Oocytes maintain low ROS levels to support the dormancy of primordial follicles.

Primordial follicles (PFs) function as the long-term reserve for female reproduction, remaining dormant in the ovaries and becoming progressively depleted with age. Oxidative stress plays an important role in promoting female reproductive senescence during aging, but the underlying mechanisms remain unclear. Here, we find that low levels of reactive oxygen species (ROS) are essential for sustaining PF dormancy. Compared to growing follicles, oocytes within PFs were shown to be more susceptible to ROS, which accumulates and damages PFs to promote reproductive senescence. Mechanistically, oocytes within PFs were shown to express high levels of the intracellular antioxidant enzyme superoxide dismutase 1 (SOD1), counteracting ROS accumulation. Decreased SOD1 expression, as a result of aging or through the experimental deletion of the Sod1 gene in oocytes, resulted in increased oxidative stress and triggered ferroptosis within PFs. In conclusion, this study identified antioxidant defense mechanisms protecting PFs in mouse ovaries and characterized cell death mechanisms of oxidative stress-induced PF death.

Preparation of sulfated arabinogalactan-loaded hydrogel for wound healing in mouse burn model.

Sulfation of polysaccharides can affect their biological activity by introducing sulfate groups. Skin burns occur regularly and have a great impact on normal survival. In this study, sulfated arabinogalactan (SAG) was prepared by sulfation, and polyvinyl alcohol (PVA) was used to prepare hydrogels for the treatment of scalded skin in mouse. The results show that the main chain of SAG consists of →3-ß-D-Galactose (Gal)-(1, →3, 6)-ß-D-Gal-(1 and →4)-ß-d-Glucose (Glc)-(1. The chain is a neutral polysaccharide composed of T-ß-L-Arabinose (Araf)-(1→, with a molecular weight of 17.9 kDa. At the same time, PVA + SAG hydrogel can promote the scald repair of mouse skin by promoting collagen deposition and angiogenesis, and regulating the TLR4/MyD88/NF-κB signaling pathway. Interestingly, the effect of SAG on promoting the repair of scald wounds is enhanced after AG is derivatized by sulfation. Therefore, the preparation of SAG by sulfation can promote scald repair, and has great application potential in the field of food and medicine.

Phloretin@cyclodextrin/natural silk protein/polycaprolactone nanofiber wound dressing with antioxidant and antibacterial activities promotes diabetic wound healing.

In patients with diabetes, chronic hyperglycemia impairs immune function at wound sites, increasing susceptibility to infections, prolonging inflammation, and delaying healing. This study aimed to develop wound dressings that control bacterial infections and accelerate healing. Phloretin (PHL), which has antibacterial and anti-inflammatory properties, was encapsulated with γ-cyclodextrin (γ-CD) to form a PHL@CD complex with enhanced bioavailability. This complex was incorporated into nanofiber wound dressings composed of polycaprolactone and natural silk protein. The resulting dressings exhibited favorable physical and chemical properties, including nutrient transport and gas exchange, which are essential for wound healing. The nanofiber membranes exhibited antibacterial activity against Staphylococcus aureus (90.31 ± 4.41 % inhibition), with high antioxidant capacity (91.48 ± 0.33 % ABTS scavenging) and blood compatibility. The membranes also promoted cell viability. Importantly, the nanofiber dressings accelerated wound healing in a diabetic mouse model by reducing the duration of inflammation. The novel nanofiber wound dressing can significantly improve the treatment of diabetic wounds.

Cardiac angiosarcoma with lung metastasis presented with multiple halo signs: One case report and literature review.

Cardiac angiosarcoma is a rare aggressive malignancy with rapid progress and poor prognosis. Here we report 1 patient with cardiac angiosarcoma with lung metastasis, which presented as multiple halo signs and ground glass opacities. The patient underwent computed tomography (CT) guided lung biopsy and postoperative tissue histology confirmed the diagnosis of angiosarcoma. Transthoracic echocardiography (TTE) and cardiac Magnetic Resonance Imaging (MRI) identified the main tumor in the right atrium. Positron emission tomography/computed tomography (PET/CT) excluded intraabdominal lesions. The patient was given chemotherapy with nab-paclitaxel, cardiac radiation therapy and remained follow-up. Considering the rapid disease progression and poor prognosis, the present case report is intended to provide diagnostic insight into cardiac angiosarcoma with lung metastasis, especially with lung CT scans of multiple halo signs and ground glass opacities.

