Proton Pump Research Articles

Proton pump inhibitor use and bone fractures in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are at high risk for bone fractures, which are associated with high morbidity and mortality. Proton pump inhibitors (PPI) have been linked to an increased risk for fractures in the general population as well as in patients with need for hemodialysis, but studies in patients with CKD are currently missing. We performed a population-based observational case-control study exploring a sample of patients with CKD derived from the IQVIATM Disease Analyzer database. Patients with and without fractures were matched using the 1:1 nearest neighbor propensity score matching method. To investigate the association between PPI use and fractures, multivariable logistic regression analyses were performed adjusting for confounding factors. In total, 6076 patients with and 6076 patients without fractures were matched and subsequently available for analyses. In the total cohort, PPI use was associated with an increased risk for fractures (OR 1.68; 95% CI 1.55-1.83). This association was noted for nearly all types of fractures. The strongest association between PPI use and fractures was found in patients below the age of 60 with a PPI prescription for longer than two years (OR 6.85, 95% CI 1.85-25.38). The same was true, when analyzing cumulative PPI doses. Here, patients below the age of 60 with a cumulative PPI dose above 16000mg (highest quartile) had the highest risk for fractures (OR 4.62, 95% CI 1.87-11.44). There was no difference between men or women regarding the association between PPI use and fractures. This study provides evidence that PPI use is associated with fractures in patients with CKD. Deprescription of PPI in patients without an indication for treatment could be a modifiable risk factor to reduce fracture risk in this high-risk group.

Morphology, behavior, and phylogenomics of Oxytoxum lohmannii, Dinoflagellata.

Dinoflagellates are an abundant and diverse group of protists representing a wealth of unique biology and ecology. While many dinoflagellates are photosynthetic or mixotrophic, many taxa are heterotrophs, often with complex feeding strategies. Compared to their photosynthetic counterparts, heterotrophic dinoflagellates remain understudied, as they are difficult to culture. One exception, a long-cultured isolate originally classified as Amphidinium but recently reclassified as Oxytoxum, has been the subject of a number of feeding, growth, and chemosensory studies. This lineage was recently determined to be closely related to Prorocentrum using phylogenetics of ribosomal RNA gene sequences, but the exact nature of this relationship remains unresolved. Using transcriptomes sequenced from culture and three single cells from the environment, we produce a robust phylogeny of 242 genes, revealing Oxytoxum is likely sister to the Prorocentrum clade, rather than nested within it. Molecular investigations uncover evidence of a reduced, nonphotosynthetic plastid and proteorhodopsin, a photoactive proton pump acquired horizontally from bacteria. We describe the ultrastructure of O. lohmannii, including densely packed trichocysts, and a new type of mucocyst. We observe that O. lohmannii feeds preferentially on cryptophytes using myzocytosis, but can also feed on various phytoflagellates using conventional phagocytosis. O. lohmannii is amenable to culture, providing an opportunity to better study heterotrophic dinoflagellate biology and feeding ecology.

Do Proton Pump Inhibitors Cause Myocardial Infarction and Stroke? Time-Variant Analyses Can Resolve the Debate.

Do Proton Pump Inhibitors Cause Myocardial Infarction and Stroke? Time-Variant Analyses Can Resolve the Debate.

Estimation of CDK inhibitors by RP-HPLC: application for pharmacokinetic interactions studies with PPIs.

Background: The study investigated pharmacokinetic interactions between palbociclib and ribociclib with proton pump inhibitors (PPIs) using the reverse-phase high-performance liquid chromatography (RP-HPLC) method. Methods: Developed RP-HPLC method quantified palbociclib and ribociclib in biological matrices. In vitro metabolic stability assays and in vivo studies in rats evaluated effect of omeprazole and esomeprazole on pharmacokinetics of palbociclib and ribociclib. Results: The RP-HPLC method was sensitive, accurate and linear. Esomeprazole and omeprazole decreased metabolic clearance of palbociclib and ribociclib by several folds. In vivo, esomeprazole elevated Cmax of palbociclib and ribociclib by 90.1% and 86.4%, whereas omeprazole reduced it by 32.0% and 16.8%, respectively. Conclusion: The RP-HPLC method was used to analyze in vitro and in vivo samples. Long-term treatment with PPIs affects pharmacokinetics of palbociclib and ribociclib, necessitating optimal chemotherapy regimen.

