Allergenicity Modulation of Casein with the Modifications of Linearization, Cross-Linking, and Glycation via the Regulation of Th1/Th2 Homeostasis.

Casein (CN) is the primary allergenic protein in cow's milk, contributing to the worldwide escalating prevalence of food allergies. However, there remains limited knowledge regarding the effect of structural modifications on CN allergenicity. Herein, we prepared three modified CNs (mCN), including sodium dodecyl sulfate and dithiothreitol-induced linear CN (LCN), transglutaminase-cross-linked CN (TCN), and glucose-glycated CN (GCN). The electrophoresis results indicated widespread protein aggregation among mCN, causing variations in their molecular weights. The unique internal and external structural characteristics of mCN were substantiated by disparities in surface microstructure, alterations in the secondary structure, variations in free amino acid contents, and modifications in functional molecular groups. Despite the lower digestibility of TCN and GCN compared to LCN, they significantly suppressed IL-8 production in Caco-2 cells without significantly promoting their proliferation. Moreover, GCN showed the weakest capacity to induce LAD2 cell degranulation. Despite the therapeutic effect of TCN, GCN-treated mice displayed the most prominent attenuation of allergic reactions and a remarkably restored Th1/Th2 imbalance, while LCN administration resulted in severe allergic phenotypes and endotypes in both cellular and murine models. This study highlighted the detrimental effect of linear modifications and underscored the significance of glycation in relation to CN allergenicity.

Mechanism of carbohydrate and protein conversion during sourdough fermentation: An analysis based on representative Chinese sourdough microbiota.

Sourdough fermentation is attracting growing attention because of its positive effects on properties of leavened baked good. However, the changes in dough features and the mechanisms behind them are not well understood, which limits its widespread use. In this study, we assessed the effects of representative lactic acid bacteria in sourdough monoculture or co-culture with yeasts on dough characteristics. Physicochemical analysis identified increased proteolysis and enhanced nutritional properties of co-culture groups. However, a reduction in organic acids contents of co-culture groups compared to monoculture was detected, and this effect was not limited by the yeast species. The RNA sequencing further demonstrated that the presence of yeast enhanced the protein metabolic activity of lactic acid bacteria, while decreased its organic acid biosynthetic activity. Moreover, the proteomic analysis revealed that endogenous metabolic proteins of flour, such as pyruvate kinase, glucosyltransferase and pyruvate dehydrogenase play a key role in carbohydrate metabolism during fermentation. This study uncovered the influence of typical microorganisms and endogenous enzymes on dough characteristics based on different aspects. Bacteria-mediated consumption of proteins and increased proteolysis in co-culture groups may underlie the improved digestibility and nutritional effects of sourdough fermented products, which provides an important basis for nutrient fortified bread making with multi-strain leavening agent.

Preclinical Evaluation of 99mTc-MAG3-5-Fab Targeting TREM2 in Lung Cancer Mouse Models: A Comparison with 99mTc-MAG3-5-F(ab')2.

