3D bioprinting of an in vitro hepatoma microenvironment model: Establishment, evaluation, and anticancer drug testing.

Tumor behavior, including its response to treatments, is influenced by interactions between mesenchymal and malignant cells, as well as their spatial arrangement. To study tumor biology and evaluate anticancer drugs, accurate 3D tumor models are essential. Here, we developed an in vitro biomimetic hepatoma microenvironment model by combining an extracellular matrix (3DM-7721). Initially, the internal grid structure, composed of 10/6 % GelMA/gelatin loaded with SMMC-7721 cells, was printed using 3D bioprinting. The external component consisted of fibroblasts and human umbilical vein endothelial cells loaded with 10/3 % GelMA/gelatin. A control model (3DP-7721) lacked external cell loading. GelMA/gelatin hydrogels provided robust structural support and biocompatibility. The SMMC-7721 cells in the 3DM-7721 model exhibit superior tumor-associated gene expression and proliferation characteristics when compared to the 3DP-7721 model. Furthermore, the 3DM-7721 type exhibited increased resistance to anticancer agents. SMMC-7721 cells in the 3DM-7721 model exhibit significant tumorigenicity in nude mice. The 3DM-7721 model group showed pathological characteristics of malignant tumors, with a high degree of deterioration, and a significant positive correlation between malignant tumor-related gene pathways. This high-fidelity 3DM-7721 tumor microenvironment model is invaluable for studying tumor progression, devising effective treatment strategies, and discovering drugs. STATEMENT OF SIGNIFICANCE.

Identification and validation of calcium extrusion-related genes prognostic signature in colon adenocarcinoma.

Background: Disruptions in calcium homeostasis are associated with a wide range of diseases, and play a pivotal role in the development of cancer. However, the construction of prognostic models using calcium extrusion-related genes in colon adenocarcinoma (COAD) has not been well studied. We aimed to identify whether calcium extrusion-related genes serve as a potential prognostic biomarker in the COAD progression. Methods: We constructed a prognostic model based on the expression of calcium extrusion-related genes (SLC8A1, SLC8A2, SLC8A3, SLC8B1, SLC24A2, SLC24A3 and SLC24A4) in COAD. Subsequently, we evaluated the associations between the risk score calculated by calcium extrusion-related genes and mutation signature, immune cell infiltration, and immune checkpoint molecules. Then we calculated the immune score, stromal score, tumor purity and estimate score using the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm. The response to immunotherapy was assessed using tumor immune dysfunction and exclusion (TIDE). Finally, colorectal cancer cells migration, growth and colony formation assays were performed in RKO cells with the overexpression or knockdown SLC8A3, SLC24A2, SLC24A3, or SLC24A4. Results: We found that patients with high risk score of calcium extrusion-related genes tend to have a poorer prognosis than those in the low-risk group. Additionally, patients in high-risk group had higher rates of KRAS mutations and lower MUC16 mutations, implying a strong correlation between KRAS and MUC16 mutations and calcium homeostasis in COAD. Moreover, the high-risk group showed a higher infiltration of regulatory T cells (Tregs) in the tumor microenvironment. Finally, our study identified two previously unreported model genes (SLC8A3 and SLC24A4) that contribute to the growth and migration of colorectal cancer RKO cells. Conclusions: Altogether, we developed a prognostic risk model for predicting the prognosis of COAD patients based on the expression profiles of calcium extrusion-related genes, Furthermore, we validated two previously unreported tumor suppressor genes (SLC8A3 and SLC24A4) involved in colorectal cancer progression.

Therapeutic potential of esculetin in various cancer types (Review).

