Tripartite Motif-Containing Protein 65 (TRIM65) Inhibits Hepatitis B Virus Transcription.

Tripartite motif (TRIM) proteins, comprising a family of over 100 members with conserved motifs, exhibit diverse biological functions. Several TRIM proteins influence viral infections through direct antiviral mechanisms or by regulating host antiviral innate immune responses. To identify TRIM proteins modulating hepatitis B virus (HBV) replication, we assessed 45 human TRIMs in HBV-transfected HepG2 cells. Our study revealed that ectopic expression of 12 TRIM proteins significantly reduced HBV RNA and subsequent capsid-associated DNA levels. Notably, TRIM65 uniquely downregulated viral pregenomic (pg) RNA in an HBV-promoter-specific manner, suggesting a targeted antiviral effect. Mechanistically, TRIM65 inhibited HBV replication primarily at the transcriptional level via its E3 ubiquitin ligase activity and intact B-box domain. Though HNF4α emerged as a potential TRIM65 substrate, disrupting its binding site on the HBV genome did not completely abolish TRIM65's antiviral effect. In addition, neither HBx expression nor cellular MAVS signaling was essential to TRIM65-mediated regulation of HBV transcription. Furthermore, CRISPR-mediated knock-out of TRIM65 in the HepG2-NTCP cells boosted HBV infection, validating its endogenous role. These findings underscore TRIM proteins' capacity to inhibit HBV transcription and highlight TRIM65's pivotal role in this process.

CD44v5 domain regulates crosstalk between TNBC cells and tumor-associated macrophages by enhancing the IL-4R/STAT3 axis.

Triple-negative breast cancer (TNBC) has greater infiltration of M2-like macrophages (TAMs), which enhances cancer cell invasion and leads to a poor prognosis. TNBC progression is mediated by both tumor cells and the tumor microenvironment (TME). Here we elucidate the mechanism of the interaction between TNBC cells and TAMs. In this study, we confirmed that CD44v5 is highly expressed in TNBC, which drives TNBC cell metastasis and promotes TAM polarization by co-localizing with IL4Rα and inhibiting its internalization and degradation, thereby promoting activation of the STAT3/IL6 signaling axis. At the same time, TAMs also facilitate TNBC cell metastasis by secreting IL-4, IL-6, and other cytokines, in which the IL-4/IL-4R/STAT3/IL-6 signaling axis plays the same role for TNBC cells responding to TAMs. Moreover, we found that the above progress could be suppressed when the CD44v5 domain was blocked. We demonstrated that the CD44v5/IL-4R/STAT3/IL-6 signaling pathway plays a key role in TNBC cell metastasis, and in TNBC cells inducing TAM polarization and responding to TAMs, promoting metastasis. Collectively, we suggest that the CD44v5 domain may be a promising target for regulating the TME of TNBC as well as treating TNBC.

Lattice Oxygen Activation through Deep Oxidation of Co4N by Jahn-Teller-Active Dopants for Improved Electrocatalytic Oxygen Evolution.

Triggering the lattice oxygen oxidation mechanism is crucial for improving oxygen evolution reaction (OER) performance, because it could bypass the scaling relation limitation associated with the conventional adsorbate evolution mechanism through the direct formation of oxygen-oxygen bond. High-valence transition metal sites are favorable for activating the lattice oxygen, but the deep oxidation of pre-catalysts suffers from a high thermodynamic barrier. Here, taking advantage of the Jahn-Teller (J-T) distortion induced structural instability, we incorporate high-spin Mn3+ ( t 2 g 3 e g 1 ${{t}_{2g}^{3}{e}_{g}^{1}}$ ) dopant into Co4N. Mn dopants enable a surface structural transformation from Co4N to CoOOH, and finally to CoO2, as observed by various in situ spectroscopic investigations. Furthermore, the reconstructed surface on Mn-doped Co4N triggers the lattice oxygen activation, as evidenced experimentally by pH-dependent OER, tetramethylammonium cation adsorption and online electrochemical mass spectrometry measurements of 18O-labelled catalysts. In general, this work not only offers the introducing J-T effect approach to regulate the structural transition, but also provides an understanding about the influence of the catalyst's electronic configuration on determining the reaction route, which may inspire the design of more efficient catalysts with activated lattice oxygen.

In situ copper faceting enables efficient CO2/CO electrolysis.

