Proton Pump Research Articles

The Effect of Liquid Saturation Transients on PEM Fuel Cell Impedance: Inductive Loop and Instability of Catalyst Layer Operation

We report a physics–based model for the electrochemical impedance of a PEM fuel cell cathode. The model takes into account the transient behavior of oxygen and proton transport in the cathode catalyst layer caused by a variation of the liquid saturation with cell current. Transients of the catalyst layer oxygen diffusivity result in a second capacitive arc in the Nyquist spectrum, while proton conductivity transients lead to the formation of an inductive loop. In the range of capillary pressures in which the liquid saturation in the catalyst layer is independent of the capillary pressures, the loop does not form. A stability analysis of a reduced system of equations reveals that the static limit of inductive loop is unstable with respect to spatial perturbations, implying that the post–oscillatory steady state is unattainable. Possible scenarios of instability development are discussed.

Maintenance proton pump inhibitor use and risk of colorectal cancer: a Swedish retrospective cohort study

ObjectivesWe aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort.DesignRetrospective cohort study.SettingThis research was conducted at...

Rational Use of Proton Pump Inhibitors among Patients Admitted in a Tertiary Care Hospital

Background: The prevalent usage of proton pump inhibitors (PPIs) is a testament to the effectiveness of this class of medications, but it also introduces risk associated with inappropriate prescriptive and consumptive practices. Because of the negative effect of incorrect usage and overdose of PPIs, it is very important for physicians to only prescribe these drugs when needed. However, recent studies showed some concerns about long-term PPIs consumption. The rational prescription of medications is vital to ensuring the optimal use of medical resources, providing effective therapy and minimizing adverse drug reactions. Methods: This observational study was conducted in the department of Pharmacology and therapeutics, Sylhet M.A.G. Osmani medical college, Sylhet, in collaboration with the department of Medicine, Surgery, Gastroenterology, Obstetrics and gynaecology, Sylhet M.A.G. Osmani medical college hospital, Sylhet, from July 2022 to June 2023. The sample size for this study was 600. Usage of PPIs was considered to be appropriate on the basis NICE guidelines and recommendations by Scarpignato et al. (2016) committees on behalf of three Italian scientific societies. Result: For 600 PPIs prescriptions, total 705 case sheets were reviewed. The mean age of the study patients was 42.94±17.16 years. Female were found more 359(59.8%) than male 241(40.2%). Out of 600 patients, based on the indications of PPI usage, 287 (47.8%) of prescriptions were found appropriate, whereas inappropriate prescriptions were found in 313 (52.2%) cases. Out of 287 patients who were prescribed PPIs in an appropriate indication, 175 (61%) patients were given PPIs in an appropriate dose, whereas inappropriate dose was found in 112 (39%) of patients. Again, among 175 patients who were prescribed PPIs for appropriate dose, 24 (13.7%) patients were given PPIs in an appropriate frequency, whereas inappropriate frequency was found in 151 (86.3%) of patients. Finally, 24/600 (4%) patients were prescribed in an appropriate indication with an appropriate dose and frequency, whereas inappropriate prescription were found in 576/600 (96%) patients. PPIs were used as prophylaxis for NSAIDs in highest number 147(51.2%) of patients. Oral was the most common 348(58%) route of prescribing PPIs. Omeprazole was the highest 577(96.2%) prescribed PPIs. Conclusion: Based on this study result, it could be concluded that in most of the patients PPIs prescriptions were not following appropriate indications, dose and frequency recommended by reference guidelines. Like any other drugs, PPIs should be prescribed for a clear indication, the minimum dose needed for the expected effect and medication halted when no longer necessary upon re-evaluation.

Ashwagandha Seeds Extract Supplementation Afford Comparable Therapeutic Effect to Proton Pump Inhibitors in Stress induced Gastric Ulcer in rats

Ashwagandha Seeds Extract Supplementation Afford Comparable Therapeutic Effect to Proton Pump Inhibitors in Stress induced Gastric Ulcer in rats

Bidirectional Optical Control of Proton Motive Force in Escherichia coli Using Microbial Rhodopsins.

