MitoQ protects against carbon tetrachloride-induced hepatocyte ferroptosis and acute liver injury by suppressing mtROS-mediated ACSL4 upregulation.

Ferroptosis has been shown to be involved in carbon tetrachloride (CCl4)-induced acute liver injury (ALI). The mitochondrion-targeted antioxidant MitoQ can eliminate the production of mitochondrial reactive oxygen species (mtROS). This study investigated the role of MitoQ in CCl4-induced hepatocytic ferroptosis and ALI. MDA and 4HNE were elevated in CCl4-induced mice. In vitro, CCl4 exposure elevated the levels of oxidized lipids in HepG2 cells. Alterations in the mitochondrial ultrastructure of hepatocytes were observed in the livers of CCl4-evoked mice. Ferrostatin-1 (Fer-1) attenuated CCl4-induced hepatic lipid peroxidation, mitochondrial ultrastructure alterations and ALI. Mechanistically, acyl-CoA synthetase long-chain family member 4 (ACSL4) was upregulated in CCl4-exposed human hepatocytes and mouse livers. The ACSL4 inhibitor rosiglitazone alleviated CCl4-induced hepatic lipid peroxidation and ALI. ACSL4 knockdown inhibited oxidized lipids in CCl4-exposed human hepatocytes. Moreover, CCl4 exposure decreased the mitochondrial membrane potential and OXPHOS subunit levels and increased the mtROS level in HepG2 cells. Correspondingly, MitoQ pretreatment inhibited the upregulation of ACSL4 in CCl4-evoked mouse livers and HepG2 cells. MitoQ attenuated lipid peroxidation in vivo and in vitro after CCl4 exposure. Finally, MitoQ pretreatment alleviated CCl4-induced hepatocytic ferroptosis and ALI. These findings suggest that MitoQ protects against hepatocyte ferroptosis in CCl4-induced ALI via the mtROS-ACSL4 pathway.

Elevated serum neurofilament light chain levels are associated with hepatic encephalopathy in patients with cirrhosis.

Increasing evidences implicate vital role of neuronal damage in the development of hepatic encephalopathy (HE). Neurofilament light chain (NfL) is the main frame component of neurons and is closely related to axonal radial growth and neuronal structural stability. We hypothesized that NfL as a biomarker of axonal injury may contribute to early diagnosis of HE. This study recruited 101 patients with liver cirrhosis, 10 healthy individuals, and 7 patients with Parkinson's disease. Minimal hepatic encephalopathy (MHE) was diagnosed using psychometric hepatic encephalopathy score. Serum NfL levels were measured by the electrochemiluminescence immunoassay. Serum NfL levels in cirrhotic patients with MHE were significantly higher than cirrhotic patients without MHE, and increased accordingly with the aggravation of HE. Serum NfL levels were associated with psychometric hepatic encephalopathy score, Child-Pugh score, model for end-stage liver disease score, and days of hospitalization. Additionally, serum NfL was an independent predictor of MHE (odds ratio of 1.020 (95% CI 1.005-1.034); P = 0.007). The discriminative abilities of serum NfL were high for identifying MHE (AUC of 0.8134 (95% CI 0.7130-0.9219); P ˂ 0.001) and OHE (AUC of 0.8852 (95% CI 0.8117-0.9587); P ˂ 0.001). Elevated serum NfL levels correlated with the presence of MHE and associated with the severity of HE, are expected to be a biomarker in patients with cirrhosis. Our study suggested that neuronal damage may play a critical role in the development of HE.

Hybrid Lamellar Superlattices with Monoatomic Platinum Layers and Programmable Organic Ligands.

Compared with layered materials such as graphite and transitional metal dichalcogenides with highly anisotropic in-plane covalent bonds, freestanding metallic two-dimensional (2D) films with atomic thickness are intrinsically more difficult to achieve. The omnidirectional nature of typical metallic bonds prevents the formation of highly anisotropic atomically thin metallic layers. Herein, we report a ligand regulation strategy to stabilize monoatomic platinum layers by forming a unique lamellar superlattice structure with self-assembled organic ligand layers. We show that the interlayer spacings and coordination environments could be systematically tuned by varying programmable molecular ligands with the designed length and structural motifs, which further modulate the electronic states and catalytic performances. The strategy can be extended for preparing lamellar superlattices with monoatomic metallic layers from silver and gold. Such general and delicate synthetic control provides an exciting model system for systematic investigation of the intriguing structure-property correlation of monoatomic layers and promises a molecular design pathway for heterogeneous catalysts.

