A nomogram of preoperative indicators predicting lymph vascular space invasion in cervical cancer.

PURPOSE: To develop predictive nomograms of lymph vascular space invasion (LVSI) in patients with early-stage cervical cancer. METHODS: We identified 403 patients with cervical cancer from the Affiliated Hospital of Jiangnan University from January 2015 to December 2019. Patients were divided into the training set (n = 242) and the validation set (n = 161), with patients in the training set subdivided into LVSI (+) and LVSI (-) groups according to postoperative pathology. Preoperative hematologic indexes were compared between the two subgroups. Univariate and multivariate logistic regression analyses were used to analyze the independent risk factors for LVSI, from which a nomogram was constructed using the R package. RESULTS: LVSI (+) was present in 94 out of 242 patients in the training set, accompanied by a significant increase in the preoperative squamous cell carcinoma antigen (SCC), white blood cells (WBC), neutrophil (NE), platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and tumor size (P < 0.05). Univariate analysis showed that SCC, WBC, NE, NLR, PLR, SII, and tumor size were correlated with LVSI (P < 0.05), and multivariate analysis showed that tumor size, SCC, WBC, and NLR were independent risk factors for LVSI (P < 0.05). A nomogram was correspondingly established with good performance in predicting LVSI [training: ROC-AUC = 0.845 (95% CI: 0.731-0.843) and external validation: ROC-AUC = 0.704 (95% CI: 0.683-0.835)] and high accuracy (training: C-index = 0.787; external validation: C-index = 0.759). CONCLUSION: The nomogram based on preoperative tumor size, SCC, WBC, and NLR had excellent accuracy and discriminative capability to assess the risk of LVSI in early-stage cervical cancer patients.

Sex Difference in the Association between Depression and Adherence to Recommended Dilated Eye Examinations among Patients with Diabetes: Findings from National Health and Nutrition Examination Survey.

INTRODUCTION: The relationship between depression and adherence to regular dilated fundus examination (DFE) in patients with diabetes remains unclear. This study aimed to assess the association between depression and adherence to annual or biennial DFE among individuals with diabetes. METHODS: In this cross-sectional study, we used the National Health and Nutrition Examination Survey database from 2005 to 2016 which contains information on demographics, clinical characteristics, health-related factors, and the time since last DFE. Participants were classified as having depression based on a score of >9 on the Patient Health Questionnaire-9. The main outcomes were the association between depression and the adherence of patients with diabetes to annual or biennial DFE. The second objective was to explore the potential influence of gender in this association. The independent association of depression with DFE compliance was explored by a series of multivariate logistic regression analyses (overall sample and then stratified by sex). RESULTS: In total, 3,656 eligible participants were identified. The adherence rates to annual or biennial DFE were all higher for participants without depression than those with depression (64.8% vs. 56.1% and 80.3% vs. 69.7%, respectively). In the multivariate analyses, depression was neither independently associated with the adherence to annual DFE nor biennial DFE in the overall sample. An interaction was observed between depression and gender for the adherence to annual or biennial DFE (p = 0.017 and p = 0.026, respectively). When analyses were stratified by sex, female patients with diabetes and depression had a significantly increased odds ratio (OR) of being nonadherent to annual and biennial DFE (OR = 1.52, 95% confidence interval [CI]: 1.02-2.25, p = 0.039; OR = 1.55, 95% CI: 1.02-2.35, p = 0.039, respectively). However, this relationship was not evident in men with diabetes. CONCLUSIONS: The independent association between depression and DFE compliance varied by sex, that is, only female patients with diabetes and depression were at a higher risk of nonadherence to annual or biennial DFE compared to those without depression.

Glycan Metabolic Fluorine Labeling for In Vivo Visualization of Tumor Cells and In Situ Assessment of Glycosylation Variations.

