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A new type of solid bismuth microelectrode array characterized by eco-friendly properties and the simplicity of its construction is presented for the first time. The proposed array of microelectrodes consists of exactly forty-three single capillaries of an inner diameter of about 10 µm filled with metallic bismuth and packed in one casing. The proposed sensor is reusable thanks to its distinctive design. The microelectrode properties of the proposed working electrodes were confirmed by comparing the analytical signals of cadmium and lead recorded from stirred and unstirred solutions during the deposition step. The practical application of the solid bismuth microelectrode array is presented by detailing the procedure for the simultaneous determination of Pb and Cd by anodic stripping voltammetry. The calibration graphs were linear from 5 × 10[sup.−9] to 2 × 10[sup.−7] mol L[sup.−1] and 2 × 10[sup.−9] to 2 × 10[sup.−7] mol L[sup.−1] for Cd(II) and Pb(II), respectively (deposition time of 60 s). The detection limits for Cd(II) and Pb(II) were equal to 2.3 × 10[sup.−9] mol L[sup.−1] and 8.9 × 10[sup.−10] mol L[sup.−1], respectively. Potential interferences were investigated. The developed procedure was successfully used for the analysis of certified water reference material and environmental water samples.

Background and aimsThis study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy.MethodsIn this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects.Results300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI −4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI −4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI −2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010).ConclusionsVT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT.Trial registration numberChiCTR2300074693.

Aim: To establish whether the addition of probiotics to a globally accepted Helicobacter pylori (H. pylori)-eradication scheme may reduce the rates of side effects and increase the eradication rates. Methods. Prospective, randomized, placebo-controlled trial of patients receiving eradication therapy for H. pylori in the eight participating centers. All patients received a 10-day proton pump inhibitor containing non-bismuth quadruple therapeutic regimen for H. pylori eradication (omeprazole 20 mg, amoxycillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg all twice daily orally) and were randomized to receive either probiotics (group A) or placebo (group B). The probiotic used combined four probiotic strains, i.e., Lactobacillus Acidophilus, Lactiplantibacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii. Results. Data were analyzed for 329 patients in group A and 335 patients in group B. Fifty six (17.0%) patients in group A and 170 (50.7%) patients in group B reported the occurrence of an H. pylori treatment-associated new symptom or the aggravation of a pre-existing symptom of any severity (p < 0.00001). H. pylori was successfully eradicated in 303 patients in group A (92.0%) and 291 patients in group B (86.8%), (p = 0.028). Conclusion: Adding probiotics to the 10-day concomitant non-bismuth quadruple H. pylori eradication regimen increases the eradication rate and decreases side effects.

Drug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti- Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems. Metallo-β-lactamases (MBL) are zinc containing enzymes that cause resistance to β-lactam antibiotics. Here the authors show that the anti- Helicobacter pylori drug colloidal bismuth subcitrate inhibits MBLs by displacing the zinc ions with Bi(III), which is of great interest for the development of antibiotics.

