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BACKGROUND With a strong ability in performing natural tasks and an easy-to-use interface, ChatGPT received a lot of attention since OpenAI released it to the public. OBJECTIVE A prospective analysis is needed to examine the accuracy and appropriateness of the medication consultation responses generated by ChatGPT. METHODS A prospective cross-sectional study was conducted by the pharmacy department of a medical center in Taiwan. The test dataset included the retrospective collection of medication consultation questions from February 1, 2023, to February 28, 2023, as well as common questions regarding drug-herb interactions. Two different sets of questions were tested: real-world medication consultation questions and common questions about interactions between traditional Chinese and Western medicines. For each ChatGPT response, the appropriateness was evaluated by two experienced pharmacists. In cases where the opinions of the two pharmacists were inconsistent, a third pharmacist would make the final determination. RESULTS From 293 real-world medication consultation questions, a random selection of 80 was used to compare ChatGPT's performance. ChatGPT demonstrated a higher appropriateness rate for answering public medication consultation questions compared to questions presented to healthcare providers in a hospital setting (61% vs 39%, p=.011). CONCLUSIONS The results of this study suggest that ChatGPT may be used to answer basic medication consultation questions. We analyzed the erroneous information and identified potential medical harms associated with certain questions, which is worthy of our attention.

Seeking health information online has gained in popularity. However, few studies have investigated seeking health information online among U.S. pregnant women. The aim of this study was to investigate the patterns, trends, and characteristics of pregnant women in the U.S. who seek health information online. We obtained data from the National Health Interview Survey from 2009 to 2018. The study population consisted of women aged 18 to 49 years who self-reported being pregnant. Complex survey weighting and Chi-squared tests were used to evaluate trends and compare characteristics of online users and nonusers. Multivariable logistic regression analyses were used to evaluate characteristics associated with seeking health information online. Significantly more pregnant women sought health information online in 2018 compared to 2009 (72.9 percent, standard error [SE]: 3.3, 95 percent confidence interval [CI]: 66.3 percent-79.5 percent, vs. 60.7 percent, SE: 3.3, 95 percent CI: 54.0 percent-67.4 percent

Remdesivir, a prodrug targeting RNA-dependent-RNA-polymerase, and cyclosporine, a calcineurin inhibitor, individually exerted inhibitory activity against human coronavirus OC43 (HCoV-OC43) in HCT-8 and MRC-5 cells at EC50 values of 96 ± 34 ∼ 85 ± 23 nM and 2,920 ± 364 ∼ 4,419 ± 490 nM, respectively. When combined, these two drugs synergistically inhibited HCoV-OC43 in both HCT-8 and MRC-5 cells assayed by immunofluorescence assay (IFA). Remdesivir and cyclosporine also separately reduced IL-6 production induced by HCoV-OC43 in human lung fibroblasts MRC-5 cells with EC50 values of 224 ± 53 nM and 1,292 ± 352 nM, respectively; and synergistically reduced it when combined. Similar trends were observed for SARS-CoV-2, which were 1) separately inhibited by remdesivir and cyclosporine with respective EC50 values of 3,962 ± 303 nM and 7,213 ± 143 nM by IFA, and 291 ± 91 nM and 6,767 ± 1,827 nM by a plaque-formation assay; and 2) synergistically inhibited by their combination, again by IFA and plaque-formation assay. Collectively, these results suggest that the combination of remdesivir and cyclosporine merits further study as a possible treatment for COVID-19 complexed with a cytokine storm.

Tylophorine-based compounds and natural cardiotonic steroids (cardenolides and bufadienolides) are two classes of transmissible gastroenteritis coronavirus inhibitors, targeting viral RNA and host cell factors, respectively We tested both types of compounds against two types of coronaviruses, to compare and contrast their antiviral properties, and with view to their further therapeutic development Examples of both types of compounds potently inhibited the replication of both feline infectious peritonitis virus and human coronavirus OC43 with EC50 values of up to 8 and 16 nM, respectively Strikingly, the tylophorine-based compounds tested inhibited viral yields of HCoV-OC43 to a much greater extent (7–8 log magnitudes of p f u /ml) than the cardiotonic steroids (about 2–3 log magnitudes of p f u /ml), as determined by end point assays Based on these results, three tylophorine-based compounds were further examined for their anti-viral activities on two other human coronaviruses, HCoV-229E and SARS-CoV-2 These three tylophorine-based compounds inhibited HCoV-229E with EC50 values of up to 6 5 nM, inhibited viral yields of HCoV-229E by 6–7 log magnitudes of p f u /ml, and were also found to inhibit SARS-CoV-2 with EC50 values of up to 2 5–14 nM In conclusion, tylophorine-based compounds are potent, broad-spectrum inhibitors of coronaviruses including SARS-CoV-2, and could be used for the treatment of COVID-19 © Copyright © 2020 Yang, Lee, Hsu, Jan, Lin, Chang, Peng, Yang, Liang, Liao, Chao, Pang, Kao, Huang, Lin, Chang, Niu, Wu, Sytwu, Chen and Lee