Triggering receptor expressed on myeloid cells-2 (TREM2), which is expressed on the surface of tumor-associated macrophages (TAMs), has been found to play a major role in the diagnosis and treatment of tumors. TREM2 expression is significantly upregulated in tumor tissues, and therefore, targeting TREM2 for tumor imaging may be of value. Previously, we performed TREM2 targeting imaging by using 68Ga-NOTA-COG1410 or a 124I-labeled monoclonal antibody (mAb) and F(ab')2 in mouse models of colon and gastric tumors. However, some of the shortcomings of these probes (i.e., the high uptake of 68Ga-NOTA-COG1410 in the liver, the difficulty of obtaining iodine-124, and the long half-life of iodine-124) have hindered their clinical use. Herein, we sought to synthesize novel molecular probes targeting TREM2 that are more conducive to clinical translation, eliminating the interference of isotope availability and in vivo probe biodistribution issues. Therefore, we established A549 cell lines with negative human TREM2 (hTREM2) expression (GFP tag; hTREM2- A549) or upregulated hTREM2 expression (GFP tag; hTREM2+ A549) using lentiviral transfection and confirmed these with Western blotting and immunocytochemistry. We then prepared a mouse anti-human TREM2 (5-mAb) by immunizing with the hTREM2 antigen. The antibody fragments 5-F(ab')2 and 5-Fab were prepared from 5-mAb, and 99mTc-MAG3-5-F(ab')2 and 99mTc-MAG3-5-Fab were then synthesized with excellent stability and specificity. 99mTc-MAG3-5-F(ab')2 had a slightly higher in vitro affinity than 99mTc-MAG3-5-Fab (Kd = 3.32 ± 0.05 nmol versus 4.62 ± 0.85 nmol). 99mTc-MAG3-5-F(ab')2 and 99mTc-MAG3-5-Fab both showed excellent specificity: after adding a 100-fold precursor, the two probes binding to the cells were almost blocked. In vivo pharmacokinetics showed that the distribution and elimination half-lives of 99mTc-MAG3-5-Fab (T1/2α = 1.25 ± 0.30 min and T1/2ß = 21.98 ± 2.80 min, respectively) were significantly reduced compared to those of 99mTc-MAG3-5-F(ab')2 (T1/2α = 2.64 ± 0.37 min and T1/2ß = 86.55 ± 26.86 min, respectively). In micro single-photon emission computed tomography/computed tomography (micro-SPECT/CT) imaging, the tumor was clearly displayed at 1 h after 99mTc-MAG3-5-Fab injection, while the blood background was extremely low at 3 h, and the probe was mainly excreted through the kidneys and biliary tract. 99mTc-MAG3-5-F(ab')2 uptake was also detected at the tumor site, although the blood background was consistently high. The biodistribution results were consistent with the micro-SPECT/CT imaging results. 99mTc-MAG3-5-Fab could clearly display hTREM2+ A549 tumors in a short time (1 h) with low uptake in nontumor organs and tissues and thus has clinical application prospects.

The synthesis of papaya fruit flavor-related linalool was regulated by CpTPS18 and CpNAC56.

Papaya is a tropical fruit crop renowned for its rich nutrition, particularly pro-vitamin A. Aroma substances are a major component of fruit quality. While extensive research has been conducted on papaya aroma, there has been a notable lack of in-depth research into a specific class of substances. To bridge this gap, our study focused on analyzing the aroma components of various papaya varieties and their biosynthesis pathways. We compared the volatile components of three papaya varieties with distinct flavors at various ripeness stages. A continuous accumulation of linalool, a volatile compound, in the 'AU9' fruit was detected as it matured. The linalool content reached 56% of the total volatile components upon full ripening. Notably, this percentage was significantly higher than that observed in the other two varieties, 'ZhongBai' and 'Malaysian 7', indicating that linalool serves as the primary component influencing the papaya's odor. Subsequently, we identified CpTPS18, a gene associated with linalool biosynthesis, and demonstrated its ability to catalyze linalool production from GPP and enhance its accumulation through overexpression in papaya fruits, both in vivo and in vitro. Based on transcriptomic analysis, it was predicted that CpMYB56 and CpNAC56 may transcriptionally activate the expression of CpTPS18. Subsequent yeast one-hybrid assay and dual luciferase analysis revealed that CpNAC56 activates the transcription of CpTPS18. Transient overexpression in vivo demonstrated that this gene could upregulate the expression of CpTPS18 and promote linalool accumulation. These results uncovered the primary volatile molecule responsible for papaya fruit odor and identified two major genes influencing its biosynthesis. The genomic resources and information obtained from this study will expedite papaya improvement for fruit quality.

2'-Fucosyllactose alleviates OVA-induced food allergy in mice by ameliorating intestinal microecology and regulating the imbalance of Th2/Th1 proportion.

