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.

A Dual-Cation Exchange Membrane Electrolyzer for Continuous H2 Production from Seawater.

Direct seawater splitting (DSS) offers an aspirational route toward green hydrogen (H2) production but remains challenging when operating in a practically continuous manner, mainly due to the difficulty in establishing the water supply-consumption balance under the interference from impurity ions. A DSS system is reported for continuous ampere-level H2 production by coupling a dual-cation exchange membrane (CEM) three-compartment architecture with a circulatory electrolyte design. Monovalent-selective CEMs decouple the transmembrane water migration from interferences of Mg2+, Ca2+, and Cl- ions while maintaining ionic neutrality during electrolysis; the self-loop concentrated alkaline electrolyte ensures the constant gradient of water chemical potential, allowing a specific water supply-consumption balance relationship in a seawater-electrolyte-H2 sequence to be built among an expanded current range. Even paired with commercialized Ni foams, this electrolyzer (model size: 2 × 2 cm2) continuously produces H2 from flowing seawater with a rate of 7.5 mL min-1 at an industrially relevant current of 1.0 A over 100 h. More importantly, the energy consumption can be further reduced by coupling more efficient NiMo/NiFe foams (≈6.2 kWh Nm-3 H2 at 1.0 A), demonstrating the potential to further optimize the continuous DSS electrolyzer for practical applications.

Albizzia chinensis (Osbeck) Merr extract YS ameliorates ethanol-induced acute gastric ulcer injury in rats by regulating NRF2 signaling pathway.

BACKGROUND: Around the world, there is a high incidence of gastric ulcers. YS, an extract from the Chinese herb Albizzia chinensis (Osbeck) Merr, has potential therapeutic applications for gastrointestinal diseases. Here we elucidated the protective effect and underlying mechanism of action of YS on gastric ulcer in rats injured by ethanol. METHODS: The ethanol-induced gastric ulcer rat model was used to assess the protective effect of YS. A pathological examination of gastric tissue was performed by H&E staining. GES-1 cells damaged by hydrogen peroxide were used to simulate oxidative damage in gastric mucosal epithelial cells. Endogenous NRF2 was knocked down using small interfering RNA. Immunoprecipitation was used to detect ubiquitination of NRF2. Co-immunoprecipitation was used to detect the NRF2-Keap1 interaction. RESULTS: YS (10 and 30 mg/kg, i.g.) significantly reduced the ulcer index, decreased MDA level, and increased SOD and GSH levels in gastric tissues damaged by ethanol. YS promoted NRF2 translocation from cytoplasm to nucleus and enhanced the NQO1 and HO-1 expression levels in injured rat gastric tissue. In addition, YS regulated NQO1 and HO-1 via NRF2 in H2O2-induced oxidative injured GES-1 cells. Further studies on the underlying mechanism indicated that YS reduced the interaction between NRF2 and Keap1 and decreased ubiquitylation of NRF2, thereby increasing its stability and expression of downstream factors. NRF2 knockdown abolished the effect of YS on MDA and SOD in GES-1 cells treated with H2O2. CONCLUSION: YS reduced the NRF2-Keap1 interaction, promoting NRF2 translocation into the nucleus, which increasing the transcription and translation of NQO1 and HO-1 and improved the antioxidant capacity of rat stomach.

Precise prostate cancer diagnosis using fluorescent nanoprobes for detecting PSA and PSMA in serum.

Novel Au-Se bond-based nanoprobes were designed for concurrent detection of PSA and PSMA in serum samples, aiming to enhance the early diagnosis of prostate cancer. These probes demonstrate robust stability, specificity and accuracy, underscoring their potential as non-invasive tools for diagnosis.

Advancing Nonsmall Cell Lung Cancer Diagnosis Accuracy via Dual Detection Fluorescent Nanoprobes.

