Polygenic risk score of metabolic dysfunction-associated steatotic liver disease amplifies the health impact on severe liver disease and metabolism-related outcomes.

BACKGROUND: Although the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants and metabolism-related outcomes. METHODS: Participants from the UK Biobank were grouped into discovery and replication cohorts for an MASLD genome-wide association study (GWAS), and base and target cohorts for polygenic risk score (PRS) analysis. Autosomal genetic variants associated with NAFLD were compared with the MASLD GWAS results. Kaplan-Meier and Cox regression analyses were used to assess associations between MASLD and metabolism-related outcomes. RESULTS: Sixteen single-nucleotide polymorphisms (SNPs) were identified at genome-wide significance levels for MASLD and duplicated in the replication cohort. Differences were found after comparing these SNPs with the results of NAFLD-related genetic variants. MASLD cases with high PRS had a multivariate-adjusted hazard ratio of 3.15 (95% confidence interval, 2.54-3.90) for severe liver disease (SLD), and 2.81 (2.60-3.03) for type 2 diabetes mellitus. The high PRS amplified the impact of MASLD on SLD and extrahepatic outcomes. CONCLUSIONS: High PRS of MASLD GWAS amplified the impact of MASLD on SLD and metabolism-related outcomes, thereby refining the process of identification of individuals at high risk of MASLD. Supplementation of this process with relevant genetic backgrounds may lead to more effective MASLD prevention and management.

High Performance Aqueous Zinc-Ion Batteries Developed by PANI Intercalation Strategy and Separator Engineering.

Aqueous zinc-ion batteries (ZIBs) have attracted burgeoning attention and emerged as prospective alternatives for scalable energy storage applications due to their unique merits such as high volumetric capacity, low cost, environmentally friendly, and reliable safety. Nevertheless, current ZIBs still suffer from some thorny issues, including low intrinsic electron conductivity, poor reversibility, zinc anode dendrites, and side reactions. Herein, conductive polyaniline (PANI) is intercalated as a pillar into the hydrated V2O5 (PAVO) to stabilize the structure of the cathode material. Meanwhile, graphene oxide (GO) was modified onto the glass fiber (GF) membrane through simple electrospinning and laser reduction methods to inhibit dendrite growth. As a result, the prepared cells present excellent electrochemical performance with enhanced specific capacity (362 mAh g-1 at 0.1 A g-1), significant rate capability (280 mAh g-1 at 10 A g-1), and admirable cycling stability (74% capacity retention after 4800 cycles at 5 A g-1). These findings provide key insights into the development of high-performance zinc-ion batteries.

SDS3 regulates microglial inflammation by modulating the expression of the upstream kinase ASK1 in the p38 MAPK signaling pathway.

BACKGROUND: Microglia, the main innate immune cells in the central nervous system, are key drivers of neuroinflammation, which plays a crucial role in the pathogenesis of neurodegenerative diseases. The Sin3/histone deacetylase (HDAC) complex, a highly conserved multiprotein co-repressor complex, primarily performs transcriptional repression via deacetylase activity; however, the function of SDS3, which maintains the integrity of the complex, in microglia remains unclear. METHODS: To uncover the regulatory role of the transcriptional co-repressor SDS3 in microglial inflammation, we used chromatin immunoprecipitation to identify SDS3 target genes and combined with transcriptomics and proteomics analysis to explore expression changes in cells following SDS3 knocking down. Subsequently, we validated our findings through experimental assays. RESULTS: Our analysis revealed that SDS3 modulates the expression of the upstream kinase ASK1 of the p38 MAPK pathway, thus regulating the activation of signaling pathways and ultimately influencing inflammation. CONCLUSIONS: Our findings provide important evidence of the contributions of SDS3 toward microglial inflammation and offer new insights into the regulatory mechanisms of microglial inflammatory responses.

Multimodal Machine Learning-Based Marker Enables Early Detection and Prognosis Prediction for Hyperuricemia.

