC on both hardware and software. This paper introduces the RISC-V instruction set extension for NIST PQC standard algorithms and round 4 candidates. The proposed programmable crypto-processor can support a wide range of PQC algorithms with the extended RISC-V instruction set and demonstrates significant reductions in code size, the number of executed instructions, and execution cycle counts of target operations in PQC algorithms of up to 79%, 92%, and 87%, respectively, compared to RV64IM with optimization level 3 (-O3) in the GNU toolchain.

Quantitative Detection of Thitsiol and Urushiol as Markers from the Gluta usitata Lacquer Tree Using HPLC.

Lacquer sap has been traditionally used in coatings and artwork. Suitable types of lacquer are required to preserve and restore artifacts. Recently, unsuitable cashew nut shell liquid (CNSL) has often been mixed with lacquer sap, so it is necessary to identify the characteristics of lacquer sap by the production area. However, research is still focused on urushiol and laccol. In this study, Myanmarese lacquer sap collected from Gluta usitata, which contains thitsiol as the main component, was analyzed by HPLC to quantify thitsiol using the standards 3-(10-phenyldecyl) benzene-1,2-diol (thitsiol 16) and 3-(8Z,11Z-pentadecadienyl)-benzenediol (urushiol 15:2) as markers, and calibration curves were plotted. The coefficients of determination (R2) for thitsiol 16 and urushiol 15:2 were 0.9985 and 0.9983, respectively. In addition, a blind test was conducted to confirm that accurate quantitative analysis was possible even when Myanmarese lacquer was mixed with lacquer from another production area, which contained urushiol as the main component, and CNSL, which contained cardol, a completely different catechol. Quantitative analysis of thitsiol 16 and urushiol 15:2 in Myanmarese lacquer using HPLC can be used to evaluate the quality of lacquer sap and for more sophisticated activities such as restoration by classifying differences in lacquer sap by the production area.

Generation of genome-edited dogs by somatic cell nuclear transfer.

BACKGROUND: Canine cloning technology based on somatic cell nuclear transfer (SCNT) combined with genome-editing tools such as CRISPR-Cas9 can be used to correct pathogenic mutations in purebred dogs or to generate animal models of disease. RESULTS: We constructed a CRISPR-Cas9 vector targeting canine DJ-1. Genome-edited canine fibroblasts were established using vector transfection and antibiotic selection. We performed canine SCNT using genome-edited fibroblasts and successfully generated two genome-edited dogs. Both genome-edited dogs had insertion-deletion mutations at the target locus, and DJ-1 expression was either downregulated or completely repressed. CONCLUSION: SCNT successfully produced genome-edited dogs by using the CRISPR-Cas9 system for the first time.

Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development.

A tumorigenic factor, AIMP2 lacking exon 2 (AIMP2-DX2), is often upregulated in many cancers. However, how its cellular level is determined is not understood. Here, we report heat-shock protein HSP70 as a critical determinant for the level of AIMP2-DX2. Interaction of the two factors was identified by interactome analysis and structurally determined by X-ray crystallography and NMR analyses. HSP70 recognizes the amino (N)-terminal flexible region, as well as the glutathione S-transferase domain of AIMP2-DX2, via its substrate-binding domain, thus blocking the Siah1-dependent ubiquitination of AIMP2-DX2. AIMP2-DX2-induced cell transformation and cancer progression in vivo was further augmented by HSP70. A positive correlation between HSP70 and AIMP2-DX2 levels was shown in various lung cancer cell lines and patient tissues. Chemical intervention in the AIMP2-DX2-HSP70 interaction suppressed cancer cell growth in vitro and in vivo. Thus, this work demonstrates the importance of the interaction between AIMP2-DX2 and HSP70 on tumor progression and its therapeutic potential against cancer.

Highly-packed self-assembled graphene oxide film-integrated resistive random-access memory on a silicon substrate for neuromorphic application.

Resistive random-access memories (RRAMs) based on metal-oxide thin films have been studied extensively for application as synaptic devices in neuromorphic systems. The use of graphene oxide (GO) as a switching layer offers an exciting alternative to other materials such as metal-oxides. We present a newly developed RRAM device fabricated by implementing highly-packed GO layers on a highly doped Si wafer to yield a gradual modulation of the memory as a function of the number of input pulses. By using flow-enabled self-assembly, highly uniform GO thin films can be formed on flat Si wafers in a rapid and simple process. The switching mechanism was explored through proposed scenarios reconstructing the density change of the sp2cluster in the GO layer, resulting in a gradual conductance modulation. We analyzed that the current in a low resistance state could flow by tunneling or hopping via clusters because the distance between the sp2clusters in closely-packed GO layers is short. Finally, through a pattern-recognition simulation with a Modified National Institute of Standards and Technology database, the feasibility of using close-packed GO layers as synapse devices was successfully demonstrated.

