Anti-liver cancer therapeutic targets and safety of usenamine A in experimental liver cancer.

BACKGROUND: Liver cancer is highly heterogeneous with poor drug response. Usenamine A has anticancer activity. Usnic acid has hepatocytotoxicity. OBJECTIVES: As a derivative of usnic acid, if usenamine A can be safely used in treatment for liver cancer is unknown. METHODS: MTT and clone formation assays assessed cell viability and proliferation. Tumor growth was determined using a xenograft model. Flow cytometry was used to detect the cell cycle. mRNA transcriptome sequencing investigated differential gene expression. Safety was evaluated in mice. KEY FINDINGS: Usenamine A inhibited proliferation and clone formation of HepG2 cells and xenograft tumor growth through cell cycle arrest at G0/G1. Usenamine A altered gene expression in a direction supporting anticancer activity. IL24, JUN, DUSP4, and DUSP5 were upregulated while PRKACA, PRKCB, TP53, WNT6, E2F3, LGR4, GPR78, and MAPK4 were downregulated. Ten of above genes overlapped in the KEGG enriched non-small cell lung cancer/glioma/cytokine-cytokine receptor interaction/Wnt/MAPK pathway network. Usenamine A has a strong binding affinity for PRKACA and PRKCB proteins. Usenamine A showed minimal toxicity in mice. CONCLUSIONS: Usenamine A is a safe anticancer agent against hepatocellular carcinoma. Regulation of 12 cancer-associated genes and the correlated pathway network are its therapeutic targets.

Solvation structure dependent ion transport and desolvation mechanism for fast-charging Li-ion batteries.

The solvation structures of Li+ in electrolytes play prominent roles in determining the fast-charging capabilities of lithium-ion batteries (LIBs), which are in urgent demand for smart electronic devices and electric vehicles. Nevertheless, a comprehensive understanding of how solvation structures affect ion transport through the electrolyte bulk and interfacial charge transfer reactions remains elusive. We report that the charge transfer reaction involving the desolvation process is the rate-determining step of the fast charging when ion conductivity reaches a certain value as determined by investigating electrolytes with eight conventional solvents (linear/cyclic carbonate/ether). The physicochemical characteristics of solvent molecules can result in strong ion-ion, moderate ion-dipole, strong ion-dipole, and weak ion-dipole/ion-ion interactions, respectively, in which the speed of the charge transfer reaction follows the above order of interactions. Among all solvents, dioxolane (DOL) is found to enable strong ion-ion interactions in electrolytes and thus exhibits exceptional fast-charging performance and it can still retain 60% of the initial capacity at 20C (1C = 170 mA g-1) with a polarization of merely 0.35 V. Further experimental characterization and theoretical calculation reveal that the aggregates in DOL electrolytes contribute to hopping assisted ion transport and facilitate the desolvation process of Li+. Our results deepen the fundamental understanding of the behavior of Li+ solvation and provide an effective guiding principle for electrolyte design for fast-charging batteries.

Screening chronic kidney disease through deep learning utilizing ultra-wide-field fundus images.

To address challenges in screening for chronic kidney disease (CKD), we devised a deep learning-based CKD screening model named UWF-CKDS. It utilizes ultra-wide-field (UWF) fundus images to predict the presence of CKD. We validated the model with data from 23 tertiary hospitals across China. Retinal vessels and retinal microvascular parameters (RMPs) were extracted to enhance model interpretability, which revealed a significant correlation between renal function and RMPs. UWF-CKDS, utilizing UWF images, RMPs, and relevant medical history, can accurately determine CKD status. Importantly, UWF-CKDS exhibited superior performance compared to CTR-CKDS, a model developed using the central region (CTR) cropped from UWF images, underscoring the contribution of the peripheral retina in predicting renal function. The study presents UWF-CKDS as a highly implementable method for large-scale and accurate CKD screening at the population level.

Charge transfer characteristics in rhodopsin mimics during photoexcitation.