Hyperuricemia (HUA) has emerged as the second most prevalent metabolic disorder characterized by prolonged and asymptomatic period, triggering gout and metabolism-related outcomes. Early detection and prognosis prediction for HUA and gout are crucial for pre-emptive interventions. Integrating genetic and clinical data from 421287 UK Biobank and 8900 Nanfang Hospital participants, a stacked multimodal machine learning model is developed and validated to synthesize its probabilities as an in-silico quantitative marker for hyperuricemia (ISHUA). The model demonstrates satisfactory performance in detecting HUA, exhibiting area under the curves (AUCs) of 0.859, 0.836, and 0.779 within the train, internal, and external test sets, respectively. ISHUA is significantly associated with gout and metabolism-related outcomes, effectively classifying individuals into low- and high-risk groups for gout in the train (AUC, 0.815) and internal test (AUC, 0.814) sets. The high-risk group shows increased susceptibility to metabolism-related outcomes, and participants with intermediate or favorable lifestyle profiles have hazard ratios of 0.75 and 0.53 for gout compared with those with unfavorable lifestyles. Similar trends are observed for other metabolism-related outcomes. The multimodal machine learning-based ISHUA marker enables personalized risk stratification for gout and metabolism-related outcomes, and it is unveiled that lifestyle changes can ameliorate these outcomes within high-risk group, providing guidance for preventive interventions.

Meta-Analyses of Methionine Source Concept Validation Trials in Broilers.

While the supplementation of methionine (Met) sources in broiler feeds has been established for several decades, there is debate on the nutritional value of the methionine hydroxy analogue of methionine (MHA) relative to DL-Met. Based on a recommendation suggesting that MHA is 65% as effective as DL-Met, many feeding trials have been conducted to challenge this recommendation. A literature search found 25 publications contributing 95 data sets suitable to compute Hedges' g effect sizes used in the meta-analysis. The data had very little heterogeneity of almost zero and the small effect sizes of the DL-Met results were not significantly different from MHA. Data were split in various subgroups, finally suggesting that neither broiler strain (Cobb 500, Ross 308), diet type (corn, wheat based), origin of data (peer-reviewed, grey literature), nor MHA product (MHA-free acid, MHA-calcium salt) impacted the outcome of the meta-analysis. Moreover, distinguishing data in groups with dietary Met+Cysteine (Cys) levels below, at, or above requirement demonstrated that there was no interaction with general Met+Cys supply. It is therefore concluded that MHA products can be replaced by DL-Met in a weight-to-weight ratio of 100:65 in any production condition without compromising broiler performance.

Bose-Einstein Condensation by Polarization Gradient Laser Cooling.

Attempts to create quantum degenerate gases without evaporative cooling have been pursued since the early days of laser cooling, with the consensus that polarization gradient cooling (PGC, also known as "optical molasses") alone cannot reach condensation. In the present work, we report that simple PGC can generate a small Bose-Einstein condensate (BEC) inside a corrugated micrometer-sized optical dipole trap. The experimental parameters enabling BEC creation were found by machine learning, which increased the atom number by a factor of 5 and decreased the temperature by a factor of 2.5, corresponding to almost 2 orders of magnitude gain in phase space density. When the trapping light is slightly misaligned through a microscopic objective lens, a BEC of ∼250 ^{87}Rb atoms is formed inside a local dimple within 40 ms of PGC after MOT loading.

Preparation of a Novel Branched Polyamide 6 (PA6) via Co-Polymerization of ε-Caprolactam and α-Amino-ε-Caprolactam.

In this study, a novel branched polyamide 6 has been synthesized via the hydrolytic ring-opening co-polymerization of ε-caprolactam (CPL) and α-Amino-ε-caprolactam (ACL). The NMR characterization proves the existence of a branched chain structure. The rheological test determines that there is a remarkable increase in the melt index (MFR), zero shear rate viscosity, and storage modulus in the low-frequency region. The shear-thinning phenomenon becomes more obvious. The thermal properties tested by differential scanning calorimetry (DSC) show that the melting point and crystallinity of co-polymers decrease with the incorporation of ACL. However, the crystal structure of the samples only exhibits a slight change. When the ACL content in the feed is 1 wt%, the tensile strength and fracture elongation rate of the co-polymers show a significant enhancement.

