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Information system development (ISD) is knowledge-intensive and contains a series of problem-solving activities. Insufficient knowledge stock is a major risk factor in ISD and results in low perfor...

RationaleImmunosuppression in the tumor microenvironment (TME) is key to the pathogenesis of solid tumors. Tumor cell-intrinsic autophagy is critical for sustaining both tumor cell metabolism and survival. However, the role of autophagy in the host immune system that allows cancer cells to escape immune destruction remains poorly understood. Here, we determined if attenuated host autophagy is sufficient to induce tumor rejection through reinforced adaptive immunity. Furthermore, we determined whether dietary glutamine supplementation, mimicking attenuated host autophagy, is capable of promoting antitumor immunity.MethodsA syngeneic orthotopic tumor model in Atg5+/+ and Atg5flox/flox mice was established to determine the impact of host autophagy on the antitumor effects against mouse malignant salivary gland tumors (MSTs). Multiple cohorts of immunocompetent mice were used for oncoimmunology studies, including inflammatory cytokine levels, macrophage, CD4+, and CD8+ cells tumor infiltration at 14 days and 28 days after MST inoculation. In vitro differentiation and in vivo dietary glutamine supplementation were used to assess the effects of glutamine on Treg differentiation and tumor expansion.ResultsWe showed that mice deficient in the essential autophagy gene, Atg5, rejected orthotopic allografts of isogenic MST cells. An enhanced antitumor immune response evidenced by reduction of both M1 and M2 macrophages, increased infiltration of CD8+ T cells, elevated IFN-γ production, as well as decreased inhibitory Tregs within TME and spleens of tumor-bearing Atg5flox/flox mice. Mechanistically, ATG5 deficiency increased glutamine level in tumors. We further demonstrated that dietary glutamine supplementation partially increased glutamine levels and restored potent antitumor responses in Atg5+/+ mice.ConclusionsDietary glutamine supplementation exposes a previously undefined difference in plasticity between cancer cells, cytotoxic CD8+ T cells and Tregs.

Rotary electroplating was employed to fabricate high-strength nanotwinned copper (nt-Cu) foils serving as a current collector for high energy-density lithium ion batteries (LIBs). The effect of Cu ion concentration on the microstructural and mechanical properties of the nt-Cu foils was then investigated. Formation of nano-scaled grains was found at the bottom. Its size gradually increases toward the top surface to form a microstructural mixture of gradient nano-scaled and columnar grains in the upper region. Experimental results show that the grains and elongation of the nt-Cu foils increase with increasing concentration of Cu ions. However, a trade-off between tensile strength and elongation is present. The elongation of nt-Cu foils has been enhanced by 22% (from 3.1% to 3.8%) while 8.3% and 3.9% reductions in ultimate tensile strength (UTS) and yield stress (YS) are seen. The current study shows a promising method to tune and optimize the microstructure and mechanical properties of such nt-Cu foils for various applications.

Surgical post-operative adhesions can lead to serious clinical complications. Barrier agent is the broad usage for the prevention of post-operative adhesions. This study aimed to evaluate the reducing adhesion efficacy of non-animal hyaluronic acid (HA) hydrogel in pigs undergoing conventional laparotomy pelvic surgery. HA hydrogel was applied to eighteen female pigs who underwent conventional laparotomy. The adhesion degrees and histopathology were evaluated in bilateral uterine horns as well as peritoneal sidewall excision. In the present study, all animals survived and had no complications after the surgery. The histopathological observations were demonstrated that HA obviously improved laparotomy pelvic surgery-induced adhesion in peritoneal sidewall and uterine horn. The anastomotic healing score of injury + HA group was significantly lower than the injury alone group. We conclude HA hydrogel can attenuate the post-operative adhesions in porcine.

