Research Progress of nucleic acid delivery vectors for gene therapy.

Gene therapy has broad prospects as an effective treatment for some cancers and hereditary diseases. However, DNA and siRNA are easily degraded in vivo because of their biological activities as macromolecules, and they need the effective transmembrane delivery carrier Selecting the appropriate carrier for delivery will allow nucleic acid molecules to reach their site of action and enhance delivery efficiency. Currently used nucleic acid delivery vectors can be divided into two major categories: viral and non-viral vectors. Viral carrier transport efficiency is high, but there are safety issues. Non-viral vectors have attracted attention because of their advantages such as low immunogenicity, easy production, and non-tumorigenicity. The construction of safe, effective, and controllable vectors is the focus of current gene therapy research. This review presents the current types of nucleic acid delivery vehicles, which focuses on comparing their respective advantages and limitations, and proposes a novel delivery system, RNTs, a novel nanomolecular material, introducing the characteristics and nucleic acid delivery process of RNTs and their latest applications.

Five novel and highly efficient endophytic fungi isolated from Huperzia serrata expressing huperzine A for the treatment of Alzheimer's disease.

Huperzine A (Hup A) is an important drug for treating Alzheimer's disease (AD) and mainly extracted from the Huperzia serrata (Thunb.) Trevis. (Lycopodiaceae) (HS). Nevertheless, the content of Hup A in HS is very low of 0.007% with growing circle of 8 to 10 years, and the chemical synthesis of Hup A still has some insurmountable limitations in the industrialized production. So, the available resources of Hup A for clinical treatment of AD are scarce. The purpose of this work was to construct a biosynthesis platform based on the endophytic fungi from HS. In this work, five endophytic fungi Mucor racemosus NSH-D, Mucor fragilis NSY-1, Fusarium verticillioides NSH-5, Fusarium oxysporum NSG-1, and Trichoderma harzianum NSW-V were firstly found and isolated from the Chinese folk medicine HS, which were identified according to their morphological characteristics and nuclear ribosomal DNA ITS sequences. The highest efficient fungus could effectively biosynthesize Hup A in a liquid culture of 319.8 ± 0.17 mg/L which were 112 times higher than that of other reported conventional endophytic fungi. Moreover, these fungi with higher hereditary stability could possess the initial expressing ability of Hup A after 40 generations, and the expressed Hup A from these biosynthesis systems has prior physicochemical properties, a better inhibition activity of acetylcholinesterase and a lower cytotoxicity compared with the listed active pharmaceutical ingredients (APIs) of Hup A. These results provide promising alternative resources for producing Hup A at an industrial scale by biosynthesis, and it may also shed light on millions of AD patients. KEY POINTS: • Five novel endophytic fungi with high stability could highly express prior Hup A Graphical abstract.

RETRACTED: Bimodal Distribution of Nuclear Factor-κB Activation and Expression of Subunits in Experimental Models of Intracerebral Hemorrhage In Vivo.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors as it contains erroneous experimental results, pictures, discussions and conclusions related to IL-1ß and TNF-α. The authors were unable to repeat the experimental results of IL-1ß and TNF-α in the subsequent 2 repeated experiments. We apologise and inform the readers of the journal that the conclusions of the manuscript are invalid.

Single Chemosensor for Double Analytes: Spectrophotometric Sensing of Cu(2+) and Fluorogenic Sensing of Al(3+) Under Aqueous Conditions.

(E)-N-((8-Hydroxy-1,2,3,5,6,7-hexahydropyrido-[3,2,1-ij]-quinolin-9-yl)methylene)-4-tert-butyl -benzhydrazide has been developed as a single, dual-functional chemosensor. The chemosensor showed a good selectivity and sensitivity toward to Al(3+) and Cu(2+) at a low detection limit, respectively. Theoretical calculations have also been carried out to understand the configuration of the complexes.