Food allergy (FA) has become a prominent problem in public health. 2'-Fucosyllactose (2'-FL) was reported to alleviate FA symptoms; however, the regulatory mechanism is still unclear. This study evaluated the 2'-FL antiallergic potential in an ovalbumin (OVA)-sensitized mouse model and explored the systemic effects of 2'-FL on gut microecology and the intestinal immune barrier. The results showed that 2'-FL alleviated allergy symptoms, decreased serum allergic indicator levels, enhanced the intestinal barrier, and attenuated low-grade inflammation. The up-regulation of G protein-coupled receptors (GPRs) was associated with higher levels of short-chain fatty acids (SCFAs) in 2'-FL intervention mice. 2'-FL also improved the intestinal microbiota diversity and increased the abundance of Akkermansia, Lachnospiraceae UCG-006, and Ruminococcaceae while suppressing Muribaculaceae, Desulfovibrionaceae, and Erysipelotrichaceae. Additionally, 2'-FL ameliorated the imbalance of Th2/Th1, mainly by decreasing Th2-type immune response and enhanced CD4 + Foxp3 + Treg immunoreaction. These results suggest that 2'-FL restores intestinal barrier defects, gut microbiota disorder, and immune impairment while alleviating ovalbumin-induced allergic symptoms in FA mice.

Combination of Gut Microbial Features and the Proteomic Pattern Revealed Changes in Specific Intestinal Luminal Factors and Mechanisms of Their Regulation of Gluten Allergy.

Recent research consensus has highlighted the role of intestinal luminal factors in the association between intestinal microenvironment homeostasis and food allergy. However, the association between intestinal immune homeostasis and food allergy-related proteomic features remains elusive. In this study, we aimed to investigate the changes in gluten allergy (GA)-defined phenotypes and endotypes and intestinal microenvironment factors in BALB/c mice and linked GA to colonic proteomic signatures. Combined with increased allergy and diarrhea scores, intense antibody responses and abnormalities in T-cell cytokine production were induced in mice. GA-associated disruption of intestinal microenvironment homeostasis was underlined by the increased colonic pH, decreased intestinal antioxidant capacity, impaired intestinal barrier function, and decreased production and imbalanced proportions of short-chain fatty acids. 16S rRNA amplicon sequencing showed that the gut microbiota dysbiosis in mice was characterized by significant enrichment of six bacterial taxonomic units, including Prevotellaceae, Escherichia Shigella, Alloprevotella, Escherichia coli, Bacteroides vulgatus, and Lachnospiraceae bacterium DW59, which was correlated with immune end points. Using a label-free proteomics quantitative approach, 24 differentially expressed proteins linking GA-induced gut dysbiosis were identified, with four of them enriched in the serine endopeptidase inhibitor activity pathway. The development of GA in mice was associated with changes in specific intestinal luminal factors and may be mediated by serine protease activity-associated metabolic routes.

Intestinal microenvironment-mediated allergic dynamic phenotypes and endotypes in the development of gluten allergy.

This study aimed to investigate the dynamic changes in intestinal microenvironment factors in the development of gluten-induced allergy (GA). Our results showed that GA provoked increasingly severe allergic phenotypes such as allergic and diarrheal symptoms with the gluten sensitization frequency, which was accompanied by dynamically rising levels of gluten-specific immunoglobulin (Ig) E, IgG2a and IgA, serum histamine, T cell-related inflammatory cytokines, and intestinal indexes. An increase in luminal pH was more significant in the large intestine versus the small intestine, which was due to a dynamic decline in colonic short-chain fatty acid levels. Both antioxidant capacity and intestinal permeability in the large intestine varied with the GA severity, as evidenced by a dynamic increase in the malondialdehyde content and a decrease in the superoxide dismutase activity and total antioxidant capacity. Moreover, we demonstrated that intestinal microenvironment dysbiosis occurred before a true allergy reaction began. Spearman correlation analysis suggested that the characteristic bacterial cluster, namely Alistipes, Desulfovibrio, Ileibacterium, Parabacteroides, and Ruminococcus torques group, are essential in the association between GA and intestinal microenvironment homeostasis.

124I-Labeled Immuno-PET Targeting hTREM2 for the Diagnosis of Gastric Carcinoma.