Proton (H+) motive force (PMF) serves as the energy source for the flagellar motor rotation, crucial for microbial motility. Here, to control PMF using light, we introduced light-driven inward and outward proton pump rhodopsins, RmXeR and AR3, into Escherichia coli. The motility of E. coli cells expressing RmXeR and AR3 significantly decreased and increased upon illumination, respectively. Tethered cell experiments revealed that, upon illumination, the torque of the flagellar motor decreased to nearly zero (28 pN nm) with RmXeR, while it increased to 1170 pN nm with AR3. These alterations in PMF correspond to +146 mV (RmXeR) and -140 mV (AR3), respectively. Thus, bidirectional optical control of PMF in E. coli was successfully achieved by using proton pump rhodopsins. This system holds a potential for enhancing our understanding of the roles of PMF in various biological functions.

Study of ATPase and GTPase levels in Fibrotic Lung Disease with and without COVID-19 Vaccination

Background: In eukaryotic cells, the acidification of intracellular compartments is the responsibility of vacuolar H+ ATPase, a family of proton pumps, sometimes known as V-ATPases. Small GTPases are signaling molecules that regulate important cellular processes as well as subcellular activities making them essential players, particularly in a wide variety of coronavirus infection processes. Objectives: The purpose of this research was to assess the levels of ATPase and GTPase in fibrotic lung disease patients who had received or had not received the COVID-19 vaccination, and then to compare these levels with those of the control group. Methods: A total of 150 individuals participated in this study, divided into three groups. The first group was the control group (N=50). In the second group (N=50) patients with fibrotic lung disease () who did not get the COVID-19 vaccination. Fifty patients who had received the COVID-19 vaccination made up the third group ()(N=50). Enzyme-linked immunosorbent assay was the method that was used to determine the amounts of ATPase and GTPase. The P- P-value of 0.05 or less is considered statistically significant. ROC tests were examined for ATPase and GTPase. Results: The data analysis reported a significant rise in alkaline phosphatase, Alanine aminotransferase, and Aspartate-aminotransferase () among the three groups. Both ATPase and GTPase levels were shown to have significantly increased in Groups 3 and 2 as compared to Group 1 levels. Moreover, a substantial rise was discovered in Group 3 in comparison to Group 2 which was detected. Conclusion: ATPase and GTPase levels are increased in patients with fibrotic lung disease regardless of the COVID-19 vaccination state.

Prognostic Impact of the Administration of Antibiotics and Proton Pump Inhibitors in Immune Checkpoint Inhibitor Combination Therapy for Advanced Renal Cell Carcinoma.

The prognostic impact of the administration of antibiotics and proton pump inhibitors (PPIs) in immune checkpoint inhibitor (ICI) therapy for advanced cancer has recently been documented. However, how these drugs affect the outcomes of first-line ICI combination therapy for advanced renal cell carcinoma (RCC) remains unclear. We retrospectively evaluated the data of 128 patients with RCC who received first-line ICI combination therapy. The patients were grouped according to their history of antibiotics and PPIs use one month before the initiation of ICI combination therapy. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) after ICI combination therapy were compared between patients treated with and without antibiotics or PPIs. Of the 128 patients, 30 (23%) and 44 (34%) received antibiotics and PPIs, respectively. Patients treated with antibiotics exhibited shorter PFS and OS compared to those who did not receive antibiotics (median PFS: 4.9 vs. 16.1 months, p<0.0001; OS: 20.8 vs. 49.0 months, p=0.0034). Multivariate analyses showed that antibiotic administration was an independent predictor of shorter PFS (hazard ratio: 2.54: p=0.0002) and OS (hazard ratio: 2.56: p=0.0067) after adjusting for other covariates. In contrast, there were no significant differences in either PFS or OS between patients who received PPIs and those who did not. (PFS: p=0.828; OS: p=0.105). Antibiotics administration before ICI combination therapy was negatively associated with outcomes of first-line ICI combination therapy for advanced RCC. Therefore, careful monitoring is required for potentially high-risk patients undergoing ICI combination therapy.

