Elucidating the Fundamental Process of Methyl-(5hydroxymethyl) Furan-2-Carboxylate Toxin Biosynthesis in Curvularia lunata Causing Maize Leaf Spot.

Maize leaf spot, which is caused by Curvularia lunata (Wakkre) Boedijn, was epidemic in the maize-growing regions of northeastern and northern China in the mid-1990s, where it led to large yield losses. Since then, the epidemic has evolved into a kind of common disease. In recent years, however, a tendency of becoming an epidemic disease again has been observed in some areas in China due to significant changes in climate, farming, systems and crop varieties. The significance of methyl-(5hydroxymethyl) furan-2-carboxylate (M5HF2C) as a nonspecific host toxin in causing maize leaf spot disease has been demonstrated in previous research. However, the key enzymes involved in M5HF2C toxin synthesis remain unclear. In our study, we demonstrate that the synthesis of M5HF2C toxin starts from a precursor substrate in the pathogen, furfural, which is then catalytically dehydrogenated into furoic acid via an alcohol dehydrogenase (CLADH6). The furoic acid was further confirmed as one of the raw materials for the biosynthesis of M5HF2C toxin based on deletion mutants of the alcohol dehydrogenase gene (Cladh6) in C. lunata, which had reduced M5HF2C toxin-producing ability; however, this ability could be restored in all deletion mutants through complementation with furoic acid, thereby confirming that furoic acid is an intermediate in the biosynthesis of M5HF2C toxin. In summary, the biosynthesis process of M5HF2C toxin in C. lunata involves three transformation steps: (1) from xylose to furfural; (2) then from furfural to furoic acid; and (3) eventually from furoic acid to M5HF2C toxin. Our research findings provide new clues in elucidating the major steps in the process of M5HF2C toxin biosynthesis in C. lunata.

The largest single-species Nanozostera japonica seagrass meadow of China: Its decline, restoration attempts, and short-term effects on macrobenthos and soil bacterial communities.

Seagrass beds support vital ecological functions so that when seagrass experience severe degradation, their ecosystem service functions are diminished or lost. The largest Nanozostera japonica seagrass bed in China, situated in the Yellow River Delta, has undergone significant degradation due to Spartina alterniflora invasion and the impact of Typhoon Lekima (2019). The lack of seeds and overwintering shoots makes natural seagrass recovery challenging, prompting the urgent need for seagrass ecological restoration. In the present study, seed sowing experiments were conducted with varying burial depths, seed sources, and sowing times, as well as transplantation experiments with different transplant unit sizes and intervals in the severely degraded seagrass bed. Subsequently, changes in macrobenthos and soil bacterial diversity were tracked after seagrass recovery. According to the results, the optimal burial depth for N. japonica seeds varies across different sediment types, with 4 cm being suitable for sandy soil and 2 cm for silty soil. Seeds sown in May did not survive due to high temperatures. Seeds from Dalian exhibited superior growth after sowing, making them ideal material for seed restoration projects. Transplanting N. japonica sods with 25 × 25 cm transplant units and 50-cm intervals resulted in the most robust growth, indicating it as a suitable method for adult transplantation. Following seagrass re-establishment, macrobenthos and soil bacterial diversity increased significantly. The findings of the present study provide valuable technical guidance and theoretical support for the ecological restoration of N. japonica. Future efforts should prioritize the restoration of seagrass bed ecological functions, with longer-term effects examined.

The complete plastome of Rorippa palustris Besser 1821 and its phylogenetic analysis.

Rorippa palustris Besser 1821, a species of Brassicaceae, is widely distributed around the world and used for both food and traditional Chinese medicinal purposes. Despite the plant's significance, its genetic diversity must be better understood. In this study, we have successfully assembled and characterized a complete plastome of R. palustris, marking a significant advancement toward comprehending its genetic composition. The plastome is 154,674 bp long and harbors 128 genes, including 83 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Our phylogenomic analysis indicated that R. palustris is closely related to R. curvipes. These findings are crucial for conserving and utilizing this important plant species. They also highlight the potential for future research into the evolution and preservation of R. palustris, which could be advantageous in pharmaceutical applications.

