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Sensitive detection and precise quantitation of trace-level crucial biomarkers in a complex sample matrix has become an important area of research. For example, the detection of high-sensitivity cardiac troponin I (hs-cTnI) is strongly recommended in clinical guidelines for early diagnosis of acute myocardial infarction. Based on the use of an electrode modified by single-walled carbon nanotubes (SWCNTs) and a Ru(bpy)32+-doped silica nanoparticle (Ru@SiO2)/tripropylamine (TPA) system, a novel type of electrochemiluminescent (ECL) magneto-immunosensor is developed for ultrasensitive detection of hs-cTnI. In this approach, a large amount of [Ru(bpy)3]2+ is loaded in SiO2 (silica nanoparticles) as luminophores with high luminescent efficiency and SWCNTs as electrode surface modification material with excellent electrooxidation ability for TPA. Subsequently, a hierarchical micropillar array of microstructures is fabricated with a magnet placed at each end to efficiently confine a single layer of immunomagnetic microbeads on the surface of the electrode and enable 7.5-fold signal enhancement. In particular, the use of transparent SWCNTs to modify a transparent ITO electrode provides a two-order-of-magnitude ECL signal amplification. A good linear calibration curve is developed for hs-cTnI concentrations over a wide range from 10 fg/ml to 10 ng/ml, with the limit of detection calculated as 8.720 fg/ml (S/N = 3). This ultrasensitive immunosensor exhibits superior detection performance with remarkable stability, reproducibility, and selectivity. Satisfactory recoveries are obtained in the detection of hs-cTnI in human serum, providing a potential analysis protocol for clinical applications.

Psoriasis, characterized by erythematous plaques, desquamation, persistent pruritus, and discomfort, significantly compromises the quality of life for afflicted individuals. The intricate interplay of immunological, genetic, and environmental factors has left the molecular intricacies of psoriasis only partially elucidated, underscoring the imperative to unravel these intricate mechanisms. In contradistinction to conventional techniques such as nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS), the burgeoning laser desorption/ionization (LDI) metabolic paradigm holds substantial promise in elucidating the molecular mechanism of psoriasis. Nonetheless, achieving heightened sensitivity and high-throughput metabolite detection within intricate clinical biosamples mandates stringent requisites, encompassing favourable ionization efficiency and high surface area. Henceforth, we proffered a dual-strategy entailing the utilization of transition metal carbides (MXene) with unique morphology and the integration of multi-walled carbon nanotubes (MWCNTs) to ameliorate these challenges for psoriasis. We have corroborated the morphological architecture, elemental composition, and efficacy of LDI when applied to MWCNTs-doped MXene. Egregiously, through the employment of both animal models and clinical specimens, we attained diagnostic efficiencies of 0.959 and 0.924 via receiver operating characteristic (ROC) curve analysis, respectively, for discrimination psoriasis from control individuals. Doped MXene evinced exceptional signal amplification and imperviousness to salt and protein interference. Furthermore, enrichment pathway analysis unveiled a significant escalation in leukotriene E4 and arachidonic acid levels within the psoriasis cohort. Harnessing LDI metabolic fingerprints, concomitant with MWCNTs-doped MXene, expedited the recognition of the distinct metabolic characteristics inherent to psoriasis, thereby laying bare the dysregulation in leukotriene metabolism. This epochal breakthrough holds immense potential to usher in new vistas for exploring the underlying mechanisms governing the onset and progression of psoriasis-related disorders, thereby significantly contributing to the refinement of psoriasis health management strategies.