Background New therapeutic options to address the ongoing COVID-19 pandemic are urgently needed. One possible strategy is the repurposing of existing drugs approved for other indications as antiviral agents for SARS-CoV-2. Due to the commercial unavailability of SARS-CoV-2 drugs for treating COVID-19, we screened approximately 250 existing drugs or pharmacologically active compounds for their inhibitory activities against feline infectious peritonitis coronavirus (FIPV) and human coronavirus OC43 (HCoV-OC43), a human coronavirus in the same genus (Betacoronavirus) as SARS-CoV-2. Methods FIPV was proliferated in feline Fcwf-4 cells and HCoV-OC43 in human HCT-8 cells. Viral proliferation was assayed by visualization of cytopathic effects on the infected Fcwf-4 cells and immunofluorescent assay for detection of the nucleocapsid proteins of HCoV-OC43 in the HCT-8 cells. The concentrations (EC50) of each drug necessary to diminish viral activity to 50% of that for the untreated controls were determined. The viabilities of Fcwf-4 and HCT-8 cells were measured by crystal violet staining and MTS/PMS assay, respectively. Results Fifteen out of the 252 drugs or pharmacologically active compounds screened were found to be active against both FIPV and HCoV-OC43, with EC50 values ranging from 11 nM to 75 μM. They are all old drugs as follows, anisomycin, antimycin A, atovaquone, chloroquine, conivaptan, emetine, gemcitabine, homoharringtonine, niclosamide, nitazoxanide, oligomycin, salinomycin, tilorone, valinomycin, vismodegib. Conclusion All of the old drugs identified as having activity against FIPV and HCoV-OC43 have seen clinical use in their respective indications and are associated with known dosing schedules and adverse effect or toxicity profiles in humans. Those, when later confirmed to have an anti-viral effect on SARS-CoV-2, should be considered for immediate uses in COVID-19 patients., Graphical abstract Image 1

In 2013, the U.S. Food and Drug Administration issued a safety warning that cautioned against using magnesium sulfate (MgSO4) injections for more than 5 to 7 days to stop preterm delivery due to the bone problems subsequently observed in infants. However, the warning was mainly based on case reports, and further investigation is necessary to determine whether prolonged MgSO4 use increased infant fractures. To evaluate whether prolonged MgSO4 use for tocolysis increased the risk of subsequent fractures among infants. A retrospective population-based cohort study was conducted with a new-user study design using the National Health Insurance Database in Taiwan. We included pregnant women aged between 12 and 55 years old who delivered a live-born singleton. The enrollment period was from January 1, 2012 to December 31, 2014. The exposure group was defined as pregnant women who received MgSO4 injection for >5 days during pregnancy, while those not receiving any tocolytics were the reference group. The outcome was any bone fracture among the infants during the 2-year follow-up period. Propensity score matching and Cox proportional hazards regression models were used to estimate the hazard of fractures. We further studied the effect of MgSO4 treatment with varied dosages and durations of treatment in the sensitivity analyses. Among the 4092 pregnant women in the database, 693 (16.9%) of them were included in the exposure group. The hazard ratio of infant fractures among prolonged MgSO4 users was not significantly different from that of tocolytic nonusers in adjusted models (adjusted hazard ratio (aHR) = 1.48; 95% confidence interval (CI) = 0.59–3.71). A similar lack of significance was found in the sensitivity analyses (aHR = 1.45; 95% CI = 0.40–5.28 for larger treatment dosage; aHR = 2.52; 95% CI = 0.49–12.98 for longer treatment duration). Prolonged MgSO4 tocolysis use did not increase the risk of infant fractures. Our findings reconfirmed the safety of MgSO4 as a tocolytic treatment.

