Design and performance analysis of low damage anti-skid crescent drills for bone drilling.

BACKGROUND: With orthopedic surgery increasing year on year, the main challenges in bone drilling are thermal damage, mechanical damage, and drill skid. The need for new orthopedic drills that improve the quality of surgery is becoming more and more urgent. METHODS: Here, we report the skidding mechanism of drills at a wide range of inclination angle and propose two crescent drills (CDTI and CDTII). The anti-skid performance and drilling damage of the crescent drills were analyzed for the first time. Inclined bone drilling experiments were carried out with crescent drills and twist drills and real-time drilling forces and temperatures were collected. RESULTS: The crescent drills are significantly better than the twist drill in terms of anti-skid, reducing skidding forces, thrust forces and temperature. The highest temperature is generated close to the upper surface of the workpiece rather than at the hole exit. Finally, the longer crescent edge with a small and negative polar angle increases the rake angle of the cutting edge and reduces thrust forces but increases skidding force and temperature. This study can promote the development of high-quality orthopedic surgery and the development of new bone drilling tools. CONCLUSION: The crescent drills did not skid and caused little drilling damage. In comparison, the CDTI performs better in reducing the skidding force, while the CDTII performs better in reducing the thrust force.

Prognostic significance of TNFRSF4 expression and development of a pathomics model to predict expression in hepatocellular carcinoma.

Background: TNFRSF4 plays a significant role in cancer progression, especially in hepatocellular carcinoma (HCC). This study aims to investigate the prognostic value of TNFRSF4 expression in patients with HCC and to develop a predictive pathomics model for its expression. Methods: A cohort of patients with HCC retrieved from the TCGA database was analyzed using RNA-seq analysis to determine TNFRSF4 expression and its impact on overall survival (OS). Additionally, hematoxylin-eosin staining analysis was performed to construct a pathomics model for predicting TNFRSF4 expression. Then, pathway enrichment analysis was conducted, immune checkpoint markers were investigated, and immune cell infiltration was examined to explore the underlying biological mechanism of the pathomics score. Results: TNFRSF4 expression was significantly higher in tumor tissues than in normal tissues. TNFRSF4 expression also exhibited significant correlations with various clinical variables, including pathologic stage III/IV and R1/R2/RX residual tumor. Furthermore, elevated TNFRSF4 expression was associated with unfavorable OS. Interestingly, in the subgroup analysis, elevated TNFRSF4 expression was identified as a significant risk factor for OS in male patients. The newly developed pathomics model successfully predicted TNFRSF4 expression with good performance and revealed a significant association between high pathomics scores and worse OS. In male patients, high pathomics scores were also associated with a higher risk of mortality. Moreover, pathomics scores were also involved in specific hallmarks, immune-related characteristics, and apoptosis-related genes in HCC, such as epithelial-mesenchymal transition, Tregs, and BAX expression. Conclusions: Our findings suggest that TNFRSF4 expression and the newly devised pathomics scores hold potential as prognostic markers for OS in patients with HCC. Additionally, gender influenced the association between these markers and patient outcomes.

Laparoscopic-assisted full-sized liver transplantation with magnetically fast portal vein anastomosis: An initial cohort study.

BACKGROUND: Some cases of laparoscopic-assisted liver transplantation (LA-LT) with utilization of reduced-size grafts has been reported. We here introduced successful utilization of LA-LT with whole liver grafts and magnetic portal vein anastomosis. METHODS: Eight patients with liver cirrhosis were included for LA-LT using donor organs after cardiac death. The surgical procedures included purely laparoscopic explant hepatectomy and whole-liver graft implantation via the midline incision. After explant removal, the whole-liver graft was then placed in situ, and a side-to-side cavo-caval anastomosis with 4-5 cm oval opening was performed. The magnetic rings were everted on the donor and recipient portal vein, respectively, and the instant attachment of the two magnets at the donor and recipient portal vein allowed fast blood reperfusion, followed by continuous suturing on the surface of the magnets. RESULTS: The median operation time was 495 (range 420-630). The median time of explant hepatectomy and IVC anastomosis was 239 (range 150-300) min and 14.5 (range 10-19) min, respectively. Of note, the median anhepatic time was 25 (range 20-35) min. All the patients were discharged home with no major complications after more than six months follow-up. CONCLUSION: LA-LT with full-size graft is feasible and utilization of magnetic anastomosis would further simplify the procedure.