To gain insights into the light-harvesting capabilities of the chromophores, it is essential to understand their molecular and electronic structures within their natural chemical or biological contexts. Rhodopsins display varied absorption characteristics due to the interaction between the chromophore retinal and its surrounding protein environments. In this study, we employed a quantum mechanics/molecular mechanics approach to examine a series of artificially designed rhodopsin mimics based on human cellular retinol acid binding protein 2 (hCRABP II). We elucidated the electron transfer within the all-trans protonated Schiff base upon light excitation, and our calculated absorption spectra show well consistency with the experimental result. Furthermore, the interaction mechanisms between the chromophore and the protein were investigated, and the relationship between the blueshifts and redshifts in the absorption spectra was analyzed. Our calculation demonstrates that the blueshifts and redshifts in the rhodopsin mimics correlate well with attractive (such as the hydrogen bonds or electrostatic interactions) and repulsive interactions (such as the steric effects) between the chromophore and the protein environment, respectively. These findings could provide hints for designing rhodopsin with absorption spectra at different wavelengths.

Black phosphorus nanosheets induce autophagy dysfunction by a size- and surface modification-related impairment of lysosomes in macrophages.

The widespread application of black phosphorus nanosheets (BPNSs) raises concerns about their potential impact on human health. Although that the autophagy-inducing properties of BPNSs in cancer cells are documented, their effects on macrophages-key components of the immune system and the mechanisms involved remain obscure, especially in terms of the influences of BPNS the size and surface modifications on the autophagic process. This study investigated the effects of bare BPNSs and PEGylated BPNSs (BP-PEG) on macrophage autophagy and its underlying mechanisms by comprehensive biochemical analyses. The results indicated that both BPNSs and BP-PEG are internalized by RAW264.7 cells through phagocytosis and caveolin-dependent endocytosis, leading to lysosomal accumulation. The internalized BPNSs induced mitochondrial dysfunction, which subsequently elevated the NAD+/NADH ratio and activated the SIRT-1 pathway, initiating autophagy. However, BPNSs disrupted the autophagic flux by impairing autolysosome formation, leading to apoptosis in a size-dependent manner. In contrast, BP-PEG preserved lysosomal integrity, maintaining autophagic activity and cell viability. These findings deepen our understanding of the influence of nanosheet size and surface modifications on macrophage autophagy, contributing to the formulation of regulatory guidelines to minimize the potential adverse effects and health risks associated with BPNS utilization in various applications.

Eliminating performance loss from perovskite films to solar cells.

Preoptimizing perovskite films may generally improve the performance of the final perovskite solar cells (PSCs). However, the research on whether the film optimization fully contributes to the enhancement of the final PSCs has been long neglected. We demonstrated that the preparation of metal electrodes by high-vacuum thermal evaporation, an unavoidable step in almost all device fabrication processes, will damage the surface of perovskite films, resulting in component escape, defect density rebound, carrier extraction barrier, and film stability deterioration. Therefore, the prepared perovskite film and the final film actually working in devices are not exactly the same, and the contribution of film optimization to the device improvement was weakened. We designed a bilayer structure composed of graphene oxide and graphite flakes to eliminate the unwanted film inconsistencies and thus save the film optimization loss. Therefore, the efficient PSCs with power conversion efficiency of 25.55% were obtained, which demonstrated negligible photovoltaic performance loss after operating for 2000 hours.

EBF1 is a potential biomarker for predicting progression from mild cognitive impairment to Alzheimer's disease: an in silico study.