Cardiovascular death risk in patients with solid tumors: a population-based study in the United States.

BACKGROUND: Previous studies have focused on the risk of cardiovascular disease (CVD)-specific death in hematological cancers and in some single anatomical tumor sites, there remains a paucity of data on systematic analyses in solid tumors. OBJECTIVE: The objective of this study is to evaluate the distribution, risk, and trends of CVD-specific death in patients with solid tumors. METHODS: A total of 2 679 293 patients with solid tumors diagnosed between 1975 and 2019 were screened from the Surveillance, Epidemiology and End Results (SEER) program across 15 anatomical sites. Standardized mortality ratios (SMRs) and absolute excess risks (AERs) were used to describe the intensity of CVD-specific death, competing risk regression models were used to assess the risk of CVD-specific death, and restricted cubic spline analyses were employed to investigate the potential linear or nonlinear relationship between age and CVD death. RESULTS: CVD-specific death in patients with solid tumors accounted for 48.95% of non-cancer deaths. Compared with the general population, patients with solid tumors had higher SMR and AER of CVD death (SMR: 1.15; AER: 21.12), heart disease-related death (SMR: 1.13; AER: 13.96), and cerebrovascular disease-related death (SMR: 1.20; AER: 4.85). Additionally, the SMR exhibited a decreasing trend with increasing time to diagnosis. Furthermore, a nonlinear relationship was observed between age and CVD-specific death in patients with solid tumors of different systems. CONCLUSION: CVD-specific death accounted for a large proportion of the cause of non-cancer deaths. Patients with solid tumors exhibit an elevated risk of CVD-specific death. Screening for CVD death and optimizing risk management in patients with solid tumors throughout anticancer treatment may be beneficial in preventing CVD death.

Severe Microbial Corrosion of L245 Transportation Pipeline Triggered by Wild Sulfate Reducing Bacteria in Shale Gas Produced Water.

The development of pitting corrosion on L245 carbon steel in a culture medium solution containing sulfate-reducing bacteria (SRB) was investigated. The results showed that the occurrence of corrosion in L245 carbon steel is closely linked to the evolution of biofilm and product film. As the test duration extended, overall corrosion was inhibited. Simultaneously, bacteria beneath the film layer promoted the generation and development of pitting corrosion, and the aggregation of bacteria (colonies) led to the aggregation of pitting corrosion.

Corrosion of Sulfate-Reducing Bacteria on L245 Steel under Different Carbon Source Conditions.

Objective Sulfate-reducing bacteria (SRB) pose a threat to the safe operation of shale-gas-gathering pipelines. Therefore, it is essential to explore the role played by SRB in dedicated pipelines. Methods In this work, the corrosion behavior of SRB was investigated by organic carbon starvation immersion experiments combined with cell number monitoring, corrosion weight loss recordings, morphology and profile observations and electrochemical measurements. Results In experiments with sodium lactate content ranging from 0-3500 ppm, the corrosion rate and pitting depth were the highest at 350 ppm. Conclusions The results indicated that the reduction in carbon sources leads to bacterial starvation, which directly obtains electrons from metals and exacerbates corrosion. It is not appropriate to use the content of bacteria to determine the strength of bacterial corrosion.

Long-lasting organics removal via •OH adsorbed transition metal flocs: Electron transfer-mediated H-bond and van der Waals force.

