Research advances of nanomaterials for the acceleration of fracture healing.

The bone fracture cases have been increasing yearly, accompanied by the increased number of patients experiencing non-union or delayed union after their bone fracture. Although clinical materials facilitate fracture healing (e.g., metallic and composite materials), they cannot fulfill the requirements due to the slow degradation rate, limited osteogenic activity, inadequate osseointegration ability, and suboptimal mechanical properties. Since early 2000, nanomaterials successfully mimic the nanoscale features of bones and offer unique properties, receiving extensive attention. This paper reviews the achievements of nanomaterials in treating bone fracture (e.g., the intrinsic properties of nanomaterials, nanomaterials for bone defect filling, and nanoscale drug delivery systems in treating fracture delayed union). Furthermore, we discuss the perspectives on the challenges and future directions of developing nanomaterials to accelerate fracture healing.

The role of m6A RNA methylation in autoimmune diseases: Novel therapeutic opportunities.

N6-methyladenosine (m6A) modifications, as one of the most common forms of internal RNA chemical modifications in eukaryotic cells, have gained increasing attention in recent years. The m6A RNA modifications exert various crucial roles in various biological processes, such as embryonic development, neurogenesis, circadian rhythms, and tumorigenesis. Recent advances have highlighted that m6A RNA modification plays an important role in immune response, especially in the initiation and progression of autoimmune diseases. In this review, we summarized the regulatory mechanisms of m6A methylation and its biological functions in the immune system and mainly focused on recent progress in research on the potential role of m6A RNA methylation in the pathogenesis of autoimmune diseases, thus providing possible biomarkers and potential targets for the prevention and treatment of autoimmune diseases.

Engineering of an adaptive tandem CRISPR/Cas12a molecular amplifier permits robust analysis of Vibrio parahaemolyticus.

Seeking new molecular diagnostic method for pathogenic bacteria detection is of utmost importance for ensuring food safety and protecting human health. Herein, we have engineered an adaptive tandem CRISPR/Cas12a molecular amplifier specifically designed for robust analysis of vibrio parahaemolyticus (V. parahaemolyticus), one of the most harmful pathogens. Our strategy involves the integration of three crucial processes: recombinase polymerase amplification (RPA) for copy number amplification, terminal deoxynucleotidyl transferase (TdT) for template-free strand elongation, and CRISPR/Cas12a-mediated trans-cleavage of a reporter molecule. By combining these processes, the target genomic DNA extracted from V. parahaemolyticus is able to activate many CRISPR/Cas12a units (CRISPR/Cas12an) simultaneously, resulting in a greatly amplified target signal to indicate the presence and concentration of V. parahaemolyticus. This unique model offers more advantages compared to traditional amplification models that use one RPA amplicon to activate one CRISPR/Cas12a unit. Under optimized conditions, our method enables the detection of target V. parahaemolyticus within a linear range of 1 × 102-1 × 107 CFU/mL, with an impressive limit of detection as low as 12.4 CFU/mL. It is conceivable that the adaptive tandem CRISPR/Cas12a molecular amplifier could be adapted as routine diagnostic kits in future for in-field detection of pathogens.

Preparation of size-tunable Fe3O4 magnetic nanoporous carbon composites by MOF pyrolysis regulation for magnetic resonance sensing of aflatoxin B1 with excellent anti-matrix effect.

Magnetic nanoporous materials represent a new emerging category of magnetic materials for construction of magnetic resonance sensors. In this study, we adopted the metal-organic framework materials, MIL-101(Fe), as the precursor to prepare series nanoporous-carbon-Fe3O4 (NPC-Fe3O4) composites. Results showed that Fe3O4 were uniformly distributed in MIL-101(Fe) and the size of MNP was precisely tuned at different pyrolysis temperatures, conferring the optimal NPC-Fe3O4-450 °C composite with dramatically improved T2 relaxivity. The NPC-Fe3O4-450 °C composite was modified with antibodies and antigens, respectively, for detection of aflatoxin B1 in various food samples with complicated matrix. Range from 0.010 ng mL-1 to 2.0 ng mL-1, extreme low detection limit of 5.0 pg mL-1, and satisfied recoveries were successfully achieved, indicating excellent anti-matrix effect. These findings offer a new dimension to engineer novel magnetic materials with improved relaxivity for simple and easy sensing of food hazards in complicated food matrix without any purification or separation procedures.