The abnormality in the glycosylation of surface proteins is critical for the growth and metastasis of tumors and their capacity for immunosuppression and drug resistance. This anomaly offers an entry point for real-time analysis on glycosylation fluctuations. In this study, we report a strategy, glycan metabolic fluorine labeling (MEFLA), for selectively tagging glycans of tumor cells. As a proof of concept, we synthesized two fluorinated unnatural monosaccharides with distinctive 19 F chemical shifts (Ac4 ManNTfe and Ac4 GalNTfa). These two probes could undergo selective uptake by tumor cells and subsequent incorporation into surface glycans. This approach enables efficient and specific 19 F labeling of tumor cells, which permits in vivo tracking of tumor cells and in situ assessment of glycosylation changes by 19 F MRI. The efficiency and specificity of our probes for labeling tumor cells were verified in vitro with A549 cells. The feasibility of our method was further validated with in vivo experiments on A549 tumor-bearing mice. Moreover, the capacity of our approach for assessing glycosylation changes of tumor cells was illustrated both in vitro and in vivo. Our studies provide a promising means for visualizing tumor cells in vivo and assessing their glycosylation variations in situ through targeted multiplexed 19 F MRI.

Bio-orthogonal Metabolic Fluorine Labeling Enables Deep-Tissue Visualization of Tumor Cells In Vivo by 19F Magnetic Resonance Imaging.

The high resolution, deep penetration, and negligible biological background of 19F magnetic resonance imaging (MRI) makes it a potential means for imaging various biological targets in vivo. However, the limited targeting strategies of current 19F MRI probes significantly restrict their applications for in vivo tracking of low-abundance targets and specific biological processes, which greatly stimulates the investigations on new targeting methods for 19F MRI. Herein, we report a strategy, termed as bio-orthogonal metabolic fluorine labeling, for selective cellular 19F labeling, which permits in vivo imaging of tumor cells with high specificity. This strategy exploits the display of azido groups on the cell surface via selective uptake and metabolic engineering of tetra-acetylated N-azidoacetylmannosamine (Ac4ManAz) by cancer cells and subsequent rapid and specific bio-orthogonal ligation between azido and cyclootynyl groups to incorporate 19F-containing moieties on the surface of cancer cells. We validated the feasibility of this method on the cellular level with A549 and HepG2 cells and further illustrated the application of this method for in vivo deep-tissue visualization of cancer cells with A549 tumor-bearing BALB/c mice using hot spot 19F MRI. Our strategy expands the arsenal for targeted 19F MRI and provides a promising method for imaging biological targets in living subjects with high tissue penetration and low biological background.

Hypoxia-Activated Prodrug Enabling Synchronous Chemotherapy and HIF-1α Downregulation for Tumor Treatment.

The overexpression of HIF-1α in solid tumors due to hypoxia is closely related to drug resistance and consequent treatment failure. Herein, we constructed a hypoxia-activated prodrug named as YC-Dox. This prodrug could be activated under hypoxic conditions and undergo self-immolation to release doxorubicin (Dox) and YC-1 hemisuccinate (YCH-1), which could execute chemotherapy and result in HIF-1α downregulation, respectively. This prodrug is capable of specifically releasing Dox and YCH-1 in response to hypoxia, leading to a substantial synergistic potency and a remarkable cytotoxic selectivity (>8-fold) for hypoxic cancer cells over normoxic healthy cells. The in vivo experiments reveal that this prodrug can selectively aim at hypoxic cancer cells and avoid undesired targeting of normal cells, leading to elevated therapeutic efficacy for tumor treatment and minimized adverse effects on normal tissues.

In vitro and in vivo activity of EDTA and antibacterial agents against the biofilm of mucoid Pseudomonas aeruginosa.