Homogenous advanced oxidation processes (AOPs) based on transition metal catalysts toward the activation of H2O2 to hydroxyl radical (•OH) have been widely applied to organic pollutants removal, such as Fenton and Fenton-like processes. These transition metal catalysts mostly flocculate as the pH increases. It's worth noting that the formed transition metal flocs are complex heterogeneous aggregations with active substances, providing diverse reaction spaces and interfaces. However, it is a challenge to distinguish the roles of transition metal flocs in the organic pollutants removal from homogeneous catalytic reactions. Herein, we unveiled a pathway for the long-lasting removal of organic pollutants via Cr flocs adsorbed with •OH (HO•-Cr flocs) using a stepwise method. First, adsorbed •OH (•OHads) within the HO•-Cr flocs was proved to be the active site forming hydrogen bond (H-bond) and van der Waals force with organic pollutants. Then, the presence of switchable electron transfer between Cr and OH groups within the HO•-Cr flocs was revealed, contributing to the persistent existence of •OHads and consequently ensuring the long-lasting organics removal. Further, this removal pathway of organic pollutants was confirmed during the leather wastewater treatment. These findings will complement a different pathway for organic pollutants removal via transition metal flocs and extend the lifetime of homogeneous AOPs based on transition metal catalysts, providing significant implications for their design and optimization.

Efficacy of Nasal Septal Complex in the Endoscopic Reconstruction of Medial Orbital Wall.

The aim of this study is to investigate the efficacy of nasal septal complex reconstructing the medial orbital wall under some specific circumstances. The authors performed a study that included 10 patients who underwent isolated medial orbital wall fracture (blow-out fracture). All the reconstruction surgery of the patient included in this study fixed defect of medial orbital wall using autologous nasal septal complex (composed of nasal septal cartilage and perpendicular plate of ethmoid). The authors observed postoperative improvements of diplopia or ocular motility disorders of the affected orbit. The surgeries had gained satisfactory results, and without severe postoperative complications. After long-term follow-up, postoperative CT indicated the implant-covered defect of medial orbital wall, and there's no incarceration of the medial rectus. Meanwhile, the authors found there is no crack in the implant, and the surgery using nasal septal complex achieved premorbid orbital form. Autologous nasal septal complex provides a better complement to endoscopic reconstruction of medial orbital wall; this strategy allows nasal septum to reconstruct isolated medial orbital wall defects of various degrees, such as nasal septum fracture and dysplasia of perpendicular plate of ethmoid.

Pyroptosis inhibition alleviates acute lung injury via E-twenty-six variant gene 5-mediated downregulation of gasdermin D.

BACKGROUND: Acute lung injury (ALI) is a life-threatening condition characterized by excessive pulmonary inflammation, yet its precise pathophysiology remains elusive. Pyroptosis, a programmed cell death mechanism controlled by gasdermin D (GSDMD), has been linked to the etiology of ALI. This study investigated the regulatory functions of the transcription factor E-twenty-six variant gene 5 (ETV5) and GSDMD in ALI. METHODS: Lipopolysaccharide (LPS) was used to treat BEAS-2B cells (50 mmol/mL) and establish an LPS-induced mouse model of ALI (by intratracheal administration, 3 mg/kg). Protein-protein docking, immunofluorescence analysis, western blotting, real-time quantitative polymerase chain reaction, and dual-luciferase reporter gene assay were used to examine ETV5-mediated negative feedback regulation of GSDMD and its effects on pyroptosis and ALI. RESULTS: Our results showed that the physiological function of ETV5 was reduced by its downregulated expression, which impeded its nuclear translocation in ALI mice. Increased pyroptosis and enhanced production of inflammatory cytokines were associated with LPS-induced ALI. ETV5 overexpression in LPS-treated BEAS-2B cells decreased the expression of total and membrane-bound GSDMD, negatively regulated GSDMD, and prevented pyroptosis. The expression of inflammatory cytokines was subsequently reduced due to this inhibition, which, in turn, reduced ALI. Molecular docking analysis and dual-luciferase reporter gene assay results indicated a direct interaction between ETV5 and GSDMD, which inhibited GSDMD production. CONCLUSION: Our results indicate that ETV5 inhibits pyroptosis, decreases the expression of inflammatory cytokines, and negatively regulates GSDMD expression to ameliorate ALI symptoms.

The complete chloroplast genome of Lindernia crustacea (L.) F. Muell 1882 (Linderniaceae) and its phylogenetic analysis.