Nuclear factor-κB activation in perihematomal brain tissue correlates with outcome in patients with intracerebral hemorrhage.

BACKGROUND: Nuclear factor-κB (NF-κB) plays an important role in the inflammatory response after intracerebral hemorrhage (ICH). We therefore proposed that NF-κB activation in perihematomal brain tissue might correlate with clinical outcome in patients with ICH. To confirm this, we studied clinical data of 45 patients with ICH and NF-κB activation in perihematomal brain tissue and analyzed predictors of clinical outcome as well as the predictive value of NF-κB activation. METHODS: Forty-five patients with spontaneous basal ganglia hemorrhage were prospectively investigated. The clinical data were collected, which include demographics, alcohol and tobacco abuse, stroke risk factors, neuroimaging variables at presentation, Glasgow Coma Scale (GCS) at admission, number of days in hospital, mechanical ventilation, pneumonia, and outcome. Clinical outcome was assessed by the modified Rankin Scale at 6 months after ICH. Perihematomal brain tissue was collected, and NF-κB activation was detected using immunohistochemistry. Univariate analysis and multivariate logistic regression analysis were performed to determine predictors of the poor outcome. RESULTS: Immunohistochemical detection showed that NF-κB p65 was expressed in the nuclei of neurons and glial cells in all patients. The number of nuclear NF-κB p65-positive cells was 54 ± 21. Six months after ICH, 18 (40%) patients achieved a favorable functional outcome (mRS ≤ 3) while 27 (60%) had a poor functional outcome (mRS 4 to 6). In univariate analysis, predictors of poor functional outcome were lower GCS score on admission (P = 0.004), larger hematoma volume (P = 0.004), intraventricular extension (P = 0.047), midline shift (P = 0.005), NF-κB activation (P < 0.0001), mechanical ventilation (P = 0.018), and co-morbidity with pneumonia (P = 0.002). In multivariate logistic regression analysis, NF-κB activation was the only independent predictor of poor outcome at 6 months after ICH. CONCLUSIONS: NF-κB activation is closely related to clinical outcome 6 months after ICH in humans. Therefore, it could be useful to predict prognosis of ICH accurately and should be further evaluated as a target for therapeutic strategies of ICH in the future.

Prognostic value of grading masticator space involvement in nasopharyngeal carcinoma according to MR imaging findings.

PURPOSE: To derive a suitable method for grading masticator space invasion in nasopharyngeal carcinoma on the basis of magnetic resonance (MR) images and to determine its prognostic value in patients undergoing intensity-modulated radiation therapy. MATERIALS AND METHODS: After institutional review board approval and informed consent were acquired, 808 patients with nasopharyngeal carcinoma who were treated with definitive intensity-modulated radiation therapy were analyzed retrospectively. The anatomic sites of masticator space involvement were identified with MR imaging. Overall survival, local relapse-free survival, and distant metastasis-free survival were calculated by using the Kaplan-Meier method and were compared by using the log-rank test. Potential prognostic factors were identified by means of multivariate analysis. RESULTS: Masticator space involvement was diagnosed in 163 of 808 patients (20.2%). Patients with lateral invasion (involvement of the lateral pterygoid muscle of the masticator space and beyond) had significantly poorer overall survival and distant metastasis-free survival than those with medial invasion (involvement of the medial pterygoid muscle of the masticator space) (P = .035 and P = .026, respectively). Furthermore, their overall survival, local relapse-free survival, and distant metastasis-free survival were significantly poorer compared with patients with stage T2 or T3 disease (all P ≤ .023) but similar to patients with stage T4 disease. The grade of masticator space involvement was an independent prognostic factor for overall survival, local relapse-free survival, and distant metastasis-free survival (all P ≤ .023). CONCLUSION: Masticator space involvement in nasopharyngeal carcinoma should be graded as medial (stage T2 disease) or lateral (stage T4 disease). This can facilitate staging of nasopharyngeal carcinoma and may be a suitable prognostic indicator of survival.