Transcatheter Arterial Radioembolization–Induced Gastric Ulcer in an Excluded Stomach After Roux-en-Y Gastric Bypass

ABSTRACT Transcatheter arterial radioembolization (TARE) is a common locoregional treatment for hepatocellular carcinoma. It is associated with peptic ulcer disease in up to 5% of patients. A 70-year-old man with Roux-en-Y gastric bypass and liver cirrhosis with hepatocellular carcinoma treated with TARE 6 months earlier was evaluated for continued melena and was found to have an ulcer in the excluded stomach. This was successfully treated with liquid proton pump inhibitor through gastrostomy tube to the excluded stomach. This represents a unique case of successful management of TARE-induced peptic ulcer disease in the excluded stomach of a Roux-en-Y gastric bypass patient.

What prognostic factors have impacted the efficacy of immune checkpoint inhibitors in patients with recurrent or metastatic oral cancer?

BackgroundImmune checkpoint inhibitors (ICIs) are widely adapted for recurrent or metastatic head and neck cancer (RM-HNC), and various studies on its prognostic factors have been reported. We aimed to elucidate the prognostic factors of ICI treatment for RM oral cancer (RM-OC) in a retrospective study. MethodsWe retrospectively reviewed patients with RM-OC treated with ICIs (nivolumab and pembrolizumab) at our department from May 2017 to February 2023. The objective response rate (ORR) for ICI treatment and the relationship between several potential prognostic factors, progression-free survival (PFS), and overall survival (OS) were analyzed statistically. ResultsThe investigation enrolled 31 patients, 16 with nivolumab and 15 with pembrolizumab. There were no significant differences in the ORR or disease control rate between the nivolumab and pembrolizumab groups (p = 0.4578 and 0.2524). In multivariate analysis, the prognostic nutritional index (PNI) and C-reactive protein to albumin ratio (CAR) exhibited statistical correlations with PFS, whereas the use of antibiotics and proton pump inhibitors (PPIs), neutrophil to lymphocyte ratio (NLR), and PNI demonstrated statistical associations with OS. ConclusionOur findings imply that the use of antibiotics and PPIs, which can modify the gut microbiota, may also serve as a prognostic determinant for ICI treatment in RM-OC, consistent with previous studies. Additionally, PNI may be essential in affecting the survival rates of both PFS and OS and could be an exceedingly valuable inflammatory biomarker for RM-OC.

Optimal Assessment, Treatment, and Monitoring of Adults with Eosinophilic Esophagitis: Strategies to Improve Outcomes.

Eosinophilic esophagitis (EoE) is a chronic type 2 inflammation-mediated disease characterized by an eosinophil-predominant inflammation of the esophagus and symptoms of esophageal dysfunction. Relevant treatment outcomes in the setting of EoE include the improvement of histology, symptoms, and endoscopy findings, quality of life (QoL), and the psychological burden of the disease. Established validated tools for the assessment of EoE include questionnaires on dysphagia and QoL (ie, DSQ, EEsAI, and EoE-IQ). More recently, esophageal symptom-specific anxiety and hypervigilance, assessed using the esophageal hypervigilance and anxiety scale (EHAS), have emerged as contributors to disease burden, confirming the importance of psychological aspects in EoE patients. The EoE endoscopic reference score (EREFS) is the only validated endoscopy score in EoE and can quantify mucosal disease burden. However, esophageal panometry using the functional lumen imaging probe (FLIP) and high-resolution manometry (HRM) have shown potential to optimize the assessment of fibrostenotic features of EoE, providing novel insights into the pathophysiology of symptoms. There is a growing number of licenced and off-label therapeutic options in EoE, with various randomized controlled trials demonstrating the efficacy of proton pump inhibitors, topical steroids, food elimination diets, biological drugs, and esophageal dilatation. However, standardized optimal management strategies of EoE are currently lacking. In this review, we provide an overview of established and novel assessment tools in EoE including patient reported outcomes, FLIP panometry, HRM, endoscopy, and histology outcome measures to improve the outcomes of EoE patients. In addition, we summarize available therapeutic options for EoE based on the most recent evidence.