A series of naturally occurring cardenolides that exhibit potent anti-transmissible gastroenteritis virus (TGEV) activity in swine testicular (ST) cells has been identified. In an immunofluorescence assay, these cardenolides were found to diminish the expressions of TGEV nucleocapsid and spike protein, which was used as an indication for viral replication; block TGEV infection induced apoptosis and cytopathic effects; and impart the same trend of inhibitory activity against Na+/K+-ATPase as for anti-TGEV activity. The viral titer inhibition was found to take place in a dose-dependent manner. Knocking down expression of Na+/K+-ATPase, the cellular receptor of cardenolides, in ST cells was found to significantly impair the susceptibility of ST cells to TGEV infectivity. Thus, we have identified Na+/K+-ATPase as an anti-viral drug target and its antagonists, cardenolides, a novel class of anti- TGEV agents.

Humans have two glutaminase genes, GLS (GLS1) and GLS2, each of which has two alternative transcripts: the kidney isoform (KGA) and glutaminase C (GAC) for GLS, and the liver isoform (LGA) and glutaminase B (GAB) for GLS2. Initial hit compound (Z)-5-((1-(4-bromophenyl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)thiazolidine-2,4-dione (2), a thiazolidine-2,4-dione, was obtained from a high throughput screening of 40 000 compounds against KGA. Subsequently, a series of thiazolidine-2,4-dione derivatives was synthesized. Most of these were found to inhibit KGA and GAC with comparable activities, were less potent inhibitors of GAB, and were moderately selective for GLS1 over GLS2. The relationships between chemical structure, activity, and selectivity were investigated. The lead compounds obtained were found to (1) offer in vitro cellular activities for inhibiting cell growth, clonogenicity, and cellular glutamate production, (2) exhibit high concentrations of exposure in plasma by a pharmacokinetic study, and (3) reduce the tumor size of xenografted human pancreatic AsPC-1 carcinoma cells in mice.

An unprecedented biological function of natural cardenolides independent of their membrane target Na

Graphical abstract, Highlights • Natural cardenolides suppress coronaviral activity via downregulating JAK1. • Natural cardenolides downregulate JAK1 in a Na+/K+-ATPase independent manner. • Ouabain (cardenolides) activates Ndfip1/2 and NEDD4 to mediate JAK1 proteolysis. • Ndfip1/2 and NEDD4 mediated JAK1 proteolysis attenuates coronaviral activity., An unprecedented biological function of natural cardenolides independent of their membrane target Na+/K+-ATPase is disclosed. Previously, we reported that cardenolides impart anti-transmissible gastroenteritis coronavirus (anti-TGEV) activity through the targeting of Na+/K+-ATPase and its associated PI3K_PDK1_RSK2 signaling. Swine testis cells with Na+/K+-ATPase α1 knocked down exhibited decreased susceptibility to TGEV infectivity and attenuated PI3K_PDK1_RSK2 signaling. Herein, we further explored a Na+/K+-ATPase-independent signaling axis induced by natural cardenolides that also afforded significant anti-coronaviral activity for porcine TGEV and human HCoV-OC43. Using pharmacological inhibition and gene silencing techniques, we found that this anti-TGEV or anti-HCoV-OC43 activity was caused by JAK1 proteolysis and mediated through upstream activation of Ndfip1/2 and its effector NEDD4. This study provides novel insights into the pharmacological effects of natural cardenolides, and is expected to inform their future development as antiviral agents.

