Reproductive and transgenerational toxicity of bisphenol S exposure in pregnant rats: Insights into hormonal imbalance and steroid biosynthesis pathway disruption.

Bisphenol S (BPS) is an alternative chemical to bisphenol A commonly used in food packaging materials. It raises concerns due to potential adverse effects on human health. However, limited evidence exists regarding reproductive toxicity from BPS exposure, and the mechanism of associated transgenerational toxicity remains unclear. In this study, pregnant SD rats were exposed to two different doses of BPS (0.05 or 20 mg/kg) from GD6 to PND21. The objective was to investigate reproductive and transmissible toxicity induced by BPS, explore endocrine effects, and uncover potential underlying mechanisms in rats. Perinatal exposure to BPS in the F0 generation significantly decreased the rate of body weight, ovarian organ coefficient, and growth and development of the F1 generation. Notably, these changes included abnormal increases in body weight and length, estrous cycle disruption, and embryonic dysplasia in F1. 4D-DIA proteomic and PRM analyses revealed that exposure to 20 mg/kg group significantly altered the expression of proteins, such as Lhcgr and Akr1c3, within the steroid biosynthetic pathway. This led to elevated levels of FSH and LH in the blood. The hypothalamic-pituitary-ovarian (HPO) axis, responsible for promoting fertility through the cyclic secretion of gonadotropins and steroid hormones, was affected. RT-qPCR and Western blot results demonstrated that the expression of GnRH in the hypothalamus was decreased, the GnRHR in the pituitary gland was decreased, and the expression of FSHß and LHß in the pituitary gland was increased. Overall, BPS exposure disrupts the HPO axis, hormone levels, and steroid biosynthesis in the ovaries, affecting offspring development and fertility. This study provides new insights into the potential effects of BPS exposure on the reproductive function of the body and its relevant mechanisms of action.

A study on flow field characteristics of a self-propelled robot fish approaching static obstacles based on artificial lateral line.

To perceive the static obstacles in still water, the flow field characteristics of a self-propelled robot fish approaching static obstacles were studied based on artificial lateral line (ALL). The pressure distribution on the fish body surface was calculated with different separation between the robot fish and the obstacle boundary, obstacle size and undulating frequency. Subsequently, an ALL system was established and five obstacle perception models were studied to analyze the perceptual characteristics of the ALL. Finally, the experiments were conducted to further reveal the effects of obstacles and motion parameters on the body surface pressure of robot fish. The results indicate that the obstacles have a significant effect on the pressure distribution of the surface of the fish body. Namely the parameters of separation, obstacle size and undulating frequency will affect the peak value of the amplitude envelope of the pressure signals. The obstacle size and distance between the obstacles can be predicted using the time parameters of the amplitude envelope of the pressure signals. Moreover, the self-propelled robot fish with a medium undulating frequency approach to the large obstacles with small separation has better perceptual performance. The findings could offer some insight into understanding the perception of complex underwater environment based on ALL.

OsCIP1, a secreted protein, binds to and stabilizes OsCR4 to promote aleurone layer development, seed germination and early seedling growth in rice.

The receptor kinase CRINKLY 4 (CR4) and its orthologs are known for their essential roles in cell differentiation and their shuttling between plasma membrane and cytoplasmic vesicles, a unique feature tied to their extracellular domain. However, the extracellular regulators of CR4 have been little known. Here we identified an OsCR4 Interacting Protein 1 (OsCIP1) (also named as OsLTPL36 in rice) by a yeast two-hybrid screen using the extracellular domain of OsCR4 (OsCR4E) as bait. OsCIP1/OsLTPL36 harbors a signal peptide and is localized to the outer surface of the plasma membrane. It interacted with the TNFR subdomain of OsCR4, causing an increase in OsCR4 recycling to the plasma membrane. oscip1, in which OsCR4 protein was decreased, exhibited thinner aleurone layer, late germination and delayed growth; while OsCIP1-overexpressing plants, in which OsCR4 protein was increased, displayed enhanced growth at the early seedling stage. OsCIP1 was cleaved between W61 and Q62, and the resulting C-terminal half exhibited a greater affinity for OsCR4E than did its precursor. Abolishing this cleavage site compromises OsCIP1's ability to promote seedling growth. Our results provide valuable clues for the regulation of CR4 activity and its functions in aleurone layer cell differentiation by a secreted small protein in rice.