Abstract Despite intensive clinical and scientific efforts, the mortality rate of sepsis remains high due to the lack of precise biomarkers for patient stratification and therapeutic guidance. Secreted human tryptophanyl-tRNA synthetase 1 (WARS1), an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4 against infection, activates the genes that signify the hyperinflammatory sepsis phenotype. High plasma WARS1 levels stratified the early death of critically ill patients with sepsis, along with elevated levels of cytokines, chemokines, and lactate, as well as increased numbers of absolute neutrophils and monocytes, and higher Sequential Organ Failure Assessment (SOFA) scores. These symptoms were recapitulated in severely ill septic mice with hypercytokinemia. Further, injection of WARS1 into mildly septic mice worsened morbidity and mortality. We created an anti-human WARS1-neutralizing antibody that suppresses proinflammatory cytokine expression in marmosets with endotoxemia. Administration of this antibody into severe septic mice attenuated cytokine storm, organ failure, and early mortality. With antibiotics, the antibody almost completely prevented fatalities. These data imply that blood-circulating WARS1-guided anti-WARS1 therapy may provide a novel theranostic strategy for life-threatening systemic hyperinflammatory sepsis.

The measurement of cardiac troponin I (cTnI) is of vital importance for the early diagnosis of acute myocardial infarction. In this study, an enhanced electrochemiluminescent immunoassay for the highly sensitive and precise determination of cTnI was reported. A biomimetic chip with nepenthes peristome surface microstructures to achieve single-layer microbead arrays and integrated microelectrode arrays (MEAs) for ECL detection was microfabricated. Ru@SiO2 nanoparticles were prepared as signal amplificators labeling immunomagnetic beads. Dendrimer-encapsulated platinum nanoparticles (Pt DENs) were electrochemically modified on ITO MEAs. The resulting Pt DEN-modified ITO MEAs preserved good optical transparency and exhibited an approximately 20-fold ECL signal amplification compared to that obtained from bare ITO. The method made full use of the biomimetic chip with Pt DENs to develop single-layer immunomagnetic bead arrays with increasingly catalyzed electrochemical oxidation of the [Ru(bpy)3]2+–TPA system. Consequently, a limit of detection calculated as 0.38 pg/mL (S/N = 3) was obtained with excellent selectivity, demonstrating significant potential for the detection of cTnI in clinical diagnostics.

Abstract The photothermal performance of black phosphorus (BP) in the near infrared (NIR)‐II bio‐window (1000–1500 nm) is low, which limits its biomedical applications. Herein, ultrasmall nickel phosphide quantum dots (Ni2P QDs) are synthesized with BP quantum dots (BPQDs) as the template by topochemical transformation. The size of Ni2P QDs is ≈3.5 nm, similar to that of BPQDs, whereas the absorption and photothermal conversion efficiency of Ni2P QDs at 1064 nm (43.5%) are significantly improved compared with those of BPQDs. To facilitate in vivo applications, an Ni2P QDs‐based liposomal nano‐platform (Ni2P‐DOX@Lipo‐cRGD) is designed by incorporation of Ni2P QDs and doxorubicin (DOX) into liposomal bilayers and the interior, respectively. The encapsulated DOX is responsively released from liposomes upon 1064‐nm laser irradiation owing to the photothermal effect of Ni2P QDs, and the drug release rate and amount are controlled by the light intensity and exposure time. In vivo, experiments show that Ni2P‐DOX@Lipo‐cRGD has excellent tumor target capability and biocompatibility, as well as complete tumor ablation through the combination of photothermal therapy and chemotherapy. The work provides a new paradigm for the NIR‐II transformation of nano‐materials and may shed light on the construction of multifunctional nano‐platforms for cancer treatment.

Various kinds of plastics have been developed over the past century, vastly improving the quality of life. However, the indiscriminate production and irresponsible management of plastics have led to the accumulation of plastic waste, emerging as a pressing environmental concern. To establish a clean and sustainable plastic economy, plastic recycling becomes imperative to mitigate resource depletion and replace non-eco-friendly processes, such as incineration. Although chemical and mechanical recycling technologies exist, the prevalence of composite plastics in product manufacturing complicates recycling efforts. In recent years, the biodegradation of plastics using enzymes and microorganisms has been reported, opening a new possibility for biotechnological plastic degradation and bio-upcycling. This review provides an overview of microbial strains capable of degrading various plastics, highlighting key enzymes and their role. In addition, recent advances in plastic waste valorization technology based on systems metabolic engineering are explored in detail. Finally, future perspectives on systems metabolic engineering strategies to develop a circular plastic bioeconomy are discussed.