Transcriptomic Analysis of Self-Incompatibility in Alfalfa.

Alfalfa (Medicago sativa L.) is an important forage crop worldwide, but molecular genetics and breeding research in this species are hindered by its self-incompatibility (SI). Although the mechanisms underlying SI have been extensively studied in other plant families, SI in legumes, including alfalfa, remains poorly understood. Here, we determined that self-pollinated pollen tubes could germinate on the stigma of alfalfa, grow through the style, and reach the ovarian cavity, but the ovules collapsed ~48 h after self-pollination. A transcriptomic analysis of dissected pistils 24 h after self-pollination identified 941 differently expressed genes (DEGs), including 784 upregulated and 157 downregulated genes. A gene ontology (GO) analysis showed that the DEGs were highly enriched in functions associated with the regulation of pollen tube growth and pollen germination. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that pentose and glucuronate interconversion, plant hormone signal transduction, the spliceosome, and ribosomes might play important roles in SI. Our co-expression analysis showed that F-box proteins, serine/threonine protein kinases, calcium-dependent protein kinases (CDPKs), bHLHs, bZIPs, and MYB-related family proteins were likely involved in the SI response. Our study provides a catalog of candidate genes for further study to understand SI in alfalfa and related legumes.

Extended depth of focus IOL in eyes with different axial myopia and targeted refraction.

AIM: To evaluate the objective visual outcomes following implantation of extended depth of focus intraocular lens (EDOF IOL) in individuals with varying axial lengths (AL) and targeted refraction. METHODS: This retrospective study comprised age-matched eyes that underwent implantation of the EDOF IOL. Eyes were categorized based on AL into groups: control group with AL < 26 mm; high myopia group with AL ≥ 26 mm. Each group was then subdivided based on postoperative spherical equivalent (SE). Follow-up at three months included assessment of uncorrected visual acuity at different distances, contrast sensitivity (CS), refractive outcomes, and spectacle independence. RESULTS: Overall, this study included 100 eyes from 100 patients, comprising 50 males (50.00%) and 50 females (50.00%), with 20 eyes in each group. In the control group, the uncorrected distance visual acuity (UDVA) at 5 and 3 m (m) in the - 1.50 to -0.75 group was inferior to that of the - 0.75 to 0.00 group (P = 0.004). Conversely, the uncorrected near visual acuity (UNVA) at 33 cm in the - 1.50 to -0.75 group was superior to that of the - 0.75 to 0.00 group (P = 0.005). Within the high myopia group, the UDVA at 5 and 3 m in the - 2.25 to -1.50 group was worse than in the - 0.75 to 0.00 group (P = 0.009 and 0.008, respectively). However, the UNVA at 33 cm in the - 2.25 to -1.50 group was better than in the - 0.75 to 0.00 group (P = 0.020). No significant differences were observed among the groups for corrected distance visual acuity (CDVA) (P > 0.05). Additionally, in the high myopia group, the CS of the - 2.25 to -1.50 group was lower compared to that of the - 0.75 to 0.00 group (P = 0.017). Among high myopia patients, 90.00% with refraction ranging from - 1.50 to -0.75 reported achieving overall spectacle independence. CONCLUSIONS: Implantation of extended depth of focus intraocular lenses (IOLs) yields satisfactory visual and refractive outcomes in eyes with axial myopia. Among high myopia patients, a refraction ranging from - 1.50 to -0.75 diopters achieves superior visual quality compared to other postoperative myopic diopters.

m6A methyltransferase METTL14­mediated RP1­228H13.5 promotes the occurrence of liver cancer by targeting hsa­miR­205/ZIK1.