Tylophorine-based compounds exert broad spectral, potent inhibition of coronaviruses. NF-κB activation is a common pro-inflammatory response of host cells to viral infection. The aims of this study were to (i) find an effective combination treatment for coronaviral infections through targeting of the virus per se and cellular NF-κB activity; and (ii) to study the underling mechanisms. We found that tylophorine-based compounds target the TGEV viral RNA and effectively inhibit TGEV replication. NF-κB inhibition also leads to anti-TGEV replication. NF-κB activation induced by TGEV infection was found to be associated with two convergent pathways, IKK-2_IκBα/p65 and JAK2 mediated p65 phosphorylation, in swine testicular cells. JAK2 inhibition either by CYT387 (a JAK family inhibitor) or by silencing JAK2-expression revealed a dominant JAK2 mediated p65 phosphorylation pathway for NF-κB activation and resulted in NF-κB inhibition, which overrode the IκBα regulation via the IKK-2. Finally, tylophorine-based compounds work cooperatively with CYT387 to impart comprehensive anti-TGEV activities. The combination treatment, wherein a tylophorine compound targets TGEV and a JAK2 inhibitor blocks the alternative dominant NF-κB activation mediated by JAK2, is more effective and comprehensive than either one alone and constitutes a feasible approach for the treatment of SARS-CoV or MERS-CoV.

// Ya-Qi Qiu 1,2 , Cheng-Wei Yang 1 , Yue-Zhi Lee 1 , Ruey-Bing Yang 3 , Chih-Hao Lee 4 , Hsing-Yu Hsu 1 , Chien-Chung Chang 2 and Shiow-Ju Lee 1 1 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan 2 Graduate Program of Biotechnology in Medicine, Institute of Molecular & Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan 3 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 4 Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, Boston, Massachusetts, USA Correspondence: Shiow-Ju Lee, email: // Keywords : Caprin-1, c-Myc, Cyclin D, G3BP1, Processing Body Received : October 02, 2014 Accepted : December 09, 2014 Published : December 10, 2014 Abstract Tylophorine compounds have been the focus of drug development for decades. Tylophorine derivatives exhibit anti-cancer activities but their cellular targets remain unknown. We used a biotinylated tylophorine derivative to probe for the interacting cellular target(s) of tylophorine. Tylophorine directly binds to caprin-1 and consequently enhances the recruitment of G3BP1, c-Myc mRNA, and cyclin D2 mRNA to form a ribonucleoprotein complex. Subsequently, this tylophorine targeted ribonucleoprotein complex is sequestered to the polysomal fractions and the protein expressions of the associated mRNA-transcripts are repressed. Caprin-1 depleted carcinoma cells become more resistant to tylophorine, associated with decreased formation of the ribonucleoprotein complex targeted by tylophorine. Consequently, tylophorine downregulates c-Myc and cyclins D1/D2, causing hypophosphorylation of Rb and suppression of both processing-body formation and the Warburg effect. Gene expression profiling and gain-of-c-Myc-function experiments also revealed that the downregulated c-Myc contributes to the anti-oncogenic effects of tylophorine compounds. Furthermore, the potent tylophorine derivative dibenzoquinoline-33b elicited a similar effect, as c-Myc protein levels were also decreased in xenograft tumors treated with dibenzoquinoline-33b. Thus, tylophorine compounds exert anti-cancer activity predominantly by targeting and sequestering the caprin-1 protein and c-Myc mRNA associated ribonucleoprotein complex.

// Yue-Zhi Lee 1,* , Cheng-Wei Yang 1,* , Hsin-Yu Chang 1,* , Hsing-Yu Hsu 1,* , Ih-Shen Chen 2 , Hsun-Shuo Chang 2 , Chih-Hao Lee 3 , Jinq-chyi Lee 1 , Chidambaram Ramesh Kumar 1 , Ya-Qi Qiu 1,4 , Yu-Sheng Chao 1 and Shiow-Ju Lee 1 1 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan 2 School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, Boston, Massachusetts, USA 4 Graduate Program of Biotechnology in Medicine, Institute of Molecular & Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan * These authors equally contributed to this work Correspondence: Shiow-Ju Lee, email: // Keywords : AMPK; Autophagy; Glutaminase; mTOR; Raptor; ULK1 Received : April 26, 2014 Accepted : July 7, 2014 Published : July 8, 2014 Abstract Glutaminase, which converts glutamine to glutamate, is involved in Warburg effect in cancer cells. Two human glutaminase genes have been identified, GLS ( GLS1 ) and GLS2 . Two alternative transcripts arise from each glutaminase gene: first, the kidney isoform (KGA) and glutaminase C (GAC) for GLS ; and, second, the liver isoform (LGA) and glutaminase B (GAB) for GLS2 . While GLS1 is considered as a cancer therapeutic target, the potential role of GLS2 in cancer remains unclear. Here, we discovered a series of alkyl benzoquinones that preferentially inhibit glutaminase B isoform (GAB, GLS2) rather than the kidney isoform of glutaminase (KGA, GLS1). We identified amino acid residues in an allosteric binding pocket responsible for the selectivity. Treatment with the alkyl benzoquinones decreased intracellular glutaminase activity and glutamate levels. GLS2 inhibition by either alkyl benzoquinones or GLS2 siRNA reduced carcinoma cell proliferation and anchorage-independent colony formation, and induced autophagy via AMPK mediated mTORC1 inhibition. Our findings demonstrate amino acid sequences for selective inhibition of glutaminase isozymes and validate GLS2 as a potential anti-cancer target.

