Mucoadhesive Thiolated Hyaluronic Acid/Pluronic F127 Nanogel Formation via Thiol-Maleimide Click Reaction for Intravesical Drug Delivery.

The development of nanocarriers to prolong the residence time and enhance the permeability of chemotherapeutic drugs on bladder mucosa is important in the postsurgery treatment of superficial bladder cancers (BCs). Here, the mucoadhesive HA-SH/PF127 nanogels composed of a temperature-sensitive Pluronic F127 (PF127) core and thiolated hyaluronic acid (HA-SH) shell were prepared by the emulsification/solvent evaporation method. The nanogels were constructed through the thiol-maleimide click reaction in the HA-SH aqueous side of the oil-water interface and self-oxidized cross-linking thiols between HA-SH. The HA-SH/PF127 nanogels prepared at different thiol-to-maleimide group molar ratios, water-to-oil volume ratios, and cross-linking reaction times were characterized regarding hydrodynamic diameter (Dh) and zeta potential (ζ), and the optimal formulation was obtained. The excellent mucoadhesive properties of the HA-SH/PF127 nanogels were evaluated by using the mucin particle method. Doxorubicin (DOX) was encapsulated in the PF127 core of DOX@HA-SH/PF127 nanogels with a high loading efficiency (87.5%) and sustained release from the nanogels in artificial urine. Ex vivo studies on porcine bladder mucosa showed that the DOX@HA-SH/PF127 nanogels enhanced the penetration of the DOX into the bladder mucosa without disrupting the mucus structure or the bladder tissue. A significant dose-dependent cytotoxic effect of DOX@HA-SH/PF127 nanogels on both T24 and MB49 cells was observed. The present study demonstrates that the mucoadhesive HA-SH/PF127 nanogels are a promising intravesical drug delivery system for superficial BC therapy.

Dynamic event-triggered consensus control for nonlinear multi-agent systems under DoS attacks.

In this paper, we investigated leader-following consensus control for nonlinear multi-agent systems (MASs) experiencing denial-of-service (DoS) attacks. We proposed a distributed control strategy incorporating an adaptive scheme and a state feedback control gain to eliminate the effects of system nonlinear dynamics and uncertainties. In addition, we introduced a dynamic event-triggered control (DETC) to minimize the utilization of communication resources. Finally, we provided simulation results to show the validity of the proposed approach.

Cordyceps militaris Solid Medium Extract Alleviates Lipoteichoic Acid-Induced MH-S Inflammation by Inhibiting TLR2/NF-κB/NLRP3 Pathways.

The aim of this study was to investigate the inhibitory effects of Cordyceps militaris solid medium extract (CME) and cordycepin (COR) on LTA-induced inflammation in MH-S cells and their mechanisms of action. In this study, the establishment of an LTA-induced MH-S inflammation model was determined, the CCK-8 method was used to determine the safe concentration range for a drug for COR and CME, the optimal concentration of COR and CME to exert anti-inflammatory effects was further selected, and the expression of inflammatory factors of TNF-α, IL-1ß, IL-18, and IL-6 was detected using ELISA. The relative expression of TNF-α, IL-1ß, IL-18, IL-6, IL-10, TLR2 and MyD88 mRNA was detected using RT-PCR, and the IL-1ß, IL-18, TLR2, MyD88, NF-κB p-p65, NLRP3, pro-caspase-1, Caspase-1 and ASC protein expression in the cells were detected using Western blot; immunofluorescence assay detected the expression of Caspase-1 in MH-S cells. The results revealed that both CME and COR inhibited the levels of IL-1ß, IL-18, IL-6, and TNF-α in the supernatants of LTA-induced MH-S cells and the mRNA expression levels of IL-1ß, IL-18, IL-6, TNF-α, TLR2 and MyD88, down-regulated the LTA-induced IL-1ß, IL-18, TLR2 in MH-S cells, MyD88, NF-κB p-p65/p65, NLRP3, ASC, pro-caspase-1, and caspase-1 protein expression levels, and inhibited LTA-induced caspase-1 activation in MH-S cells. In conclusion, CME can play a therapeutic role in LTA-induced inflammation in MH-S cells via TLR2/NF-κB/NLRP3, and may serve as a potential drug for bacterial pneumonia caused by Gram-positive bacteria.