The aim of the present study was to explore the association between N6­methyladenosine (m6A) modification regulatory gene­related long noncoding (lnc)RNA RP1­228H13.5 and cancer prognosis through bioinformatics analysis, as well as the impact of RP1­228H13.5 on cell biology­related behaviors and specific molecular mechanisms. Bioinformatics analysis was used to construct a risk model consisting of nine genes. This model can reflect the survival time and differentiation degree of cancer. Subsequently, a competing endogenous RNA network consisting of 3 m6A­related lncRNAs, six microRNAs (miRs) and 201 mRNAs was constructed. A cell assay confirmed that RP1­228H13.5 is significantly upregulated in liver cancer cells, which can promote liver cancer cell proliferation, migration and invasion, and inhibit liver cancer cell apoptosis. The specific molecular mechanism may be the regulation of the expression of zinc finger protein interacting with K protein 1 (ZIK1) by targeting the downstream hsa­miR­205. Further experiments found that the m6A methyltransferase 14, N6­adenosine­methyltransferase subunit mediates the regulation of miR­205­5p expression by RP1­228H13.5. m6A methylation regulatory factor­related lncRNA has an important role in cancer. The targeting of hsa­miR­205 by RP1­228H13.5 to regulate ZIK1 may serve as a potential mechanism in the occurrence and development of liver cancer.

Adsorption of levofloxacin by ultraviolet aging microplastics.

Microplastics can combine with pollutants such as antibiotics and pose a threat to the environment and organisms. At the same time, the inevitable aging behavior of microplastics in the actual environment leads to changes in their physical and chemical properties, and thus changes the reaction mechanism between microplastics and other pollutants. In this study, we used three common microplastics PE/PS/PA to study the adsorption behavior of levofloxacin hydrochloride. Ultraviolet aging method was used to simulate the aging process of levofloxacin hydrochloride under sunlight, and compared with that of before aging. The results showed that the order of adsorption capacity was PS-UV > PA-UV > PE-UV > PA > PS > PE. Aging behavior can significantly enhance the adsorption capacity of microplastics to pollutants. Both Langmuir and Freundlich models can be used to fit the isothermal adsorption process well, indicating that the adsorption process was not a simple monolayer adsorption, but also a multi-molecular layer adsorption. The experiments showed that the adsorption process was affected by various mechanisms, including π-π conjugation, hydrogen bond, ion exchange and electrostatic interaction. This study elucidated the interaction mechanism between microplastics and levofloxacin hydrochloride, which has important significance for future control of microplastics and antibiotic pollution.

Cognitive control subprocess deficits and compensatory modulation mechanisms in patients with frontal lobe injury revealed by EEG markers: a basic study to guide brain stimulation.