Effects of in vitro fecal fermentation on the metabolism and antioxidant properties of cyanidin-3-O-glucoside.

Anthocyanins' potential health benefits have garnered significant interest. However, due to low bioavailability, the gut microbiota-associated metabolites are suspected to mediate their bioactivity. In this study, cyanidin-3-glucoside (C3G) was fermented with fecal inoculum to simulate colonic microbiota interaction in vitro. The metabolites and antioxidant properties of pre- (P-C3G) and post-fermentation (F-C3G) were determined. Fermentation significantly increased contents of five metabolites (cyanidin, protocatechuic acid, phloroglucinaldehyde, 4-hydroxybenzoic acid and 4-hydroxyphenylacetic acid). Additionally, F-C3G demonstrated superior radicals scavenging than P-C3G, as well as to alleviate H2O2-induced damage in HepG2 cell via increasing superoxide dismutase by 43.26% and catalase by 39.83%, reducing malonaldehyde by 16.40% and cellular ROS production, and activating Nrf2 pathway. Moreover, F-C3G significantly extended the survival rate by 20.67% of Caenorhabditis elegans under heat stress by antioxidation in vivo. This study suggested that anthocyanins metabolism by gut microbiota produce specific metabolites, which potentially exerts protection.

Uncovering Predictive Factors and Interventions for Restoring Microecological Diversity after Antibiotic Disturbance.

Antibiotic treatment can lead to a loss of diversity of gut microbiota and may adversely affect gut microbiota composition and host health. Previous studies have indicated that the recovery of gut microbes from antibiotic-induced disruption may be guided by specific microbial species. We expect to predict recovery or non-recovery using these crucial species or other indices after antibiotic treatment only when the gut microbiota changes. This study focused on this prediction problem using a novel ensemble learning framework to identify a set of common and reasonably predictive recovery-associated bacterial species (p-RABs), enabling us to predict the host microbiome recovery status under broad-spectrum antibiotic treatment. Our findings also propose other predictive indicators, suggesting that higher taxonomic and functional diversity may correlate with an increased likelihood of successful recovery. Furthermore, to explore the validity of p-RABs, we performed a metabolic support analysis and identified Akkermansia muciniphila and Bacteroides uniformis as potential key supporting species for reconstruction interventions. Experimental results from a C57BL/6J male mouse model demonstrated the effectiveness of p-RABs in facilitating intestinal microbial reconstitution. Thus, we proved the reliability of the new p-RABs and validated a practical intervention scheme for gut microbiota reconstruction under antibiotic disturbance.

Trajectories of cognitive reactivity and its predictive value on postpartum depression in Chinese women: a latent class growth modeling analysis.

Many women are experiencing postpartum depression (PPD) after giving birth. How to recognize and intervene in high-risk PPD women early and effectively remains unknown. Our objective is to describe the latent trajectory groups of cognitive reactivity (CR) in perinatal women, and their relationship to demographic and disease-related factors, as well as investigate the associations with PPD. Data from 321 perinatal women who were evaluated in urban tertiary hospitals in China at three-time points: 32-35 weeks of pregnancy, 1 week postpartum, and 6 weeks postpartum. Latent class growth modeling was used to identify the trajectory patterns of CR and logistic regression was used to explore the association between demographic and disease-related factors, CR trajectories, and depression. Three trajectory groups were identified: the continuing deterioration group (17.2%), the postpartum deterioration group (22.1%), and the consistent resilient group (60.7%). Participants with a bachelor's degree or higher and with gestational diabetes diagnosis were more likely to be in the continuing deterioration group. Those who were from only-child families were more likely to be in the postpartum deterioration group. Women in the continuing deterioration group and postpartum deterioration group were more likely to experience PPD. Targeted interventions should be developed based on trajectory group of CR.

Transcriptional heterogeneity overcomes super-enhancer disrupting drug combinations in multiple myeloma.

