Harnessing Bioluminescent Bacteria to Develop an Enzymatic-free Enzyme-linked immunosorbent assay for the Detection of Clinically Relevant Biomarkers.

Enzyme-linked immunosorbent assay (ELISA) is the gold standard technique for measuring protein biomarkers due to its high sensitivity, specificity, and throughput. Despite its success, continuous advancements in ELISA and immunoassay formats are crucial to meet evolving global challenges and to address new analytical needs in diverse applications. To expand the capabilities and applications of immunoassays, we introduce a novel ELISA-like assay that we call Bioluminescent-bacteria-linked immunosorbent assay (BBLISA). BBLISA is an enzyme-free assay that utilizes the inner filter effect between the bioluminescent bacteriaAllivibrio fischeriand metallic nanoparticles (gold nanoparticles and gold iridium oxide nanoflowers) as molecular absorbers. Functionalizing these nanoparticles with antibodies induces their accumulation in wells upon binding to molecular targets, forming the classical immune-sandwich complex. Thanks to their ability to adsorb the light emitted by the bacteria, the nanoparticles can suppress the bioluminescence signal, allowing the rapid quantification of the target. To demonstrate the bioanalytical properties of the novel immunoassay platform, as a proof of principle, we detected two clinically relevant biomarkers (human immunoglobulin G and SARS-CoV-2 nucleoprotein) in human serum, achieving the same sensitivity and precision as the classic ELISA. We believe that BBLISA can be a promising alternative to the standard ELISA techniques, offering potential advancements in biomarker detection and analysis by combining nanomaterials with a low-cost, portable bioluminescent platform.

Integration of metabolomics and transcriptomics reveals the therapeutic mechanism underlying Chelidonium majus L. in the treatment of allergic asthma.

BACKGROUND: Chelidonium majus is a well-known traditional Chinese medicine, and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown. METHODS: Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, Hematoxylin and eosin (H&E) staining, Masson's trichrome (Masson) staining, Periodic acid-Schiff (PAS) staining and inflammatory cytokines assay of interleukin (IL)-4, IL-6, IL-17 were implemented to evaluate the protective effects of Chelidonium majus on asthma. Then, the effects of Chelidonium majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses. RESULTS: After administration with Chelidonium majus, the histological injuries of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after Chelidonium majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC (10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs were mainly related to energy metabolism and inflammation, and may be potential therapeutic targets. CONCLUSION: Chelidonium majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation.

A new method to analysis synthetic acetic acid to vinegar: Hydrogen isotope ratio at the methyl site of acetic acid in vinegar by GC-IRMS.

Acetic acid is the key organic substance used to verify the authenticity of vinegar. A new method for precisely determining acetic acid δDCH3 in vinegar via gas chromatography -pyrolytic-stable isotope ratio mass spectrometry (GC-P-IRMS) was established. The δDCH3 values were obtained via calibration with a series of standards. The optimised method demonstrated a repeatability standard deviation within 3 ‰. The standard deviation of accuracy of the new method compared with that of the SNIF-NMR method was within 2.6 ‰. The synthetic acetic acid δDCH3 values was -136.7 ‰ ± 29.6 ‰, and the δDCH3 value of acetic acid in vinegar was -414.9 ‰ ± 40.5 ‰, with significant isotopic distribution characteristics. This methodology serves as a supplementary method for measuring the δDCH3 value of acetic acid in vinegar. It has advantages over other methods in terms of time, sensitivity and operability. And provides a new idea for solving the problem of analyzing substances in the presence of exchangeable groups.

Discovery of Novel 5,6-Dihydro-4H-pyrido[2,3,4-de]quinazoline Irreversible Inhibitors Targeting Both Wild-Type and A775_G776insYVMA Mutated HER2 Kinases.

HER2 mutations were seen in 4% of non-small-cell lung cancer (NSCLC) patients. Most of these mutations (90%) occur as an insertion mutation within the exon 20 frame, leading to the downstream activation of the PI3K-AKT and RAS/MAPK pathways. However, no targeted therapies have yet been approved worldwide. Here a novel series of highly potent HER2 inhibitors with a pyrido[2,3,4-de]quinazoline core were designed and developed. The derivatives with the pyrido[2,3,4-de]quinazoline core displayed superior efficacy of antiproliferation in BaF3 cells harboring HER2insYVMA mutation compared with afatinib and neratinib. Rat studies showed that 8a and 9a with the newly developed core have good pharmacokinetic properties with an oral bioavailability of 41.7 and 42.0%, respectively. Oral administration of 4a and 10e (30 mg/kg, QD) displayed significant antitumor efficacy in an in vivo xenograft model. We proposed promising strategies for the development of HER2insYVMA mutant inhibitors in this study.