Multifunctional elastomeric composites based on 3D graphene porous materials.

3D graphene porous materials (3GPM), which have low density, large porosity, excellent compressibility, high conductivity, hold huge promise for a wide range of applications. Nevertheless, most 3GPM have brittle and weak network structures, which limits their widespread use. Therefore, the preparation of a robust and elastic graphene porous network is critical for the functionalization of 3GPM. Herein, the recent research of 3GPM with excellent mechanical properties are summarized and the focus is on the effect factors that affect the mechanical properties of 3GPM. Moreover, the applications of elastic 3GPM in various fields, such as adsorption, energy storage, solar steam generation, sensors, flexible electronics, and electromagnetic wave shielding are comprehensively reviewed. At last, the new challenges and perspective for fabrication and functionalization of robust and elastic 3GPM are outlined. It is expected that the perspective will inspire more new ideas in preparation and functionalization of 3GPM.

Facilitating the dry reforming of methane with interfacial synergistic catalysis in an Ir@CeO2-x catalyst.

The dry reforming of methane provides an attractive route to convert greenhouse gases (CH4 and CO2) into valuable syngas, so as to resolve the carbon cycle and environmental issues. However, the development of high-performance catalysts remains a huge challenge. Herein, we report a 0.6% Ir/CeO2-x catalyst with a metal-support interface structure which exhibits high CH4 (~72%) and CO2 (~82%) conversion and a CH4 reaction rate of ~973 µmolCH4 gcat-1 s-1 which is stable over 100 h at 700 °C. The performance of the catalyst is close to the state-of-the-art in this area of research. A combination of in situ spectroscopic characterization and theoretical calculations highlight the importance of the interfacial structure as an intrinsic active center to facilitate the CH4 dissociation (the rate-determining step) and the CH2* oxidation to CH2O* without coke formation, which accounts for the long-term stability. The catalyst in this work has a potential application prospect in the field of high-value utilization of carbon resources.

Unveiling Drivers of Retinal Degeneration in RCS Rats: Functional, Morphological, and Molecular Insights.

Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, significantly contribute to adult blindness. The Royal College of Surgeons (RCS) rat is a well-established disease model for studying these dystrophies; however, molecular investigations remain limited. We conducted a comprehensive analysis of retinal degeneration in RCS rats, including an immunodeficient RCS (iRCS) sub-strain, using ocular coherence tomography, electroretinography, histology, and molecular dissection using transcriptomics and immunofluorescence. No significant differences in retinal degeneration progression were observed between the iRCS and immunocompetent RCS rats, suggesting a minimal role of adaptive immune responses in disease. Transcriptomic alterations were primarily in inflammatory signaling pathways, characterized by the strong upregulation of Tnfa, an inflammatory signaling molecule, and Nox1, a contributor to reactive oxygen species (ROS) generation. Additionally, a notable decrease in Alox15 expression was observed, pointing to a possible reduction in anti-inflammatory and pro-resolving lipid mediators. These findings were corroborated by immunostaining, which demonstrated increased photoreceptor lipid peroxidation (4HNE) and photoreceptor citrullination (CitH3) during retinal degeneration. Our work enhances the understanding of molecular changes associated with retinal degeneration in RCS rats and offers potential therapeutic targets within inflammatory and oxidative stress pathways for confirmatory research and development.

In Situ Hybridization Strategy Constructs Heterogeneous Interfaces to Form Electronically Modulated MoS2/FeS2 as the Anode for High-Performance Lithium-Ion Storage.