Introduction: The prediction of progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is an important clinical challenge. This study aimed to identify the independent risk factors and develop a nomogram model that can predict progression from MCI to AD. Methods: Data of 141 patients with MCI were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We set a follow-up time of 72 months and defined patients as stable MCI (sMCI) or progressive MCI (pMCI) according to whether or not the progression of MCI to AD occurred. We identified and screened independent risk factors by utilizing weighted gene co-expression network analysis (WGCNA), where we obtained 14,893 genes after data preprocessing and selected the soft threshold ß = 7 at an R 2 of 0.85 to achieve a scale-free network. A total of 14 modules were discovered, with the midnightblue module having a strong association with the prognosis of MCI. Using machine learning strategies, which included the least absolute selection and shrinkage operator and support vector machine-recursive feature elimination; and the Cox proportional-hazards model, which included univariate and multivariable analyses, we identified and screened independent risk factors. Subsequently, we developed a nomogram model for predicting the progression from MCI to AD. The performance of our nomogram was evaluated by the C-index, calibration curve, and decision curve analysis (DCA). Bioinformatics analysis and immune infiltration analysis were conducted to clarify the function of early B cell factor 1 (EBF1). Results: First, the results showed that 40 differentially expressed genes (DEGs) related to the prognosis of MCI were generated by weighted gene co-expression network analysis. Second, five hub variables were obtained through the abovementioned machine learning strategies. Third, a low Montreal Cognitive Assessment (MoCA) score [hazard ratio (HR): 4.258, 95% confidence interval (CI): 1.994-9.091] and low EBF1 expression (hazard ratio: 3.454, 95% confidence interval: 1.813-6.579) were identified as the independent risk factors through the Cox proportional-hazards regression analysis. Finally, we developed a nomogram model including the MoCA score, EBF1, and potential confounders (age and gender). By evaluating our nomogram model and validating it in both internal and external validation sets, we demonstrated that our nomogram model exhibits excellent predictive performance. Through the Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes Genomes (KEGG) functional enrichment analysis, and immune infiltration analysis, we found that the role of EBF1 in MCI was closely related to B cells. Conclusion: EBF1, as a B cell-specific transcription factor, may be a key target for predicting progression from MCI to AD. Our nomogram model was able to provide personalized risk factors for the progression from MCI to AD after evaluation and validation.

Enhanced Interfacial Modification by Ordered Discotic Liquid Crystals for Thermotolerance Perovskite Solar Cells.

Traditionally used phenylethylamine iodide (PEAI) and its derivatives, such as ortho-fluorine o-F-PEAI, in interfacial modification, are beneficial for perovskite solar cell (PSC) efficiency but vulnerable to heat stability above 85 °C due to ion migration. To address this issue, we propose a composite interface modification layer incorporating the discotic liquid crystal 2,3,6,7,10,11-hexa(pentoxy)triphenylene (HAT5) into o-F-PEAI. The triphenyl core in HAT5 promotes π-π stacking self-assembly and enhances its interaction with o-F-PEAI, forming an oriented columnar phase that improves hole extraction along the one-dimensional direction. HAT5 repairs structural defects in the interfacial layer and retains the layered structure to inhibit ion migration after annealing. Ultimately, our approach increases the efficiency of solar cells from 23.36% to 25.02%. The thermal stability of the devices retains 80.1% of their initial efficiency after aging at 85 °C for 1008 hours without encapsulation. Moreover, the optimized PSCs maintained their initial efficiency of 82.4% after aging under one sunlight exposure for 1008 hours. This study provides a novel strategy using composite materials for interface modification to enhance the thermal and light stability of semiconductor devices.

Cancellation of the more complicated ophthalmic inpatient surgeries in a tertiary general hospital: a 10-year retrospective study.

Background: Although ophthalmic ambulatory surgeries are less costly and may enhance the more efficient utilization of hospital resources, inpatient surgeries were preferable alternatives for patients with complicated eye diseases or poor general health. However, the incidence, causes, and related factors of ophthalmic inpatient surgery cancellation remained largely unknown. Methods: The electronic medical records of ophthalmic inpatient surgeries between January 2012 and December 2022 was retrospectively reviewed. Cancellation-related factors were explored using multivariate logistic regression analysis and the reasons of cancellation were also evaluated. Results: In total, 820 cancelled surgeries and 42,073 performed surgeries were included, with a cancellation rate of 1.9%. Any other ocular comorbidities were risk factors for cancellation (odds ratio (OR) 1.872, 95% confidence intervals (CI) 1.504-2.331; p < 0.001), while older age (OR 0.990, 95% CI 0.986-0.995; p < 0.001), local residence (OR 0.809, 95% CI 0.692-0.947; p = 0.008), any systemic comorbidities (OR 0.740, 95% CI 0.616-0.889; p = 0.001), and previous history of surgeries (OR 0.403, 95% CI 0.341-0.476; p < 0.001) were negatively associated with surgery cancellation. The top two categorical cancellation reasons were medical factors (508, 62.0%) and patient-related factors (285, 34.8%). "Patient/family refused surgery" (127, 15.5%), "acute conjunctivitis or uveitis relapse" (103, 12.6%), and "ocular condition improved and procedure no longer indicated" (71, 8.7%) were the three most common single cancellation reasons. Conclusion: Any other ocular comorbidities, younger age, no systemic comorbidities, non-local residence, and no past surgical history were related factors for ophthalmic inpatient surgery cancellation. The majority of cancellations were due to patient-related or medical factors. Great importance should be attached to the cancellation of the more complicated inpatient surgeries and further efforts are warranted to explore how to reduce cancellation.