A novel sequential extraction method for the measurement of Cr(VI) and Cr(III) species distribution in soil: New insights into the chromium speciation.

The distribution characteristics of Cr(VI) species in contaminated soil is crucial for soil remediation; however, there is currently a lack of methods for analysing anionic Cr(VI) species in soil. This study has developed a novel sequential extraction method for speciation of Cr(VI) and Cr(III). Besides extraction experiments, simulated chromium species were prepared to verify the presence of proposed chromium species. The results show that Cr(VI) species in soil can be categorized into water-soluble Cr(VI), electrostatically adsorbed Cr(VI), Cr(VI) specifically adsorbed by minerals containing exchangeable Ca2+, Cr(VI) specifically adsorbed by hydrous metal oxides, calcium chromate Cr(VI) and stable complexed adsorption Cr(VI). These Cr(VI) species can be selectively extracted by specific solutions through ion exchange or weak acid dissolution. The most stable Cr(VI) species is Cr(VI) complexed by hydrous iron oxides through bidentate ligand binding; only by dissolution of hydrous iron oxides can this Cr(VI) species be leached. The distribution of Cr(VI) species is closely linked to particular soil compositions including exchangeable Ca2+ and hydrous iron oxides which determinate the Cr(VI) adsorption in soil. Cr(III) species comprise Fe-Cr coprecipitate hydroxides Cr(III), Fe-Mn oxide-bound Cr(III), organic matter-bound Cr(III) and residual Cr(III). Their distribution depends on the types of reductants present in the soil.

Causal role of peripheral immune cells in epilepsy: A large-scale genetic correlation study.

BACKGROUND: While an increasing number of researchers have focused on the correlation between the immune system and epilepsy, the precise causal role of immune cells in epilepsy continues to elude scientific understanding. The aim of the study was to examine the causal relationship between peripheral immune phenotypes and epilepsy. METHODS: Mendelian randomization (MR) analysis and linkage disequilibrium score regression (LDSC) were utilized to determine the causal relationship between 731 immune cell traits and various types of epilepsy in this study. RESULTS: LDSC revealed that 80 immunophenotypes showed genetic correlation with epilepsy, including 58 immunophenotypes associated with a single type of epilepsy (72.5 %),14 immunophenotypes associated with two types of epilepsy (17.5 %),7 immunophenotypes with 3 types of epilepsy (8.75 %) and 1 immunophenotype with 5 types of epilepsy (1.25 %). Although none of the types of epilepsy had a statistically significant effect on immunophenotypes, it is noteworthy that the MR revealed the protective effects of five immunophenotypes on epilepsy: CD45RA+CD8br AC (OR:0.86, 95 %CI:0.80-0.93), FSC-A on myeloid DC (OR:0.95, 95 %CI:0.91-0.98）, CM CD8br AC (OR:0.69, 95 %CI:0.59--0.82), CD33 on CD66b++ Myeloid cell (OR:0.88, 95 %CI:0.83-0.93) and CD127 on CD28- CD8br (OR:0.97, 95 %CI:0.95-0.98). Additionally, harmful effects were observed for two immunophenotypes on epilepsy:CD4 Treg %CD4 (OR:1.04, 95 %CI:1.02-1.06) and SSC-A on plasmacytoid DC (OR:1.01, 95 %CI:1.00-1.02). CONCLUSION: Our research has demonstrated the causal connections between immune cells and epilepsy, potentially providing valuable insights for future clinical studies.

Fenitrothion induces glucose metabolism disorders in rat liver BRL cells by inhibiting AMPKα and IRS1/PI3K/AKT signaling pathway.

Fenitrothion (FNT) is a common organophosphorus pesticide that is widely used in both agricultural and domestic pest control. FNT has been frequently detected in various environmental media, including the human body, and is a notable contaminant. Epidemiological investigations have recently shown the implications of exposure to FNT in the incidence of various metabolic diseases, such as diabetes mellitus in humans, indicating that FNT may be a potential endocrine disruptor. However, the effects of FNT exposure on glucose homeostasis and their underlying mechanisms in model organisms remain largely unknown, which may limit our understanding of the health risks of FNT. In this study, FNT (4 5, 90, 180, and 4 50 µM) exposure model of rat hepatocytes (Buffalo Rat Liver, BRL cells) was established to investigate the effects and potential mechanisms of its toxicity on glucose metabolism. Several key processes of glucose metabolism were detected in this study. The results showed significantly increased glucose levels in the culture medium and decreased glycogen content in the FNT-exposed BRL cells. The results of quantitative real-time PCR and enzymology showed the abnormal expression of genes and activity/content of glucose metabolic enzymes involved in glucose metabolism, which might promote gluconeogenesis and inhibit glucose uptake, glycolysis, and glycogenesis. Furthermore, gluconeogenesis and glycolytic were carried out in the mitochondrial membrane. The abnormal of mitochondrial membrane potential may be a potential mechanism underlying FNT-induced glucose metabolism disorder. In addition, the mRNA and protein expression implicated that FNT may disrupt glucose metabolism by inhibiting the AMPKα and IRS1/PI3K/AKT signaling pathways. In conclusion, results provide in vitro evidence that FNT can cause glucose metabolism disorder, which emphasizes the potential health risks of exposure to FNT in inducing diabetes mellitus.