The interfacial effect is important for anodes of transition metal dichalcogenides (TMDs) to achieve superior lithium-ion storage performance. In this paper, a MoS2/FeS2 heterojunction is synthesized by a simple hydrothermal reaction to construct the interface effect, and the heterostructure introduces an inherent electric field that accelerates the de-embedding process of lithium ions, improves the electron transfer capability, and effectively mitigates volume expansion. XPS analysis confirms evident chemical interaction between MoS2 and FeS2 via an interfacial covalent bond (Mo-S-Fe). This MoS2/FeS2 anode shows a distinct interfacial effect for efficient interatomic electron migration. The electrochemical performance demonstrated that the discharge capacity can reach up to 1217.8 mA h g-1 at 0.1 A g-1 after 200 cycles, with a capacity retention rate of 72.9%. After 2000 cycles, the capacity retention is about 61.6% at 1.0 A g-1, and the discharge capacity can still reach 638.9 mA h g-1. Electrochemical kinetic analysis indicated an enhanced pseudocapacitance contribution and that the MoS2/FeS2 had sufficient adsorption of lithium ions. This paper therefore argues that this interfacial engineering is an effective solution for designing sulfide-based anodes with good electrochemical properties.

Comprehensive analysis of the prognostic value and immunological role of IDO1 gene in pan-cancer.

OBJECTIVE: It has been demonstrated that IDO1, a target of immune checkpoint inhibition, functions as an oncogene in the majority of human malignancies. IDO1's function in human pan-cancers hasn't been thoroughly studied, though. MATERIALS AND METHODS: The Kaplan-Meier (K-M) and COX analyses were applied to the survival analysis. Furthermore, we used Spearman's correlation analysis to examine the associations between IDO1 and microsatellite instability (MSI), DNA methyltransferases (DNMTs), tumor mutational burden (TMB), the associated genes of mismatch repair (MMR), and immune checkpoint biomarkers. Moreover, immunohistochemical analysis and qRT-PCR were used to evaluate IDO1's expression in pan-cancer cells. RESULTS: The findings of this study reveal that IDO1 has abnormal expression in a number of malignancies and is related to the prognosis for UVM, LGG, KIRP, GBM, LAML, OV, READ, MESO, SARC, SKCM, and HNSC. Furthermore, the aberrant IDO1 expression was connected to the TMB, MSI, MMR, drug sensitivity, immune cells infiltrating, and tumor immune microenvironment across a variety of cancer types. The PCR results showed that in contrast to normal cells, IDO1 was found to be significantly highly expressed in breast cancer cells and hepatocellular carcinoma cells, and significantly lowly expressed in gastric cancer cells. CONCLUSION: The clinical treatment of IDO1 is now better supported by a theoretical basis and guidelines provided by our study.

Abnormal phosphorylation / dephosphorylation and Ca2+ dysfunction in heart failure.

Heart failure (HF) can be caused by a variety of causes characterized by abnormal myocardial systole and diastole. Ca2+ current through the L-type calcium channel (LTCC) on the membrane is the initial trigger signal for a cardiac cycle. Declined systole and diastole in HF are associated with dysfunction of myocardial Ca2+ function. This disorder can be correlated with unbalanced levels of phosphorylation / dephosphorylation of LTCC, endoplasmic reticulum (ER), and myofilament. Kinase and phosphatase activity changes along with HF progress, resulting in phased changes in the degree of phosphorylation / dephosphorylation. It is important to realize the phosphorylation / dephosphorylation differences between a normal and a failing heart. This review focuses on phosphorylation / dephosphorylation changes in the progression of HF and summarizes the effects of phosphorylation / dephosphorylation of LTCC, ER function, and myofilament function in normal conditions and HF based on previous experiments and clinical research. Also, we summarize current therapeutic methods based on abnormal phosphorylation / dephosphorylation and clarify potential therapeutic directions.

Endoscopic Supracerebellar Infratentorial Transpineal Approach for Posterior-Medial Thalamic Lesions: Surgical Technique and Clinical Experience.

