Synchronous Diagnosis of Respiratory Viruses Variants via Receptonics Based on Modeling Receptor-Ligand Dynamics.

The transmission and pathogenesis of highly contagious fatal respiratory viruses are increasing, and the need for an on-site diagnostic platform has arisen as an issue worldwide. Furthermore, as the spread of respiratory viruses continues, different variants have become the dominant circulating strains. To prevent virus transmission, the development of highly sensitive and accurate on-site diagnostic assays is urgently needed. Herein, a facile diagnostic device is presented for multi-detection based on the results of detailed receptor-ligand dynamics simulations for the screening of various viral strains. The novel bioreceptor-treated electronics (receptonics) device consists of a multichannel graphene transistor and cell-entry receptors conjugated to N-heterocyclic carbene (NHC). An ultrasensitive multi-detection performance is achieved without the need for sample pretreatment, which will enable rapid diagnosis and prevent the spread of pathogens. This platform can be applied for the diagnosis of variants of concern in clinical respiratory virus samples and primate models. This multi-screening platform can be used to enhance surveillance and discriminate emerging virus variants before they become a severe threat to public health.

Second Skin as Self-Protection Against γ-Hydroxybutyrate.

γ-Hydroxybutyrate (GHB), a date-rape drug, causes certain symptoms, such as amnesia, confusion, ataxia, and unconsciousness, when dissolved in beverages and consumed by a victim. Commonly, assailants use GHB in secret for the crime of drug-facilitated sexual assault because it is tasteless, odorless, and colorless when dissolved in beverages. Generally, GHB detection methods are difficult to use promptly and secretly in situ and in real life because of the necessary detection equipment and low selectivity. To overcome this problem, we have developed a fast, simple, and easy-to-use second skin platform as a confidential self-protection platform that can detect GHB in situ or in real life without equipment. The second skin platform for naked-eye detection of GHB is fabricated with poly(vinyl alcohol) (PVA), polyurethane (PU), and polyacrylonitrile (PAN) included in the chemical receptor 2-(3-bromo-4-hydroxystyryl)-3-ethylbenzothiazol-3-ium iodide (BHEI). PAN conjugated with BHEI nanofibers (PB NFs) has various characteristics, such as ease of use, high sensitivity, and fast color change. PB NFs rapidly detected GHB at 0.01 mg/mL. Furthermore, the second-skin platform attached to the fingertip and wrist detected both 1 and 0.1 mg/mL GHB in solution within 50 s. The color changes caused by the interaction of GHB and the second skin platform cannot be stopped due to strong chemical reactions. In addition, a second skin platform can be secretly utilized in real life because it can recognize fingerprints and object temperatures. Therefore, the second skin platform can be used to aid daily life and prevent drug-facilitated sexual assault crime when attached to the skin because it can be exposed anytime and anywhere.

Dietary supplementation of solubles from shredded, steam-exploded pine particles modulates cecal microbiome composition in broiler chickens.

This study evaluated the effects of supplementing solubles from shredded, steam-exploded pine particles (SSPP) on growth performances, plasma biochemicals, and microbial composition in broilers. The birds were reared for 28 days and fed basal diets with or without the inclusion of SSPP from 8 days old. There were a total of three dietary treatments supplemented with 0% (0% SSPP), 0.1% (0.1% SSPP) and 0.4% (0.4% SSPP) SSPP in basal diets. Supplementation of SSPP did not significantly affect growth or plasma biochemicals, but there was a clear indication of diet-induced microbial shifts. Beta-diversity analysis revealed SSPP supplementation-related clustering (ANOSIM: r = 0.31, p < 0.01), with an overall lower (PERMDISP: p < 0.05) individual dispersion in comparison to the control group. In addition, the proportions of the Bacteroides were increased, and the relative abundances of the families Vallitaleaceae, Defluviitaleaceae, Clostridiaceae, and the genera Butyricicoccus and Anaerofilum (p < 0.05) were significantly higher in the 0.4% SSPP group than in the control group. Furthermore, the linear discriminant analysis effect size (LEfSe) also showed that beneficial bacteria such as Ruminococcus albus and Butyricicoccus pullicaecorum were identified as microbial biomarkers of dietary SSPP inclusion (p < 0.05; | LDA effect size | > 2.0). Finally, network analysis showed that strong positive correlations were established among microbial species belonging to the class Clostridia, whereas Erysipelotrichia and Bacteroidia were mostly negatively correlated with Clostridia. Taken together, the results suggested that SSPP supplementation modulates the cecal microbial composition of broilers toward a "healthier" profile.