Among the primary threats to human health worldwide, nonsmall cell lung cancer (NSCLC) remains a significant factor and is a leading cause of cancer-related deaths. Due to subtle early symptoms, NSCLC patients are diagnosed at advanced stages, resulting in low survival rates. Herein, novel Au-Se bond nanoprobes (NPs) designed for the specific detection of Calpain-2 (CAPN2) and Human Neutrophil Elastase (HNE), pivotal biomarkers in NSCLC, were developed. The NPs demonstrated exceptional specificity and sensitivity toward CAPN2 and HNE, enabling dual-color fluorescence imaging to distinguish between NSCLC cells and normal lung cells effectively. The NPs' performance was consistent across a wide pH range (6.2 to 8.0), and it exhibited remarkable resistance to biological thiol interference, indicating its robustness in complex physiological environments. These findings suggest the nanoprobe is a promising tool for early NSCLC diagnosis, offering a novel approach for enhancing the accuracy of cancer detection.

Eco-environmental changes due to human activities in the Erhai Lake Basin from 1990 to 2020.

Human activities have increased with urbanisation in the Erhai Lake Basin, considerably impacting its eco-environmental quality (EEQ). This study aims to reveal the evolution and driving forces of the EEQ using water benefit-based ecological index (WBEI) in response to human activities and policy variations in the Erhai Lake Basin from 1990 to 2020. Results show that (1) the EEQ exhibited a pattern of initial degradation, subsequent improvement, further degradation and a rebound from 1990 to 2020, and the areas with poor and fair EEQ levels mainly concentrated around the Erhai Lake Basin with a high level of urbanisation and relatively flat terrain; (2) the EEQ levels were not optimistic in 1990, 1995 and 2015, and areas with poor and fair EEQ levels accounted for 43.41%, 47.01% and 40.05% of the total area, respectively; and (3) an overall improvement in the EEQ was observed in 1995-2000, 2000-2005, 2005-2009 and 2015-2020, and the improvement was most significant in 1995-2000, covering an area of 823.95 km2 and accounting for 31.79% of the total area. Results also confirmed that the EEQ changes in the Erhai Lake Basin were primarily influenced by human activities and policy variations. Moreover, these results can provide a scientific basis for the formulation and planning of sustainable development policy in the Erhai Lake Basin.

A small-molecule Fenton reagent for self-augmented chemodynamic therapy by intelligently regulating intracellular acidosis.

A small-molecule Fenton reagent, integrating ferrocene with a carbonic anhydrase inhibitor, was designed to intelligently regulate intracellular acidosis for self-augmented chemodynamic therapy. Acidosis coupled with up-regulated ROS levels demonstrated potent cytotoxicity and effective tumor suppression.

Efficient bubble/precipitate traffic enables stable seawater reduction electrocatalysis at industrial-level current densities.

Seawater electroreduction is attractive for future H2 production and intermittent energy storage, which has been hindered by aggressive Mg2+/Ca2+ precipitation at cathodes and consequent poor stability. Here we present a vital microscopic bubble/precipitate traffic system (MBPTS) by constructing honeycomb-type 3D cathodes for robust anti-precipitation seawater reduction (SR), which massively/uniformly release small-sized H2 bubbles to almost every corner of the cathode to repel Mg2+/Ca2+ precipitates without a break. Noticeably, the optimal cathode with built-in MBPTS not only enables state-of-the-art alkaline SR performance (1000-h stable operation at -1 A cm-2) but also is highly specialized in catalytically splitting natural seawater into H2 with the greatest anti-precipitation ability. Low precipitation amounts after prolonged tests under large current densities reflect genuine efficacy by our MBPTS. Additionally, a flow-type electrolyzer based on our optimal cathode stably functions at industrially-relevant 500 mA cm-2 for 150 h in natural seawater while unwaveringly sustaining near-100% H2 Faradic efficiency. Note that the estimated price (~1.8 US$/kgH2) is even cheaper than the US Department of Energy's goal price (2 US$/kgH2).

Regulating the Topology of Covalent Organic Frameworks for Boosting Overall H2O2 Photogeneration.