BACKGROUND AND OBJECTIVES: Accessing lesions in the posterior-medial thalamus can be challenging because of their deep location and intricate neurovascular anatomy. This study aims to describe the techniques and feasibility of the endoscopic supracerebellar infratentorial transpineal approach for treating posterior-medial thalamus lesions. METHODS: We reviewed and analyzed the clinical outcomes and endoscopic surgical experience of 11 patients with posterior-medial thalamic lesions. The first 4 cases used the endoscopic midline supracerebellar infratentorial transpineal approach, whereas the subsequent 7 cases used the endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach. All cases involved the upward transposition of the pineal gland to access the posterior-medial thalamus. The extent of resection and the endoscopic techniques were the main focus of analysis. Neurological examinations and MRI/computed tomography follow-up were conducted for 3-12 months after surgery. RESULTS: The pathology of the group included 6 gliomas, 1 cavernous malformation, 1 inflammation, 1 melanoma, and 2 hematomas. All 11 patients achieved gross total resection (6 patients, 54.5%) or subtotal resection (5 patients, 45.5%) with no new neurological deficits. Most patients (9 patients, 81.8%) experienced improvement in Karnofsky Performance Status after surgery. Postoperative hydrocephalus occurred in 2 patients (18.2%) and was relieved by endoscopic third ventriculostomy. CONCLUSION: The endoscopic supracerebellar infratentorial transpineal approach is an effective approach for removing posterior-medial thalamic lesions that require access through the third ventricle surfaces of the thalamus. The endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach provides a more superior and lateral view of the posterior-medial thalamic lesions.

Association between sarcopenia-related markers and cholelithiasis: A prospective and Mendelian randomization study.

Cholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia-related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia-related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two-sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow-up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis.

Na2MnSiO4/C as hybrid capacitive deionization electrode material to enhance desalination performance.

The utilization of Na2MnSiO4 as a Faraday electrode in hybrid capacitive deionization (HCDI) is investigated to achieve efficient desalination. The Na2MnSiO4/C (NMSO) materials were fabricated via a simple sol-gel method, in which the synthesis process was modulated by adjusting the volume ratio of ethanol to water. When maintaining the volume ratio of water to ethanol at 3:1, the resultant NMSO-3/1 exhibited expected salt adsorption capacity of 31.06 mg g-1 and salt adsorption rate of 20.43 mg g-1 min-1. This distinguished desalination performance was mainly attributed to its inherent multiple redox pairs, as well as the integration of ethanol, which enhanced both specific capacitance and hydrophilicity of the material. This study opens a new perspective for the development of highly efficient materials in HCDI.

Assembly and characterization of the complete mitochondrial genome of Ventilago leiocarpa.

KEY MESSAGE: We reported the mitochondrial genome of Ventilago leiocarpa for the first time. Two and one sites lead to the generation of stop and stat codon through editing were verified. Ventilago leiocarpa, a member of the Rhamnaceae family, is frequently utilized in traditional medicine due to the medicinal properties of its roots. In this study, we successfully assembled the mitogenome of V. leiocarpa using both BGI short reads and Nanopore long reads. This mitogenome has a total length of 331,839 bp. The annotated results showed 36 unique protein-coding, 16 tRNA and 3 rRNA genes in this mitogenome. Furthermore, we confirmed the presence of a branched structure through the utilization of long reads mapping, PCR amplification, and Sanger sequencing. Specifically, the ctg1 can form a single circular molecule or combine with ctg4 to form a linear molecule. Likewise, ctg2 can form a single circular molecule or can be connected to ctg4 to form a linear molecule. Subsequently, through a comparative analysis of the mitogenome and cpgenome sequences, we identified ten mitochondrial plastid sequences (MTPTs), including two complete protein-coding genes and five complete tRNA genes. The existence of MTPTs was verified by long reads. Colinear analysis showed that the mitogenomes of Rosales were highly divergent in structure. Finally, we identified 545 RNA editing sites involving 36 protein-coding genes by Deepred-mt. To validate our findings, we conducted PCR amplification and Sanger sequencing, which confirmed the generation of stop codons in atp9-223 and rps10-391, as well as the generation of a start codon in nad4L-2. This project reported the complex structure and RNA editing event of the V. Leiocarpa mitogenome, which will provide valuable information for the study of mitochondrial gene expression.

