Performance of the multi-U-style structure based flow field for polymer electrolyte membrane fuel cell.

The design of the reactant gas flow field structure in bipolar plates significantly influences the performance of proton exchange membrane fuel cells (PEMFCs). In this study, we introduced four innovative U-shaped flow field designs, namely: In-Out Multi-U, Out-In Multi-U, Distro In-Out Multi-U, and Distro Out-In Multi-U. To investigate the impact of these various flow fields on PEMFC performance, we conducted computational fluid dynamics (CFD) numerical simulations, validated through model experiments. Our results indicate that the Distro Out-In Multi-U flow field offers notable advantages compared to the conventional parallel flow field (CPFF) and conventional serpentine flow field (CSFF). These benefits include reduced inlet and outlet pressures, lower liquid water content, more uniform liquid water distribution, and a more even current density distribution. Furthermore, the Distro Out-In Multi-U design demonstrates improved efficiency, consuming less H2 (91.9%) than the CSFF while achieving a higher net power density output (10.1%). As a result, for the same power output, the Distro Out-In Multi-U utilizes only 83.5% of the H2 consumed by the CSFF. In summary, the U-shaped structured flow field exhibits superior output performance, enhanced energy efficiency, and improved resistance to flooding. These findings suggest that the U-shaped flow field design holds significant potential as a reactive flow field for PEMFCs.

Phosphorylation of the DNA damage repair factor 53BP1 by ATM kinase controls neurodevelopmental programs in cortical brain organoids.

53BP1 is a well-established DNA damage repair factor that has recently emerged to critically regulate gene expression for tumor suppression and neural development. However, its precise function and regulatory mechanisms remain unclear. Here, we showed that phosphorylation of 53BP1 at serine 25 by ATM is required for neural progenitor cell proliferation and neuronal differentiation in cortical brain organoids. Dynamic phosphorylation of 53BP1-serine 25 controls 53BP1 target genes governing neuronal differentiation and function, cellular response to stress, and apoptosis. Mechanistically, ATM and RNF168 govern 53BP1's binding to gene loci to directly affect gene regulation, especially at genes for neuronal differentiation and maturation. 53BP1 serine 25 phosphorylation effectively impedes its binding to bivalent or H3K27me3-occupied promoters, especially at genes regulating H3K4 methylation, neuronal functions, and cell proliferation. Beyond 53BP1, ATM-dependent phosphorylation displays wide-ranging effects, regulating factors in neuronal differentiation, cytoskeleton, p53 regulation, as well as key signaling pathways such as ATM, BDNF, and WNT during cortical organoid differentiation. Together, our data suggest that the interplay between 53BP1 and ATM orchestrates essential genetic programs for cell morphogenesis, tissue organization, and developmental pathways crucial for human cortical development.

Effect of Chlorine Salt Content on the Microstructural Development of C-S-H Gels and Ca(OH)2 at Different Curing Temperatures.

Freshwater resources are scarce in coastal areas, and using seawater as mixing water can alleviate the scarcity of freshwater resources. However, the presence of chloride ions in seawater affects the generation of hydration products and the durability of concrete structures. In order to investigate the effect of hydrated calcium silicate (C-S-H) gel and calcium hydroxide (CH) generation in seawater-mixed cement pastes under 50 °C curing, their microscopic morphology was investigated using differential scanning calorimetry analysis, X-ray diffraction (XRD), and scanning electron microscopy (SEM). The relationship between the amount of C-S-H gel and CH production and the amount of chloride ion dosing, fly ash dosing, and the age of curing were investigated. The degree of influence between hydration products and influencing factors was analyzed using the grey correlation analysis. It was shown that 50 °C curing promoted the hydration reaction and generated more hydration products compared with ASTM standard. The content of C-S-H gel and CH increased with chloride dosage. The content of C-S-H gel increased by 13.5% under 50 °C curing compared with the control group at a chloride dosage of 1.3%. Fly ash is rich in active SiO2 and AI2O3, and other components, which can react with Ca(OH)2 generated by cement hydration and then generate C-S-H gel. With the increase of fly ash, the content of C-S-H gel also increases, but the CH content decreases. When 25% of fly ash was doped under 50 °C curing, the C-S-H gel content increased by 5.02% compared to the control group. The CH content decreased by 31.8% compared to the control group. With the growth of the maintenance age, the hydration reaction continues, the generation of C-S-H gel and CH will continue to increase, and their microstructures will become denser. C-S-H gel and CH content increased the most by raising the curing temperature at 7 days of curing, increasing by 10.11% and 22.62%, respectively. C-S-H gel and CH content had the highest gray relation with fly ash dosing. Chloride dosage and age of maintenance had the highest correlation with CH content at room temperature maintenance of 0.788 and 0.753, respectively.