Photocatalytic oxygen reduction reactions and water oxidation reactions are extremely promising green approaches for massive H2O2 production. Nonetheless, constructing effective photocatalysts for H2O2 generation is critical and still challenging. Since the network topology has significant impacts on the electronic properties of two dimensional (2D) polymers, herein, for the first time, we regulated the H2O2 photosynthetic activity of 2D covalent organic frameworks (COFs) by topology. Through designing the linking sites of the monomers, we synthesized a pair of novel COFs with similar chemical components on the backbones but distinct topologies. Without sacrificial agents, TBD-COF with cpt topology exhibited superior H2O2 photoproduction performance (6085 and 5448 µmol g-1 h-1 in O2 and air) than TBC-COF with hcb topology through the O2-O2•--H2O2, O2-O2•--O21-H2O2, and H2O-H2O2 three paths. Further experimental and theoretical investigations confirmed that during the H2O2 photosynthetic process, the charge carrier separation efficiency, O2•- generation and conversion, and the energy barrier of the rate determination steps in the three channels, related to the formation of *OOH, *O21, and *OH, can be well tuned by the topology of COFs. The current study enlightens the fabrication of high-performance photocatalysts for H2O2 production by topological structure modulation.

Efficient Electrochemical Co-Reduction of Carbon Dioxide and Nitrate to Urea with High Faradaic Efficiency on Cobalt-Based Dual-Sites.

Renewable electricity-powered nitrate/carbon dioxide co-reduction reaction toward urea production paves an attractive alternative to industrial urea processes and offers a clean on-site approach to closing the global nitrogen cycle. However, its large-scale implantation is severely impeded by challenging C-N coupling and requires electrocatalysts with high activity/selectivity. Here, cobalt-nanoparticles anchored on carbon nanosheet (Co NPs@C) are proposed as a catalyst electrode to boost yield and Faradaic efficiency (FE) toward urea electrosynthesis with enhanced C-N coupling. Such Co NPs@C renders superb urea-producing activity with a high FE reaching 54.3% and a urea yield of 2217.5 µg h-1 mgcat. -1, much superior to the Co NPs and C nanosheet counterparts, and meanwhile shows strong stability. The Co NPs@C affords rich catalytically active sites, fast reactant diffusion, and sufficient catalytic surfaces-electrolyte contacts with favored charge and ion transfer efficiencies. The theoretical calculations reveal that the high-rate formation of *CO and *NH2 intermediates is crucial for facilitating urea synthesis.

The association between serum 25-hydroxyvitamin D levels and erectile dysfunction: a two-sample Mendelian randomization analysis.

Considering that vascular endothelial cell dysfunction is the pathological basis of erectile dysfunction (ED), and recognizing the beneficial effects of 25-hydroxyvitamin D (25(OH)D) on vascular endothelial cell protection, the researchers diligently investigated the causal relationship between serum 25(OH)D levels and ED. However, inconsistent clinical evidence has left the association between serum 25(OH)D levels and ED unclear. The objective of this work was to employ Mendelian randomization (MR) analysis to ascertain the potential causal relationship between serum 25(OH)D levels and ED. We conducted a two-sample MR analysis utilizing data from publicly available genome-wide association studies (GWASs). The primary analysis method for the MR analysis was the inverse-variance weighted (IVW) method, supplemented by the MR-Egger and weighted median methods. In addition, we evaluated heterogeneity with Cochran's Q test, assessed pleiotropy using the MR-Egger intercept test, and performed a leave-one-out analysis to identify single-nucleotide polymorphisms (SNPs) with potential effects. Outliers were detected using MR-pleiotropy residual sum and outlier (MR-PRESSO). Genetically predicted serum 25(OH)D levels were not found to be causally associated with ED in IVW method (OR = 1.028, 95% CI = 0.845-1.250, P = 0.785), MR-Egger method (OR = 1.057, 95% CI = 0.782-1.430, P = 0.720), and weighted median method (OR = 1.225, 95% CI = 0.920-1.633, P = 0.165). The results of sensitivity analyses reinforced our conclusion, indicating no evidence of heterogeneity or directional pleiotropy. In summary, our findings do not substantiate a genetic-level causal link between serum 25(OH)D levels and the prevalence of ED. Nonetheless, future research, including larger MR studies, clinical trials, and additional observational studies, is essential to validate and reinforce the outcomes of our present study.