Functionalized Modified Ti4O7 Polyaniline Coating for 316SS Bipolar Plate in Proton-Exchange Membrane Fuel Cells.

In this paper, the PANI/PDA-Ti4O7 composite coating was prepared on 316L by constant current deposition with a current density of 2.8 mA·cm-2, in which the Ti4O7 powders were modified by PDA (polydopamine). The open-circuit potential of the obtained PANI/PDA-Ti4O7 composite coating is about 365 mVAg/AgCl, which is more positive than that of the bare 316L. During immersion in 1 M H2SO4 + 2 ppm HF for 200 h, the high stable corrosion potential and the lower Rf indicate that the composite coating has long-term corrosion resistance.

Application of polysaccharide-based crosslinking agents based on schiff base linkages for biomedical scaffolds.

Chemical crosslinking is a method widely used to enhance the mechanical strength of biopolymer-based scaffolds. Polysaccharides are natural and biodegradable carbohydrate polymers that can act as crosslinking agents to promote the formation of scaffolds. Compared to synthetic crosslinking agents, Polysaccharide-based crosslinking agents have better biocompatibility for cell adhesion and growth. Traditional Chinese medicine has special therapeutic effects on various diseases and is rich in various bioactive ingredients. Among them, polysaccharides have immune regulatory, antioxidant, and anti-inflammation effects, which allow them to not only act as crosslinking agents but endow the scaffold with greater bioactivity. This article focuses on the latest developments of polysaccharide-based crosslinking agents for biomedical scaffolds, including hyaluronic acid, chondroitin sulfate, dextran, alginate, cellulose, gum polysaccharides, and traditional Chinese medicine polysaccharides. Also, we provide a summary and prospects on the research of polysaccharide-based crosslinking agents.

A comprehensive review of Sjögren's syndrome: Classification criteria, risk factors, and signaling pathways.

Sjögren's syndrome (SS) is a chronic autoimmune disease that affects the exocrine glands and may lead to a range of systemic symptoms that impact various organs. Both innate and adaptive immune pathways might trigger the disease. Studying the signaling pathways underlying SS is crucial for enhancing diagnostic and therapeutic effectiveness. SS poses an ongoing challenge for medical professionals owing to the limited therapeutic options available. This review offers a comprehensive understanding of the intricate nature of SS, encompassing disease classification criteria, risk factors, and signaling pathways in immunity and inflammation. The advancements summarized herein have the potential to spark new avenues of research into SS.

Only FLT3-ITD co-mutation did not have a deleterious effect on acute myeloid leukemia patients with NPM1 mutation, but concomitant with DNMT3A co-mutation or a < 3log reduction of MRD2 predicted poor survival.