Generalized Rapid Synthesis of Supported Nanocluster Catalyst for Mild Hydrogenation of Phenol toward KA Oil.

Homogeneous and nanometric metal clusters with unique electronic structures are promising for catalysis, however, common synthesis techniques for metal clusters suffer from large size and even metal nanocrystals attributing to their high surface energy and unsaturated configurations. Herein, a generalized rapid annealing strategy for synthesizing a series of supported metal clusters as superior catalysts is developed. Remarkably, TiO2 supported platinum nanoclusters (Pt NC/TiO2 ) exhibits the excellent catalytic activity to realize phenol hydrogenation under mild conditions. The complete phenol conversion rate and 100% selectivity toward KA oil are achieved in aqueous solution at room temperature and normal pressure. Semi-continuous scale up production of KA oil is successfully performed under mild conditions. Such excellent performance mainly originates from the partial reconstruction of Pt NC/TiO2 in aqueous phenol solution. Considering that the phenol can be produced from lignin, this study underpins a facile, sustainable, and economical route to synthesize nylon from biomass.

Realizing Two-Electron Transfer in Ni(OH)2 Nanosheets for Energy Storage.

The theoretical capacity of a given electrode material is ultimately determined by the number of electrons transferred in each redox center. The design of multi-electron transfer processes could break through the limitation of one-electron transfer and multiply the total capacity but is difficult to achieve because multiple electron transfer processes are generally thermodynamically and kinetically more complex. Here, we report the discovery of two-electron transfer in monolayer Ni(OH)2 nanosheets, which contrasts with the traditional one-electron transfer found in multilayer materials. First-principles calculations predict that the first oxidation process Ni2+ → Ni3+ occurs easily, whereas the second electron transfer in Ni3+ → Ni4+ is strongly hindered in multilayer materials by both the interlayer hydrogen bonds and the domain H structure induced by the Jahn-Teller distortion of the Ni3+ (t2g6eg1)-centered octahedra. In contrast, the second electron transfer can easily occur in monolayers because all H atoms are fully exposed. Experimentally, the as-prepared monolayer is found to deliver an exceptional redox capacity of ∼576 mA h/g, nearly 2 times the theoretical capacity of one-electron processes. In situ experiments demonstrate that monolayer Ni(OH)2 can transfer two electrons and most Ni ions transform into Ni4+ during the charging process, whereas bulk Ni(OH)2 can only be transformed partially. Our work reveals a new redox reaction mechanism in atomically thin Ni(OH)2 nanosheets and suggests a promising path toward tuning the electron transfer numbers to multiply the capacity of the relevant energy storage materials.

Identification of osteosarcoma by microRNA-coupled nuclease digestion on interdigitated electrode sensor.

Osteosarcoma is a type of tumor originating from the bone cells, most often from long bones. Children and adolescents are mainly affected by osteosarcoma. Identifying the condition with osteosarcoma is mandatory to provide proper treatment to the affected patients. This research work has introduced an identification of an osteosarcoma biomarker "miRNA-21" on the interdigitated electrochemical sensor by nuclease digestion. The target RNA sequence of miRNA-21 was hybridized to the capture DNA and placed on the sensing electrode surface with the aid of the biotin-streptavidin interaction. The unhybridized immobilized single-standard capture DNA was digested by S1-nuclease. The current response of the digestion level was considered as the duplex formation between the target and capture DNA. Using this technique, the detection limit of the target was reached to 1 fM and a similar response of current was noted with the target RNA-spiked human serum, indicating the selective identification of target RNA. Further, single mismatched, triple mismatched, and random miRNA sequences (miRNA-195) failed to interact with the immobilized capture DNA, representing the specific identification of target RNA. This nuclease digestion technique with miRNA-21 identification helps in detecting osteosarcoma and related issues.

Biosynthesis of a New Fusaoctaxin Virulence Factor in Fusarium graminearum Relies on a Distinct Path To Form a Guanidinoacetyl Starter Unit Priming Nonribosomal Octapeptidyl Assembly.