The copper (Cu)-catalyzed electrochemical CO2 reduction provides a route for the synthesis of multicarbon (C2+) products. However, the thermodynamically favorable Cu surface (i.e. Cu(111)) energetically favors single-carbon production, leading to low energy efficiency and low production rates for C2+ products. Here we introduce in situ copper faceting from electrochemical reduction to enable preferential exposure of Cu(100) facets. During the precatalyst evolution, a phosphate ligand slows the reduction of Cu and assists the generation and co-adsorption of CO and hydroxide ions, steering the surface reconstruction to Cu (100). The resulting Cu catalyst enables current densities of > 500 mA cm-2 and Faradaic efficiencies of >83% towards C2+ products from both CO2 reduction and CO reduction. When run at 500 mA cm-2 for 150 hours, the catalyst maintains a 37% full-cell energy efficiency and a 95% single-pass carbon efficiency throughout.

The knowledge and attitude on the prevention of pressure ulcers in Chinese nurses: A cross-sectional study in 93 tertiary and secondary hospitals.

Although pressure ulcers are related to substantial health burdens, they may be preventable. Since nurses play a fundamental role in pressure ulcer prevention, their knowledge and attitude are of great importance. This study aims to investigate the current situation and associated factors of nurses' knowledge and attitude on the prevention of pressure ulcers from both tertiary and secondary hospitals. A total of 11 347 nurses were recruited including 7108 nurses (62.6%) from tertiary hospitals and 4239 nurses (37.4%) from secondary hospitals. The median (interquartile range) of the pressure ulcer knowledge score was 51% (38%, 90%) for all the participants with the lowest scores on prevention of pressure ulcers (51.33%). The mean (standard deviation) of attitude towards pressure ulcer prevention was 39.64 (4.65) with the lowest scores on personal competency to prevent pressure ulcers (mean 3.09). The results of multivariate linear regression showed that hospital level, nurses' age, years of work experience, initial education level at work and time of last training significantly associated with nurses' knowledge of pressure ulcer prevention. Meanwhile, hospital level, job title, previous training, time of last training and subjective needs for further training had significant association with nurses' attitude towards pressure ulcer prevention (all p < 0.05). Results showed inadequate knowledge but relative positive attitudes in nurses indicating the importance to deliver continuing education and training regarding pressure ulcer prevention in practice to improve the quality of care.

Entropy engineering of La-based perovskite for simultaneous photocatalytic CO2 reduction and biomass oxidation.

Herein, the high-entropy perovskite, i.e. La(FeCoNiCrMn)O3, was prepared for simultaneous CO2 reduction and biomass upgrading. Based on the synergistic effect between the elements in the high-entropy material, an excellent CO evolution rate of 131.8 µmol g-1 h-1 and a xylonic acid yield of 63.9% were gained.

Urinary mitochondrial DNA may be useful in diagnosing early diabetic nephropathy.

The present study aimed to determine whether urinary mitochondrial (mt)DNA could be combined as a non-invasive biomarker with other clinical findings of kidney injury to help diagnose early diabetic nephropathy (DN). A total of 165 patients with type 2 diabetes mellitus (T2DM) were enrolled in the present study and the mtDNA levels in urine were measured using quantitative PCR. The diagnostic value of urinary mtDNA levels in patients with T2DM was compared using estimated glomerular filtration rate (eGFR) or albumin-to-creatinine ratio staging. Spearman correlation analysis was used to analyze the correlation between urinary mtDNA and other clinical findings. Correlation factors for early DN were assessed using univariate logistic regression analysis. Urinary leukocyte and glucose levels do not interfere with urinary mtDNA levels. In patients with T2DM, the level of urinary mtDNA increases in the early stages of kidney injury and further increases with the severity of kidney injury. Urinary mtDNA levels in patients with eGFR 60-90 ml/min/1.73 m2 were higher than that in patients with eGFR >90 ml/min/1.73 m2. The levels of urinary mt89DNA and mt349DNA were negatively correlated with the eGFR level (ρ=-0.437; P<0.001; ρ=-0.390; P<0.001) and positively correlated with the level of cystatin C (ρ=0.177; P=0.025; ρ=0.144; P=0.070). Urinary mtDNA is positively correlated with early DN occurrence [odds ratio (OR), 1.330; 95% confidence interval (CI), 1.175-1.507; P<0.001; OR, 1.328; 95% CI, 1.156-1.525; P<0.001]. In conclusion, urinary mtDNA combined with other clinical indicators of kidney injury may help the diagnosis of early DN.