Investigating EGF and PAG1 as necroptosis-related biomarkers for diabetic nephropathy: an in silico and in vitro validation study.

The current study aims to understand the mechanisms behind regulated cell death (RCD) in diabetic nephropathy and identify related biomarkers through bioinformatics and experimental validation. Datasets of bulk and single-cell RNA sequencing were obtained from public databases and analyzed using gene set variation analysis (GSVA) with gene sets related to RCD, including autophagy, necroptosis, pyroptosis, apoptosis, and ferroptosis. RCD-related gene biomarkers were identified using weighted gene correlation network analysis (WGCNA). The results were verified through experiments with an independent cohort and in vitro experiments. The GSVA revealed higher necroptosis scores in diabetic nephropathy. Three necroptosis-related biomarkers, EGF, PAG1, and ZFP36, were identified and showed strong diagnostic ability for diabetic kidney disease. In vitro experiments showed high levels of necroptotic markers in HK-2 cells treated with high glucose. Bioinformatics and experimental validation have thus identified EGF and PAG1 as necroptosis-related biomarkers for diabetic nephropathy.

Design, Synthesis, and Evaluation of 18F-Labeling CYP1B1 PET Tracer Based on 2-Phenylquinazolin.

Cytochrome P450 (CYP)1B1 has been identified to be specifically overexpressed in several solid tumors, thus it's a potential target for the detection of tumors. Based on the 2-Phenylquinazolin CYP1B1 inhibitors, we designed and synthesized several positron emission computed tomography (PET) imaging probes targeting CYP1B1. Through IC50 determinations, most of these probes exhibited good affinity and selectivity to CYP1B1. Considering their affinity, solubility, and their 18F labeling methods, we chose compound 5c as the best candidate. The 18F radiolabeling of [18F] 5c was easy to handle with good radiolabeling yield and radiochemical purity. In vitro and in vivo stability study indicated that probe [18F]5c has good stability. In cell binding assay, [18F]5c could be specifically taken up by tumor cells, especially HCT-116 cells. Although the tumor-blood (T/B) and tumor-muscle (T/M) values and PET imaging results were unsatisfied, it is still possible to develop PET probes targeting CYP1B1 by structural modification on the basis of 5c in the future.

Comparative effects of hepatocyte growth factor and tacrolimus on acute liver allograft early tolerance.

Allostimulated CD8+ T cells (aCD8+ T cells), as the main mediators of acute liver rejection (ARJ), are hyposensitive to apoptosis due to the inactivation of death receptor FAS-mediated pathways and fail to allow tolerance induction, eventually leading to acute graft rejection. Although tacrolimus (FK506), the most commonly used immunosuppressant (IS) in the clinic, allows tolerance induction, its use is limited because its target immune cells are unknown and it is associated with increased incidences of malignancy, infection, and nephrotoxicity, which substantially impact long-term liver transplantation (LTx) outcomes. The dark agouti (DA)-to-Lewis rat LTx model is a well-known ARJ model and was hence chosen for the present study. We show that both hepatocyte growth factor (HGF) (cHGF, containing the main form of promoting HGF production) and recombinant HGF (h-rHGF) exert immunoregulatory effects mainly on allogeneic aCD8+ T cell suppression through FAS-mediated apoptotic pathways by inhibiting cMet to FAS antagonism and Fas trimerization, leading to acute tolerance induction. We also showed that such inhibition can be abrogated by treatment with neutralizing antibodies against cMet (HGF-only receptor). In contrast, we did not observe these effects in rats treated with FK506. However, we observed that the effect of anti-rejection by FK506 was mainly on allostimulated CD4+ T cell (aCD4+ T cell) suppression and regulatory T cell (Treg) promotion, in contrast to the mechanism of HGF. In addition, the protective mechanism of HGF in FK506-mediated nephrotoxicity was addressed. Therefore, HGF as a tolerance inducer, whether used in combination with FK506 or as monotherapy, may have good clinical value. Additional roles of these T-cell subpopulations in other biological systems and studies in these fields will also be meaningful.