Esculetin (Esc), a coumarin derivative and herbal medicinal compound used in traditional Chinese medicine, is extracted from Fraxinus chinensis. Esc has shown notable potential in the inhibition of proliferation, metastasis and cell cycle arrest in various cancer cell lines. The present review is based on research articles regarding Esc in the field of carcinoma, published between 2009 and 2023. These studies have unanimously demonstrated that Esc can effectively inhibit cancer cell proliferation through diverse mechanisms and modulate multiple signaling pathways, such as Wnt/ß-catenin, PI3K/Akt, MAPK and janus kinase/signal transducer and activator of transcription-3. In addition, the safety profile of Esc has been demonstrated in credible animal experiments, which has indicated Esc as an effective compound. Furthermore, the combination therapy of Esc with commonly used chemotherapeutic drugs holds great promise. The aim of the present review was to encourage further studies and applications of Esc in cancer therapy.

Integrated transmission electron microscopy and proteomic analyses reveal the cytoarchitectural response to cucumber mosaic virus infection in tobacco.

Cucumber mosaic virus (CMV) causes huge economic losses to agriculture every year; thus, understanding the mechanism of plant resistance to CMV is imperative. In this study, an integrated analysis of transmission electron microscopy (TEM) observations and proteomic results was used to identify cytoarchitectural differences in Nicotiana tabacum cv. NC82 (susceptible) and cv. Taiyan 8 (T.T.8; resistant) following infection with CMV. The TEM observations showed that the structure of the chloroplasts and mitochondria was severely damaged at the late stage of infection in NC82. Moreover, the chloroplast stroma and mitochondrial cristae were reduced and disaggregated. However, in T.T.8, organelle structure remained largely intact Selective autophagy predominated in T.T.8, whereas non-selective autophagy dominated in NC82, resembling cellular disorder. Proteomic analysis of T.T.8 revealed differentially expressed proteins (DEPs) mostly associated with photosynthesis, respiration, reactive oxygen species (ROS) scavenging, and cellular autophagy. Biochemical analyses revealed that ROS-related catalase, autophagy-related disulfide isomerase, and jasmonic acid and antioxidant secondary metabolite synthesis-related 4-coumarate:CoA ligase (Nt4CL) exhibited different trends and significant differences in expression in the two cultivars after CMV inoculation. Furthermore, mutant phenotyping verified that reduced Nt4CL expression impaired resistance in T.T.8. The identified DEPs are crucial for maintaining intracellular homeostatic balance and likely contribute to the mechanism of CMV resistance in tobacco. These findings increase our understanding of plant cytological mechanisms conferring resistance to CMV infection.

Resurfacing of Sleeve-Like Circumferential Giant Congenital Melanocytic Nevi on the Upper Extremity With Pre-Expanded Pedicled Flap.

As the relative shortage of healthy tissue obviates the option of local soft tissue coverage, reconstruction of circumferential giant congenital melanocytic nevi (GCMN) on the upper extremity remains particularly challenging. Here the authors report a 3-stage procedure involving pre-expanded pedicled flap from the torso for the reconstruction of upper extremity after circumferential GCMN excision in pediatric patients. The giant nevus was completely removed and the size of the excised nevus was 31 × 14.5 cm. The donor site was primarily closed. No major complication was encountered. Reconstruction with expanded pedicled flap achieved satisfactory results, both functionally and cosmetically.

Synergistic anticancer effect by targeting CDK2 and EGFR-ERK signaling.

The EGFR-RAS-ERK pathway is one of the most important signaling cascades in cell survival, growth, and proliferation. Aberrant activation of this pathway is a common mechanism in various cancers. Here, we report that CDK2 is a novel regulator of the ERK pathway via USP37 deubiquitinase (DUB). Mechanistically, CDK2 phosphorylates USP37, which is required for USP37 DUB activity. Further, USP37 deubiquitinates and stabilizes ERK1/2, thereby enhancing cancer cell proliferation. Thus, CDK2 is able to promote cell proliferation by activating USP37 and, in turn, stabilizing ERK1/2. Importantly, combined CDK1/2 and EGFR inhibitors have a synergetic anticancer effect through the downregulation of ERK1/2 stability and activity. Indeed, our patient-derived xenograft (PDX) results suggest that targeting both ERK1/2 stability and activity kills cancer cells more efficiently even at lower doses of these two inhibitors, which may reduce their associated side effects and indicate a potential new combination strategy for cancer therapy.

