The Hippo Pathway Kinases LATS1/2 Suppress Cancer Immunity.

Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy. Mechanistically, LATS1/2-null tumor cells secrete nucleic-acid-rich extracellular vesicles, which induce a type I interferon response via the Toll-like receptors-MYD88/TRIF pathway. LATS1/2 deletion in tumors thus improves tumor immunogenicity, leading to tumor destruction by enhancing anti-tumor immune responses. Our observations uncover a key role of the Hippo pathway in modulating tumor immunogenicity and demonstrate a proof of concept for targeting LATS1/2 in cancer immunotherapy.

DCAF13 promotes ovarian cancer progression by activating FRAS1-mediated FAK signaling pathway.

Cullin-RING ubiquitin ligase 4 (CRL4) is closely correlated with the incidence and progression of ovarian cancer. DDB1- and CUL4-associated factor 13 (DCAF13), a substrate-recognition protein in the CRL4 E3 ubiquitin ligase complex, is involved in the occurrence and development of ovarian cancer. However, its precise function and the underlying molecular mechanism in this disease remain unclear. In this study, we confirmed that DCAF13 is highly expressed in human ovarian cancer and its expression is negatively correlated with the overall survival rate of patients with ovarian cancer. We then used CRISPR/Cas9 to knockout DCAF13 and found that its deletion significantly inhibited the proliferation, colony formation, and migration of human ovarian cancer cells. In addition, DCAF13 deficiency inhibited tumor proliferation in nude mice. Mechanistically, CRL4-DCAF13 targeted Fraser extracellular matrix complex subunit 1 (FRAS1) for polyubiquitination and proteasomal degradation. FRAS1 influenced the proliferation and migration of ovarian cancer cell through induction of the focal adhesion kinase (FAK) signaling pathway. These findings collectively show that DCAF13 is an important oncogene that promotes tumorigenesis in ovarian cancer cells by mediating FRAS1/FAK signaling. Our findings provide a foundation for the development of targeted therapeutics for ovarian cancer.

[Follow-up and prognostic study of infants with positional plagiocephaly]. / å©´å„¿ä½“ä½æ€§æ–œå¤´å¼‚å¸¸çš„éšè®¿å’Œé¢„åŽç ”ç©¶.

OBJECTIVES: To study the effects of infantile positional plagiocephaly on the growth and neural development. METHODS: A retrospective study was conducted on the medical data of 467 children who underwent craniographic examination and were followed up to 3 years of age in Peking University Third Hospital from June 2018 to May 2022. They were divided into four groups: mild positional plagiocephaly (n=108), moderate positional plagiocephaly (n=49), severe positional plagiocephaly (n=12), and normal cranial shape (n=298). The general information of the four groups and the weight, length, head circumference, visual acuity screening results, hearing test results, and the scores of Pediatric Neuropsychological Developmental Scales/Gesell Developmental Schedules of the four groups from 6 to 36 months old were compared. RESULTS: The rates of adverse perinatal factors, congenital muscular torticollis, and supine fixed sleeping posture in the mild, moderate, and severe positional plagiocephaly groups were higher than the normal cranial group (P<0.05). There was no significant difference in weight, length, and head circumference among the four groups at 6, 12, 24 and 36 months of age (P>0.05). The incidence rate of abnormal vision in the severe positional plagiocephaly group was higher than that in the mild positional plagiocephaly, moderate positional plagiocephaly and normal cranial shape groups at 24 and 36 months of age (P<0.05). The scores of the Pediatric Neuropsychological Developmental Scales at 12 and 24 months of age and the scores of the Gesell Developmental Schedules at 36 months of age in the severe positional plagiocephaly group were lower than those in the mild positional plagiocephaly, moderate positional plagiocephaly and normal cranial shape groups, but the difference was not statistically significant (P>0.05). CONCLUSIONS: Adverse perinatal factors, congenital muscular torticollis, and supine fixed sleeping position may be associated with infantile positional plagiocephaly. Mild or moderate positional plagiocephaly has no significant impact on the growth and neural development of children. Severe positional plagiocephaly have adverse effects on the visual acuity. However, it is not considered that severe positional plagiocephaly can affect the neurological development.