Conditional replication and secretion of hepatitis B virus genome uncover the truncated 3' terminus of encapsidated viral pregenomic RNA.

IMPORTANCE: The biogenesis and clinical application of serum HBV pgRNA have been a research hotspot in recent years. This study further characterized the heterogeneity of the 3' terminus of capsid RNA by utilizing a variety of experimental systems conditionally supporting HBV genome replication and secretion, and reveal that the 3' truncation of capsid pgRNA is catalyzed by cellular ribonuclease(s) and viral RNaseH at positions after and before 3' DR1, respectively, indicating the 3' DR1 as a boundary between the encapsidated portion of pgRNA for reverse transcription and the 3' unprotected terminus, which is independent of pgRNA length and the 3' terminal sequence. Thus, our study provides new insights into the mechanism of pgRNA encapsidation and reverse transcription, as well as the optimization of serum HBV RNA diagnostics.

Persistent neuroinflammation of the right insular cortex in children with juvenile idiopathic arthritis: a proton MRS study.

OBJECTIVE: The aim of this study of children with juvenile idiopathic arthritis (JIA) was to use proton magnetic resonance spectroscopy (1H-MRS) to compare the levels of five neurometabolites in the right and left insular cortexes of subjects in three groups: JIA-active, JIA-inactive, and healthy controls (HCs). METHODS: Two inflammation markers and five psychometric scores were determined. 1H-MRS was used to measure the levels of total N-acetylaspartate (NAA), total choline (Cho), myo-inositol (mI), and glutamate (Glu), and the complex of glutamine and glutamate (Glx) relative to total creatine (tCr) in the right and left insular cortexes of participants. RESULTS: Intra-group comparisons indicated that each group had higher levels of NAA/tCr, Glu/tCr, Glx/tCr, and mI/tCr in the right insula, and higher levels of Cho/tCr in the left insula. Inter-group comparisons of the right insula indicated that the JIA-active and JIA-inactive groups had higher levels of Cho/tCr than the HC group, but none of the other inter-group differences were statistically significant. The score of the Sleep Disturbance Scale for Children (SDCD) had an inverse correlation with the level of Cho/tCr in the right insular cortex of patients in the JIA-inactive group. CONCLUSIONS: Relative to the HC group, the right insular cortex of subjects in the JIA-active and the JIA-inactive groups had greater levels of Cho/tCr, suggesting increased inflammation in this region. The Cho/tCr level in the right insular cortex had an inverse correlation with SDCD score in the JIA-inactive group. Key Points • Healthy controls and JIA patients had higher levels of tNAA/tCr, Glu/tCr, Glx/tCr, and mI/tCr in the right insula, and higher levels of Cho/tCr in the left insula. • A greater level of Cho/tCr in the right insula of JIA-active and JIA-inactive patients indicated neuroinflammation in this region. • The Cho/tCr level in the right insular cortex had an inverse correlation with SDCD score in the JIA-inactive group.

Doping Shortens the Metal/Metal Distance and Promotes OH Coverage in Non-Noble Acidic Oxygen Evolution Reaction Catalysts.

Acidic water electrolysis enables the production of hydrogen for use as a chemical and as a fuel. The acidic environment hinders water electrolysis on non-noble catalysts, a result of the sluggish kinetics associated with the adsorbate evolution mechanism, reliant as it is on four concerted proton-electron transfer steps. Enabling a faster mechanism with non-noble catalysts will help to further advance acidic water electrolysis. Here, we report evidence that doping Ba cations into a Co3O4 framework to form Co3-xBaxO4 promotes the oxide path mechanism and simultaneously improves activity in acidic electrolytes. Co3-xBaxO4 catalysts reported herein exhibit an overpotential of 278 mV at 10 mA/cm2 in 0.5 M H2SO4 electrolyte and are stable over 110 h of continuous water oxidation operation. We find that the incorporation of Ba cations shortens the Co-Co distance and promotes OH adsorption, findings we link to improved water oxidation in acidic electrolyte.

A Survey of Therapeutic Drug Monitoring Status in China.

