Hernandonine-mediated autophagic cell death in hepatocellular carcinoma: Interplay of p53 and YAP signaling pathways.

Hepatocellular carcinoma (HCC), the primary form of liver cancer, is the third leading cause of cancer-related death globally. Hernandonine is a natural alkaloid derived from Hernandia nymphaeifolia that has been shown to exert various biological functions. In a previous study, hernandonine was shown to suppress the proliferation of several solid tumor cell lines without affecting normal human cell lines. However, little is known about the effect of hernandonine on HCC. Therefore, this study aimed to investigate the effect and mechanism of hernandonine on HCC in relation to autophagy. We found that hernandonine inhibited HCC cell growth in vitro and in vivo. In addition, hernandonine elicited autophagic cell death and DNA damage in HCC cells. RNA-seq analysis revealed that hernandonine upregulated p53 and Hippo signaling pathway-related genes in HCC cells. Small RNA interference of p53 resulted in hernandonine-induced autophagic cell death attenuation. However, inhibition of YAP sensitized HCC cells to hernandonine by increasing the autophagy induction. This is the first study to illustrate the complex involvement of p53 and YAP in the hernandonine-induced autophagic cell death in human HCC cells. Our findings provide novel evidence for the potential of hernandonine as a therapeutic agent for HCC treatment.

Atmospheric particulate matter retention capacity of bark and leaves of urban tree species.

Urban vegetation can effectively filter and adsorb particulate matter (PM). However, limited studies have been conducted on the PM retention capacity of tree barks. This study investigated the ability of five common urban tree species in the Yangtze River Delta region to retain PM through their barks and leaves by conducting a 14-day tree PM retention experiment on the five tree species during autumn and winter. The results showed that (1) the PM retention per unit area of bark was 6.9 times and 11.8 times higher than that of leaves during autumn and winter, respectively; (2) when considering total surface area, bark and leaves exhibited comparable PM retention capacities at the whole-plant scale; (3) the ability of bark to retain PM is species-specific, which can be attributed to different bark morphology among different tree species; and (4) bark and leaves exhibited distinct preferences for retaining PM of different particle sizes, even when exposed to similar environmental conditions. This study highlights the remarkable ability of tree bark to PM removal and provides valuable insights into the role of urban trees in mitigating PM pollution. Furthermore, these findings can provide valuable insights into studies on dry deposition modelling, urban planning, and green space management strategies.

Lysosomal-targeted doxorubicin delivery using RBC-derived vesicles to overcome drug-resistant cancer through mitochondrial-dependent cell death.

Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. Nanoparticles as drug delivery systems (DDSs) show promise for MDR cancer therapy. However, current DDSs require sophisticated design and construction based on xenogeneic nanomaterials, evoking feasibility and biocompatibility concerns. Herein, a simple but versatile biological DDS (bDDS) composed of human red blood cell (RBC)-derived vesicles (RDVs) with excellent biocompatibility was surface-linked with doxorubicin (Dox) using glutaraldehyde (glu) to form Dox-gluRDVs that remarkably suppressed MDR in uterine sarcoma through a lysosomal-mitochondrial axis-dependent cell death mechanism. Dox-gluRDVs can efficiently deliver and accumulate Dox in lysosomes, bypassing drug efflux transporters and facilitating cellular uptake and retention of Dox in drug-resistant MES-SA/Dx5 cells. The transfer of lysosomal calcium to the mitochondria during mitochondria-lysosome contact due to lysosomal Dox accumulation may result in mitochondrial ROS overproduction, mitochondrial membrane potential loss, and activation of apoptotic signaling for the superior anti-MDR activity of Dox-gluRDVs in vitro and in vivo. This work highlights the great promise of RDVs to serve as a bDDS of Dox to overcome MDR cancers but also opens up a reliable strategy for lysosomal-mitochondrial axis-dependent cell death for fighting against other inoperable cancers.

Alkaloids and Polyacetylenes from Hippobroma longiflora with Antiangiogenesis Properties.