Exploring the impact of variable power outputs on the efficacy and safety during microwave ablation for lung carcinoma: a real-world study.

Background: Microwave ablation (MWA) is an important method for the treatment of lung cancer, but there is still a lack of standard guidelines for the selection of power. This study aimed to explore the effectiveness and safety of MWA at different power levels. Methods: The study gathered individuals underwent MWA for lung cancer between January 2012 and December 2020. All patients were divided into low power group and high power group based on the power of MWA. By intergroup comparisons, we clarified the differences between the two groups. Results: In this study, 265 participants were involved, with 192 in the low power group and 73 in the high power group. Compared to the low power group, the high power group had a significantly higher incidence of postoperative complications (63.0% vs. 24.0%). In the Kaplan-Meier analysis, overall survival (OS) and disease-free survival (DFS) of the high power group were both better than the low power group. We found through Cox regression analysis that smoking, tumor volume, tumor differentiation, gene mutation, neutrophil count, and lymphocyte count were independent factors affecting the OS of patients. Based on the above factors, we constructed a nomogram, with areas under the curve (AUCs) of 0.941, 0.903, and 0.905 for predicting 1-, 2-, and 3-year OS after MWA, respectively. Conclusions: While high-power MWA brings better long-term prognosis to patients, it also leads to an increase in postoperative complications. The application of a nomogram for stratifying the prognosis of patients may be a more feasible approach to further develop individualized treatment plans.

Age- and sex-related differences in risk factors for perioperative intra-aortic balloon pump application in patients undergoing coronary artery bypass grafting.

Background: An intra-aortic balloon pump (IABP) is a mechanical circulatory device frequently used in patients undergoing coronary artery bypass grafting (CABG). As a treatment for perioperative haemodynamic instability, IABP insertion often implicates an adverse outcome. This study aimed to investigate the age- and sex-related disparity in risk factors for perioperative IABP insertion in CABG patients. Methods: A total of 2,460 CABG patients were included and divided into subgroups by age (elderly subgroup, ≥65 years; young subgroup, <65 years) and sex. Basic characteristics were compared between IABP and non-IABP patients in the overall patient group and the subgroups. Multivariate logistic analysis was used to investigate the significant risk factors for perioperative IABP application, and interaction effects among the potential risk factors were analysed. Combined receiver operating characteristic analysis was used to evaluate the prediction value of combined risk factors. Results: The overall patient group had a mean age of 61.5 years. The application rate of perioperative IABP was 8.0%. A left ventricular ejection fraction (LVEF) <50% significantly correlated with perioperative IABP application in the overall patient group and the subgroups. Traditional factors such as myocardial infarction history, atrial fibrillation history, and intraoperative estimated blood loss were significant risk factors in certain subgroups. Small dense low-density lipoprotein levels were significantly associated with IABP insertion in the male subgroup and young subgroup. The area under the curve of combined risk factors was significantly higher than that of LVEF <50% alone in the overall patient group and subgroups. Conclusion: Age- and sex-related differences were present in the risk factor distribution for perioperative IABP insertion in CABG patients.

Untargeted metabolomics analysis of the urinary metabolic signature of acute and chronic gout.