Aberrant PI3Kδ splice isoform as a potential biomarker and novel therapeutic target for endocrine cancers.

Introduction: PI3K/AKT signaling pathway is upregulated in a broad spectrum of cancers. Among the class I PI3Ks (PI3Kδ/ß/δ isoforms), PI3Kδ has been implicated in hematologic cancers and solid tumors. Alternative splicing is a post-transcriptional process for acquiring proteomic diversity in eukaryotic cells. Emerging evidence has highlighted the involvement of aberrant mRNA splicing in cancer development/progression. Methods: Our previous studies revealed that PIK3CD-S is an oncogenic splice variant that promotes tumor aggressiveness and drug resistance in prostate cancer (PCa). To further evaluate the potential of utilizing PI3Kδ-S (encoded from PIK3CD-S) as a cancer biomarker and/or drug target, comprehensive analyses were performed in a series of patient samples and cell lines derived from endocrine/solid tumors. Specifically, IHC, immunofluorescence, western blot and RT-PCR assay results have demonstrated that PI3Kδ isoforms were highly expressed in endocrine/solid tumor patient specimens and cell lines. Results: Differential PIK3CD-S/PIK3CD-L expression profiles were identified in a panel of endocrine/solid tumor cells. SiRNA knockdown of PIK3CD-L or PIK3CD-S differentially inhibits AKT/mTOR signaling in PCa, breast, colon and lung cancer cell lines. Moreover, siRNA knockdown of PTEN increased PI3Kδ levels and activated AKT/mTOR signaling, while overexpression of PTEN reduced PI3Kδ levels and inhibited AKT/mTOR signaling in cancer cells. Intriguingly, PI3Kδ-S levels remained unchanged upon either siRNA knockdown or overexpression of PTEN. Taken together, these results suggested that PTEN negatively regulates PI3Kδ-L and its downstream AKT/mTOR signaling, while PI3Kδ-S promotes AKT/mTOR signaling without regulation by PTEN. Lastly, PI3Kδ inhibitor Idelalisib and SRPK1/2 inhibitor SRPIN340 were employed to assess their efficacies on inhibiting the PI3Kδ-expressing endocrine/solid tumors. Our results have shown that Idelalisib effectively inhibited PI3Kδ-L (but not PI3Kδ-S) mediated AKT/mTOR signaling. In contrast, SRPIN340 reversed the aberrant mRNA splicing, thereby inhibiting AKT/mTOR signaling. In-vitro functional assays have further demonstrated that a combination of Idelalisib and SRPIN340 achieved a synergistic drug effect (with drastically reduced cell viabilities/growths of tumor spheroids) in inhibiting the advanced tumor cells. Conclusion: In summary, our study has suggested a promising potential of utilizing PI3Kδ-S (an oncogenic isoform conferring drug resistance and exempt from PTEN regulation) as a prognostic biomarker and drug target in advanced endocrine cancers.

Deregulated microRNAs Involved in Prostate Cancer Aggressiveness and Treatment Resistance Mechanisms.