Accelerating Anhydrous Proton Transport in Covalent Organic Frameworks: Pore Chemistry and its Impacts

AbstractProton conduction is important in both fundamental research and technological development. Here we report designed synthesis of crystalline porous covalent organic frameworks as a new platform for high‐rate anhydrous proton conduction. By developing nanochannels with different topologies as proton pathways and loading neat phosphoric acid to construct robust proton carrier networks in the pores, we found that pore topology is crucial for proton conduction. Its effect on increasing proton conductivity is in an exponential mode other than linear fashion, endowing the materials with exceptional proton conductivities exceeding 10−2 S cm−1 over a broad range of temperature and a low activation energy barrier down to 0.24 eV. Remarkably, the pore size controls conduction mechanism, where mesopores promote proton conduction via a fast‐hopping mechanism, while micropores follow a sluggish vehicle process. Notably, decreasing phosphoric acid loading content drastically reduces proton conductivity and greatly increases activation energy barrier, emphasizing the pivotal role of well‐developed proton carrier network in proton transport. These findings and insights unveil a new general and transformative guidance for designing porous framework materials and systems for high‐rate ion conduction, energy storage, and energy conversion.

Accelerating Anhydrous Proton Transport in Covalent Organic Frameworks: Pore Chemistry and its Impacts.

Proton conduction is important in both fundamental research and technological development. Here we report designed synthesis of crystalline porous covalent organic frameworks as a new platform for high-rate anhydrous proton conduction. By developing nanochannels with different topologies as proton pathways and loading neat phosphoric acid to construct robust proton carrier networks in the pores, we found that pore topology is crucial for proton conduction. Its effect on increasing proton conductivity is in an exponential mode other than linear fashion, endowing the materials with exceptional proton conductivities exceeding 10-2 S cm-1 over a broad range of temperature and a low activation energy barrier down to 0.24 eV. Remarkably, the pore size controls conduction mechanism, where mesopores promote proton conduction via a fast-hopping mechanism, while micropores follow a sluggish vehicle process. Notably, decreasing phosphoric acid loading content drastically reduces proton conductivity and greatly increases activation energy barrier, emphasizing the pivotal role of well-developed proton carrier network in proton transport. These findings and insights unveil a new general and transformative guidance for designing porous framework materials and systems for high-rate ion conduction, energy storage, and energy conversion.

Medium-term outcomes after magnetic sphincter augmentation vs. fundoplication for reflux disease due to hiatal hernia: a propensity-score matched comparison in 282 patients.

An increasing number of reflux patients opt for magnetic sphincter augmentation (MSA) instead of fundoplication. However, few studies comparethe medium-term efficacy and safety of the procedures. We conducted a retrospective single-center analysis of consecutive MSA and Nissen fundoplication cases between 01/2015 and 06/2020. Patients underwent surgery, including hiatoplasty, for medical treatment-resistant reflux due to hiatal hernia. Surgical revision and proton pump inhibitor (PPI) reuptake rates were the primary outcomes. We also compared adverse event rates. Patients with severe preoperative dysphagia/motility disorders were assigned different treatment pathways and excluded from the analysis. We used propensity-score matching to reduce confounding between treatments. Out of 411 eligible patients, 141 patients who underwent MSA and 141 with fundoplication had similar propensity scores and were analyzed. On average, patients were 55 ± 12years old and overweight (BMI: 28 ± 5). At 3.9years of mean follow-up, MSA was associated with lower surgical revision risk as compared to fundoplication (1.2% vs 3.0% per year, respectively; HR: 0.38; 95% CI 0.15-0.96; p = 0.04), and similar PPI-reuptake risk (2.6% vs 4.2% per year; HR: 0.59; 95% CI 0.30-1.16; p = 0.12). Adverse event rates during primary stay were similar (MSA vs. fundoplication: 1% vs. 3%, p = 0.68). Fewer patients experienced adverse events in the MSA group after discharge (24% vs. 33%, p = 0.11), driven by higher rates of self-limiting dysphagia (1% vs. 9%, p < 0.01) and gas/bloating (10% vs. 18%, p = 0.06) after fundoplication. Differences between MSA and fundoplication in dysphagia requiring diagnostic endoscopy (11% vs. 8%, p = 0.54) or surgical revision (2% vs. 1%, p = 1.0) were non-significant. The device explantation rate was 4% (5/141). MSA reduces the re-operation risk compared to fundoplication and may decrease adverse event rates after discharge. Randomized head-to-head studies between available surgical options are needed.

Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population-based cohort study.

Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections. The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12-1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99-1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11-1.27) and mortality (HR 1.37. 95% CI 1.29-1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19-2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident. PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required. This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).

Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population-based cohort study

Background:Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections.Methods:The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).Results:Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12–1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26–1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99–1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11–1.27) and mortality (HR 1.37. 95% CI 1.29–1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19–2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident.Conclusions:PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required.Funding:This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People’s Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).

An essential role for the Hv1 voltage-gated proton channel in Pseudomonas aeruginosa corneal infection.

Assembly of NADPH oxidase 2 (NOX2) proteins in neutrophils plays an essential role in controlling microbial infections by producing high levels of reactive oxygen species (ROS). In contrast, the role of the Hv1 voltage-gated proton channel that is required for sustained NOX2 activity is less well characterized. We examined the role of Hv1 in a murine model of blinding Pseudomonas aeruginosa corneal infection and found that in contrast to C57BL/6 mice, Hvcn1 -/- mice exhibit an impaired ability to kill bacteria and regulate disease severity. In vitro, we used a novel Hv1 Inhibitor Flexible (HIF) to block ROS production by human and murine neutrophils and found that HIF inhibits ROS production in a dose-dependent manner following stimulation with PMA or infection with P. aeruginosa. Collectively, these findings demonstrate an important role for Hv1 on controlling bacterial growth in a clinically relevant bacterial infection model.

Society of Critical Care Medicine and American Society of Health-System Pharmacists Guideline for the Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults.

Critically ill adults can develop stress-related mucosal damage from gastrointestinal hypoperfusion and reperfusion injury, predisposing them to clinically important stress-related upper gastrointestinal bleeding (UGIB). The objective of this guideline was to develop evidence-based recommendations for the prevention of UGIB in adults in the ICU. A multiprofessional panel of 18 international experts from dietetics, critical care medicine, nursing, and pharmacy, and two methodologists developed evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guideline development including task force selection and voting. The panel members identified and formulated 13 Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and then assessed the certainty of the evidence using the GRADE approach. We used the evidence-to-decision framework to formulate the recommendations. Good practice statements were included to provide additional guidance. The panel generated nine conditional recommendations and made four good practice statements. Factors that likely increase the risk for clinically important stress-related UGIB in critically ill adults include coagulopathy, shock, and chronic liver disease. There is no firm evidence for mechanical ventilation alone being a risk factor. Enteral nutrition probably reduces UGIB risk. All critically ill adults with factors that likely increase the risk for stress-related UGIB should receive either proton pump inhibitors or histamine-2 receptor antagonists, at low dosage regimens, to prevent UGIB. Prophylaxis should be discontinued when critical illness is no longer evident or the risk factor(s) is no longer present despite ongoing critical illness. Discontinuation of stress ulcer prophylaxis before transfer out of the ICU is necessary to prevent inappropriate prescribing. The guideline panel achieved consensus regarding the recommendations for the prevention of stress-related UGIB. These recommendations are intended for consideration along with the patient's existing clinical status.