Fusarium graminearum is a pathogenic fungus causing huge economic losses worldwide via crop infection leading to yield reduction and grain contamination. The process through which the fungal invasion occurs remains poorly understood. We recently characterized fusaoctaxin A in F. graminearum, where this octapeptide virulence factor results from an assembly line encoded in fg3_54, a gene cluster proved to be involved in fungal pathogenicity and host adaptation. Focusing on genes in this cluster that are related to fungal invasiveness but not to the biosynthesis of fusaoctaxin A, we here report the identification and characterization of fusaoctaxin B, a new octapeptide virulence factor with comparable activity in wheat infection. Fusaoctaxin B differs from fusaoctaxin A at the N-terminus by possessing a guanidinoacetic acid (GAA) unit, formation of which depends on the combined activities of the protein products of fgm1-3. Fgm1 is a cytochrome P450 protein that oxygenates l-Arg to 4(R)-hydroxyl-l-Arg in a regio- and stereoselective manner. Then, Cß-Cγ bond cleavage proceeds in the presence of Fgm3, a pyridoxal-5'-phosphate-dependent lyase, giving guanidinoacetaldehyde and l-Ala. Rather than being directly oxidized to GAA, the guanidine-containing aldehyde undergoes spontaneous cyclization and subsequent enzymatic dehydrogenation to provide glycociamidine, which is linearized by Fgm2, a metallo-dependent amidohydrolase. The GAA path in F. graminearum is distinct from that previously known to involve l-Arg:l-Gly aminidotransferase activity. To provide this nonproteinogenic starter unit that primes nonribosomal octapeptidyl assembly, F. graminearum employs new chemistry to process l-Arg through inert C-H bond activation, selective C-C bond cleavage, cyclization-based alcohol dehydrogenation, and amidohydrolysis-associated linearization.

Correction: NocU is a cytochrome P450 oxygenase catalyzing N-hydroxylation of the indolic moiety during the maturation of the thiopeptide antibiotics nocathiacins.

Correction for 'NocU is a cytochrome P450 oxygenase catalyzing N-hydroxylation of the indolic moiety during the maturation of the thiopeptide antibiotics nocathiacins' by Heng Guo et al., Org. Biomol. Chem., 2021, DOI: 10.1039/d1ob01284c.

NocU is a cytochrome P450 oxygenase catalyzing N-hydroxylation of the indolic moiety during the maturation of the thiopeptide antibiotics nocathiacins.

The ribosomally synthesized and post-translationally modified peptide (RiPP) natural products include the family of thiopeptide antibiotics, where nocathiacins (NOCs) and nosiheptide (NOS) are structurally related bicyclic members featuring an indolic moiety within the side ring system. Compared with NOS, NOCs bear additional functionalities that lead to the improvement of water solubility and bioavailability, a problem inherent to most of the thiopeptide antibiotics, and thus hold potential for clinical use in anti-infective agent development. The process through which post-translational modifications (PTMs) occur to afford these functionalities remains unclear. In this study, an engineered NOS-producing strain is applied to study the function of NocU, a cytochrome P450 oxygenase unique during the PTMs in NOC biosynthesis. Benefiting from the isolation and structure characterization of nosiheptide U (NOS-U), a new NOS-type compound with an extra hydroxyl group at the indole nitrogen, we report that NocU is responsible for the N-hydroxylation of the indolic moiety during the maturation of NOCs. This finding reveals the cause of structural differences at the indole nitrogen of NOCs, which will not only accelerate the biosynthetic studies of NOCs, but also promote new analog development by utilizing the compatibility of the biosynthetic machinery of thiopeptide antibiotics.

Oxidative Indole Dearomatization for Asymmetric Furoindoline Synthesis by a Flavin-Dependent Monooxygenase Involved in the Biosynthesis of Bicyclic Thiopeptide Thiostrepton.

The interest in indole dearomatization, which serves as a useful tool in the total synthesis of related alkaloid natural products, has recently been renewed with the intention of developing new methods efficient in both yield and stereoselective control. Here, we report an enzymatic approach for the oxidative dearomatization of indoles in the asymmetric synthesis of a variety of furoindolines with a vicinal quaternary carbon stereogenic center. This approach depends on the activity of a flavin-dependent monooxygenase, TsrE, which is involved in the biosynthesis of bicyclic thiopeptide antibiotic thiostrepton. TsrE catalyzes 2,3-epoxidation and subsequent epoxide opening in a highly enantioselective manner during the conversion of 2-methyl-indole-3-acetic acid or 2-methyl-tryptophol to furoindoline, with up to >99 % conversion and >99 % ee under mild reaction conditions. Complementing current chemical methods for oxidative indole dearomatization, the TsrE activity-based approach enriches the toolbox in the asymmetric synthesis of products possessing a furoindoline skeleton.