The associations of cola intake with adverse birth outcomes among pregnant women after assisted reproductive technology treatment and women naturally conceived: a birth cohort study.

The influence of cola intake on birth outcomes is unclear. This study sought to describe and compare the associations between cola intake and adverse birth outcomes among women following assisted reproductive technology (ART) and women spontaneously conceived (SC). Participants (736 ART women and 1,270 SC women) were from the Chinese National Birth Cohort collected in Anhui province. Cola intake was assessed by self-reported questionnaires at each trimester. Outcome measures including preterm birth (PTB) and low birth weight (LBW) were extracted from medical records. The association between cola intake during pregnancy and PTB was found using multivariable log-binomial regression in combined ART and SC women. Separately, for ART women, cola intake during pregnancy increased the risk of PTB (risk ratios were 2.10, 1.65, and 1.81 for all three trimesters, respectively, all p < 0.05), and cola intake in the 1st trimester increased the risk of LWB (risk ratio 2.58, 95% confidence interval 1.29 to 5.16). Cola intake during pregnancy was not associated with PTB or LBW for SC women. Our findings indicate a detrimental effect of cola intake during pregnancy on birth outcomes for ART women. Thus, avoidance of cola intake should be counselled by medical doctors in women prescribed with ART treatment.

Decreased Incidence of Influenza During the COVID-19 Pandemic.

Background: The aim of this study was to analyse changes in influenza detection rates of the influenza seasons 2017/2018, 2018/2019, 2019/2020, and 2020/2021 and the changes in personal awareness of protection during the COVID-19 pandemic. Methods: This retrospective study included patients tested for influenza virus A and B from November 2017 to March 2021 at the Affiliated People's Hospital of Ningbo University (Ningbo, China). Influenza virus A and B tested by direct RT-PCR. A small group of 100 regular participants in influenza virus detection were surveyed on the use of protective measures in four different influenza seasons. Results: There were 14,902, 14,762, 25,070, and 1107 tests of influenza virus A and B in the four influenza periods, for total positive rates of 32.45%, 35.77%, 29.40%, and 0.54%, respectively. In the two periods of four influenza seasons, from November to January, the total number of influenza samples was 8530, 4980, 22,925, 868; from February to March, the number of tests was 6372, 9782, 2145, 239. Total number of tests and positive rate decreased significantly from February/March onwards of the 2019/2020 season, coinciding with the beginning of COVID-19. The proportion of people taking protective measures also increased during the 2019/20 and 2020/21 flu seasons. Conclusion: The influenza virus has a high incidence in this area. The diagnosis rate of influenza decreased after the start of the COVID-19 pandemic. The COVID-19 pandemic had an important impact on the detection rates for influenza virus.

Cardiac echinococcosis secondary to hepatic echinococcosis: a rare case report.

Cystic echinococcosis (CE) is a zoonotic parasitic infection, which is very rare in developed countries. It can affect all internal organs, while cardiac echinococcosis is extremely rare, especially in children. Slowly enlarging hydatid cyst usually remains asymptomatic until the size or space occupying effects the involved organ and induces symptoms. The progression of cardiac echinococcosis can be very hidden, and the symptoms are similar to that of other cardiovascular diseases, which raises the difficulty in accurate diagnosis. We present a 13-year-old young girl with a history of hepatic echinococcosis who developed a huge cardiac hydatid cyst, but her symptoms were not specific, while the physical tests and biochemical examinations were unremarkable. Her residential area in Tibet and previous medical history of hepatic echinococcosis gave us clues in the diagnosis of cardiac echinococcosis. Combined with computed tomography (CT) and magnetic resonance imaging (MRI), the cardiac echinococcosis was finally confirmed, and the cardiac symptoms were relieved after surgical removal of the cardiac hydatid cyst. This is the first report of children's cardiac echinococcosis secondary to hepatic echinococcosis, and it remarks on the importance of rapid consideration of cardiac echinococcosis even if no remarkable symptoms or indexes are present. Moreover, the combination of previous history and imaging techniques are indispensable for obtaining a definite diagnosis.