Lindernia crustacea (L.) F. Muell 1882, a species in the Linderniaceae family, holds traditional medicinal value in China. To investigate its genetic diversity, we assembled, annotated, and characterized the first complete chloroplast genome of L. crustacea using Illumina sequencing data and various bioinformatics tools. The genome is 153,647 bp in length, with a GC content of 37.6%. It exhibits a typical quadripartite structure, consisting of a large single-copy region (LSC) of 85,411 bp, a small single-copy region (SSC) of 18,724 bp, and two inverted repeat sequences (IRa and IRb) of 25,816 bp each. The genome was predicted to contain 131 genes, including 87 protein-coding genes, 36 tRNA genes, and eight rRNA genes. Phylogenomic analysis indicated that L. crustacea is closely related to L. stricta. These findings provide a foundation for further research on the evolution and potential medicinal applications of the Linderniaceae family.

Exploring the Expression Profiles of Serum Inflammatory Proteins and Potential Antiaging Targets in Chinese Long-Living People.

Chronic inflammation (inflammaging) is one of the important reasons for the development of age-related diseases and aging. Carrying out aging research and mining inflammatory markers can develop antiaging intervention targets, thus promoting healthy aging. By comparing the levels of inflammatory proteome in the serum of Chinese long-living people over 90 years and elderly aged 60∼79 which was detected by Olink platform, this study found that some pro-inflammatory or pro-aging proteins increased significantly in the long-living people, such as c-x-c motif chemokine ligand 9, accompanied by a significant increase in the levels of several anti-inflammatory or antiaging proteins, including fibroblast growth factor 19 and fibroblast growth factor 23, which confirmed that compared with elderly people, pro-inflammatory and anti-inflammatory (pro-aging and antiaging) tend to be balanced in long-living people, thus reducing the risk of age-related diseases and prolonging the lifespan of the elderly. These differently expressed proteins could serve as therapeutic targets and monitoring indicators for antiaging. At the same time, a few inflammatory protein markers, especially c-x-c motif chemokine ligand 9 and osteoprotegerin, could distinguish long-living and elderly correctly, which could be used to predict lifespan combined with other antiaging markers.

Sudden sulfamethoxazole shock leads to nitrite accumulation in microalgae-nitrifying bacteria consortia: Physiological responses and light regulating strategy.

Antibiotic shock may potentially impact the performance of promising microalgae-nitrifying bacteria consortia (MNBC) processes. This study investigated physiological behaviors of MNBC under sulfamethoxazole (SMX) shock (mg/L level) and verified a light regulating strategy for improving process performance. Results showed that SMX shock did not affect ammonium removal but caused nitrite accumulation, resulting from combined effects of excessive reactive oxidative species (ROS) production, inhibited microalgal photosynthetic activity, upregulated expressions of amoA and hao, and downregulated expression of nxrA. Moreover, high ammonium concentration aggravated nitrite accumulation and reduced ammonium removal owing to significantly reduced dissolved oxygen (DO). Increasing light intensity enhanced microalgal photo-oxygenation and promoted expressions of all nitrification-related genes, thus improving ammonium removal and alleviating nitrite accumulation. A central composite design coupled with response surface methodology (CCD-RSM) further demonstrated the negative impacts of SMX shock and high ammonium on MNBC and the effectiveness of the light regulation in maintaining stable process performance. This study provides theoretical basis for physiological responses and regulatory strategy of the MNBC process facing short-term antibiotic shock.

The protective effect and bioactive compounds of Astragalus membranaceus against neurodegenerative disorders via alleviating oxidative stress in Drosophila.