Identification, expression profiles, and binding properties of chemosensory protein 18 in Plutella xylostella (Lepidoptera: Plutellidae).

Chemosensory proteins (CSPs) are highly efficient carry tools to bind and deliver hydrophobic compounds, which play an important role in the chemosensory process in insects. The diamondback moth, Plutella xylostella L. (Lepidoptera: Plutellidae), is a cosmopolitan pest that attacks cruciferous crops. However, the detailed physiological functions of CSPs in P. xylostella remain limited to date. Here, we identified a typical CSP, named PxylCSP18, in P. xylostella and investigated its expression patterns and binding properties of volatiles. PxylCSP18 was highly expressed in antennae and head (without antennae), and the expression level in the male antennae of P. xylostella was obviously higher than that in the female antennae. Moreover, PxylCSP18 has a relatively broad binding spectrum. Fluorescence competitive binding assays showed that PxylCSP18 had strong binding abilities with 14 plant volatiles (Ki < 10 µM) that were repellent or attractive to P. xylostella. Notably, PxylCSP18 had no significant binding affinity to (Z)-11-hexadecenal, (Z)-11-hexadecenyl acetate, and (Z)-11-hexadecenyl alcolol, which are the pheromone components of P. xylostella. The attractive effects of trans-2-hexen-1-ol and isopropyl isothiocyanate to male adults and the attractive effects of isopropyl isothiocyanate and the repellent effects of linalool to female adults were significantly decreased after knocked down the expression of PxylCSP18. Our results revealed that PxylCSP18 might play an important role in host plant detection, avoidance of unsuitable hosts, and selection of oviposition sites; however, it does not participate in mating behavior. Overall, these results extended our knowledge on the CSP-related functions, which provided insightful information about CSP-targeted insecticides.

Single-Atom Site SERS Chip for Rapid, Ultrasensitive, and Reproducible Direct-Monitoring of RNA Binding.

Ribonucleic acids (RNA) play active roles within cells or viruses by catalyzing biological reactions, controlling gene expression, and communicating responses to cellular signals. Rapid monitoring RNA variation has become extremely important for appropriate clinical decisions and frontier biological research. However, the most widely used method for RNA detection, nucleic acid amplification, is restricted by a mandatory temperature cycling period of ≈1 h required to reach target detection criteria. Herein, a direct detection approach via single-atom site integrated surface-enhanced Raman scattering (SERS) monitoring nucleic acid pairing reaction, can be completed within 3 min and reaches high sensitivity and extreme reproducibility for COVID-19 and two other influenza viruses' detection. The mechanism is that a single-atom site on SERS chip, enabled by positioning a single-atom oxide coordinated with a specific complementary RNA probe on chip nanostructure hotspots, can effectively bind target RNA analytes to enrich them at designed sites so that the binding reaction can be detected through Raman signal variation. This ultrafast, sensitive, and reproducible single-atom site SERS chip approach paves the route for an alternative technique of immediate RNA detection. Moreover, single-atom site SERS is a novel surface enrichment strategy for SERS active sites for other analytes at ultralow concentrations.

Internal Validation of Automated Visual Evaluation (AVE) on Smartphone Images for Cervical Cancer Screening in a Prospective Study in Zambia.

Objectives: Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests like histopathology, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment performance of VIA. Design: Prospective study. Setting: Eight public health facilities in Zambia. Participants: 8,204 women aged 25-55. Interventions: Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive. Main outcome measures: Area under the receiver operating curve (AUC); sensitivity; specificity. Results: As a general population screening for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89 to 0.93), which translates to a sensitivity of 85% (95% CI = 81% to 90%) and specificity of 86% (95% CI = 84% to 88%) based on maximizing the Youden's index. This represents a considerable improvement over VIA, which a meta-analysis by the World Health Organization (WHO) estimates to have sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88 to 0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83 to 0.91). Conclusions: These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by screening nurses and support our transition to clinical evaluation of AVE's sensitivity, specificity, feasibility, and acceptability across a broader range of settings. The performance of the algorithm as reported may be inflated, as biopsies were obtained only from study participants with visible aceto-white cervical lesions, which can lead to verification bias; and the images and data sets used for testing of the model, although "unseen" by the algorithm during training, were acquired from the same set of patients and devices, limiting the study to that of an internal validation of the AVE algorithm.