PURPOSE: Refractory infection caused by bacterial biofilm is an important clinical problem. Pseudomonas aeruginosa is a common pathogen responsible for persistent and chronic biofilm infections. We aimed to explore the in vitro and in vivo activity of ethylenediamine tetraacetic acid (EDTA) in combination with antibacterial agents against mucoid P. aeruginosa biofilm. METHODS: The minimal inhibitory concentration (MIC) and minimal bactericidal concentration of ciprofloxacin, gentamicin, and ampicillin alone or with EDTA against P. aeruginosa were determined in vitro. Extracellular polysaccharides (EPS) and structural parameters of the biofilm were monitored. P. aeruginosa was aerosolized and delivered into the lungs of guinea pigs, which were treated with ciprofloxacin with or without EDTA. The colony-forming units (CFUs) of P. aeruginosa were determined from the lungs. RESULTS: EDTA reduced the MIC of ciprofloxacin and ampicillin by about 30-fold and that of gentamicin by twofold. EDTA reduced the biofilm EPS and the proportion of viable bacteria. The thickness, average diffusion distance, and textural entropy of EDTA-treated biofilm were significantly decreased. EDTA plus antibiotics reduced the colony counting from 107 to 103 CFU/mL. In vivo, EDTA plus ciprofloxacin had a significantly lower mean CFU/g of lung tissue (EDTA + ciprofloxacin 1.3 ± 0.19; EDTA 4.4 ± 0.57; ciprofloxacin 4.2 ± 0.47), and lung lesions were less severe compared with the single treatment groups. CONCLUSIONS: EDTA can destroy the biofilm structures of mucoid P. aeruginosa in vitro. Moreover, EDTA and ciprofloxacin had a significant bactericidal effect against biofilm in vivo.

Immigrant-native differences in caries-related knowledge, attitude, and oral health behaviors: a cross-sectional study in Taiwan.

BACKGROUND: With the growing number of transnational marriages in Taiwan, oral health disparities have become a public health issue. This study assessed immigrant-native differences in oral health behaviors of urban mothers and their children. METHODS: We used the baseline data of an oral health promotion program to examine the immigrant-native differences in caries-related knowledge, attitude, and oral health behaviors. A cross-sectional study was conducted to collect data from mothers in urban area, Taiwan. A total of 150 immigrant and 440 native mothers completed the self-report questionnaires. Logistic regression models analyzed the racial differences in oral health behaviors. RESULTS: Approximately 37% of immigrant mothers used dental floss, 25% used fluoride toothpaste, and only 13.5% of them regularly visited a dentist. Less that 40% of immigrant mothers brush their children's teeth before aged one year, 45% replaced child's toothbrush within 3 months, and only half of the mothers regularly took their child to the dentist. Immigrant mothers had lower level of caries-related knowledge and attitudes than native mothers (p < .001). Compared to native group, the immigrant mothers were less likely to use of dental floss ([Adjusted odds ratio (aOR) =0.35], fluoride toothpaste (aOR = 0.29), visit a dentist in the past 2 years (aOR = 0.26), and take their children to regular dental check-up (aOR = 0.38); whereas, they were more likely to not consume sweeten beverages (aOR = 3.13). CONCLUSIONS: The level of caries-related knowledge, attitudes and oral health behaviors were found lower in immigrant mothers than native ones. The findings suggested cross-cultural caries prevention programs aimed at reducing immigrant-native disparities in child oral health care must be developed for these immigrant minorities.

Cost-effectiveness evaluation of mass-rearing Cadra cautella (Lepidoptera: Pyralidae) based on harvest theory for sustainable alternative prey production.

Cadra cautella (Walker) (Lepidoptera: Pyralidae) is a pest in barn, and its eggs are often utilized as an alternative prey or as hosts for mass production of insect predators and parasitoids. To aid in developing a mass-rearing system for C. castella, the suitability of using an artificial diet based on brown rice flour and whole brown rice was compared using the age-stage, 2-sex life table. Compared with those reared on brown rice, the insects reared on an artificial diet had a shorter preadult period (32.08 vs 37.38 d), higher fecundity (468.14 vs 356.20 eggs/female), greater intrinsic rate of increase (0.1509 vs 0.1145 d-1), and higher net reproductive rate (199.28 vs 103.52 offspring). Small populations were required to rear the moth on an artificial diet to achieve the same daily production of C. cautella. Still, the food expense was only 60.2% of that of C. cautella reared on brown rice. Approximately 99.44% of the eggs in each rearing procedure could be supplied as alternative prey for predators, with the remainder served to maintain the colonies for subsequent batches. Only eggs laid within 6 d would be utilized to ensure the high quality of alternative prey for the mass production of predacious bugs. Additionally, a multifunctional device was designed for moth rearing and egg collection, reducing labor input and minimizing health risks for workers coping with inhaled scales. To encourage the production of natural enemies, a cost-effective diet for maintaining a sustainable colony, and a system for daily egg-harvesting of alternative prey were proposed.

