Gamma-type immunoglobulin enhances phagocytosis of amyloid-beta fibrils by microglia.

The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer's disease. Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system, though the mechanisms are unclear. Here, we found that gamma-type immunoglobulin, a product originating from peripheral blood B cells, localized in the brain parenchyma of multiple mouse models with amyloid pathology, and was enriched on microglia but not on other brain cell types. Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes, including upregulation of pathways related to phagocytosis and immunity. Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc, but not Fab, fragment. Our data indicate that microglia, when exposed to gamma-type immunoglobulin, exhibit an enhanced capacity for clearing amyloid-beta fibrils, potentially via the gamma-type immunoglobulin Fc fragment signaling pathway. This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer's disease by enhancing microglial function.

Framework restoration on Tang Dynasty garden as a multiple-histories environment: Regions, ecology, architecture, and human behavior.

From a multiple-histories perspective, this paper attempts to restore the feature framework of Tang Dynasty gardens by describing the environment panorama of that era. Tang Dynasty gardens have their own unique and complex environment features, which is crucial for understanding Chinese classical gardens. This research developed a massive text mining method of historical-document to detect all garden-related elements in Tang poetry. By sorting out these elements, it has been restored the original appearance of Tang Dynasty gardens and summarized its feature framework. The resulting model included 199 factors, 173 of which are correlating with gardens. Among the 173 factors, 129 are risk factors and 44 are protective factors. This paper restores the feature framework of Tang Dynasty gardens from the following four points, namely regions, ecology, architecture and human behavior. Understanding the Tang Dynasty gardens would help understand the development context of Chinese classical gardens, and should provide new paths for contemporary environment creation.

Asymmetric Cycloaddition of N-2,2,2-Trifluoroethylisatin Ketimines and Unsymmetrical Dicarbonyl-Activated Alkenes: Construction of 5'-Trifluoromethylated 3,2'-Pyrrolidinyl Spirooxindoles with Three Carbonyl Groups.

The asymmetric cycloaddition between N-2,2,2-trifluoroethylisatin ketimines and unsymmetrical dicarbonyl-activated alkenes catalyzed by a bifunctional squaramide has been discovered. The present study demonstrates an efficient approach for the regio-, diastereo-, and enantioselective synthesis of densely functionalized 5'-trifluoromethylated 3,2'-pyrrolidinyl spirooxindoles featuring three different types of carbonyl groups.

Construction of Coordination Spaces with Narrow Pore Windows in Co-Based Metal-Organic Frameworks toward CO2/N2 Separation.

Carbon emission reduction is an important measure to mitigate the greenhouse effect, which has become a hotspot in global climate change research. To contribute to this, here, we fabricated two Co-based metal-organic frameworks (Co-MOFs), namely, {[Co3(NTB)2(bib)]·(DMA)2·(H2O)4}n (DZU-211) and {[Co3(NTB)2(bmip)]·(DMA)2}n (DZU-212) (H3NTB = 4,4',4″-nitrilotribenzoic acid, bib = 1,4-bis(imidazol-1-yl)-butane, bmip = 1,3-bis(2-methyl-1H-imidazol-1-yl)propane) to realize efficient CO2/N2 separation by dividing coordination spaces into suitable pores with narrow windows. DZU-211 reveals a 3D open porous framework, while DZU-212 exhibits a 3D double-fold interpenetrated structure. The two MOFs both possess large coordination spaces and small open pore sizes, via the bib ligand insertion and framework interpenetration, respectively. Comparatively, DZU-211 reveals superior selective CO2 uptake properties due to its more suitable pore characteristics. Gas sorption experiments show that DZU-211 has a CO2 uptake of 52.6 cm3 g-1 with a high simulated CO2/N2 selectivity of 101.7 (298 K, 1 atm) and a moderate initial adsorption heat of 38.1 kJ mol-1. Moreover, dynamic breakthrough experiments confirm the potential application of DZU-211 as a CO2 separation material from postcombustion flue gases.

Tris(triazolo)triazine-Based Covalent Organic Frameworks for Efficiently Photocatalytic Hydrogen Peroxide Production.