BACKGROUND: Gout is a common kind of inflammatory arthritis with metabolic disorders. However, the detailed pathogenesis of gout is complex and not fully clear. We investigated the urine metabolic profiling of gout patients by ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). METHOD: Urine metabolites were extracted from 26 acute gout patients, 31 chronic gout patients, and 32 healthy controls. Metabolite extracts were analyzed by UPLC-Q-TOF-MS for untargeted metabolomics. The peak area of creatinine was used to correct the content variations of urine samples for the semi-quantitative analysis. The value of variable importance in the projection (VIP) was obtained through the orthogonal partial least squares-discrimination analysis (OPLS-DA), and several differential metabolites were screened out. RESULTS: The potential metabolic markers of gout in different stages were found based on the t-test. Finally, 18 different metabolites were identified through Human Metabolome Database (HMDB) and Targeted-MS/MS. The receiver operating characteristic (ROC) curve results revealed that all the screened biomarkers exerted high accuracy and diagnostic value. Pathway analysis indicated that the significantly different metabolites were mainly involved in purine metabolism and amino acid metabolism. CONCLUSION: The identified potential biomarkers are mainly involved in purine metabolism and amino acid metabolism, which leads us to further explore the pathogenesis of gout. This will lead us to further explore the pathogenesis of gout and provide the basis and ideas for the prevention and treatment of gout.

Functional evolution and diversification of the CYP82D subfamily members shape flavonoid diversification in the genus Scutellaria.

Flavonoids, the largest class of polyphenols, exhibit substantial structural and functional diversity, yet their evolutionary diversification and specialized functions remain largely unexplored. The genus Scutellaria is notable for its rich flavonoid diversity, particularly the 6/8-hydroxylated variants biosynthesized by the cytochrome P450 subfamily CYP82D. Our study analyzes metabolic differences between Scutellaria baicalensis and Scutellaria barbata, suggesting that CYP82Ds have acquired a broad range of catalytic functions over their evolution. By integrating analyses of metabolic networks and gene evolution across 22 Scutellaria species, we rapid identified 261 flavonoids and delineated five clades associated with various catalytic functions of CYP82Ds. This approach uncovered a unique catalytic mode for 6/8-hydroxylated function under flavanone substrates and the first instance of 7-O-demethylation of flavonoid substrates catalyzed by cytochrome P450. Ancestral sequence reconstruction and functional validation demonstrated that gradual neofunctionalization of CYP82Ds has driven the chemical diversity of flavonoids in Scutellaria throughout its evolutionary history. Our study enhances the understanding of flavonoid diversity, elucidates the intricate roles of CYP82Ds in Scutellaria plants, and underscores the extensive catalytic versatility of cytochrome P450 members within plant taxa.

Contributions of individual qSOFA elements to assessment of severity and for prediction of mortality.

BACKGROUND: The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown. METHODS: A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden's index were employed to assess discrimination. RESULTS: Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden's index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices. CONCLUSIONS: Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.

Respiratory rate ≥22/min demonstrated the most superior diagnostic value.Respiratory rate ≥22/min showed the strongest association with severity.Respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg predicted mortality well, adequately and poorly, respectively.

Differences between phytophagous and predatory species in Pentatomidae based on the mitochondrial genome.

Pentatomidae includes many species of significant economic value as plant pests and biological control agents. The feeding habits of Pentatomidae are closely related to their energy metabolism and ecological adaptations. In this study, we sequenced the mitochondrial genomes of 12 Asopinae species using the next-generation sequencing to explore the effect of dietary changes on mitochondrial genome evolution. Notably, all sequences were double-stranded circular DNA molecules containing 37 genes and one control region. We then compared and analyzed the mitochondrial genome characteristics of phytophagous and predatory bugs. Notably, no significant difference was observed in the length of the mitochondrial genomes between the predatory and phytophagous bugs. However, the AT content was higher in the mitochondrial genomes of phytophagous bugs than that of predatory bugs. Moreover, phytophagous bugs prefer codon usage patterns ending in A/T compared with predatory bugs. The evolution rate of predatory bugs was lower than that of phytophagous bugs. The phylogenetic relationships across phytophagous bugs' lineages were largely consistent at depth nodes based on different datasets and tree-reconstructing methods, and strongly supported the monophyly of predatory bugs. Additionally, the estimated divergence times indicated that Pentatomidae explosively radiated in the Early Cretaceous. Subsequently, the subfamily Asopinae and the genus Menida diverged in the Late Cretaceous. Our research results provide data supporting for the evolutionary patterns and classification of Pentatomidae.

Non-invasive TMS attenuates neuropathic pain after spinal cord injury associated with enhancing brain functional connectivity and HPA axis activity.