Metabolic regulation of homologous recombination repair by MRE11 lactylation.

Lactylation is a lactate-induced post-translational modification best known for its roles in epigenetic regulation. Herein, we demonstrate that MRE11, a crucial homologous recombination (HR) protein, is lactylated at K673 by the CBP acetyltransferase in response to DNA damage and dependent on ATM phosphorylation of the latter. MRE11 lactylation promotes its binding to DNA, facilitating DNA end resection and HR. Inhibition of CBP or LDH downregulated MRE11 lactylation, impaired HR, and enhanced chemosensitivity of tumor cells in patient-derived xenograft and organoid models. A cell-penetrating peptide that specifically blocks MRE11 lactylation inhibited HR and sensitized cancer cells to cisplatin and PARPi. These findings unveil lactylation as a key regulator of HR, providing fresh insights into the ways in which cellular metabolism is linked to DSB repair. They also imply that the Warburg effect can confer chemoresistance through enhancing HR and suggest a potential therapeutic strategy of targeting MRE11 lactylation to mitigate the effects.

The Corrosion Behavior of X100 Pipeline Steel in a Sodium Chloride Solution Containing Magnesium and Calcium.

The influences of Mg2+ and Ca2+ on the short-term (1800 s) corrosion behavior of X100 pipeline steel were investigated in a sodium chloride (NaCl) solution saturated with CO2. Either Ca2+ or Mg2+ in the solution inhibited the short-term corrosion of X100 pipeline steel, with the corrosion current density decreasing from 262.4 µA cm-2 to 163.5 µA cm-2 or 80.8 µA cm-2. During longer-term (8-48 h) immersion, the Mg2+ inhibited the formation of the protective scale, whereas the Ca2+ accelerated the formation of the scale. Further, an experimental equation establishing the relationship between the precipitation rate of the corrosion scale and the exposure time was proposed to quantitatively study the effects of Mg2+ and Ca2+ on the precipitation rate of the corrosion scale.

Superior Enhancement of the UHMWPE Fiber/Epoxy Interface through the Combination of Plasma Treatment and Polypyrrole In-Situ Grown Fibers.

Obtaining a robust fiber/matrix interface is crucial for enhancing the mechanical performance of fiber-reinforced composites. This study addresses the issue by presenting a novel physical-chemical modification method to improve the interfacial property of an ultra-high molecular weight polyethylene (UHMWPE) fiber and epoxy resin. The UHMWPE fiber was successfully grafted with polypyrrole (PPy) for the first time after a plasma treatment in an atmosphere of mixed oxygen and nitrogen. The results demonstrated that the maximum value of the interfacial shear strength (IFSS) of the UHMWPE fiber/epoxy reached 15.75 MPa, which was significantly enhanced by 357% compared to the pristine UHMWPE fiber. Meanwhile, the tensile strength of the UHMWPE fiber was only slightly reduced by 7.3%, which was furtherly verified by the Weibull distribution analysis. The surface morphology and structure of the PPy in-situ grown UHMWPE fibers were studied using SEM, FTIR, and contact angle measurement. The results showed that the enhancement of the interfacial performance was attributed to the increased fiber surface roughness and in-situ grown groups, which improved the surface wettability between the UHMWPE fibers and epoxy resins.

RIIß-PKA in GABAergic Neurons of Dorsal Median Hypothalamus Governs White Adipose Browning.