Two-dimensional covalent organic frameworks (2D-COFs) have recently emerged as fascinating scaffolds for solar-to-chemical energy conversion because of their customizable structures and functionalities. Herein, two tris(triazolo)triazine-based COF materials (namely COF-JLU51 and COF-JLU52) featuring large surface area, high crystallinity, excellent stability and photoelectric properties were designed and constructed for the first time. Remarkably, COF-JLU51 gave an outstanding H2O2 production rate of over 4200 µmol g-1 h-1 with excellent reusability in pure water and O2 under one standard sun light, that higher than its isomorphic COF-JLU52 and most of the reported metal-free materials, owing to its superior generation, separation and transport of photogenerated carriers. Experimental and theoretical researches prove that the photocatalytic process undergoes a combination of indirect 2e- O2 reduction reaction (ORR) and 4e- H2O oxidation reaction (WOR). Specifically, an ultrahigh yield of 7624.7 µmol g-1 h-1 with apparent quantum yield of 18.2 % for COF-JLU52 was achieved in a 1 : 1 ratio of benzyl alcohol and water system. This finding contributes novel, nitrogen-rich and high-quality tris(triazolo)triazine-based COF materials, and also designate their bright future in photocatalytic solar transformations.

Identification and biological evaluation of fused tetrahydroisoquinoline derivatives as Wnt/ß-catenin signaling inhibitors to suppress colorectal cancer.

Colorectal cancer (CRC) has been becoming one of the most common causes of cancer mortality worldwide. Accumulating studies suggest that the progressive up-regulation of Wnt/ß-catenin signaling is a crucial hallmark of CRC, and suppressing it is a promising strategy to treat CRC. Herein, we reported our latest efforts in the discovery of novel fused tetrahydroisoquinoline derivatives with good anti-CRC activities by screening our in-house berberine-like library and further structure-activity relationship (SAR) studies, in which we identified compound 10 is a potent lead compound with significant antiproliferation potencies. By the biotinylated probe and LC-MS/MS study, Hsp90 was identified as its molecular target, which is a fully different mechanism of action from what we reported before. Further studies showed compound 10 directly engaged the N-terminal site of Hsp90 and promoted the degradation of ß-catenin, thereby suppressing the Wnt/ß-catenin signaling. More importantly, compound 10 exhibits favorable pharmacokinetic parameters and significant anti-tumor efficacies in the HCT116 xenograft model. Taken together, this study furnished the discovery of candidate drug compound 10 possessing a novel fused tetrahydroisoquinoline scaffold with excellent in vitro and in vivo anti-CRC activities by targeting Hsp90 to disturb Wnt/ß-catenin signaling pathway, which lay a foundation for discovering more effective CRC-targeted therapies.

Integrated analysis of single-cell and bulk RNA-sequencing identifies a signature based on drug response genes to predict prognosis and therapeutic response in ovarian cancer.

Ovarian cancer represents a severe gynecological malignancy with a dire prognosis, underscoring the imperative need for dependable biomarkers that can accurately predict drug response and guide therapeutic choices. In this study, we harnessed online single-cell RNA sequencing (scRNAseq) and bulk RNA sequencing (RNAseq) datasets, applying the Scissor algorithm to identify cells responsive to paclitaxel. From these cells, we derived a gene signature, subsequently used to construct a prognostic model that demonstrated high sensitivity and specificity in predicting patient outcomes. Moreover, we conducted pathway and functional enrichment analyses to uncover potential molecular mechanisms driving the prognostic gene signature. This study illustrates the critical role of scRNAseq and bulk RNAseq in developing precise prognostic models for ovarian cancer, potentially transforming clinical decision-making.

Medicinal Plant Root Exudate Metabolites Shape the Rhizosphere Microbiota.

The interactions between plants and rhizosphere microbes mediated by plant root exudates are increasingly being investigated. The root-derived metabolites of medicinal plants are relatively diverse and have unique characteristics. However, whether medicinal plants influence their rhizosphere microbial community remains unknown. How medicinal plant species drive rhizosphere microbial community changes should be clarified. In this study involving high-throughput sequencing of rhizosphere microbes and an analysis of root exudates using a gas chromatograph coupled with a time-of-flight mass spectrometer, we revealed that the root exudate metabolites and microorganisms differed among the rhizosphere soils of five medicinal plants. Moreover, the results of a correlation analysis indicated that bacterial and fungal profiles in the rhizosphere soils of the five medicinal plants were extremely significantly or significantly affected by 10 root-associated metabolites. Furthermore, among the 10 root exudate metabolites, two (carvone and zymosterol) had opposite effects on rhizosphere bacteria and fungi. Our study findings suggest that plant-derived exudates modulate changes to rhizosphere microbial communities.