Low ß-2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake in gastric mucinous adenocarcinoma may cause false-negative diagnosis and erroneous staging. Thus, there is an urgent need for developing tumor-specific imaging agents in gastric cancer diagnostics. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein expressed on the surface of tumor-associated macrophages (TAMs) and is considerably overexpressed in tumor tissues. This study aimed to develop new human TREM2 (hTREM2)-targeting imaging agents to diagnose and monitor gastric cancer. We established a cell line, MGC803, with upregulated expression of hTREM2, at the cell surface. We produced a monoclonal antibody (5-mAb) against hTREM2 by immunizing mice with the hTREM2 antigen to obtain the antibody fragment 5-F(ab')2 using an immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS). Another anti-TREM2-mAb (clone 237920) and its fragment anti-TREM2-F(ab')2 were employed for the comparative study in vitro and in vivo. After 124I labeling, we constructed the probes: 124I-5-mAb, 124I-5-F(ab')2, 124I-anti-TREM2-mAb, and 124I-anti-TREM2-F(ab')2. We found that 5-mAb exhibited higher hTREM2 affinity and slower blood clearance than anti-TREM2-mAb, whose corresponding F(ab')2 fragments demonstrated the same trend. The micro-PET/CT revealed that 124I-5-F(ab')2 exhibited advantages of tumor enrichment and fast metabolism. The biodistribution study results were consistent with those of micro-PET/CT. Among the four tracers, 124I-5-F(ab')2 was the most suitable specific radiotracer for targeting hTREM2 and displayed potential utility as a tumor-imaging tracer for diagnosing gastric carcinoma.

Noninvasive evaluation of PD-L1 expression in non-small cell lung cancer by immunoPET imaging using an acylating agent-modified antibody fragment.

PURPOSE: The aim of this study was to explore an effective 124I labeling strategy and improve the signal-to-noise ratio when evaluating the expression of PD-L1 using an 124I-iodinated durvalumab (durva) F(ab')2 fragment. METHODS: The prepared durva F(ab')2 fragments were incubated with N-succinimidyl-3-(4-hydroxyphenyl) propionate (SHPP); after purification, the HPP-durva F(ab')2 was iodinated using Iodo-Gen method. After the radiochemical purity, stability, and specific activities were determined, the binding affinities of probes prepared using different labeling strategies were compared in vitro. The clinical application value of [124I]I-HPP-durva-F(ab')2 was confirmed by PET imaging. To more objectively evaluate the in vivo distribution and clearance of tracers, the pharmacokinetics and biodistribution assays were also performed. RESULTS: After being modified with SHPP, the average conjugation number of SHPP per durva-F(ab')2 identified by LC-MS was about 8.92 ± 2.84. The prepared [124I]I-HPP-durva F(ab')2 was obtained with a satisfactory radiochemical purity of more than 98% and stability of more than 93% when incubated for 72 h. Compared with unmodified [124I]I-durva F(ab')2, the specific activity of [124I]I-HPP-durva-F(ab')2 was improved (52.91 ± 5.55 MBq/mg and 15.91 ± 0.74 MBq/mg), while the affinity did not significantly change. The biodistribution experiments and PET imaging showed that the prepared [124I]I-HPP-durva-F(ab')2 exhibited an accelerated clearance and improved tumor-to-background ratio compared with [124I]I-durva-F(ab')2. The specificity of [124I]I-HPP-durva-F(ab')2 to PD-L1 was well demonstrated both in vitro and in vivo. CONCLUSIONS: A PD-L1 PET imaging probe [124I]I-HPP-durva F(ab')2 was successfully synthesized through the SHPP modification strategy. The prepared probe was able to accurately evaluate the PD-L1 expression level through high-contrast noninvasive imaging.

The high dose of inulin exacerbated food allergy through the excess accumulation of short-chain fatty acids in a BABL/c mouse model.

Inulin dietary supplement is conventionally beneficial to gut health and can potentially prevent food allergy (FA). This study aimed to determine how dietary inulin interventions at different doses affect the OVA-induced FA in a BALB/c mouse model. Although the middle dose of inulin (50 mg per mouse) showed the best therapeutic effect on FA, high-inulin supplementation (80 mg per mouse) provoked severe allergic and intestinal inflammatory responses, which were characterized by elevated serum allergic inflammation-related factor levels, dysfunctional gut barrier, unbalanced luminal pH value, decrease in intestinal antioxidant capacity, and disordered gut microecology. Moreover, profiling of SCFAs indicated that the high-inulin-induced excess accumulation of SCFAs in the colon was responsible for the gut immune disorders. Spearman correlation analysis unraveled that the featured bacterial taxa in the high-inulin-treated mice were Ruminococcaceae and Bifidobacterium, of which the relative abundance was negatively correlated with expression of tight junction proteins and improvement of T cell homeostasis, and positively correlated with levels of allergic inflammation-related indexes. Our work suggested that high-inulin dietary supplementation can be detrimental to allergic individuals and highlighted the importance for personalized use of inulin-type dietary supplements to safely improve human health.