Study on the Binding Behavior of Chloride Ion and Ettringite in Nano-Metakaolin Cement by Seawater Mixing and Curing Temperatures.

Mixing cement with seawater will cause the hydration process of cement to be different from that of ordinary cement, which will significantly affect cement's mechanical properties and durability. This article investigates the effects of chloride ion concentration, curing temperature, and nano-metakaolin content on the evolution process of Friedel's salts and ettringite (AFt) crystals in cement pastes. The study was conducted using X-ray diffraction (XRD), thermal analysis (TG), scanning electron microscopy (SEM), and mercury-intrusion porosimetry (MIP). The results show that chlorine salt can increase the production of Friedel's salt and ettringite, and the delayed AFt production increases by up to 27.95% after the addition of chlorine salt, which has an adverse effect on cement-based materials. Increasing the curing temperature and increasing the nano-metakaolin dosage increased the generation of Friedel's salt and decreased the delayed AFt generation, which resulted in a decrease in the length and diameter of the AFt crystals. After 28 days of high-temperature curing and the addition of nano-metakaolin, Friedel's salt production increased by 13.40% and 14.34%, respectively, and ettringite production decreased by 9.68% and 7.93%, respectively. Increasing the curing temperature and adding nano-metakaolin can reduce the adverse effect of delayed ettringite increases due to chloride ion binding.

Regulating Local Electron Density of Cyano Sites in Graphitic Nitride Carbon by Giant Internal Electric Field for Efficient CO2 Photoreduction to Hydrocarbons.

Selective photocatalytic CO2 reduction to high-value hydrocarbons using graphitic carbon nitride (g-C3N4) polymer holds great practical significance. Herein, the cyano-functionalized g-C3N4 (CN-g-C3N4) with a high local electron density site is successfully constructed for selective CO2 photoreduction to CH4 and C2H4. Wherein the potent electron-withdrawing cyano group induces a giant internal electric field in CN-g-C3N4, significantly boosting the directional migration of photogenerated electrons and concentrating them nearby. Thereby, a high local electron density site around its cyano group is created. Moreover, this structure can also effectively promote the adsorption and activation of CO2 while firmly anchoring *CO intermediates, facilitating their subsequent hydrogenation and coupling reactions. Consequently, using H2O as a reducing agent, CN-g-C3N4 achieves efficient and selective photocatalytic CO2 reduction to CH4 and C2H4 activity, with maximum rates of 6.64 and 1.35 µmol g-1 h-1, respectively, 69.3 and 53.8 times higher than bulk g-C3N4 and g-C3N4 nanosheets. In short, this work illustrates the importance of constructing a reduction site with high local electron density for efficient and selective CO2 photoreduction to hydrocarbons.

Dynamic Foxp3-chromatin interaction controls tunable Treg cell function.