Extracellular-proton-transfer driving high energy-conserving methanogenesis in anaerobic digestion

Anaerobic digestion (AD) is a promising technology to realize the conversion from organic matters to methane, which is highly mediated by syntrophic microbial community via mutualistic interactions. However, small energy available in methanogenic conversion usually limits the metabolic activity. To adapt such energy-limited environment, efficient energy conservation is critical to support active physiological functions of anaerobic consortia for methanogenic metabolism. In this study, the contribution of extracellular proton transfer (EPT) enhancement to achieving energy-conserving methanogenesis in AD was explored. Proton-conductive medium (PCM) was applied to construct efficient proton transport pathway, and a large number of protons from extracellular water were found available to upregulate methanogenesis in AD, as indicated by the increase in the content of 2H (D) in methane molecules (over 40.7%), among which CO2-reduction-to-CH4 was effectively enhanced. The increases of adenosine triphosphate (ATP) concentration (+54.1%) and gene expression activities related to ATPase (+100.0%) and proton pump (+580.1%) revealed that enhanced EPT by PCM promoted transmembrane proton motive force generation to facilitate ATP synthesis. Based on genome-centric metatranscriptomic analyses, MAG14, MAG63 and MAG61 with high energy conservation activity displayed most pronounced positive response to the EPT enhancement. In these core MAGs, the metabolic pathway reconstruction and the key genes activity identification further proved that EPT enhancement-driven efficient ATP synthesis stimulated the cross-feeding of carbon and proton/electron to facilitate microbial mutualism, thereby resulting in the high energy-conserving methanogenesis. Overall, our work provides new insights into how EPT enhancement drives high energy-conserving methanogenesis, expanding our understanding of the ecological role of EPT in AD.

Ultrahigh proton conductivity of four ionic hydrogen-bonded organic frameworks based on functionalized terephthalates

Recently, the utilization of hydrogen-bonded organic frameworks (HOFs) with high crystallinity and inherent well-defined H-bonding networks in the field of proton conduction has received increasing attention, but obtaining HOFs with excellent water stability and prominent proton conductivity (σ) remains challenging. Herein, by employing functionalized terephthalic acids, 2,5-dihydroxyterephthalic acid, 2-hydroxyterephthalic acid, 2-nitro terephthalic acid, and terephthalic acid, respectively, four highly water-stable ionic HOFs (iHOFs), [(C8H5O6)(Me2NH2)]∙2H2O (iHOF 1), [(C8H5O5)(Me2NH2)] (iHOF 2), [(C8H4NO6)(Me2NH2)] (iHOF 3) and [(C8H5O4)(Me2NH2)] (iHOF 4) were efficiently prepared by a straightforward synthesis approach in DMF and H2O solutions. The alternating-current (AC) impedance testing in humid conditions revealed that all four iHOFs were temperature- and humidity-dependent σ, with the greatest value reaching 10-2 S·cm−1. As expected, the high density of free carboxylic acid groups, crystallization water, and protonated [Me2NH2]+ units offer adequate protons and hydrophilic environments for effective proton transport. Furthermore, the σ values of these iHOFs with different functional groups were compared. It was discovered that it dropped in the following order under 100 °C and 98 % relative humidity (RH): σ iHOF 1 (1.72 × 10−2 S·cm−1) > σ iHOF 2 (4.03 × 10−3 S·cm−1) > σ iHOF 3 (1.46 × 10−3 S·cm−1) > σ iHOF 4 (4.86 × 10−4 S·cm−1). Finally, we investigated the causes of the above differences and the proton transport mechanism inside the framework using crystal structure data, water contact angle tests, and activation energy values. This study provides new motivation to develop highly proton-conductive materials.