Tylophorine, a phenanthroindolizidine alkaloid, is the major medicinal constituent of herb Tylophora indica. Tylophorine treatment increased the accumulation of c-Jun protein, a component of activator protein 1 (AP1), in carcinoma cells. An in vitro kinase assay revealed that the resultant c-Jun phosphorylation was primarily mediated via activated c-Jun N-terminal protein kinase (JNK). Moreover, flow cytometry indicated that ectopically overexpressed c-Jun in conjunction with tylophorine significantly increased the number of carcinoma cells that were arrested at the G1 phase. The tylophorine-mediated downregulation of cyclin A2 protein levels is known to be involved in the primary G1 arrest. Chromatin immunoprecipitation and reporter assays revealed that tylophorine enhanced the c-Jun downregulation of the cyclin A2 promoter activity upon increased binding of c-Jun to the deregulation AP1 site and decreased binding to the upregulation activating transcription factor (ATF) site in the cyclin A2 promoter, thereby reducing cyclin A2 expression. Further, biochemical studies using pharmacological inhibitors and RNA silencing approaches demonstrated that tylophorine-mediated elevation of the c-Jun protein level occurs primarily via two discrete prolonged signaling pathways: (i) the NF-κB/PKCδ_(MKK4)_JNK cascade, which phosphorylates c-Jun and increases its stability by slowing its ubiquitination, and (ii) the PI3K_PDK1_PP2A_eEF2 cascade, which sustains eukaryotic elongation factor 2 (eEF2) activity and thus c-Jun protein translation. To the best of our knowledge, this report is the first to demonstrate the involvement of c-Jun in the anticancer activity of tylophorine and the release of c-Jun translation from a global translational blockade via the PI3K_PDK1_eEF2 signaling cascade.

A series of naturally occurring cardenolides that exhibit potent anti-transmissible gastroenteritis virus (TGEV) activity in swine testicular (ST) cells has been identified. In an immunofluorescence assay, these cardenolides were found to diminish the expressions of TGEV nucleocapsid and spike protein, which was used as an indication for viral replication; block TGEV infection induced apoptosis and cytopathic effects; and impart the same trend of inhibitory activity against Na+/K+-ATPase as for anti-TGEV activity. The viral titer inhibition was found to take place in a dose-dependent manner. Knocking down expression of Na+/K+-ATPase, the cellular receptor of cardenolides, in ST cells was found to significantly impair the susceptibility of ST cells to TGEV infectivity. Thus, we have identified Na+/K+-ATPase as an anti-viral drug target and its antagonists, cardenolides, a novel class of anti- TGEV agents., Graphical abstract Image 2, Highlights • Cardenolides were identified as a novel class of anti-TGEV agents. • Cardenolides diminished TGEV replication/viral titers in a dose dependent manner. • Cardenolides blocked TGEV infection induced apoptosis and cytopathic effect. • These cardenolides imparted the same trend of inhibitory activity for Na+/K+-ATPase. • Na+/K+-ATPase was identified as an anti-viral drug target.

Bioassay-guided fractionation of the fruits of Reevesia formosana led to isolation of three cardenolides (reevesioside J, reevesioside K, and epi-reevesioside K), three sesquiterpenoids (reevesiterpenol C, reevesiterpenol D, and reevesiterpenol E), and two glycosides (reevesianin A and reevesianin B), along with 46 known compounds. Their structures were determined using spectroscopic techniques. In addition to the reported cytotoxic cardenolides, reevesioside J and strophanthidin exhibited moderate cytotoxicity against the cell lines MCF-7, NCI-H460, and HepG2, with IC50 values of 0.39 ± 0.06 μM and 1.06 ± 0.12 μM for MCF-7, 0.12 ± 0.01 μM and 0.29 ± 0.01 μM for NCI-H460, and 1.09 ± 0.02 μM and 1.72 ± 0.02 μM for HepG2, respectively. Reevesiterpenol E also exhibited the best selective cytotoxicity to the NCI-H460 cell line, with an IC50 value of 3.15 ± 0.22 μM.