OBJECTIVE: To understand the status of therapeutic drug monitoring (TDM) in China Mainland, and thus lay down the foundation for further improvement in TDM. METHODS: In the present study, a nationwide questionnaire survey was conducted, which was distributed and collected using a mobile-based application. Clinicians, pharmacists, and clinical laboratory physicians belonging to different levels of public hospitals were involved as subjects/objects. The contents of the survey included TDM implementation in their hospital and information regarding their opinions and suggestions on TDM work. Mann-Whitney test was used to compare the difference between top tertiary hospitals and non-top tertiary hospitals. RESULTS: A total of 475 questionnaires were collected, 383 from top tertiary hospitals (3A hospitals) and 92 from non-top tertiary hospitals (other than 3A hospitals). A total of 240 clinicians, TDM pharmacists, and clinical laboratory physicians were involved, with an effective rate of 50.5%. Top tertiary hospitals were associated with certain advantages, such as the number of TDM testing facilities, annual sample size, number of monitoring varieties, and interpretation rate of monitoring reports, compared with non-top tertiary hospitals. In particular, ß-lactamase inhibitor, olanzapine, carbamazepine, and glucocorticoids seemed to be the main projects that clinicians wanted to assess. The drugs for which TDM was commonly performed included vancomycin, valproic acid, carbamazepine, phenytoin sodium, and methotrexate. The most commonly used detection methods include high-performance liquid chromatography, immunization, 2D-LC, and LC-MS. The monitoring concentration range was found to be inconsistent for most of the drugs. Currently, no unified regulation exists for TDM charges in China, which is no more than ¥200 in general. Clinicians rely on pharmacists for professional guidance. Importantly, improvement in the interpretation of monitoring reports, proficiency testing, and cooperation with clinical departments may aid in improving the level of TDM service. CONCLUSIONS: This survey objectively reflected the current status of TDM work in hospitals in China, and provided a strong reference base for devising strategies for improvement and effective execution of TDM work.

Strong-Proton-Adsorption Co-Based Electrocatalysts Achieve Active and Stable Neutral Seawater Splitting.

Direct electrolysis of pH-neutral seawater to generate hydrogen is an attractive approach for storing renewable energy. However, due to the anodic competition between the chlorine evolution and the oxygen evolution reaction (OER), direct seawater splitting suffers from a low current density and limited operating stability. Exploration of catalysts enabling an OER overpotential below the hypochlorite formation overpotential (≈490 mV) is critical to suppress the chloride evolution and facilitate seawater splitting. Here, a proton-adsorption-promoting strategy to increase the OER rate is reported, resulting in a promoted and more stable neutral seawater splitting. The best catalysts herein are strong-proton-adsorption (SPA) materials such as palladium-doped cobalt oxide (Co3- x Pdx O4 ) catalysts. These achieve an OER overpotential of 370 mV at 10 mA cm-2 in pH-neutral simulated seawater, outperforming Co3 O4 by a margin of 70 mV. Co3- x Pdx O4 catalysts provide stable catalytic performance for 450 h at 200 mA cm-2 and 20 h at 1 A cm-2 in neutral seawater. Experimental studies and theoretical calculations suggest that the incorporation of SPA cations accelerates the rate-determining water dissociation step in neutral OER pathway, and control studies rule out the provision of additional OER sites as a main factor herein.

The Chinese version of the skin tear knowledge assessment instrument (OASES): Cultural adaptation and validation.

BACKGROUND: Skin tear knowledge is an important predictor of the decreased incidence and management of skin tears, and the knowledge level among Chinese nurses is unknown so far. A validated instrument for measuring skin tear knowledge is urgent. OBJECTIVE: To culturally adapt the skin tear knowledge assessment instrument (OASES) into Chinese and verify its validity and reliability in the Chinese context. METHODS: The cultural adaptation process for OASES into Chinese was established on Beaton's translation model. Content validity was determined by the 8-expert group in wound care. A nationwide psychometric validation study was performed on a convenience sample of 3333 nurses from 113 tertiary hospitals, of whom 98 nurses finished the test-retest procedure for reliability analysis. Item validity (item difficulty and discriminating index) and construct validity (known-groups technique) were tested. RESULTS: The content validity index was 0.88-1.00. The item validity was as follows: Item difficulty ranged from 0.16 to 0.86, with an average value of 0.52; the discriminating index varied between 0.05 and 0.61. The known-group technique demonstrated excellent construct validity with a significant difference between predefined groups with theoretically expected higher knowledge scores and theoretically expected lower knowledge scores (P < 0.001). For the test-retest reliability, the Intraclass correction coefficient (ICC) during a 14-day interval for the overall tool was 0.79 (95% CI = 0.71-0.86), and Cohen's kappa value for each item varied from 0.17 to 0.62. CONCLUSIONS: The Chinese version of OASES was validated to be suitable for skin tear knowledge assessment with acceptable psychometric properties, through which the knowledge and training priorities of skin tear among Chinese nurses can be quantified.