Background: Frontal lobe injury (FLI) is related to cognitive control impairments, but the influences of FLI on the internal subprocesses of cognitive control remain unclear. Aims: We sought to identify specific biomarkers for long-term dysfunction or compensatory modulation in different cognitive control subprocesses. Methods: A retrospective case-control study was conducted. Event-related potentials (ERP), oscillations and functional connectivity were used to analyse electroencephalography (EEG) data from 12 patients with unilateral frontal lobe injury (UFLI), 12 patients with bilateral frontal lobe injury (BFLI) and 26 healthy controls (HCs) during a Go/NoGo task, which included several subprocesses: perceptual processing, anticipatory preparation, conflict monitoring and response decision. Results: Compared with the HC group, N2 (the second negative peak in the averaged ERP waveform) latency, and frontal and parietal oscillations were decreased only in the BFLI group, whereas P3 (the third positive peak in the averaged ERP waveform) amplitudes and sensorimotor oscillations were decreased in both patient groups. The functional connectivity of the four subprocesses was as follows: alpha connections of posterior networks in the BFLI group were lower than in the HC and UFLI groups, and these alpha connections were negatively correlated with neuropsychological tests. Theta connections of the dorsal frontoparietal network in the bilateral hemispheres of the BFLI group were lower than in the HC and UFLI groups, and these connections in the uninjured hemisphere of the UFLI group were higher than in the HC group, which were negatively correlated with behavioural performances. Delta and theta connections of the midfrontal-related networks in the BFLI group were lower than in the HC group. Theta across-network connections in the HC group were higher than in the BFLI group but lower than in the UFLI group. Conclusions: The enhancement of low-frequency connections reflects compensatory mechanisms. In contrast, alpha connections are the opposite, therefore revealing more abnormal neural activity and less compensatory connectivity as the severity of injury increases. The nodes of the above networks may serve as stimulating targets for early treatment to restore corresponding functions. EEG biomarkers can measure neuromodulation effects in heterogeneous patients.

Hsa_circ_0001479 accelerates tumorigenesis of gastric cancer and mediates immune escape.

Gastric cancer (GC) is a common fatal malignant tumor of the digestive tract, particularly in Asia. Circular RNA (circRNA) has been proved to regulate malignancy progression and immunotherapeutic efficacy in multiple tumors, including GC. Notably, the function of circRNAs in GC has not been completely revealed. Therefore, exploration of more GC related circRNAs may provide potential strategies for GC treatment. In the study, it was observed that hsa_circ_0001479 exhibited a high level of expression in GC and was subsequently found to be associated with the depth of invasion, lymph node metastasis, and TNM stage. Functionally, the overexpression of hsa_circ_0001479 was found to enhance the proliferation and migration of GC cells, as evidenced by various experiments such as CCK-8, EdU, colony forming and transwell. Dual-luciferase reporter assay verified that hsa_circ_0001479 upregulated DEK expression by sponge targeting miR-133a-5p. Further investigations indicated DEK affected the entry of ß-catenin into the nucleus by activating Wnt/ß-catenin signaling pathway to promote accumulation of downstream c-Myc. As a transcription factor, c-Myc combined with the promoter of hsa_circ_0001479 parent gene to stimulate hsa_circ_0001479 generation. Besides, hsa_circ_0001479 inhibited theinfiltration with CD8+T cells in GC and associated with immune checkpoints. In summary, hsa_circ_0001479 accelerated the development and metastasis of GC and mediates immune escape of CD8+T cells. Targeting it may provide a novel immunotherapy to better locally treat GC and reduce the incidence of metastases.

Synthesis of Free-Standing Pd-Ni-P Metallic Glass Nanoparticles with Durable Medium-Range Ordered Structure for Enhanced Electrocatalytic Properties.

Topologically disordered metallic glass nanoparticles (MGNPs) with highly active and tailorable surface chemistries have immense potential for functional uses. The synthesis of free-standing MGNPs is crucial and intensively pursued because their activity strongly depends on their exposed surfaces. Herein, a novel laser-evaporated inert-gas condensation method is designed and successfully developed for synthesizing free-standing MGNPs without substrates or capping agents, which is implemented via pulse laser-induced atomic vapor deposition under an inert helium atmosphere. In this way, the metallic atoms vaporized from the targets collide with helium atoms and then condense into short-range-order (SRO) clusters, which mutually assemble to form the MGNPs. Using this method, free-standing Pd40 Ni40 P20 MGNPs with a spherical morphology are synthesized, which demonstrates satisfactory electrocatalytic activity and durability in oxygen reduction reactions. Moreover, local structure investigations using synchrotron pair distribution function techniques reveal the transformation of SRO cluster connection motifs of the MGNPs from face-sharing to edge-sharing modes during cyclic voltammetry cycles, which enhances the electrochemical stability by blocking crystallization. This approach provides a general strategy for preparing free-standing MGNPs with high surface activities, which may have widespread functional applications.