Summary: While cytoplasmic tryptophanyl-tRNA synthetase (WARS1) ligates tryptophan (Trp) to its cognate tRNAs for protein synthesis, it also plays a role as an innate immune activator in extracellular space. However, its secretion mechanism remains elusive. Here, we report that in response to stimuli, WARS1 can be secreted via two distinct pathways: via Trp-dependent secretion of naked protein and via Trp-independent plasma-membrane-derived vesicles (PMVs). In the direct pathway, Trp binding to WARS1 induces a “closed” conformation, generating a hydrophobic surface and basic pocket. The Trp-bound WARS1 then binds stable phosphatidylinositol (4,5)-biphosphate and inner plasma membrane leaflet, passing across the membrane. In the PMV-mediated secretion, WARS1 recruits calpain 2, which is activated by calcium. WARS1 released from PMVs induces inflammatory responses in vivo. These results provide insights into the secretion mechanisms of WARS1 and improve our understanding of how WARS1 is involved in the control of local and systemic inflammation upon infection.

Abstract Background The effectiveness of erythropoiesis-stimulating agents, which are the main stay of managing anaemia of chronic kidney disease (CKD), is largely dependent on adequate body iron stores. The iron stores are determined by the levels of serum ferritin concentration and transferrin saturation. These two surrogate markers of iron stores are used to guide iron replacement therapy. Most Aboriginal and/or Torres Islander Australians of the Northern Territory (herein respectfully referred to as First Nations Australians) with end-stage kidney disease have ferritin levels higher than current guideline recommendations for iron therapy. There is no clear evidence to guide safe and effective treatment with iron in these patients. We aim to assess the impact of intravenous iron treatment on all-cause death and hospitalisation with a principal diagnosis of all-cause infection in First Nations patients on haemodialysis with anaemia, high ferritin levels and low transferrin saturation Methods In a prospective open-label blinded endpoint randomised controlled trial, a total of 576 participants on maintenance haemodialysis with high ferritin (> 700 μg/L and ≤ 2000 μg/L) and low transferrin saturation (

IntroductionPrevious studies have shown that in addition to having impairments in facial emotion recognition, patients with schizophrenia also show a lack of facial expression. Although negative symptoms such as decreased facial activity are common symptoms of schizophrenia, the related factors remain inconclusive. Therefore, this study compared healthy controls to explore the characteristics of facial muscle activity intensity in patients with schizophrenia and its relationship with negative symptoms.MethodsThis observational and cross-sectional study conducted in a psychiatric hospital in China included a total of 135 patients with schizophrenia and 134 healthy controls. The negative symptoms of schizophrenia were evaluated using the Brief Negative Symptom Scale. The intensity of facial muscle activity under positive, neutral, and negative emotional stimuli conditions was automatically collected by a computer, including 17 values (F01-F17) that represent different facial muscle activities. Statistical tests were performed to analyze facial muscle activity indexes, to explore an objective and quantitative method to evaluate the negative symptoms of schizophrenia.ResultsThe facial muscle activity intensity of the schizophrenia group at F02 (outer eyebrow), F04 (upper eyelid), F07 (nose), F10 (dimple), F12 (lower jaw 1), F14 (lip 2), and F17 (blink) was lower than that of the healthy controls (p < 0.05). Under positive, neutral, and negative emotional stimuli conditions, the facial muscle activity intensity of F16 (lower jaw 2) was positively correlated with negative symptoms (p < 0.05).ConclusionOur study indicated that patients with schizophrenia show defects in facial muscle activity and that is associated with negative symptoms.