Longitudinal Positron Emission Tomography Imaging with P2X7 Receptor-Specific Radioligand 18F-FTTM in a Kainic Acid Rat Model of Temporal Lobe Epilepsy.

P2X7 receptors (P2X7R), as a brain inflammation biomarker, play important roles in the epileptogenic progress. Mounting evidence supports their activation in the brain during epilepsy, and inhibition of the P2X7 receptor reduces the seizure frequency and severity. In this study, we investigate P2X7R-targeted (18F-FTTM) position emission tomography (PET) imaging in a rat model of temporal lobe epilepsy to obtain further insights into the role of P2X7R during epileptogenesis. 18F-FTTM (5-10% radiochemical yield, over 99% radiochemical purity, and a specific activity of 270-300 MBq/nmol, n = 6, EOS) was first synthesized. Then, the rat models induced by intrahippocampal injection of saline (1.2 µL, n = 15) or kainic acid (1.2 µL, 0.5 µg/µL, n = 35) were examined using 18F-FTTM Micro-PET/CT longitudinal imaging, respectively. The imaging results showed that increases in the 18F-FTTM uptake was evident after status epilepticus (SE) in the epileptogenesis-associated brain regions, such as the hippocampus, amygdala, or temporal cortex, and this peaked during the latent period. The histopathological analysis revealed that the P2X7R PET uptake reached a peak at 7 days after SE and was mostly related to microglial activation. Thus, P2X7R-targeted PET imaging agent 18F-FTTM may act as a useful tool for identifying brain inflammation during epilepsy. P2X7R PET is a highly potent longitudinal biomarker of epilepsy and could be of interest to determine the therapeutic windows in epilepsy and to monitor treatment response, and it warrants further clinical studies.

Pediococcus acidilactici Strain Alleviates Gluten-Induced Food Allergy and Regulates Gut Microbiota in Mice.

Wheat flour, the most important source of food globally, is also one of the most common causative agents of food allergy. Wheat gluten protein, which accounts for 80% of the total wheat protein, is a major determinant of important wheat-related disorders. In this study, the effects of Pediococcus acidilactici XZ31 against gluten-induced allergy were investigated in a mouse model. The oral administration of P. acidilactici XZ31 attenuated clinical and intestinal allergic responses in allergic mice. Further results showed that P. acidilactici XZ31 regulated Th1/Th2 immune balance toward Th1 polarization, which subsequently induced a reduction in gluten-specific IgE production. We also found that P. acidilactici XZ31 modulated gut microbiota homeostasis by balancing the Firmicutes/Bacteroidetes ratio and increasing bacterial diversity and the abundance of butyrate-producing bacteria. Specifically, the abundance of Firmicutes and Erysipelotrichaceae is positively correlated with concentrations of gluten-specific IgE and may act as a fecal biomarker for diagnosis. The evidence for the role of P. acidilactici XZ31 in alleviating gluten-induced allergic responses sheds light on the application of P. acidilactici XZ31 in treating wheat allergy.

124I-Labeled Monoclonal Antibody and Fragment for the Noninvasive Evaluation of Tumor PD-L1 Expression In Vivo.