Low beauvericin concentrations promote PC-12 cell survival under oxidative stress by regulating lipid metabolism and PI3K/AKT/mTOR signaling.

Beauvericin (BEA), a naturally occurring cyclic peptide with good pharmacological activity, has been widely explored in anticancer research. Although BEA is toxic, studies have demonstrated its antioxidant activity. However, to date, the antioxidant mechanisms of BEA remain unclear. Herein, we conducted a comprehensive and detailed study of the antioxidant mechanism of BEA using an untargeted metabolomics approach, subsequently validating the results. BEA concentrations of 0.5 and 1 µM significantly inhibited H2O2-induced oxidative stress (OS), decreased reactive oxygen species levels in PC-12 cells, and restored the mitochondrial membrane potential. Untargeted metabolomics indicated that BEA was primarily involved in lipid-related metabolism, suggesting its role in resisting OS in PC-12 cells by participating in lipid metabolism. BEA combated OS damage by increasing phosphatidylcholine, phosphatidylethanolamine, and sphingolipid levels. In the current study, BEA upregulated proteins related to the PI3K/AKT/mTOR pathway, thereby promoting cell survival. These findings support the antioxidant activity of BEA at low concentrations, warranting further research into its pharmacological effects.

Risk factors for epidural anesthesia blockade failure in cesarean section: a retrospective study.

BACKGROUND: Epidural anesthesia (EA) is the regional anesthesia technique preferred over spinal anesthesia for pregnant women requiring cesarean section and post-operative pain control. EA failure requires additional sedation or conversion to general anesthesia (GA). This may be hazardous during sedation or GA conversion because of potentially difficult airways. Therefore, this retrospective study aimed to determine the risk factors for epidural failure during cesarean section anesthesia. METHODS: We retrospectively analyzed parturients who underwent cesarean section under EA and catheterization at the Chang Gung Memorial Hospital in Taiwan between January 1 and December 31, 2018. Patient data were collected from the medical records. EA failure was defined as the administration of any intravenous anesthetic at any time during a cesarean section, converting it into GA. RESULTS: A total of 534 parturients who underwent cesarean section were recruited for this study. Of them, 94 (17.6%) experienced EA failure during cesarean section. Compared to the patients with successful EA, those with EA failure were younger (33.0 years vs. 34.7 years), had received EA previously (60.6% vs. 37%), were parous (72.3% vs. 55%), and had a shorter waiting time (14.9 min vs. 16.5 min) (p < 0.05). Younger age (OR 0.91, 95% CI 0.86-0.95), history of epidural analgesia (OR 2.61, 95% CI 1.38-4.94), and shorter waiting time (OR 0.91, 95% CI 0.87-0.97) were estimated to be significantly associated with a higher risk of epidural anesthesia failure. CONCLUSION: The retrospective study found that parturients of younger age, previous epidural catheterization history, and inadequate waiting time may have a higher risk of EA failure. Previous epidural catheterization increased the risk of EA failure by 2.6-fold compared to patient with no history of catheterization.

Integrated molecular modeling and dynamics approaches revealed the mechanism of selective inhibition of HDAC6/8.

The high structural homology of histone deacetylases 6 and 8 (HDAC6/8) poses a challenge in achieving isoform selectivity and has resulted in adverse side effects due to pan-inhibition in clinical applications. Additionally, the rational design of dual-target inhibitors, centered on HDAC6/8, demands a profound understanding of their selectivity mechanisms. Addressing the urgent need for enhanced specificity in the development of inhibitors targeting specific isoforms, we elucidate the mechanism underpinning the selective inhibition of HDAC6/8 inhibitors through in-silico strategies. The hydrogen bonding interaction with Asp101 and Tyr306 is a key factor that enables compound 12b to selectively inhibit HDAC8. Its favorable spatial orientation places the Cap group of 12b between Tyr306 and Tyr100, resulting in an overall L-shaped conformation. These two factors significantly contribute to the selective inhibitory activity of 12b against HDAC8. The zinc binding group (ZBG) of compound NN-390 forms a hydrogen bond with His610, a key residue of HDAC6, facilitating stable chelation with zinc ions. In addition, the Cap group of NN-390 interacts with Phe620 and Phe680 via van der Waals forces, leading to an overall Y-shaped conformation. The aforementioned factors are the main reasons for the selective inhibition of HDAC6 by NN-390. Furthermore, whether the Cap group is in the para or meta-position will influence the selective inhibition of either HDAC6 or HDAC8. We believe these clues can offer valuable insights for the rational design of selective inhibitors targeting HDAC6/8 and pave the way for rational design of dual-target HDAC6/8-based inhibitors.Communicated by Ramaswamy H. Sarma.