Familial hemophagocytic lymphohistiocytosis (HLH) is a rare genetic and life-threatening immunodeficiency disease. Here, we present a 38-year-old male who initially developed multiple annular to irregular erythema accompanied by a fever after COVID-19 vaccination. He was diagnosed with HLH with evidence of leukocytopenia in a full blood test, elevations of ferritin and sCD25, decreased NK cell function, and hemophagocytosis of a bone marrow biopsy specimen. A genetic examination revealed two probable disease-causing heterozygous mutations on UNC13D associated with type 3 familial HLH. A review of the case reports relevant to HLH following COVID-19 vaccination and the cutaneous manifestations of HLH with genetic defects suggests the necessity that individuals with preexisting immune dysregulation or diseases not classified should be cautious about COVID-19 vaccination and reminds clinicians that various recalcitrant skin lesions may be a sign of HLH.

Abstract Background The World Health Organization has highlighted the paucity of research into the oral health needs of older adults. In Singapore, until recently, publically funded/subsidized oral health care for adults has been limited to basic primary care at government-funded polyclinics. Access to a more comprehensive range of subsidized care in the private sector was widened through the government-funded Community Health Assistance Scheme (CHAS) in 2012 and Pioneer Generation (PG) scheme in 2015. Little is known about the attitude to dental service utilization among older adults in Singapore since then. Methods We conducted semi-structured individual interviews with 25 participants above 65 years of age who were eligible for subsidized dental care plans. Participants were recruited from a public teaching hospital and a public primary care clinic in Singapore. The duration of each interview was 15–30 min. Interviews were transcribed verbatim and the transcripts were analyzed thematically using a phenomenological approach. Results Pertinent themes emerged related to four major areas: (a) general awareness towards oral health, (b) life course perspective of oral health, (c) barriers to visit the dentist, (d) shaping dental service utilisation behaviours through provision of financial subsidies for dental care. Most participants perceived a strong relationship between oral health and systemic health. However, there were erroneous traditional beliefs such as oral health is not part of physical health and edentulous participants did not need to visit a dentist. Fear, anxiety, previous negative experience and lack of knowledge were barriers to visiting the dentist. Trust and convenience were considerations for patients when deciding whether to switch from public to private dental services where CHAS/PG were only available. Conclusion Our study provided important insights regarding oral health perceptions and beliefs of older people residing in the community which may affect their dental service utilization. This further highlights the importance of understanding the concerns of this group when implementing healthcare policies for elderly in Singapore. The findings of our study will serve as a baseline for future studies in Singapore and inform studies in other countries that implement targeted schemes for older adults.

The release of chemicals and microorganisms from various sources, such as industry, agriculture, animal farming, wastewater treatment plants, and flooding, into water systems have caused water pollution in several parts of our world, endangering aquatic ecosystems and individual health. World Health Organization (WHO) has introduced strict standards for the maximum concentration limits for nutrients and chemicals in drinking water, surface water, and groundwater. It is crucial to have rapid, sensitive, and reliable analytical detection systems to monitor the pollution level regularly and meet the standard limit. Electrochemical biosensors are advantageous analytical devices or tools that convert a bio-signal by biorecognition elements into a significant electrical response. Thanks to the micro/nano fabrication techniques, electrochemical biosensors for sensitive, continuous, and real-time detection have attracted increasing attention among researchers and users worldwide. These devices take advantage of easy operation, portability, and rapid response. They can also be miniaturized, have a long-life span and a quick response time, and possess high sensitivity and selectivity and can be considered as portable biosensing assays. They are of special importance due to their great advantages such as affordability, simplicity, portability, and ability to detect at on-site. This review paper is concerned with the basic concepts of electrochemical biosensors and their applications in various water quality monitoring, such as inorganic chemicals, nutrients, microorganisms’ pollution, and organic pollutants, especially for developing real-time/online detection systems. The basic concepts of electrochemical biosensors, different surface modification techniques, bio-recognition elements (BRE), detection methods, and specific real-time water quality monitoring applications are reviewed thoroughly in this article.