Engineering Atomic-to-Nano Scale Structural Homogeneity towards High Corrosion Resistance of Amorphous Magnesium-Based Alloys.

Magnesium-based amorphous alloys have aroused broad interest in being applied in marine use due to their merits of lightweight and high strength. Yet, the poor corrosion resistance to chloride-containing seawater has hindered their practical applications. Herein, we propose a new strategy to improve the chloride corrosion resistance of amorphous Mg65Cu15Ag10Gd10 alloys by engineering atomic-to-nano scale structural homogeneity, which is implemented by heating the material to the critical temperature of the liquid-liquid transition. By using various electrochemical, microscopic, and spectroscopic characterization methods, we reveal that the liquid-liquid transition can rearrange the local structural units in the amorphous structure, slightly decreasing the alloy structure's homogeneity, accelerate the formation of protective passivation film, and, therefore, increase the corrosion resistance. Our study has demonstrated the strong coupling between an amorphous structure and corrosion behavior, which is available for optimizing corrosion-resistant alloys.

Understanding the thrust force evolution and primary stability for dental implantation - An in-vitro experimental investigation.

The dental implant is challenging due to the unstable quality of the surrounding bone. This study aimed to explore the feasibility of using thrust force characteristics to identify different bone types and the influencing mechanisms of spindle speed and feed rate on primary stability of dental implants through in-vitro experiments. 13 groups of osteotomy experiments were performed on mandibles and maxillae of pigs with different bone types (I, II, and III) under different spindle speeds (600 and 800 rpm) and feed rates (20 and 60 mm/min). The thrust force evolution under different conditions was extracted and analysed to elaborate the distribution and thickness of the cortical and trabecular bone layers on different bone types. Dental implant placements were performed, and corresponding primary stabilities were obtained. Furthermore, histologic observation was conducted to reveal the bone/implant contact morphology. From the results, the amplitude and trend of thrust force show a regular variation during drilling different bone types. The highly dynamic information of thrust force can be analysed to characterise the distribution and thickness of the cortical and trabecular bone layers, hence effectively detecting different bone types. Since a lower feed rate and resulting bone temperature elevation lead to more thermal damages, primary stability decreases with the decrease of feed rate. Spindle speed has no significant effect. This study establishes a more in-depth understanding into the thrust force evolution and also provide a clinical option for reducing the complexity of bone type and drilling parameters determination in osteotomy.

Reduced number of IFN-γ producing cells in peripheral blood is a biomarker for patients with renal cell carcinoma.

Renal cell cancer (RCC) is the most lethal of all the common urologic cancers and constitutes 2.2% of all malignancy diagnoses. The incidence of RCC has been steadily increasing in recent decades. The classic risk factors of RCC include smoking, hypertension, obesity, genetics, and genetic mutations. Recent studies also revealed that RCC was an immunogenic tumor and affected by host immune status. Among the pan-cance, RCC presented with the highest degree of immune infiltration, indicating RCC patients might benefit from immunotherapy. A new immune classification of RCC has been developed by Su et al. based on tumor-infiltrating lymphocytes to guide clinical practice. However, these studies mainly focus on biomarkers derived from tumor microenvironment (TME), the biomarkers based on peripheral blood samples to RCC have rarely been described. We collected peripheral blood samples from RCC patients and their matched healthy controls and detected the number of IL-2 and IFN-γ producing cells by implementing an enzyme-linked immunospot (ELISPOT) assay. This is the first study to report blood-based immune biomarkers for RCC using an ELISPOT assay. Our results suggested the frequency of IFN-γ producing cells but not IL-2 producing cells was associated with RCC risk. These findings warrant further validation in larger prospective studies.

Novel crescent drill design and mechanistic force modeling for thrust force reduction in bone drilling.