Co-occurring mutations are frequently observed in acute myeloid leukemia (AML) with NPM1 mutation, and NPM1 measurable residual disease (MRD) is an effective prognostic biomarker. This retrospective study investigated the impact of gene co-mutations and NPM1 MRD on outcomes in these patients. Among 234 patients, 11.5% carried the rare type NPM1 mutation (NPM1RT). The median age was 49 years (IQR 36-58), with a median follow-up of 30.4 months (IQR 12.1-55.7). Nine genes were mutated in > 10%, with DNMT3A (53.8%) and FLT3-ITD (44.4%) being most prevalent. Univariable analysis in 137 patients showed FLT3-ITD, DNMT3A co-mutations, and MRD2 < 3 log reduction predicted poorer survival. FLT3-ITD and DNMT3A co-mutations correlated with the lowest event-free (EFS) and overall survival (OS) (3-year EFS 30.0%; 3-year OS 34.4%; both p < 0.001). FLT3-ITD alone did not worsen survival compared to patients without FLT3-ITD. Multivariable analysis identified DNMT3A co-mutation [EFS, HR = 1.9, p = 0.021; OS, HR = 2.2, p = 0.023] and MRD2 ≥ 3 log reduction (EFS, HR = 0.2; OS, HR = 0.1, both p < 0.001) as independent survival predictors. Patients with FLT3-ITD and DNMT3A co-mutations or a MRD2 < 3 log reduction were identified as high risk, but allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved survival significantly compared to chemotherapy only (3-year EFS, 57.9% vs. 30.0%, p = 0.012; 3-year OS, 72.9% vs. 34.4%, p = 0.001). In AML patients with NPM1 mutation, the detrimental impact of FLT3-ITD mutation was exacerbated by DNMT3A co-mutation. Poor-risk younger patients identified by FLT3-ITD and DNMT3A co-mutations or MRD2 < 3 log reduction benefit from allo-HSCT.

Unraveling the protein post-translational modification landscape: Neuroinflammation and neuronal death after stroke.

The impact of stroke on global health is profound, with both high mortality and morbidity rates. This condition can result from cerebral ischemia, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). The pathophysiology of stroke involves secondary damage and irreversible loss of neuronal function. Post-translational modifications (PTMs) have been recognized as crucial regulatory mechanisms in ischemic and hemorrhagic stroke-induced brain injury. These PTMs include phosphorylation, glycosylation, ubiquitination, SUMOylation, acetylation, and succinylation. This comprehensive review delves into recent research on the PTMs landscape associated with neuroinflammation and neuronal death specific to cerebral ischemia, ICH, and SAH. This review aims to explain the role of PTMs in regulating pathologic mechanisms and present critical techniques and proteomic strategies for identifying PTMs. This knowledge helps us comprehend the underlying mechanisms of stroke injury and repair processes, leading to the development of innovative treatment strategies. Importantly, this review underscores the significance of exploring PTMs to understand the pathophysiology of stroke.

The role of phlorizin liposome-embedded oxidized sodium alginate/carboxymethyl chitosan in diabetic wound healing.

Wound healing in diabetic patients is often complicated by issues like inflammation, infection, bleeding, and fluid retention. To tackle these challenges, it is essential to create hydrogel dressings with anti-inflammatory, antibacterial, and antioxidative properties. This study aimed to synthesize Phlorizin-Liposomes (PL) through the thin-film dispersion method and integrate them into an oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMCS) hydrogel scaffold, resulting in an OSA/CMCS/PL (PLOCS) composite hydrogel via a Schiff base reaction. Characterization of the composite was performed using FTIR, TEM, and SEM techniques. The research assessed the swelling behavior, antibacterial effectiveness, and biocompatibility of the PLOCS composite hydrogel, while also investigating how PLOCS facilitates diabetic wound healing. The results demonstrated that PLOCS effectively controls drug release, possesses favorable swelling and degradation characteristics, and shows significant antioxidative properties along with in vitro biocompatibility. Histological analysis confirmed that PLOCS supports the proliferation of healthy epithelial tissue and collagen production. Western blotting indicated that PLOCS diminishes inflammation by inhibiting the TLR4/NF-κB/MyD88 pathway and activates Nrf2 to boost wound healing, increasing the levels of antioxidative enzymes such as HO-1, NQO1, and GCLC. In summary, PLOCS presents a promising new option for advanced wound dressings aimed at treating diabetic ulcers.

Clinicopathological and Ultrasonographic Characteristics of Breast Cancer in Young Women.

Purpose: The early detection of breast cancer in women under the age of 40 has posed significant challenges. This can be attributed in part to the limited research conducted on the breast cancer in this age group, particularly with regards to large sample sizes. We aimed to address this gap by analyzing and comparing the ultrasound imaging and pathological characteristics of breast cancer in women aged under 40 and those aged 40 and above. Methods: A retrospective assessment was conducted to examine the ultrasound imaging and clinicopathologic characteristics of 555 women with surgically confirmed breast cancers. The patient cohort consisted of 160 individuals below the age of 40 and 395 individuals aged 40 years and above. Results: Our study identified the breast cancer in patients under 40 years was more likely to show regular shape (p = 0.043) compared with tumors in patients who were 40 years and over. Furthermore, in young female patients (<40 years), irregular shape was correlated with the HER2-enriched type (p = 0.02), circumscribed margin (p = 0.001), and a lack of calcifications (p = 0.02) were associated with the triple-negative type. In another group (≥40 years), only a lack of calcifications (p = 0.003) were associated with the triple-negative type. Conclusion: Breast cancer in women under the age of 40 exhibits distinct ultrasonographic characteristics patterns that vary across different immunophenotypes, which may provide certain predictive information for physicians.