Tylophorine and its derivatives exhibit anti-cancer activities, but their cellular targets remain to be elucidated. We used a biotinylated tylophorine derivative to probe for the interacting cellular target(s) of tylophorine. Tylophorine targets and sequesters caprin-1, G3BP1, c-Myc mRNA and cyclin D1/D2 mRNA-associated ribonucleoprotein complexes to the polysomal fractions, thereby repressing the protein expression of the associated mRNA-transcripts. Gene expression profiling and gain-of-c-Myc-function experiments in tylophorine-treated carcinoma cells revealed that the down-regulation of c-Myc contributes to the anti-oncogenic effects of tylophorine. Furthermore, the potent tylophorine derivative dibenzoquinoline-33b elicited a similar effect, as c-Myc protein levels were also decreased in xenograft tumors treated with dibenzoquinoline-33b.Thus, tylophorine compounds exert anti-cancer activity predominantly by targeting and sequestering the caprin-1 protein and c-Myc mRNA associated ribonucleoprotein co...

Herein, we report that c-Jun protein, a component of AP-1, was elevated in the carcinoma cells by tylophorine treatment and the c-Jun phosphorylation was mainly through activated JNK. Moreover, ect...

A series of novel tylophorine-derived dibenzoquinolines has been synthesized and their biological activity evaluated. Three assays were conducted: inhibition of cancer cell proliferation, inhibition of TGEV replication for anticoronavirus activity, and suppression of nitric oxide production in RAW264.7 cells (a measure of anti-inflammation). The most potent compound from these assays, dibenzoquinoline 33b, showed improved solubility compared to tylophorine 9a, in vivo efficacies in a lung A549 xenografted tumor mouse model and a murine paw edema model, good bioavailability, and no significant neurotoxicity (as tested by a rota-rod test for motor coordination). This is the first study to explore in detail the role of the tylophorine E ring on biological activity and very strongly suggests that tylophorine-derived dibenzoquinolines merit further development into orally active agents.

An investigation of alkaloids present in the leaves and stems of Tylophora ovata led to the isolation of two new septicine alkaloids and one new phenanthroindolizidine alkaloid, tylophovatines A, B, C (1, 2, and 5), respectively, together with two known septicine and six known phenanthroindolizidine alkaloids. The structures of the new alkaloids 1, 2, and 5 were established by means of spectroscopic analyses. These eleven alkaloids show in vitro anti-inflammatory activities with IC₅₀ values ranging from 84 nM to 20.6 μM through their suppression of nitric oxide production in RAW264.7 cells stimulated by lipopolysaccharide and interferon-γ. Moreover, these substances display growth inhibition in HONE-1, NUGC-3, HepG2, SF-268, MCF-7, and NCI-H460 cancer cell lines, with GI₅₀ values ranging from 4 nM to 24.2 μM. In addition, tylophovatine C (5) and 13a(S)-(+)-tylophorine (7) were found to exhibit potent in vivo anti-inflammation activities in a rat paw edema model. Finally, structure–activity relationships were probed by using the isolated phenanthroindolizidines and septicines. Phenanthroindolizidines are suggested to be divided into cytotoxic agents (e.g., 10 and 11) and anti-inflammation based anticancer agents (e.g., 5–9).

Real-time and specific detection of single bacterium remains a fundamental challenge and draws very much attention. Using test patterns composed of interdigitated Au-electrode arrays modified with antibody, the specific and quantitative detection of the electrical conductivity of a single Escherichia coli (E. coli, JM109) has been carried out in this work. The key is to ensure low background current of the antibody-modified test patterns before bacteria detection (0.7pA in this case) and minimize the residual moisture or hydration after E. coli immobilization, such as via the use of 1-min bake at 50 degrees C prior to electrical measurement. This method holds great potential for future application in the real-time, specific, and quantitative bacterium detection down to a single bacterium cell.