Table_1_Longitudinal analysis of ovarian cancer death patterns during a rapid transition period (2005-2020) in Shanghai, China: A population-based study.xlsx

ObjectivesIt is important to assess the burden of ovarian cancer related premature death so as to develop appropriate evidence-based care and improve women’s health. This study aimed to characterize the long-term trends in mortality, survival and disease burden of ovarian cancer in Shanghai, China.Materials and MethodsCo-morbidities, crude mortality rate (CMR), age-standardised mortality rate by Segi’s world standard population (ASMRW), years of life lost (YLL), and survival rates were analysed. Temporal trends for the mortality rates and disease burden were analyzed using the Joinpoint Regression Program. Mortality rate increases by demographic and non-demographic factors were estimated by the decomposition method.ResultsA total of 1088 ovarian cancer as underlying cause of deaths were recorded. CMR and ASMRW were 4.82/105 and 2.32/105 person-years, respectively. The YLL was 16372.96 years, and the YLL rate was 72.46/105 person-years. The YLL rate increased only in the age group of 70-79 years (P = 0.017). The survival rates of ovarian cancer patients did not improve during the ten year period (2005-2015). The top co-morbidities were diseases of the respiratory system, digestive system, and circulatory system. The rates of ovarian cancer deaths caused by non-demographic and demographic factors increased by 21.29% (95%CI: 4.01% to 41.44%, P = 0.018) and 25.23% (95%CI: 14.64% to 36.81%, P ConclusionsPopulation ageing and all cause of death may affect ovarian cancer related deaths in Pudong, Shanghai. The high mortality and the stagnant survival rates suggest the need for more efforts in targeted prevention and treatment of this disease.</p

Table_6_Longitudinal analysis of ovarian cancer death patterns during a rapid transition period (2005-2020) in Shanghai, China: A population-based study.xlsx

ObjectivesIt is important to assess the burden of ovarian cancer related premature death so as to develop appropriate evidence-based care and improve women’s health. This study aimed to characterize the long-term trends in mortality, survival and disease burden of ovarian cancer in Shanghai, China.Materials and MethodsCo-morbidities, crude mortality rate (CMR), age-standardised mortality rate by Segi’s world standard population (ASMRW), years of life lost (YLL), and survival rates were analysed. Temporal trends for the mortality rates and disease burden were analyzed using the Joinpoint Regression Program. Mortality rate increases by demographic and non-demographic factors were estimated by the decomposition method.ResultsA total of 1088 ovarian cancer as underlying cause of deaths were recorded. CMR and ASMRW were 4.82/105 and 2.32/105 person-years, respectively. The YLL was 16372.96 years, and the YLL rate was 72.46/105 person-years. The YLL rate increased only in the age group of 70-79 years (P = 0.017). The survival rates of ovarian cancer patients did not improve during the ten year period (2005-2015). The top co-morbidities were diseases of the respiratory system, digestive system, and circulatory system. The rates of ovarian cancer deaths caused by non-demographic and demographic factors increased by 21.29% (95%CI: 4.01% to 41.44%, P = 0.018) and 25.23% (95%CI: 14.64% to 36.81%, P ConclusionsPopulation ageing and all cause of death may affect ovarian cancer related deaths in Pudong, Shanghai. The high mortality and the stagnant survival rates suggest the need for more efforts in targeted prevention and treatment of this disease.</p

Facile and Selective Enrichment of Intact Sialoglycopeptides Using Graphitic Carbon Nitride

Combining powerful selectivity, high stability, convenient operation, mild condition, and eco-friendliness, a novel graphitic carbon nitride (g-C₃N₄)-based enrichment method of intact sialoglycopeptides (SGs) was developed. The intact SGs could be simply enriched and separated from protein tryptic digests by hydrogen bonding without damage of glycan structures due to the specific structure of g-C₃N₄. By optimizing the enrichment and elution conditions, 45 and 38 SGs were detected from the tryptic digests of bovine fetuin and transferrin, respectively. Under the synergistic effect of hydrogen bonding and electrostatic adsorption, the SGs could be enriched simply in less than 2 h with a detection limit of 50 fmol. The method is repeatable due to the high stability of g-C₃N₄ and the simple protocol of the method, indicating the potential application of g-C₃N₄ in efficient and selective enrichment of intact SGs