Multiple myeloma (MM) is a malignancy that is often driven by MYC and that is sustained by IRF4, which are upregulated by super-enhancers. IKZF1 and IKZF3 bind to super-enhancers and can be degraded using immunomodulatory imide drugs (IMiDs). Successful IMiD responses downregulate MYC and IRF4; however, this fails in IMiD-resistant cells. MYC and IRF4 downregulation can also be achieved in IMiD-resistant tumors using inhibitors of BET and EP300 transcriptional coactivator proteins; however, in vivo these drugs have a narrow therapeutic window. By combining IMiDs with EP300 inhibition, we demonstrate greater downregulation of MYC and IRF4, synergistic killing of myeloma in vitro and in vivo, and an increased therapeutic window. Interestingly, this potent combination failed where MYC and IRF4 expression was maintained by high levels of the AP-1 factor BATF. Our results identify an effective drug combination and a previously unrecognized mechanism of IMiD resistance.

Biomimetic Structural Protein Based Magnetic Responsive Scaffold for Enhancing Bone Regeneration by Physical Stimulation on Intracellular Calcium Homeostasis.

Bone matrix has distinct architecture and biochemistry which present a barrier on synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, we prepared the biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) using a facile synthetic methodology. The ECM/RSF/MNP scaffold is hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers, mimicking the bone minimum unit morphology. The scaffold demonstrated saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the ß-sheet crystalline domain of RSF and the chelated magnetic nanoparticles could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by approximately 20%. The results indicated that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promoted cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro and new bone formation in a critical-size femur defect rat model. RNA sequencing revealed that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+ /calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition and external physical stimulation on intracellular Ca2+ homeostasis. This article is protected by copyright. All rights reserved.

RAGE acted as a new anti-inflammatory target for Icariin's treatment against vascular dementia based on network pharmacology-directed verification.

Vascular dementia (VaD) ranks as the second most prevalent form of dementia and poses a considerable global health challenge. Icariin has been recognized for its robust neuroprotective effects in combating VaD. Nonetheless, the underlying mechanisms have not been fully elucidated. An integrated approach involving network pharmacology, molecular docking, and molecular dynamics simulations (MDS) was employed to systematically investigate the potential pharmacological actions of Icariin in counteracting VaD. The AGE/RAGE pathway was identified as a promising anti-inflammatory pathway. A chronic cerebral hypoperfusion mouse model was utilized to establish VaD. Both Icariin and FP S-ZM1 (a RAGE inhibitor) were administered through oral gavage and intraperitoneal injection, respectively. The Morris water maze (MWZ) was used to evaluate cognitive functions. Moreover, immunofluorescence, RT-qP CR, and Western blot analyses were carried out to evaluate the effects of FP S-ZM1 on neuroinflammation. Network analysis identified 14 crucial targets and highlighted the AGE-RAGE signaling cascade in diabetic complications as the foremost KEGG pathway with potential anti-neuroinflammatory property. MDS results suggested a stable binding of the RAGE-Icariin complex. Remarkably, Icariin was found to effectively mitigate cognitive deficits in VaD mice, which was correlated with the upregulation of the P I3K/AKT pathway and downregulation of the JNK/cJUN signaling cascade. Critically, co-administration of FP S-ZM1 enhanced Icariin's ameliorative effects on cognitive deficits, owing to bolstered anti-neuroinflammatory action. This study unveils the potential of Icariin in alleviating cognitive dysfunction and neuroinflammation in VaD, which may be attributed to the modulation of the AGE/RAGE pathway.Communicated by Ramaswamy H. Sarma.

Superconducting quantum interference device readout circuit with tunable feedback polarity.

Feedback circuits, which act as functional units in superconducting quantum interference device (SQUID) readout circuits, such as positive feedback circuits for suppressing the preamplifier noise contribution or negative feedback circuits for increasing the linear flux range of SQUID, enable SQUIDs to achieve high performance in practical applications. Integrating feedback circuits with different functions into a single SQUID chip contributes to the construction of highly compact SQUID electronics. Here, we propose a SQUID readout circuit with tunable feedback polarity (TFP). The switching of the feedback polarity is easily realized by applying a control current to the superconducting switches integrated into the SQUID chip. The enhancement of the flux-to-voltage transfer coefficient or the linear flux range depends on the choice of feedback polarity. In addition, we introduce a two-stage scheme to address the degraded noise performance induced by negative feedback. This work attempts to develop a compact and versatile architecture of SQUID readout by using a set of compatible superconducting technologies.