Redox balance is the critical liaison for cancer homeostasis. Moderate increases in reactive oxygen species (ROS) levels can lead to cancer formation and progression. However, a disproportional increase of ROS levels changes equilibrium in cell redox status and leads to cancer cell death. Therefore, exogenous agents or antioxidant inhibitors which augment ROS generation become a potential new way to target cancer cells. We have found excessive accumulation of cellular proteins during arginine starvation causes stresses on the endoplasmic reticulum (ER) protein folding machinery resulting in elevated ROS levels. In this study, we continue to examine that arginine starvation-attenuated heme oxygenase-1 (HO-1) translation exacerbates the high ROS level to kill the cancer cells. In addition, HO-1 translational downregulation is due to arginine starvation-induced O-GlcNAcylation of eIF2α at S219, T239, and T241 residues. Loss of O-GlcNAcylation at eIF2α significantly rescues arginine starvation-reduced HO-1 protein level, resulting in better recovery and migratory properties from starvation and lower ROS level. In addition, arginine starvation-induced O-GlcNAcylation of eIF2α to suppress HO-1 translation is independent of its phosphorylation at S51, which is another stress-stimuli modification that regulates eIF2 involved protein translation. Arginine starvation exploits O-GlcNAcylation to antagonize eIF2α phosphorylation-induced HO-1 expression. Taken together, arginine starvation is a potential anti-cancer therapy in which induced eIF2α O-GlcNAcylation presents itself as a critical role for metabolic adaptation and tumor growth by dysregulating the antioxidant protein in cancer cells. Citation Format: Yu-Wen Hung, Yi-Chang Wang, David K. Ann. eIF2α O-GlcNAcylation promotes oxidative stress in arginine-starved triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5809.

The aim of the study was to develop a simple, rapid, and reliable technique to detect the pharmacokinetics and the residual of florfenicol (FFC) in Bester sturgeon, a cultured hybrid of Huso huso × Acipenser ruthenus by high performance liquid chromatography (HPLC) with UV detector. The results showed that the concentration-time course of the FFC was described by one-compartment model with 1st order absorption in the blood. The retention time of FFC was 7.3 min. The limit of detection of FFC concentration using our developed method was 0.01 mg kg−1 BW. After given single dose 10 mg kg−1 BW per day of FFC via oral administration for sturgeon, the main pharmacokinetic parameters in blood were found as following: Cmax (maximum concentration) was 10.9568 μg mL−1, Tmax (time to Cmax) was 10 h, AUC (area under the curve) was 251.064 μg × hr mL−1, t1/2 (half-life) was 12.1301 h, CL (total body clearance) was 0.0387 L kg−1, V/F (apparent volume of distribution) was 0.6777 L kg−1, and MRT (the mean residence time) was 23.7431 h. Additionally, the concentration-time course of the FFC was also described by two-compartment model with 1st order absorption in the muscle and liver. The recoveries of muscle and liver from sturgeon were 92–108% and 90–104%, respectively. Taken together, the results showed that the developed method technique may be a valuable tool was efficient in detecting the pharmacokinetics of FFC in Bester sturgeon.

Long noncoding RNAs (lncRNAs) have been implicated in hypoxia/HIF-1-associated cancer progression through largely unknown mechanisms. Here we identify MIR31HG as a hypoxia-inducible lncRNA and therefore we name it LncHIFCAR (long noncoding HIF-1α co-activating RNA); we describe its oncogenic role as a HIF-1α co-activator that regulates the HIF-1 transcriptional network, crucial for cancer development. Extensive analyses of clinical data indicate LncHIFCAR level is substantially upregulated in oral carcinoma, significantly associated with poor clinical outcomes and representing an independent prognostic predictor. Overexpression of LncHIFCAR induces pseudo-hypoxic gene signature, whereas knockdown of LncHIFCAR impairs the hypoxia-induced HIF-1α transactivation, sphere-forming ability, metabolic shift and metastatic potential in vitro and in vivo. Mechanistically, LncHIFCAR forms a complex with HIF-1α via direct binding and facilitates the recruitment of HIF-1α and p300 cofactor to the target promoters. Our results uncover an lncRNA-mediated mechanism for HIF-1 activation and establish the clinical values of LncHIFCAR in prognosis and potential therapeutic strategy for oral carcinoma., Cancer cells adapt to the changing microenvironment by activating different pathways through multiple mechanisms. Here the authors identify long noncoding RNA MIR31HG as a HIF-1α co-activator required for the induction of the hypoxic response and show its oncogenic role in oral carcinogenesis.