Rifasutenizol (TNP-2198) is a new molecular entity with a synergistic dual mechanism of action under clinical development for the treatment of Helicobacter pylori infection. We aimed to evaluate the efficacy and safety of a rifasutenizol-based triple therapy (RTT) versus bismuth plus clarithromycin-based triple therapy (BCTT) for the treatment of H pylori infection in treatment-naive patients. EVEREST-HP was a phase 3, randomised, triple-dummy, double-blind, active-controlled, non-inferiority trial with adaptive design for sample size re-estimation conducted at 40 research hospitals in China. Treatment-naive patients aged 18–65 years, with a positive [13C]urea breath test ([13C]UBT), further confirmed by gastric biopsy and histological examination, were randomly assigned (1:1) to receive RTT (rifasutenizol 400 mg oral capsules, amoxicillin 1 g oral capsules, and rabeprazole 20 mg enteric-coated tables) or BCTT (bismuth potassium citrate 240 mg oral tablets, clarithromycin 500 mg oral tablets, amoxicillin 1 g oral capsules, and rabeprazole 20 mg enteric-coated tablets), all twice a day for 14 days. Randomisation was done centrally by a secure interactive web response system using block sizes of two or four and stratified by study site. RTT was compared against BCTT using a triple-dummy approach to ensure masking. The primary endpoint was H pylori eradication rate based on [13C]UBT 4–6 weeks after the end of treatment in the modified intention-to-treat population, which included all participants who received at least one dose of the study drugs. The eradication rates of RTT and BCTT were compared using a one-sided α value of 0·025 and a non-inferiority margin of –10%. Safety endpoints included investigator assessed treatment-emergent adverse events, the severity and relationship with study drugs, findings from physical examinations, vital signs, laboratory tests, and electrocardiogram. An interim analysis was conducted by an independent data monitoring committee after 50% (350) of patients completed the last [13C]UBT. The trial is registered with ClinicalTrials.gov, NCT05857163. Between May 18, 2023, and Nov 10, 2023, 1267 patients were screened and 700 patients were randomly assigned to receive either RTT (n=353) or BCTT (n=347). 261 (37%) patients were men and 439 (63%) were women. 351 patients in the RTT group and 346 in the BCTT group took at least one dose of the study drugs and were included in the modified intention-to-treat group and the safety set. H pylori was successfully cultured from 579 (83%) of 697 patients. 236 (41%) of 579 patients had H pylori infection resistant to clarithromycin, 395 (68%) to metronidazole, 203 (35%) to levofloxacin, and 47 (8%) to amoxicillin. All H pylori clinical isolates were susceptible to rifasutenizol. In the modified intention-to-treat analysis, the H pylori eradication rate in the RTT group was non-inferior to that in the BCTT group (92·0% [95% CI 88·7 to 94·6; 323 of 351] vs 87·9% [83·9 to 91·1; 304 of 346]; absolute difference 4·2% [95% CI –0·3 to 8·8]). 131 (37%) of 351 patients in the RTT group and 184 (53%) of 346 in the BCTT group had treatment-emergent adverse events. Treatment-emergent adverse events occurring in more than 5% of patients in the RTT group were diarrhoea (in 24 [7%] patients), nausea (22 [6%]), and dizziness (21 [6%]), and in more than 5% of patients in the BCTT group were taste perversion (125 [36%]), nausea (21 [6%]), and diarrhoea (19 [5%]) Most of the treatment-emergent adverse events were mild or moderate in severity. No serious adverse event related to study drugs was reported. As the first novel antimicrobial agent specifically developed for H pylori infection, rifasutenizol represents a promising addition to the existing options for tackling antimicrobial resistance, and RTT represents a promising first-line treatment option for H pylori infection. TenNor Therapeutics. For the Chinese translation of the abstract see Supplementary Materials section.

BackgroundBismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori.MethodsTreatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication.ResultsThe per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups.ConclusionCompared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

INTRODUCTION:Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment.METHODS:This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori-infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups.RESULTS:Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% (P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% (P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% (P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group (P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group (P < 0.001), while not in the B-quadruple group (P = 0.110).DISCUSSION:The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy.TRAIL REGISTRATION NUMBER:ChiCTR2300070100.

Nanocatalytic immunotherapy holds excellent potential for future cancer therapy due to its rapid activation of the immune system to attack tumor cells. However, a high level of N-glycosylation can protect tumor cells, compromising the anticancer immunity of nanocatalytic immunotherapy. Here, we show a 2-deoxyglucose (2-DG) and bismuth ferrite co-loaded gel (DBG) scaffold for enhanced cancer piezocatalytic immunotherapy. After the implantation in the tumor, DBG generates both reactive oxygen species (ROS) and piezoelectric signals when excited with ultrasound irradiation, significantly promoting the activation of anticancer immunity. Meanwhile, 2-DG released from ROS-sensitive DBG disrupts the N-glycans synthesis, further overcoming the immunosuppressive microenvironment of tumors. The synergy effects of ultrasound-triggered and glycosylation inhibition enhanced tumor piezocatalytic immunotherapy are demonstrated on four mouse cancer models. A “hot” tumor-immunity niche is produced to inhibit tumor progress and lung metastasis and elicit strong immune memory effects. This work provides a promising piezocatalytic immunotherapy for malignant solid tumors featuring both low immunogenicity and high levels of N-glycosylation. N-glycosylation has a significant role in immunosuppressive tumor microenvironment (TME). Here, the authors design an injectable ROS-sensitive hydrogel scaffold co-delivering piezocatalyst BiFeO 3 and glucose/mannose analog 2-deoxy-d-glucose alleviating N-glycosylation inhibition and thereby effectively stimulating immune responses within TME.