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer deaths among American men. Complex genetic and epigenetic mechanisms are involved in the development and progression of PCa. MicroRNAs (miRNAs) are short noncoding RNAs that regulate protein expression at the post-transcriptional level by targeting mRNAs for degradation or inhibiting protein translation. In the past two decades, the field of miRNA research has rapidly expanded, and emerging evidence has revealed miRNA dysfunction to be an important epigenetic mechanism underlying a wide range of diseases, including cancers. This review article focuses on understanding the functional roles and molecular mechanisms of deregulated miRNAs in PCa aggressiveness and drug resistance based on the existing literature. Specifically, the miRNAs differentially expressed (upregulated or downregulated) in PCa vs. normal tissues, advanced vs. low-grade PCa, and treatment-responsive vs. non-responsive PCa are discussed. In particular, the oncogenic and tumor-suppressive miRNAs involved in the regulation of (1) the synthesis of the androgen receptor (AR) and its AR-V7 splice variant, (2) PTEN expression and PTEN-mediated signaling, (3) RNA splicing mechanisms, (4) chemo- and hormone-therapy resistance, and (5) racial disparities in PCa are discussed and summarized. We further provide an overview of the current advances and challenges of miRNA-based biomarkers and therapeutics in clinical practice for PCa diagnosis/prognosis and treatment.

Reusable Electronic Tongue Based on Transient Receptor Potential Vanilloid 1 Nanodisc-Conjugated Graphene Field-Effect Transistor for a Spiciness-Related Pain Evaluation.

The sense of spiciness is related to the stimulation of vanilloid compounds contained in the foods. Although, the spiciness is commonly considered as the part of taste, it is more classified to the sense of pain stimulated on a tongue, namely, pungency, which is described as a tingling or burning on the tongue. Herein, first, a reusable electronic tongue based on a transient receptor potential vanilloid 1 (TRPV1) nanodisc conjugated graphene field-effect transistor is fabricated and spiciness-related pain evaluation with reusable electrode is demonstrated. The pungent compound reactive receptor TRPV1 is synthesized in the form of nanodiscs to maintain stability and reusability. The newly developed platform shows highly selective and sensitive performance toward each spiciness related vanilloid compound repeatably: 1 aM capsaicin, 10 aM dihydrocapsaicin, 1 fM piperine, 10 nM allicin, and 1 pM AITC. The binding mechanism is also examined by simulation. Furthermore, the elimination of the burning sensation on the tongue after eating spicy foods is not investigated. Based on the synthesis of micelles composed of casein protein (which is contained in skim milk) that remove pungent compounds bound to TRPV1 nanodisc, the deactivation of TRPV1 is investigated, and the electrode is reusable that mimics electronic tongue.

Molecular Insight into Drug Resistance Mechanism Conferred by Aberrant PIK3CD Splice Variant in African American Prostate Cancer.

Targeting PI3Kδ has emerged as a promising therapy for hematologic and non-hematologic malignancies. Previously, we identified an oncogenic splice variant, PIK3CD-S, conferring Idelalisib resistance in African American (AA) prostate cancer (PCa). In the current study, we employed a comprehensive analysis combining molecular biology, biochemistry, histology, in silico simulation, and in vitro functional assays to investigate the PIK3CD-S expression profiles in PCa samples and to elucidate the drug resistance mechanism mediated by PI3Kδ-S (encoded by PIK3CD-S). The immunohistochemistry, RT-PCR, and Western blot assays first confirmed that PI3Kδ-S is highly expressed in AA PCa. Compared with PCa expressing the full-length PI3Kδ-L, PCa expressing PI3Kδ-S exhibits enhanced drug resistance properties, including a higher cell viability, more antiapoptotic and invasive capacities, and constitutively activated PI3K/AKT signaling, in the presence of PI3Kδ/PI3K inhibitors (Idelalisib, Seletalisib, Wortmannin, and Dactolisib). Molecular docking, ATP-competitive assays, and PI3 kinase assays have further indicated a drastically reduced affinity of PI3Kδ inhibitors with PI3Kδ-S vs. PI3Kδ-L, attributed to the lack of core binding residues in the PI3Kδ-S catalytic domain. Additionally, SRSF2 has been identified as a critical splicing factor mediating exon 20 skipping in PIK3CD pre-mRNA. The inhibition of the SRSF2 activity by SRPIN340 successfully sensitizes AA PCa cells to PI3Kδ inhibitors, suggesting a novel therapeutic option for Idelalisib-resistant tumors.

Dietary supplementation of solubles from shredded, steam-exploded pine particles modifies gut length and cecum microbiota in cyclic heat-stressed broilers.