Arming Amorphous NiMoO4 on Nickel Phosphide Enables Highly Stable Alkaline Seawater Oxidation.

Seawater electrolysis holds tremendous promise for the generation of green hydrogen (H2 ). However, the system of seawater-to-H2 faces significant hurdles, primarily due to the corrosive effects of chlorine compounds, which can cause severe anodic deterioration. Here, a nickel phosphide nanosheet array with amorphous NiMoO4 layer on Ni foam (Ni2 P@NiMoO4 /NF) is reported as a highly efficient and stable electrocatalyst for oxygen evolution reaction (OER) in alkaline seawater. Such Ni2 P@NiMoO4 /NF requires overpotentials of just 343 and 370 mV to achieve industrial-level current densities of 500 and 1000 mA cm-2 , respectively, surpassing that of Ni2 P/NF (470 and 555 mV). Furthermore, it maintains consistent electrolysis for over 500 h, a significant improvement compared to that of Ni2 P/NF (120 h) and Ni(OH)2 /NF (65 h). Electrochemical in situ Raman spectroscopy, stability testing, and chloride extraction analysis reveal that is situ formed MoO4 2- /PO4 3- from Ni2 P@NiMoO4 during the OER test to the electrode surface, thus effectively repelling Cl- and hindering the formation of harmful ClO- .

In Situ Imaging of GGT and HOBr-Triggered Atherosclerotic Plaque Rupture via Activating the RunX2/Col IV Signaling Pathway.

Calcification and abnormal collagen deposition within blood vessels constitute causative factors for atherosclerotic plaque rupture, and their occurrence is intimately linked with γ-glutamyltranspeptidase (GGT) and hypobromous acid (HOBr). However, the underlying regulatory mechanisms of GGT and HOBr in plaque rupture remain unclear. Hence, we developed a dual-responsive near-infrared (NIR) fluorescent probe (BOC-H) that effectively avoids spectral crosstalk for the in situ visualization of the fluctuations in GGT and HOBr levels during atherosclerotic plaque rupture. We found that both GGT and HOBr contents increase significantly in the calcification models of cells and animals. The overexpressed GGT participated in intracellular oxygen-promoting behavior, which obviously upregulated the expression of RunX2 and Col IV by facilitating H2O2 and HOBr secretion. This process triggered calcification and abnormal collagen deposition within the plaque, which raised the risk of plaque rupture. PM2.5-induced arteriosclerotic calcification models further verified the results that GGT and HOBr accelerate plaque rupture via activation of the RunX2/Col IV signaling pathway. Moreover, the assessment of GGT and HOBr in serum samples from patients with acute myocardial infarction further confirmed the co-regulation of GGT and HOBr in the plaque rupture. Together, our studies highlight the involvement of GGT and HOBr in driving plaque rupture and offer new targets for the prevention and treatment of acute cardiovascular disease.

DPPX antibody-mediated autoimmune encephalitis：the first case with breast cancer and review of the literature.

Dipeptidyl-peptidase-like protein 6 (DPPX) antibody-mediated encephalitis is a rare type of autoimmune encephalitis (AE), which mainly manifests as diarrhea accompanied by weight loss, cognitive decline, epileptic seizures, and even psychiatric symptoms. Remarkably, it is also reported to be associated with tumors, predominantly B-cell lymphoma. Overall, the AE remains uncharacterized clinically and its long-term prognosis remains elusive. Herein, we report the first case of DPPX antibody-mediated AE secondary to breast cancer. Importantly, it substantially improves after aggressive immunotherapy. Our case highlights DPPX antibody-mediated AE as a paraneoplastic syndrome and discusses the pearls in its diagnosis and management.

WDR4 promotes HCC pathogenesis through N7-methylguanosine by regulating and interacting with METTL1.