Table_3_Longitudinal analysis of ovarian cancer death patterns during a rapid transition period (2005-2020) in Shanghai, China: A population-based study.xlsx

ObjectivesIt is important to assess the burden of ovarian cancer related premature death so as to develop appropriate evidence-based care and improve women’s health. This study aimed to characterize the long-term trends in mortality, survival and disease burden of ovarian cancer in Shanghai, China.Materials and MethodsCo-morbidities, crude mortality rate (CMR), age-standardised mortality rate by Segi’s world standard population (ASMRW), years of life lost (YLL), and survival rates were analysed. Temporal trends for the mortality rates and disease burden were analyzed using the Joinpoint Regression Program. Mortality rate increases by demographic and non-demographic factors were estimated by the decomposition method.ResultsA total of 1088 ovarian cancer as underlying cause of deaths were recorded. CMR and ASMRW were 4.82/105 and 2.32/105 person-years, respectively. The YLL was 16372.96 years, and the YLL rate was 72.46/105 person-years. The YLL rate increased only in the age group of 70-79 years (P = 0.017). The survival rates of ovarian cancer patients did not improve during the ten year period (2005-2015). The top co-morbidities were diseases of the respiratory system, digestive system, and circulatory system. The rates of ovarian cancer deaths caused by non-demographic and demographic factors increased by 21.29% (95%CI: 4.01% to 41.44%, P = 0.018) and 25.23% (95%CI: 14.64% to 36.81%, P ConclusionsPopulation ageing and all cause of death may affect ovarian cancer related deaths in Pudong, Shanghai. The high mortality and the stagnant survival rates suggest the need for more efforts in targeted prevention and treatment of this disease.</p

Table_4_Longitudinal analysis of ovarian cancer death patterns during a rapid transition period (2005-2020) in Shanghai, China: A population-based study.xlsx

ObjectivesIt is important to assess the burden of ovarian cancer related premature death so as to develop appropriate evidence-based care and improve women’s health. This study aimed to characterize the long-term trends in mortality, survival and disease burden of ovarian cancer in Shanghai, China.Materials and MethodsCo-morbidities, crude mortality rate (CMR), age-standardised mortality rate by Segi’s world standard population (ASMRW), years of life lost (YLL), and survival rates were analysed. Temporal trends for the mortality rates and disease burden were analyzed using the Joinpoint Regression Program. Mortality rate increases by demographic and non-demographic factors were estimated by the decomposition method.ResultsA total of 1088 ovarian cancer as underlying cause of deaths were recorded. CMR and ASMRW were 4.82/105 and 2.32/105 person-years, respectively. The YLL was 16372.96 years, and the YLL rate was 72.46/105 person-years. The YLL rate increased only in the age group of 70-79 years (P = 0.017). The survival rates of ovarian cancer patients did not improve during the ten year period (2005-2015). The top co-morbidities were diseases of the respiratory system, digestive system, and circulatory system. The rates of ovarian cancer deaths caused by non-demographic and demographic factors increased by 21.29% (95%CI: 4.01% to 41.44%, P = 0.018) and 25.23% (95%CI: 14.64% to 36.81%, P ConclusionsPopulation ageing and all cause of death may affect ovarian cancer related deaths in Pudong, Shanghai. The high mortality and the stagnant survival rates suggest the need for more efforts in targeted prevention and treatment of this disease.</p

Myoinhibitory peptides regulate polyamine sensitivity in the context of mating.