This study was conducted to investigate the effect of supplementing solubles from steam-exploded pine particles (SSPP) on mitigating the adverse effects of cyclic heat stress (CHS) in broilers which were distributed into 3 dietary treatment groups and 2 temperature conditions. Heat stress (HS) exposure for 6 h daily for 7 d adversely affected performance parameters and rectal temperature of chickens. The absolute and relative weights of the liver and bursa of Fabricius decreased in the CHS group while the relative lengths of the jejunum and ileum increased, which was rescued by dietary supplementation with SSPP. The expression of mucin2 (MUC2) and occludin (OCLN) genes was decreased in CHS birds. The expression of heat shock protein -70 and -90 increased in 0% HS compared to that in 0% NT. Birds supplemented with 0.4% SSPP had higher NADPH oxidase -1 expression than birds in the 0% and 0.1% SSPP treatments. Beta diversity of gut microbiota evaluated through unweighted UniFrac distances was significantly different among treatments. Bacteroidetes was among the 2 most abundant phyla in the cecum, which decreased with 0.1% NT and increased with 0.1% HS in comparison to 0% NT. A total of 13 genera were modified by HS, 5 were altered by dose, and nine showed an interaction effect. In conclusion, CHS adversely affects performance and gut health which can be mitigated with dietary SSPP supplementation that modifies the cecal microbiota in broilers.

Dietary shredded steam-exploded pine particle supplementation as a strategy to mitigate chronic cyclic heat stress by modulating gut microbiota in broilers.

Improving the availability of underutilized waste for the economic use of livestock feed can be important in countries where feed grain production is scarce. Modulating the gut microbiota through the fibrous content present in these wastes may help mitigate the adverse effects of heat stress (HS). Here, we investigated the effects of dietary steam-exploded pine particle (SPP), a value-added waste product, on the performance, gut health, and cecum microbiota in heat-stressed broilers. Ross 308 broilers (n = 180) at 29 days of age were distributed into three dietary treatment groups (0%, 1%, and 2% SPP) and two temperature conditions (NT: 21 °C; CHS: 31 °C) and grown for seven days. CHS, but not SPP, adversely affected performance parameters, but SPP did not interactively modulate these results. On the contrary, both differently affected other parameters. CHS resulted in increased rectal temperature, total protein in serum, and Nox4 gene expression, whereas 2% SPP increased GLP-2 and the Nox4 gene expression in the duodenum in comparison to 0% and 1% SPP. CHS significantly modified the beta-diversity of cecal microbiota while 1% SPP supplementation in diets increased the abundance of the favorable bacterial genera in chicken. Concludingly, CHS adversely affects growth performances, gut health, stress-related genes, and cecal microbiota while dietary 1% SPP may facilitate the proliferation of beneficial microorganisms in the cecum of broilers.

Downregulation of miR-99b-5p and Upregulation of Nuclear mTOR Cooperatively Promotes the Tumor Aggressiveness and Drug Resistance in African American Prostate Cancer.

Mammalian target of rapamycin (mTOR) regulates various fundamental cellular events including cell proliferation, protein synthesis, metabolism, apoptosis, and autophagy. Tumor suppressive miR-99b-5p has been implicated in regulating PI3K/AKT/mTOR signaling in a variety of types of cancer. Our previous study suggested the reciprocal miR-99b-5p/MTOR (downregulated/upregulated) pairing as a key microRNA-mRNA regulatory component involved in the prostate cancer (PCa) disparities. In this study, we further validated the expression profiles of mTOR and miR-99b-5p in the PCa, colon, breast, and lung cancer specimens and cell lines. The immunohistochemistry (IHC), immunofluorescence, Western blot, and RT-qPCR assays have confirmed that mTOR is upregulated while miR-99b-5p is downregulated in different patient cohorts and a panel of cancer cell lines. Intriguingly, elevated nuclear mTOR expression was observed in African American PCa and other advanced cancers. Transfection of the miR-99b-5p mimic resulted in a significant reduction in nuclear mTOR and androgen receptor (AR), while a slight/moderate to no decrease in cytoplasmic mTOR and AR in PCa and other cancer cells, suggesting that miR-99b-5p inhibits mTOR and AR expression and their nuclear translocation. Moreover, overexpression of miR-99b-5p targets/inhibits AR-mTOR axis, subsequently initiating cell apoptosis and sensitizing docetaxel-induced cytotoxicity in various cancers. In conclusion, our data suggest that reciprocal miR-99b-5p/nuclear mTOR pairing may be a more precise diagnostic/prognostic biomarker for aggressive PCa, than miR-99b-5p/MTOR pairing or mTOR alone. Targeting the AR-mTOR axis using miR-99b-5p has also been suggested as a novel therapeutic strategy to induce apoptosis and overcome chemoresistance in aggressive PCa.