Drug-Associated Acute Kidney Disease: Data From a World Pharmacovigilance Database.

Background Drugs are a frequent cause of nephrotoxicity, especially in the context of acute kidney disease (AKD), with a significant number of cases being drug-associated. The WHO's VigiBase is a powerful tool for identifying drugs described and associated with the development of AKD. Methods We retrieved data from the period 1968 to 2022 regarding notifications of adverse drug reactions (ADR). The extracted medications were evaluated for their nephrotoxicity based on the bibliographic score (BS)developed through pre-selected references. The main medications involved were classified as 'non-nephrotoxic', 'potentially nephrotoxic', and 'nephrotoxic'. We utilized the IC025 and reporting odds ratio (ROR) disproportionality indexes to study the relationship between medications and the odds of being included in an AKD notification. Results During the period, a total of 33,932,051 notifications were obtained, revealing 435,677 cases related to drug-associated AKD following MedDRA term filtering, predominantly affecting males aged 45-64. We identified 8,991 active ingredients or suspected combinations associated with AKD development, with the ATC class A - Alimentary Tract and Metabolism being the most frequently described. Among the medications most strongly associated with this phenotype, classes J and N stood out. Among the most notable medications collected, 8.3% were classified as "non-nephrotoxic," 16.7% as "potentially nephrotoxic," and 75% as "known nephrotoxic." Notable active ingredients included cobicistat + elvitegravir + emtricitabine + tenofovir disoproxil (IC025 8.7; ROR 786.96), inotersen (IC025 7.7; ROR 604.57), emtricitabine + tenofovir disoproxil (IC025 7.9; ROR 432.36), esomeprazole (IC025 6.8; ROR 184.23), and pantoprazole (IC025 6.3; ROR 109.86), with proton pump inhibitors dominating the top four positions among the most frequently involved medications. Conclusion AKD is a frequent adverse reaction in VigiBase, with a significantly high reported mortality rate. Evaluation of the notifications revealed medications with a high disproportionality index and a strong association with AKD. We also highlight the potential nephrotoxic role of less suspected medications. This study emphasizes the need to consider AKD as a condition potentially associated with iatrogenic etiology, highlighting various medications and their respective involvement in the various possible manifestations of AKD.

The V-ATPase/ATG16L1 axis is controlled by the V1H subunit

Defects in organellar acidification indicate compromised or infected compartments. Recruitment of the autophagy-related ATG16L1 complex to pathologically neutralized organelles targets ubiquitin-like ATG8 molecules to perturbed membranes. How this process is coupled to proton gradient disruption is unclear. Here, we reveal that the V1H subunit of the vacuolar ATPase (V-ATPase) proton pump binds directly to ATG16L1. The V1H/ATG16L1 interaction only occurs within fully assembled V-ATPases, allowing ATG16L1 recruitment to be coupled to increased V-ATPase assembly following organelle neutralization. Cells lacking V1H fail to target ATG8s during influenza infection or after activation of the immune receptor stimulator of interferon genes (STING). We identify a loop within V1H that mediates ATG16L1 binding. A neuronal V1H isoform lacks this loop and is associated with attenuated ATG8 targeting in response to ionophores in primary murine and human iPSC-derived neurons. Thus, V1H controls ATG16L1 recruitment following proton gradient dissipation, suggesting that the V-ATPase acts as a cell-intrinsic damage sensor.