<p>(A) Loss of sex peptide (SP) in the sperm of the male does not significantly affect chemosensory attraction of mated females to 10 ppm of polyamines. Wild-type (wt) Canton S females mated to wild-type or sex peptide mutant (<i>SP</i>^<i>0</i>) males do not show a significantly altered level of attraction to the odor of putrescine or cadaverine. (<i>n</i> = 8, 60 flies/trial). (B) <i>SP</i>^<i>0</i> male-mated Canton S females lay their low numbers of eggs on either site of the oviposition assay and show no preference behavior. (<i>n</i> = 8, 60 flies/trial). (C) Myoinhibitory peptide (MIP) expression in the AL and SEZ regions in the female brain. In the AL, the glomerulus innervated by IR41a OSNs is displayed (<i>IR41a-Gal4;UAS-mCD8GFP</i>). Note that MIP staining is detected in close proximity to IR41a axon terminals. In the SEZ, anti-MIP staining (green) localizes close to IR76b neuron axons and axon terminals (magenta) consistent with MIPs being secreted by IR76b neurons (<i>IR76b-QF;QUAS-mtd-tomato</i>) (see arrowheads). (D,E) MIPs modulate olfactory attraction to polyamines selectively in mated females but not males. RNAi-mediated knockdown of MIPs with four different RNAi transgenic lines in IR76b neurons (<i>IR76b-Gal4;UAS-MIPi</i>) selectively reduces the olfactory preference of mated females but not of males to 10 ppm of putrescine (D) or 10 ppm of cadaverine (E) (<i>n</i> = 8, 60 flies/trial). (F) The effect of MIP knockdown (<i>IR76b-Gal4;UAS-MIPi</i>) depends on the mating state of the female, as the low attraction of virgin females to 10 ppm polyamine odor was not further reduced in virgin females with MIP knockdown compared to virgin controls without RNAi against MIPs. Box plots show median and upper/lower quartiles (<i>n</i> = 8, 60 flies/trial). (G) Knockdown of MIPs in IR76b neurons abolishes oviposition preference to 1 mM putrescine and cadaverine using three different MIPi transgenic lines (<i>IR76b-Gal4;UAS-MIPi</i>). Females laid their eggs on either side of the assay. All box plots show median and upper/lower quartiles (<i>n</i> = 8, 60 flies/trial). All <i>p</i>-values were calculated via two-way ANOVA with the Bonferroni multiple comparison post-hoc test (ns > 0.05, *<i>p</i> ≤ 0.05, **<i>p</i> ≤ 0.01, ***<i>p</i> ≤ 0.001).</p

SPR/MIP signaling in chemosensory neurons adjusts female preference behavior upon mating.

<p>Model for mating-state-dependent modulation of olfactory and gustatory polyamine preference. (Left side) Upon mating, increased amounts of SPR in the sensory neuron suppress the output of IR41a/IR76b olfactory neurons, thereby increasing the female’s preference for higher concentrations of polyamine. (Right side) Mating increases the SPR amount in gustatory sensory neurons, and in contrast to the situation in OSNs increases the presynaptic output of IR76b taste neurons. This change increases the mated female’s preference for polyamine taste. In conclusion, mating increases SPR expression in chemosensory neurons and by two different cellular mechanisms enhances the mated female’s preference for beneficial polyamines.</p

SPR decreases sensitivity of olfactory neurons to polyamines after mating.