Enhanced crow search algorithm with multi-stage search integration for global optimization problems.

Crow search algorithm (CSA), as a new swarm intelligence algorithm that simulates the crows' behaviors of hiding and tracking food in nature, performs well in solving many optimization problems. However, while handling complex and high-dimensional global optimization problems, CSA is apt to fall into evolutionary stagnation and has slow convergence speed, low accuracy, and weak robustness. This is mainly because it only utilizes a single search stage, where position updating relies on random following among individuals or arbitrary flight of individuals. To address these deficiencies, a CSA with multi-stage search integration (MSCSA) is presented. Chaos and multiple opposition-based learning techniques are first introduced to improve original population quality and ergodicity. The free foraging stage based on normal random distribution and Lévy flight is designed to conduct local search for enhancing the solution accuracy. And the following stage using mixed guiding individuals is presented to perform global search for expanding the search space through tracing each other among individuals. Finally, the large-scale migration stage based on the best individual and mixed guiding individuals concentrates on increasing the population diversity and helping the population jump out of local optima by moving the population to a promising area. All of these strategies form multi-level and multi-granularity balances between global exploration and local exploitation throughout the evolution. The proposed MSCSA is compared with a range of other algorithms, including original CSA, three outstanding variants of CSA, two classical meta-heuristics, and six state-of-the-art meta-heuristics covering different categories. The experiments are conducted based on the complex and high-dimensional benchmark functions CEC 2017 and CEC 2010, respectively. The experimental and statistical results demonstrate that MSCSA is competitive for tackling large-scale complicated problems, and is significantly superior to the competitors.

Regeneration of T cells from human-induced pluripotent stem cells for CAR-T cell medicated immunotherapy.

Background: Chimeric antigen receptor (CAR) T cell treatment involves in vitro production of T cells from patient blood with synthetic receptors specific to a cancer antigen. They circumvent the major histocompatibility complex to recognize the tumor antigen, reducing hematologic malignancy remission rates by 80%. Considering the efficacy of CAR-T treatment, the present work aimed at generating functional clusters of differentiation (CD)8 + T cells from human induced pluripotent stem cells (hiPSC) and to generate hiPS-CAR-T cells with high antigen-specific cytotoxicity. Methods: The Alkaline phosphatase assay and MycoEasy rapid mycoplasma detection kit was implemented for detection of hiPSCs and mycoplasma, respectively. The CD34+ HSPCs were harvested in AggreWellTM 400 using a 37-micron reversible strainer. Likewise, the lymphoid progenitor and CD4+CD8+ DP T cells were also harvested. The Cell Counting Kit-8 (CCK-8) assay was used to mark cytotoxicity and ELISA was used to detect IFN-γ secretion. Further, flow cytometry and transwell chambers were used to assess cell cycle, and migration and invasion. Finally, the in vivo antitumor effects of the CAR-T cells were evaluated using experimental animals (mice). Results: Results revealed that a serum-free, feeder layer-free differentiation system significantly yielded hiPSC-based T cell immunotherapy with interleukin-2, interleukin-15, and activators at the differentiation stage to promote the maturation of these cells into human induced pluripotent stem (hiPS)-T cells. The infection of hiPSCs with the CD19 CAR lentivirus resulted in the production of the hiPSC-CAR-T cells. We validated the function of hiPS-CAR-T cells in vivo and in vitro experimentation which revealed no significant differences in cell morphology and function between hiPSC-derived hiPS-CAR-T cells and peripheral blood-derived CAR-T cells. Conclusion: This study developed a culture method that is efficient and clinically useful to make functional CD8+ T cells from hiPSC and to get hiPS-CAR-T cells with high antigen-specific cytotoxicity that are not very different from CAR T cells found in peripheral blood. As a result, our findings may open the way for the clinical use of hiPSC to create functional CD8+ T and hiPS-CAR-T cells cells for use in cell-based cancer therapy.

Development of [18F]Thiazolylacylaminopyridine-Based Glycogen synthase Kinase-3ß ligands for positron emission tomography imaging.