Nuclear factor Foxp3 determines regulatory T (Treg) cell fate and function via mechanisms that remain unclear. Here, we investigate the nature of Foxp3-mediated gene regulation in suppressing autoimmunity and antitumor immune response. Contrasting with previous models, we find that Foxp3-chromatin binding is regulated by Treg activation states, tumor microenvironment, and antigen and cytokine stimulations. Proteomics studies uncover dynamic proteins within Foxp3 proximity upon TCR or IL-2 receptor signaling in vitro, reflecting intricate interactions among Foxp3, signal transducers, and chromatin. Pharmacological inhibition and genetic knockdown experiments indicate that NFAT and AP-1 protein Batf are required for enhanced Foxp3-chromatin binding in activated Treg cells and tumor-infiltrating Treg cells to modulate target gene expression. Furthermore, mutations at the Foxp3 DNA-binding domain destabilize the Foxp3-chromatin association. These representative settings delineate context-dependent Foxp3-chromatin interaction, suggesting that Foxp3 associates with chromatin by hijacking DNA-binding proteins resulting from Treg activation or differentiation, which is stabilized by direct Foxp3-DNA binding, to dynamically regulate Treg cell function according to immunological contexts.

Antibiotic combinations prediction based on machine learning to multicentre clinical data and drug interaction correlation.

BACKGROUND: With increasing antibiotic resistance and regulation, the issue of antibiotic combination has been emphasised. However, antibiotic combination prescribing lacks a rapid identification of feasibility, while its risk of drug interactions is unclear. METHODS: We conducted statistical descriptions on 16 101 antibiotic coprescriptions for inpatients with bacterial infections from 2015 to 2023. By integrating the frequency and effectiveness of prescriptions, we formulated recommendations for the feasibility of antibiotic combinations. Initially, a machine learning algorithm was utilised to optimise grading thresholds and habits for antibiotic combinations. A feedforward neural network (FNN) algorithm was employed to develop antibiotic combination recommendation model (ACRM). To enhance interpretability, we combined sequential methods and DrugBank to explore the correlation between antibiotic combinations and drug interactions. RESULTS: A total of 55 antibiotics, covering 657 empirical clinical antibiotic combinations were used for ACRM construction. Model performance on the test dataset showed AUROCs of 0.589-0.895 for various antibiotic recommendation classes. The ACRM showed satisfactory clinical relevance with 61.54-73.33% prediction accuracy in a new independent retrospective cohort. Antibiotic interaction detection showed that the risk of drug interactions was 29.2% for strongly recommended and 43.5% for not recommended. A positive correlation was identified between the level of clinical recommendation and the risk of drug interactions. CONCLUSIONS: Machine learning modelling of retrospective antibiotic prescriptions habits has the potential to predict antibiotic combination recommendations. The ACRM plays a supporting role in reducing the incidence of drug interactions. Clinicians are encouraged to adopt such systems to improve the management of antibiotic usage and medication safety.

[Research progress of artificial intelligence technology in early diagnosis of sepsis].

Sepsis is caused by infection, which can ultimately lead to multiple organ dysfunction and even life-threatening. Early recognition and early treatment can significantly improve the prognosis of sepsis patients. However, the effect of using a single biomarker for early diagnosis of sepsis is still not ideal. In recent years, researchers have turned their attention to artificial intelligence technology for early diagnosis of sepsis. This paper briefly introduces the advantages and disadvantages of sepsis related inflammatory indicators, biomarkers, and scoring systems of disease severity for early identification of sepsis, and focuses on the research progress and limitations of artificial intelligence technology for early diagnosis of sepsis, aiming to seek new methods and ideas for early diagnosis of sepsis.

Effects of climate factors and Demodex infestation on meibomian gland dysfunction-associated dry eye diseases.