Strain in Copper/Ceria Heterostructure Promotes Electrosynthesis of Multicarbon Products.

Elastic strains in metallic catalysts induce enhanced selectivity for carbon dioxide reduction (CO2R) toward valuable multicarbon (C2+) products. However, under working conditions, the structure of catalysts inevitably undergoes reconstruction, hardly retaining the initial strain. Herein, we present a metal/metal oxide synthetic strategy to introduce and maintain the tensile strain in a copper/ceria heterostructure, enabled by the presence of a thin interface layer of Cu2O/CeO2. The tensile strain in the copper domain and deficient electron environment around interfacial Cu sites resulted in strengthened adsorption of carbonaceous intermediates and promoted *CO dimerization. The strain effect in the copper/ceria heterostructure leads to an improved C2+ selectivity with a maximum Faradaic efficiency of 76.4% and a half-cell power conversion efficiency of 49.1%. The fundamental insights gained from this system can facilitate the rational design of heterostructure catalysts for CO2R.

Tension-free hiatal hernia repair with biological mesh: A real-world experience.

Laparoscopic Nissen fundoplication and esophagoplasty are the standards for gastroesophageal reflux disease (GERD) and hiatal hernia (HH) repair. Biologically derived mesh is also associated with reduced recurrence. This study attempted to evaluate the effectiveness of a biological mesh in the 4K laparoscopic repair of HH. This retrospective study reviewed patients with a severe GERD complicated with HH from August 2019 to August 2020. All patients underwent the HH repair using a biological mesh under a 4K laparoscope accompanying Nissen fundoplication. Up to 16 months postoperatively, GERD-health-related quality-of-life (GERD-HRQL) scale, radiologic studies on HH recurrence, and symptoms were recorded. The mean surgical time and postoperative hospital stay were 70.9 ±â€…8.72 min, 4.8 ±â€…0.76 days, respectively. The postoperative symptom relief rate was 96.5%, and no recurrence exhibited during follow-up. Dysphagia occurred in 10 (9.43%) patients. There were no intraoperative vagus nerve injury or postoperative complications, mesh infection, and reoperation for mesh. The tension-free repair of HH with the biological mesh is an option for clinical use, with effectiveness and few short-term complications being reported.

Developments of Conventional and Microfluidic Flow Cytometry Enabling High-Throughput Characterization of Single Cells.

This article first reviews scientific meanings of single-cell analysis by highlighting two key scientific problems: landscape reconstruction of cellular identities during dynamic immune processes and mechanisms of tumor origin and evolution. Secondly, the article reviews clinical demands of single-cell analysis, which are complete blood counting enabled by optoelectronic flow cytometry and diagnosis of hematologic malignancies enabled by multicolor fluorescent flow cytometry. Then, this article focuses on the developments of optoelectronic flow cytometry for the complete blood counting by comparing conventional counterparts of hematology analyzers (e.g., DxH 900 of Beckman Coulter, XN-1000 of Sysmex, ADVIA 2120i of Siemens, and CELL-DYN Ruby of Abbott) and microfluidic counterparts (e.g., microfluidic impedance and imaging flow cytometry). Future directions of optoelectronic flow cytometry are indicated where intrinsic rather than dependent biophysical parameters of blood cells must be measured, and they can replace blood smears as the gold standard of blood analysis in the near future.

Mechanistic Insights into OC-COH Coupling in CO2 Electroreduction on Fragmented Copper.

The carbon-carbon (C-C) bond formation is essential for the electroconversion of CO2 into high-energy-density C2+ products, and the precise coupling pathways remain controversial. Although recent computational investigations have proposed that the OC-COH coupling pathway is more favorable in specific reaction conditions than the well-known CO dimerization pathway, the experimental evidence is still lacking, partly due to the separated catalyst design and mechanistic/spectroscopic exploration. Here, we employ density functional theory calculations to show that on low-coordinated copper sites, the *CO bindings are strengthened, and the adsorbed *CO coupling with their hydrogenation species, *COH, receives precedence over CO dimerization. Experimentally, we construct a fragmented Cu catalyst with abundant low-coordinated sites, exhibiting a 77.8% Faradaic efficiency for C2+ products at 300 mA cm-2. With a suite of in situ spectroscopic studies, we capture an *OCCOH intermediate on the fragmented Cu surfaces, providing direct evidence to support the OC-COH coupling pathway. The mechanistic insights of this research elucidate how to design materials in favor of OC-COH coupling toward efficient C2+ production from CO2 reduction.