Delving deeper into the mechanisms fundamental to HIV-associated immunopathology using single-cell sequencing techniques: A scoping review of current literature.

Human immunodeficiency virus (HIV) infection has evolved into an established global pandemic over the past four decades; however, despite massive research investment globally, the precise underlying mechanisms which are fundamental to HIV-related pathogenesis remain unclear. Single cell ribonucleic acid (RNA) sequencing methods are increasingly being used for the identification of specific cell-type transcriptional changes in HIV infection. In this scoping review, we have considered information extracted from fourteen published HIV-associated single-cell RNA sequencing-related studies, hoping to throw light on the underlying mechanisms of HIV infection and pathogenesis, and to explore potential candidate biomarkers for HIV disease progression and antiviral treatment. Generally, HIV positive individuals tend to manifest disturbances of frequency of multiple cellular types, and specifically exhibit diminished levels of CD4+ T-cells and enriched numbers of CD8+ T-cells. Cell-specific transcriptional changes tend to be linked to cell permissiveness, hyperacute or acute HIV infection, viremia, and cell productivity. The transcriptomes of CD4+ T-cell and CD8+ T-cell subpopulations are also observed to change in HIV-positive diabetic individuals, spontaneous HIV controllers, individuals with high levels of HIV viremia, and those in an acute phase of HIV infection. The transcriptional changes seen in B cells, natural killer (NK) cells, and myeloid dendritic cells (mDCs) of HIV-infected individuals demonstrate that the humoral immune response, antiviral response, and immune response regulation, respectively, are all altered following HIV infection. Antiretroviral therapy (ART) plays a crucial role in achieving immune reconstitution, in improving immunological disruption, and in mitigating immune system imbalances in HIV-infected individuals, while not fully restoring inherent cellular transcription to levels seen in HIV-negative individuals. The preceding observations not only illustrate compelling advances in the understanding of HIV-associated immunopathogenesis, but also identify specific cell-type transcriptional changes that may serve as potential biomarkers for HIV disease monitoring and therapeutic targeting.

Comparing Baseline VAF in Circulating tumor DNA and Tumor Tissues Predicting Prognosis of Patients with Colorectal Cancer Liver Metastases After Curative Resection.

INTRODUCTION: The prognostic value of baseline variant allele frequency (VAF) in circulating tumor DNA (ctDNA) of colorectal cancer liver metastases (CRLM) patients after curative resection was rarely investigated. METHODS: A single-center prospective study was performed to investigate the prognostic impact of baseline VAF in ctDNA and matched tumor tissues of CRLM patients after curative resection between May 2019 and May 2021 by the Illumina NovoSeq 6000 platform. The relationship of the tumor burden score (TBS) and the VAF in ctDNA and matched tumor tissues was evaluated by the Pearson correlation method. The survival curves of recurrence-free survival (RFS) and overall survival (OS) were plotted. Factors associated with RFS were calculated using Cox regression analysis, and an integrated prognostic model using significant baseline variables was proposed. RESULTS: There were 121 patients with baseline ctDNA and matched tumor tissues enrolled in the study. A total of 417 mutations spanning 20 genes were identified in baseline tumor tissues of 119/121 (98.3%) cases. The overall mutations in tumor tissues were completely covered by ctDNA in 52 of 121(43.0%) patients. Baseline VAF in ctDNA but not in tumor tissues was significantly correlated to TBS of CRLM (R=0.36, p<0.001). Significantly longer RFS but not OS was observed in patients with lower VAF in ctDNA compared to those with higher one (p<0.001 and p=0.33 respectively). Multivariate Cox regression analysis showed higher VAF in baseline ctDNA was an independent risk factor for RFS. An integrated prognostic model including baseline metastasis location and VAF in ctDNA outperformed the traditional CRS model in predicting RFS. CONCLUSION: Baseline VAF in ctDNA but not in tumor tissues influenced RFS of CRLM patients after curative resection.

The Impact of Unrelated Future Medical Costs on Economic Evaluation Outcomes for Different Models of Diabetes.