DCAF13 promotes breast cancer cell proliferation by ubiquitin inhibiting PERP expression.

Evolutionarily conserved DDB1-and CUL4-associated factor 13 (DCAF13) is a recently discovered substrate receptor for the cullin RING-finger ubiquitin ligase 4 (CRL4) E3 ubiquitin ligase that regulates cell cycle progression. DCAF13 is overexpressed in many cancers, although its role in breast cancer is currently elusive. In this study we demonstrate that DCAF13 is overexpressed in human breast cancer and that its overexpression closely correlates with poor prognosis, suggesting that DCAF13 may serve as a diagnostic marker and therapeutic target. We knocked down DCAF13 in breast cancer cell lines using CRISPR/Cas9 and found that DCAF13 deletion markedly reduced breast cancer cell proliferation, clone formation, and migration both in vitro and in vivo. In addition, DCAF13 deletion promoted breast cancer cell apoptosis and senescence, and induced cell cycle arrest in the G1/S phase. Genome-wide RNAseq analysis and western blotting revealed that loss of DCAF13 resulted in both mRNA and protein accumulation of p53 apoptosis effector related to PMP22 (PERP). Knockdown of PERP partially reversed the hampered cell proliferation induced by DCAF13 knockdown. Co-immunoprecipitation assays revealed that DCAF13 and DNA damage-binding protein 1 (DDB1) directly interact with PERP. Overexpression of DDB1 significantly increased PERP polyubiquitination, suggesting that CRL4DCAF13 E3 ligase targets PERP for ubiquitination and proteasomal degradation. In conclusion, DCAF13 and the downstream effector PERP occupy key roles in breast cancer proliferation and potentially serve as prognostics and therapeutic targets.

Experimental optimal generation of hybrid entangled states in photonic quantum walks.

While the existence of disorders is commonly believed to weaken the unique properties of quantum systems, recent progress has predicted that it can exhibit a counterintuitive enhanced effect on the behavior of entanglement generation, which is even independent of the chosen initial conditions and physical platforms. However, to achieve a maximally entangled state in such disordered quantum systems, the key limitation of this is the scarcity of an infinite coherence time, which makes its experimental realization challenging. Here, we experimentally investigate the entanglement entropy dynamics in a photonic quantum walk with disorders in time. Through the incorporation of a classic optimization algorithm, we experimentally demonstrate that such disordered systems can relax to a high-entanglement hybrid state at any given time step. Moreover, this prominent entangling ability is universal for a wide variety of initial conditions. Our results may inspire achieving a well-controlled entanglement generator for quantum computation and information tasks.

[Risk factors for metabolic bone disease of prematurity in very/extremely low birth weight infants: a multicenter investigation in China].

OBJECTIVE: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP. RESULTS: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation (P < 0.05). Compared with the non-MBDP group, the MBDP group had significantly higher incidence rates of neonatal sepsis, anemia, hypocalcemia, and retinopathy of prematurity (P < 0.05). The MBDP group had a significantly lower mean feeding speed, a significantly higher age when reaching total enteral feeding, and a significantly longer duration of parenteral nutrition (P < 0.05). The use rate of caffeine citrate in the MBDP group was significantly higher, but the use rate of erythropoietin was significantly lower than that in the non-MBDP group (P < 0.05). The multivariate logistic regression analysis showed that gestational age < 32 weeks, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis were risk factors for MBDP (P < 0.05). CONCLUSIONS: A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.

Experimental extraction of nonlocal weak values for demonstrating the failure of a product rule.

We experimentally demonstrate an alternative method for measuring nonlocal weak values in linear optics, avoiding the use of second-order interaction. The method is based on the concept of modular values. The paths of two photons, initialized in hyperentangled states, are adopted as the meter with the polarization acting as the system. The modular values are read out through the reconstructed final states of the meter. The weak value of nonlocal observables is given through its connection to the modular value. Comparing the weak values of local and nonlocal observables, we demonstrate the failure of product rules for an entangled system. Our results significantly simplify the task of measuring nonlocal weak values and will play an important role in the application of weak measurement.

Direct Measurement of a Nonlocal Entangled Quantum State.