We examined the effects of climatic factors and Demodex infestations on meibomian gland dysfunction (MGD)-associated dry eye disease (DED) in a cross-sectional study. This study included 123 patients from Tianjin and Chengdu regions, and climate factors and the Air Quality Index (AQI) were recorded for one year. Ocular surface parameters and Demodex infestations were evaluated using various tests. Significant differences in all climatic factors and AQI were observed between Tianjin and Chengdu (P < 0.01), and ocular surface parameters also differed significantly between the two regions (P < 0.05). Temperature, relative humidity, and precipitation positively correlated with tear break-up time (BUT), meibum gland expressibility, and lid margin irregularity but negatively correlated with lissamine green staining scores (P < 0.05). Wind speed and atmospheric pressure positively correlated with corneal fluorescein staining and lissamine green staining but negatively correlated with BUT and lid margin irregularity (P < 0.05). AQI positively correlated with DED symptoms and corneal findings but negatively correlated with tear film stability and meibomian gland characteristics (P < 0.05). Demodex infestation was only positively correlated with meibum quality scores (P < 0.05). Our findings suggest that geographic climates influence ocular surface characteristics in MGD-associated DED, with daily precipitation potentially playing a significant role, and Demodex infestation contributes to meibum gland degeneration.

Systematic characterization of the HOXA9 downstream targets in MLL-r leukemia by noncoding CRISPR screens.

Accumulating evidence indicates that HOXA9 dysregulation is necessary and sufficient for leukemic transformation and maintenance. However, it remains largely unknown how HOXA9, as a homeobox transcriptional factor, binds to noncoding regulatory sequences and controls the downstream genes. Here, we conduct dropout CRISPR screens against 229 HOXA9-bound peaks identified by ChIP-seq. Integrative data analysis identifies reproducible noncoding hits, including those located in the distal enhancer of FLT3 and intron of CDK6. The Cas9-editing and dCas9-KRAB silencing of the HOXA9-bound sites significantly reduce corresponding gene transcription and impair cell proliferation in vitro, and in vivo by transplantation into NSG female mice. In addition, RNA-seq, Q-PCR analysis, chromatin accessibility change, and chromatin conformation evaluation uncover the noncoding regulation mechanism of HOXA9 and its functional downstream genes. In summary, our work improves our understanding of how HOXA9-associated transcription programs reconstruct the regulatory network specifying MLL-r dependency.

Interpretable predictive models of genome-wide aryl hydrocarbon receptor-DNA binding reveal tissue-specific binding determinants.

The aryl hydrocarbon receptor (AhR) is an inducible transcription factor whose ligands include the potent environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Ligand-activated AhR binds to DNA at dioxin response elements (DREs) containing the core motif 5'-GCGTG-3'. However, AhR binding is highly tissue specific. Most DREs in accessible chromatin are not bound by TCDD-activated AhR, and DREs accessible in multiple tissues can be bound in some and unbound in others. As such, AhR functions similarly to many nuclear receptors. Given that AhR possesses a strong core motif, it is suited for a motif-centered analysis of its binding. We developed interpretable machine learning models predicting the AhR binding status of DREs in MCF-7, GM17212, and HepG2 cells, as well as primary human hepatocytes. Cross-tissue models predicting transcription factor (TF)-DNA binding generally perform poorly. However, reasons for the low performance remain unexplored. By interpreting the results of individual within-tissue models and by examining the features leading to low cross-tissue performance, we identified sequence and chromatin context patterns correlated with AhR binding. We conclude that AhR binding is driven by a complex interplay of tissue-agnostic DRE flanking DNA sequence and tissue-specific local chromatin context. Additionally, we demonstrate that interpretable machine learning models can provide novel and experimentally testable mechanistic insights into DNA binding by inducible TFs.

CLINICAL CHARACTERISTICS AND PREDICTORS OF MORTALITY DIFFER BETWEEN PULMONARY AND ABDOMINAL SEPSIS.

