Exploring the Diagnostic and Prognostic Significance of Alkaline Phosphatase on Neutrophil Surface Membrane in Patients with Sepsis.

Background: Sepsis, characterized by life-threatening organ dysfunction, stems from an unregulated host response. Timely identification is pivotal for enhancing the prognosis of sepsis patients. Objective: This study aims to explore the diagnostic and prognostic values of alkaline phosphatase on the surface membrane of neutrophils (mNAP) in peripheral blood among sepsis patients. Design: The study employed a retrospective design. Setting: This study was conducted at Donghai County People's Hospital. Participants: A total of 180 sepsis patients were selected and categorized into the sepsis shock group (n=45) and the sepsis non-shock group (n=135). Additionally, 35 patients with non-infectious systemic inflammatory response syndrome served as the control group. Interventions: mNAP was assessed via flow cytometry, while serum procalcitonin (PCT) and C-reactive protein (CRP) levels were measured through immunoassay. Primary Outcome Measures: (1) Changes in mNAP, PCT, and CRP. (2) Correlation of mNAP with CRP and PCT in sepsis patients. (3) Diagnostic values of mNAP, PCT, and CRP in sepsis. Results: Statistically significant differences in mNAP, PCT, and CRP were observed between the sepsis shock group, the sepsis non-shock group, and the control group (P = .000). The median value of mNAP (22627 Ab/c) in the 28-day death group was significantly higher than that (5100 Ab/c) in the survival group (P = .000). Spearman rank correlation analysis indicated a positive correlation between mNAP, PCT, and CRP in sepsis patients (P < .01). Conclusions: Both mNAP and PCT exhibit superior diagnostic specificity and sensitivity compared to CRP. While mNAP demonstrates similar sensitivity to PCT in diagnosing sepsis, its diagnostic specificity surpasses that of PCT. mNAP holds promise as a novel marker for the diagnosis and prognosis of sepsis.

Establishment of reference intervals for plasma IL-2, IL-4, IL-5, and IL-17A in healthy adults from the Jiangsu region of eastern China using flow cytometry: A single-center study.

BACKGROUND: Cytokines are of utmost importance in both the physiological and pathological immune responses of the human body. This study utilized flow cytometry to measure the levels of plasma interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-17A (IL-17A) and established their reference intervals, aiming to provide data support for the diagnosis and treatment of clinical diseases. METHODS: According to the inclusion and exclusion criteria, a total of 728 reference individuals were included in this study from January 2023 to June 2023. The Kolmogorov-Smirnov test was used to analyse the distributions of plasma IL-2, IL-4, IL-5 and IL-17A. The reference intervals of plasma IL-2, IL-4, IL-5 and IL-17A were established by the unilateral percentile method (95th percentile) based on the guidelines of C28-A 3 and WS/T 402-2012. RESULTS: In this study, the levels of plasma IL-2, IL-4, IL-5 and IL-17A were nonnormally distributed. The concentrations of plasma IL-2, IL-4, IL-5 and IL-17A in healthy adults were not significantly different by sex or age (all P > 0.05). Therefore, all the reference individuals were combined into one group, and the reference intervals of plasma IL-2, IL-4, IL-5 and IL-17 were established by flow cytometry (IL-2 ≤ 10.25 pg/mL, IL-4 ≤ 9.87 pg/mL, IL-5 ≤ 3.36 pg/mL and IL-17A ≤ 9.46 pg/mL). CONCLUSIONS: We first established the reference intervals of plasma IL-2, IL-4, IL-5 and IL-17A in healthy adults based on a single-center population in the Jiangsu region in eastern China, which will provide an important reference value for evaluating human immune status and the diagnosis and treatment of clinical diseases.

A mini review of reinfection with the SARS-CoV-2 Omicron variant.

Background: COVID-19 has caused severe morbidity and mortality worldwide. After the end of the dynamic zero-COVID policy in China in December, 2022, concerns regarding reinfection were raised while little was known due to the lack of surveillance data in this country. Aims: This study reviews the probability, risk factors, and severity of severe acute respiratory syndrome coronavirus 2 Omicron variant reinfection, as well as the interval between infections, risk of onward transmission by reinfected cases, and the role of booster vaccination against reinfection. Sources: References for this review were identified through searches of PubMed and Web of Science up to September 24, 2023. Results: The rate of reinfection ranges from 3.1% to 13.0%. Factors associated with a higher risk of reinfection include being female, having comorbidities, and being unvaccinated. Reinfection with the BA.4 or BA.5 variant occurs approximately 180 days after the initial infection. Reinfections are less clinically severe than primary infections, and there is evidence of lower transmissibility. The debate surrounding the effectiveness and feasibility of booster vaccinations in preventing reinfection continues. Conclusions: The reinfection rate during the Omicron epidemic is significantly higher than in previous epidemic periods. However, the symptoms and infectivity of reinfection were weaker than those of the prior infection. Medical staff and individuals at high risk of reinfection should be vigilant. The efficacy of booster vaccinations in reducing reinfection is currently under debate.