Entanglement and the wave function description are two of the core concepts that make quantum mechanics such a unique theory. A method to directly measure the wave function, using weak values, was demonstrated by Lundeen et al. [Nature 474, 188 (2011)]. However, it is not applicable to a scenario of two disjoint systems, where nonlocal entanglement can be a crucial element, since that requires obtaining weak values of nonlocal observables. Here, for the first time, we propose a method to directly measure a nonlocal wave function of a bipartite system, using modular values. The method is experimentally implemented for a photon pair in a hyperentangled state, i.e., entangled both in polarization and momentum degrees of freedom.

Measurements of Nonlocal Variables and Demonstration of the Failure of the Product Rule for a Pre- and Postselected Pair of Photons.

We report the first implementation of the von Neumann instantaneous measurements of nonlocal variables, which becomes possible due to technological achievements in creating hyperentangled photons. Tests of reliability and of the nondemolition property of the measurements have been performed with high precision, showing the suitability of the scheme as a basic ingredient of numerous quantum information protocols. The method allows us to demonstrate for the first time with strong measurements a special feature of pre- and postselected quantum systems: the failure of the product rule. It has been verified experimentally that for a particular pre- and postselected pair of particles, a single measurement on particle A yields with certainty σ_{x}^{A}=-1, a single measurement on particle B yields with certainty σ_{y}^{B}=-1, and a single nonlocal measurement on particles A and B yields with certainty σ_{x}^{A}σ_{y}^{B}=-1.

Measuring the Winding Number in a Large-Scale Chiral Quantum Walk.

We report the experimental measurement of the winding number in an unitary chiral quantum walk. Fundamentally, the spin-orbit coupling in discrete time quantum walks is implemented via a birefringent crystal collinearly cut based on a time-multiplexing scheme. Our protocol is compact and avoids extra loss, making it suitable for realizing genuine single-photon quantum walks at a large scale. By adopting a heralded single photon as the walker and with a high time resolution technology in single-photon detection, we carry out a 50-step Hadamard discrete-time quantum walk with high fidelity up to 0.948±0.007. Particularly, we can reconstruct the complete wave function of the walker that starts the walk in a single lattice site through the local tomography of each site. Through a Fourier transform, the wave function in quasimomentum space can be obtained. With this ability, we propose and report a method to reconstruct the eigenvectors of the system Hamiltonian in quasimomentum space and directly read out the winding numbers in different topological phases (trivial and nontrivial) in the presence of chiral symmetry. By introducing nonequivalent time frames, we show that whole topological phases in a periodically driven system can also be characterized by two different winding numbers. Our method can also be extended to the high winding number situation.

[Treatment and prognosis of pulmonary hemorrhage in preterm infants during 2007-2016].

OBJECTIVE: To study the treatment and prognosis of pulmonary hemorrhage in preterm infants. METHODS: A total of 106 preterm infants diagnosed with pulmonary hemorrhage, who were hospitalized in the neonatal ward of Peking University Third Hospital between 2007 and 2016, were enrolled. These patients were divided into 2007-2011 group (34 cases) and 2012-2016 group (72 cases) according to the time of hospitalization, divided into conventional-frequency ventilation group (43 cases) and high-frequency oscillatory ventilation (HFOV) group (63 cases) according to the respiratory support method used after the development of pulmonary hemorrhage, and divided into non-operation group (34 cases) and operation group (14 cases) according to whether PDA ligation was performed for the unclosed PDA before pulmonary hemorrhage. The general data, treatment, and prognosis were compared between different groups. RESULTS: Compared with the 2007-2011 group, the 2012-2016 group had higher rates of HFOV and PDA ligation (P<0.05), a lower mortality rate during hospitalization (P<0.05), a longer length of hospital stay (P<0.05), and higher incidence rates of intracranial hemorrhage and bronchopulmonary dysplasia (P<0.05). Compared with the conventional-frequency ventilation group, the HFOV group had a lower mortality rate during hospitalization (P<0.05), a longer length of hospital stay (P<0.05), and higher incidence rates of intracranial hemorrhage and bronchopulmonary dysplasia (P<0.05). Compared with the non-operation group, the operation group had a lower mortality rate during hospitalization (P<0.05), a longer length of hospital stay (P<0.05), and higher incidence rates of intracranial hemorrhage and bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: The application of HFOV and PDA ligation can improve the survival rate of preterm infants with pulmonary hemorrhage, but the incidence of intracranial hemorrhage and bronchopulmonary dysplasia is also increased.