Cascade Tumor Therapy Platform for Sensitized Chemotherapy and Penetration Enhanced Photothermal Therapy.

As a stand-alone therapy strategy may not be sufficient for effective cancer treatment and a combination of chemotherapy with other therapies is a main trend in cancer treatment. A combination of chemotherapy and photothermal therapy (PTT) is reported here to achieve the goal of cascade multistage cancer treatment. A thermally responsive amphiphilic copolymer is designed and then a CuS nanoparticles (NPs)-based carbon monoxide (CO) photoinduced release system and doxorubicin (Dox) are encapsulated to construct the nanomedicine. The large-sized nanomedicine can accumulate in tumors after long circulation in vivo and will generate heat to act as a photothermal therapeutic agent by near infrared (NIR) light. Moreover, synergically release of CO and Dox is achieved and acted as a sensitized chemotherapeutic agent. The combination of PTT and chemotherapy sensitization can effectively eliminate active tumor cells in the periphery of the tumor. CuS NPs are also released after the degradation of nanomedicine and small-sized CuS NPs possess better tumor penetration and achieve penetration-enhanced PTT by further NIR irradiation, thereby effectively eliminating tumor cells inside solid tumors. Hence, cascade multistage cancer treatment of "combined PTT and chemotherapy sensitization"-"penetration-enhanced PTT" is achieved, and tumor cells are comprehensively and effectively eliminated.

Analysis of SIRT4 gene single-nucleotide polymorphisms in a Han Chinese population with dilated cardiomyopathy.

Aim: We aimed to investigate the association of SIRT4 gene polymorphisms with the susceptibility and prognosis of dilated cardiomyopathy (DCM) in a Chinese population. Materials & methods: A total of 369 controls and 373 DCM patients were enrolled. Three tag single-nucleotide polymorphisms (rs2261612, rs2522138 and rs16950058) on SIRT4 were evaluated. Results: G carriers of rs2261612 were associated with the susceptibility of DCM in codominant, dominant and overdominant genetic models (all p < 0.01). Furthermore, the AG/GG and AG genotype of rs2261612 in dominant and overdominant models correlated with poor prognosis of DCM, independent of left ventricular ejection fraction and cardiac resynchronization therapy (p < 0.001). Conclusion:SIRT4 polymorphisms were associated with the susceptibility and prognosis of DCM in a Chinese population.

Tumor Cell Distinguishable Nanomedicine Integrating Chemotherapeutic Sensitization and Protection.

Theoretically, with a high enough drug dosage, cancer cells could be eliminated. However, the dosages that can be administered are limited by the therapeutic efficacy and side effects of the given drug. Herein, a nanomedicine integrating chemotherapeutic sensitization and protection was developed to relieve the limitation of administration dosage and to improve the efficacy of chemotherapy. The nanomedicine was endowed with the function of synergistically controlled release of CO and drugs under near-infrared (NIR) light irradiation. CO photo-induced release system (COPIRS) was synthesized by constructing an electron excitation-electron transfer group-electron-induced CO release structure and was used as the hydrophobic part, and then hydrophilic polymer (polyethylene glycol; PEG) was introduced by a thermal-responsive groups (DA group), forming a near-infrared-induced burst-release nanocarrier. In vitro and in vivo experiments showed that the nanomedicine can distinguish between tumor and normal cells and regulates the resistance of these different cells through the controlled release of carbonic oxide (CO), simultaneously enhancing the efficacy of chemotherapy drugs on tumor cells and chemotherapeutic protection on normal cells. This strategy could solve the current limitations on dosages due to toxicity and provide a solution for tumor cure by chemotherapy.