The RIIß subunit of  cAMP-dependent protein kinase A (PKA) is expressed in the brain and adipose tissue. RIIß-knockout mice show leanness and increased UCP1 in brown adipose tissue. The authors have previously reported that RIIß reexpression in hypothalamic GABAergic neurons rescues the leanness. However, whether white adipose tissue (WAT) browning contributes to the leanness and whether RIIß-PKA in these neurons governs WAT browning are unknown. Here, this work reports that RIIß-KO mice exhibit a robust WAT browning. RIIß reexpression in dorsal median hypothalamic GABAergic neurons (DMH GABAergic neurons) abrogates WAT browning. Single-cell sequencing, transcriptome sequencing, and electrophysiological studies show increased GABAergic activity in DMH GABAergic neurons of RIIß-KO mice. Activation of DMH GABAergic neurons or inhibition of PKA in these neurons elicits WAT browning and thus lowers body weight. These findings reveal that RIIß-PKA in DMH GABAergic neurons regulates WAT browning. Targeting RIIß-PKA in DMH GABAergic neurons may offer a clinically useful way to promote WAT browning for treating obesity and other metabolic disorders.

Short Nose Lengthening in Primary and Revision Rhinoplasty in Asians.

BACKGROUND: Surgical techniques and graft materials are important factors for short nose lengthening in both primary and revision rhinoplasty in Asian patients. Other subunit of the nose need to be improved as well to achieve aesthetic perfection. MATERIALS AND METHODS: A cohort of 98 patients who underwent primary and revision rhinoplasty for moderate to severe short nose deformity from January 1, 2019, to December 31, 2020, were enrolled. Nasal elongation was achieved via an open rhinoplasty approach using autologous costal cartilage exclusively for grafting. Aesthetic outcomes were evaluated by anthropometric measurement and satisfaction assessment from patients and physicians. RESULTS: The mean duration of follow-up was 10.6 months. In both primary and revision cases, nasal length relative to preoperative measurements increased significantly, while nasal tip projection did not differ significantly. Columellar-facial angle and nasofrontal angle decreased significantly in both groups. Both physicians and patients reported improvement in aesthetic outcomes. CONCLUSIONS: Aesthetic satisfaction was reported from both patients and physicians. Autologous costal cartilage is an ideal graft material that offers strong structural support. Caudal septal extension graft using autologous costal cartilage sandwiched by extended spreader grafts achieve satisfactory lengthening of the central compartment and also increase nasal tip projection and rotation.

A Combination Method of Costal Cartilage Injection Techniques for Augmentation Rhinoplasty.

BACKGROUND: The multiple toothpick-shaped costal cartilage (MTCC) injection technique was introduced as an improvement based on the free diced costal cartilage (FDCC) injection technique for augmentation rhinoplasty. However, radix irregularities may occur when using the MTCC technique. Considering that the FDCC grafts are easier to shape at the nasal radix, we adopted a combination method of the 2 techniques to achieve natural and smooth contour. METHODS: Four patients accepted this method for augmentation rhinoplasty. Through a unilateral marginal incision, the costal cartilage grafts were injected for nasal augmentation at the subperiosteal plane. The FDCC grafts and the MTCC grafts were used for nasal radix and dorsum augmentation, respectively. Nasal contour was adjusted by external shaping. The follow-up ranged from 24 to 43 months. RESULTS: All patients were satisfied with the surgical outcome. There were no major complications occurred during the follow-up. One patient underwent rasping revision due to her own beauty-appreciation changes. CONCLUSIONS: The combination method can take advantages of the FDCC and MTCC injection techniques. It can effectively lower the incidence of contour irregularities and graft displacement. Meanwhile, it is easy to perform without special procedure, and is time-saving and cartilage-saving.

BMP-2 promotes osteogenic differentiation of mesenchymal stem cells by enhancing mitochondrial activity.