PKCλ is critical in AMPA receptor phosphorylation and synaptic incorporation during LTP.

Direct phosphorylation of GluA1 by PKC controls α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor (AMPAR) incorporation into active synapses during long-term potentiation (LTP). Numerous signalling molecules that involved in AMPAR incorporation have been identified, but the specific PKC isoform(s) participating in GluA1 phosphorylation and the molecule triggering PKC activation remain largely unknown. Here, we report that the atypical isoform of PKC, PKCλ, is a critical molecule that acts downstream of phosphatidylinositol 3-kinase (PI3K) and is essential for LTP expression. PKCλ activation is required for both GluA1 phosphorylation and increased surface expression of AMPARs during LTP. Moreover, p62 interacts with both PKCλ and GluA1 during LTP and may serve as a scaffolding protein to place PKCλ in close proximity to facilitate GluA1 phosphorylation by PKCλ. Thus, we conclude that PKCλ is the critical signalling molecule responsible for GluA1-containing AMPAR phosphorylation and synaptic incorporation at activated synapses during LTP expression.

A model to predict the onset of non-alcoholic fatty liver disease within 2 years in elderly adults.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic hepatitis, which leads to cirrhosis and hepatocellular carcinoma. However, it is difficult to identify subjects at high risk for NAFLD onset. This study aims to construct a model to predict the onset of NAFLD within 2 years in elderly adults. METHODS: This study included and followed 3378 initial NAFLD-free subjects aged 60 years or over for 2 years, which were randomly divided into a training set and a validation set. NAFLD was diagnosed on ultrasound. Clinical and laboratory data were recorded at baseline. A model was constructed in the training set to predict the onset of NAFLD and validated in the validation set. RESULTS: Body mass index, hemoglobin, fasting blood glucose, and triglycerides were identified as predictors for the onset of NAFLD. A risk score (R) was calculated by them. It classified the subjects into low-risk group (R ≤ -2.88), moderate-risk group (-2.88 < R ≤ -1.26), and high-risk group (R > -1.26). In the training set, 4.68% of the participants in the low-risk group, 11.59% of the participants in the moderate-risk group, and 31.02% of the participants in the high-risk group developed NAFLD. In the validation set, 5.84% of the participants in the low-risk group, 10.57% of the participants in the moderate-risk group, and 29.44% of the participants in the high-risk group developed NAFLD. CONCLUSIONS: This study developed a model to predict the onset of NAFLD in elderly adults, which might provide indications for intervention to these subjects.

[Management of positional head deformity in 31 infants].

OBJECTIVE: To investigate the clinical effect of postural correction training and helmet therapy in the treatment of moderate-severe positional head deformity defined as asymmetric head shape in infants. METHODS: A total of 31 infants who were diagnosed with moderate-severe plagiocephaly and/or brachiocephaly were enrolled. According to the different treatment methods, the infants were divided into helmet therapy group with 11 infants and postural correction training group with 20 infants. The cranial vault asymmetry index (CVAI), cephalic ratio (CR), and head circumference growth were compared between the two groups before and after treatment. RESULTS: Compared with the postural correction training group, the helmet therapy group had significantly lower CVAI and CR after treatment. The helmet therapy group had significantly better improvements in CVAI and CR after treatment compared with the postural correction training group (CVAI difference: 6.0±1.9 vs 0.7±0.8, P=0.001; CR difference: 0.047±0.009 vs 0.008±0.005, P<0.001). There was no significant difference in head circumference growth between the two groups (P=0.55). CONCLUSIONS: Helmet therapy has a significantly better effect in the treatment of moderate-severe positional head deformity than postural correction training in infants. Helmet therapy does not limit head circumference growth.

[A clinical analysis of 101 infants with plagiocephaly].

