Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents.

BACKGROUND: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant's emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. OBJECTIVE: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. DESIGN: Comparative effectiveness research accounting for underreported vaccination in 3 study cohorts: adolescents (12 to 20 years) during the Delta phase and children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. SETTING: A national collaboration of pediatric health systems (PEDSnet). PARTICIPANTS: 77 392 adolescents (45 007 vaccinated) during the Delta phase and 111 539 children (50 398 vaccinated) and 56 080 adolescents (21 180 vaccinated) during the Omicron phase. INTERVENTION: First dose of the BNT162b2 vaccine versus no receipt of COVID-19 vaccine. MEASUREMENTS: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100, with confounders balanced via propensity score stratification. RESULTS: During the Delta period, the estimated effectiveness of the BNT162b2 vaccine was 98.4% (95% CI, 98.1% to 98.7%) against documented infection among adolescents, with no statistically significant waning after receipt of the first dose. An analysis of cardiac complications did not suggest a statistically significant difference between vaccinated and unvaccinated groups. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (CI, 72.2% to 76.2%). Higher levels of effectiveness were seen against moderate or severe COVID-19 (75.5% [CI, 69.0% to 81.0%]) and ICU admission with COVID-19 (84.9% [CI, 64.8% to 93.5%]). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (CI, 83.8% to 87.1%), with 84.8% (CI, 77.3% to 89.9%) against moderate or severe COVID-19, and 91.5% (CI, 69.5% to 97.6%) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined 4 months after the first dose and then stabilized. The analysis showed a lower risk for cardiac complications in the vaccinated group during the Omicron variant period. LIMITATION: Observational study design and potentially undocumented infection. CONCLUSION: This study suggests that BNT162b2 was effective for various COVID-19-related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time. PRIMARY FUNDING SOURCE: National Institutes of Health.

Advancing MicroRNA Detection: Enhanced Biotin-Streptavidin Dual-Mode Phase Imaging Surface Plasmon Resonance Aptasensor.

MicroRNAs (miRNAs) are novel tumor biomarkers owing to their important physiological functions in cell communication and the progression of multiple diseases. Due to the small molecular weight, short sequence length, and low concentration levels of miRNA, miRNA detection presents substantial challenges, requiring the advancement of more refined and sensitive techniques. There is an urgent demand for the development of a rapid, user-friendly, and sensitive miRNA analysis method. Here, we developed an enhanced biotin-streptavidin dual-mode phase imaging surface plasmon resonance (PI-SPR) aptasensor for sensitive and rapid detection of miRNA. Initially, we evaluated the linear sensing range for miRNA detection across two distinct sensing modalities and investigated the physical factors that influence the sensing signal in the aptamer-miRNA interaction within the PI-SPR aptasensor. Then, an enhanced biotin-streptavidin amplification strategy was introduced in the PI-SPR aptasensor, which effectively reduced the nonspecific adsorption by 20% and improved the limit of detection by 548 times. Furthermore, we have produced three types of tumor marker chips, which utilize the rapid sensing mode (less than 2 min) of PI-SPR aptasensor to achieve simultaneous detection of multiple miRNA markers in the serum from clinical cancer patients. This work not only developed a new approach to detect miRNA in different application scenarios but also provided a new reference for the application of the biotin-streptavidin amplification system in the detection of other small biomolecules.

Robust machine-learning based prognostic index using cytotoxic T lymphocyte evasion genes highlights potential therapeutic targets in colorectal cancer.