Dipeptidyl peptidase-4 inhibitors (or gliptins), a class of antidiabetic drugs, have recently been shown to have protective actions in the central nervous system. Their cellular and molecular mechanisms responsible for these effects are largely unknown. In the present study, two structurally different gliptins, sitagliptin and vildagliptin, were examined for their therapeutic actions in a controlled cortical impact (CCI) model of moderate traumatic brain injury (TBI) in mice. Early post-CCI treatment with sitagliptin, but not vildagliptin, significantly reduced body asymmetry, locomotor hyperactivity, and brain lesion volume. Sitagliptin attenuated post-CCI microglial deramification in the ipsilateral dorsolateral (DL) striatum, while vildagliptin had no effect. Sitagliptin also reduced striatal expression of galectin-3 and monocyte chemoattractant protein 1(MCP-1), and increased the cortical and striatal levels of the anti-inflammatory cytokine IL-10 on the ipsilateral side. These data support a differential protective effect of sitagliptin against TBI, possibly mediated by an anti-inflammatory effect in striatum to preserve connective network. Both sitagliptin and vildagliptin produced similar increases of active glucagon-like peptide-1 (GLP-1) in blood and brain. Increasing active GLP-1 may not be the sole molecular mechanisms for the neurotherapeutic effect of sitagliptin in TBI.

Ultraviolet (UV) light has been developed for surface decontamination. However, UV light has some limitations at harmful effects for human and animals

Farming of sturgeon in worldwide has increased in recent years. The use of antibiotics to minimize the impact of disease outbreak in sturgeon aquaculture becomes very important.

It is generally understood that continuing neuroinflammation after ischemic stroke can exacerbate the brain damage. During the inflammatory hematogenous recruitment process, the monocytes and macrophages are activated into proinflammatory M1 and anti-inflammatory M2 cell types. Inhibition of soluble epoxide hydrolase (sEH) activity has been reported to regulate monocytes/macrophages, and attenuates neuroinflammation. This study aimed to evaluate whether a selective sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), can regulate monocyte/macrophage polarization and improve motor function in the rats with ischemic stroke induced by middle cerebral artery occlusion. We measured the infarct volume with 2,3,5-triphenyltetrazolium chloride staining and used the rotarod test to assess motor performance in rats. The monocyte/macrophage activation and mRNA expression of proinflammatory mediators were measured by flow cytometry and reverse-transcription quantitative PCR, respectively. Our results showed better neurological function and less infarct volume in the rats treated with AUDA. Compared with the vehicle group, the AUDA-treated group showed a reduction in M1 monocyte/macrophage activation and proinflammatory mRNA expressions in the infarct cortex of rats. Our data suggest that the sEH inhibition may regulate monocyte/macrophage polarization and improve neurological outcome after ischemic stroke.