Holistic quality assessment and monitoring of YiXinShu capsule based on three-dimensional fingerprints combined with quantitative analysis, antioxidant activity and chemometrics.

ETHNOPHARMACOLOGICAL RELEVANCE: YiXinShu capsule (YXSC), originally from the classical TCM formula named "Sheng-Mai-San", has been extensively utilized in clinic for the treatment of cardiovascular diseases. However, there were few reports about the quality assessment of YXSCs both internationally and domestically. AIM OF THE STUDY: The objective was to develop a multi-strategy platform incorporating systematic quantitative fingerprint analysis and antioxidant activity determination, with chemometric analysis and bivariate correlation analysis as the auxiliary approaches, to assess and monitor the quality of YXSCs. MATERIALS AND METHODS: Firstly, according to the Chinese Pharmacopoeia (2020 edition), 12 key indicator components from seven herb medicines were quantified by HPLC method. Then, three-dimensional fingerprints comprising five-wavelength fusion fingerprint (FWF-FP), electrochemical fingerprint (EC-FP) and Differential Scanning Calorimetry fingerprint (DSC-FP) were established to assess and monitor YXSCs using systematically quantified fingerprint method (SQFM) and principal component analysis (PCA). Moreover, by integrating the analysis of the three-dimensional fingerprints, the quality of YXSCs from different batches was effectively screened. Finally, the antioxidant activity of this TCM was assessed through DPPH and ABTS methods, and the L-ascorbic acid equivalent antioxidant capacity (AEAC) values were compared to evaluate the antioxidant activities of the two methods. A Partial Least Squares (PLS) model was used to develop the spectrum-activity relationship between FWF-FP and AEAC, and a bivariate correlation analysis (BCA) was used to assess the correlation between FWF-FP and EC-FP. RESULTS: The key indexes including tanshinone I, tol, toe, Atp, first exothermic peak, and second exothermic peak can differentiate between various batches of YXSCs based on their three-dimensional fingerprint profiles. The integration evaluation results from 42 batches of YXSCs were categorized into 2-5 grades, indicating good quality consistency across different batches. In vitro studies have indicated a significant antioxidant activity capacity of YXSCs. The PLS model revealed that 37 out of the 41 fingerprint peaks exhibited antioxidant activity. The overall trend of BCA was consistent with PLS model results. CONCLUSION: This research presents a scientific and holistic strategy for the quality consistency evaluation of YXSCs, thereby offering an effective approach for the thorough evaluation of TCMs.

Squaramide-catalyzed enantioselective Michael addition of nitromethane to 2-enoylazaarenes: synthesis of chiral azaarene-containing γ-nitroketones.

Bifunctional chiral squaramide-catalyzed highly enantioselective Michael addition of nitromethane to diverse 2-enoylazaarenes was successfully performed. This protocol provided a set of chiral azaarene-containing γ-nitroketones with up to 98% yield and 98% ee in a solvent-free catalytic system under mild conditions. Furthermore, gram-scale synthetic utility was also showcased.

Pitfalls in Developing Machine Learning Models for Predicting Cardiovascular Diseases: Challenge and Solutions.

In recent years, there has been explosive development in artificial intelligence (AI), which has been widely applied in the health care field. As a typical AI technology, machine learning models have emerged with great potential in predicting cardiovascular diseases by leveraging large amounts of medical data for training and optimization, which are expected to play a crucial role in reducing the incidence and mortality rates of cardiovascular diseases. Although the field has become a research hot spot, there are still many pitfalls that researchers need to pay close attention to. These pitfalls may affect the predictive performance, credibility, reliability, and reproducibility of the studied models, ultimately reducing the value of the research and affecting the prospects for clinical application. Therefore, identifying and avoiding these pitfalls is a crucial task before implementing the research. However, there is currently a lack of a comprehensive summary on this topic. This viewpoint aims to analyze the existing problems in terms of data quality, data set characteristics, model design, and statistical methods, as well as clinical implications, and provide possible solutions to these problems, such as gathering objective data, improving training, repeating measurements, increasing sample size, preventing overfitting using statistical methods, using specific AI algorithms to address targeted issues, standardizing outcomes and evaluation criteria, and enhancing fairness and replicability, with the goal of offering reference and assistance to researchers, algorithm developers, policy makers, and clinical practitioners.

Prevalence and relevant factors of nocturia and its impact on sleep quality in Chinese university students.