Effects of Dietary Supplementation of Solubles from Shredded, Steam-Exploded Pine Particles on the Performance and Cecum Microbiota of Acute Heat-Stressed Broilers.

Heat stress (HS) negatively influences livestock productivity, but it can be, at least in part, mitigated by nutritional interventions. One such intervention is to use byproducts from various sources that are likely to be included in the consumer chain. Thus, the present study investigated the effects of dietary supplementation of solubles from shredded, steam-exploded pine particles (SSPPs) on the performance and cecum microbiota in broilers subjected to acute HS. One-week-old Ross 308 broilers (n = 108) were fed 0%, 0.1%, or 0.4% SSPP in their diets. On the 37th day, forty birds were allocated to one of four groups; namely, a group fed a control diet without SSPPs at thermoneutral temperature (NT) (0% NT) and acute heat-stressed birds with 0% (0% HS), 0.1% (0.1% HS), and 0.4% (0.4% HS) SSPP-supplemented diets. The NT was maintained at 21.0 °C, while the HS room was increased to 31 °C. The final BW, percent difference in body weight (PDBW), and feed intake (FI) were lower in HS birds, but PDBW was reversely associated with dietary SSPP. Similarly, HS birds had a higher rectal temperature (RT) and ΔT in comparison to birds kept at NT. The FI of SSPP-supplemented birds was not significant, indicating lower HS effects. Plasma triglyceride was decreased in HS birds but not affected in 0.1% HS birds in comparison to 0% NT birds. OTUs and Chao1 were increased by 0.1% HS compared to 0% NT. Unweighted Unifrac distances for 0.1% HS were different from 0% NT and 0.4% HS. The favorable bacterial phylum (Tenericutes) and genera (Faecalibacterium and Anaerofustis) were increased, while the pathogenic genus (Enterococcus) was decreased, in SSPP-supplemented birds. In sum, production performances are negatively affected under acute HS. Dietary supplementation of SSPPs is beneficial for improving community richness indices and unweighted Unifrac distances, and it enhanced the advantageous bacterial phyla and reduced virulent genera and triglyceride hydrolysis in acute HS broilers. Our results indicate that dietary SSPPs modulates the microbial profile of the cecum while resulting in relatively less weight loss and lower rectal temperature compared to control.

Wireless portable bioelectronic nose device for multiplex monitoring toward food freshness/spoilage.

Monitoring food freshness/spoilage is important to ensure food quality and safety. Current methods of food quality monitoring are mostly time-consuming and labor intensive processes that require massive analytical equipment. In this study, we developed a portable bioelectronic nose (BE-nose) integrated with trace amine-associated receptor (TAAR) nanodiscs (NDs), allowing food quality monitoring via the detection of food spoilage indicators, including the biogenic amines cadaverine (CV) and putrescine (PT). The olfactory receptors TAAR13c and TAAR13d, which have specific affinities for CV and PT, were produced and successfully reconstituted in ND structures. TAAR13 NDs BE-nose-based side-gated field-effect transistor (SG-FET) system was constructed by utilizing a graphene micropattern (GM) into which two types of olfactory NDs (TAAR13c ND and TAAR13d ND) were introduced, and this system showed ultrahigh sensitivity for a limit of detection (LOD) of 1 fM for CV and PT. Moreover, the binding affinities between the TAAR13 NDs and the indicators were confirmed by a tryptophan fluorescence quenching assay and biosimulations, in which the specific binding site was confirmed. Gas-phase indicators were detected by the TAAR13 NDs BE-nose platform, and the LODs for CV and PT were confirmed to be 26.48 and 7.29 ppb, respectively. In addition, TAAR13 NDs BE-nose was fabricated with commercial gas sensors as a portable platform for the measurement of NH3 and H2S, multiplexed monitoring was achieved with similar performance, and the change ratio of the indicators was observed in a real sample. The integration of commercial gas sensors on a BE-nose enhanced the accuracy and reliability for the quality monitoring of real food samples. These results indicate that the portable TAAR13 NDs BE-nose can be used to monitor CV and PT over a wide range of concentrations, therefore, the electronic nose platform can be utilized for monitoring the freshness/spoilage step in various foods.