Identification of Mycobacterium tuberculosis Resistance to Common Antibiotics: An Overview of Current Methods and Techniques.

Multidrug-resistant tuberculosis (MDR-TB) is an essential cause of tuberculosis treatment failure and death of tuberculosis patients. The rapid and reliable profiling of Mycobacterium tuberculosis (MTB) drug resistance in the early stage is a critical research area for public health. Then, most traditional approaches for detecting MTB are time-consuming and costly, leading to the inappropriate therapeutic schedule resting on the ambiguous information of MTB drug resistance, increasing patient economic burden, morbidity, and mortality. Therefore, novel diagnosis methods are frequently required to meet the emerging challenges of MTB drug resistance distinguish. Considering the difficulty in treating MDR-TB, it is urgently required for the development of rapid and accurate methods in the identification of drug resistance profiles of MTB in clinical diagnosis. This review discussed recent advances in MTB drug resistance detection, focusing on developing emerging approaches and their applications in tangled clinical situations. In particular, a brief overview of antibiotic resistance to MTB was present, referred to as intrinsic bacterial resistance, consisting of cell wall barriers and efflux pumping action and acquired resistance caused by genetic mutations. Then, different drug susceptibility test (DST) methods were described, including phenotype DST, genotype DST and novel DST methods. The phenotype DST includes nitrate reductase assay, RocheTM solid ratio method, and liquid culture method and genotype DST includes fluorescent PCR, GeneXpert, PCR reverse dot hybridization, ddPCR, next-generation sequencing and gene chips. Then, novel DST methods were described, including metabolism testing, cell-free DNA probe, CRISPR assay, and spectral analysis technique. The limitations, challenges, and perspectives of different techniques for drug resistance are also discussed. These methods significantly improve the detection sensitivity and accuracy of multidrug-resistant tuberculosis (MRT) and can effectively curb the incidence of drug-resistant tuberculosis and accelerate the process of tuberculosis eradication.

Cytochrome P450 Mining for Bufadienolide Diversification.

Bufadienolides are a class of steroids with a distinctive α-pyrone ring at C17, mostly produced by toads and consisting of over 100 orthologues. They exhibit potent cardiotonic and antitumor activities and are active ingredients of the traditional Chinese medicine Chansu and Cinobufacini. Direct extraction from toads is costly, and chemical synthesis is difficult, limiting the accessibility of active bufadienolides with diverse modifications and trace content. In this work, based on the transcriptome and genome analyses, using a yeast-based screening platform, we obtained eight cytochrome P450 (CYP) enzymes from toads, which catalyze the hydroxylation of bufalin and resibufogenin at different sites. Moreover, a reported fungal CYP enzyme Sth10 was found functioning in the modification of bufalin and resibufogenin at multiple sites. A total of 15 bufadienolides were produced and structurally identified, of which six were first discovered. All of the compounds were effective in inhibiting the proliferation of tumor cells, especially 19-hydroxy-bufalin (2) and 1ß-hydroxy-bufalin (3), which were generated from bufalin hydroxylation catalyzed by CYP46A35. The catalytic efficiency of CYP46A35 was improved about six times and its substrate diversity was expanded to progesterone and testosterone, the common precursors for steroid drugs, achieving their efficient and site-specific hydroxylation. These findings elucidate the key modification process in the synthesis of bufadienolides by toads and provide an effective way for the synthesis of unavailable bufadienolides with site-specific modification and active potentials.

A three-level regulatory mechanism of the aldo-keto reductase subfamily AKR12D.