Protective effect of scorpion venom oligopeptides in human umbilical vein endothelial cells under benzo(α)pyrene exposure.

Inflammation and oxidative stress play pivotal role in the process of atherosclerosis. Scorpion venom is widely used as anti-cancer agent, however, the anti-inflammatory and antioxidant activities of scorpion venom peptides (SVPs) are rarely explored. In the current study, seven novel SVPs were isolated in a protective activity tracking isolation method in a cell model of benzo(α)pyrene (BaP)-induced human umbilical vein endothelial cells (HUVECs). The current study showed that SVP-1 [Tyr-Thr-Trp-Glu-Ala] significantly attenuated BaP-induced reactive oxygen species (ROS) over-production and inflammatory cytokines (IL-6, IL-1ß, TNF-α, NO and PGE2) over-expression. Furthermore, SVP-1 attenuated BaP-induced adhesion molecules over-expression and inhibited the NF-κB and AhR signalling pathways activation. Collectively, the present study, for the first time, shows that SVPs inhibit the NF-κB and AhR signalling pathways in HUVECs under BaP-exposure, which strongly suggests the therapeutic potential of SVPs against atherosclerosis.

Radial Planes in Hip Magnetic Resonance Imaging: Techniques, Applications, and Perspectives.

The hip cartilage and labrum, as the main targets of femoroacetabular impingement, sports-related or traumatic damage, as well as congenital and developmental abnormalities, have attracted increasing attention with the development of magnetic resonance imaging (MRI) and hip arthroscopy. MRI is a commonly used imaging modality to noninvasively visualize the hip cartilage and labral lesions. However, conventional orthogonal MRI planes encounter unique challenges given the ball-and-socket configuration of the hip joint, its anatomically abducted and anteverted orientation, and the thin, closely apposed cartilage enveloping the femoral head and acetabulum. Advancements in hip MRI's radial plane, which is acquired through the center of the hip joint, offer a solution. This technology provides true cross-sectional images of the cartilage and labrum perpendicular to the curvature of the joint, thereby mitigating the partial-volume-averaging effects. The integration of 3.0-Tesla high field strength and three-dimensional (3D) acquisition techniques further enhances the capabilities of the radial plane. This combination yields a high signal-to-noise ratio, high spatial resolution, high contrast between intraarticular structures, while minimizing partial-volume-averaging effects. Such improvements potentially facilitate the comprehensive detection of even minor chondral and labral lesions. The capability for multiplanar reconstruction from a single 3D volumetric acquisition further strengthens the usefulness of the radial plane by aiding in precise localization of hip cartilage and labral lesions, in line with hip arthroscopy findings. These advancements have the potential to standardize MRI evaluations and radiographic reporting systems for hip cartilage and labrum, offering precise guidance for hip arthroscopy. This article presents a comprehensive review of radial plane technology applied to the hip MRI, and discusses the morphological assessment and localization of hip cartilage and labral lesions utilizing this advanced imaging technique. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

Characterization of mismatch-repair (MMR)/microsatellite instability (MSI)-discordant endometrial cancers.