Background: Scarce literature has yet to characterize the tactile discrimination capability as well as the underlying mechanism of tactile deficits in psychotic disorder. In particular, very little is known regarding the tactile perception acuity in schizophrenia.Methods: A total of 131 clinically stable patients with schizophrenia (SCZ) and 79 healthy control (HC) volunteers were enrolled in the study. All the participants were tested on a tactile stimulus device which could quantify the tactile discrimination capability with right index finger scanned over the angles via the passive finger-movement apparatus. The MATRICS Consensus Cognitive Battery (MCCB) was adapted to assess the neurocognition of the participants. Correlation analysis and multivariate linear regression analysis were performed to investigate the relationship between tactile perception performance and neurocognitive function.Results: It was discovered that there existed a significant deficits in the tactile passive perception acuity (i.e., tactile angle discrimination threshold) in patients with schizophrenia compared with their healthy controls (F (3, 206) = 11.458, P = 0.001,partial η2 = 0.053). The MCCB total score and its six domains were significantly lower in SCZ patients than those in HCs (all p < 0.001). In the SCZ group, the composite score of the MCCB (r = −0.312, P < 0.001) and domains of neurocognition including speed of processing (r = −0.191, P = 0.031), attention/vigilance (r = −0.177, P = 0.047), working memory (r = −0.316, P < 0.001), verbal learning (r = − 0.332, P < 0.001), visual learning (r = −0.260, P = 0.004), and reasoning and problem solving (r = −0.209, P = 0.018) showed significant negative correlations with the tactile angle discrimination threshold. Multivariate linear regression analysis revealed that neurocognition impairment, especially the decline of working memory (B = −0.312, P < 0.001),underpin the tactile perception discrimination deficits in patients with SCZ.Conclusion: To the best of our knowledge, this is the first study to unravel the deficits of tactile passive perception acuity and its underlying neurocognition basis in patients with SCZ. This finding adds novel evidence to the subtle variation in haptic discrimination skills in schizophrenia which contributes to a more comprehensive understanding of the sensory profiles of this disorder.

Abstract Background Periodontitis is an infectious disease that manifests as alveolar bone loss surrounding the roots of teeth. Diabetes aggravates periodontitis-induced alveolar bone loss via suppression of bone formation. Intermittent parathyroid hormone (PTH) administration displays an anabolic effect on bone. In this study, we investigated the effect of intermittent PTH administration on alveolar bone loss in type 1 diabetic rats with periodontitis. Methods Rats were divided into control (C), periodontitis (P), periodontitis treated with PTH (P + PTH), diabetes with periodontitis (DP), and diabetes with periodontitis treated with PTH (DP + PTH) groups. To induce type 1 diabetes, rats were injected with streptozotocin and periodontitis was induced bilaterally by applying ligatures to the mandibular first molars for 30 days. During the experimental period, the P + PTH and DP + PTH groups were subcutaneously injected with PTH (40 μg/kg) three times per week, whereas the C, P, and DP groups were injected with citrate buffer. To observe the mineralization of the alveolar bone, the DP and DP + PTH groups were injected with calcein on days 10 and 27, and with alizarin red on day 20. Thirty days after ligation, histological findings and fluorescence labeling were analyzed in the furcations of the mandibular first molars. Sclerostin-positive osteocytes were assessed by immunohistochemical analyses. Results The DP groups had smaller areas of alveolar bone than the other groups, and the DP + PTH group had a larger alveolar bone area than the DP group. The DP group had less osteoid formation than the C group, whereas the DP + PTH had greater osteoid formation than the DP group. Fluorescence labeling results revealed that the DP + PTH group had more mineral deposition on the alveolar bone than the DP group. The DP + PTH group exhibited lower percentage of sclerostin-positive osteocytes in alveolar bone than the DP group. Conclusions Intermittent PTH administration diminishes alveolar bone loss and sclerostin expression in osteocytes, but increases osteoid formation and mineralization, suggesting that intermittent PTH administration attenuates diabetes-aggravated alveolar bone loss by the induction of bone formation. PTH-induced bone formation may be related to the regulation of osteocytic sclerostin expression in type 1 diabetic rats with periodontitis.