BACKGROUND: A minute fraction of patients stands to derive substantial benefits from immunotherapy, primarily attributable to immune evasion. Our objective was to formulate a predictive signature rooted in genes associated with cytotoxic T lymphocyte evasion (CERGs), with the aim of predicting outcomes and discerning immunotherapeutic response in colorectal cancer (CRC). METHODS: 101 machine learning algorithm combinations were applied to calculate the CERGs prognostic index (CERPI) under the cross-validation framework, and patients with CRC were separated into high- and low-CERPI groups. Relationship between immune cell infiltration levels, immune-related scores, malignant phenotypes and CERPI were further analyzed. Various machine learning methods were used to identify key genes related to both patient survival and immunotherapy benefits. Expression of HOXC6, G0S2, and MX2 was evaluated and the effects of HOXC6 and G0S2 on the viability and migration of a CRC cell line were in-vitro verified. RESULTS: The CERPI demonstrated robust prognostic efficacy in predicting the overall survival of CRC patients, establishing itself as an independent predictor of patient outcomes. The low-CERPI group exhibited elevated levels of immune cell infiltration and lower scores for tumor immune dysfunction and exclusion, indicative of a greater potential benefit from immunotherapy. Moreover, there was a positive correlation between CERPI levels and malignant tumor phenotypes, suggesting that heightened CERPI expression contributes to both the occurrence and progression of tumors. Thirteen key genes were identified, and their expression patterns were scrutinized through the analysis of single-cell datasets. Notably, HOXC6, G0S2, and MX2 exhibited upregulation in both CRC cell lines and tissues. Subsequent knockdown experiments targeting G0S2 and HOXC6 resulted in a significant suppression of CRC cell viability and migration. CONCLUSION: We developed the CERPI for effectively predicting survival and response to immunotherapy in patients, and these results may provide guidance for CRC diagnosis and precise treatment.

Engineering lactate-modulating nanomedicines for cancer therapy.

Lactate in tumors has long been considered "metabolic junk" derived from the glycolysis of cancer cells and utilized only as a biomarker of malignancy, but is presently believed to be a pivotal regulator of tumor development, maintenance and metastasis. Indeed, tumor lactate can be a "fuel" for energy supply and functions as a signaling molecule, which actively contributes to tumor progression, angiogenesis, immunosuppression, therapeutic resistance, etc., thus providing promising opportunities for cancer treatment. However, the current approaches for regulating lactate homeostasis with available agents are still challenging, which is mainly due to the short half-life, low bioavailability and poor specificity of these agents and their unsatisfactory therapeutic outcomes. In recent years, lactate modulation nanomedicines have emerged as a charming and efficient strategy for fighting cancer, which play important roles in optimizing the delivery of lactate-modulating agents for more precise and effective modulation and treatment. Integrating specific lactate-modulating functions in diverse therapeutic nanomedicines may overcome the intrinsic restrictions of different therapeutic modalities by remodeling the pathological microenvironment for achieving enhanced cancer therapy. In this review, the most recent advances in the engineering of functional nanomedicines that can modulate tumor lactate for cancer therapy are summarized and discussed, and the fundamental mechanisms by which lactate modulation benefits various therapeutics are elucidated. Finally, the challenges and perspectives of this emerging strategy in the anti-tumor field are highlighted.

DNA Assembly of Plasmonic Nanostructures Enables In Vivo SERS-Based MicroRNA Detection and Tumor Photoacoustic Imaging.

Controllable self-assembly of the DNA-linked gold nanoparticle (AuNP) architecture for in vivo biomedical applications remains a key challenge. Here, we describe the use of the programmed DNA tetrahedral structure to control the assembly of three different types of AuNPs (∼20, 10, and 5 nm) by organizing them into defined positioning and arrangement. A DNA-assembled "core-satellite" architecture is built by DNA sequencing where satellite AuNPs (10 and 5 nm) surround a central core AuNP (20 nm). The density and arrangement of the AuNP satellites around the core AuNP were controlled by tuning the size and amount of the DNA tetrahedron functionalized on the core AuNPs, resulting in strong electromagnetic field enhancement derived from hybridized plasmonic coupling effects. By conjugating with the Raman molecule, strong surface-enhanced Raman scattering photoacoustic imaging signals could be generated, which were able to image microRNA-21 and tumor tissues in vivo. These results provided an efficient strategy to build precision plasmonic superstructures in plasmonic-based bioanalysis and imaging.

Two-Dimensional FePS3 Nanosheets as an Integrative Sonosensitizer/Nanocatalyst for Efficient Nanodynamic Tumor Therapy.