Glycogen synthase kinase-3ß (GSK-3ß) regulates numerous of CNS-specific signaling pathways, and is particularly implicated in various pathogenetic mechanisms of Alzheimer's disease (AD). A noninvasive method for detecting GSK-3ß in AD brains via positron emission tomography (PET) imaging could enhance the understanding of AD pathogenesis and aid in the development of AD therapeutic drugs. In this study, an array of fluorinated thiazolyl acylaminopyridines (FTAAP) targeting GSK-3ß were designed and synthesized. These compounds showed moderate to high affinities (IC50 = 6.0 - 426 nM) for GSK-3ß in vitro. A potential GSK-3ß tracer, [18F]8, was successfully radiolabeled. [18F]8 had unsatisfactory initial brain uptake despite its suitable lipophilicity, molecular size and good stability. Further structural refinement of the lead compound is needed to develop promising [18F]-labeled radiotracers for the detection of GSK-3ß in AD brains.

Biochar-Dual Oxidant Composite Particles Alleviate the Oxidative Stress of Phenolic Acid on Tomato Seed Germination.

Phenolic acid is a well-known allelochemical, but also a pollutant in soil and water impeding crop production. Biochar is a multifunctional material widely used to mitigate the phenolic acids allelopathic effect. However, phenolic acid absorbed by biochar can still be released. In order to improve the removal efficiency of phenolic acids by biochar, the biochar-dual oxidant (BDO) composite particles were synthesized in this study, and the underlying mechanism of the BDO particles in ameliorating p-coumaric acid (p-CA) oxidative damage to tomato seed germination was revealed. Upon p-CA treatment, the BDO composite particles application increased the radical length, radical surface area, and germination index by 95.0%, 52.8%, and 114.6%, respectively. Compared to using biochar or oxidants alone, the BDO particles addition resulted in a higher removal rate of p-CA and produced more O2•-, HO•, SO4•- and 1O2 radicals via autocatalytic action, suggesting that BDO particles removed phenolic acid by both adsorption and free radical oxidation. The addition of BDO particles maintained the levels of the antioxidant enzyme activity close to the control, and reduced the malondialdehyde and H2O2 by 49.7% and 49.5%, compared to the p-CA treatment. Integrative metabolomic and transcriptomic analyses revealed that 14 key metabolites and 62 genes were involved in phenylalanine and linoleic acid metabolism, which increased dramatically under p-CA stress but down-regulated with the addition of BDO particles. This study proved that the use of BDO composite particles could alleviate the oxidative stress of phenolic acid on tomato seeds. The findings will provide unprecedented insights into the application and mechanism of such composite particles as continuous cropping soil conditioners.

Maresin-1 improves LPS-induced depressive-like behavior by inhibiting hippocampal microglial activation.

Maresin-1 is an antiphlogistic agonist synthesized by macrophages from docosahexaenoic acid (DHA). It has both anti-inflammatory and pro-inflammatory properties and has been found to enhance neuroprotection and cognitive function. However, there is limited knowledge of its effects on depression and the potential mechanism remains unclear. In this study, the effects of Maresin-1 on lipopolysaccharide (LPS)-induced depressive symptoms and neuroinflammation were investigated in mice and the possible cellular and molecular mechanisms were further clarified. Maresin-1 treatment (5 µg/kg, i.p.) led to improved tail suspension times, as well as distances moved in an open-field test but it did not improve reductions in sugar-water consumption in mice with depressive-like behaviors induced by LPS (1 mg/kg, i.p.); TSPO PETCT scanning showed that Maresin-1 reduced the standardized uptake value (SUV) of [18 F] DPA-714 in brain regions associated with depression (e.g., hippocampus and pre-frontal cortex), while immunofluorescence of hippocampal and indicated that Maresin-1 inhibited microglial activation reducing the expression of the pro-inflammatory cytokine IL-1ß and NLRP3. The RNA sequencing of mouse hippocampi showed that genes expressed differentially between Maresin-1-treated and LPS-treated tissue were associated with tight connections between cells and the stress-activated MAPK cascade negative regulatory pathways. Overall, this study demonstrates that peripheral application of Maresin-1 could partially relieve LPS-induced depressive-like behaviors and showed for the first time that this effect was related to its anti-inflammatory action on microglia, thus providing new clues for the pharmacological mechanism underlying the anti-depression properties of Maresin-1.