Choice of Initial Brain Imaging in Patients with Suspected Acute Stroke: STROKE69, a Population-Based Study.

BACKGROUND: In patients with suspected stroke, brain imaging is recommended in the acute phase for appropriate management and treatment. Both computed tomography (CT) and magnetic resonance imaging (MRI) are considered reasonable choices for initial brain imaging. When both techniques are available, choosing one or the other might be associated with specific factors related either to patients, stroke symptoms, and severity or management organization. METHODS: The study was performed within the STROKE 69 database, a population-based cohort of all adult patients with suspected stroke admitted in one of the emergency departments (ED), primary stroke center, or stroke center of the Rhône County, from November 2015 to December 2016. Patients were included if they were admitted within 24 h following either symptom onset or last known normal. To identify factors potentially associated with the choice of initial brain imaging, a multivariate logistic regression was performed. RESULTS: Among the 3,244 patients with suspected stroke enrolled in the STROKE69 cohort, 3,107 (95.8%) underwent brain imaging within the first 24 h after admission. Among those 74.6% underwent CT as initial imaging while 25.4% had an MRI. In multivariate analyses, several factors were associated with a lower probability of having an MRI as initial brain imaging versus CT. These were either patient characteristics: older age (>80 years old, OR 0.39 [95% CI 0.28-0.54]), preexisting disability (OR 0.55 [95% CI 0.36-0.84]), use of anticoagulants (OR 0.52 [95% CI 0.33-0.81]), stroke characteristics: stroke of unknown onset (OR 0.42 [95% CI 0.31-0.58]) or factors associated with overall management: onset-to-door time (>6 h, OR 0.38 [95% CI 0.23-0.60]), initial admission to ED (OR 0.02 [95% CI 0.02-0.04]) or intensive care unit (OR 0.01 [95% CI 0.001-0.08]), personal transport (OR 0.66 [95% CI 0.45-0.96]), and admission during working hours (OR 0.65 [95% CI 0.51-0.84]). CONCLUSIONS: Besides CT or MRI availability, a number of other parameters could influence the choice of first imaging in case of stroke suspicion. These are related to patient characteristics, type of stroke symptoms, and type of organization.

A simple method based on laboratory inoculum and field inoculum for evaluating potato resistance to black scurf caused by Rhizoctonia solani.

A two-step method was developed to evaluate potato resistance to black scurf caused by Rhizoctonia solani. Tuber piece inoculum was first conducted in the laboratory, which was also first reported in this study. After inoculation with pathogen discs and culture for 48 h, the necrotic spots on the inoculated potato pieces were generated and measured by the crossing method. Further evaluation was conducted through field experiments using a wheat bran inoculum method. The wheat bran inoculum was placed into the pit dispersedly and surrounded seed tubers. Each cultivar or line was subjected to five treatments of 0-, 2-, 3-, 4-, and 5-g soil inoculum. The results showed that 2-4 g of wheat bran inoculum was the optimum for identifying tuber black scurf resistance. The laboratory scores positively correlated with the incidence and severity of black scurf in the field. According to the results in the laboratory, relatively resistant cultivars could be selected for further estimation of tuber black scurf resistance in field experiments. It is a practical and effective screening method for rapid identification of resistant potato germplasm, which can reduce workload in the field, shorten time required for identification.

Global health diplomacy in humanitarian action.

This commentary explores the intersection of Global Health Diplomacy (GHD) and humanitarian action within Fragility, Conflict, and Violence (FCV) contexts. It aims at addressing the multifaceted challenges faced by communities living in these environments, where a convergence of multiple factors, including over 110 active armed conflicts, creates complex emergencies impact on large populations globally. This commentary holds three primary significances: 1)  it scrutinizes the profound and enduring health consequences of major humanitarian crises on last-mile populations, highlighting the pivotal role of health diplomacy for better navigating humanitarian challenges; 2) it advocates for a paradigm shift in humanitarian approaches, recognizing GHD's potential in shaping international cooperation, building consensus on inclusive global health policies, and enabling more effective interventions; 3) it underscores the operational impact of health diplomacy, both at diplomatic tables and on the frontlines of humanitarian efforts. Through real-world cases such as the cholera outbreak in Yemen and the response to Ebola outbreaks in DRC, the paper illustrates how diplomatic dialogue can impact health outcomes in fragile settings.

Isostructural doping for organic persistent mechanoluminescence.