Constructing sequence-controlled heterolayered dendritic lanthanide chelates via a one-pot strategy using orthogonal chemistry.

The construction of sequence-controlled heterometallic lanthanide complexes is challenging despite their intriguing physical/chemical properties and enormous potential applications. Here we report a one-pot strategy that exploits orthogonal chemical reactions for modular assembly, which allows for rapid preparation of sequence-controlled heterolayered lanthanide-complex dendritic structures.

Allometric scaling of interspecific RNA transcript abundance to extend the use of metatranscriptomics in characterizing complex communities.

Metatranscriptomics allows profiling of community mRNA and rRNA transcript abundance under certain environmental conditions. However, variations in the proportion of RNA transcripts across different community size structures remain less explained, thus limiting the possible applications of metatranscriptomics in community studies. Here, we extended the assumptions of the growth-rate hypothesis (GRH) and the metabolic theory of ecology (MTE) to validate the allometric scaling of interspecific RNA transcript (mRNA and rRNA) abundance through metatranscriptomic analysis of mock communities consisting of model organisms. The results suggest that body size imposes significant constraints on RNA transcript abundance. Interestingly, the relationship between the total mitochondrial transcript abundance (mRNA and rRNA slopes were -0.30 and -0.28, respectively) and body size aligned with the MTE assumptions with slopes close to -», while the nuclear transcripts displayed much steeper slopes (mRNA and rRNA slopes were -0.33 and -0.40, respectively). The assumed temperature dependence was not observed in this study. At the gene level, the allometric slopes range from 0 to -1. Overall, the above results showed that larger individuals have lesser RNA transcript abundance per tissue mass than smaller ones regardless of temperature. Analyses of field-collected microcrustacean zooplankton samples demonstrated that the correction of size effect, using the allometric exponents derived from the model organism mock community, explains better the patterns of interspecific RNA transcripts abundance within the metatranscriptome. Integrating allometry with metatranscriptomics can extend the use of RNA transcript reads in estimating ecological processes within complex communities.

Household secondhand smoke exposure of elementary schoolchildren in Southern Taiwan and factors associated with their confidence in avoiding exposure: a cross-sectional study.

BACKGROUND: Exposure to household Secondhand Smoke (SHS) poses a major health threat to children after an indoor smoking ban was imposed in Taiwan. This study aimed to assess the household SHS exposure in elementary school children in southern Taiwan and the factors associated with their avoidance of SHS exposure before and after the implementation of Taiwan's new Tobacco Hazards Prevention Act in 2009. METHODS: In this cross-sectional school-based study, data on household SHS exposure, avoidance of SHS and related variables was obtained from the 2008 and 2009 Control of School-aged Children Smoking Study Survey. A random sample of 52 elementary schools was included. A total of 4450 3-6 graders (aged 8-13) completed the questionnaire. Regression models analyzed factors of children's self-confidence to avoid household SHS exposure. RESULTS: Over 50% of children were found to have lived with a family member who smoked in front of them after the new law enacted, and 35% of them were exposed to household SHS more than 4 days a week. Having a positive attitude toward smoking (ß = -0.05 to -0.06) and high household SHS exposure (ß = -0.34 to -0.47) were significantly associated with a lower avoidance of SHS exposure. Comparing to girls, boys had lower scores in their knowledge of tobacco hazards; and this factor was significantly related to their SHS avoidance (ß = 0.13-0.14). CONCLUSIONS: The intervention program should enhance school children do actively avoid exposure to SHS in home settings, and more importantly, provide tobacco hazard knowledge to male students to avoid exposure to household SHS for themselves. The results also provide further evidence that Tobacco Hazards Prevention Act should perhaps be extended to the family environment in order to protect children from the hazards of household SHS exposure.