A Robust Visual System for Looming Cue Detection Against Translating Motion.

Collision detection is critical for autonomous vehicles or robots to serve human society safely. Detecting looming objects robustly and timely plays an important role in collision avoidance systems. The locust lobula giant movement detector (LGMD1) is specifically selective to looming objects which are on a direct collision course. However, the existing LGMD1 models cannot distinguish a looming object from a near and fast translatory moving object, because the latter can evoke a large amount of excitation that can lead to false LGMD1 spikes. This article presents a new visual neural system model (LGMD1) that applies a neural competition mechanism within a framework of separated ON and OFF pathways to shut off the translating response. The competition-based approach responds vigorously to monotonous ON/OFF responses resulting from a looming object. However, it does not respond to paired ON-OFF responses that result from a translating object, thereby enhancing collision selectivity. Moreover, a complementary denoising mechanism ensures reliable collision detection. To verify the effectiveness of the model, we have conducted systematic comparative experiments on synthetic and real datasets. The results show that our method exhibits more accurate discrimination between looming and translational events-the looming motion can be correctly detected. It also demonstrates that the proposed model is more robust than comparative models.

A new class of CYP1B1 inhibitors derived from bentranil.

Cytochrome P450 1B1 (CYP1B1) is highly expressed in a variety of tumors and implicated to drug resistance. More and more researches have suggested that CYP1B1 is a new target for cancer prevention and therapy. Various CYP1B1 inhibitors with a rigid polycyclic skeleton have been developed, such as flavonoids, trans-stilbenes, and quinazolines. To obtain a new class of CYP1B1 inhibitors, we designed and synthesized a series of bentranil analogues, moreover, IC50 determinations were performed for CYP1B1 inhibition of five of these compounds and found that 6o and 6q were the best inhibitors, with IC50 values in the nM range. The selectivity index (SI) of CYP1B1 over CYP1A1 and CYP1A2 was 30-fold higher than that of α-naphthoflavone (ANF). The molecular docking results showed that compound 6q fitted better into the CYP1B1 binding site than other compounds, which was consistent with our experimental results. On the basis of 6o and 6q, it is expected to develop CYP1B1 inhibitors with stronger affinity, higher selectivity and better solubility.

Generation of a NIS-EGFP-Fluc triple-reporter human embryonic stem cell line by PiggyBac transposon system.

One major challenge in stem cell therapy is to longitudinally track cell fate after cells transplantation. Molecular Imaging approaches enabling noninvasive long-term monitoring the transplanted cells are imperative for assessment of the safety and efficiency. Here, we used PiggyBac technology to insert triple reporter genes: NIS, EGFP and Firefly luciferase into a human embryonic stem cell line (hESCs, H9) and obtained a reporter hESCs line (NIS-EGFP-Fluc H9). The triple-reporters allows the transplanted NIS-EGFP-Fluc H9 cells and their derivates to be fluorescence, bioluminescence and even PET/SPECT imaged. This triple-reporter hESCs line provides a valuable imaging platform for cell-based therapeutics clinical translation.

Asiatic Acid Attenuates Inflammation Induced by Salmonella via Upregulating LncRNA TVX1 in Microglia.

Salmonella typhimurium (S.T) induces damage to the central nervous system; however, the role of Asiatic acid (AA) in this is still unknown. Microglia play a role as macrophages to recognize the invaded pathogenic microbes in the brain. The aim of this study was to investigate the protective effect and mechanism of AA on the central nervous system through an in vitro model of S.T infection in microglia. We pre-treated microglia with AA before S.T infection and explored the anti-infection mechanism of AA by sequencing, quantitative reverse transcription PCR (RT-qPCR), and Western blotting. Long non-coding RNA (lncRNA) sequencing demonstrated that inflammation is a major factor in S.T infection of microglia. RT-qPCR data demonstrated that AA inhibited S.T-induced increases in the mRNA levels of the pro-inflammatory factors interleukin (IL)-1ß, IL-6, and IL-18. Western blotting demonstrated that AA inhibited S.T-induced activation of the nuclear factor (NF)-κB pathway and activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome. Expression of the lncRNA TVX1 in microglia was decreased by S.T infection and increased by pretreatment with AA. Inhibition of TVX1 expression reversed the anti-inflammatory effect of AA, and overexpression of TVX1 in microglia suppressed S.T-induced inflammation. In conclusion, AA attenuated S.T-induced microglial inflammation by upregulating the expression of the lncRNA TVX1.