Physicochemically modulated fluorescence-scattering ratiometric sensor for selective and visual detection of levodopa.

In this study, a facile fluorescence-scattering ratiometric sensor was designed for visual and selective detection of levodopa (LD) via a clever physicochemical modulation scheme. The alkalized products of LD can rapidly react with polyethyleneimine (PEI) to exhibit an intense blue fluorescence and decrease the second-order scattering (SOS) signal of PEI. As the concentration of LD increased, the fluorescence intensity at 420 nm increased and the SOS intensity at 675 nm decreased synchronously. Thus the fluorescence-scattering ratiometric sensor was constructed by virtue of the two simultaneously changed signals. Furthermore, red light-emitting Au nanoclusters (AuNCs) were added into the above mixture solution to enlarge the SOS signal and provide a stable red background fluorescence. The intensity ratio of fluorescence to SOS (F/(S/Sblank)) is linear dependent on CLD in the wide range of 50.0---30000.0 nM, and LD as low as 50.0 nM can be identified with the naked eye via change of fluorescence color. The developed ratiometric sensor is smart, simple and efficient, and has been applied to the convenient assay of LD in real samples. The proposed physicochemical modulation strategy provides a new and facile path for selectively and visually identifying the target from its analogues.

Effect of electroacupuncture of "Zusanli" (ST36) combined with capeOX on apoptosis and ferroptosis in nude mice with colorectal cancer. / 电针"足三里"联合capeOXæ–¹æ¡ˆå¯¹ç»“ç›´è‚ ç™Œè£¸é¼ è‚¿ç˜¤ç»†èƒžå‡‹äº¡å’Œé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. METHODS: Female Balb/c nude mice were randomly assigned to 3 groups：model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. RESULTS: Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). CONCLUSIONS: EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.

Artemdubosides A-G, seven unusual polyacetylenes from Artemisia dubia var. subdigitata and their antihepatoma activity.

Artemdubosides A-E (1-5), the first examples of natural polyacetylenes substituted by 6'-O-crotonyl ß-glucopyranoside, and artemdubosides F-G (6-7) that were two unusual polyacetylenes featuring a 6'-O-acetyl ß-glucopyranoside moiety, were isolated from Artemisia dubia var. subdigitata. Their structures were elucidated based on the spectral data including HRESIMS, UV, IR, 1D and 2D NMR, and ECD calculations. Antihepatoma assay suggested that compound 1 exhibited activity against HepG2, Huh7, and SK-Hep-1 cells with inhibitory ratios of 77.1%, 90.8%, and 73.1% at 200.0 µM, respectively.

[Prognostic correlation of intracranial pressure monitoring in patients with severe craniocerebral injury].

OBJECTIVE: To explore the clinical application of intracranial pressure (ICP) monitoring and its prognostic correlation in patients with severe craniocerebral injury. METHODS: A total of 216 severe craniocerebral injury patients with scores of Glasgow coma scale 3-8 underwent craniotomy at Affiliated Qilu Hospital, Shandong University.And 168 cases of ICP monitoring were divided into 3 treatment groups and another 48 cases without ICP monitoring selected as the control group.According to ICP, stepwise treatment was administered to control the level of ICP and maintain the cerebral perfusion pressure to analyze the relationship between ICP monitoring and prognosis. RESULTS: As compared with the control group, there were significant decreases of disability and mortality rate for patients with ICP monitoring (A, B, C group). Especially group C had a better prognosis than the other groups for statistical significance.In addition, the dose and duration of mannitol of group A, B or C were significantly lower than those of the control group (P < 0.05). CONCLUSION: The application of ICP monitoring is capable of reducing mortality, improving prognosis and enhancing success rate of treating severe craniocerebral injury.

Preparation and properties of lignin-based dual network hydrogel and its application in sensing.