Modulation of protein function through allosteric regulation is central in biology, but biomacromolecular systems involving multiple subunits and ligands may exhibit complex regulatory mechanisms at different levels, which remain poorly understood. Here, we discover an aldo-keto reductase termed AKRtyl and present its three-level regulatory mechanism. Specifically, by combining steady-state and transient kinetics, X-ray crystallography and molecular dynamics simulation, we demonstrate that AKRtyl exhibits a positive synergy mediated by an unusual Monod-Wyman-Changeux (MWC) paradigm of allosteric regulation at low concentrations of the cofactor NADPH, but an inhibitory effect at high concentrations is observed. While the substrate tylosin binds at a remote allosteric site with positive cooperativity. We further reveal that these regulatory mechanisms are conserved in AKR12D subfamily, and that substrate cooperativity is common in AKRs across three kingdoms of life. This work provides an intriguing example for understanding complex allosteric regulatory networks.

The Impact of Sleep Quality on Cognitive Function in Patients with Chronic Subjective Tinnitus.

BACKGROUND: The aim of this study was to explore the impact of sleep quality on cognitive function in patients with chronic subjective tinnitus. METHODS: The Pittsburgh Sleep Quality Index (PSQI) and the Montreal Cognitive Assessment Scale (MoCA) were used to assess sleep quality and cognitive function in patients with chronic subjective tinnitus, sleep disorder patients (SD), and normal controls (NC). The tinnitus evaluation questionnaire (TEQ) and tinnitus loudness were used to assess the severity in patients with chronic subjective tinnitus. Tinnitus patients were divided into two groups based on PSQI results: "tinnitus with sleep disorder (TwSD)" and "tinnitus without sleep disorder (TnSD)." The MoCA scores in TwSD and TnSD groups were compared with those in SD and NC groups, and the correlation between PSQI, TEQ, tinnitus loudness, and MoCA scores in subjective tinnitus patients were analyzed. RESULTS: Whether TwSD group or TnSD group, the MoCA score was significantly lower than those in the NC group and SD group. Meanwhile, there was no significant difference between TwSD and TnSD groups in MoCA score, and PSQI, TEQ, and tinnitus loudness were not significantly correlated with MoCA. CONCLUSION: Subjective tinnitus may be an independent risk factor for cognitive impairment. The underlying neural mechanisms between subjective tinnitus, sleep disorders, and cognitive impairment need to be further explored and clarified.

Zwitterionic Tröger's Base Microfiltration Membrane Prepared via Vapor-Induced Phase Separation with Improved Demulsification and Antifouling Performance.

The fouling of separation membranes has consistently been a primary factor contributing to the decline in membrane performance. Enhancing the surface hydrophilicity of the membrane proves to be an effective strategy in mitigating membrane fouling in water treatment processes. Zwitterionic polymers (containing an equimolar number of homogeneously distributed anionic and cationic groups on the polymer chains) have been used extensively as one of the best antifouling materials for surface modification. The conventional application of zwitterionic compounds as surface modifiers is intricate and inefficient, adding complexity and length to the membrane preparation process, particularly on an industrial scale. To overcome these limitations, zwitterionic polymer, directly used as a main material, is an effective method. In this work, a novel zwitterionic polymer (TB)-zwitterionic Tröger's base (ZTB)-was synthesized by quaternizing Tröger's base (TB) with 1,3-propane sultone. The obtained ZTB is blended with TB to fabricate microfiltration (MF) membranes via the vapor-induced phase separation (VIPS) process, offering a strategic solution for separating emulsified oily wastewater. Atomic force microscopy (AFM), scanning electron microscopy (SEM), water contact angle, and zeta potential measurements were employed to characterize the surface of ZTB/TB blended membranes, assessing surface morphology, charge, and hydrophilic/hydrophobic properties. The impact of varying ZTB levels on membrane surface morphology, hydrophilicity, water flux, and rejection were investigated. The results showed that an increase in ZTB content improved hydrophilicity and surface roughness, consequently enhancing water permeability. Due to the attraction of water vapor, the enrichment of zwitterionic segments was enriched, and a stable hydration layer was formed on the membrane surface. The hydration layer formed by zwitterions endowed the membrane with good antifouling properties. The proposed mechanism elucidates the membrane's proficiency in demulsification and the reduction in irreversible fouling through the synergistic regulation of surface charge and hydrophilicity, facilitated by electrostatic repulsion and the formation of a hydration layer. The ZTB/TB blended membranes demonstrated superior efficiency in oil-water separation, achieving a maximum flux of 1897.63 LMH bar-1 and an oil rejection rate as high as 99% in the oil-water emulsion separation process. This study reveals the migration behavior of the zwitterionic polymer in the membrane during the VIPS process. It enhances our comprehension of the antifouling mechanism of zwitterionic membranes and provides guidance for designing novel materials for antifouling membranes.