Next-generation 5G fusion-based intelligent health-monitoring platform for ethylene cracking furnace tube.

This study aimed to develop a 5G + "mixed computing" + deep learning-based next-generation intelligent health-monitoring platform for an ethylene cracking furnace tube based on 5G communication technology, with the goal of improving the health management level of the key component of ethylene production, that is, the cracking furnace tube, and focusing on the key common technical difficulties of ethylene production of tube outer-surface temperature sensing and tube slagging diagnosis. It also integrated the edge-fog-cloud "mixed computing" technology and deep learning technology in artificial intelligence, which had a higher degree in the research and development of automation and intelligence, and was more versatile in an industrial environment. The platform included a 5G-based tube intelligent temperature-measuring device, a 5G-based intelligent peep door gearing, a 5G-based edge-fog-cloud collaboration mechanism, and a mixed deep learning-related application. The platform enhanced the automation and intelligence of the enterprise, which could not only promote the quality and efficiency of the enterprise but also protect the safe operation of the cracking furnace device and lead the technological progress and transformation and upgrading of the industry through the application.

Microglia Loss and Astrocyte Activation Cause Dynamic Changes in Hippocampal [18F]DPA-714 Uptake in Mouse Models of Depression.

Major depression is a serious and chronic mental illness. However, its etiology is poorly understood. Although glial cells have been increasingly implicated in the pathogenesis of depression, the specific role of microglia and astrocytes in stress-induced depression remains unclear. Translocator protein (TSPO) has long been considered a marker of neuroinflammation and microglial activation. However, this protein is also present on astrocytes. Thus, it is necessary to explore the relationships between TSPO, microglia, and astrocytes in the context of depression. In this study, C57BL/6J male mice were subjected to chronic unpredictable stress (CUS) for 5 weeks. Subsequently, sucrose preference and tail suspension tests (TSTs) were performed to assess anhedonia and despair in these mice. [18F]DPA-714 positron emission tomography (PET) was adopted to dynamically assess the changes in glial cells before and 2, 4, or 5 weeks after CUS exposure. The numbers of TSPO+ cells, ionized calcium-binding adaptor molecule (Iba)-1+ microglial cells, TSPO+/Iba-1+ cells, glial fibrillary acidic protein (GFAP)+ astrocytes, TSPO+/GFAP+ cells, and TUNEL-stained microglia were quantified using immunofluorescence staining. Real-time PCR was used to evaluate interleukin (IL)-1ß, IL-4, and IL-18 expression in the hippocampus. We observed that hippocampal [18F]DPA-714 uptake significantly increased after 2 weeks of CUS. However, the signal significantly decreased after 5 weeks of CUS. CUS significantly reduced the number of Iba-1+, TSPO+, and TSPO+/Iba-1+ cells in the hippocampus, especially in the CA1 and dentate gyrus (DG) subregions. However, this intervention increased the number of GFAP+ astrocytes in the CA2/CA3 subregions of the hippocampus. In addition, microglial apoptosis in the early stage of CUS appeared to be involved in microglia loss. Further, the expression of pro-inflammatory cytokines (IL-1ß and IL-18) was significantly decreased after CUS. In contrast, the expression of the anti-inflammatory cytokine IL-4 was significantly increased after 2 weeks of CUS. These results suggested that the CUS-induced dynamic changes in hippocampal [18F]DPA-714 uptake and several cytokines may be due to combined microglial and astrocyte action. These findings provide a theoretical reference for the future clinical applications of TSPO PET.

Evaluation of [18F]tetrafluoroborate as a Potential PET Imaging Agent in a Sodium Iodide Symporter-Transfected Cell Line A549 and Endogenous NIS-Expressing Cell Lines MKN45 and K1.