Lycium barbarum polysaccharide inhibits blue-light-induced skin oxidative damage with the involvement of mitophagy.

Although blue light can damage the skin to a certain extent, the pathogenesis of its damage remains still unclear. The available evidence suggests that oxidative stress may be the main cause of its damage. Lycium barbarum polysaccharide (LBP) has antioxidative effects in a variety of cells. In this paper, we investigated the protective role of LBP and its mechanism of action related to mitophagy in blue-light-damaged skin cells. The findings indicated that in HaCaT cells and mouse skin, LBP pretreatment was effective in reducing blue-light-induced apoptosis and ameliorating the elevated level of cellular autophagy/mitophagy caused by excessive blue light exposure. The markers reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were used to assess oxidative stress. LBP could effectively inhibit blue-light-induced oxidative stress. It was also found that blue light exposure caused mitochondrial dysfunction in HaCaT cells, including increased intracellular calcium ion levels and decreased mitochondrial membrane potential. LBP pretreatment significantly relieved mitochondrial dysfunction in HaCaT cells. These findings imply that LBP pretreatment protects skin cells from damage induced by blue light irradiation and that mitophagy may be a significant factor in skin photodamage.

Incidence of Inflammatory Bowel Disease in Urban China: A Nationwide Population-based Study.

BACKGROUND & AIMS: Limited studies have evaluated the burden of inflammatory bowel disease (IBD) in China. We aimed to estimate the incidence of IBD including ulcerative colitis (UC) and Crohn's disease (CD) in urban China. METHODS: The national urban incidence in 2016 was calculated based on urban basic medical insurance from 2012 to 2016 in China by using a 4-year washout period. The incidence in Yinzhou District estimated from the Yinzhou electronic health care record database was used to test the accuracy of the results from insurance data. RESULTS: A total of 95,555 patients with IBD were identified. The incidence in 2016 was 10.04 (95% confidence interval, 6.95-13.71) per 100,000 person-years. The incidence rates of both UC and CD were higher among males than among females. There was a sharp increase in UC incidence before the age of 30 years and stabilization in later years (50-79 years old), whereas CD incidence peaked at 30 to 34 years old and experienced decline subsequently. The incidence of UC was much greater than that of CD, with a UC-to-CD incidence ratio of 12.61. The results from the Yinzhou database confirmed these results. CONCLUSIONS: This study is the first to draw a portrait of the distribution of IBD in urban China. The difference in IBD incidence between urban China and other countries suggests an association between the IBD burden and industrialization process. The accelerating urbanization and industrialization process in China, a country with a population of 1.4 billion people, will likely increase the burden of IBD.

Recent Progress of Spectroscopic Probes for Peroxynitrite and Their Potential Medical Diagnostic Applications.

Peroxynitrite (ONOO-) is a crucial reactive oxygen species that plays a vital role in cellular signal transduction and homeostatic regulation. Determining and visualizing peroxynitrite accurately in biological systems is important for understanding its roles in physiological and pathological activity. Among the various detection methods, fluorescent probe-based spectroscopic detection offers real-time and minimally invasive detection, high sensitivity and selectivity, and easy structural and property modification. This review categorizes fluorescent probes by their fluorophore structures, highlighting their chemical structures, recognition mechanisms, and response behaviors in detail. We hope that this review could help trigger novel ideas for potential medical diagnostic applications of peroxynitrite-related molecular diseases.

Performance and response of coupled microbial fuel cells for enhanced anaerobic treatment of azo dye wastewater with simultaneous recovery of electrical energy.