Oxidative stress is proposed as a regulatory element in various neurological disorders, which is involved in the progress of several neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Antioxidant drugs are widely used to alleviate neurodegenerative disorders. Astragalus membranaceus (Huangqi, AM) is a commonly used medicinal herb with a wide range of pharmacological effects. Here, the protective effect and mechanism of AM extract (AME) and its bioactive compounds against neurodegenerative disorders via alleviating oxidative stress were detected using adult Drosophila melanogaster. The drug safety was measured by development analysis; oxidative stress resistance ability was detected by survival rate under H2O2 environment; ROS level was detected by DHE staining and gstD1-GFP fluoresence assay; antioxidative abilitiy was represent by measuring antioxidant enzyme activity, antioxidative-related gene expression, and ATP and MFN2 levels. The neuroprotective effect was evaluated by lifespan and locomotion analysis in Aß42 transgenic and Pink1B9 mutants. AME dramatically increased the survival rates, improved the CAT activity, restored the decreased mRNA expressions of Sod1, Cat, and CncC under H2O2 stimulation, and ameliorated the neurobehavioral defects of the AD and PD. Thirteen small molecules in AM had antioxidant function, in which vanillic acid and daidzein had the most potent antioxidant effect. Vanillic acid and daidzein could increase the activities of SOD and CAT, GSH level, and the expressions of antioxidant genes. Vanillic acid could improve the levels of ATP and MFN2, and mRNA expressions of ND42 and SDHC to rescue mitochondrial dysfunction. Furthermore, vanillic acid ameliorated neurobehavioral defects of PD. Daidzein ameliorated neurobehavioral defect of Aß-induced AD mode. Taken together, AM plays a protective role in oxidative damage, thereby as a potential natural drug to treat neurodegenerative disorders.

A novel endocardial activation-derived predictor for focal paraseptal atrial tachycardias: Evidence from a multicenter cohort study.

BACKGROUND: The electrocardiogram-based algorithm for predicting paraseptal atrial tachycardia (PSAT) is limited by the significant overlaps in P-wave morphology originating from various paraseptal sites. OBJECTIVES: The goals of this study were to investigate the endocardial activation characteristics of PSAT and to seek an endocardial activation-derived predictor for the ablation site. METHODS: Forty-four patients [11 men (25%); mean age 62.6 ± 14.7 years] with PSAT ablation in 4 tertiary medical centers were assigned to 3 groups according to the ablation site: right atrial (RA) para-Hisian region (group 1, n = 10), noncoronary cusp (NCC) (group 2, n = 13), and left atrial (LA) paraseptal area (group 3, n = 21). Multiple-chamber activation mapping was performed guided by a 3-dimensional navigation system. The discrepancies in the earliest activation time between 2 of 3 chambers (ΔRA-LA, ΔRA-NCC, and ΔLA-NCC) were calculated in each group and used for pairwise comparisons. RESULTS: There was a significant difference in ΔRA-LA, ΔRA-NCC, and ΔLA-NCC among the 3 groups. ΔRA-LA was the only parameter that could consistently predict the ablation site of PSAT with good accuracy (area under the curve 1.000, sensitivity 100% and specificity 100%, and cutoff value 7 ms for predicting right para-Hisian or NCC ablation; area under the curve 0.974, sensitivity 92.3% and specificity 95.2%, and cutoff value -4 ms for predicting NCC or left paraseptal ablation). Based on 2 cutoff values, a 2-step algorithm was developed to predict the ablation site of PSAT with a positive predictive value of 95.4% and a negative predictive value of 97.0%. CONCLUSION: ΔRA-LA is a useful endocardial activation-derived parameter for predicting the successful ablation site of PSAT.

C-H Bond Sulfonylation from Thianthrenium Salts and DABCO·(SO2)2: Synthesis of 2-Sulfonylindoles.

A three-component reaction of 1-(1H-indol-1-yl)isoquinolines or 1-(pyridin-2-yl)-1H-indoles, DABCO·(SO2)2, and thianthrenium salts under synergistic photoredox and palladium catalysis is accomplished. This direct C-H bond sulfonylation of indoles with the insertion of sulfur dioxide under mild conditions works efficiently, giving rise to a wide range of 2-sulfonated indoles in moderate to good yields under mild conditions. In this protocol, the generality of aryl/alkyl thianthrenium salts is demonstrated as well. A photoredox radical process combined with palladium catalysis is proposed.