[18F]tetrafluoroborate (TFB) has been introduced as the 18F-labeled PET imaging probe for the human sodium iodide symporter (NIS). Noninvasive NIS imaging using [18F]TFB has received much interest in recent years for evaluating various NIS-expressing tumors. Cancers are a global concern with enormous implications; therefore, improving diagnostic methods for accurate detection of cancer is extremely important. Our aim was to investigate the PET imaging capabilities of [18F]TFB in NIS-transfected lung cell line A549 and endogenous NIS-expressing tumor cells, such as thyroid cancer K1 and gastric cancer MKN45, and broaden its application in the medical field. Western blot and flow cytometry were used to assess the NIS expression level. Radioactivity counts of [18F]TFB, in vitro, in the three tumor cells were substantially higher than those in the KI inhibition group in the uptake experiment. In vivo PET imaging clearly delineated the three tumors based on the specific accumulation of [18F]TFB in a mouse model. Ex vivo biodistribution investigation showed high [18F]TFB absorption in the tumor location, which was consistent with the PET imaging results. These results support the use of NIS-transfected lung cell line A549 and NIS-expressing tumor cells MKN45 and K1, to investigate probing capabilities of [18F]TFB. We also demonstrate, for the first time, the feasibility of [18F]TFB in diagnosing stomach cancer. In conclusion, this study illustrates the promising future of [18F]TFB for tumor diagnosis and NIS reporter imaging.

The research of recognition of peep door open state of ethylene cracking furnace based on deep learning.

In the chemical industry, the ethylene cracking furnace is the core ethylene production equipment, and its safe and stable operation must be ensured. The fire gate is the only observation window to understand the high temperature operating conditions inside the cracking furnace. In the automatic monitoring process of ethylene production, the accurate identification of the opening and closing status of the fire door is particularly important. Through the research on the ethylene cracking production process, based on deep learning, the open and closed state of the fire gate is recognized and studied. First of all, a series of preprocessing and augmentation are performed on the originally collected image data of the fire gate. Then, a recognition model is constructed based on convolutional neural network, and the preprocessed data is used to train the model. Optimization algorithms such as Adam are used to update the model parameters to improve the generalization ability of the model. Finally, the proposed recognition model is verified based on the test set and is compared with the transfer learning model. The experimental results show that the proposed model can accurately recognize the open state of the fire door and is more stable than the migration learning model.

Dynamic microglial activation is associated with LPS-induced depressive-like behavior in mice: An [18F] DPA-714 PET imaging study.

Major depressive disorder (MDD) is a highly pervasive, severe psychological condition for which the precise underlying pathophysiology is incompletely understood, although microglial activation is known to play a role in this context. In this study we analyzed the association between neuroinflammation and depressive-like behaviors in a lipopolysaccharide (LPS)-induced mouse model system using 10-12-week-old male C57BL/6 mice. Microglial activation and associated neuroinflammatory activity were monitored via positron emission tomography (PET) imaging. Animals were assessed at three time points, including 24 h prior to LPS injection, 24 h post-LPS injection, and 72 h post-LPS injection. Analyses of microglial activation and hippocampal neuroinflammation were conducted through [18]F DPA-714 PET imaging and immunohistochemical staining for ionized calcium-binding adapter molecule 1 (Iba-1) and translocator protein (TSPO). Moreover, NOD-like receptor protein 3 (NLRP3) inflammasome activity and interleukin-1ß (IL-1ß) levels were assessed at 24 h post-LPS injection. We found that LPS treatment was associated with a marked increase in depressive-like behavior at 24 h post-injection time point, and that it was less pronounced at the 72 h post-injection time point. These changes coincided with enhanced [18F] DPA-714 PET uptake in the whole brain, hippocampus, cortex and amygdala together with increased hippocampal microglial activation as evidenced by immunofluorescent staining. By 72 h post-injection, however, these PET and immunofluorescence phenotypes had returned to baseline levels. Furthermore, increased NLRP3 inflammasome activation and IL-1ß expression were evident at 24 h post-LPS injection. These data demonstrate that dynamic microglial activation is associated with LPS-induced depressive-like behaviors and hippocampal neuroinflammation in a mouse model system.