Mechanoluminescence, featuring light emission triggered by mechanical stimuli, holds immense promise for diverse applications. However, most organic Mechanoluminescence materials suffer from short-lived luminescence, limiting their practical applications. Herein, we report isostructural doping as a valuable strategy to address this challenge. By strategically modifying the host matrices with specific functional groups and simultaneously engineering guest molecules with structurally analogous features for isostructural doping, we have successfully achieved diverse multicolor and high-efficiency persistent mechanoluminescence materials with ultralong lifetimes. The underlying persistent mechanoluminescence mechanism and the universality of the isostructural doping strategy are also clearly elucidated and verified. Moreover, stress sensing devices are fabricated to show their promising prospects in high-resolution optical storage, pressure-sensitive displays, and stress monitoring. This work may facilitate the development of highly efficient organic persistent mechanoluminescence materials, expanding the horizons of next-generation smart luminescent technologies.

Circumventing the Theoretical Scaling Relation Limit for the Oxygen Evolution Reaction.

Transition metal hydr(oxy)oxides (TMHs) are considered efficient electrocatalysts for the oxygen evolution reaction (OER) under alkaline conditions. Toward identification of potential descriptors to circumvent the scaling relation limit for the OER, first-principles calculations were used to quantify the effects on the overpotential of different s (Mg), p (Al), and d (Ti, V, Cr, Fe, Co, Sc, and Zn) electron dopants in Ni-based TMHs. Both the adsorbate evolution mechanism (AEM) and the lattice oxygen-mediated mechanism (LOM) were examined. The results demonstrate that the formation energy of oxygen vacancies (EVO) is strongly affected by the chemical nature of the dopants. A linear relationship is identified between EVO and the free energy difference for the oxygen-oxygen coupling. A descriptor could be employed to discriminate whether the LOM is energetically favored over the AEM. These findings fill existing gaps in appropriate yet computationally light descriptors for direct identification between the AEM and LOM.

Comparison of the effects of probiotics, rifaximin, and lactulose in the treatment of minimal hepatic encephalopathy and gut microbiota.

Background: Minimal hepatic encephalopathy (MHE) is an early stage in the pathogenesis of hepatic encephalopathy. Intestinal microbiota is involved in the pathogenesis of hepatic encephalopathy and has become an important therapeutic target. Since there is no unified treatment principle for MHE, this study was conducted to determine the safety and efficacy of different intestinal microecological modulators in the treatment of MHE, and to explore the potential mechanism through intestinal microbiota analysis. Methods: Patients with liver cirrhosis were screened for MHE using psychometric hepatic encephalopathy score test. Patients diagnosed with MHE were enrolled and received probiotics, rifaximin, or lactulose for 4 weeks. Adverse events were recorded. The psychometric hepatic encephalopathy score test was performed after treatment. Samples of blood and stool were collected at entry and 4 weeks. Blood samples were analyzed to assess blood ammonia, liver, kidney, and hemostatic functions. Stool microbiota were sequenced to confirm changes in microbial composition. Results: Of 323 patients with liver cirrhosis, 74 patients were diagnosed with MHE. In all, 54 patients were enrolled and 52 who agree to follow-up were included in analysis. The recovery rates of MHE patients received probiotics, rifaximin, and lactulose were 58.8% (20/34), 45.5% (5/11), and 57.1% (4/7), respectively. Probiotics and rifaximin improved liver function in MHE patients to a certain extent. Taxonomic compositions of gut microbiota in MHE patients were distinct from healthy people before treatment; the differences were significantly reduced after treatment, and the gut microbiota gradually resembled the structure of healthy individuals. We found that the relative abundance of specific taxa associated with anti-inflammatory and good cognitive functions was increased in MHE patients after treatment. Accordingly, metabolic pathways in MHE patients were altered before and after treatment. Downregulated pathways after probiotics treatment included glycometabolism and degradation of aromatic compounds. After lactulose treatment, degradation pathways of arginine and ornithine showed a downward trend. Conclusion: Probiotics, rifaximin, and lactulose are safe and effective in the treatment of MHE, and improve the composition of gut microbiota to some extent.

The upregulation of Nur77 decreases ketamine-induced hippocampal neurons toxicity in rats.