Antimicrobial second skin using copper nanomesh.

The functional support and advancement of our body while preserving inherent naturalness is one of the ultimate goals of bioengineering. Skin protection against infectious pathogens is an application that requires common and long-term wear without discomfort or distortion of the skin functions. However, no antimicrobial method has been introduced to prevent cross-infection while preserving intrinsic skin conditions. Here, we propose an antimicrobial skin protection platform copper nanomesh, which prevents cross-infectionmorphology, temperature change rate, and skin humidity. Copper nanomesh exhibited an inactivation rate of 99.99% for Escherichia coli bacteria and influenza virus A within 1 and 10 min, respectively. The thin and porous nanomesh allows for conformal coating on the fingertips, without significant interference with the rate of skin temperature change and humidity. Efficient cross-infection prevention and thermal transfer of copper nanomesh were demonstrated using direct on-hand experiments.

MicroRNA-mRNA Regulatory Network Mediates Activation of mTOR and VEGF Signaling in African American Prostate Cancer.

African American (AA) men exhibit 1.6-fold higher prostate cancer (PCa) incidence and 2.4-fold higher mortality rates compared to European American (EA) men. In addition to socioeconomic factors, emerging evidence suggests that intrinsic biological differences may explain part of PCa disparities. In this study, we applied microRNA (miRNA)-driven bioinformatics to evaluate whether differential miRNA-mRNA regulatory networks play a role in promoting the AA PCa disparities. 10 differentially expressed miRNAs were imported to mirPath V.3 algorithm, leading to identification of 58 signaling pathways differentially regulated in AA PCa versus EA PCa. Among these pathways, we particularly focused on mTOR and VEGF signaling, where we identified 5 reciprocal miRNA-mRNA pairings: miR-34a-5p/HIF1A, miR-34a-5p/PIK3CB, miR-34a-5p/IGFBP2, miR-99b-5p/MTOR and miR-96-5p/MAPKAPK2 in AA PCa versus EA PCa. RT-qPCR validation confirmed that miR-34a-5p, miR-99b-5p and MAPKAPK2 were downregulated, while miR-96-5p, IGFBP2, HIF1A, PIK3CB and MTOR were upregulated in AA PCa versus EA PCa cells. Transfection of miRNA mimics/antagomir followed by RT-qPCR and Western blot analysis further verified that IGFBP2, HIF1A and PIK3CB are negatively regulated by miR-34a-5p, whereas MTOR and MAPKAPK2 are negatively regulated by miR-99b-5p and miR-96-5p, respectively, at mRNA and protein levels. Targeting reciprocal pairings by miR-34a-5p mimic, miR-99b-5p mimic or miR-96-5p antagomir downregulates HIF1α, PI3Kß, mTOR, IGFBP2 but upregulates MAPKAPK2, subsequently reducing cell proliferation and sensitizing docetaxel-induced cytotoxicity in PCa cells. These results suggest that miRNA-mRNA regulatory network plays a critical role in AA PCa disparities, and targeting these core miRNA-mRNA pairings may reduce PCa aggressiveness and overcome the chemoresistance in AA patients.