Effect of microwave alone and microwave-assisted modification on the physicochemical properties of starch and its application in food.

Native starch has poor stability and usually requires modification to expand its industrial application range. Commonly used methods are physical, chemical, enzymatic and compound modification. Microwave radiation, as a kind of physical method, is promising due to its uniform energy radiation, greenness, safety, non-toxicity. It can meet the demand of consumers for safe food. Microwave-assisted modification with other methods can directly or indirectly affect the structure of starch granules to obtain modified starch with high degree of substitution and low viscosity, and the modification efficiency is greatly improved. This paper reviews the effect of microwave radiation on the physicochemical properties of starch, such as granule morphology, crystallization characteristics, and gelatinization characteristics, as well as the application of microwave radiation in starch modification and starch food processing. It provides theoretical references and suggestions for the research of microwave heating modified starch and the deep processing of starchy foods.

Salmonella Enteritidis antitoxin DinJ inhibits NLRP3-dependent canonical inflammasome activation in macrophages.

The inflammasome is a pivotal component of the innate immune system, acting as a multiprotein complex that plays an essential role in detecting and responding to microbial infections. Salmonella Enteritidis have evolved multiple mechanisms to regulate inflammasome activation and evade host immune system clearance. Through screening S. Enteritidis C50336ΔfliC transposon mutant library, we found that the insertion mutant of dinJ increased inflammasome activation. In this study, we demonstrated the genetic connection between the antitoxin DinJ and the toxin YafQ in S. Enteritidis, confirming their co-transcription. The deletion mutant ΔfliCΔdinJ increased cell death and IL-1ß secretion in J774A.1 cells. Western blotting analysis further showed elevated cleaved Caspase-1 product (p10 subunits) and IL-1ß secretion in cells infected with ΔfliCΔdinJ compared to cells infected with ΔfliC. DinJ was found to inhibit canonical inflammasome activation using primary bone marrow-derived macrophages (BMDMs) from Casp-/- C57BL/6 mice. Furthermore, DinJ specifically inhibited NLRP3 inflammasome activation, as demonstrated in BMDMs from Nlrp3-/- and Nlrc4-/- mice. Fluorescence resonance energy transfer (FRET) experiments confirmed the translocation of DinJ into host cells during infection. Finally, we revealed that DinJ could inhibit the secretion of IL-1ß and IL-18 in vivo, contributing to S. Enteritidis evading host immune clearance. In summary, our findings provide insights into the role of DinJ in modulating the inflammasome response during S. Enteritidis infection, highlighting its impact on inhibiting inflammasome activation and immune evasion.

Integrative omics studies revealed synergistic link between sucrose metabolic isogenes and carbohydrates in poplar roots infected by Fusarium wilt.

Advances in carbohydrate metabolism prompted its essential role in defense priming and sweet immunity during plant-pathogen interactions. Nevertheless, upstream responding enzymes in the sucrose metabolic pathway and associated carbohydrate derivatives underlying fungal pathogen challenges remain to be deciphered in Populus, a model tree species. In silico deduction of genomic features, including phylogenies, exon/intron distributions, cis-regulatory elements, and chromosomal localization, identified 59 enzyme genes (11 families) in the Populus genome. Spatiotemporal expression of the transcriptome and the quantitative real-time PCR revealed a minuscule number of isogenes that were predominantly expressed in roots. Upon the pathogenic Fusarium solani (Fs) exposure, dynamic changes in the transcriptomics atlas and experimental evaluation verified Susy (PtSusy2 and 3), CWI (PtCWI3), VI (PtVI2), HK (PtHK6), FK (PtFK6), and UGPase (PtUGP2) families, displaying promotions in their expressions at 48 and 72 h of post-inoculation (hpi). Using the gas chromatography-mass spectrometry (GC-MS)-based non-targeted metabolomics combined with a high-performance ion chromatography system (HPICS), approximately 307 metabolites (13 categories) were annotated that led to the quantification of 46 carbohydrates, showing marked changes between three compared groups. By contrast, some sugars (e.g., sorbitol, L-arabitol, trehalose, and galacturonic acid) exhibited a higher accumulation at 72 hpi than 0 hpi, while levels of α-lactose and glucose decreased, facilitating them as potential signaling molecules. The systematic overview of multi-omics approaches to dissect the effects of Fs infection provides theoretical cues for understanding defense immunity depending on fine-tuned Suc metabolic gene clusters and synergistically linked carbohydrate pools in trees.

Triplet energy transfer from quantum dots increases Ln(iii) photoluminescence, enabling excitation at visible wavelengths.