The anaerobic baffled reactor (ABR) is an anaerobic bioreactor that uses baffles to separate the working area into multiple reaction zones. The ABR-microbial fuel cell (MFC) reactor was constructed by embedding MFC in each reaction zone of the ABR. Its degradation of azo dye type (acid mordant red) wastewater and microbial power generation performance were investigated. For different electrode area ratios, the best enhanced treatment and electrical energy output of the coupled system was achieved with an anode/cathode area ratio of 1:1. Compared with the electrode area ratio of 2:1 and 1:2, the power density increased by 82.5% and 80.6%, and the Coulomb efficiency increased by 133.3% and 64.7%. In addition, the best enhanced treatment of printing and dyeing wastewater was achieved by ABR-MFC at 1:1. At a dye concentration of 200 mg/L and a sucrose concentration of 1000 mg/L, the coupled system obtained a COD removal of 92.85% and a chromaticity removal of 96.2%, which achieved a relative COD and chromaticity removal improvement of 1.82% and 2.64%, respectively, relative to the ABR. Scanning electron microscopy (SEM) observation of the electrodes at 1:1 revealed that more microorganisms were attached to the anode surface of the coupled system, the particle size of the granular sludge within the system was larger, and the UV scanning pattern showed lower dye concentration in the water. In conclusion, the microbial fuel cell enhanced anaerobic treatment of dyeing wastewater was the most effective when the electrode area ratio was 1:1, and the best electrical energy output was obtained at the same time. ABR-MFC provides a new idea for the enhanced treatment of dyeing wastewater and electrical energy production.

Nicotine-mediated dopamine regulates short neuropeptide F to inhibit brown planthopper feeding behavior in tobacco-rice rotation cropping.

BACKGROUND: The tobacco-rice rotation cropping (TRRC) is an ecologically friendly system that can both alleviate soil nicotine pollution and decrease the brown planthopper (BPH, Nilaparvata lugens Stål) fitness on rice. However, few studies on this green and effective rotational cropping system have been reported. In particular, the underlying mechanisms of TRRC on the significant reduction of field pest population at the molecular level is still unknown. RESULTS: Field investigation showed that BPH population decreased significantly in TRRC than in rice-rice successive cropping (RRSC) field. In addition, the short neuropeptide F (NlsNPF) and its receptor NlA7 of BPH had half-times lower levels in the TRRC field. Behavioral bioassay indicated a 1.93-fold increase in the number of salivary flanges of the dsNlsNPF group, while BPH fitness parameters, such as honeydew, weight gain, and mortality decreased significantly. Dopamine (DA) content in BPH decreased by ~11.1% under the influence of nicotine, and its presence increased the expression levels of NlsNPF and NlA7. Exogenous DA application eliminated the inhibitory effects of nicotine on BPH feeding and restored the fitness levels of its parameters. Independent application of either a mixture of dsNlsNPF with a nanocarrier or nicotine to the normal rice field revealed that the latter could produce better effects in combination with dsRNA. CONCLUSION: These findings confirmed that DA regulated NlsNPF to inhibit the BPH feeding behavior in TRRC. The results not only provided novel findings on the mechanism of pest-host interactions, but also presented new method for integrated pest management. © 2023 Society of Chemical Industry.

Thermal desorption mechanism of n-dodecane on unsaturated clay: Experimental study and molecular dynamics simulation.

Thermal desorption technology can effectively remediate fuels-contaminated clayey soil. However, the microscopic mechanism for the contaminant desorption on clay is still unclear, especially with the existence of water on clay surfaces. In this study, a combination method including TGA experiments, multi-phase and multi-component kinetic models, and MD simulation was proposed to reveal the thermal desorption mechanism of n-dodecane in unsaturated clay. Results showed that the thermal desorption behavior of the free nonaqueous phase liquid (NAPL) and the adsorbed phase of n-dodecane or water could be identified by the multi-phase and multi-component kinetic models based on the desorption process rate obtained by thermogravimetric analysis (TGA) experiments. The activation energy of the NAPL phase (49-69.9 kJ/mol) was lower than the adsorbed phase (90 kJ/mol). The activation energy of the NAPL phase had the same linear relationship with its mass on kaolinite and montmorillonite, while adsorbed phase only existed on the kaolinite surface. MD simulation showed that water demonstrated competitive adsorption with n-dodecane on montmorillonite surfaces and prevented the formation of the adsorbed phase while having little influence on the n-dodecane adsorption on kaolinite surface, which agrees well with the kinetic analysis of the TGA experiments. With the combination of macroscopic experimental analysis and microscopic molecular simulation, it can be concluded that the mass of the NAPL phase limited the desorption behavior, while the interaction between the clay mineral surface and n-dodecane was the key factor that dominated the thermal desorption behavior of the adsorbed phase. The presented results provide new insight into the desorption mechanism of hydrocarbon on clay minerals, which is of significance for the design of thermal desorption remediation.