OBJECTIVE: This study leveraged data from 11 independent international diabetes models to evaluate the impact of unrelated future medical costs on the outcomes of health economic evaluations in diabetes mellitus. METHODS: Eleven models simulated the progression of diabetes and occurrence of its complications in hypothetical cohorts of individuals with type 1 (T1D) or type 2 (T2D) diabetes over the remaining lifetime of the patients to evaluate the cost effectiveness of three hypothetical glucose improvement interventions versus a hypothetical control intervention. All models used the same set of costs associated with diabetes complications and interventions, using a United Kingdom healthcare system perspective. Standard utility/disutility values associated with diabetes-related complications were used. Unrelated future medical costs were assumed equal for all interventions and control arms. The statistical significance of changes on the total lifetime costs, incremental costs and incremental cost-effectiveness ratios (ICERs) before and after adding the unrelated future medical costs were analysed using t-test and summarized in incremental cost-effectiveness diagrams by type of diabetes. RESULTS: The inclusion of unrelated costs increased mean total lifetime costs substantially. However, there were no significant differences between the mean incremental costs and ICERs before and after adding unrelated future medical costs. Unrelated future medical cost inclusion did not alter the original conclusions of the diabetes modelling evaluations. CONCLUSIONS: For diabetes, with many costly noncommunicable diseases already explicitly modelled as complications, and with many interventions having predominantly an effect on the improvement of quality of life, unrelated future medical costs have a small impact on the outcomes of health economic evaluations.

Site-specific N-glycan alterations on haptoglobin as potential biomarkers for distinguishing intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

Intrahepatic cholangiocellular carcinoma (ICC) is a challenging malignancy marked by subtle early symptoms and a high mortality rate, making effective diagnostic markers crucial for early detection and improved patient outcomes. Currently, the conventional diagnosis of ICC is not easily distinguishable from Hepatocellular Carcinoma (HCC) and lacks highly specific and sensitive diagnostic markers. Protein glycosylation, pivotal in biological processes, shows promise for cancer biomarkers due to its association with disease progression. This study aims to develop a novel biomarker discovery framework for ICC utilizing site-specific quantitative N-glycoproteomics to overcome the limitations of existing diagnostic approaches. Employing a tandem mass tag (TMT)-based quantitative analysis, we profiled serum glycoproteins from ICC, HCC, and control cohorts at site-specific glycosylation level. The identified markers underwent further validation in an independent cohort using label-free quantitative methods. Ultimately, we identified five site-specific N-glycans on haptoglobin (HP) as potential biomarkers (AUC > 0.9) for distinguishing ICC from HCC. This finding represents a considerable advance over traditional biomarkers, highlighting the significance of protein glycosylation alterations in ICC pathogenesis. This research, therefore, sets a new precedent for biomarker discovery in ICC, with potential applications in other cancers characterized by glycosylation abnormalities.

HMGB3 and SUB1 Bind to and Facilitate the Repair of N2-Alkylguanine Lesions in DNA.

N2-Alkyl-2'-deoxyguanosine (N2-alkyl-dG) is a major type of minor-groove DNA lesions arising from endogenous metabolic processes and exogenous exposure to environmental contaminants. The N2-alkyl-dG lesions, if left unrepaired, can block DNA replication and transcription and induce mutations in these processes. Nevertheless, the repair pathways for N2-alkyl-dG lesions remain incompletely elucidated. By utilizing a photo-cross-linking coupled with mass spectrometry-based quantitative proteomic analysis, we identified a series of candidate N2-alkyl-dG-binding proteins. We found that two of these proteins, i.e., high-mobility group protein B3 (HMGB3) and SUB1, could bind directly to N2-nBu-dG-containing duplex DNA in vitro and promote the repair of this lesion in cultured human cells. In addition, HMGB3 and SUB1 protected cells against benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE). SUB1 exhibits preferential binding to both the cis and trans diastereomers of N2-BPDE-dG over unmodified dG. On the other hand, HMGB3 binds favorably to trans-N2-BPDE-dG; the protein, however, does not distinguish cis-N2-BPDE-dG from unmodified dG. Consistently, genetic ablation of HMGB3 conferred diminished repair of trans-N2-BPDE-dG, but not its cis counterpart, whereas loss of SUB1 conferred attenuated repair of both diastereomers. Together, we identified proteins involved in the cellular sensing and repair of minor-groove N2-alkyl-dG lesions and documented a unique role of HMGB3 in the stereospecific recognition and repair of N2-BPDE-dG.