Europium(iii) complexes are promising for bioimaging because of their long-lived, narrow emission. The photoluminescence (PL) from europium(iii) complexes is usually low. Thus, the effective utilization of low-energy light >400 nm and enhancement of PL are long-standing goals. Here, we show for the first time that 1-naphthoic acid triplet transmitter ligands bound to CdS quantum dots (QDs) and europium(iii) complexes create an energy transfer cascade that takes advantage of the strong QD absorption. This is confirmed by transient absorption spectroscopy, which shows hole mediated triplet energy transfer from QDs to 1-NCA, followed by triplet transfer from 1-NCA to europium(iii) complexes with an efficiency of 65.9 ± 7.7%. Smaller CdS QDs with a larger driving force lead to higher triplet transfer efficiency, with Eu(iii) PL intensity enhanced up to 21.4 times, the highest value ever reported. This hybrid QD system introduces an innovative approach to enhance the brightness of europium complexes.

Organocatalytic enantioselective synthesis of Csp2-N atropisomers via formal Csp2-O bond amination.

Compared with well-developed construction of Csp2-Csp2 atropisomers, the synthesis of Csp2-N atropisomers remains in its infancy, which is recognized as both appealing and challenging. Herein, we achieved the first organocatalyzed asymmetric synthesis of Csp2-N atropisomers by formal Csp2-O amination. With the aid of a suitable acid, 3-alkynyl-3-hydroxyisoindolinones reacted smoothly with 1-methylnaphthalen-2-ols to afford a wide range of atropisomers by selective formation of the Csp2-N axis. Particularly, both the kinetic (Z)-products and the thermodynamic (E)-products could be selectively formed. Furthermore, the rarely used combination of two chiral Brønsted acid catalysts achieved excellent enantiocontrol, which is intriguing and unusual in organocatalysis. Based on control experiments and DFT calculations, a cascade dehydration/addition/rearrangement process was proposed. More importantly, this work provided a new plat-form for direct atroposelective construction of the chiral Csp2-N axis.

Illness Perception and Benefit Finding of Thyroid Cancer Survivors: A Chain Mediating Model of Sense of Coherence and Self-disclosure.

BACKGROUND: Benefit finding is gaining attention as a strong predictor of quality of life, but few studies have addressed the mechanisms of its development. OBJECTIVE: The purpose of this study was to determine the relationship between illness perception and benefit finding in female thyroid cancer survivors and to further elucidate the mechanisms by which illness perception contributes to benefit finding through sense of coherence and self-disclosure. METHODS: A total of 280 female thyroid cancer survivors completed the questionnaire between January and August 2023. The study investigated participants' baseline information, illness perception, sense of coherence, self-disclosure, and benefit finding. The bootstrap method was used to test the chain mediation effect. RESULTS: The findings showed that in the chain-mediated model, illness perception negatively predicted sense of coherence (ß = -.475, P < .001) and self-disclosure (ß = -.335, P < .001). Sense of coherence positively predicted self-disclosure (ß = .272, P < .001) and benefit finding (ß = .251, P < .001). Self-disclosure positively predicted benefit finding (ß = .213, P < .001). The separate mediating roles of sense of coherence and self-disclosure between illness perception and benefit finding were both significant, as were the chained mediating roles of sense of coherence, and self-disclosure. CONCLUSION: This study provides a theoretical basis for elucidating the mechanisms of benefit finding and provides precise targets for clinical intervention. IMPLICATIONS FOR PRACTICE: Healthcare professionals can improve mental health outcomes by improving cancer survivors' disease awareness, fostering their sense of coherence, and encouraging moderate self-disclosure to achieve benefit finding.

Effect of vanillin-conjugated chitosan-stabilized emulsions on dough and bread characteristics.

In this study, the effect of chitosan-vanillin Schiff base emulsions (CSVAEs) on dough and bread characteristics was investigated. The results revealed that CSVAEs were embedded in the gluten and that the viscoelasticity and mechanical strength of the dough gradually increased with increasing CSVAEs concentration, α-helical and ß-fold content, and elastic structure in the dough increased with the same patterns. The basic properties of bread were measured, and it was found that low concentrations of CSVAEs were effective in improving the quality of bread and slowing the staling rate. As the storage time increased, CSVAEs had less effect on the rate of moisture loss, hardness and springiness of the bread and more effect on the inhibition of the acidity of the bread. The addition of CSVAEs slowed the increase in bacteria and molds and extended the shelf life of the bread.