ABSTRACT: Background: Pulmonary sepsis and abdominal sepsis have pathophysiologically distinct phenotypes. This study aimed to compare their clinical characteristics and predictors of mortality. Methods: In this multicenter retrospective trial, 1,359 adult patients who fulfilled the Sepsis-3 criteria were enrolled and classified into the pulmonary sepsis or abdominal sepsis groups. Plasma presepsin was measured, and the scores of Acute Physiology and Chronic Health Evaluation (APACHE) II, Mortality in Emergency Department Sepsis (MEDS), and Simplified Acute Physiology Score (SAPS) II were calculated at enrollment. Data on 28-day mortality were collected for all patients. Results: Compared with patients with abdominal sepsis (n = 464), patients with pulmonary sepsis (n = 895) had higher 28-day mortality rate, illness severity scores, incidence of shock and acute kidney injury, and hospitalization costs. Lactate level and APACHE II and MEDS scores were independently associated with 28-day mortality in both sepsis types. Independent predictors of 28-day mortality included Pa o2 /F io2 ratio (hazard ratio [HR], 0.998; P < 0.001) and acute kidney injury (HR, 1.312; P = 0.039) in pulmonary sepsis, and SAPS II (HR, 1.037; P = 0.017) in abdominal sepsis. A model that combined APACHE II score, lactate, and MEDS score or SAPS II score had the best area under the receiver operating characteristic curve in predicting mortality in patients with pulmonary sepsis or abdominal sepsis, respectively. Interaction term analysis confirmed the association between 28-day mortality and lactate, APACHE II score, MEDS score, SAPS II score, and shock according to the sepsis subgroups. The mortality of patients with pulmonary sepsis was higher than that of patients with abdominal sepsis among patients without shock (32.9% vs. 8.8%; P < 0.001) but not among patients with shock (63.7 vs. 48.4%; P = 0.118). Conclusions: Patients with pulmonary sepsis had higher 28-day mortality than patients with abdominal sepsis. The study identified sepsis subgroup-specific mortality predictors. Shock had a larger effect on mortality in patients with abdominal sepsis than in those with pulmonary sepsis.

Hotspots and Frontiers of Host Immune Response in Idiopathic Pulmonary Fibrosis: A Bibliometric and Scientific Visual Research from 2000 to 2022.

Background: Idiopathic pulmonary fibrosis (IPF) is a disease with significant morbidity, progressive deterioration of lung function till death, and lack of effective treatment options. This study aims to explore the global research trends in IPF and immune response to predict the research hotspot in the future. Materials and methods. All related publications on IPF and immune response since the establishment of diagnostic criteria for IPF were retrieved using the Web of Science (WOS) database. VOSviewer, GraphPad Prism 6, CiteSpace version 5.6. R5 64-bit, and a bibliometrics online platform were used to extract and analyze the trends in relevant fields. Results: From March 1, 2000, to September 30, 2022, a total of 658 articles with 25,126 citations met the inclusion criteria. The United States ranked first in number of publications (n = 217), number of citations (n = 14,745), and H-index (62). China ranked second in publications (n = 124) and seventh and fifth for citation frequency and H-index, respectively. The American Journal of Respiratory and Critical Care Medicine (impact factor = 30.528) published the most articles in the field. The author Kaminski N. from the United States was the most influential author with 26 publications and an H-index of 24. Among the 52 keywords that co-occurred at least 20 times, the main keywords were concentrated in "Inflammation related" and "Biomarker related" clusters. "biomarker" (AAY 2018.64, 25 times) was a newly emerged keyword. Conclusions: The United States has an unequivocal advantage in IPF and immunization, but China shows a faster developing trend. The American Journal of Respiratory and Critical Care Medicine should be prioritized for leading articles. This study indicates that exploration of ideal immune-related biomarkers to provide evidence for the clinical work of IPF might be a hotspot in the near future.

Berberine in Sepsis: Effects, Mechanisms, and Therapeutic Strategies.

Sepsis is defined as a dysregulated immune response to infection that leads to multiple organ dysfunction. To date, though a growing body of knowledge has gained insight into the clinical risk factors, pathobiology, treatment response, and recovery methods, sepsis remains a significant concern and clinical burden. Therefore, further study is urgently needed to alleviate the acute and chronic outcomes. Berberine (BBR), a traditional Chinese medicine with multiple actions and mechanisms, has been investigated in cellular and rodent animal models of sepsis mainly based on its anti-inflammatory effect. However, the practical application of BBR in sepsis is still lacking, and it is imperative to systematically summarize the study of BBR in sepsis. This review summarized its pharmacological activities and mechanisms in septic-related organ injuries and the potential BBR-based therapeutic strategies for sepsis, which will provide comprehensive references for scientific research and clinical application.