<p>(A) Schematic diagram of a fly brain and its antennal appendages with olfactory sensory neurons (OSNs). OSNs project into the antennal lobe (AL), where they innervate a specific glomerulus (green). Projection neurons (PN) send the information mainly to two higher brain centers, the mushroom body (MB) and the lateral horn (LH) (top). Illustrative confocal image stack showing the IR41a and IR76b OSN innervation in the AL (bottom). VC5 is the glomerulus innervated by the polyamine-responding IR41a/IR76b sensory neurons. (B) Illustration of the in vivo calcium imaging setup. (C–E) In vivo calcium imaging of <i>IR41-Gal4;UAS-GCaMP6f</i> flies stimulated with water and 10 ppm putrescine, respectively. Mated females’ OSN axon terminals show a significant reduction in their sensitivity to putrescine at 1–6 h post-mating. (C) Quantification of peak ΔF responses (in %ΔF/F) in virgin and mated females. Boxes show median and upper/lower quartiles, and whiskers show minimum/maximum values. *<i>p <</i> 0.05, unpaired <i>t</i> test (<i>n</i> = 8). (D) Representative pseudo-color images showing the response to water and 10 ppm putrescine in virgin and mated flies at 1–6 h and 1 wk post-mating. (E) Average response trace (in %ΔF/F) of the VC5 glomerulus peak response at 1–6 h and 1 wk post-mating compared to traces from virgin females. The dark colored line in the middle presents the average value and the light shade presents the SEM. (F–H) In vivo calcium imaging of test (<i>IR41a-Gal4</i>,<i>UAS-SPRi;UAS-GCaMP5</i>) and control (<i>IR41a-Gal4;UAS-GCaMP5)</i> mated female flies. OSN axon terminals of <i>IR41a>SPRi</i> females show significantly enhanced responses to putrescine compared to control females. (F) Representative pseudo-color images showing the response to water and 10 ppm putrescine in <i>IR41a>SPRi</i> and control females, respectively. (G) Average response trace of the VC5 glomerulus in <i>IR41a>SPRi</i> and control females at 1–6 h post-mating for 10 ppm putrescine. (E,G) The gray column represents the 0.5 s stimulation period. Dark colored line is the average response and the light shade is the SEM. (H) Quantification of peak ΔF responses (in %ΔF/F) in <i>IR41a>SPRi</i> and control females for 0 ppm, 6 ppm, 8 ppm, and 10 ppm putrescine, respectively (<i>n</i> = 7 ± SEM). All <i>p</i>-values were calculated using an unpaired <i>t</i> test (*<i>p</i> ≤ 0.05, **<i>p</i> ≤ 0.01, ***<i>p</i> ≤ 0.001).</p

MIP expression is increased in the AL upon mating.

<p>(A) SPR and MIP expression analysis before and after mating of antenna and brain of virgin or mated females. Quantitative PCR (<i>n</i> = 3 genetic variants with 200 females per <i>n</i> and condition) of the antenna and brain of virgin and mated flies reveals that SPR expression upon mating increases upon mating ~10-fold in the antenna and ~3-fold in the brain. Graph displays 2^∆∆CT ± SEM (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002455#sec014" target="_blank">Materials and Methods</a> for details). (B) Quantification of MIP protein expression in the AL. Mated flies show a small but significant increase of MIP expression in the AL. <i>n</i> = 20 flies per group. *<i>p</i> = 0.0113, unpaired <i>t</i> test. (C) Overexpression of SPR under the control of the IR41a enhancer (<i>IR41a-Gal4;UAS-SPR</i>) or IR76b enhancer (<i>IR76b-Gal4;UAS-SPR</i>) in virgin females increases their attraction to polyamine odor in the T-maze assay (<i>n</i> = 8). (D) Overexpression of MIP under the control of the IR41a enhancer (<i>IR41a-Gal4;UAS-MIP</i>) or IR76b enhancer (<i>IR76b-Gal4;UAS-MIP</i>) in virgin females induces a strongly increased attraction to polyamine odor in olfactory T-maze assay (<i>n</i> = 8). (E,F) No egg-laying preference was observed in virgin females overexpressing SPR or MIP under the control of the IR41a enhancer (<i>IR41a-Gal4;UAS-SPR</i> or <i>IR41a-Gal4;UAS-MIP</i>) or IR76b enhancer (<i>IR76b-Gal4;UAS-SPR</i> or <i>IR76b-Gal4;UAS-MIP</i>) in oviposition assays compared to controls (<i>n</i> = 8). Virgin females overexpressing SPR or MIP laid very few eggs, similar to control virgins, which results in the high variability observed in the data. (G–I) In vivo calcium imaging of presynaptic terminals of OSNs in the AL expressing <i>IR41a-Gal4</i>,<i>UAS-SPR;UAS-GCaMP5</i> or <i>IR41a-Gal4;UAS-GCaMP5</i> (control). Virgin females overexpressing SPR in IR41a OSNs show significantly suppressed calcium signals to putrescine compared to virgin control females. (G) Representative pseudo-color images showing the response to 0 ppm and 10 ppm putrescine in SPR-overexpressing and control virgin females, respectively. (H) Average activity trace of the VC5 glomerulus in SPR-overexpressing and control virgin females for 10 ppm putrescine. (I) Quantification of peak ΔF responses in SPR-overexpressing (<i>n</i> = 7) and control (<i>n</i> = 8) females for 0 ppm and 10 ppm putrescine. Boxes show median and upper/lower quartiles, and whiskers show minimum/maximum values. All <i>p</i>-values were calculated via two-way ANOVA with the Bonferroni multiple comparison post-hoc test (ns > 0.05, *<i>p</i> ≤ 0.05, **<i>p</i> ≤ 0.01, ***<i>p</i> ≤ 0.001) except for Fig 6B and 6I, where <i>p</i>-values were calculated via an unpaired t-test (*<i>p</i> ≤ 0.05, **<i>p</i> ≤ 0.01, ***<i>p</i> ≤ 0.001).</p