OBJECTIVES: Mesenchymal stem cells (MSCs) have become seed cells and basic elements for bone regeneration and bone tissue engineering. The aim of the present study was to investigate the roles and mechanisms of bone morphogenetic protein 2 (BMP-2) on osteogenic differentiation of MSCs. METHODS: Primary MSCs were isolated from the femur and tibia bone of rats and then transfected with BMP-2 and PGC-1α adenovirus vectors. Alkaline phosphatase (ALP) activity and alizarin red staining were used to measure osteogenic differentiation of MSCs. Real-time PCR and western blot assays were performed to assess osteogenic differentiation-related proteins levels. The activities of mitochondrial respiratory chain complexes I and II and mitochondrial fluorescence intensity were used to explore mitochondria status during osteogenic differentiation of MSCs. RESULTS: We found that the ability of BMP-2 overexpressed (OE) group osteogenic differentiation was significantly improved, compared with the negative control (NC) group. The results also indicated that BMP-2 can promote the activity of mitochondria. We further used the gain- and loss-of-function approaches to demonstrate that BMP-2 promotes mitochondrial activity by up-regulating PGC-1α to promote osteogenic differentiation of MSCs. CONCLUSIONS: These results explored the important role of BMP-2 in the osteoblast differentiation of MSCs from a new perspective, providing a theoretical and experimental basis for bone defect and repair.

Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer.

BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).

FGF21 alleviates acute liver injury by inducing the SIRT1-autophagy signalling pathway.

Liver injury can lead to different hepatic diseases, which are the mainly causes of high global mortality and morbidity. Autophagy and Sirtuin type 1 (SIRT1) have been shown protective effects in response to liver injury. Previous studies have showed that Fibroblast growth factor 21 (FGF21) could alleviate acute liver injury (ALI), but the mechanism remains unclear. Here, we verified the relationship among FGF21, autophagy and SIRT1 in carbon tetrachloride (CCl4 )-induced ALI. We established CCl4 -induced ALI models in C57BL/6 mice and the L02 cell line. The results showed that FGF21 was robustly induced in response to stress during the development of ALI. After exogenous FGF21 treatment in ALI models, liver damage in ALI mice was significantly reduced, as well as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Consistently, FGF21 also greatly reduced the levels of ALT, AST, pro-inflammatory cytokines interleukin 6 (IL6) and tumour necrosis factor-alpha (TNFα) in ALI cell lines. Mechanistically, exogenous FGF21 treatment efficiently upregulated the expression of autophagy marker microtubule-associated protein light chain-3 beta (LC3 II) and autophagy key molecule coiled-coil myosin-like BCL2-interacting protein (Beclin1), which was accompanied by alleviating hepatotoxicity in CCl4 -treated wild-type mice. Then, we examined how FGF21 induced autophagy expression and found that SIRT1 was also upregulated by FGF21 treatment. To further verify our results, we constructed an anti-SIRT1 lentit-RNAi to inhibit SIRT1 expression in mice and L02 cells, which reversed the protective effect of FGF21 on ALI. In summary, these results indicate that FGF21 alleviates ALI by enhancing SIRT1-mediated autophagy.

Comparison of Free Diced and Multiple Toothpick-Shaped Costal Cartilage Injection Techniques for Augmentation Rhinoplasty.

BACKGROUND: The free diced costal cartilage (FDCC) injection technique has been used in the augmentation rhinoplasty for a long time. In order to lower the incidence of nasal contour irregularities and graft displacement, we developed the multiple toothpick-shaped costal cartilage (MTCC) injection technique. This comparative study was conducted to introduce and assess this new technique. METHODS: This retrospective analysis included 51 patients who underwent augmentation rhinoplasty with either the FDCC or MTCC injection technique at the 17th Department of Plastic Surgery in the Plastic Surgery Hospital between July 2014 and May 2020. The patients were divided into the FDCC (n = 30, 58.82%) and MTCC (n = 21, 41.18%) groups. General data, postoperative patient satisfaction, complications and revision rate were compared between the groups. RESULTS: Except for the follow-up period, there were no significant differences in general data (age, sex, preoperative dorsum deformity, preoperative rhinoplasty history) between the groups. Postoperative patient satisfaction, complications and revision rate were similar between the two groups. CONCLUSIONS: The MTCC injection is a safe and effective technique for augmentation rhinoplasty. Like the FDCC injection technique, the new technique is relatively easy to perform and time-saving with concealed scarring and minimal postoperative edema. Most of its revision surgeries are also easy to perform by simple rasping and reinjection. According to our experience, the new technique may have wider indication as well as lower incidence of nasal contour irregularities and graft displacement. Therefore, we suggest that the MTCC injection technique is reliable and worthy of recommendation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Insulin promotes hepatocarcinoma tumorigenesis by up-regulating PKM2 expression.