Biopolymeric electrolyte-based membrane on nanocrystalline cellulose/polyvinyl alcohol for a conceivable usage in proton exchange membrane fuel cell

In this study, we developed eco-friendly biopolymer electrolytes by blending nanocrystalline cellulose (NCC) with polyvinyl alcohol (PVA) and crosslinking them using glutaraldehyde. These membranes, denoted as NCC-x/PVA-y, were fabricated via the solution casting method. We thoroughly investigated the effects of different NCC to PVA ratios on various properties, including water uptake, swelling ratio, thermal and mechanical characteristics, proton conductivity, hydrogen permeation, and single Proton Exchange Membrane Fuel Cell (PEMFC) performances. Increasing the NCC concentration (ranging from 20 % to 60 %) led to enhanced surface roughness and compactness of ionic domains, resulting in improved dimensional stability and reduced hydrogen permeability across the membranes. Among the tested ratios, NCC-50/PVA-50 exhibited the highest proton conductivity, measuring 0.3 × 10−2 S cm−1. Notably, this ratio demonstrated a 60 % lower swelling ratio and lower hydrogen permeability (0.76 × 10−13 cm2/scmHg) compared to Nafion 117 (514 × 10−13 cm2/scmHg), indicating its superior performance. Furthermore, the NCC-50/PVA-50 membrane consistently maintained open-circuit voltages exceeding 0.9 V under all conditions, highlighting its effective proton transport capabilities and minimal fuel penetration. Density Functional Theory (DFT) analysis confirmed the successful cross-linking of NCC/PVA with glutaraldehyde, emphasizing its compatibility and potential for proton conductivity in PEMFC applications.

High-resolution electron cryomicroscopy of V-ATPase in native synaptic vesicles.

Intercellular communication in the nervous system occurs through the release of neurotransmitters into the synaptic cleft between neurons. In the presynaptic neuron, the proton pumping vesicular- or vacuolar-type ATPase (V-ATPase) powers neurotransmitter loading into synaptic vesicles (SVs), with the V1 complex dissociating from the membrane region of the enzyme before exocytosis. We isolated SVs from rat brain using SidK, a V-ATPase-binding bacterial effector protein. Single-particle electron cryomicroscopy allowed high-resolution structure determination of V-ATPase within the native SV membrane. In the structure, regularly spaced cholesterol molecules decorate the enzyme's rotor and the abundant SV protein synaptophysin binds the complex stoichiometrically. ATP hydrolysis during vesicle loading results in a loss of the V1 region of V-ATPase from the SV membrane, suggesting that loading is sufficient to induce dissociation of the enzyme.

Dynamic Second Harmonic Imaging of Proton Translocation Through Water Needles in Lipid Membranes.

Proton translocation through lipid membranes is a fundamental process in the field of biology. Several theoretical models have been developed and presented over the years to explain the phenomenon, yet the exact mechanism is still not well understood. Here, we show that proton translocation is directly related to membrane potential fluctuations. Using high-throughput wide-field second harmonic (SH) microscopy, we report apparently universal transmembrane potential fluctuations in lipid membrane systems. Molecular simulations and free energy calculations suggest that H+ permeation proceeds predominantly across a thin, membrane-spanning water needle and that the transient transmembrane potential drives H+ ions across the water needle. This mechanism differs from the transport of other cations that require completely open pores for transport and follows naturally from the well-known Grotthuss mechanism for proton transport in bulk water. Furthermore, SH imaging and conductivity measurements reveal that the rate of proton transport depends on the structure of the hydrophobic core of bilayer membranes.

Humidity-Mediated Dual Ionic-Electronic Conductivity Enables High Sensitivity in MOF Chemiresistors.

In the presence of water, the electrically conductive metal-organic framework (MOF) Cu3HHTT2 (H6HHTT = 2,3,7,8,12,13-hexahydroxy-4b1,5,10,15-tetraazanaphtho[1,2,3-gh]tetraphene) provides a conduit for proton transport, thereby becoming a dual ionic-electronic conductor. Owing to its dual conducting nature and its high density of imine and open metal sites, the MOF operates as a particularly sensitive chemiresistor, whose sensing mechanism changes with relative humidity. Thus, the interaction of NH3 gas with the MOF under low humidity promotes proton transport, which translates to high sensitivity for ammonia detection. Conversely, NO2 gas hinders proton conductivity, even under high relative humidity conditions, leading to large resistance variations in the humid regime. This dual ionic-electronic conduction-based gas sensor provides superior sensitivity compared to other conventional chemiresistors under similar conditions and highlights its potential as a platform for room-temperature gas sensors.