Ionic conductive hydrogels prepared from various biological macromolecules are ideal materials for the manufacture of human motion sensors from the perspective of resource regeneration and environmental sustainability. However, it is now difficult to develop conductive hydrogels including excellent self-healing and mechanical properties, mainly due to their inherent trade-off between dynamic cross-linked healing and stable cross-linked mechanical strength. In this work, alkali lignin-Polyvinyl alcohol-polyacrylic acid double network conductive hydrogels with high mechanical strength and good self-healing properties were prepared. We formed the primary network structure by hydrogen bonding interaction between polyvinyl alcohol, alkali lignin and polyacrylic acid, and the secondary network structure by coordination interaction with polyacrylic acid through the addition of Fe3+. The added lignin acts as a dynamic linkage bridge in a porous network mediated by multiple ligand bonds, imparting superior mechanical properties to the hydrogels. The relationships between the alkali lignin and iron ion dosage and the comprehensive properties of hydrogels (adhesion, antibacterial, self-healing, electrical conductivity and mechanical properties) were studied in detail. On this basis, the hydrogels explored the role of lignin in the regulation of hydrogels properties and revealed the self-healing and conductive mechanism.

Clinical Characteristics and Treatment of Early and Delayed Intra-Ccranial Infection After Ventriculoperitoneal Shunt in Adults: Retrospective Analysis of Nineteen Cases.

Objectives: Intra-cranial infection is the most serious complication after ventriculoperitoneal shunt (VPS). There were differences in clinical characteristics between early (occurs within one month after VPS, the early group) and delayed (occurs 1 month or more after VPS, the delayed group) infections. The aim of this study is to clarify the differences between the two groups. Patients and Methods: All cases diagnosed as intracranial infection after VPS between September 2017 and December 2021 were collected. Clinical data were reviewed and analyzed retrospectively. Results: Nineteen cases met the inclusion criteria, including 12 cases in the early group and seven cases in the delayed group. There were no significant differences between the two groups in gender, age, and etiology of hydrocephalus. Cases in the early group usually had fever with worsening consciousness (11; 91.7%), which was caused by surgical operations (10; 83.3%) with gram-positive coccis infection (9; 75.0%), whereas those in the delayed group had abdominal pain (5; 71.4%), caused by abdominal factor (7; 100%) with gram-negative bacilli infection (6; 85.7%). There were differences in symptoms (p < 0.01), causes of infection (p < 0.001), and pathogens (p < 0.05). Shunt removal was performed for all 19 cases. After the infection was controlled, eight cases received VPS again, and no re-infection occurred after a follow-up of four to 22 months. Conclusions: It is suggested in this study that there were differences between the two groups in terms of etiology, symptoms, and pathogens. The results can provide theoretical basis for prevention, early diagnosis, and reasonable treatment of infection after VPS.

Temperature-dependent electronic structure of γ-phase CuI: first-principles insights.

To deepen the understanding of CuI that emerges as a promising next-generation transparent display material, we investigate the temperature effect on the electronic structures of its room-temperature phase γ-CuI. Using density-functional-theory-based approaches, we investigate the bandgap renormalization, which is contributed by the electron-phonon (el-ph) interaction and lattice thermal expansion. Different from most semiconductors, the bandgap widens as temperature increases, although it only widens by 88.3 meV from 0 to 600 K. In addition, based on the temperature-dependent band structure and conventional Drude model, we investigate the influences of the effective masses and evaluate the hole mobilities limited by phonon scattering along different directions. The calculated mobilities agree well with existing experimental values. Our study not only provides a fundamental understanding of the temperature effect on the electronic structure of CuI, but also gives insights for further improvement of the electronic and thermoelectric devices based on CuI.

Fe-Based Theranostic Agents Respond to the Tumor Microenvironment for MRI-Guided Ferroptosis-/Apoptosis-Inducing Anticancer Therapy.