Trace mercury ion (Hg2+) detection is important for environmental monitoring and water safety. In this work, we study the electrochemical strategy to detect trace Hg2+ based on the preconcentration of temperature-controlled N-octylpyridinium tetrafluoroborate ([OPy][BF4]) dispersive liquid–liquid microextraction. The [OPy][BF4] selectively extracted Hg2+ from aqueous solution by the adsorption of unsaturated N in [OPy][BF4], which increased the concentration of Hg2+ and decreased that of other interference ions. It was noted that the adsorption of [OPy][BF4] to Hg2+ was weakened by aqueous solution. Hence, after extraction, precipitated [OPy][BF4] was diluted by a buffer solution comprising a mixture of water and acetonitrile to release Hg2+ and the single was detected by electrochemistry. Water is proposed to release Hg2+ adsorbed by [OPy][BF4], and the acetonitrile serves as a co-solvent in buffer solution. Sensitivity and anti-inference ability of sensors were improved using the proposed method and Hg2+ releasing procedure. The detection limit (S/N = 3) of the sensor is 0.0315 μg/L with a linear range from 0.1 to 1 μg/L. And the sensor exhibits good recovery with an range from 106 % to 118%, which has great potential for trace Hg2+ determination.

Abstract: Primary cutaneous amyloidosis is limited to the skin without involving any other tissue. Nodular amyloidosis is rare, and atrophic nodular cutaneous amyloidosis is even rarer. We describe the fourth case of atrophic nodular cutaneous amyloidosis by searching PubMed databases. A 52-year-old female presented to our hospital with a 2-year history of orange papules and nodules without subjective symptom on her right abdomen. Review of systems was negative. Atrophic nodular amyloidosis may progress to primary systemic disease in up to 7% of cases. Because our patient had no systemic involvement, she was diagnosed with atrophic nodular cutaneous amyloidosis based on characteristic symptoms and histopathologic examination. Routine follow-up for this patient is necessary to detect any potential disease progression.

In order to improve the portability of basic absorbents monoethanolamine (MEA) and glycine (Gly), both were supported on microporous activated carbon (AC). Chemical modification by alkali-metal ion exchange (of Li, Na, K) was carried out on Gly-based absorbents. All supported absorbents were subjected to CO2 absorption capacity (pure CO2) and selectivity (indoor level) tests. Textural and chemical characterizations were carried out on test sorbents. All impregnation brought about significant reduction of specific surface area and microporosity of the adsorbent Depreciation in the textural properties was found to result to reduction in pure CO2 sorption. Contrarily, low-level CO2 removal capacity was enhanced as the absorbent dosage increases, resulting in supported 5 molar MEA in methanol solution. Adsorption capacities were improved from 0.016 and 0.8 in raw ACs to 1.065 mmol/g for MEA’s. Surface chemistry via X-ray photoelectron spectroscopy (XPS) of the supported sorbents showed the presence of amine, pyrrole and quaternary-N. In reducing sequence of potency, pyridine, amine and pyrrolic-N were noticed to contribute significantly to CO2 selective adsorption. Furthermore, the adsorption isotherm study confirms the presence of various SNGs heterogeneously distributed on AC. The adsorption mechanism of the present AC adsorbents favored Freundlich and Langmuir isotherm at lower and higher CO2 concentrations respectively.