The purpose of this study was to investigate the prevalence and relevant factors of nocturia and its impact on sleep quality in university students in Mainland China. A large-scale survey was conducted on 14,000 university students from 3 universities in Henan province, China by using an anonymous questionnaire. The questionnaire collected the information from the past six months. The relationships between the prevalence of nocturia and its relevant factors were evaluated. A total of 13,874 questionnaires were collected and 13,104 qualified for statistical analysis. A total of 659 students suffered from clinically relevant nocturia (CRN) (4.56% in male and 5.34% in female). Both univariate analysis and the logistic stepwise regression model showed that the prevalence of nocturia was significantly related to female, history of enuresis, ease of waking up, urgency, frequency and RUTI (P < 0.05). The sleep quality and the university entrance score of CRN group was significantly lower than that of control group (P < 0.05). Nocturia was common in Chinese university students and showed a negative impact on sleep and academic performance. Gender of female, history of enuresis, ease of waking up, urgency, frequency and RUTI were relevant factors for CRN.

Directly targeting BAX for drug discovery: Therapeutic opportunities and challenges.

For over two decades, the development of B-cell lymphoma-2 (Bcl-2) family therapeutics has primarily focused on anti-apoptotic proteins, resulting in the first-in-class drugs called BH3 mimetics, especially for Bcl-2 inhibitor Venetoclax. The pro-apoptotic protein Bcl-2-associated X protein (BAX) plays a crucial role as the executioner protein of the mitochondrial regulated cell death, contributing to organismal development, tissue homeostasis, and immunity. The dysregulation of BAX is closely associated with the onset and progression of diseases characterized by pathologic cell survival or death, such as cancer, neurodegeneration, and heart failure. In addition to conducting thorough investigations into the physiological modulation of BAX, research on the regulatory mechanisms of small molecules identified through biochemical screening approaches has prompted the identification of functional and potentially druggable binding sites on BAX, as well as diverse all-molecule BAX modulators. This review presents recent advancements in elucidating the physiological and pharmacological modulation of BAX and in identifying potentially druggable binding sites on BAX. Furthermore, it highlights the structural and mechanistic insights into small-molecule modulators targeting diverse binding surfaces or conformations of BAX, offering a promising avenue for developing next-generation apoptosis modulators to treat a wide range of diseases associated with dysregulated cell death by directly targeting BAX.

Multimodal Sensing for Depression Risk Detection: Integrating Audio, Video, and Text Data.

Depression is a major psychological disorder with a growing impact worldwide. Traditional methods for detecting the risk of depression, predominantly reliant on psychiatric evaluations and self-assessment questionnaires, are often criticized for their inefficiency and lack of objectivity. Advancements in deep learning have paved the way for innovations in depression risk detection methods that fuse multimodal data. This paper introduces a novel framework, the Audio, Video, and Text Fusion-Three Branch Network (AVTF-TBN), designed to amalgamate auditory, visual, and textual cues for a comprehensive analysis of depression risk. Our approach encompasses three dedicated branches-Audio Branch, Video Branch, and Text Branch-each responsible for extracting salient features from the corresponding modality. These features are subsequently fused through a multimodal fusion (MMF) module, yielding a robust feature vector that feeds into a predictive modeling layer. To further our research, we devised an emotion elicitation paradigm based on two distinct tasks-reading and interviewing-implemented to gather a rich, sensor-based depression risk detection dataset. The sensory equipment, such as cameras, captures subtle facial expressions and vocal characteristics essential for our analysis. The research thoroughly investigates the data generated by varying emotional stimuli and evaluates the contribution of different tasks to emotion evocation. During the experiment, the AVTF-TBN model has the best performance when the data from the two tasks are simultaneously used for detection, where the F1 Score is 0.78, Precision is 0.76, and Recall is 0.81. Our experimental results confirm the validity of the paradigm and demonstrate the efficacy of the AVTF-TBN model in detecting depression risk, showcasing the crucial role of sensor-based data in mental health detection.

Glutaryl-CoA dehydrogenase suppresses tumor progression and shapes an anti-tumor microenvironment in hepatocellular carcinoma.