BACKGROUND: Mismatch-repair (MMR)/microsatellite instability (MSI) status has therapeutic implications in endometrial cancer (EC). The authors evaluated the concordance of testing and factors contributing to MMR expression heterogeneity. METHODS: Six hundred sixty-six ECs were characterized using immunohistochemistry (IHC), MSI testing, and mut-L homolog 1 (MLH1) methylation. Select samples underwent whole-transcriptome analysis and next-generation sequencing. MMR expression of metastatic/recurrent sites was evaluated. RESULTS: MSI testing identified 27.3% of cases as MSI-high (n = 182), MMR IHC identified 25.1% cases as MMR-deficient (n = 167), and 3.8% of cases (n = 25) demonstrated discordant results. A review of IHC staining explained discordant results in 18 cases, revealing subclonal loss of MLH1/Pms 1 homolog 2 (PMS2) (n = 10) and heterogeneous MMR IHC (mut-S homolog 6 [MSH6], n = 7; MLH1/PMS2, n = 1). MSH6-associated Lynch syndrome was diagnosed in three of six cases with heterogeneous expression. Subclonal or heterogeneous cases had a 38.9% recurrence rate (compared with 16.7% in complete MMR-deficient cases and 9% in MMR-proficient cases) and had abnormal MMR IHC results in all metastatic recurrent sites (n = 7). Tumors with subclonal MLH1/PMS2 demonstrated 74 differentially expressed genes (determined using digital spatial transcriptomics) when stratified by MLH1 expression, including many associated with epithelial-mesenchymal transition. CONCLUSIONS: Subclonal/heterogeneous MMR IHC cases showed epigenetic loss in 66.7%, germline mutations in 16.7%, and somatic mutations in 16.7%. MMR IHC reported as intact/deficient missed 21% of cases of Lynch syndrome. EC with subclonal/heterogeneous MMR expression demonstrated a high recurrence rate, and metastatic/recurrent sites were MMR-deficient. Transcriptional analysis indicated an increased risk for migration/metastasis, suggesting that clonal MMR deficiency may be a driver for tumor aggressiveness. Reporting MMR IHC only as intact/deficient, without reporting subclonal and heterogeneous staining, misses opportunities for biomarker-directed therapy. PLAIN LANGUAGE SUMMARY: Endometrial cancer is the most common gynecologic cancer, and 20%-40% of tumors have a defect in DNA proofreading known as mismatch-repair (MMR) deficiency. These results can be used to guide therapy. Tests for this defect can yield differing results, revealing heterogeneous (mixed) proofreading capabilities. Tumors with discordant testing results and mixed MMR findings can have germline or somatic defects in MMR genes. Cells with deficient DNA proofreading in tumors with mixed MMR findings have DNA expression profiles linked to more aggressive characteristics and cancer spread. These MMR-deficient cells may drive tumor behavior and the risk of spreading cancer.

Oxygen evolution catalyzed by Ni-Co-Nb ternary metal sulfides on plasma-activated Ni-Co support.

As a four-electron-proton coupled reaction, the oxygen evolution reaction (OER) requires a high overpotential for electrocatalytic water splitting. Most of the reported OER catalysts still need higher overpotentials than the thermodynamic water decomposition potential (1.23 V). Therefore, developing the efficient and cost-effective OER electrocatalysts remains a challenge in the electrocatalysis filed. Herein, multiphase Ni-Co-Nb sulfides (NiCoNbSx) are in-situ engineered on the plasma-activated nickel-cobalt foam (PNCF), and the synthesized NiCoNbSx/PNCF exhibits rich heterointerfaces and active sites, causing a high OER performance in an alkaline medium. The NiCoNbSx/PNCF catalyst features the low overpotentials of 48 and 382 mV for delivering the current densities of 10 (j10) and 1000 mA cm-2 (j1000), with a good electrocatalytic stability. The theoretical calculations reveal that the heterojunction interface of NiS (401)-Co9S8 (440) acts as the active center for OER. These results provide a new effective surface modification approach and insights into catalytic processes enabling water electrolysis pursued for clean and sustainable energy applications.

Microbial influence on triggering and treatment of host cancer: An intestinal barrier perspective.

Inflammatory bowel disease (IBD) is associated with complex complications that may lead to tumors. However, research on the mechanisms underlying susceptibility to chronic immune diseases and cancer pathogenesis triggered by the inflammatory environment remains limited. An imbalance in the host gut microbiota often accompanies intestinal inflammation. The delayed recovery of the dysregulated intestinal microbiota may exacerbate systemic inflammatory responses, multiorgan pathology, and metabolic disorders. This delay may also facilitate bacterial translocation. This review examined the relationship between gut barrier disruption and unbalanced microbial translocation and their impact on the brain, liver, and lungs. We also explored their potential roles in tumor initiation. Notably, the role of the intestinal microbiota in the development of inflammation is linked to the immune surveillance function of the small intestine and the repair status of the intestinal barrier. Moreover, adherence to a partially anti-inflammatory diet can aid in preventing the malignant transformation of inflammation by repairing the intestinal barrier and significantly reducing inflammation. In conclusion, enhancing intestinal barrier function may be a novel strategy for preventing and treating chronic malignancies in the intestine and other body areas.