Gate-Tunable Positive and Negative Photoconductance in Near-Infrared Organic Heterostructures for In-Sensor Computing.

The rapid growth of sensor data in the artificial intelligence often causes significant reductions in processing speed and power efficiency. Addressing this challenge, in-sensor computing is introduced as an advanced sensor architecture that simultaneously senses, memorizes, and processes images at the sensor level. However, this is rarely reported for organic semiconductors that possess inherent flexibility and tunable bandgap. Herein, an organic heterostructure that exhibits a robust photoresponse to near-infrared (NIR) light is introduced, making it ideal for in-sensor computing applications. This heterostructure, consisting of partially overlapping p-type and n-type organic thin films, is compatible with conventional photolithography techniques, allowing for high integration density of up to 520 devices cm-2 with a 5 µm channel length. Importantly, by modulating gate voltage, both positive and negative photoresponses to NIR light (1050 nm) are attained, which establishes a linear correlation between responsivity and gate voltage and consequently enables real-time matrix multiplication within the sensor. As a result, this organic heterostructure facilitates efficient and precise NIR in-sensor computing, including image processing and nondestructive reading and classification, achieving a recognition accuracy of 97.06%. This work serves as a foundation for the development of reconfigurable and multifunctional NIR neuromorphic vision systems.

Reducing Indoor Particulate Air Pollution Improves Student Test Scores: A Randomized Double-Blind Crossover Study.

Short-term exposure to air pollution is associated with a decline in cognitive function. Standardized test scores have been employed to evaluate the effects of air pollution exposure on cognitive performance. Few studies aimed to prove whether air pollution is responsible for reduced test scores; none have implemented a "gold-standard" method for assessing the association such as a randomized, double-blind intervention. This study used a "gold-standard" method─randomized, double-blind crossover─to assess whether reducing short-term indoor particle concentrations results in improved test scores in college students in Tianjin, China. Participants (n = 162) were randomly assigned to one of two similar classrooms and completed a standardized English test on two consecutive weekends. Air purifiers with active or sham (i.e., filter removed) particle filtration were placed in each classroom. The filtration mode was switched between the two test days. Linear mixed-effect models were used to evaluate the effect of the intervention mode on the test scores. The results show that air purification (i.e., reducing PM) was significantly associated with increases in the z score for combined (0.11 [95%CI: 0.02, 0.21]) and reading (0.11 [95%CI: 0.00, 0.22]) components. In conclusion, a short-term reduction in indoor particle concentration led to improved test scores in students, suggesting an improvement in cognitive function.

Investigating the effects of Laggera pterodonta on H3N2-Induced inflammatory and immune responses through network pharmacology, molecular docking, and experimental validation in a mice model.

For centuries, Laggera pterodonta (LP), a Chinese herbal medicine, has been widely employed for treating respiratory infectious diseases; however, the mechanism underlying LP's effectiveness against the influenza A/Aichi/2/1968 virus (H3N2) remains elusive. This study aims to shed light on the mechanism by which LP combats influenza in H3N2-infected mice. First, we conducted quasi-targeted metabolomics analysis using liquid chromatography-mass spectrometry to identify LP components. Subsequently, network pharmacology, molecular docking, and simulation were conducted to screen candidate targets associated with AKT and NF-κB. In addition, we conducted a series of experiments including qPCR, hematoxylin-eosin staining, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay to provide evidence that LP treatment in H3N2-infected mice can reduce pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1ß, and MCP-1) while increasing T cells (CD3+, CD4+, and CD8+) and syndecan-1 and secretory IgA expression. This, in turn, aids in the prevention of excessive inflammation and the fortification of immunity, both of which are compromised by H3N2. Finally, we utilized a Western blot assay to confirm that LP indeed inhibits the AKT/NF-κB signaling cascade. Thus, the efficacy of LP serves as a cornerstone in establishing a theoretical foundation for influenza treatment.

Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial.

PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.