BACKGROUND & AIMS: Crotonylation, a crotonyl-CoA-based non-enzymatic protein translational modification, affects diverse biological processes, such as spermatogenesis, tissue injury, inflammation, and neuropsychiatric diseases. Crotonylation is decreased in hepatocellular carcinomas (HCCs), but the mechanism remains unknown. In this study, we aim to describe the role of glutaryl-CoA dehydrogenase (GCDH) in tumor suppression. METHODS: Three cohorts containing 40, 248 and 17 pairs of samples were used to evaluate the link between GCDH expression levels and clinical characteristics of HCC, as well as responses to anti-programmed cell death protein 1 (PD-1) treatment. Subcutaneous xenograft, orthotopic xenograft, Trp53Δhep/Δhep; MYC- and Ctnnboe;METoe-driven mouse models were adopted to validate the effects of GCDH on HCC suppression. RESULTS: GCDH depletion promoted HCC growth and metastasis, whereas its overexpression reversed these processes. As GCDH converts glutaryl-CoA to crotonyl-CoA to increase crotonylation levels, we performed lysine crotonylome analysis and identified the pentose phosphate pathway (PPP) and glycolysis-related proteins PGD, TKT, and ALDOC as GCDH-induced crotonylation targets. Crotonyl-bound targets showed allosteric effects that controlled their enzymatic activities, leading to decreases in ribose 5-phosphate and lactate production, further limiting the Warburg effect. PPP blockade also stimulated peroxidation, synergizing with senescent modulators to induce senescence in GCDHhigh cells. These cells induced the infiltration of immune cells by the SASP (senescence-associated secretory cell phenotype) to shape an anti-tumor immune microenvironment. Meanwhile, the GCDHlow population was sensitized to anti-PD-1 therapy. CONCLUSION: GCDH inhibits HCC progression via crotonylation-induced suppression of the PPP and glycolysis, resulting in HCC cell senescence. The senescent cell further shapes an anti-tumor microenvironment via the SASP. The GCDHlow population is responsive to anti-PD-1 therapy because of the increased presence of PD-1+CD8+ T cells. IMPACT AND IMPLICATIONS: Glutaryl-CoA dehydrogenase (GCDH) is a favorable prognostic indicator in liver, lung, and renal cancers. In addition, most GCDH depletion-induced toxic metabolites originate from the liver, accumulate locally, and cannot cross the blood-brain barrier. Herein, we show that GCDH inhibits hepatocellular carcinoma (HCC) progression via crotonylation-induced suppression of the pentose phosphate pathway and glycolysis, resulting in HCC cell senescence. We also found that more PD-1+CD8+ T cells are present in the GCDHlow population, who are thus more responsive to anti-PD-1 therapy. Given that the GCDHlow and GCDHhigh HCC population can be distinguished based on serum glucose and ammonia levels, it will be worthwhile to evaluate the curative effects of pro-senescent and immune-therapeutic strategies based on the expression levels of GCDH.

Discovery and Optimization of Tetrahydroisoquinoline Derivatives To Enhance Lysosome Biogenesis as Preclinical Candidates for the Treatment of Alzheimer's Disease.

More than 55 million individuals are suffering from Alzheimer's disease (AD), while the effective therapeutic strategies remain elusive. Our previous study identified a lysosome-enhancing lead compound LH2-051 with a tetrahydroisoquinoline scaffold through a novel dopamine transporter-cyclin-dependent kinase 9-transcription factor EB (DAT-CDK9-TFEB) regulation mechanism to promote TFEB activation and lysosome biogenesis. Here, we launched a comprehensive structure-activity relationship study for LH2-051, and 47 new derivatives were designed and synthesized, in which several compounds exhibited remarkable lysosome-enhancing activities. Notably, compounds 37 and 45 exhibited more favorable TFEB activation and lysosome biogenesis capabilities, good safety profiles, and excellent pharmacokinetic profiles with high brain penetration. Further investigations demonstrated that both compounds significantly enhance the clearance of Aß aggregates and ameliorate the impairment of learning, memory, and cognition in APP/PS1 mice. Overall, these results indicated that compounds 37 and 45 are promising preclinical drug candidates for the treatment of AD.

Rh-Catalyzed α-Arylation of Cyclic 1,3-Dicarbonyls with Benzocyclobutenols Enabled by a Cyclic Iodonium Ylide Strategy.

To date, the general and catalytic α-arylation of cyclic 1,3-dicarbonyls remains elusive. We now report the first Rh-catalyzed α-arylation of cyclic 1,3-dicarbonyls with benzocyclobutenols through a cyclic iodonium ylide strategy. Our strategy represents a good solution for the previously challenging α-arylation of cyclic 1,3-dicarbonyls with sterically demanding aryl partners, which is especially appropriate for structurally unique heteroaromatic 1,3-dicarbonyls. Our approach features mild conditions, readily available starting materials, high yields, excellent functional group-tolerance, and simple operation, providing expedient access toward medically important 2-aryl (hetero)cyclic 1,3-dicarbonyls. The practicality of this approach is demonstrated by the gram-scale synthesis, one-pot synthesis, and numerous downstream transformations.