Bone drilling tends to cause mechanical damages and thermal necrosis in the vicinity of the drilled hole, which can deteriorate the surgery quality and patients' recovery. Understanding the cutting forces generation mechanism is crucial in controlling thrust force and bone temperature for optimum tool design. In this study, a novel crescent drill bit featuring an improved positive rake angle distribution was designed to reduce the thrust force and temperature elevation. On this basis, a mechanistic model for predicting thrust force and torque was proposed for drill bits with different geometries (twist drill and crescent drill). The proposed model was established in the polar coordinate system to precisely calculate the curvilinear integral of the crescent cutting edges. Drilling experiments were carried out using two types of drill bit under different cutting conditions and results showed that our proposed model agrees well with the experimental data. The experimental results also demonstrated that our tool design can significantly reduce the thrust force and reduce the bone temperature below the thermal threshold without coolant, providing a clinical option for coolant free drilling.

Spatiotemporal Dynamics of Covert Attention With Different Degrees of Central Visual Field Defects: An ERP and sLORETA Study.

Purpose: The present study aimed to investigate the spatiotemporal dynamics of covert attention by simulating different degrees of central visual field defects in healthy subjects. Methods: An electroencephalogram (EEG) was recorded while 40 normal-sighted subjects performed a target discrimination task. Target stimuli simulated different defect degrees of the central visual field by artificially central scotomas (5, 10, 20, and 30 degrees of visual angle) masked on the center of black-and-white checkerboards. Event-related potentials (ERPs) and standardized low-resolution brain electromagnetic tomography (sLORETA) based on ERPs were analyzed. Results: ERP results indicated that during early perceptual processes, compared with 5-degree and 10-degree defects, N1 amplitudes of 20-degree and 30-degree defects decreased, whereas P2 amplitudes significantly reduced in 30-degree defects. During later discrimination and decision processing, N2 amplitudes gradually increased from 5-degree to 30-degree defects, whereas P3 amplitudes gradually decreased. Source localization indicated that 5-degree and 10-degree defects had stronger activations than 20-degree and 30-degree defects from the occipital cortex to the ventral stream and dorsal streams. Especially, 30-degree defects primarily recruited additional activations in the ventrolateral prefrontal cortex and ventral stream and later caused the disconnection of dorsolateral prefrontal-posterior parietal cortices in the dorsal stream. Conclusions: Different degrees of central visual field defects differed in distinct spatiotemporal characteristics at multiple stages of covert attention, from top-down forward feedback and attentional allocation to executive controls through ventral and dorsal processing streams, suggesting that the combination of ERP and source localization can reveal the spatiotemporal control capacity of the cortex on central visual field defects.

Effects of incineration leachate on anaerobic digestion of excess sludge and the related mechanisms.

Anaerobic digestion (AD) refers to a reliable channel for energy recovery from organics. However, the digestion efficiency of excess sludge (ES) has been unsatisfactory since there are defects relating to ES hydrolysis. Therefore, this study explored a method to improve the anaerobic digestion of ES, which could simultaneously treat ES and incineration leachate, and revealed the potential mechanism of AD process. As the investigation was conducted on the influences exerted by incineration leachate on the four phases (i.e., solubilization, methanogenesis, acidogenesis and hydrolysis) of ES anaerobic digestion, and the effect mechanism. According to obtained results, adding appropriate amounts of incineration leachate could facilitate the steps of solubilization, hydrolysis, acidogenesis and methanogenesis of ES. The hydrolysis and acidogenesis efficiency in the leachate added digesters were 5.7%-17.1% and 13%-45% higher than that of the control digester, respectively. Meanwhile, cumulative methane yields (CMY) were 27-86 mL/gVS higher than that in the control digester. Besides, the sludge floc stability was reduced by the leachate with the decrease in the median particle size (MPS) and apparent activation energy (AAE) of the sludge. According to microbial community and diversity analysis, adding incineration leachate increased the relative abundance of hydrolytic-acidification bacteria in the digesters and the relative abundance of Methanosaeta and Methanosarcina. Thus, the digestive performance exhibited by the leachate participated system was improved. These mentioned findings may provide an approach for treating ES and incineration leachate in practical engineering.