Feasibility and acceptability of a digital tele-guided intervention targeting components of the addictive appetite model for bulimia nervosa and binge-eating disorder in Korea.

OBJECTIVE: We aimed to evaluate the feasibility, acceptability, and potential impact of a tele-guided digital-based intervention based on the addictive appetite model of recurrent binge eating. METHOD: Female college students with bulimia nervosa (BN) or binge-eating disorder (BED) (n = 22) received a 6-week guided intervention targeting addictive processes and emotion regulation. The feasibility of the intervention was evaluated, and the outcomes were assessed at baseline, the end of the intervention, and 1-month follow-up. RESULTS: Of the participants, 86.4% (n = 19) completed the intervention. The self-help materials were viewed 6.03 ± 3.06 times per week, and the duration of using the self-help materials was 113.16 ± 160.19 min/week. The intervention group experienced a significant reduction with a moderate effect on binge eating at the end of the intervention (Hedges' g = 0.58), and the effects lasted through follow-up (Hedges' g = 0.82). DISCUSSION: The results suggest that the digital intervention targeting a maintenance mechanism of recurrent binge eating was feasible and acceptable for patients with BN and BED, proving the potential for symptom improvement. PUBLIC SIGNIFICANCE: The addictive appetite model provides the framework for new interventions to improve treatments for BN and BED. This study found that the digital intervention based on the model was feasible and acceptable for patients with BN and BED.

Ultrasound-guided bilateral subcostal transversus abdominis plane block in gastric cancer patients undergoing laparoscopic gastrectomy: a randomised-controlled double-blinded study.

BACKGROUND: The effectiveness of subcostal transversus abdominis plane block (TAPB) in laparoscopic gastric cancer surgery is unknown. We aimed to investigate its opioid-sparing and pain-relief effects in laparoscopic gastrectomy for gastric cancer. METHOD: One hundred and twelve patients undergoing elective laparoscopic gastrectomy were randomised to the TAPB or control group. The TAPB group received ultrasound-guided bilateral subcostal TAPB at the end of surgery, while the control group did not. We investigated fentanyl consumption administered via intravenous patient-controlled analgesia and as a rescue analgesic, the numeric rating scale (NRS) pain scores at rest and during coughing, and the opioid-related side effects at 6, 12, 24, and 48 h postoperatively. The primary outcome was cumulative fentanyl consumption at 24 h postoperatively. RESULTS: The study included 53 patients in each group. The cumulative fentanyl consumption 24 h postoperatively was significantly lower in the TAPB group than in the control group (median difference -170 mcg, P = 0.03, 95% CI -360 to -15 mcg). Subcostal TAPB also significantly reduced the resting NRS score at 48 h postoperatively (median difference -1, 95% CI -1 to 0, P = 0.01) and coughing NRS score at all time points (all median difference -1, 95% CI -2 to 0, P < 0.01, P  = 0.02, 0.01, and 0.01, respectively). However, it did not reduce the occurrence of opioid-related side effects, except the use of antiemetics during the first 6 h postoperatively (TAPB, 1.9% vs. Control, 15.1%, P = 0.03). CONCLUSION: Ultrasound-guided bilateral subcostal TAPB provides efficient postoperative analgesia with an opioid-sparing effect after laparoscopic gastrectomy.

Predictive capacity of COVID-19-related risk beliefs on weight management behaviors on a commercial weight loss program and speed of COVID-19 vaccination uptake: prospective cohort study.