Lung cancer is a highly heterogeneous cancer and is divided broadly into small and nonsmall cell lung cancer (SCLC or NSCLC). In all NSCLC patients, it is estimated that 50%-60% are programmed cell death ligand 1 (PD-L1) positive, and anti-PD-1/PD-L1 therapies have shown their clinical application prospects in advanced NSCLC. To avoid unnecessary adverse effects and provide anti-PD-1/PD-L1 therapy to the most appropriate patient population, the PD-L1 expression in patients preparing for treatment must be evaluated accurately and in real time. In this study, we noninvasively evaluate the PD-L1 expression in an NSCLC xenograft using 124I-labeled F(ab')2 fragments of durvalumab (Durva) and compared it with the 124I-labeled intact antibody in terms of the biodistribution and dosimetry. The aim is to develop a nuclide labeled molecular probe with better performance for PD-L1 immunoPET imaging. After cleaving using IdeS protease, the F(ab')2 fragments of Durva were labeled with 124I. The radioligand showed a high radiochemical purity (>96%) and outstanding stability. Western blot, quantitative real-time polymerase chain reaction, and flow cytometry were performed on the two selected NSCLC cell lines to measure the in vitro PD-L1 expression. The H460 cells showed a much higher PD-L1 expression than the A549 cells, both at the protein level and the mRNA level. In the following cell binding experiment and binding specificity assay, the labeled radioligand showed good affinity to high PD-L1 expression cells and could be blocked with excess unlabeled intact Durva. The results of the biodistribution and the positron emission tomography (PET) image showed that the peak tumor uptake of 124I-Durva-F(ab')2 was close to 124I-Durva, but much earlier (5.29 ± 0.42% ID/g for 124I-Durva-F(ab')2 at 12 h vs 5.18 ± 0.73% ID/g for 124I-Durva at 48 h). Compared with 124I-Durva, an accelerated blood clearance was observed for 124I-Durva-F(ab')2. The faster blood clearance allowed for a higher tumor-to-background ratio, which was reflected on the image in contrast. The H460 tumors showed excellent contrast as early as 4 h after injection with 124I-Durva-F(ab')2, and for 124I-Durva, the xenograft could not be distinguished clearly until 24 h after injection. Interestingly, 124I-Durva-F(ab')2 showed lower accumulations compared to other metal isotopes labeled PD-L1 antibodies in bone, liver, spleen etc., which will be beneficial for metastasis detection. Another benefit of accelerated blood clearance was a reduction in the radiation dose. According to the results of the OLINDA/EXM, the effective dose for the total body of 124I-Durva was 4.25-times greater than that of 124I-Durva-F(ab')2 (186 µSv/MBq vs 43.8 µSv/MBq). All of these data indicated that 124I-Durva-F(ab')2 is a promising immunoPET tracer for evaluating the in vivo PD-L1 levels in an NSCLC model and is expected to be successful in future clinical application.

Preparation, Characterization, and Preliminary Imaging Study of [188Re]Re-Ibandronate as a Novel Theranostic Radiopharmaceutical for Bone Metastasis.

Background: Bone is a common site of metastasis from a malignant tumor. Several radiopharmaceuticals are available to relieve bone pain in patients with cancer. However, every radiopharmaceutical has its own disadvantages, and there is still a need to investigate easily accessible and high bone affinity radiopharmaceuticals. Ibandronate (IBA) and 188Re were used for radiolabeling to develop and evaluate a novel type of bone-seeking radiopharmaceutical. Methods: The preparation conditions of [188Re]Re-IBA were investigated, and thin-layer chromatography was used to analyze radiochemical purity. The stability, plasma protein binding rate, lipid-water distribution coefficient, safety and biodistribution in normal mice, and bone imaging of [188Re]Re-IBA in New Zealand rabbits were studied. In addition, the nude mice model of bone metastasis was established, and biodistribution and imaging characteristics of [188Re]Re-IBA in these nude mice were studied. Results: [188Re]Re-IBA was successfully prepared with radiochemical purity >95%. The optimum preparation conditions were as follows: IBA, 0.8-1.4 mg; ascorbic acid, 0.2-0.5 mg; stannous chloride, 0.14-0.18 mg; potassium perrhenate, 0.005 mg; and [188Re]ReO4 - activity, 18.5-296 MBq, reacted for 30 min at 95°C with pH = 2. [188Re]Re-IBA demonstrated good stability, high plasma protein binding rate, good hydrophilicity, and low toxicity. The biodistribution and bone imaging in normal animals showed rapid blood clearance, high bone uptake, low uptake in the solid organs and soft tissue, and high contrast during imaging. The biodistribution and imaging of bone metastasis in nude mice showed that [188Re]Re-IBA has higher uptake in bone metastasis lesions than normal bone. Conclusions: Our study encompassed the successful preparation of [188Re]Re-IBA, a novel bone-seeking radiopharmaceutical, and confirmed it has potential in the treatment of bone metastasis and monitoring through imaging.

Oxygen-Vacancy-Induced Synaptic Plasticity in an Electrospun InGdO Nanofiber Transistor for a Gas Sensory System with a Learning Function.