As the emerging modalities for tumor therapy, sonodynamic therapy (SDT) and chemodynamic therapy (CDT) can generate reactive oxygen species (ROS), typically inducing tumor cell apoptosis. However, the construction of more efficient sonosensitizers integrated with excellent Fenton/Fenton-like catalytic activity to improve the synergistic therapeutic effect of SDT and CDT is still highly challenging. In this study, 2D semiconductor FePS3 nanosheets (NSs), as one of the metal phosphorus trichalcogenides for both sonosensitizer and Fenton catalyst, are successfully synthesized via an ultrasonic-assisted liquid phase exfoliation method from bulk FePS3 and further modified with lipoic acid-polyethylene glycol (LA-PEG) to obtain FePS3 -PEG NSs with desirable biocompatibility. The in vitro and in vivo results demonstrate that the engineered FePS3 -PEG NSs induce the combinatorial SDT/CDT effect attributing to the enhanced ROS generation and significant glutathione depletion, which can conduct highly efficient and safe tumor inhibition and prolong the life span of tumor-bearing mice. This work provides the paradigm of semiconductor FePS3 NSs as the integrative sonosensitizer/Fenton nanocatalyst for dual nanodynamic tumor therapy, paving the new way for exploring other 2D metal phosphorus trichalcogenides in biomedicine.

Dietary γ-mangostin triggers immunogenic cell death and activates cGAS signaling in acute myeloid leukemia.

Immunogenic cell death (ICD), one of cell-death types through release of damage-associated molecular patterns from dying tumor cells, activates tumor-specific immune response and elicits anti-tumor immunity by traditional radiotherapy and chemotherapy. However, whether natural products could induce ICD in leukemia is not elucidated. Here, we report dietary γ-mangostin eradicates murine primary leukemic cells and prolongs the survival of leukemic mice. As well, it restrains primary leukemic cells and CD34+ leukemic progenitor cells from leukemia patients. Strikingly, γ-mangostin attenuates leukemic cells by inducing ICD as characterized by expression of HSP90B1, ANXA1 and IL1B. Additionally, γ-mangostin accelerates cytoplasmic chromatin fragments generation, promoting DNA damage response, and enhances cGAS activation, leading to up-regulation of chemokines. Meanwhile, it induces HDAC4 degradation and acetylated histone H3 accumulation, which promotes chemokines transcription. Ultimately, CD8+ T cell is activated and recruited by γ-mangostin-induced chemokines in the microenvironment. Our study identifies γ-mangostin triggers ICD and activates cGAS signaling through DNA damage response and epigenetic modification. Therefore, dietary γ-mangostin would act as a potential agent to provoke anti-tumor immunity in the prevention and treatment of leukemia.

Abnormal cerebral metabolism and metabolic connectivity in individuals with heroin dependence: an integrated resting-state PET/fMRI study in large-scale networks.

BACKGROUND: Increasing evidence suggests that heroin addiction may be related to the dysfunction among the triple brain network (default mode network [DMN], salience network [SN] and executive control network [ECN]). However, the characteristics of glucose metabolism and metabolic connectivity among core regions of the triple brain network remain unknown. Therefore, we hypothesized that individuals with heroin dependence would show abnormal glucose metabolism and accompanied abnormal metabolic connectivity within the triple brain network. METHODS: Individuals with heroin dependence and healthy controls matched for age and sex underwent integrated positron emission tomography/magnetic resonance imaging (PET/MRI). Differences in glucose metabolism and metabolic connectivity among the DMN, SN and ECN were analyzed based on 18F-fluorodeoxyglucose PET and resting-state fMRI data. RESULTS: We included 36 individuals with heroin dependence and 30 matched healthy controls in our study. The heroin dependence group showed a significant reduction of glucose metabolism in the bilateral anterior insula (AI) and inferior parietal lobule (IPL), and a significantly decreased metabolic connectivity between the right AI and the left dorsolateral prefrontal cortex (DLPFC). The daily dose of methadone was negatively correlated with glucose metabolism of the right AI and right IPL. LIMITATIONS: The results revealed the glucose metabolism alterations and metabolic connectivity only within the triple brain network in individuals with heroin dependence; additional brain networks should be investigated in future studies. Although methadone is an opioid with a similar neurophysiological mechanism as heroin, the specific chronic effects of methadone on cerebral metabolism and metabolic connectivity should also be investigated in future studies. CONCLUSION: Our findings suggest that long-term opioid use might, to some extent, be associated with reduced synergistic ability between the SN and ECN, which may be associated with the dysfunction of cognitive control. In particular, the right AI, which showed hypometabolism and related reduction in SN-ECN metabolic connectivity, should receive increasing attention in future studies.