Pre-lithiation strategy to design a high-performance zinc oxide anode for lithium-ion batteries.

Zinc oxide (ZnO) shows great potential as an anode material for advanced energy storage devices owing to its good structural stability and low cost. However, its inferior cycling capacity seriously restricts its practical application. In this work, a pre-lithiation strategy is adopted to construct pre-lithiated ZnO (Li-ZnO) via the facile solid-state reaction method. This well-designed Li-ZnO is polycrystalline, consisting of fine particles. XPS analysis and Raman results confirm the successful pre-lithiation strategy. The pre-lithiation strategy increases the electronic conductivity of Li-ZnO without further carbon coating and suppresses the volume expansion during the electrochemical reaction. As a result, 5 mol% Li-ZnO displays good reversible capacity with a specific capacity of 639 mA h g-1 after 200 cycles at 0.1 A g-1. After 1440 cycles at 1.0 A g-1, the capacity retention is 380 mA h g-1. The pseudocapacitance contribution can reach up to 72.5% at 1.0 mV s-1. Electrochemical kinetic analysis shows that this pre-lithiation strategy can accelerate the lithium-ion diffusion and charge transfer kinetics of the Li-ZnO anode and suppress the pulverization of the electrochemical reaction. This study demonstrates the necessity of developing new anode materials with good cycling stability via this pre-lithiation strategy.

Loss of 15-Lipoxygenase in Retinodegenerative RCS Rats.

Retinitis pigmentosa (RP) is a retinal degenerative disease associated with a diversity of genetic mutations. In a natural progression study (NPS) evaluating the molecular changes in Royal College of Surgeons (RCS) rats using lipidomic profiling, RNA sequencing, and gene expression analyses, changes associated with retinal degeneration from p21 to p60 were evaluated, where reductions in retinal ALOX15 expression corresponded with disease progression. This important enzyme catalyzes the formation of specialized pro-resolving mediators (SPMs) such as lipoxins (LXs), resolvins (RvDs), and docosapentaenoic acid resolvins (DPA RvDs), where reduced ALOX15 corresponded with reduced SPMs. Retinal DPA RvD2 levels were found to correlate with retinal structural and functional decline. Retinal RNA sequencing comparing p21 with p60 showed an upregulation of microglial inflammatory pathways accompanied by impaired damage-associated molecular pattern (DAMP) clearance pathways. This analysis suggests that ALXR/FPR2 activation can ameliorate disease progression, which was supported by treatment with an LXA4 analog, NAP1051, which was able to promote the upregulation of ALOX12 and ALOX15. This study showed that retinal inflammation from activated microglia and dysregulation of lipid metabolism were central to the pathogenesis of retinal degeneration in RP, where ALXR/FPR2 activation was able to preserve retinal structure and function.

Biomechanical analysis of combi-hole locking compression plate during fracture healing: A numerical study of screw configuration.

Locking compression plates (LCPs) have become a widely used option for treating femur bone fractures. However, the optimal screw configuration with combi-holes remains a subject of debate. The study aims to create a time-dependent finite element (FE) model to assess the impacts of different screw configurations on LCP fixation stiffness and healing efficiency across four healing stages during a complete fracture healing process. To simulate the healing process, we integrated a time-dependent callus formation mechanism into a FE model of the LCP with combi-holes. Three screw configuration parameters, namely working length, screw number, and screw position, were investigated. Increasing the working length negatively affected axial stiffness and healing efficiency (p < 0.001), while screw number or position had no significant impact (p > 0.01). The time-dependent model displayed a moderate correlation with the conventional time-independent model for axial stiffness and healing efficiency (ρ ≥ 0.733, p ≤ 0.025). The highest healing efficiency (95.2%) was observed in screw configuration C125 during the 4-8-week period. The results provide insights into managing fractures using LCPs with combi-holes over an extended duration. Under axial compressive loading conditions, the use of the C125 screw configuration can enhance callus formation during the 4-12-week period for transverse fractures. When employing the C12345 configuration, it becomes crucial to avoid overconstraint during the 4-8-week period.