Androgen-mediated Perturbation of the Hepatic Circadian System Through Epigenetic Modulation Promotes NAFLD in PCOS Mice.

In women, excess androgen causes polycystic ovary syndrome (PCOS), a common fertility disorder with comorbid metabolic dysfunctions including diabetes, obesity, and nonalcoholic fatty liver disease. Using a PCOS mouse model, this study shows that chronic high androgen levels cause hepatic steatosis while hepatocyte-specific androgen receptor (AR)-knockout rescues this phenotype. Moreover, through RNA-sequencing and metabolomic studies, we have identified key metabolic genes and pathways affected by hyperandrogenism. Our studies reveal that a large number of metabolic genes are directly regulated by androgens through AR binding to androgen response element sequences on the promoter region of these genes. Interestingly, a number of circadian genes are also differentially regulated by androgens. In vivo and in vitro studies using a circadian reporter [Period2::Luciferase (Per2::LUC)] mouse model demonstrate that androgens can directly disrupt the hepatic timing system, which is a key regulator of liver metabolism. Consequently, studies show that androgens decrease H3K27me3, a gene silencing mark on the promoter of core clock genes, by inhibiting the expression of histone methyltransferase, Ezh2, while inducing the expression of the histone demethylase, JMJD3, which is responsible for adding and removing the H3K27me3 mark, respectively. Finally, we report that under hyperandrogenic conditions, some of the same circadian/metabolic genes that are upregulated in the mouse liver are also elevated in nonhuman primate livers. In summary, these studies not only provide an overall understanding of how hyperandrogenism associated with PCOS affects liver gene expression and metabolism but also offer insight into the underlying mechanisms leading to hepatic steatosis in PCOS.

Cardiorenal Syndrome in COVID-19 Patients: A Systematic Review.

Aims: To perform a systematic review assessing the clinical manifestations and outcomes of cardiorenal syndrome or the presence of both cardiac and renal complications in the 2019 coronavirus disease (COVID-19) patients. Methods: All relevant studies about cardiorenal syndrome or both cardiac and renal complications in COVID-19 patients were retrieved on PUBMED, MEDLINE, and EMBASE from December 1, 2019 to February 20, 2022. Results: Our search identified 15 studies including 637 patients with a diagnosis of cardiorenal syndrome or evidence of both cardiac and renal complications followingSARS-CoV-2 infection. They were male predominant (66.2%, 422/637), with a mean age of 58 years old. Cardiac complications included myocardial injury (13 studies), heart failure (7 studies), arrhythmias (5 studies), or myocarditis and cardiomyopathy (2 studies). Renal complications manifested as acute kidney injury with or without oliguria. Patients with cardiorenal injury were often associated with significantly elevated levels of inflammatory markers (CRP, PCT, IL-6). Patients with a diagnosis of cardiorenal syndrome or evidence of both cardiac and renal complications had more severe disease and poorer prognosis (9 studies). Conclusion: The presence of either cardiorenal syndrome or concurrent cardiac and renal complications had a significant impact on the severity of the disease and the mortality rate among patients with COVID-19 infection. Therefore, careful assessment and management of potential cardiac and renal complications in patients with COVID-19 infection are important to improve their outcomes.

A new electrochemical angular microaccelerometer with integrated sensitive electrodes perpendicular to flow channels.