Engineering bionanoreactor in bacteria for efficient hydrogen production

Hydrogen production through water splitting is a vital strategy for renewable and sustainable clean energy. In this study, we developed an approach integrating nanomaterial engineering and synthetic biology to establish a bionanoreactor system for efficient hydrogen production. The periplasmic space (20 to 30 nm) of an electroactive bacterium, Shewanella oneidensis MR-1, was engineered to serve as a bionanoreactor to enhance the interaction between electrons and protons, catalyzed by hydrogenases for hydrogen generation. To optimize electron transfer, we used the microbially reduced graphene oxide (rGO) to coat the electrode, which improved the electron transfer from the electrode to the cells. Native MtrCAB protein complex on S. oneidensis and self-assembled iron sulfide (FeS) nanoparticles acted in tandem to facilitate electron transfer from an electrode to the periplasm. To enhance proton transport, S. oneidensis MR-1 was engineered to express Gloeobacter rhodopsin (GR) and the light-harvesting antenna canthaxanthin. This led to efficient proton pumping when exposed to light, resulting in a 35.6% increase in the rate of hydrogen production. The overexpression of native [FeFe]-hydrogenase further improved the hydrogen production rate by 56.8%. The bionanoreactor engineered in S. oneidensis MR-1 achieved a hydrogen yield of 80.4 μmol/mg protein/day with a Faraday efficiency of 80% at a potential of -0.75 V. This periplasmic bionanoreactor combines the strengths of both nanomaterial and biological components, providing an efficient approach for microbial electrosynthesis.

Impact of proton pump inhibitors on the efficacy of androgen receptor signaling inhibitors in metastatic castration-resistant prostate cancer patients.

Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups. The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered. The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.

Identification and Functional Analysis of V-ATPaseA and C Genes in Hyphantria cunea.

Vacuolar (H+)-ATPases (V-ATPases) are ATP-driven proton pumps that play multifaceted roles across various organisms. Despite their widespread significance, the functional implications of V-ATPase genes in Hyphantria cunea, an invasive forest pest with a global presence, have yet to be elucidated. In this study, two specific V-ATPase genes from H. cunea were identified and analyzed, namely HcV-ATPase A (accession number: OR217451) and HcV-ATPase C (accession number: OR217452). Phylogenetic analysis and multiple sequence alignment reveal that HcV-ATPase A shares the highest amino acid sequence similarity with SfV-ATPase A, while HcV-ATPase C is most similar to HaV-ATPase C. Spatiotemporal expression profiles, determined via RT-qPCR, demonstrate that both HcV-ATPase A and HcV-ATPase C are expressed throughout all larval developmental stages, with HcV-ATPase A predominantly expressed in the midgut and HcV-ATPase C showing high expression in the epidermis. RNA interference (RNAi) targeting of these genes significantly suppressed their expression by 62.7% and 71.0% 120 h post-injection, leading to halted larval growth and increased mortality rates of 61.7% and 46.7%, respectively. Further investigations using immunohistochemistry, hematoxylin and eosin (HE) staining, and transmission electron microscopy (TEM) revealed that gene silencing induced vesiculation and subsequent losses or sloughing of intestinal parietal cells, alongside an increase in the number of autophagic cells. Additionally, the silencing of HcV-ATPase A and C genes resulted in a reduced gut epidermal cell layer thickness and further increases in goblet cell numbers. Importantly, RNAi of HcV-ATPase A and C did not affect the expression levels of one another, suggesting independent functional pathways. This study provides foundational insights into the role of V-ATPase in H. cunea and identifies potential targets for the biocontrol of its larvae, contributing to the understanding of V-ATPase mechanisms and their application in pest management strategies.