A Rapid Dual-Responsive Releasing Nano-Carrier by Decomposing the Copolymer and Reversing the Core Dissolution.

The accumulation of nanotechnology-based drugs has been realized in various ways. However, the concentration of drugs encapsulated by nanomaterials is not equal to the concentration of effective drugs; often, the drugs become effective only when they are released from the nanomaterials as free drugs. This means only when the drugs are rapidly released after the accumulated drug-encapsulating nanomaterials can they truly achieve the purpose of increasing the concentration of drugs in the tumor. Therefore, we herein report a dual-response nano-carrier of glutathione and acid to achieve the rapid release of encapsulated drug and increase the effective drug concentration in the tumor. The nano-carrier was constructed using a dual-responsive amphiphilic copolymer, composed of polyethylene glycol and hydrophobic acetylated dextran and connected by a disulfide bond. In the tumor microenvironment, disulfide bonds could be biodegraded by glutathione that is overexpressed in the tumor, exposing the core of nano-carrier composed of acetylated dextran. Then the acidic environment would induce the deacetylation of acetylated dextran into water-soluble dextran. In this way, the nano-carrier will degrade quickly, realizing the purpose of rapid drug release. The results showed that the drug release rate of dual-responsive nano-carrier was much higher than that of glutathione or acid-responsive nano-carrier alone. Furthermore, both in vitro and in vivo experiments confirmed that dual-responsive nano-carrier possessed more efficient anti-tumor effects. Therefore, we believe that dual-responsive nano-carriers have better clinical application prospects.

Sensitive fluorescence and visual detection of organophosphorus pesticides with a Ru(bpy)32+-ZIF-90-MnO2 sensing platform.

Fluorescence sensing organophosphorus pesticides (OPs) is of great importance for both food safety and global environment; however, the reported fluorescent probes are usually directly exposed to the external environment, resulting in premature leakage or photobleaching and thus limiting their photostability and assay sensitivity. In this work, a fluorescent sensing platform consisting of a novel luminescent metal-organic framework (Ru(bpy)32+-ZIF-90) and manganese dioxide nanosheets (MnO2 NSs) was prepared for sensing OPs. Due to the protection and improvement in the fluorescence of Ru(bpy)32+ by ZIF-90, the Ru(bpy)32+-ZIF-90 probe displayed remarkable photostability and high stability in water. By virtue of the high stability of Ru(bpy)32+-ZIF-90, as well as the outstanding fluorescence quenching and notable recognition ability of the MnO2 NSs, this sensing platform provided excellent detection capability for parathion-methyl, with a wide concentration range of 0.050-60 ng mL-1 and a low detection limit of 0.037 ng mL-1. Additionally, the system exhibited a visual color change with the concentration of the OPs under sunlight. Moreover, satisfactory recoveries ranging from 93.3% to 103.6% were obtained for the real samples. The results indicated that the Ru(bpy)32+-ZIF-90-MnO2-based OP sensing platform is promising for applications in food safety and environmental monitoring.

Associations between TAB2 gene polymorphisms and dilated cardiomyopathy in a Chinese population.

Aim: The present study aimed to investigate the role of TAB2 gene polymorphisms in dilated cardiomyopathy (DCM) susceptibility and prognosis in a Chinese population. Materials & methods: A total of 343 DCM patients and 451 controls were enrolled and had their blood genotyped. Survival analysis was evaluated with Kaplan-Meier curves and Cox regression analysis. Results: G carriers (AG/GG) and AG genotype of rs237028 had a higher DCM susceptibility as well as a worse DCM prognosis. Additionally, C carriers (CT/CC) of rs652921 and G carriers (TG/GG) of rs521845 had a higher DCM risk and CC homozygote of rs652921 had a worse DCM prognosis. These associations were still significant after adjustment for the Bonferroni correction. Conclusion:TAB2 gene polymorphisms were associated with DCM susceptibility and prognosis in the Chinese population.