A dual-responsive doxorubicin-indoximod conjugate for programmed chemoimmunotherapy.

Herein we report a dual-responsive doxorubicin-indoximod conjugate (DOXIND) for programmed chemoimmunotherapy. This conjugate is able to release doxorubicin and indoximod upon exposure to appropriate stimuli for synergistic chemotherapy and immunotherapy, respectively. We demonstrate its promoting effects on immune response and inhibiting effects on tumor growth through a series of in vitro and in vivo experiments.

An Activatable 19 F MRI Molecular Probe for Sensing and Imaging of Norepinephrine.

Norepinephrine (NE), acting as both a neurotransmitter and hormone, plays a significant role in regulating the action of the brain and body. Many studies have demonstrated a strong correlation between mental disorders and aberrant NE levels. Therefore, it is of urgent demand to develop in vivo analytical methods of NE for diagnostic assessment and mechanistic investigations of mental diseases. Herein, we report a 19 F MRI probe (NRFP) for sensing and imaging NE, which is constructed by conjugating a gadolinium chelate to a fluorine-containing moiety through a NE-responsive aromatic thiocarbonate linkage. The capacity and specificity of NRFP for detecting NE is validated with in vitro detecting/imaging experiments. Furthermore, the feasibility of NRFP for visualizing NE in animals is illustrated by ex vivo and in vivo imaging experiments, demonstrating the promising potential of NRFP for selective detection and specific imaging of NE in deep tissues of living subjects.

Tandem Chemoimmunotherapy by a Cascade-Responsive Molecular Prodrug.

The limited therapeutic effects of immunotherapy for most types of cancer stimulates the pursuit for efficient methods to improve its response rate. Herein we report the design and synthesis of a cascade-responsive molecular prodrug for tandem chemoimmunotherapy. This molecular prodrug first releases doxorubicin (DOX) in the mildly acidic tumor microenvironment (TME) to induce immunogenic cell death (ICD) of tumor cells. Caspase 3/7 released during tumor cell apoptosis liberates NLG919 from the prodrug, which inhibits the activity of indoleamine 2,3-dioxygenase (IDO) and results in relief of TME immunosuppression. Meanwhile, tumor-associated antigens and immune stimulatory cytokines released during ICD activate the immune response against the tumor, leading to synergistic chemoimmunotherapy. The efficacy of this prodrug is validated by in vitro and in vivo experiments, demonstrating the success of this strategy for cancer treatment.

Demographic Characteristics and Population Simulation of Newly Invasive Fall Armyworm on Arachis hypogaea (Fabales: Fabaceae) and Dominant Green Manure Plant in Taiwan.

Spodoptera frugiperda (J.E. Smith) is a severe and fast-spreading pest of numerous agro-economic crops, including miscellaneous, vegetables, and green manure crops. Understanding pest ecology represents a core component in integrated pest management decision-making. In Taiwan, peanut (Arachis hypogaea L.) is an important miscellaneous crop, whereas sesbania (Sesbania roxburghii Merr.) is the most frequently used green manure crop. To improve the S. frugiperda management in Taiwan, the demographic characteristics and population simulation of this pest reared on peanut and sesbania leaves were analyzed using the age-stage, two-sex life table theory. The intrinsic rate of increase, finite rate of increase, and net reproductive rate of S. frugiperda were higher when reared on peanut (0.1625 d-1, 1.1764 d-1, 264.9 offspring) than on sesbania (0.0951 d-1, 1.0997 d-1, and 30.3 offspring). Population projection of S. frugiperda on peanut demonstrated that this crop is a more suitable host plant than sesbania. Yet, this suboptimal host still assures an increasing trend of more than 357-fold individuals in 75 d, from the initial cohort of 10 eggs. Our data suggest that green manure plants in fallowing fields may support the pest's survival all year round, and may be responsible for a successful establishment and unexpected outbreaks of this invasive pest on the neighboring crops in Taiwan. Our study thus highlights the importance of assessing the population dynamics and areawide pest management of an invasive polyphagous pest on a noneconomic crop to mitigate the potential risk of reinfestation and thus outbreaks.