OBJECTIVE: To investigate the possible causes of plagiocephaly in infants and the therapeutic effect of postural correction training on plagiocephaly. METHODS: A total of 101 infants who were diagnosed with plagiocephaly were enrolled. According to the age at diagnosis, these infants were divided into 1-4 month group (31 infants), 5-8 month group (40 infants), and 9-12 month group (30 infants). The possible causes of plagiocephaly were analyzed in three groups. The cranial vault asymmetry index (CVAI) before and after postural correction training was compared in three groups. RESULTS: Of the 101 infants, 89 (88.1%) had a sleeping posture in the supine position, and there was no significant difference in the percentage of infants with such posture between the three groups. Compared with the 5-8 month group and the 9-12 month group, the 1-4 month group had significantly higher rate of preterm birth, incidence rate of adverse perinatal factors, and incidence rate of congenital muscular torticollis. The three groups showed a significant decrease in CVAI 3 months after postural correction training (P<0.001). Compared with the 5-8 month group and the 9-12 month group, the 1-4 month group had a significantly greater change in CVAI after postural correction training (P<0.001). CONCLUSIONS: The sleeping posture in the supine position may be associated with the development of plagiocephaly. Adverse perinatal factors, preterm birth, and congenital muscular torticollis as possible causes of plagiocephaly are commonly seen in early infancy. Postural correction training has a significant effect in improving plagiocephaly, especially in early infancy.

[Clinical study of neonatal twin-twin transfusion syndrome].

OBJECTIVE: To explore the clinical manifestations and short-term prognosis of twin-twin transfusion syndrome (TTTS) in neonates with different disease stages, receiving different intrauterine interventions, or as blood donors and recipients. METHODS: The study retrospectively collected 76 TTTS neonates who were hospitalized in the Neonatal Ward, Peking University Third Hospital. The participants were classified into mild TTTS (n=38) and severe TTTS groups (n=21), or into amnioreduction (n=20), laser surgery (n=21), and expectant therapy groups (n=32), or into donor (n=23) and recipient groups (n=30). RESULTS: The severe TTTS group had higher incidences of brain injury, heart disease, asphyxia, and renal damage and in-hospital mortality rate compared with the mild TTTS group, but the differences had no statistical significance. The laser surgery group displayed decreasing trends in the incidences of brain injury, heart disease, and renal damage and in-hospital mortality rate compared with the amnioreduction and expectant therapy groups. The recipient group had higher incidences of heart diseases and pathological jaundice than the donor group (P<0.05). The donor group had higher incidences of asphyxia and renal damage than the recipient group, but with no significant difference. CONCLUSIONS: The neonates with severe TTTS have higher rates of organ damages and in-hospital mortality. Intrauterine laser surgery seems to lead to a better prognosis compared with the amnioreduction and expectant therapy. The recipients are more susceptible to heart diseases and pathological jaundice, whereas the donors are more susceptible to asphyxia and renal damage.

Ubiquitin E3 ligase CRL4(CDT2/DCAF2) as a potential chemotherapeutic target for ovarian surface epithelial cancer.

Cullin-RING ubiquitin ligases (CRLs) are the largest family of E3 ligases and require cullin neddylation for their activation. The NEDD8-activating enzyme inhibitor MLN4924 reportedly blocked cullin neddylation and inactivated CRLs, which resulted in apoptosis induction and tumor suppression. However, CRL roles in ovarian cancer cell survival and the ovarian tumor repressing effects of MLN4924 are unknown. We show here that CRL4 components are highly expressed in human epithelial ovarian cancer tissues. MLN4924-induced DNA damage, cell cycle arrest, and apoptosis in ovarian cancer cells in a time- and dose-dependent manner. In addition, MLN4924 sensitized ovarian cancer cells to other chemotherapeutic drug treatments. Depletion of CRL4 components Roc1/2, Cul4a, and DDB1 had inhibitory effects on ovarian cancer cells similar to MLN4924 treatment, which suggested that CRL4 inhibition contributed to the chemotherapeutic effect of MLN4924 in ovarian cancers. We also investigated for key CRL4 substrate adaptors required for ovarian cancer cells. Depleting Vprbp/Dcaf1 did not significantly affect ovarian cancer cell growth, even though it was expressed by ovarian cancer tissues. However, depleting Cdt2/Dcaf2 mimicked the pharmacological effects of MLN4924 and caused the accumulation of its substrate, CDT1, both in vitro and in vivo. MLN4924-induced DNA damage and apoptosis were partially rescued by Cdt1 depletion, suggesting that CRL4(CDT2) repression and CDT1 accumulation were key biochemical events contributing to the genotoxic effects of MLN4924 in ovarian cancer cells. Taken together, these results indicate that CRL4(CDT2) is a potential drug target in ovarian cancers and that MLN4924 may be an effective anticancer agent for targeted ovarian cancer therapy.