Quasi-phase extraction-based surface plasmon resonance imaging method for coffee ring effect monitoring and biosensing.

Wavelength interrogation surface plasmon resonance imaging (WSPRi) sensing has unique advantages in high-throughput imaging detection. The refractive index resolution (RIR) of WSPRi is limited to the order of 10-6 RIU. This paper demonstrates a novel WSPRi sensing system with a wavelength scanning device of an acousto-optic tunable filter (AOTF) and a low-cost speckle-free SPR excitation source of a halogen lamp. We developed a sensitive quasi-phase extraction method for data processing. The new technique achieved an RIR of 8.84×10-7 RIU, which is the first WSPRi system that has an RIR in the order of 10-7 RIU. Moreover, we performed a real-time recording of the formation of the coffee ring effect during brine evaporation and enhanced the biosensor performance of SPR for the first time. We believe the higher RIR and accuracy of the system will benefit more potential applications toward exploring the biomolecules' behaviors in biological and biochemistry studies.

Efficient nitrogen removal through coupling biochar with zero-valent iron by different packing modes in bioretention system.

Three kinds of bioretention were designed to explore the effects of zero-valent iron (ZVI) and biochar on the nitrogen removal performance and to seek a more reasonable packing method in this study. The results showed that the effluent removal rates of nitrate, ammonium and total nitrogen were 53.30 ± 12.68%, 98.41 ± 0.38% and 64.03 ± 8.72% respectively in Bioretention-3 during the rainfall events, while the nitrate concentration decreased gradually with the increase of drying time. According to the batch experiment, it was found that zero-valent iron could release continuously and stably in Bioretention-3 and Bioretention-1 due to the interception effect of biochar on dissolved oxygen. In addition, biochar in soil layer could protect zero-valent iron from excessive oxidation while biochar in the substrate layer could release organic matter to promote heterotrophic denitrification. Microbial community analysis showed that the dominant phyla were Proteobacteria (20.92-40.81%) and Actinobacteriota (9.89-24.54%). The dominant nitrifying genera was Nitrospira while there were also aerobic denitrifying bacteria (Sphingomonas, Bradyrhizobium and Chryseolinea, etc.) in soil layer. In the substrate layer, there was more ferrous iron-mediated autotrophic denitrification process (Thiobacillus, Geobacter and Denitratisoma, etc.) in Bioretention-1 and Bioretention-3 while a larger proportion of Dissimilatory Nitrate Reduction to Ammonium process (DNRA) (Bacillus, Desulfovibrio and Pseudomonas, etc.) in Bioretention-2. In general, this study showed that biochar addition in soil coupled with mixing zero-valent iron and biochar as substrate layer was a more stable and efficient design through various aspects of evidence. It provides a new way for how to use zero-valent iron and biochar to improve nitrogen removal capacity in stormwater management.

Effects of ferrous addition to Vallisneria natans: An attempt to apply ferrous to submerged macrophyte restoration.

Restoration of submerged macrophytes is an efficient way for endogenous nutrient control and aquatic ecological restoration, but slow growth and limited reproduction of submerged macrophytes still exist. In this research, the effect of ferrous on the seed germination and growth of Vallisneria natans (V. natans) were studied through aquatic simulation experiments and its influence on the rhizosphere microbial community was also explored. The seed germination, growth, and physiological and ecological parameters of V. natans were significantly affected by the ferrous treatments. Ferrous concentration above 5.0 mg/L showed significant inhibition of seed germination of V. natans and the best concentration for germination was 0.5 mg/L. During the growth of V. natans, after ferrous was added, a brief period of stress occurred, which then promoted the growth lasting for about 19 days under one addition. The diversity and richness of the rhizospheric microbial were increased after the ferrous addition. However, the function of the rhizospheric microbial community showed no significant difference between different concentrations of ferrous adding in the overlying water. Ferrous addition affected the growth condition of plants (content of CAT, Chl a, Chl b, etc.), thus indirectly affecting the rhizospheric microbial community of V. natans. These impacts on V. natans and rhizosphere microorganisms could generalize to other submerged macrophytes in freshwater ecosystems, particularly which have similar habits. These findings would contribute to the ecological evaluation of ferrous addition or iron-containing water, and provide a reference for submerged macrophytes restoration and ecological restoration in freshwater ecosystems.