Chien-Fu Yeh,1–3,* Tung‐Yueh Chuang,4,* Yu-Wen Hung,5 Ming-Ying Lan,2,3 Ching-Han Tsai,4 Hao-Xiang Huang,4 Yung-Yang Lin1,4,6–8 1Institute of Brain Science, National Yang-Ming University, Taipei 11221, Taiwan; 2Department of Otorhinolaryngology, National Yang-Ming University, Taipei 11221, Taiwan; 3Department of Otolaryngology-Head and Neck Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan; 4Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; 5Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County 35053, Taiwan; 6Institute of Physiology, National Yang-Ming University, Taipei 11221, Taiwan; 7Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan; 8Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan*These authors contributed equally to this workCorrespondence: Yung-Yang LinDepartment of Critical Care Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Taipei 11217, TaiwanTel +886-2-2871-2121Fax +886-2-2875-7890Email g2000kev@gmail.comBackground: Ischemic stroke triggers inflammatory responses and oxidative stress in the brain, and microglia polarization affects the degree of neuroinflammation. It has been reported that the inhibition of soluble epoxide hydrolase (sEH) activity protects brain tissue. However, the anti-inflammatory and antioxidative effects of sEH inhibition in the ischemic brain are not fully understood. This study aimed to investigate the effects of a selective sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), after ischemic stroke.Methods: Adult male rats with middle cerebral artery occlusion (MCAO) were administered with AUDA or a vehicle. Behavioral outcome, infarct volume, microglia polarization, and gene expression were assessed.Results: Rats treated with AUDA showed better behavioral outcomes and smaller infarct volumes after MCAO. After AUDA treatment, a reduction of M1 microglia and an increase of M2 microglia occurred at the ischemic cortex of rats. Additionally, there was an increase in the mRNA expressions of antioxidant enzymes and anti-inflammatory interleukin-10, and pro-inflammatory mediators were decreased after AUDA administration. Heme oxygenase-1 was mainly expressed by neurons, and AUDA was found to improve the survival of neurons.Conclusion: The results of this study provided novel and significant insights into how AUDA can improve outcomes and modulate inflammation and oxidative stress after ischemic stroke.Keywords: ischemic stroke, microglia polarization, middle cerebral artery occlusion, soluble epoxide hydrolase, anti-inflammation, antioxidant

Background/Aim: Middle cerebral artery occlusion (MCAO) in rodents is an essential animal model for research focusing on ischemic stroke. To date, several kinds of surgical methods for MCAO have been developed and the craniotomy method has the advantage of direct visualization of the middle cerebral artery (MCA). MCAO at a more proximal site produces better surgical results, but it is a more invasive technique. The aim of this study was to evolve the surgical technique for simulating ischemic cerebral cortex injury in rats. Materials and Methods: To approach proximal MCA with a less invasive procedure, a modified surgical technique for MCAO in rats was developed. Besides, rats receiving the modified and conventional method were compared with regard to infarct volume and by behavioral tests. Results: Following craniotomy, we proposed that the inferior edge of the craniotomy should be enlarged with fine forceps. This modified surgical method induces larger infarct volume, significant behavioral impairment and can induce ischemic stroke. Additionally, it does not significantly increase the operation time, and has produced no obvious complications. Conclusion: This modified surgical technique may serve as a practical method for performing MCAO.

Colon cancer is very important cancer worldwide. Although many therapies and therapeutic strategies are applied in the patients with cancer, however, the deaths of patients with cancer maintain in the top of the dead people worldwide...