Death domain-associated protein DAXX promotes ovarian cancer development and chemoresistance.

BACKGROUND: The role of DAXX in ovarian cancer development and metastasis has not been investigated before now. RESULTS: Overexpression of DAXX enhanced ovarian cancer cell proliferation, colony formation, and migration, whereas Daxx depletion had the opposite effects. CONCLUSION: DAXX promotes ovarian cancer cell proliferation and chemoresistance. SIGNIFICANCE: ModulatingDAXXmay be an effective strategy for preventing the recurrence and chemoresistance of ovarian cancers. Understanding the genes involved in apoptosis and DNA damage responses may improve therapeutic strategies for ovarian cancer. The death domain-associated protein DAXX can be either a pro-apoptotic or an anti-apoptotic factor, depending on the cell type and context. In this study, we found that DAXX was highly expressed in human ovarian surface epithelial tumors but not in granulosa cell tumors. In cultured ovarian cancer cells, DAXX interacted with promyelocytic leukemia protein (PML) and localized to subnuclear domains (so-called PML nuclear bodies). A role for DAXX in ovarian cancer cell proliferation, metastasis, and radio/chemoresistance was examined. Overexpression of DAXX enhanced multiple ovarian cancer cell lines' proliferation, colony formation, and migration, whereas Daxx depletion by RNA interference had the opposite effects. When transplanted into nude mice, ovarian cancer cells that overexpressed DAXX displayed enhanced tumorigenesis capability in vivo, whereas Daxx depletion inhibited tumor development. Importantly, Daxx induced tumorigenic transformation of normal ovarian surface epithelial cells. Daxx also protected ovarian cancer cells against x-irradiation- and chemotherapy-induced DNA damage by interacting with PML. Taken together, our results suggest that DAXX is a novel ovarian cancer oncogene that promotes ovarian cancer cell proliferation and chemoresistance in ovarian cancer cells. Thus, modulating DAXX-PML nuclear body activity may be an effective strategy for preventing the recurrence and chemoresistance of ovarian cancers.

Characterization and biological evaluation of six new dimeric lignans with an unusual α,ß-unsaturated ketone motif from Zanthoxylum simulans.

Investigation of the bark of Zanthoxylum simulans afforded six new dimeric lignans zanthpodocarpins C-H (1-6) bearing an unusual α,ß-unsaturated ketone group. The new structures of 1-6 were determined by using detailed spectroscopic analysis. All of the isolated compounds were examined for their inhibitory effects against rat joint synovial cell and splenocyte proliferation. Compounds 1-6 showed potent anti-inflammatory activities with IC50 values ranging from 18.6 to 36.1µM, and 13.8 to 74.3µM.

[Study on Chemical Constituents from Carpesium abrotanoides].

OBJECTIVE: To study the chemical constituents from Carpesium abrotanoides. METHODS: Compounds were isolated and pu- rified by silica gel and Sephadex LH-20 column chromatography, their structures were determined by using spectroscopic analysis. RESULTS: Ten compounds were isolated and identified as Vomifoliol (I), 2-Desoxy-4-epi-pulchellin (II), 8-epi-Confertin (III), 1-epi-Inuviscolide (IV), Telekin (V), Isotelekin (VI), 4 (15)-ß-Epoxyisotelekin (VII), Carabrone (VIII), Carabrol (IX), and 3- Deuteriomethyl-5-methyl-2,3-dihydrobenzofuran (X). CONCLUSION: Compounds I, III, IV,VII, VII and X are isolated from this plant for the first time.