In situ, real-time, colorimetric detection of γ-hydroxybutyric acid (GHB) using self-protection products coated with chemical receptor-embedded hydrogel.

Due to the increase in drug-facilitated sexual assault (DFSA) enabled by the illegal use of drugs, there have been constant demands for simple methods that can be used to protect oneself against crime in real life. γ-Hydroxybutyric acid (GHB), a central nervous system depressant, is one of the most dangerous drugs for use in DFSA because it is colorless and has slow physiological effects, which pose challenges for developing in situ, real-time GHB monitoring techniques. In this study, we developed a method for in situ colorimetric GHB detection using various self-protection products (SPPs) coated with 2-(3-bromo-4-hydroxystyryl)-3-ethylbenzothiazol-3-ium iodide (BHEI) as a chemical receptor embedded in hydrogels. Additionally, smartphone-based detection offers enhanced colorimetric sensitivity compared to that of the naked eye. The developed SPPs will help address drug-facilitated social problems.

Wearable Cortisol Aptasensor for Simple and Rapid Real-Time Monitoring.

The necessity of managing stress levels is becoming increasingly apparent as the world suffers from different kinds of stresses including the extent of pandemic, the corona virus disease 2019 (COVID-19). Cortisol, a clinically confirmed stress hormone related to depression and anxiety, affects individuals mentally and physically. However, current cortisol monitoring methods require expert personnel, large and complex machines, and long time for data analysis. Here, we present a flexible and wearable cortisol aptasensor for simple and rapid cortisol real-time monitoring. The sensing channel was produced by electrospinning conducting polyacrylonitrile (PAN) nanofibers (NFs) and subsequent vapor deposition of carboxylated poly(3,4-ethylenedioxythiophene) (PEDOT). The conjugation of the cortisol aptamer on the PEDOT-PAN NFs provided the critical sensing mechanism for the target molecule. The sensing test was performed with a liquid-ion gated field-effect transistor (FET) on a polyester (polyethylene terepthalate). The sensor performance showed a detection limit of 10 pM (<5 s) and high selectivity in the presence of interference materials at 100 times higher concentrations. The practical usage and real-time monitoring of the cortisol aptasensor with a liquid-ion gated FET system was demonstrated by successful transfer to the swab and the skin. In addition, the real-time monitoring of actual sweat by applying the cortisol aptasensor was also successful since the aptasensor was able to detect cortisol approximately 1 nM from actual sweat in a few minutes. This wearable biosensor platform supports the possibility of further application and on-site monitoring for changes of other numerous biomarkers.

In-situ food spoilage monitoring using a wireless chemical receptor-conjugated graphene electronic nose.

Monitoring food spoilage is one of the most effective methods for preventing food poisoning caused by biogenic amines or microbes. Therefore, various analytical techniques have been introduced to detect low concentrations of cadaverine (CV) and putrescine (PT), which are representative biogenic polyamines involved in food spoilage (5-8 ppm at the stage of initial decomposition after storage for 5 days at 5 °C and 17-186 ppm at the stage of advanced decomposition after storage for 7 days at 5 °C). Although previous methods showed selective CV and PT detection even at low concentrations, the use of these methods remains challenging in research areas that require in-situ, real-time, on-site monitoring. In this study, we demonstrated for the first time an in-situ high-performance chemical receptor-conjugated graphene electronic nose (CRGE-nose) whose limits of detection (LODs), 27.04 and 7.29 ppb, for CV and PT are up to 102 times more sensitive than those of conventional biogenic amine sensors. Specifically, the novel chemical receptors 2,7-bis(3-morpholinopropyl)benzo[lmn][3,8] phenanthroline-1,3,6,8(2H,7H)-tetraone (NaPhdiMor (NPM)) and 2,7-bis(2-((3-morpholinopropyl)amino)ethyl)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone (NaPhdiEtAmMor (NPEAM)) were designed on the basis of density functional theory (DFT) calculations, and their interaction mechanism was characterized by a DFT 3D simulation. Interestingly, the CRGE-nose was connected on a micro sim chip substrate via wire bonding and then integrated into wireless portable devices, resulting in a cost-effective, high-performance prototype CRGE-nose device capable of on-site detection. The portable CRGE-nose can be used for in-situ monitoring of CV and PT concentration changes as low as 27.04 and 7.29 ppb in real meats such as pork, beef, lamb and chicken.