Antimicrobial and Microbiological Characteristics of Critically Ill Patients with Complicated Intra-Abdominal Infection: Observational Data from Beth Israel Deaconess Medical Center.

PURPOSE: We describe the clinical characteristics, isolated microorganisms and antibiotics used in patients with cIAIs during ICU stay. METHODS: A retrospective analysis of data from Beth Israel Deaconess Medical Center was performed. RESULTS: A total of 316 patients with cIAIs were included, 57.0% of them were male and the median age was 63 years. A total of 239 patients did have cultures taken, and 74 patients had a positive microbial result. The main pathogens were Escherichia coli, Staphylococci (coagulase negative), Enterococcus sp. and Bacteroides fragilis. The main antibiotics given were vancomycin, metronidazole, piperacillin tazobactam and ciprofloxacin. Univariable and multivariable Cox regression analyses showed that receiving more antibiotics reduced ICU mortality, but the same results were not obtained in the analysis of hospital mortality. CONCLUSION: The main Gram-positive microorganisms for empirical antimicrobial therapy were Staphylococci (coagulase negative), Enterococcus sp. and Staphylococcus aureus, and Gram-negative microorganisms were Escherichia coli, Bacteroides fragilis and Klebsiella pneumoniae. The use of more antibiotics reduced ICU mortality, but the same results were not obtained in the analysis of hospital mortality.

Lactylation: a Passing Fad or the Future of Posttranslational Modification.

Lactate is a glycolytic product and a significant energy source. Moreover, it regulates gene transcription via lactylation of histones and non-histone proteins, i.e., a novel posttranslational modification. This review summarizes recent advances related to lactylation in lactate metabolism and diseases. Notably, lactylation plays a vital role in cancer, inflammation, and regeneration; however, the specific mechanism remains unclear. Histone lactylation regulates oncogenic processes by targeting gene transcription and inflammation via macrophage activation. Eventually, we identified research gaps and recommended several primary directions for further studies.

An Interpretable Early Dynamic Sequential Predictor for Sepsis-Induced Coagulopathy Progression in the Real-World Using Machine Learning.

Sepsis-associated coagulation dysfunction greatly increases the mortality of sepsis. Irregular clinical time-series data remains a major challenge for AI medical applications. To early detect and manage sepsis-induced coagulopathy (SIC) and sepsis-associated disseminated intravascular coagulation (DIC), we developed an interpretable real-time sequential warning model toward real-world irregular data. Eight machine learning models including novel algorithms were devised to detect SIC and sepsis-associated DIC 8n (1 ≤ n ≤ 6) hours prior to its onset. Models were developed on Xi'an Jiaotong University Medical College (XJTUMC) and verified on Beth Israel Deaconess Medical Center (BIDMC). A total of 12,154 SIC and 7,878 International Society on Thrombosis and Haemostasis (ISTH) overt-DIC labels were annotated according to the SIC and ISTH overt-DIC scoring systems in train set. The area under the receiver operating characteristic curve (AUROC) were used as model evaluation metrics. The eXtreme Gradient Boosting (XGBoost) model can predict SIC and sepsis-associated DIC events up to 48 h earlier with an AUROC of 0.929 and 0.910, respectively, and even reached 0.973 and 0.955 at 8 h earlier, achieving the highest performance to date. The novel ODE-RNN model achieved continuous prediction at arbitrary time points, and with an AUROC of 0.962 and 0.936 for SIC and DIC predicted 8 h earlier, respectively. In conclusion, our model can predict the sepsis-associated SIC and DIC onset up to 48 h in advance, which helps maximize the time window for early management by physicians.