Ketamine is clinically used as a narcotic. However, ketamine has certain deficits and produces toxicity to neurons. As a member of the NR4A receptor subfamily, Nur77 decreases neurodegenerative disorders. The study aims to investigate the effects of upregulated Nur77 on ketamine-induced rat hippocampal neurons damage and the active mechanism. Neurons were obtained from rat hippocampal and identified by immunofluorescence assays. The treatment groups contained ketamine group, Nur77 group, ketamine + Nur77 group and ketamine + L-cam group. Neurons apoptosis and reactive oxygen species (ROS) were determined by a related kit using flow cytometry. Enzyme NAD(P)H quinone oxidoreductase 1 (NQO1), enzyme heme oxygenase 1 (HO1), Nur77, the expression of Bax, Bcl-2 and cleaved-caspase-3 and inflammatory cytokines were measured using western blot assays and reverse transcription-quantitative PCR (RT-qPCR) assays. Ketamine-induced neurons apoptosis; however, Nur77 decreased ketamine-induced neurons apoptosis. A low level of ROS was observed in two combination groups. Neurons treated by ketamine only had the lowest levels of Nur77, NQO1 and HO1, compared with other treatment groups. The levels of Bax and cleaved-caspase-3 in two combination groups were lower than those in the ketamine group. Furthermore, the ketamine group had higher levels of tumor necrosis factor alpha, IL-1ß and IL-6 but the lowest level of IL-4. Upregulated Nur77 reduced the ketamine-induced toxicity in neurons. The mechanism of Nur77 involved antioxidation, apoptosis signaling pathway and inflammation signaling pathway. Our study provides a novel therapy that could attenuate ketamine-induced toxicity.

Preparation of Graphene Oxide/La2Ti2O7 Composites with Enhanced Electrochemical Performances for Supercapacitors.

A series of graphene oxide (GO)/lanthanum titanate (La2Ti2O7, LTO) fiber composites were prepared through a hydrothermal method. The LTO fibers were homogeneously dispersed between the GO sheets. The structure and micromorphology of the GO/LTO composites were systematically studied. The composite exhibited a high specific capacitance of 900.6 F g-1 at a current density of 1 A g-1 in the 1 M H2SO4 and 10 wt % sucrose aqueous solution as the electrolyte. With the extended potential window of 1.8 V, the fabricated asymmetric supercapacitor device delivered a maximum energy density of 94.0 Wh kg-1 at a power density of 750.1 W kg-1. The GO/LTO composites could be promising materials for energy storage.

The oxygen vacancy in Li-ion battery cathode materials.

The substantial capacity gap between available anode and cathode materials for commercial Li-ion batteries (LiBs) remains, as of today, an unsolved problem. Oxygen vacancies (OVs) can promote Li-ion diffusion, reduce the charge transfer resistance, and improve the capacity and rate performance of LiBs. However, OVs can also lead to accelerated degradation of the cathode material structure, and from there, of the battery performance. Understanding the role of OVs for the performance of layered lithium transition metal oxides holds great promise and potential for the development of next generation cathode materials. This review summarises some of the most recent and exciting progress made on the understanding and control of OVs in cathode materials for Li-ion battery, focusing primarily on Li-rich layered oxides. Recent successes and residual unsolved challenges are presented and discussed to stimulate further interest and research in harnessing OVs towards next generation oxide-based cathode materials.

Adherence with brand versus generic bisphosphonates among osteoporosis patients: a new-user cohort study in the French National Healthcare Insurance database.

Several studies documented declines in treatment adherence with generic forms of oral bisphosphonates in osteoporosis compared to branded forms, while others did not support this relation. Our aim was to compare medication adherence with brand versus generic forms of oral bisphosphonates. A new-user cohort study was conducted using routinely collected administrative and healthcare data linked at the individual level extracted from a nationwide representative sample of the French National Healthcare Insurance database. We included all patients aged 50 and older, new users of oral bisphosphonates for primary osteoporosis between 01/01/2009 and 31/12/2015. Two components of adherence were measured: implementation (continuous multiple-interval measure of medication availability version 7; CMA7) and persistence (time to discontinuation). The sample was composed of 1,834 in the "brand bisphosphonate" group and 1,495 patients in the "generic bisphosphonate" group. Initiating oral bisphosphonate treatment with brand was associated with a higher risk of discontinuation within 12 months (Hazard Ratio = 1.08; 95%CI = [1.02;1.14]). The risk of good implementation (CMA7 ≥ 0.90) was significantly lower in "brand bisphosphonate" group (Risk Ratio = 0.90; 95%CI = [0.85; 0.95]). We did not find any evidence to support the hypothesis of a lower adherence to generic bisphosphonates. In fact, prescribing of generic bisphosphonates led to a higher persistence rate and to better implementation at 1 year.