Using metatranscriptomics to estimate the diversity and composition of zooplankton communities.

DNA metabarcoding is a rapid, high-resolution tool used for biomonitoring complex zooplankton communities. However, diversity estimates derived with this approach can be biased by the co-detection of sequences from environmental DNA (eDNA), nuclear-encoded mitochondrial (NUMT) pseudogene contamination, and taxon-specific PCR primer affinity differences. To avoid these methodological uncertainties, we tested the use of metatranscriptomics as an alternative approach for characterizing zooplankton communities. Specifically, we compared metatranscriptomics with PCR-based methods using genomic (gDNA) and complementary DNA (cDNA) amplicons, and morphology-based data for estimating species diversity and composition for both mock communities and field-collected samples. Mock community analyses showed that the use of gDNA mitochondrial cytochrome c oxidase I (mtCO1) amplicons inflates species richness due to the co-detection of extra-organismal eDNA. Significantly more amplicon sequence variants, nucleotide diversity, and indels were observed with gDNA amplicons than with cDNA, indicating the presence of putative NUMT pseudogenes. Moreover, PCR-based methods failed to detect the most abundant species in mock communities due to priming site mismatch. Overall, metatranscriptomics provided estimates of species richness and composition that closely resembled those derived from morphological data. The use of metatranscriptomics was further tested using field-collected samples, with the results showing consistent species diversity estimates among biological and technical replicates. Additionally, temporal zooplankton species composition changes could be monitored using different mitochondrial markers. These findings demonstrate the advantages of metatranscriptomics as an effective tool for monitoring diversity in zooplankton research.

Approaches in the Treatment of Cesarean Scar Pregnancy and Risk Factors for Intraoperative Hemorrhage: A Retrospective Study.

Background: Cesarean scar pregnancy (CSP) involves a rare form of placental attachment that often leads to life-threatening conditions. The best treatment for CSP has been debated for decades. We aimed to evaluate the different treatments for CSP and analyzed the risk factors for intraoperative hemorrhage. Methods: CSP patients treated at the Affiliated Hospital of Jiangnan University were reviewed retrospectively from January 2014 to 2020. CSP was classified into three types based on the location and shape of gestational tissue, blood flow features, and thickness of the myometrium at the incision site. The clinical characteristics, types, approaches of treatment, and clinical outcomes of CSP were analyzed. Results: A total of 55 patients were included in this study, 29 (52.7%) of whom underwent transvaginal curettage after uterine artery embolization (UAE) and 22 (40%) of whom underwent transabdominal ultrasound-guided hysteroscopic curettage (USHC) in type I and II. Four patients (7.3%) classified as type III underwent laparoscopic cesarean scar resection (LCSR). Intraoperative blood loss, blood transfusion rate, and scar diverticulum were significantly higher in type II than in type I (P < 0.05). Even though USHC showed no differences in intraoperative blood loss, length of stay, and scar diverticulum compared with curettage after UAE (P > 0.05), superiority was found in surgical time and hospitalization cost (P < 0.05). Furthermore, the type of CSP (OR = 10.53, 95% CI: 1.69-65.57; P = 0.012) and diameter of the gestational sac (OR = 25.76, 95% CI: 2.67-248.20; P = 0.005) were found to be risk factors for intraoperative hemorrhage. Conclusions: Transabdominal ultrasound-guided hysteroscopic curettage is an effective and relatively safe treatment option for patients with CSP. Type of CSP and diameter of the gestational sac were found to be associated with excessive intraoperative hemorrhage.

Exosome Component 4 Promotes Epithelial Ovarian Cancer Cell Proliferation, Migration, and Invasion via the Wnt Pathway.