Neuroinflammation is known to be involved in epileptogenesis with unclear mechanisms. Inhibition of soluble epoxide hydrolase (sEH) seems to offer anti-inflammatory protection to ischemic brain injury in rodents. Thus, it is hypothesized that sEH inhibition might also affect the neuroinflammatory responses caused by epileptic seizures. In the present study, we investigated the involvement of sEH in neuroinflammation, seizure generation and subsequent epileptogenesis using two mouse models of temporal lobe epilepsy. Experimental epileptic seizures were induced by either pilocarpine or electrical amygdala kindling in both wild-type (WT) C57BL/6 mice and sEH knockout (sEH KO) mice. The sEH expression in the hippocampus was detected by immunohistochemistry and Western blot analysis. The effects of the sEH hydrolase inhibitors, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) and N-[1-(1-oxopropyl)-4-piperidinyl]-N′-[4-(trifluoromethoxy) phenyl)-urea (TPPU), and of the genetic deletion of sEH on seizure-induced neuroinflammatory responses and the development of epilepsy were evaluated. In the hippocampus of WT mice, sEH was mainly expressed in astrocytes (GFAP+), neurons (NeuN+) and scattered microglia (Iba-1+) in the regions of CA1, CA3 and dentate gyrus. Expression of sEH was significantly increased on day 7, 14, 21 and 28 after pilocarpine-induced status epilepticus (SE). Administration with sEH inhibitors attenuated the SE-induced up-regulation of interleukin-1β (IL-1β) and interleukin-6 (IL-6), the degradation of EETs, as well as IκB phosphorylation. Following treatment with AUDA, the frequency and duration of spontaneous motor seizures in the pilocarpine-SE mice were decreased and the seizure-induction threshold of the fully kindled mice was increased. Up-regulation of hippocampal IL-1β and IL-6 was found in both WT and sEH KO mice after successful induction of SE. Notably, sEH KO mice were more susceptible to seizures than WT mice. Seizure related neuroinflammation and ictogenesis were attenuated by pharmacological inhibition of sEH enzymatic activity but not by sEH genetic deletion. Therefore, sEH may play an important role in the generation of epilepsy. Furthermore, the effectiveness of AUDA in terms of anti-inflammatory and anti-ictogenesis properties suggests that it may have clinical therapeutic implication for epilepsy in the future, particularly when treating temporal lobe epilepsy.

Paeonol is a key phenolic compound in the root bark of Moutan Cortex Radicis that has been used in traditional Chinese Medicine to ameliorate inflammation. A series of aminothiazole-paeonol derivatives (APDs) were synthesized in this work and subjected to preliminary evaluation in cells followed by verification in animals. Quantification of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in culture media of LPS-activated A549 cells, a lung epithelial adenocarcinoma cell line, were used to investigate the anti-inflammatory capability of APDs. ALI-bearing rats were employed to verify therapeutic efficacy of APDs according to observations of total cells, protein amounts, MCP-1 and IL-6 in bronchoalveolar lavage fluid (BALF). Histopathological examinations of lung tissues were consequently applied for validation of APDs. Among these compounds, 2-(2-aminothiazol-4-yl)-5-methoxyphenol (4) had the most potent activity, showing comparable inhibition of MCP-1/IL-6 and superior elimination of neutrophil infiltration and protein exudation in lungs compared to others as well as dexamethasone. This study demonstrated a comprehensive strategy to evaluate APDs through integration of cell-based screening and animal-based verification. In order to fulfill unmet needs of treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), APDs introduced in this work could be promising lead compounds to develop high potent anti-inflammation agents.

This paper presents a solid-state sensor for rapidly detecting the acidity and the total dissolved ions of urine. The sensor is produced by direct laser engraving the commercial touch panel film to pattern the sensing areas. Since the indium tin oxide on the touch panel film is an n-type degenerate semiconductor, hydrogen ions in the solution spontaneously attach onto the ITO surface and change the zeta potential of it. The sensing area is connected to the gate of a commercial N-MOSFET CD4007 to establish the extended-gate FET sensing scheme. Full ITO-based sensing chips for pH and total dissolved ions in urine can be easily produced in the developed rapid manufacturing process. Home-build circuits embedded in hand-held devices are produced for the measurement. Results show that the developed ITO-based sensor exhibits high sensing performance for acidity measurement of 0.11 V pH−1 with rapid responses of less than 1 s and low temperature drifting of 0.0205 pH °C−1. The sensor can also detect total dissolved ions with a concentration of 0.1−30 mS in urine. The performance of the developed sensor is characterized by a classic physiology experiment of kidney elution after taking various liquids of reverse osmosis water, beer, and normal saline.