BACKGROUND: Recent work has shown that obesity may be a risk factor for severe COVID-19. However, it is unclear to what extent individuals have heard or believe this risk factor information, and how these beliefs may predict their preventive behaviors (e.g., weight management behaviors or COVID-19 preventive behaviors). Previous work has primarily looked at overall risk likelihood perceptions (i.e., not about obesity as a risk factor) within general populations of varying weight and concentrated on COVID-19-related preventive behaviors. Therefore, this prospective cohort study explored whether beliefs about obesity as a risk factor and overall risk likelihood perceptions predicted weight management and COVID-19 preventive behaviors over the next 16 weeks in individuals with obesity or overweight. METHODS: Participants were 393 individuals in the US who joined a commercial weight management program in January, 2021. We leveraged the mobile program's automatic measurement of real-time engagement in weight management behaviors (e.g., steps taken), while surveys measured risk beliefs at baseline as well as when individuals received COVID-19 vaccination doses (asked monthly) over the next 16 weeks. Mixed effects models predicted engagement and weight loss each week for 16 weeks, while ordinal logistic regression models predicted the month that individuals got vaccinated against COVID-19. RESULTS: We found that belief in obesity as a risk factor at baseline significantly predicted greater engagement (e.g., steps taken, foods logged) in program-measured weight management behaviors over the next 16 weeks in models adjusted for baseline BMI, age, gender, and local vaccination rates (minimally adjusted) and in models additionally adjusted for demographic factors. Belief in obesity as a risk factor at baseline also significantly predicted speed of COVID-19 vaccination uptake in minimally adjusted models but not when demographic factors were taken into account. Exposure to obesity risk factor information at baseline predicted greater engagement over 16 weeks in minimally adjusted models. CONCLUSIONS: The results highlight the potential utility of effective education to increase individuals' belief in obesity risk factor information and ultimately promote engagement or faster vaccination. Future research should investigate to what extent the results generalize to other populations.

Verteporfin synergizes the efficacy of anti-PD-1 in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is one of the primary hepatobiliary malignant neoplasms with only 10% of 5-year survival rate. Promising immunotherapy with the blockade of immune checkpoints has no clear benefit in CCA. The inhibition of YAP1 signaling by verteporfin has shown encouraging results by inhibiting cell proliferation and inducing apoptosis. This study aimed to evaluate the potential benefit of the combination of verteporfin and anti-programmed cell death 1 (PD-1) in CCA mouse model. METHODS: We assessed the cytotoxicity of verteporfin in human CCA cell lines in vitro, including both intrahepatic CCA and extrahepatic CCA cells. We examined the in vitro effect of verteporfin on cell proliferation, apoptosis, and stemness. We evaluated the in vivo efficacy of verteporfin, anti-PD-1, and a combination of both in subcutaneous CCA mouse model. RESULTS: Our study showed that verteporfin reduced tumor cell growth and enhanced apoptosis of human CCA tumor cells in vitro in a dose-dependent fashion. Nevertheless, verteporfin impaired stemness evidenced by reduced spheroid formation and colony formation, decreased numbers of cells with aldehyde dehydrogenase activity and positive cancer stem cell markers (all P < 0.05). The combination of verteporfin and anti-PD-1 reduced tumor burden in CCA subcutaneous SB1 tumor model compared to either agent alone. CONCLUSIONS: Verteporfin exhibits antitumor effects in both intrahepatic and extrahepatic CCA cell lines and the combination with anti-PD-1 inhibited tumor growth.

Endoplasmic Reticulum (ER) Stress and Its Role in Pancreatic ß-Cell Dysfunction and Senescence in Type 2 Diabetes.

An increased life span and accompanying nutritional affluency have led to a rapid increase in diseases associated with aging, such as obesity and type 2 diabetes, imposing a tremendous economic and health burden on society. Pancreatic ß-cells are crucial for controlling glucose homeostasis by properly producing and secreting the glucose-lowering hormone insulin, and the dysfunction of ß-cells determines the outcomes for both type 1 and type 2 diabetes. As the native structure of insulin is formed within the endoplasmic reticulum (ER), ER homeostasis should be appropriately maintained to allow for the proper metabolic homeostasis and functioning of ß-cells. Recent studies have found that cellular senescence is critically linked with cellular stresses, including ER stress, oxidative stress, and mitochondrial stress. These studies implied that ß-cell senescence is caused by ER stress and other cellular stresses and contributes to ß-cells' dysfunction and the impairment of glucose homeostasis. This review documents and discusses the current understanding of cellular senescence, ß-cell function, ER stress, its associated signaling mechanism (unfolded protein response), and the effect of ER stress on ß-cell senescence and dysfunction.

Vitamin C Suppresses Pancreatic Carcinogenesis through the Inhibition of Both Glucose Metabolism and Wnt Signaling.

Cumulative studies have indicated that high-dose vitamin C has antitumor effects against a variety of cancers. However, the molecular mechanisms underlying these inhibitory effects against tumorigenesis and metastasis, particularly in relation to pancreatic cancer, are unclear. Here, we report that vitamin C at high concentrations impairs the growth and survival of pancreatic ductal adenocarcinoma (PDAC) cells by inhibiting glucose metabolism. Vitamin C was also found to trigger apoptosis in a caspase-independent manner. We further demonstrate that it suppresses the invasion and metastasis of PDAC cells by inhibiting the Wnt/ß-catenin-mediated epithelial-mesenchymal transition (EMT). Taken together, our results suggest that vitamin C has therapeutic effects against pancreatic cancer.