BACKGROUND: The N7-methylguanosine (m7G), a modification at defined internal positions within tRNAs and rRNAs, is correlated with tumor progression. Methyltransferase like 1 (METTL1)/ WD repeat domain 4 (WDR4) mediated tRNA m7G modification, which could alter many oncogenic mRNAs translation to promote progress of multiple cancer types. However, whether and how the internal mRNA m7G modification is involved in tumorigenesis remains unclear. METHODS: The immunohistochemistry assay was conducted to detect the expression of WDR4 and METTL1 in hepatocellular carcinoma (HCC) and the expression of both genes whether contributes to the prognosis of the survival rate of HCC patients. Then, CCK8, colony formation assays and tumor xenograft models were conducted to determine the effects of WDR4 on HCC cells in vitro and vivo. Besides, dot blot assay, m7G-MeRIP-seq and RNA-seq analysis were conducted to determine whether WDR4 contributes to m7G modification and underlying mechanism in HCC cells. Finally, rescue and CO-IP assay were conducted to explore whether WDR4 and METTL1 proteins form a complex in Huh7 cells. RESULTS: WDR4 modulates m7G modification at the internal sites of tumor-promoting mRNAs by forming the WDR4-METTL1 complex. WDR4 knockdown downregulated the expression of mRNA and protein levels of METTL1 gene and thus further modulate the formation of WDR4-METTL1 complex indirectly. METTL1 expression was markedly correlated with WDR4 expression in HCC tissues. HCC patients with high expression of both genes had a poor prognosis. CONCLUSIONS: WDR4 may contribute to HCC pathogenesis by interacting with and regulating the expression of METTL1 to synergistically modulate the m7G modification of target mRNAs in tumor cells.

Tris-assisted one-step fabrication of functional carbon dots for specific folate receptor positive-expressed cancer cell imaging.

Specific staining of cancer cells is momentous for cancer research. Nanoprobe with multivalent recognition is emerging as powerful tools for bioimaging, but the nonspecific cell uptake and complex functional modification procedures are still obstacles for specific detection and convenient synthesis. Carbon dots (CDs) with an intrinsic targeting ability, excellent optical properties and biocompatibility acquired from an efficient one-step fabrication procedure were urgently desired in specific cancer cells visualization. Herein, inspired by the interrelationships between interface and biomolecular mechanisms, we suggested that it was possible to construct CDs with the desired characteristics for folate receptor (FR) positive-expressed cancer cell imaging via rich hydroxyl groups Tris-assisted one-step hydrothermal treatment of folate acid (FA) and l-Arginine (L-Arg) precursors. The prepared small-sized F-CDs were equipped with abundant hydroxyl, pterin and negative charge surface, and possessed environmental friendliness, outstanding photostability and biocompatibility. Moreover, F-CDs had an intrinsic FR positive-expressed cancer cell targeting ability without any post-modification of the ligands. Rich hydroxyl groups play a vital role in endowing the optical properties and biological effects of F-CDs. F-CDs could be used as a promising candidate for FR-expressed cancer cell labeling and tracking. In addition, the caveolae-mediated endocytosis pathway of F-CDs was ascertained. More importantly, experimental results confirmed that the combination of physicochemical properties may provide an efficient strategy to overcome non-specific cell uptake interactions for cell labeling. Our strategy put forward a promising alternative to design fluorescent CDs for extensive chemical and biomedical applications.

Efficacy, Safety, and Population Pharmacokinetics of Eltrombopag in Children with Different Severities of Aplastic Anemia.