Enhanced interlayer interaction in sulfonated CONs membrane by amino-rich CONs enabling ultrafast proton transport

Covalent organic framework nanosheets (CONs) with porous crystalline features and ultrathin thickness are ideal candidates as membrane building blocks to form well-defined transfer nanochannels. The formidable challenge behind self-supporting CONs membrane lies in weak non-covalent interlayer interactions and thus loose stacking, insufficient strength and structure stabilities. Herein, we propose the fabrication of interlayer force-strengthened freestanding CONs membrane through the electrostatic attraction bridge effect of positively-charged amino-rich CONs (CON–NH2) to negatively-charged sulfonated CONs (CON–SO3H). Ultrathin and large lateral sized CON–SO3H and CON–NH2 are synthesized, followed by restacking to prepare freestanding CONs membrane with CON–SO3H as the membrane bulk. Benefiting from effective interlayer interconnection due to strong electrostatic interaction, the obtained CON–SO3H/CON–NH2 membrane displays features of ultrahigh integrity, dense stacking, eminent water/acid/base/organic solvents stabilities and mechanical strength (109 MPa). The shortened –SO3H distance contributes to construct site-continuous transfer pathways, and the deprotonated –SO3H and protonated –NH2 form acid–base pairs to decrease interfacial resistance, which impart membrane superior proton conductivity of 486 mS cm−1 (80 °C, 100% RH). This interlayer force enhancement strategy offers a promising perspective on achieving densely-stacked CONs membrane with ultrahigh mechanical property and conduction performance for fuel cell application.

Ethylenediamine tetramethylenephosphonic acid boosting the electrocatalytic interface construct and proton transfer for high-temperature polymer electrolyte membrane fuel cells

High-temperature polymer electrolyte membrane fuel cells (HT-PEMFCs) show excellent application prospects due to its enhanced tolerance of hydrogen impurity. However, the sluggish electrode kinetics caused by its inefficient electrocatalytic interface and proton transfer severely restricts its performance. To overcome the sluggish electrode kinetics, the ethylenediamine tetramethylenephosphonic acid (EDTMPA) was successfully incorporated into the catalysts layer to regulate the phosphoric acid (PA) distribution to boost the electrocatalytic reaction interface and proton transfer, thus increasing the output power and stability of HT-PEMFCs. The hydrophilic H2PO4− and electron donor N atom of EDTMPA could efficiently decrease the absorption of PA on the catalyst surface and facilitate proton transportation in the membrane electrode, as demonstrated by our experiments. The fuel cell assembled with the prepared membrane electrode shows a high reactivity of 1175 mW cm−2 and excellent stability, which is much better than the past reference report. The results of this work provide new insights into the utilization of small molecules with phosphate groups to enhance phosphate tolerance and proton conduction, and there is also a further improvement in the reactivity, durability, and utilization of the electrocatalysts in HT-PEMFCs.

Dimerization is required for the glycosylation of S1-S2 linker of sea urchin voltage-gated proton channel Hv1

Multimerization of ion channels is essential for establishing the ion-selective pathway and tuning the gating regulated by membrane potential, second messengers, and temperature. Voltage-gated proton channel, Hv1, consists of voltage-sensor domain and coiled-coil domain. Hv1 forms dimer, whereas voltage-dependent channel activity is self-contained in monomer unlike many ion channels, which assemble to form ion-conductive pathways among multiple subunits. Dimerization of Hv1 is necessary for cooperative gating, but other roles of dimerization in physiological aspects are still largely unclear. In this study, we show that dimerization of Hv1 takes place in ER. Sea urchin Hv1 (Strongylocentrotus purpuratus Hv1: SpHv1) was glycosylated in the consensus sequence for N-linked glycosylation within the S1-S2 extracellular loop. However, glycosylation was not observed in the monomeric SpHv1 that lacks the coiled-coil domain. A version of mHv1 in which the S1-S2 loop was replaced by that of SpHv1 showed glycosylation and its monomeric form was not glycosylated. Tandem dimer of monomeric SpHv1 underwent glycosylation, suggesting that dimerization of Hv1 is required for glycosylation. Moreover, when monomeric Hv1 has a dilysine motif in the C-terminal end, which is known to act as a retrieval signal from Golgi to ER, prolonging the time of residency in ER, it was glycosylated. Overall, our results suggest that monomeric SpHv1 does not stay long in ER, thereby escaping glycosylation, while the dimerization causes the proteins to stay longer in ER. Thus, the findings highlight the novel significance of dimerization of Hv1: regulation of biogenesis and maturation of the proteins in intracellular compartments.