Analysis of related factors affecting hemoporfin-mediated photodynamic therapy for port-wine stain: A retrospective study.

BACKGROUND: Hemoporfin-mediated photodynamic therapy (HMME-PDT) is currently considered one of the most promising therapies for port-wine stain (PWS). However, the efficacy of this is very variable and needs further studies. METHODS: A total of 101 patients with PWS in the face, neck, or extremities who received at least 2 HMME-PDT sessions were included in the study, and correlations of efficacy with age, gender, locations, treatment sessions, and PDL treatment history were analyzed. RESULTS: The efficacy of HMME-PDT in patients with different ages, locations, and different numbers of prior PDL treatment showed constantly significant differences after 1/2/last session (p < .05). The number of treatments was associated with efficacy, and patients who received more than two sessions had a better response than those who underwent two sessions only (p < .001). Ordinal logistic regression analysis confirmed the above-mentioned associations. Nevertheless, patients of different sex, subtype, and lesion size showed no significant differences. CONCLUSIONS: Our studies demonstrated that HMME-PDT is effective in the treatment of PWS. The more prior PDL treatments, older age, lips involvement, PWS on limbs were adverse factors for Hemoporfin-PDT, while multiple HMME-PDT sessions can improve effective and response rate. Besides, ambient temperature and lesions temperature should be concerned, local cooling provides some relief from pain but may influence effect.

Formononetin Inhibits Mast Cell Degranulation to Ameliorate Compound 48/80-Induced Pseudoallergic Reactions.

Formononetin (FNT) is a plant-derived isoflavone natural product with anti-inflammatory, antioxidant, and anti-allergic properties. We showed previously that FNT inhibits immunoglobulin E (IgE)-dependent mast cell (MC) activation, but the effect of FNT on IgE-independent MC activation is yet unknown. Our aim was to investigate the effects and possible mechanisms of action of FNT on IgE-independent MC activation and pseudoallergic inflammation. We studied the effects of FNT on MC degranulation in vitro with a cell culture model using compound C48/80 to stimulate either mouse bone marrow-derived mast cells (BMMCs) or RBL-2H3 cells. We subsequently measured ß-hexosaminase and histamine release, the expression of inflammatory factors, cell morphological changes, and changes in NF-κB signaling. We also studied the effects of FNT in several in vivo murine models of allergic reaction: C48/80-mediated passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA), and 2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD). The results showed that FNT inhibited IgE-independent degranulation of MCs, evaluated by a decrease in the release of ß-hexosaminase and histamine and a decreased expression of inflammatory factors. Additionally, FNT reduced cytomorphological elongation and F-actin reorganization and attenuated NF-κB p65 phosphorylation and NF-κB-dependent promoter activity. Moreover, the administration of FNT alleviated pseudoallergic responses in vivo in mouse models of C48/80-stimulated PCA and ASA, and DNCB-induced AD. In conclusion, we suggest that FNT may be a novel anti-allergic drug with great potential to alleviate pseudoallergic responses via the inhibition of IgE-independent MC degranulation and NF-κB signaling.

Simulation of the temporal resolution uniformity of a dilation framing camera.

The temporal resolution uniformity of a time-dilation framing camera is studied, and the ideal photocathode (PC) pulse curve is determined, while the temporal magnification factor is kept constant. To obtain the ideal curve, a series of linear pulses with the same slope are superposed. The variance in the temporal resolution and the number of linear pulses required are compared, while the superposition results with different slopes are used as the PC voltage. As the slope of the linear pulses decreases, the variance decreases, which means that the uniformity of the temporal resolution is improved, but the number of linear pulses required increases. In this study, linear pulses with a slope of 1 V/ps are superposed. Nine linear pulses with a front edge time of 200 ps, amplitude of 200 V, and flat top time of 1 ns are superimposed to approximate the ideal PC pulse curve with a constant temporal magnification factor of 10; the trigger times of the pulses are 0, 0, 0, 185, 200, 350, 450, 605, and 790 ps. When the superposition result is applied as the PC voltage and the measured signal is synchronized to the PC pulse at 128 ps-1 ns, the temporal resolution error is within 5%.

Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation.

Mast cells (MCs) are an important treatment target for high-affinity IgE Fc receptor (FcεRI)-mediated allergic diseases. The plant-derived molecule 4-methylumbelliferone (4-MU) has beneficial effects in animal models of inflammation and autoimmunity diseases. The aim of this study was to examine 4-MU effects on MC activation and probe the underlying molecular mechanism(s). We sensitized rat basophilic leukemia cells (RBLs) and mouse bone marrow-derived mast cells (BMMCs) with anti-dinitrophenol (DNP) immunoglobulin (Ig)E antibodies, stimulated them with exposure to DNP-human serum albumin (HSA), and then treated stimulated cells with 4-MU. Signaling-protein expression was determined by immunoblotting. In vivo allergic responses were examined in IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) mouse models. 4-MU inhibited ß-hexosaminidase activity and histamine release dose-dependently in FcεRI-activated RBLs and BMMCs. Additionally, 4-MU reduced cytomorphological elongation and F-actin reorganization while down-regulating IgE/Ag-induced phosphorylation of SYK, NF-κB p65, ERK1/2, p38, and JNK. Moreover, 4-MU attenuated the PCA allergic reaction (i.e., less ear thickening and dye extravasation). Similarly, we found that 4-MU decreased body temperature, serum histamine, and IL4 secretion in OVA-challenged ASA model mice. In conclusion, 4-MU had a suppressing effect on MC activation both in vitro and in vivo and thus may represent a new strategy for treating IgE-mediated allergic conditions.

Ultrafast Surface Plasmon Resonance Imaging Sensor via the High-Precision Four-Parameter-Based Spectral Curve Readjusting Method.

A variety of surface plasmon resonance (SPR) sensing devices have been extensively used in biochemical detection for their characteristics of label-free, highly sensitive, and faster detecting. Among them, the spectrum-based SPR sensing devices have offered us great advantages in high-throughput sensing due to their large dynamic range and the possibility of detection resolution similar to that offered by angle interrogation. This paper demonstrates a spectrum-based SPR imaging sensing system with fast wavelength scanning capability achieved by an acousto-optic tunable filter (AOTF) and a low-cost and speckle-free halogen lamp implemented as the SPR excitation source. Especially, we developed a novel four-parameter-based spectral curve readjusting (4-PSCR) method for data processing, which offered us a faster and more accurate spectral data curve fitting process than the traditional polynomial fitting method. With the configuration, we have also conducted an SPR high-throughput detection of the novel coronavirus (COVID-19) spike protein, proving its application possibility in the screening of COVID-19 with high accuracy. We believe that the higher sensitivity and accuracy of the system have made it readily used in biochemical imaging and detecting applications.

Inhibition of c-Fos expression attenuates IgE-mediated mast cell activation and allergic inflammation by counteracting an inhibitory AP1/Egr1/IL-4 axis.

BACKGROUND: Activator protein-1 (AP1), a c-Fos-JUN transcription factor complex, mediates many cytobiological processes. c-Fos has been implicated in immunoglobulin (Ig)E activation of mast cells (MCs) via high-affinity IgE Fc receptor (FcεRI) binding. This study examined c-Fos involvement in MC activation and tested the effects of the c-Fos/AP1 inhibitor T-5224 on MCs activation and allergic responses. METHODS: In vitro studies were conducted with two MC model systems: rat basophilic leukemia cells (RBLs) and mouse bone marrow derived mast cells (BMMCs). MC degranulation and effector functions were examined with ß-hexosaminidase release and cytokine secretion assays. c-Fos/AP1 was inhibited with T-5224. c-Fos activity was suppressed with short hairpin RNA targeting c-Fos (shFos). In vivo immune responses were evaluated in passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models, as well as in an oxazolone (OXA)-induced model of atopic dermatitis, a common allergic disease. RESULTS: c-Fos expression was elevated transcriptionally and translationally in IgE-stimulated MCs. c-Fos binding of the Egr1 (early growth response 1) promoter upregulated Egr1 transcription, leading to production of interleukin (IL)4. T-5224 reduced FcεRI-mediated MC degranulation (evidenced by ß-hexosaminidase activity and histamine levels) and diminished EGR1 and IL4 expression. T-5224 attenuated IgE-mediated allergic responses in PCA and ASA models, and it suppressed MC-mediated atopic dermatitis in mice. CONCLUSION: IgE binding can activate MCs via a c-Fos/Egr1/IL-4 axis. T-5224 suppresses MC activation in vitro and in vivo and thus represents a promising potential strategy for targeting MC activation to treat allergic diseases.