Mineralogical characteristics and photocatalytic properties of natural sphalerite from China.

Different natural sphalerites have a range of photocatalytic properties that can potentially be exploited for environmental remediation purposes. To develop value in the exploitation of sphalerite, samples were collected from 19 ore deposits in China and characterized for their mineralogical and photocatalytic properties. X-ray diffraction (XRD) and electron probe micro analysis (EPMA) measurements indicated that all the natural sphalerites from various localities crystallized in cubic phases with various chemical compositions. The substitution of Fe for Zn ranged from 0.235% to 14.826% by weight, Mn from 0.004% to 4.868%, Cu from 0.009% to 5.529% and Cd from 0.133% to 1.576%. As Fe became more abundant, the color of natural sphalerite darkened, becoming almost black; and higher Fe content was associated with stronger visible light absorption. Photoluminescence spectra showed emission mainly related to S-vacancies and progressively decreasing fluorescence intensity with increasing Fe content. Tests of the photocatalytic degradation of methyl orange indicated that the sample with the highest Cd content but moderate Fe content had the highest photocatalytic activity. Specifically, the degradation of Methyl Orange (30 mg/L) attained 82.11% efficiency under visible light irradiation for 4 hr of natural sphalerite with 4.262% Fe and 1.576% Cd. Overall, the Fe content in sphalerite was found to contribute to the visible light absorption ability and the recombination rate of photo-generated electrons and holes, while substitution by Cd was observed to have a greater effect on the photocatalytic properties. These findings provide a scientific basis for the profitable utilization of base metal resources like sphalerite.

Functional and structural properties of spirulina phycocyanin modified by ultra-high-pressure composite glycation.

Phycocyanin (PC), a plant-based protein with interesting biological activity, is rarely directly applied in the food industry because it has structural and functional limitations. This study combined ultra-high-pressure (UHP) treatment with glycation to improve PC functionality and explored resulting structural changes using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, scanning electron microscopy, Fourier-transform infrared spectroscopy, circular dichroism, and UV-visible spectroscopy. The UHP treatment obviously improved the speed and degree of glycation and the composite-modified PC (CM-PC) showed high solubility and good emulsifying and foaming performance. Scanning electron microscopy images showed the CM-PC surface was loose and fluffy. Gel electrophoresis, Fourier-transform infrared spectroscopy, and circular dichroism results demonstrated that the content of α-helix decreased from 78.1% in PC to 26.6% in CM-PC, and hydroxyl groups were introduced. UV-visible spectroscopy showed that the mechanism of composite modification involved stretching of the PC and promotion of binding with sugars.

Associations between TAB2 Gene Polymorphisms and Epithelial Ovarian Cancer in a Chinese Population.

BACKGROUND: Epithelial ovarian cancer (EOC) is highly lethal worldwide. Factors involved in the inflammation and hormone-associated signaling pathway play vital roles in EOC carcinogenesis. The transforming growth factor-ß- (TGF-ß-) activated kinase 1 (MAP3K7) binding protein 2 (TAB2), mediating convergence of inflammatory and estrogen, may be implicated in EOC. The present study is aimed at exploring the association between the TAB2 gene polymorphisms and EOC. METHODS: Three single nucleotide polymorphisms (SNPs) (rs237028, rs521845, and rs652921) of TAB2 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 221 patients and 252 healthy controls. Associations between SNPs and clinical characteristics were performed either with the χ 2 test or with Fisher's exact test. The Kaplan-Meier method and Cox proportional hazard models were used to detect associations between genotypes and overall survival. RESULTS: The rs237028 polymorphism was significantly associated with an increased risk of EOC with an allelic genetic model (A vs. G; OR = 1.45; 95%CI = 1.07-1.96; P = 0.016), dominant genetic model (AA vs. AG-GG; OR = 1.66; CI 1.14-2.41; P = 0.008), and overdominant genetic model (AA-GG vs. AG; OR = 1.60; CI 1.08-2.36; P = 0.017). However, no significant association was observed between rs237028 polymorphism and overall survival. CONCLUSIONS: Our study indicated that the rs237028 polymorphism in the TAB2 gene was associated with EOC susceptibility and the TAB2 gene might contribute to the initiation of EOC.