Laser Reduced Graphene Oxide Electrode for Pathogenic Escherichia coli Detection.

Graphene-based materials are of interest in electrochemical biosensing due to their unique properties, such as high surface areas, unique electrochemical properties, and biocompatibility. However, the scalable production of graphene electrodes remains a challenge; it is typically slow, expensive, and inefficient. Herein, we reported a simple, fast, and maskless method for large-scale, low-cost reduced graphene oxide electrode fabrication; using direct writing (laser scribing and inkjet printing) coupled with a stamp-transferring method. In this process, graphene oxide is simultaneously reduced and patterned with a laser, before being press-stamped onto polyester sheets. The transferred electrodes were characterized by SEM, XPS, Raman, and electrochemical methods. The biosensing utility of the electrodes was demonstrated by developing an electrochemical test for Escherichia coli. These biosensors exhibited a wide dynamic range (917-2.1 × 107 CFU/mL) of low limits of detection (283 CFU/mL) using just 5 µL of sample. The test was also verified in spiked artificial urine, and the sensor was integrated into a portable wireless system driven and measured by a smartphone. This work demonstrates the potential to use these biosensors for real-world, point-of-care applications. Hypothetically, the devices are suitable for the detection of other pathogenic bacteria.

Synthesis of Heptamethine Cyanines from Furfural Derivatives.

Despite the widespread theranostic utilization of cyanine dyes (Cy7), their synthetic method is still limited with pyridine or cyclohexanone derivatives as starting materials. Herein, we report the synthesis of Cy7 from furfural derivatives. First, a one-pot reaction strategy is developed to solve the unstable problem of the Stenhouse salts. Second, a stepwise condensation strategy is exploited to regioselectively synthesize asymmetrical Cy7. The methodology possesses advantages, such as easy handling, high yield, wide substrate scopes, and good functional group tolerance.

Prediction of gas production rate from shale gas reservoirs using a micro-macro analysis.

Shale gas has become one of the important contributors to the global energy supply. The declining pattern of the gas production rate with time from an unconventional gas reservoir is due to the depletion of shale gas stored in the nanovoids of the shale formation. However, there are only limited ways to predict the variation of the gas production rate with time from an unconventional gas reservoir. This is due to the multiple transport mechanisms of gas in nano-scale pores and changes in shale gas permeability with pressures in nano-scale pores, which is impacted by the pore structure of the shale. In this study, the permeability-pressure (K-p) relationship for different shales (Eagle Ford, Haynesville, Longmaxi and Opalinus) were determined using an equivalent anisotropic pore network model (PNM). This PNM has REV-scale shale gas flow in randomly generated nanovoids and their connection in the shale matrix, and the multiphase flow of shale gas including viscous flow, slip flow and Knudsen diffusion. These predicted K-p correlations were then used in a finite element model (FEM) to predict the variation of the gas production rate with time (flux-time curves) at the macroscale. The simulation results show that the flux-time curves can be simplified to two linear segments in logarithmic coordinates, which are influenced by the fracture length and initial gas pressure. The predicted results using the PNM-FEM were validated by comparing them with the reported field test data. The method described in this study can be used to upscale the gas transport process from micro- to macroscale, which can provide a predictive tool for the gas production in shales.

Design, synthesis and biological evaluation of novel 3,4-dihydro-2H-[1,4]oxazino [2,3-f]quinazolin derivatives as EGFR-TKIs.

Starting with our previously reported work, a novel series of 3,4-dihydro-2H-[1,4]oxazino[2,3-f]quinazolin-derivatives were designed, synthesized and evaluated as potent EGFR tyrosine kinase inhibitors. All of the compounds showed significant inhibitory activities against EGFRwt kinase (IC50 ≤ 937.7 nM). Among them, compound 7j demonstrated the most potent inhibitory activity toward EGFRwt tyrosine kinase with IC50 value of 25.69 nM and showed good antiproliferative activities against NCI-H1563 and H1975 cells. The median cytotoxic concentration (CC50) showed that most of the tested compounds displayed almost no cytotoxicity in vitro against 16HBE cells. In view of the reported compounds activity, the structure deserves further optimization as cancer treatment agents.