Tumor microenvironment-specific magnetic resonance imaging (MRI) contrast agents are conducive to accurate diagnoses by visualization of biochemical and pathological changes for suitable treatment. Herein, we reported a pH-responsive contrast agent DFeZd NP with MRI diagnosis and tumor treatment capabilities. DFeZd NPs can map the pH change by modulating the MR signal in different acid-base environments. Moreover, T1 signals are stronger in the tumor site, which proves efficient in distinguishing malignant tumors from normal tissues, as well as demarcating the tumor boundary. Subsequently, sustained supply of Fe through the Fe-based contrast agent leads to Fe redox cycling and lipid peroxides, inducing ferroptosis in tumor cells. Furthermore, under an acidic tumor microenvironment, in the presence of ascorbic acid, increased Fe2+ is generated, which serves as a stronger inducer of ferroptosis. Moreover, due to the different relaxivity of Fe3+ and Fe2+, redox cycling and ferroptosis in tumors can be monitored by MRI. Therefore, we propose DFeZd NPs as accessible and promising Fe-based dopamine-derived contrast agents for specific MRI imaging and ferroptosis induction for anticancer therapy.

Development and Application of Global Health Events-Mental Stress Scale for Assessment of Medical Staff's Acute Mental Stress Responses.

Background: Medical workers have been increasingly involved in emergent public health events, which can lead to severe stress. However, no standardized, officially recognized, unified tool exists for mental distress measurement in medical workers who experienced the public health events. Purpose: In the present study, we propose the Global Health Events-Mental Stress Scale (GHE-MSS), as a revised version of the Impact of Event Scale-Revision (IES-R), for assessment of medical workers' acute mental stress responses within one month and their chronic mental stress responses within six months after major health events. Patients and methods: The IES-R was slightly modified, developed, and its reliability and validity were tested using the Delphi survey, primary survey with 115 participants, formal survey with 300 participants, and clinical evaluation with 566 participants. Results: Exploratory factor analysis and confirmatory factor analysis confirmed a promising validity of the scale. The values of Cronbach's alpha coefficient, the Spearman-Brown coefficient, and the retested Cronbach's alpha coefficient of the scale applied for the clinical evaluation were 0.88, 0.87, and 0.98, respectively, which confirmed a good internal consistency and stability. The results of the goodness-of-fit test indicated a good adaptation of the model. A correlation analysis was conducted to assess the correlation between the GHE-MSS and the PCL-C, which had a correlation coefficient of 0.68 (P<0.01). Conclusion: GHE-MSS can be applied with a promising reliability and validity for the assessment of the acute mental stress response of medical workers experiencing public health events. This method can also be used for the screening of mental stress-associated disorders.

[Effect of exogenous nitric oxide donor SNP on seed germination and antioxidase activities of Perilla frutescens seedlings under NaCl stress].

OBJECTIVE: To explore the method of improving the salt resistance ability of seeds and seedlings of Perilla frutescens under NaCl stress. METHODS: Physiological indexes of Perilla frutescens seeds treated by sodium nitroprusside (SNP) under NaCl stress like the germination vigor, germination rate, germination index and vigor index were measured. And other indexes like the activities of nitrate reductase (NR), malondialdehyde (MDA), superoxide (SOD), peroxidase (POD) and catalase (CAT) were also measured. RESULTS: The germination indexes of Perilla frutescens seeds under NaCl stress had obvious inhibition. But after the treatment with different concentrations of SNP, every germination indexes were all increased. And the seeds that treated with SNP with the concentration of 0.1 mmol/L has the most significantly increase in every index. The germination vigor was 60.4%, the germination rate was 78.3%, the germination index and vigor index were 13.7 and 0.1093 respectively. The content of MDA was decreased after the treatment of SNP. The activities of four enzymes included NR, SOD, POD and CAT were increased with the treatment of SNP, and get the maximin (1.52 microg/g x h, 0.32 U/mg, 5.9 U/mg and 4.8 U/mg respectively) with the concentration of 0.1 mmol/L SNP. CONCLUSION: SNP with concentration of 0.1 mmol/L could significantly alleviate the damages to the seeds and seedlings of Perilla frutescens under NaCl stress, and promote the salt resistance of the seeds and seedlings.