Patients with spinal cord injury (SCI) often suffer from varying degrees of neuropathic pain. Non-invasive repetitive transcranial magnetic stimulation (TMS) has been shown to improve neuropathic pain, while the appropriate intervention strategies of TMS treatment and how TMS affects brain function after SCI were not entirely clear. To investigate the effects and mechanisms of TMS on neuropathic pain after SCI, high-frequency TMS on primary motor cortex (M1) of mice was performed after SCI and pain response was evaluated through an electronic Von-Frey device and cold/hot plates. Functional magnetic resonance imaging (fMRI), bulk RNA sequencing, immunofluorescence and molecular experiments were used to evaluate brain and spinal cord function changes and mechanisms. TMS significantly improved SCI induced mechanical allodynia, cold and thermal hyperalgesia with a durative effect, and TMS intervention at 1 week after SCI had pain relief advantages than at 2 weeks. TMS intervention not only affected the functional connections between the primary motor cortex and the thalamus, but also increased the close connection of multiple brain regions. Importantly, TMS treatment activated the hypothalamic pituitary adrenal (HPA) axis and increased the transcript levels of genes encode hormone proteins, accompanied with the attenuation of inflammatory microenvironment in spinal cord associated with pain relief. Totally, these results elucidate that early intervention with TMS could improve neuropathic pain after SCI associated with enhancing brain functional connectivity and HPA axis activity which should be harnessed to modulate neuropathic pain after SCI.

Clinical efficacy of a head-mounted device for central vision loss.

Central vision loss (CVL) is a major form of low vision that remains inadequately managed worldwide. This study evaluated the clinical efficacy of a novel head-mounted device (HMD), Onyx, designed to enhance visual function and vision-related quality of life for CVL patients. It employs a projection system that enables patients to leverage their residual peripheral vision for environmental awareness. It also integrates artificial intelligence to augment the automatic recognition of text, faces, and objects. In this single-center, prospective cohort study, 41 binocularly low vision patients with CVL were instructed to use Onyx for 4 to 6 h daily over a one-month period. Various metrics were assessed, including near and distance visual acuity (VA), recognition abilities for faces and objects, and the low vision quality-of-life (LVQOL) questionnaire scores, at the start and end of the study. The results showed significant improvements in near VA for 60.98% of the participants, distance VA for 80.49%, and recognition ability for 90.24%. 68.29% of the participants showed significant improvements in the LVQOL scores. Improvement in recognition ability was negatively correlated with baseline recognition ability. Additionally, improvement in the LVQOL scores was correlated with age and the baseline LVQOL score. Overall, the study found that the novel HMD significantly improved visual function and vision-related quality of life for low vision patients with CVL, highlighting the potential benefits and the need for further evaluation of such devices.

Role of microenvironment characteristics and MRI radiomics in the risk stratification of distant metastases in rectal cancer: A diagnostic study.

OBJECTIVES: To compare the value of tumor stroma ratio (TSR) and radiomic signature from baseline MRI for stratifying the risk of distant metastases (DM) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Data from 302 patients with LARC who underwent neoadjuvant chemoradiotherapy and total mesorectal excision in our hospital between 2015 and 2018 were retrospectively reviewed, and the patients were randomly allocated into the training and validation cohorts in a ratio of 7:3. Patients were followed-up for more than 3 years postoperatively with metachronous DM as the endpoint. Independent risk factors for DM-free survival (DMFS) were analyzed using Cox regression. The TSR of endoscopic biopsy specimens was scored automatically. Totally 1229 radiomic features of each tumor were extracted from baseline MRI, and the Radscore was calculated. RESULTS: The median follow-up time was 54.3 (51.6-57.1) months, and the 3-year DMFS was 83.8%. The best cutoff value of the TSR to distinguish patient's DM risk was 0.477 (Sen=70.8%, Sep=78%, P<0.001). Increased TSR (HR=3.072, P=0.006) and Radscore (HR=719.231, P=0.023), advanced MR-evaluated T stage (HR=2.660, P=0.023) and ypN (HR=2.362, P=0.028) stage were independent risk factors for DMFS. The area under the curve of the combined model was significantly higher than that of the radiomic model (P=0.013) but without significant advantage over the TSR model (P=0.086). CONCLUSION: TSR of colonoscopic biopsies can independently stratify DM risk in patients with LARC. The TSR model is the most convenient and efficient method for DM risk stratification in LARC.