BACKGROUND: Of gynecologic malignancies, ovarian cancer is the leading cause of death, mainly due to the lack of sensitive tumor markers, which means it almost always presents at an advanced stage. Exosome Component 4 (EXOSC4) is involved in RNA degradation, but its role in epithelial ovarian cancer (EOC) is unclear. METHODS: The expression levels of EXOSC4 in EOC and normal ovarian tissue specimens were determined by immunohistochemical staining. The overall survival (OS) and progression-free survival (PFS) of patients with EOC were evaluated after patients were classified into high and low EXOSC4 expression groups, and the Cox regression model was established to identify independent predictors of patient prognosis. The effects of EXOSC4 on proliferation, colony formation, migration, and invasion were examined in the SKOV-3 and HO8910 cell lines by lentivirus-mediated shRNA knockdown. Flow cytometry was used to detect cell cycle changes. The mRNA levels of cyclin D1, CDK4, and c-myc were detected by RT-PCR. The protein expression levels of ß-catenin, cyclin D1, CDK4, c-myc, vimentin, N-cadherin, and E-cadherin were assessed by western blot. Wnt/ß-catenin activation was measured by TCF/LEF reporter assay. RESULTS: EXOSC4 was significantly elevated in EOC tissues and cell lines. High EXOSC4 expression was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and pathological grade, and identified as an independent predictor of shorter OS and PFS. EXOSC4 knockdown suppressed proliferation, migration, and invasion in EOC cell lines. Cells were arrested at G0/G1 phase after EXOSC4 knockdown. The mRNA levels of cyclin D1, CDK4, and c-myc were decreased. ß-catenin, cyclin D1, CDK4, c-myc, vimentin, and N-cadherin protein expression levels were reduced, while those of E-cadherin was increased. Wnt/ß-catenin activity was suppressed after the EXOSC4 knockdown. CONCLUSIONS: EXOSC4 is involved in EOC. Knockdown of EXOSC4 can inhibit the proliferation, migration, and invasion ability of EOC by suppressing the Wnt pathway. EXOSC4 is expected to be a novel biomarker and molecular target in EOC.

A camptothecin prodrug induces mitochondria-mediated apoptosis in cancer cells with cascade activations.

Mitochondria are crucial regulators of the intrinsic pathway of apoptosis. Herein, we report a photosensitizer-conjugated camptothecin (CPT)-based prodrug for combinative chemo-photodynamic treatment of solid tumors with cascade activations. Upon light irradiation, our prodrug can effectively target the mitochondria of cancer cells, generate singlet oxygen to increase the level of reactive oxygen species (ROS) and trigger ROS-responsive release of CPT, which synergistically induce mitochondrial damage and cause the apoptosis of cancer cells, therefore achieving high therapeutic efficacy for solid tumors and minimized adverse effects to normal tissues. Our prodrug holds great promise as a potent and inspiring means for cancer treatment.

Direct and Knock-on Effects of Water Stress on the Nutrient Contents of Triticum aestivum (Poales: Poaceae) and Population Growth of Rhopalosiphum padi (Hemiptera: Aphididae).

To ascertain the direct effects of water stress upon wheat plants (Triticum aestivum L.) and how these effects, in turn, influence the population growth of the bird cherry-oat aphid (Rhopalosiphum padi L.), we conducted a physiological analysis of wheat seedlings grown under three different watering regimes and subsequently determined the population parameters of the aphid using the age-stage, two-sex life table. A significantly higher content of free amino acids and soluble sugars were observed in wheat seedlings exposed to drought stress compared to seedlings that were well-watered and those that were grown under waterlogged conditions. Extended phloem salivation and stylet penetration with shorter duration of sustained ingestion from phloem was observed in an electrical penetration graph (EPG) of R. padi on drought-stressed wheat seedlings. This suggested that the aphid's feeding activity, as well as nutrient intake, were impeded. The significantly higher percentage of essential amino acids found in wheat seedlings grown under waterlogged conditions promoted significantly higher fecundity and intrinsic rate of increase in R. padi populations compared to aphids fed on drought-treated or well-watered wheat seedlings. Our findings suggest that wheat seedling responses to water stress involve changes in sap composition that are responsible for altering the aphids' nutrient intake and consequently affect their population growth. From a grower's perspective, extending wheat cultivation in a rice-wheat rotation paddy field during the winter season may not be economically profitable if the fields are chronically waterlogged, since this may potentially lead to a higher infestation of cereal aphids.