Tomato CYP94C1 inactivates bioactive JA-Ile to attenuate jasmonate-mediated defense during fruit ripening.

As the master regulators of the ET signaling pathway, EIL transcription factors directly activate the expression of CYP94C1 to inactivate bioactive JA-Ile, thereby attenuating JA-mediated defense during fruit ripening. Knockout of CYP94C1 improves tomato fruit resistance to necrotrophs without compromising fruit quality.

Sodium sulfite-driven Helicobacter pylori eradication: Unraveling oxygen dynamics through multi-omics investigation.

Due to the emergence and spread of multidrug resistance in Helicobacter pylori (H. pylori), its eradication has become difficult. Sodium sulfite (SS), a widely used food additive for ensuring food safety and storage, has been recognized as an effective nonbactericidal agent for H. pylori eradication. However, the mechanism by which H. pylori adapts and eventually succumbs under low- or no-oxygen conditions remains unknown. In this study, we aimed to evaluate the anti-H. pylori effect of SS and investigated the multiomics mechanism by which SS kills H. pylori. The results demonstrated that SS effectively eradicated H. pylori both in vitro and in vivo. H. pylori responds to the oxygen changes regulated by SS, downregulates the HcpE gene, which is responsible for redox homeostasis in bacteria, decreases the activities of enzymes related to oxidative stress, and disrupts the outer membrane structure, increasing susceptibility to oxidative stress. Furthermore, SS downregulates the content of cytochrome C in the microaerobic respiratory chain, leading to a sharp decrease in ATP synthesis. Consequently, the accumulation of triglycerides (TGs) in bacteria due to oxidative stress supports anaerobic respiration, meeting their energy requirements. The multifaceted death of H. pylori caused by SS does not result in drug resistance. Thus, screening of the redox homeostasis of HcpE as a new target for H. pylori infection treatment could lead to the development of a novel approach for H. pylori eradication therapy.

Epigenetic regulations of cellular senescence in osteoporosis.

Osteoporosis (OP) is a prevalent age-related disease that is characterized by a decrease in bone mineral density (BMD) and systemic bone microarchitectural disorders. With age, senescent cells accumulate and exhibit the senescence-associated secretory phenotype (SASP) in bone tissue, leading to the imbalance of bone homeostasis, osteopenia, changes in trabecular bone structure, and increased bone fragility. Cellular senescence in the bone microenvironment involves osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells (BMSCs), whose effects on bone homeostasis are regulated by epigenetics. Therefore, the epigenetic regulatory mechanisms of cellular senescence have received considerable attention as potential targets for preventing and treating osteoporosis. In this paper, we systematically review the mechanisms of aging-associated epigenetic regulation in osteoporosis, emphasizing the impact of epigenetics on cellular senescence, and summarize three current methods of targeting cellular senescence, which is helpful better to understand the pathogenic mechanisms of cellular senescence in osteoporosis and provides strategies for the development of epigenetic drugs for the treatment of osteoporosis.

A murine model to evaluate immunotherapy effectiveness for human Fanconi anemia-mutated acute myeloid leukemia.

Fanconi anemia (FA)-mutated acute myeloid leukemia (AML) is a secondary AML with very poor prognosis and limited therapeutic options due to increased sensitivity to DNA-damaging agents. PD-1 immune checkpoint inhibitors upregulate T-cell killing of cancer cells and is a class of promising treatment for FA-AML. Here, we developed a novel FA-AML murine model that allows the study of human AML with a humanized immune system in order to investigate immunotherapeutic treatments in vivo. FA-AML1 cells and non-FA-mutated Kasumi-1 cells were injected into 8-10 week old NSG mice. Once leukemic engraftment was confirmed by HLA-DR expression in the peripheral blood, human peripheral blood mononuclear cells (hPBMCs) were injected into the mice. One week post-hPBMCs injection, Nivolumab (PD-1 inhibitor) or PBS vehicle control was administered to the mice bi-weekly. In our Nivolumab treated mice, FA-AML1, but not Kasumi-1-engrafted mice, had significantly prolonged overall survival. Both FA-AML1 and Kasumi-1 engrafted mice had decreased spleen weights. Higher leukemic infiltration into vital organs was observed in FA-AML1 engrafted mice compared to Kasumi-1 engrafted mice. In conclusion, our novel humanized murine model of FA-mutated AML is an attractive tool for supporting further studies and clinical trials using PD-1 inhibitors to treat FA-mutated AML.