Table_1_APOBEC3B is overexpressed in cervical cancer and promotes the proliferation of cervical cancer cells through apoptosis, cell cycle, and p53 pathway.docx

ObjectiveAPOBEC3B (A3B), a member of the APOBEC family of cytidine deaminases, has been gradually regarded as a key cancerous regulator. However, its expression and mechanism in cervical cancer (CC) have not been fully elucidated. This study was to investigate its expression pattern and potential mechanism on the cell cycle, as well as HPV oncogenes in CC.MethodsData from The Cancer Genome Atlas (TCGA) and Gene Expression (GEO) were used to indicate the mRNA expression pattern of A3B in cervical cancer. Western blot assay was used to detect A3B levels in SiHa and Hela cell lines. Immunohistochemistry (IHC) was used to explore A3B protein abundance and sublocation in cervical cancer as well as normal cervical tissues. Based on the Protein atlas (www.proteinatlas.org), A3B expression in the SiHa cell line is lower than in the HeLa cell line. Therefore, the SiHa cell line was used for A3B gene overexpression experiments while the HeLa cell line was used for knockdown experiments. Flow cytometry analysis was used to detect cell apoptosis. Biological function and cancer-related pathways of A3B were conducted using bioinformatics analysis.ResultsA3B mRNA was significantly overexpressed in cervical cancer in TCGA-cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), GSE67522, and GSE7803. A3B was more highly expressed in cervical cancers than in high-grade squamous intraepithelial lesions and normal controls. A3B expression was found to be progressively activated during cervical cancer development. IHC results showed that A3B was significantly higher in cervical cancer tissues than in normal cervical tissues. A3B plasmid-mediated overexpression experiments and A3B siRNA-mediated knockdown experiments showed that A3B significantly promotes cell proliferation, migration, cell cycle, and chemoresistance in cervical cancer cells by the p53 pathway. GO and KEGG analyses showed that A3B expression was strikingly associated with cell proliferation, apoptosis, and immune-associated pathways.ConclusionsTaken together, our study implies that A3B promotes cell proliferation, migration, and cell cycle and inhibits cancer cell apoptosis through the p53-mediated signaling pathway. Moreover, A3B could also contribute to chemoresistance in cervical cancer cells. It may be a potential diagnostic biomarker and therapeutic target for chemoresistant cervical cancers.</p