Donor-acceptor type triphenylamine-based porous aromatic frameworks (TPA-PAFs) for photosynthesis of benzimidazoles.

The development of efficient and recyclable photocatalysts for organic synthesis is of great interest. This study presents the synthesis of triphenylamine-based porous aromatic frameworks (TPA-PAFs) in an alternating donor-acceptor (D-A) manner. The light absorption range and the optical band gaps of TPA-PAFs are effectively tuned by changing the electron acceptor units, which further determine their photocatalytic properties. As a result, TPA-PAFs exhibit excellent catalytic performance for the photosynthesis of benzimidazoles in high yields (up to 99%), broad substrate scope (18 examples), and good recyclability (up to 10 cycles). This work provides a feasible approach toward the facile design and synthesis of efficient and stable PAF-based photocatalysts, which further broadens the application of PAFs catalytic materials in photocatalytic organic synthesis.

Structural insights into the cross-exon to cross-intron spliceosome switch.

Early spliceosome assembly can occur through an intron-defined pathway, whereby U1 and U2 small nuclear ribonucleoprotein particles (snRNPs) assemble across the intron1. Alternatively, it can occur through an exon-defined pathway2-5, whereby U2 binds the branch site located upstream of the defined exon and U1 snRNP interacts with the 5' splice site located directly downstream of it. The U4/U6.U5 tri-snRNP subsequently binds to produce a cross-intron (CI) or cross-exon (CE) pre-B complex, which is then converted to the spliceosomal B complex6,7. Exon definition promotes the splicing of upstream introns2,8,9 and plays a key part in alternative splicing regulation10-16. However, the three-dimensional structure of exon-defined spliceosomal complexes and the molecular mechanism of the conversion from a CE-organized to a CI-organized spliceosome, a pre-requisite for splicing catalysis, remain poorly understood. Here cryo-electron microscopy analyses of human CE pre-B complex and B-like complexes reveal extensive structural similarities with their CI counterparts. The results indicate that the CE and CI spliceosome assembly pathways converge already at the pre-B stage. Add-back experiments using purified CE pre-B complexes, coupled with cryo-electron microscopy, elucidate the order of the extensive remodelling events that accompany the formation of B complexes and B-like complexes. The molecular triggers and roles of B-specific proteins in these rearrangements are also identified. We show that CE pre-B complexes can productively bind in trans to a U1 snRNP-bound 5' splice site. Together, our studies provide new mechanistic insights into the CE to CI switch during spliceosome assembly and its effect on pre-mRNA splice site pairing at this stage.

Impact of removing ESBL status labelling from culture reports on the use of carbapenems for non-bacteraemic patients diagnosed with ESBL-positive urinary tract infections.

OBJECTIVES: To evaluate carbapenem prescribing rates for initial definitive treatment of urinary tract infections and clinical outcomes before and after removing ESBL status labels on antibiotic susceptibility reports. METHODS: This was a retrospective cohort study of adult patients treated for at least 48 h for an ESBL-producing/ceftriaxone-resistant Enterobacterales urinary tract infection. ESBL status reporting ceased in September 2022 for a network of seven community hospitals within the USA. The primary endpoint was the rate of carbapenem prescribing for initial definitive treatment of urinary tract infections. Secondary endpoints included total days of therapy for initial definitive treatment with carbapenems, clinical cure rates, time to transition to oral antibiotic therapy for initial definitive treatment, rate of guideline-compliant therapy, rate of relapsed infection within 30 days, 30 day readmission rate, and 30 day all-cause in-hospital mortality. RESULTS: Of 3055 patients screened, 199 were included in the pre group and 153 were included in the post group. The rate of carbapenem prescribing for initial definitive treatment was 156 patients (78%) in the pre group, compared with 93 patients (61%) in the post group (P = <0.01). Days of therapy for initial definitive therapy with carbapenem was 620 in the pre group compared with 372 in the post group (P < 0.01). There was no difference between other secondary outcomes. CONCLUSIONS: Removing ESBL status labels from laboratory reports reduced carbapenem use for initial definitive treatment of urinary tract infections from 78% to 61% (P < 0.01) without impacting clinical outcomes.