Effects of climate variables on the transmission of COVID-19: a systematic review of 62 ecological studies.

The new severe acute respiratory syndrome coronavirus 2 was initially discovered at the end of 2019 in Wuhan City in China and has caused one of the most serious global public health crises. A collection and analysis of studies related to the association between COVID-19 (coronavirus disease 2019) transmission and meteorological factors, such as humidity, is vital and indispensable for disease prevention and control. A comprehensive literature search using various databases, including Web of Science, PubMed, and Chinese National Knowledge Infrastructure, was systematically performed to identify eligible studies from Dec 2019 to Feb 1, 2021. We also established six criteria to screen the literature to obtain high-quality literature with consistent research purposes. This systematic review included a total of 62 publications. The study period ranged from 1 to 8 months, with 6 papers considering incubation, and the lag effect of climate factors on COVID-19 activity being taken into account in 22 studies. After quality assessment, no study was found to have a high risk of bias, 30 studies were scored as having moderate risks of bias, and 32 studies were classified as having low risks of bias. The certainty of evidence was also graded as being low. When considering the existing scientific evidence, higher temperatures may slow the progression of the COVID-19 epidemic. However, during the course of the epidemic, these climate variables alone could not account for most of the variability. Therefore, countries should focus more on health policies while also taking into account the influence of weather.

Digestive Tract Injuries Caused by Ingested Foreign Bodies Containing Magnets.

We report on 16 children with ingestion of magnetic foreign bodies, who were identified by a medical record review of our hospital data for the time period between January, 2017 and May, 2018. Digestive tract wall was sandwiched in 13 (75%) children and 11 (74%) had gaptic intestinal perforation.

Synthesis of a New Phenyl Chlormethine-Quinazoline Derivative, a Potential Anti-Cancer Agent, Induced Apoptosis in Hepatocellular Carcinoma Through Mediating Sirt1/Caspase 3 Signaling Pathway.

Quinazoline derivatives display multiple pharmacological activities and target various biological receptors. Based on the skeleton of quinazoline core, we designed and synthesized three new quinazoline-phenyl chlormethine conjugates (I-III) bearing a Schiff base (C = N) linker, and investigated their anti-tumor effects on HepG2-xenografted tumor and human cancer cell line HepG2. Among these compounds, compound II showed better inhibitory effect against HepG2 cells. In the present study, TUNEL staining, western blot, molecular docking, and siRNA were used to investigate the inhibitory mechanism of compound II towards hepatoma. Compound II inhibited HepG2-xenografted tumor growth in nude mice. Moreover, Compound II not only up-regulated Bax/Bcl-2 ratio and active-caspase 3 level, but also down-regulated Sirt1 expression and its activity, as well as PGC-1α expression. Furthermore, compound II also significantly suppressed the promotion of HepG2 cell proliferation, as evidenced by MTT assay and lactate dehydrogenase (LDH) release assay. Of note, the cytotoxicity of Compound II on HepG2 cells mainly via regulating Sirt1/caspase 3 signaling pathway, consisting with the results in vivo. Intriguingly, z-DEVD-FMK, a caspase 3 inhibitor, almost abolished the inhibitory effects of compound II. Of note, knockdown of caspase 3 by siRNA significantly reversed the inhibitory effect of compound II on HepG2. Interestingly, compound II directly bonded to Sirt1, indicating that Sirt1 might be a promising therapeutic target of compound II. In summary, our findings reveal that compound II, a new synthetical phenyl chlormethine-quinazoline derivative, contributes to the apoptosis of HepG2 cells both in vivo and in vitro through mediating Sirt1/caspase 3 singling pathway. These findings demonstrate that compound II may be a new potent agent against hepatocellular carcinoma.