Oridonin overcomes the gemcitabine resistant PANC-1/Gem cells by regulating GST pi and LRP/1 ERK/JNK signalling.

Background: Chemotherapy remains a primary treatment method for advanced pancreatic cancer. However, chemotherapy resistance can influence the therapeutic effect of pancreatic cancer. The resistance mechanism of chemotherapeutic agents such as gemcitabine, which is an agent typically used to treat pancreatic cancer, is complicated and can be influenced by genes and the environment. Oridonin is a tetracyclic diterpenoid compound extracted from the traditional Chinese herb Rabdosia labtea. Oridonin may overcome drug resistance in pancreatic cancer, but researching pancreatic cancer drug resistance of chemotherapy by oridonin is not completely understood. Purpose: The present study aimed to assess the impact of oridonin on multidrug resistance proteins, apoptosis-associated proteins and energy metabolism in gemcitabine-resistant PANC-1 (PANC-1/Gem) pancreatic cancer cells. Methods: Gemcitabine resistance in PANC-1/Gem cells was induced using a concentration gradient of gemcitabine. Cell Counting Kit-8 assays were used to detect the impact of gemcitabine and oridonin on the proliferation of PANC-1 and PANC-1/Gem cells. Western blot analysis and immunofluorescence were used to detect the expression of multidrug resistance proteins, apoptosis-associated proteins and low-density lipoprotein receptor protein 1 (LRP1) proteins in PANC-1/Gem cells. The effects of gemcitabine and oridonin on PANC-1/Gem cells apoptosis were detected using flow cytometry. Animal xenograft tumor assays were used to detect the effect of gemcitabine and oridonin on pancreatic cancer in vivo. Furthermore, the ATP Assay kit was used to determine the effects of gemcitabine and oridonin on ATP levels in PANC-1/Gem cells. Immunofluorescence assays were used to detect the effects of gemcitabine and oridonin on the expression of low-density lipoprotein receptor protein 1 (LRP1) in PANC-1/Gem cells. In addition, LRP1 expression was knocked down in PANC-1/Gem cells via lentiviral vector-mediated RNA silencing. Clone formation assays and Western blot analysis were used to detect the effect of LRP1 knockdown on the proliferation of PANC-1/Gem cells. Results: The present results demonstrate that oridonin overcomes PANC-1/Gem cells gemcitabine reistance by regulating GST pi and LRP1/ERK/JNK signaling. Conclusion: In conclusion, the present study indicated that oridonin could overcome gemcitabine resistance in PANC-1/Gem cells by regulating GST pi and LRP1/ ERK/JNK signaling, inducing cell apoptosis. Therefore, oridonin with gemcitabine may be a promising preoperative treatment for patients who suffer from pancreatic cancer.

Isolation, Purification and Structural Characterization of Two Novel Water-Soluble Polysaccharides from Anredera cordifolia.

Anredera cordifolia, a climber and member of the Basellaceae family, has long been a traditional medicine used for the treatment of hyperglycemia in China. Two water-soluble polysaccharides, ACP1-1 and ACP2-1, were isolated from A. cordifolia seeds by hot water extraction. The two fractions, ACP1-1 and ACP2-1 with molecular weights of 46.78 kDa ± 0.03 and 586.8 kDa ± 0.05, respectively, were purified by chromatography. ACP1-1 contained mannose, glucose, galactose in a molar ratio of 1.08:4.65:1.75, whereas ACP2-1 contained arabinose, ribose, galactose, glucose, mannose in a molar ratio of 0.9:0.4:0.5:1.2:0.9. Based on methylation analysis, ultraviolet and Fourier transform-infrared spectroscopy, and periodate oxidation the main backbone chain of ACP1-1 contained (1→3,6)-galacturonopyranosyl residues interspersed with (1→4)-residues and (1→3)-mannopyranosyl residues. The main backbone chain of ACP2-1 contained (1→3)-galacturonopyranosyl residues interspersed with (1→4)-glucopyranosyl residues.