Dietary Supplementation of Shredded, Steam-Exploded Pine Particles Decreases Pathogenic Microbes in the Cecum of Acute Heat-Stressed Broilers.

The gut microbiome stimulates nutrient metabolism and could effectively generate heat tolerance in chickens. This study investigates the effects of dietary steam-exploded pine particle (SPP) supplementation and subsequent acute heat stress on productive performance and cecum microbiome in broilers. Eight-day Ross 308 broilers were distributed in three groups with 0%, 1%, and 2% SPP in diets. On the 41st day, forty birds were allocated to four groups with ten birds each. The treatments were control diet at thermoneutral temperature (0% NT) and acute heat-stressed (HS) birds fed control (0% HS), 1% (1% HS), and 2% (2% HS) SPP. Parameters recorded were body weight (BW), feed intake (FI), rectal temperature (RT), relative organ weight, and metagenome analysis from cecum samples. Percent difference in BW, FI, and RT was decreased in HS birds. Metagenome analysis revealed similar richness and diversity in microbial communities. The relative abundance of the bacterial genus such as Limosilactobacillus, Drancourtella, and Ihubacter was increased while that of Alistipes, Alkalibacter, Lachnotalea, and Turicibacter was decreased in SPP supplemented HS birds. Concludingly, the production performance of broilers is negatively influenced during HS, and 2% dietary SPP supplementation may reduce the adverse effects of HS by modifying the microbiota in chickens.

Real-time monitoring of geosmin based on an aptamer-conjugated graphene field-effect transistor.

In this paper, we propose a novel field-effect transistor (FET) using graphene, which is a two-dimensional (2D) nanomaterial, capable of evaluating water quality, and immobilizing the surface of a graphene micropatterned transistor with a highly responsive bioprobe for a water contamination indicator, geosmin, with high selectivity. A high-quality bioprobe-immobilized graphene FET (GFET) was fabricated for the real-time monitoring of geosmin using a liquid-gate measurement configuration. Immobilization was confirmed by measuring the change in the electrical characteristics of the platform (slope of the current-voltage (I-V) curve) and fluorescence images. In addition, a selectivity test showed remarkable implementation of the highly sensitive sensing platform with an insignificant signal when a nontarget was added. Using the fabricated device, the linear range for geosmin detection was determined to be from 0.01 nM - 1 µM with a detection limit of 0.01 nM. In addition, geosmin concentrations as low as 10 nM could be determined from river water samples with the sensor platform. This sensor can be utilized to immediately determine the presence of odorous substances by analyzing a water supply source without additional pretreatment. Another advantage is that the sensor device is a promising tool that does not have special equipment that requirs careful maintenance. In addition, the device provides a new platform for detecting harmful substances in various water sources by varying the bioprobes that are empolyed.

Macrophage activation by a substituted pyrimido[5,4-b]indole increases anti-cancer activity.

Immunotherapy has become a promising new approach for cancer treatment due to the immune system's ability to remove tumors in a safe and specific manner. Many tumors express anti-inflammatory factors that deactivate the local immune response or recruit peripheral macrophages into pro-tumor roles. Because of this, effective and specific ways of activating macrophages into anti-tumor phenotypes is highly desirable for immunotherapy purposes. Here, the use of a small molecule TLR agonist as a macrophage activator for anti-cancer therapy is reported. This compound, referred to as PBI1, demonstrated unique activation characteristics and expression patterns compared to treatment with LPS, through activation of TLR4. Furthermore, PBI1 treatment resulted in anti-tumor immune behavior, enhancing macrophage phagocytic efficiency five-fold versus non-treated macrophages. Additive effects were observed via use of a complementary strategy (anti-CD47 antibody), resulting in ∼10-fold enhancement of phagocytosis, suggesting this small molecule approach could be used in conjunction with other therapeutics.