A new electrochemical angular microaccelerometer with integrated sensitive electrodes perpendicular to flow channels was developed in this paper. Based on a liquid inertial mass, an incoming angular acceleration was translated into varied concentrations of reactive ions around sensitive microelectrodes, generating a detection current. Key structural parameters of the sensitive microelectrodes were designed and compared based on theoretical analysis and numerical simulations. An angular microaccelerometer incorporating sensitive microelectrodes was then fabricated, assembled and characterized, producing a sensitivity of 338 V/(rad/s2), a -3 dB bandwidth of 0.01-10 Hz and a noise level of 4.67 × 10-8 (rad/s2)/Hz1/2 @ 1 Hz. These performances were better than their commercial counterparts based on traditional electrodes and previously reported microaccelerometers based on microsensitive electrodes in parallel with flow channels, which can be applied to measure rotational accelerations in earthquakes and buildings.

Anti-Müllerian hormone treatment enhances oocyte quality, embryonic development and live birth rate†.

The anti-Müllerian hormone (AMH) produced by the granulosa cells of growing follicles is critical for folliculogenesis and is clinically used as a diagnostic and prognostic marker of female fertility. Previous studies report that AMH-pretreatment in mice creates a pool of quiescent follicles that are released following superovulation, resulting in an increased number of ovulated oocytes. However, the quality and developmental competency of oocytes derived from AMH-induced accumulated follicles as well as the effect of AMH treatment on live birth are not known. This study reports that AMH priming positively affects oocyte maturation and early embryonic development culminating in higher number of live births. Our results show that AMH treatment results in good-quality oocytes with greater developmental competence that enhances embryonic development resulting in blastocysts with higher gene expression. The transcriptomic analysis of oocytes from AMH-primed mice compared with those of control mice reveal that AMH upregulates a large number of genes and pathways associated with oocyte quality and embryonic development. Mitochondrial function is the most affected pathway by AMH priming, which is supported by more abundant active mitochondria, mitochondrial DNA content and adenosine triphosphate levels in oocytes and embryos isolated from AMH-primed animals compared with control animals. These studies for the first time provide an insight into the overall impact of AMH on female fertility and highlight the critical knowledge necessary to develop AMH as a therapeutic option to improve female fertility.

Potential Value of Presepsin Guidance in Shortening Antibiotic Therapy in Septic Patients: a Multicenter, Prospective Cohort Trial.

INTRODUCTION: Long-term use of antibiotics for septic patients leads to bacterial resistance, increased mortality, and hospital stay. In this study, we investigated an emerging biomarker presepsin-guided strategy, which can be used to evaluate the shortening of antibiotic treatment in patients with sepsis without risking a worse outcome. METHODS: In this multicenter prospective cohort trial, patients were assigned to the presepsin or control groups. In the presepsin group, antibiotics were ceased based on predefined cut-off ranges of presepsin concentrations. The control group stopped antibiotics according to international guidelines. The primary endpoints were the number of days without antibiotics within 28 days and mortality at 28 and 90 days. Secondary endpoints were the percentage of patients with a recurrent infection, length of stay in ICU and hospital, hospitalization costs, days of first episode of antibiotic treatment, percentage of antibiotic administration and multidrug-resistant bacteria, and SOFA score. RESULTS: Overall, 656 out of an initial 708 patients were eligible and assigned to the presepsin group (n = 327) or the control group (n = 329). Patients in the presepsin group had significantly more days without antibiotics than those in the control group (14.54 days [SD 9.01] vs. 11.01 days [SD 7.73]; P < 0.001). Mortality in the presepsin group showed no difference to that in the control group at days 28 (17.7% vs. 18.2%; P = 0.868) and 90 (19.9% vs. 19.5%; P = 0.891). Patients in the presepsin group had a significantly shorter mean length of stay in the hospital and lower hospitalization costs than control subjects. There were no differences in the rate of recurrent infection and multidrug-resistant bacteria and the SOFA score tendency between the two groups. CONCLUSIONS: Presepsin guidance has potential to shorten the duration of antibiotic treatment in patients with sepsis without risking worse outcomes of death, recurrent infection, and aggravation of organ failure. TRIAL REGISTRATION: ChiCTR, ChiCTR1900024391. Registered 9 July 2019-Retrospectively registered, http://www.chictr.org.cn.