Interior pH-sensing residue of human voltage-gated proton channel Hv1 is histidine 168

The molecular mechanisms governing the human voltage-gated proton channel hHv1 remain elusive. Here, we used membrane-enabled hybrid-solvent continuous constant pH molecular dynamics (CpHMD) simulations with pH replica exchange to further evaluate the structural models of hHv1 in the closed (hyperpolarized) and open (depolarized) states recently obtained with MD simulations and explore potential pH-sensing residues. The CpHMD titration at a set of symmetric pH conditions revealed three residues that can gain or lose protons upon channel depolarization. Among them, residue H168 at the intracellular end of the S3 helix switches from the deprotonated to the protonated state and its protonation is correlated with the increased tilting of the S3 helix during the transition from the closed to the open state. Thus, the simulation data suggest H168 as an interior pH sensor, in support of a recent finding based on electrophysiological experiments of Hv1 mutants. We propose that protonation of H168 acts as a key that unlocks the closed channel configuration by increasing the flexibility of the S2-S3 linker, which increases the tilt angle of S3 and enhances the mobility of the S4 helix, thus promoting channel opening. Our work represents an important step toward deciphering the pH-dependent gating mechanism of hHv1.

Evaluation of first hospital entry and hospitalization related prescription polypharmacy targeting patients of fifty years old and more at a general hospital, Duhok, Iraq

Background: Polypharmacy is the intake of ≥ 5 medications. This study evaluates the prevalence of polypharmacy among elderly patients hospitalized during October 2023 at Azadi Hospital in Duhok, Iraq. Methods: This was a retrospective cross-sectional study. The files of 373 patients aged ≥ 50 years were reviewed for the occurrence of polypharmacy (5 medications), major polypharmacy (6-9 medications) and excessive polypharmacy (≥ 10 medications) as well as their disease conditions. Results: The 373 patients received 5 to 10 medications at first hospital entry, and during hospitalization (1-29 days), 220 (58.98%) of them received 5 to 12 medications. Cardiovascular disorders (44.04%) were the most encountered conditions in the hospitalized patients, followed by endocrine disorders (26.4%) and gastrointestinal disorders (8.14%). Polypharmacy occurred in 63 (16.89%) patients on the first day of hospital entry and in 73 (19.57%) during the hospitalization period. Major and excessive polypharmacy occurred among 90 (24.13%) and 2 (0.54%) of patients at the first entry and among 129 (34.58%) and 18 (4.83%) patients during the hospitalization, respectively. During hospitalization, polypharmacy significantly (Chi squared=22.655; df=1; p=1.9387˟10-6) increased by 17.43% when compared to that of the first hospital entry. The most commonly used medications at the first hospital entry were paracetamol (17.18%) followed by antibiotics (11.8%). During hospitalization the most commonly used medications were antibiotics (13.52%) followed by proton pump inhibitors (11.43%). Conclusion: The prevalence of polypharmacy was high among elderly hospitalized patients. This condition might increase the risk of potential drug-drug interaction and the intake of inappropriate medications. Alerting clinicians about the significance of polypharmacy is necessary in prescribing and deprescribing medications to hospitalized elderly patients.