Based on a coproduction concept highlighted by service-dominant logic, this study attempts to understand the antecedents and consequences of user coproduction in information system development projects. As a key contribution, we posit that user coproduction is influenced by social capital between users and developers; we then postulate that user coproduction determines the project outcomes. Paired data collected from both user representatives and developers by using a survey approach was used to test proposed hypotheses. The results showed that user coproduction has a positively significant influence on project outcomes, and social capital between user representatives and developers is also associated with user coproduction.

Pompe disease is a rare inherited metabolic disorder of glycogen metabolism caused by mutations in the GAA gene, encoding the acid α-1,4 glucosidase. Successful diagnosis of Pompe disease is achieved by clinical and biochemical evaluation followed by confirmation with DNA testing. Here, we report a male infant with a prenatal onset of cardiac symptoms and enzyme testing consistent with Pompe disease, but DNA testing by Sanger sequencing revealed no pathogenic variants. Due to the strong indication from clinical, enzymatic, and histological studies (despite the absence of molecular confirmation by traditional Sanger sequencing), enzyme replacement therapy (ERT) for Pompe disease was initiated. Reanalysis of the patient's DNA sample using next generation sequencing (NGS) of a panel of target genes causing glycogen storage disorders demonstrated compound heterozygosity for a point mutation and an exonic deletion in the GAA gene. This case illustrates the value of astute clinical judgement in patient management as well as the power of target capture deep NGS in the simultaneous detection of both a point mutation and a heterozygous exonic deletion by correcting pitfalls of the traditional PCR based sequencing, namely; allele dropout and the inability to detect exonic deletions.

Summary The duration of sustained seizures (SS) plays a crucial role in the occurrence of spontaneous recurrent seizures (SRS) in experimental animals. We tested whether rats with varying durations of initial convulsive SS exhibited differential neurogenesis patterns in the hippocampal dentate gyrus that may be related to subsequent epileptogenesis. Sprague-Dawley rats with pilocarpine-induced convulsive SS were divided into short SS (30 min) and long SS (2 h) groups. Their behavior was monitored to identify convulsive SRS. From 1 to 28 days post-SS, cell proliferation was evaluated by 5′-bromo-2′-deoxyuridine (BrdU) labeling and immature neuroblasts in the dentate gyrus were identified by doublecortin immunohistochemistry. Convulsive SRS was detected in 8 out of the 9 long SS rats, but not in the 9 short SS rats. During day 1–3, proliferative cells were diffusely localized throughout the hippocampus in the long SS rats but were primarily confined within the subgranular zone in the short SS rats. Within the subgranular zone, a significant increase in the number of BrdU-positive cells was found at days 3 and 7 after the long SS and on day 1 after the short SS. Notably, abnormal dendritic outgrowth and hilar-ectopic localization of doublecortin-positive cells were present in the long SS rats. In conclusion, aberrant hippocampal neurogenesis following long SS may contribute to the development of SRS.

This study investigates the role of users as knowledge co-producers in different stages of the information system development project. Data collected from 269 IS professionals supported our hypotheses that common knowledge has an impact on requirement determination, which, in turn, leads to better project performance. User–IS relationship can substitute the effect of common knowledge on requirement determination in the design stage and user review can ensure that the obtained requirements are actually carried out by developers in the development stage. As a result, higher project performance can be obtained. Discussion of the results and conclusions is also provided.

Online shopping has grown substantially across the globe. Understanding how to increase customers' loyalty through lifting up the level of satisfaction has been emphasized by both researchers and practitioners. Prior research focuses on overall satisfaction and continuance intention. In this study, we integrate expectation-confirmation theory (ECT) and IS success model to examine how consumers' expectation, perception and confirmation and satisfaction on information quality, system quality, and service quality affects their continuance intention toward online shopping. We surveyed 368 full- and part-time students to test and validate the model and relationship. The results showed that confirmation and satisfaction are strongly affected by perceived quality but not expectation. However, the impact of satisfaction on continuance intention is not as strong as expected.