Eltrombopag was approved as a first-line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non-severe AA (NSAA), are limited. We performed a prospective, single-arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA). The efficacy and safety were assessed every 3 months. The population pharmacokinetic (PPK) model was used to depict the pharmacokinetic profile of eltrombopag. Twenty-three AA children with an average age of 7.9 (range of 3.0-14.0) years were enrolled. The response (complete and partial response) rate was 12.5%, 50.0%, and 100.0% after 3, 6, and 12 months in patients with NSAA. For patients with SAA and VSAA, these response rates were 46.7%, 61.5%, and 87.5%. Hepatotoxicity occurred in one patient. Fifty-three blood samples were used to build the PPK model. Body weight was the only covariate for apparent clearance (CL/F) and volume of distribution. The allele-T carrier of adenosine triphosphate-binding cassette transporter G2 was found to increase eltrombopag's clearance. However, when normalized by weight, the clearance between the wild-type and variant showed no statistical difference. In patients with response, children with NSAA exhibited lower area under the curve from time zero to infinity, higher CL/F, and higher weight-adjusted CL/F than those with SAA or VSAA. However, the differences were not statistically significant. The results may support further individualized treatment of eltrombopag in children with AA.

Monolithic back-end-of-line integration of phase change materials into foundry-manufactured silicon photonics.

Monolithic integration of novel materials without modifying the existing photonic component library is crucial to advancing heterogeneous silicon photonic integrated circuits. Here we show the introduction of a silicon nitride etch stop layer at select areas, coupled with low-loss oxide trench, enabling incorporation of functional materials without compromising foundry-verified device reliability. As an illustration, two distinct chalcogenide phase change materials (PCMs) with remarkable nonvolatile modulation capabilities, namely Sb2Se3 and Ge2Sb2Se4Te1, were monolithic back-end-of-line integrated, offering compact phase and intensity tuning units with zero-static power consumption. By employing these building blocks, the phase error of a push-pull Mach-Zehnder interferometer optical switch could be reduced with a 48% peak power consumption reduction. Mirco-ring filters with >5-bit wavelength selective intensity modulation and waveguide-based >7-bit intensity-modulation broadband attenuators could also be achieved. This foundry-compatible platform could open up the possibility of integrating other excellent optoelectronic materials into future silicon photonic process design kits.

OCTN2- and ATB0,+-targeted nanoemulsions for improving ocular drug delivery.

Traditional eye drops are administered via topical instillation. However, frequent dosing is needed due to their relatively rapid precorneal removal and low ocular bioavailability. To address these issues, stearoyl L-carnitine-modified nanoemulsions (SC-NEs) were fabricated. The physicochemical properties of SC-NEs in terms of size, morphology, zeta potential, encapsulation efficiency, and in vitro drug release behavior were characterized. The cellular uptake and mechanisms of SC-NEs were comprehensively studied in human corneal epithelial cells and the stearoyl L-carnitine ratio in SC-NEs was optimized. The optimized SC-NEs could target the novel organic cation/carnitine transporter 2 (OCTN2) and amino acid transporter B (0 +) (ATB0,+) on the corneal epithelium, which led to superior corneal permeation, ocular surface retention ability, ocular bioavailability. Furthermore, SC-NEs showed excellent in vivo anti-inflammatory efficacy in a rabbit model of endotoxin-induced uveitis. The ocular safety test indicated that the SC-NEs were biocompatible. In general, the current study demonstrated that OCTN2 and ATB0,+-targeted nanoemulsions were promising ophthalmologic drug delivery systems that can improve ocular drug bioavailability and boost the therapeutic effects of drugs for eye diseases.

Exploration of glutaredoxin-1 oxidative modification in carbon nanomaterial-induced hepatotoxicity.

Herein, we present toxicological assessments of carbon nanomaterials in HL-7702 cells, and it was found that reactive oxygen species (ROS) levels were elevated. Mass spectrometry results indicated that cysteine sulfhydryl of glutaredoxin-1 (GLRX1) was oxidized to sulfenic acids and sulfonic acids by excessive ROS, which broke the binding of GLRX1 to apoptosis signal-regulating kinase 1, causing the activation of the JNK/p38 signaling pathway and ultimately hepatocyte apoptosis. However, a lower level of ROS upregulated GLRX1 instead of sulfonation modification of its active sites. Highly expressed GLRX1 in turn enabled the removal of intracellular ROS, thereby exerting inconspicuous toxic effects on cells. Taken together, these findings emphasized that CNM-induced hepatotoxicity is attributable to oxidative modifications of GLRX1 arising from redox imbalance.