Introduction of polymeric ionic liquids containing quaternary ammonium groups to construct high-temperature proton exchange membranes with high proton conductivity and stability

A series of membrane materials suitable for high-temperature proton exchange membranes (HT-PEM) were successfully prepared by introducing polymeric ionic liquids (PILs) containing quaternary ammonium groups into ether-bonded polybenzimidazole (OPBI). The structure of the cross-linked membrane has a strong interaction with phosphoric acid (PA), which enhances proton transport and PA retention. To ensure better overall performance of the cross-linked membrane, the optimal PIL content is 30 wt% (OPBI-PIL-30 %). The PA uptake of OPBI-PIL-30 % membrane was 323.24 %, and the proton conductivity at 180 ℃ was 113.94 mS cm−1, which was much higher than that of OPBI membrane. It is noteworthy that the PA retention of OPBI-PIL-30 % membrane could reach 71.38 % after 240 h of testing under the harsh environment of 80 ℃/40 % RH. The membrane showed better acid retention capacity of 86.89 % at 160 ℃ under anhydrous environment. The OPBI-PIL-20 % membrane achieved the maximum power density of 436.19 mW cm−2, attributed to its favorable mechanical characteristics and proton conductivity. By these excellent properties, it is shown that OPBI-PIL-X membranes containing quaternary ammonium groups have the potential to be applied in high temperature proton exchange membrane fuel cells (HT-PEMFCs).

Diversity, abundance, and expression of proteorhodopsin genes in the northern South China Sea

Proteorhodopsins have been suggested as an important strategy among phototrophs to capture solar energy in marine environments. The goals of this study was to investigate the diversity of proteorhodopsin genes and to explore their abundance, distribution, and expression in the coastal surface waters of the northern South China Sea, one of the largest marginal seas of the western North Pacific Ocean. Using 21 metagenomes, we recovered proteorhodopsin genes from a wide range of prokaryotic taxa, and chlorophyll a contributed significantly to the community composition of proteorhodopsin-containing microbes. Most proteorhodopsin sequences were predicted to encode green light-absorbing proton pumps and green light-absorbing proteorhodopsin genes were more abundant than blue-absorbing ones. The variations in the conserved residues involved in ion pumping and several uncharacterized proteorhodopsins were observed. The gene abundance pattern of proteorhodopsin types were significantly influenced by the levels of total organic carbon and soluble reactive phosphorus. Gene expression analysis confirmed the importance of proteorhodopsin-based phototrophy and revealed different expressional patterns among major phyla. In tandem, we screened 2295 metagenome-assembled genomes to describe the taxonomic distribution of proteorhodopsins. Bacteroidota are the key lineages encoding proteorhodopsins, but proteorhodopsins were predicated from members of Proteobacteria, Marinisomatota, Myxococcota, Verrucomicrobiota and Thermoplasmatota. Our study expanded the diversity of proteorhodopsins and improve our understanding on the significance of proteorhodopsin-mediated phototrophy in the marine ecosystem.

Genetic Markers of Helicobacter pylori Resistance to Clarithromycin and Levofloxacin in Moscow, Russia.

The Maastricht VI/Florence consensus recommends, as one of the measures to enhance the efficacy of Helicobacter pylori infection eradication, a personalized treatment approach involving the selection of an antimicrobial agent based on the pre-determined resistance of H. pylori. To address the need to develop test systems for personalized drug selection, this study was designed to analyze the molecular resistance of H. pylori using a newly developed Sanger sequencing test platform. The characteristics of the test system were determined on 25 pure culture samples of H. pylori with known resistance. Sensitivity and specificity for detecting resistance to clarithromycin was 100% and those to levofloxacin were 93% and 92%, respectively. The test system has been tested in real clinical practice on 112 H. pylori-positive patients who had not previously received proton pump inhibitors (PPIs) or antibacterial drugs. Mutations indicating resistance to clarithromycin were found in 27 (24%) samples and those indicating resistance to levofloxacin were found in 26 (23%) samples. Double resistance was observed in 16 (14%) samples. The most common mutations leading to clarithromycin resistance were 2143G and 2142G and to levofloxacin resistance-261A and 271A in the gyrA gene, which account for 69% of all identified genetic determinants in levofloxacin-resistant bacteria. Thus, a personalized approach to the selection of H. pylori eradication therapy based on the detection of bacterial resistance before prescribing first-line therapy could help to avoid the prescription of ineffective H. pylori eradication therapies and, overall, contribute to the control of antibiotic resistance of H. pylori.