Novel electromagnetic navigation bronchoscopy system for the diagnosis of peripheral pulmonary nodules: a prospective, multicentre study.

BACKGROUND: Traditional electromagnetic navigation bronchoscopy (ENB) is a real-time image-guided system and used with thick bronchoscopes for the diagnosis of peripheral pulmonary nodules (PPNs). A novel ENB that could be used with thin bronchoscopes was developed. This study aimed to evaluate the diagnostic yield and the experience of using this ENB system in a real clinical scenario. METHODS: This multicentre study enrolled consecutive patients with PPNs adopting ENB from March 2019 to August 2021. ENB was performed with different bronchoscopes, ancillary techniques and sampling instruments according to the characteristics of the nodule and the judgement of the operator. The primary endpoint was the diagnostic yield. The secondary endpoints included the diagnostic yield of subgroups, procedural details and complication rate. RESULTS: In total, 479 patients with 479 nodules were enrolled in this study. The median lesion size was 20.9 (IQR, 15.9-25.9) mm. The overall diagnostic yield was 74.9% (359/479). A thin bronchoscope was used in 96.2% (461/479) nodules. ENB in combination with radial endobronchial ultrasound (rEBUS), a guide sheath (GS) and a thin bronchoscope was the most widely used guided method, producing a diagnostic yield of 74.1% (254/343). The median total procedural time was 1325.0 (IQR, 1014.0-1676.0) s. No severe complications occurred. CONCLUSION: This novel ENB system can be used in combination with different bronchoscopes, ancillary techniques and sampling instruments with a high diagnostic yield and safety profile for the diagnosis of PPNs, of which the combination of thin bronchoscope, rEBUS and GS was the most common method in clinical practice. TRIAL REGISTRATION NUMBER: NCT03716284.

Susceptibility of gram-negative isolates collected in Taiwan to imipenem/relebactam and comparator agents - SMART 2018-2021.

BACKGROUND: Imipenem/relebactam (IMR) was approved for patient use in Taiwan in 2023. We evaluated the in vitro susceptibility of recent Gram-negative pathogens collected in Taiwan hospitals to IMR and comparators with a focus on carbapenem-resistant and KPC-carrying non-Morganellaceae Enterobacterales (NME), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). METHODS: From 2018 to 2021, eight hospitals in Taiwan each collected up to 250 consecutive, aerobic or facultative, Gram-negative pathogens per year from patients with bloodstream, intraabdominal, lower respiratory tract, and urinary tract infections. MICs were determined using Clinical Laboratory Standards Institute (CLSI) broth microdilution. Most isolates that were IMR-, imipenem-, or ceftolozane/tazobactam-nonsusceptible were screened for ß-lactamase genes by PCR or whole-genome sequencing. RESULTS: Ninety-eight percent of NME (n = 5063) and 94% of P. aeruginosa (n = 1518) isolates were IMR-susceptible. Percent susceptible values for non-carbapenem ß-lactam comparators, including piperacillin/tazobactam, were 68-79% for NME isolates, while percent susceptible values for all ß-lactam comparators, including meropenem, were 73-81% for P. aeruginosa. IMR retained activity against 93% of multidrug-resistant (MDR) NME and 70% of MDR P. aeruginosa. Sixty-five percent of carbapenem-resistant NME and 81% of KPC-positive NME (n = 80) were IMR-susceptible. IMR inhibited 70% of CRPA (n = 287). Fifty percent of IMR-nonsusceptible NME tested for ß-lactamase carriage had an MBL or OXA-48-like enzyme, whereas most (95%) IMR-nonsusceptible P. aeruginosa examined did not carry acquired ß-lactamase genes. CONCLUSION: Based on our in vitro data, IMR may be a useful option for the treatment of hospitalized patients in Taiwan with infections caused by common Gram-negative pathogens, including carbapenem-resistant NME, KPC-positive NME, and CRPA.