Phase interrogation surface plasmon resonance hyperspectral imaging sensor for multi-channel high-throughput detection.

Phase interrogation surface plasmon resonance (SPR) imaging is, in principle, suitable in multiple samples and high-throughput detection, but the refractive index difference of various samples can be largely varied, while the dynamic range of phase interrogation SPR is narrow. So it is difficult to perform multi-sample detection in phase interrogation mode. In this paper, we successfully designed a multi-channel phase interrogation detection SPR imaging sensing scheme based on a common optical interference path between p- and s-polarized light without using any mechanical moving components. The fixed optical path difference between p- and s-polarized light is introduced by a birefringence crystal to produce sinusoidal spectral interference fringes. We adopted a time-division-multiplexing peak-finding algorithm to track the resonance wavelength so that the detection range can cover every channel. The phase values which carry the high sensitivity signal of the corresponding samples are calculated by the iterative parameter scanning cross-correlation algorithm.

Assessing effect of long-term abstinence on coupling of three core brain networks in male heroin addicts: A resting-state functional magnetic resonance imaging study.

Abstinence is one of the important measures for heroin addiction. However, it is unknown whether long-term abstinence (LA) would improve the coupling among three core brain networks (salience, default mode, and executive control) and decrease craving in treated heroin addicts. Forty-three heroin addicts with LA, 27 heroin addicts with short-term abstinence (SA), and 46 demographically matched healthy controls (HC) participated in the resting-state functional magnetic resonance imaging study. The authors compared the functional connectivity among the three groups and examined how the coupling among salience, default mode, and executive control networks related to duration of abstinence and craving before and after drug cue exposure among heroin addicts. Compared with the SA group, with a tendency toward the HC group, the LA group showed lower drug cue-induced craving, stronger connectivity between the dorsal anterior cingulate cortex (a key node of salience network) and left dorsolateral prefrontal cortex and right posterior parietal cortex (key nodes of executive control network), and stronger connectivity between the right dorsolateral prefrontal cortex and precuneus (a key node of default mode network). Meanwhile, the right dorsolateral prefrontal cortex-precuneus connectivity positively correlated with duration of abstinence. The LA and SA groups demonstrated lower connectivity between the left anterior insula (a key node of salience network) and dorsolateral prefrontal cortex and lower connectivity within the left dorsolateral prefrontal cortex, compared with the HC group. Our findings revealed that LA is associated with lower drug cue induced craving and improve the coupling among the three core brain networks in heroin addicts.

Nanoplatform-based cascade engineering for cancer therapy.

Various therapeutic techniques have been studied for treating cancer precisely and effectively, such as targeted drug delivery, phototherapy, tumor-specific catalytic therapy, and synergistic therapy, which, however, evoke numerous challenges due to the inherent limitations of these therapeutic modalities and intricate biological circumstances as well. With the remarkable advances of nanotechnology, nanoplatform-based cascade engineering, as an efficient and booming strategy, has been tactfully introduced to optimize these cancer therapies. Based on the designed nanoplatforms, pre-supposed cascade processes could be triggered under specific conditions to generate/deliver more therapeutic species or produce stronger tumoricidal effects inside tumors, aiming to achieve cancer therapy with increased anti-tumor efficacy and diminished side effects. In this review, the recent advances in nanoplatform-based cascade engineering for cancer therapy are summarized and discussed, with an emphasis on the design of smart nanoplatforms with unique structures, compositions and properties, and the implementation of specific cascade processes by means of endogenous tumor microenvironment (TME) resources and/or exogenous energy inputs. This fascinating strategy presents unprecedented potential in the enhancement of cancer therapies, and offers better controllability, specificity and effectiveness of therapeutic functions compared to the corresponding single components/functions. In the end, challenges and prospects of such a burgeoning strategy in the field of cancer therapy will be discussed, hopefully to facilitate its further development to meet the personalized treatment demands.