Evidence of persistent glial cell dysfunction in the anterior cingulate cortex of juvenile idiopathic arthritis children: a proton MRS study.

BACKGROUND: This study aims to investigate whether the neurometabolites of the anterior cingulate cortex (ACC) were distinct in patients with active and inactive juvenile idiopathic arthritis (JIA) using the proton magnetic resonance spectroscopy. METHODS: We measured the levels of total N-acetylaspartate (tNAA), choline (Cho), myo-inositol (ml), glutamate (Glu) and the complex of glutamate and glutamine (Glx) relative to total creatine (tCr) in ACC of each participant. RESULTS: Compared with the healthy controls, a significant decrease of total Cho/tCr and Glx/tCr ratio in ACC occurred in active and inactive JIA group. The tCho/Cr level was negatively associated with the serum level of ESR in active JIA patients. There was no difference in NAA/tCr ratio among the three groups, which may imply that no neuron and axonal losses occurred in either active or inactive JIA patients. CONCLUSIONS: The abnormal neurometabolites in tCho/tCr and Glx/tCr in ACC may indicate that persistent dysfunction of glial cell, while neither neuron nor axonal losses occurred in active and inactive JIA patients.

Novel Combined Enzymatic Approach to Analyze Nonsialylated N-Linked Glycans through MALDI Imaging Mass Spectrometry.

Alterations to N-glycan expression are relevant to the progression of various diseases, particularly cancer. In many cases, specific N-glycan structural features such as sialylation, fucosylation, and branching are of specific interest. A novel MALDI imaging mass spectrometry workflow has been recently developed to analyze these features of N-glycosylation through the utilization of endoglycosidase enzymes to cleave N-glycans from associated glycoproteins. Enzymes that have previously been utilized to cleave N-glycans include peptide-N-glycosidase F (PNGase F) to target N-glycans indiscriminately and endoglycosidase F3 (Endo F3) to target core fucosylated N-glycans. In addition to these endoglycosidases, additional N-glycan cleaving enzymes could be used to target specific structural features. Sialidases, also termed neuraminidases, are a family of enzymes that remove terminal sialic acids from glycoconjugates. This work aims to utilize sialidase, in conjunction with PNGase F/Endo F3, to enzymatically remove sialic acids from N-glycans in an effort to increase sensitivity for nonsialylated N-glycan MALDI-IMS peaks. Improving detection of nonsialylated N-glycans allows for a more thorough analysis of specific structural features such as fucosylation or branching, particularly of low abundant structures. Sialidase utilization in MALDI-IMS dramatically increases sensitivity and increases on-tissue endoglycosidase efficiency, making it a very useful companion technique to specifically detect nonsialylated N-glycans.

Whole-genome CRISPR screening identifies N-glycosylation as a genetic and therapeutic vulnerability in CALR-mutant MPNs.

Calreticulin (CALR) mutations are frequent, disease-initiating events in myeloproliferative neoplasms (MPNs). Although the biological mechanism by which CALR mutations cause MPNs has been elucidated, there currently are no clonally selective therapies for CALR-mutant MPNs. To identify unique genetic dependencies in CALR-mutant MPNs, we performed a whole-genome clustered regularly interspaced short palindromic repeats (CRISPR) knockout depletion screen in mutant CALR-transformed hematopoietic cells. We found that genes in the N-glycosylation pathway (among others) were differentially depleted in mutant CALR-transformed cells as compared with control cells. Using a focused pharmacological in vitro screen targeting unique vulnerabilities uncovered in the CRISPR screen, we found that chemical inhibition of N-glycosylation impaired the growth of mutant CALR-transformed cells, through a reduction in MPL cell surface expression. We treated Calr-mutant knockin mice with the N-glycosylation inhibitor 2-deoxy-glucose (2-DG) and found a preferential sensitivity of Calr-mutant cells to 2-DG as compared with wild-type cells and normalization of key MPNs disease features. To validate our findings in primary human cells, we performed megakaryocyte colony-forming unit (CFU-MK) assays. We found that N-glycosylation inhibition significantly reduced CFU-MK formation in patient-derived CALR-mutant bone marrow as compared with bone marrow derived from healthy donors. In aggregate, our findings advance the development of clonally selective treatments for CALR-mutant MPNs.