HighlightsCatalytically inert 2D Bi2O3 is activated for boosting electrochemical hydrogen evolution reaction (HER) via oxygen vacancy concentration modulation.The relationship between the varied oxygen vacancy concentrations and the corresponding HER activity is revealed by both experimental Vo verification and theoretical density-functional theory calculations.This work provides insights into activating catalytically inert materials into high-performance catalysts.Oxygen vacancies (Vo) in electrocatalysts are closely correlated with the hydrogen evolution reaction (HER) activity. The role of vacancy defects and the effect of their concentration, however, yet remains unclear. Herein, Bi2O3, an unfavorable electrocatalyst for the HER due to a less than ideal hydrogen adsorption Gibbs free energy (ΔGH*), is utilized as a perfect model to explore the function of Vo on HER performance. Through a facile plasma irradiation strategy, Bi2O3 nanosheets with different Vo concentrations are fabricated to evaluate the influence of defects on the HER process. Unexpectedly, while the generated oxygen vacancies contribute to the enhanced HER performance, higher Vo concentrations beyond a saturation value result in a significant drop in HER activity. By tunning the Vo concentration in the Bi2O3 nanosheets via adjusting the treatment time, the Bi2O3 catalyst with an optimized oxygen vacancy concentration and detectable charge carrier concentration of 1.52 × 1024 cm−3 demonstrates enhanced HER performance with an overpotential of 174.2 mV to reach 10 mA cm−2, a Tafel slope of 80 mV dec−1, and an exchange current density of 316 mA cm−2 in an alkaline solution, which approaches the top-tier activity among Bi-based HER electrocatalysts. Density-functional theory calculations confirm the preferred adsorption of H* onto Bi2O3 as a function of oxygen chemical potential (∆μO) and oxygen partial potential (PO2) and reveal that high Vo concentrations result in excessive stability of adsorbed hydrogen and hence the inferior HER activity. This study reveals the oxygen vacancy concentration-HER catalytic activity relationship and provides insights into activating catalytically inert materials into highly efficient electrocatalysts.

Vonoprazan, a novel and potent acid suppressant, has recently been incorporated into Helicobacter pylori eradication regimens. However, the data on combination of vonoprazan with levofloxacin remains scarce. This study represents one of the first evaluations comparing 7-day and 14-day once-daily regimens containing vonoprazan, levofloxacin, clarithromycin-MR, and bismuth for H. pylori eradication in regions characterized by high clarithromycin and metronidazole resistance. Between March 2022 and December 2023, patients presenting with dyspepsia who underwent upper gastrointestinal endoscopy at a tertiary care hospital in Thailand were recruited. Those testing positive for H. pylori infection were randomly assigned to receive either a 7-day or 14-day once-daily regimen comprising vonoprazan 40 mg, clarithromycin-MR 1 g, levofloxacin 500 mg, and bismuth subsalicylate 1,048 mg. CYP3A4 polymorphism testing and antimicrobial susceptibility assessment (using either the Epsilometer test or the GenoType ® HelicoDR assay) were performed. Eradication was confirmed by a negative ¹³C-urea breath test conducted no sooner than four weeks after completing therapy. A total of 312 dyspeptic patients who underwent EGD were screened, and 102 (32.7%) were diagnosed with H. pylori infection. The study enrolled and randomized these patients into two treatment groups: 51 received the 7-day once-daily vonoprazan-based bismuth therapy, and 51 received the 14-day regimen. Baseline characteristics were similar between the two groups, except for a higher prevalence of hypertension in the 7-day regimen group (49% vs. 27.5%, p  = 0.025). The eradication rates for the 7-day regimen were 88.2% (45/51) in the intention-to-treat (ITT) analysis and 89.6% (43/48) in the per-protocol (PP) analysis. Similarly, the 14-day regimen achieved eradication rates of 88.2% (45/51) in the ITT analysis and 93.8% (45/48) in the PP analysis. The risk difference for eradication in the PP analysis was 4.17% (95% CI: -6.86 to 15.19, p  = 0.71). Adverse events were comparable between the two regimens, occurring in 35.3% (18/51) of patients in the 7-day regimen and 38.8% (19/51) in the 14-day regimen ( p  = 0.130). The most frequently reported adverse event was black stool (35.3% vs. 38.8%, p  = 0.130). Other adverse events included nausea and vomiting (15.7% vs. 22.5%, p  = 0.742), bitter taste (17.7% vs. 18.4%, p  = 1.000), and dizziness (7.8% vs. 6.1%, p  = 0.113). All adverse events resolved spontaneously without requiring medical intervention, and no serious adverse events were reported. The 14-day regimen demonstrated excellent eradication rate (> 90%) regardless of CYP3A4 polymorphisms. These findings suggest that vonoprazan, levofloxacin, clarithromycin-MR, and bismuth for 14 days is a promising alternative first-line treatment option, particularly in regions with high clarithromycin and metronidazole resistance.