Oridonin inhibition and miR­200b­3p/ZEB1 axis in human pancreatic cancer.

The relationship among oridonin, miR-200b-3p and pancreatic cancer on epithelial-to-mesenchymal transition (EMT) was investigated for the molecular mechanism or signaling pathways on the migration in pancreatic cancer. BxPC-3 and PANC-1 cells were cultivated and the IC50 of oridonin in BxPC-3 and PANC-1 cells were obtained by the CCK-8 array. The expression of miR­200b-3p was verified by using real-time PCR and its target gene was predicted. BxPC-3 and PANC-1 cells were treated with oridonin or transfected by miR-200b-3p, those cells were used for western blot assay, Transwell assay, ELISA, immunofluorescence staining, tumorigenesis assay in nude mice and immunohistochemical assay to verify the effects of oridonin or miR-200b-3p on pancreatic cancer. We found that oridonin inhibited the proliferation of BxPC-3 and PANC-1 cells in a dose-dependent manner. miR-200b-3p was downregulated by oridonin in BxPC-3 and PANC-1 cells. ZEB1 was a target gene for miR-200b-3p. Oridonin or overexpression of miR­200b-3p can inhibit the cell migration in BxPC-3 and PANC-1 cells. miR-200b-3p can inhibit the EMT and oridonin can inhibit the expression of ZEB1, N-cadherin and fibronectin but not increase the expression of E-cadherin, while the cell adhesion molecules ICAM-1 and VCAM-1 were decreased by oridonin in BxPC-3 and PANC-1 cells and the cytoskeleton was altered by oridonin in PANC-1 cells compared with the control. In summary, the results demonstrate that miR­200b-3p was able to inhibit the EMT of human pancreatic cancer in vivo and in vitro by targeted ZEB1. In vitro, oridonin had a certain effect on the migration in BxPC-3 and PANC-1 cells, but not though type III EMT by miR-200-3p/ZEB1 axis, and may be related to type â…¡ EMT, tumor microenvironment or altering the cytoskeleton. In vivo, oridonin inhibited the cancer migration in the nude mouse model though inhibiting EMT.

Liberation of SARS-CoV main protease from the viral polyprotein: N-terminal autocleavage does not depend on the mature dimerization mode.

The main protease (M(pro)) plays a vital role in proteolytic processing of the polyproteins in the replicative cycle of SARS coronavirus (SARS-CoV). Dimerization of this enzyme has been shown to be indispensable for trans-cleavage activity. However, the auto-processing mechanism of M(pro), i.e. its own release from the polyproteins through autocleavage, remains unclear. This study elucidates the relationship between the N-terminal autocleavage activity and the dimerization of "immature" M(pro). Three residues (Arg4, Glu290, and Arg298), which contribute to the active dimer conformation of mature M(pro), are selected for mutational analyses. Surprisingly, all three mutants still perform N-terminal autocleavage, while the dimerization of mature protease and trans-cleavage activity following auto-processing are completely inhibited by the E290R and R298E mutations and partially so by the R4E mutation. Furthermore, the mature E290R mutant can resume N-terminal autocleavage activity when mixed with the "immature" C145A/E290R double mutant whereas its trans-cleavage activity remains absent. Therefore, the N-terminal auto-processing of M(pro) appears to require only two "immature" monomers approaching one another to form an "intermediate" dimer structure and does not strictly depend on the active dimer conformation existing in mature protease. In conclusion, an auto-release model of M(pro) from the polyproteins is proposed, which will help understand the auto-processing mechanism and the difference between the autocleavage and trans-cleavage proteolytic activities of SARS-CoV M(pro).