The perceptual learning function of a simulating human body is very important for constructing a neural computing system and a brainlike computer in the future. The sense of smell is an important part of the human sensory nervous system. However, current gas sensors simply convert gas concentrations into electrical signals and do not have the same learning and memory function as synapses. To solve this problem, we propose a new sensing idea to induce and activate the synaptic properties of transistors by adjusting the oxygen vacancy in the active layer. This sensor combines gas detection with synaptic memory and learning and overcomes the disadvantage of the separation of synaptic transistors and sensors, thus greatly reducing the cost of production. This work combines the detection of N,N-dimethylformamide (DMF) gas with the synaptic mechanism of human olfactory nerves. We successfully fabricated an InGdO nanofiber field-effect transistor by electrostatic spinning and simulated the response of human olfactory synapses to target gas by regulating the oxygen vacancy of the InGdO nanofiber. The synaptic transistor response under different concentrations of unmodulated pulses is tested, and the pavlovian conditioned reflex experiment is simulated successfully. This work provides a new idea of a gas sensor device, which is very important for the development of high-performance gas sensors and bionic electronic devices in the future.

Mg-doped InSnO nanofiber field-effect transistor for methanol gas detection at room temperature.

Research on high-performance gas sensors for detecting toxic and harmful methanol gas is still a very important issue. For gas sensors, it is very important to be able to achieve low concentration detection at room temperature. In this work, we used the electrospinning method to prepare Mg-doped InSnO nanofiber field-effect transistors (FETs) methanol gas sensor. When the Mg element doping concentration is 2.3 mol.%, InSnO nanofiber FET exhibits excellent electrical properties, including higher mobility of 3.17 cm2V-1s-1, threshold voltage of 1.51 V, subthreshold swing of 0.42 V/decade, the excellent on/off current ratio is about 108and the positive bias stress stability of the InSnO nanofiber FET through Mg doping has been greatly improved. In addition, the InSnMgO nanofiber FET gas sensor exhibits acceptable gas selectivity and sensitivity to methanol gas at room temperature. In the methanol gas sensor test at room temperature, when the methanol gas concentration is 60 ppm at room temperature, the response value of the InSnMgO nanofiber FET gas sensor is 81.92; and when the methanol concentration is 5 ppm, the response value is still 1.21. This work provides an effective and novel way to build a gas sensor at room temperature and use it to detect methanol gas at room temperature.

Synthesis and Evaluation of 68Ga-NOTA-COG1410 Targeting to TREM2 of TAMs as a Specific PET Probe for Digestive Tumor Diagnosis.

Currently, positron emission tomography/computed tomography (PET/CT) is an important method for the discovery and diagnosis of digestive system tumors. However, the shortage of specific imaging tracer limits the effectiveness of PET. Triggering receptor expressed on myeloid cells 2 (TREM2) as an M2-type macrophage biomarker is receiving much attention considering its high abundance and specificity, which could be an ideal target for PET imaging. First, the expression of TREM2 in tumors and corresponding normal tissues was analyzed using a database and was verified by tissue microarrays and murine model slices, and we found that the expression of TREM2 in tumor tissues was significantly higher than that in normal tissues and enteritis tissues. Then, we established a macrophage co-culture system to obtain tumor-associated macrophages (TAMs). Compared with M1-type macrophages and tumor cells, TAMs had a higher expression level of TREM2. The novel radioligand 68Ga-NOTA-COG1410 was successfully synthesized for TREM2 targeting PET imaging. The biodistribution and micro-PET/CT results showed high uptake of 68Ga-NOTA-COG1410 in the tumor but not in areas of inflammation. The data testified that 68Ga-NOTA-COG1410 was a specific radioligand targeting TREM2, which could be used to distinguish tumors from inflammation. Using 68Ga-NOTA-COG1410, the effectiveness of PET on digestive tumors imaging may be enhanced.

A Traditional Chinese Medicine for the Treatment of Endometrial Hyperplasia via Regulating the HPO Axis in Rats.