Tryptophanyl-tRNA synthetase 1 (WARS1) is an endogenous ligand of mammalian Toll-like receptors (TLR) 2 and TLR4. Microarray data, using mRNA from WARS1-treated human peripheral blood mononuclear cells (PBMCs), had indicated WARS1 to mainly activate innate inflammatory responses. However, exact molecular mechanism remains to be understood. The triggering receptor expressed on myeloid cells (TREM)-1 is an amplifier of pro-inflammatory processes. We found WARS1 to significantly activate TREM-1 at both mRNA and protein levels, along with its cell surface expression and secretion in macrophages. WARS1 stimulated TREM-1 production via TLR2 and TLR4, mediated by both MyD88 and TRIF, since targeted deletion of TLR4, TLR2, MyD88, and TRIF mostly abrogated TREM-1 activation. Furthermore, WARS1 promoted TREM-1 downstream phosphorylation of DAP12, Syk, and AKT. Knockdown of TREM-1 and inhibition of Syk kinase significantly suppressed the activation of inflammatory signaling loop from MyD88 and TRIF, leading to p38 MAPK, ERK, and NF-κB inactivation. Finally, MyD88, TRIF, and TREM-1 signaling pathways were shown to be cooperatively involved in WARS1-triggered massive production of IL-6, TNF-α, IFN-β, MIP-1α, MCP-1, and CXCL2, where activation of Syk kinase was crucial. Taken together, our data provided a new insight into WARS1′s strategy to amplify innate inflammatory responses via TREM-1.

In this paper, a thermo-responsive shape memory effect in a polyvinyl chloride thermoset foam is characterized. Excellent shape recovery performance is observed in foam samples programmed both at room temperature and above their transition temperature. The conversion of porous structures in the foam from closed-cell to open-cell after a shape memory effect cycle is revealed via a series of specially designed oil-dripping experiments and optical images of the micro pores. Programming the strain higher than 20% results in an apparent increase in open-cell level, whereas programming temperatures have almost no influence.

C46H32Cu2N8O12, monoclinic, P21/c, a = 9.5638(9)Å, b = 20.2142(19) Å, c = 12.0825(11) Å, β = 94.696(1)°, V = 2328.0(4) Å3, Z = 2, Rgt(F) = 0.0273, wRref(F2) = 0.0711, T = 100 K.

Helicobacter pylori is associated with hypergastrinemia, which has been linked to the development of gastric diseases. Although the molecular mechanism is not fully understood, H. pylori is known to modulate the Erk pathway for induction of gastrin expression. Herein we found that an epidermal growth factor (EGF) receptor kinase inhibitor significantly blocked H. pylori-induced gastrin promoter activity, suggesting involvement of EGF receptor ligands. Indeed, H. pylori induced mRNA expression of EGF family members such as amphiregulin, EGF, heparin-binding EGF-like growth factor (HB-EGF), and transforming growth factor-α. Of these, specific siRNA targeting of HB-EGF significantly blocked H. pylori-induced gastrin expression. Moreover, H. pylori induced HB-EGF ectodomain shedding, which we found to be a critical process for H. pylori-induced gastrin expression. Thus, we demonstrate a novel role for human mature HB-EGF in stimulating gastrin promoter activity during H. pylori infection. Further investigation using specific siRNAs targeting each isoform of Raf, Mek, and Erk elucidated that the mechanism underlying H. pylori-induced gastrin expression can be delineated as the sequential activation of HB-EGF, the EGF receptor, C-Raf, Mek1, and the Erk2 molecules in the MAPK pathway. Surprisingly, whereas Erk2 acts as a potent activator of gastrin expression, siRNA knockdown of Erk1 induced gastrin promoter activity, suggesting that Erk1 typically acts as a repressor of gastrin expression. Elucidation of the mechanism of gastrin modulation by HB-EGF-mediated EGF receptor transactivation should facilitate the development of therapeutic strategies against H. pylori-related hypergastrinemia and consequently gastric disease development, including gastric cancers.