Insulin, as a growth factor, can increase the risk of certain types of cancer. The present study showed that insulin promoted the proliferation of hepatocellular carcinoma cells in vitro and in vivo through pyruvate kinase M2 (PKM2), which is a rate-limiting enzyme in the process of glycolysis. Moreover, the expression of PKM2 was up-regulated by insulin at the posttranslational level in a nuclear orphan receptor TR3-dependent manner. In addition, insulin could enhance the interaction between PKM2 and TR3 and protect PKM2 from degradation. Our results identified a specific mechanism of insulin affecting cancer metabolism and thus promoting cancer progression, and they contribute to a better understanding of the observation that insulin is linked to an increased cancer risk under hyperinsulinemic conditions.

Comparison of the Efficacy of Two Elastic Bandages for Forearm Hematoma After Transradial Coronary Intervention.

Background: This study compares the efficacy of two elastic bandages in treating forearm hematoma after transradial coronary intervention. Methods: A total of 60 patients with moderate or severe forearm hematoma following transradial coronary intervention were enrolled in this study. They were randomly divided into two groups, as follows: an Idealast-haft elastic bandage group (the observation group) and a control group. The patients in the Idealast-haft elastic bandage group received compression bandaging with Idealast-haft elastic bandages and the patients in the control group received compression bandaging with Nylexorgrip elastic bandages. Observation indexes related to, for example, forearm pain, arterial pulsation, blistering, skin color, and hemostasis time were compared between the two groups. Results: The results revealed that the times taken for pain disappearance, arterial pulse recovery, blister disappearance, skin color recovery, and compression hemostasis were significantly shorter in the Idealast-haft elastic bandage group than in the control group, and the differences were statistically significant (P < 0.05). The hematoma range and the arm circumference at the severest part of the hematoma decreased faster in the observation group than in the control group, and the differences were statistically significant (P < 0.05). Conclusion: The Idealast-haft elastic bandage is more effective than the Nylexorgrip elastic bandage in patients with forearm hematoma following transradial coronary intervention and should therefore be used in such cases.

Myricetin protects natural killer cells from arsenite induced DNA damage by attenuating oxidative stress and retaining poly(ADP-Ribose) polymerase 1 activity.

Environmental exposure to arsenite (As+3) is known to induce immunotoxicity. Natural killer (NK) cells are innate lymphoid cells act as professional killers of tumor cells. Our previous report indicated that 500 ppb As+3 drinking water exposure induced significant DNA damage in the NK cells of C57BL/6 mice. Myricetin is a plant-derived flavonoid known as a strong antioxidant. In this study, daily administration of myricetin at 20 mg/kg was found to alleviate the cell population decrease and DNA damage in the NK cells of BALB/c mice exposed to 500 and 1000 ppb As+3 via drinking water. Oxidative stress and poly(ADP-ribose) polymerase 1 (PARP-1) inhibition were induced by As+3 at 1 and 2 µM in isolated mouse NK cells in vitro, which were attenuated by 20 µM myricetin. The mitigatory effect of myricetin on the PARP-1 inhibition in NK cells treated with As+3 was also found to be the result of its prevention of the zinc loss induced by As+3 on PARP-1. Collectively, these results demonstrated, for the first time, that myricetin could protect NK cells from As+3 induced DNA through attenuating oxidative stress and retaining PARP-1 activity, indicating that myricetin may be utilized for the prevention of the immunotoxicity induced by As+3 in NK cells.