Dysfunctional uterine bleeding, accompanied by endometrial hyperplasia (EH), is a common gynecological disease that seriously affects female physical and mental health. Some drugs have been prompted to cure the disease, but most medications have certain side effects and limitations. In the present study, we demonstrated an unexploited Chinese traditional medicine, a combination of Saururus chinensis, Celosia cristata, and Spatholobus suberectus (SCS), which could be used for the treatment of EH and associated complications in rats. We identified the active components from the three Chinese herbs via thin-layer chromatography and high-performance liquid chromatography methods. In addition, serum biochemical indexes and histologic section results found that acute high-dose SCS exerted no adverse impacts on the rats. We then showed that SCS shortened coagulation time (p=0.018) and degree of swelling (p=0.021) on rats at 30 min compared to blank control. Further studies proved that recovered endometrial thickness was associated with the modulation of four hormones (follicle-stimulating hormone, luteinizing hormone, estrogen, and progesterone). Specifically, follicle-stimulating hormone and progesterone contents increased gradually with time, and estrogen was decreased, whereas luteinizing hormone content was returned to normal after a short-term elevation (p < 0.05). Besides, SCS increased uterine endometrium's mRNA expression levels of matrix metalloproteinase-1 (p < 0.001) and tissue inhibitor of matrix metalloproteinase-1 (p < 0.001), promoting the repair of proliferating endometrium in the rats. Collectively, our study indicates that SCS harbors a profoundly curative effect on the treatment of EH and relative complications and uncovers the mechanism at molecular and gene expression levels.

P2X7 receptor-specific radioligand 18F-FTTM for atherosclerotic plaque PET imaging.

PURPOSE: P2X7 receptors have been considered as a promising biomarker for vulnerable atherosclerotic plaques, which are highly expressed by that instability-associated factors such as macrophages. Thus, we aim to investigate the feasibility of using specific P2X7-targeted 18F-labeled tracer 18F-FTTM ((2-chloro-3-[18F]fluorophenyl)[1,4,6,7-tetrahydro-1-(2-pyrimidinyl)-5H-1,2,3-triazolo[4,5-c]pyridin-5-yl]methanone) for PET study of vulnerable atherosclerotic plaques identification. METHOD: The radioligand 18F-FTTM was achieved based on the copper-mediated radiofluorination of arylstannane. In vitro and in vivo experiments were performed to verify the biochemical properties. Dynamic 18F-FTTM Micro-PET/CT imaging was performed for 1 h on ApoE-/- mice (10, 20, 30 weeks on high-fat diet) and wild-type C57BL/6 J mice on normal diet. Ex vivo PET imaging was conducted to verify the specificity of the radioligand. Serum inflammatory cytokines, lipids, and lipoproteins profiles were detected by ELISA. The lipid distribution and morphology of plaques were evaluated by Oil Red O, HE, Masson, and immunofluorescence stainings. RESULTS: 18F-FTTM was afforded with decay-corrected radiochemical yields of 5-10%, specific activity of 269-320 MBq/nmol (n = 8, EOS), and radiochemical purity of above 99%. 18F-FTTM showed excellent stability in vitro, rapid blood clearance in mice, good affinity to RAW264.7 cells. We observed an increase in both in vivo and ex vivo imagings as disease progressed, and the imaging signatures correlated with histopathological features. Furthermore, compared with 18F-FDG imaging, the SUVmax values of 18F-FTTM at the aortic arch of ApoE-/- mice of high-fat feeding for 20 and 30 weeks were 43% and 53% higher than those of the control group, respectively. CONCLUSION: We innovatively apply a new type P2X7-targeted PET probe (18F-FTTM) to identify vulnerable atherosclerotic plaques, to detect the inflammatory response of atherosclerosis, and to provide a powerful non-invasive method for the diagnosis of atherosclerotic lesions and new drug screening for accurate treatment.

Increased 68Ga-FAPI Uptake in Avascular Necrosis of Femoral Head in a Patient With Nasopharyngeal Carcinoma.

ABSTRACT: A 73-year-old man with newly diagnosed nasopharyngeal carcinoma included in a clinical trial of 68Ga-FAPI PET/CT study in tumors (ChiCTR2100044131). Increased tracer uptake was noted in nasopharyngeal carcinoma and cervical lymph nodes metastases. In addition, avascular necrosis of right femoral head also revealed increased FAPI activity.