Four new alkaloids, hippobrines A-D (1-4), along with three new polyacetylenes, hippobrenes A-C (5-7), were isolated from Hippobroma longiflora. Compounds 1-3 possess an unprecedented carbon skeleton. All of the new structures were determined by analyzing their mass and NMR spectroscopic data. The absolute configurations of 1 and 2 were confirmed by single-crystal X-ray analyses, and the absolute configurations of 3 and 7 were deduced using their ECD spectra. Plausible biogenetic pathways of 1 and 4 were proposed. In regard to bioactivities, all compounds (1-7) exhibited weak antiangiogenic activity against human endothelial progenitor cells, with IC50 values ranging from 21.1 ± 1.1 to 44.0 ± 2.3 µg/mL.

Rhinitis symptom in patients with self-reported allergic rhinitis is influenced by sensitization pattern: A cross-sectional study of China.

BACKGROUND: Allergic rhinitis (AR) is characterized by distinct clinical heterogeneity and allergic sensitization patterns. We aimed to quantify rhinitis symptoms in patients with self-reported allergic rhinitis according to the potential sensitization patterns for relevant allergens in China. METHODS: We used latent class analysis (LCA; a subset of structural equation modeling) to independently cluster patients into different patterns of atopic sensitization in an unsupervised manner, based on specific immunoglobulin E tests. AR symptom severity was assessed by the visual analogue scale. We evaluated the association between the severity of AR and the allergen sensitization patterns. RESULTS: LCA revealed four phenotypes of atopic sensitization among 967 patients with self-report AR. We labeled latent classes as: Class 1, weed pollens and indoor sensitization (n = 74 [7.7%]); Class 2, weed pollen with low indoor sensitization (n = 275 [28.4%]); Class 3, low or no sensitization (n = 350 [36.2%]); and Class 4, house dust mite-dominated sensitization (n = 268 [27.7%]). AR was more severe in Class 2 compared to the other 3 classes, indicating that upper respiratory symptoms are more severe among patients with isolated seasonal rhinitis. CONCLUSION: We have identified four sensitization patterns in patients with self-reported AR, which were associated with different clinical symptoms and comorbidities.

Sensitization to Furry Animals in Patients with Suspected Allergic Disease in China: A Multicenter Study.

Purpose: An objective of this study was to investigate the allergen sensitization characteristics of cat, dog and horse dander in patients with suspected allergic diseases in different geographical regions of Chinese mainland. Patients and Methods: We invited 2377 patients aged 0-86 years with suspected allergic diseases to participate in a cross-sectional survey in 11 provinces in China. Combined with the questionnaires and animal-specific IgE levels, we analyzed the epidemiological characteristics and risk factors of furry animal sensitization in different regions and populations of Chinese Mainland. Results: Among the 2377 patients with suspected allergic diseases, 14.9% were sensitized to cat dander, 9.3% to dog dander and 5.5% to horse dander. Animal allergens mainly cause low-level sensitization (class 1-3). There was a significant correlation between cat, dog and horse dander allergen sIgE, with correlation coefficients (rs) all greater than 0.750. The majority (46.5%) of sIgE-positive patients were sensitized to at least two animal allergens simultaneously. The prevalence of these animals all showed a trend of increasing first and then decreasing with age, and all reached the peak in young adolescence. As for the geographical factors, the sensitization rate of cats and dogs in Western was significantly higher than that in Eastern (cat: 18.4% vs 9.2%, dog: 11.6% vs 5.5%, all P < 0.001), however, no significant differences were found in horses. Aged ≤6 years, living in Western, and high animal allergen exposure elevated the risk of cat or dog sensitization. Living on a lower floor (aOR: 0.56) was a protective factor for horse sensitization. Conclusion: In this representative sample of Chinese patients with suspected allergic diseases, there was an apparent geographic variation in sensitization to cats and dogs. Age factor and living in Western also had a significant impact on animal allergen sensitization rate.

An Emerging Duck Egg-Reducing Syndrome Caused by a Novel Picornavirus Containing Seven Putative 2A Peptides.

Since 2016, frequent outbreaks of egg-reducing syndromes caused by an unknown virus in duck farms have resulted in huge economic losses in China. The causative virus was isolated and identified as a novel species in Avihepatovirus of the picornavirus family according to the current guidelines of the International Committee on Taxonomy of Viruses (ICVT), and was named the duck egg-reducing syndrome virus (DERSV). The DERSV was most closely related to wild duck avihepatovirus-like virus (WDALV) with 64.0%, 76.8%, 77.5%, and 70.7% of amino acid identities of P1, 2C, 3C, and 3D proteins, respectively. The DERSV had a typical picornavirus-like genomic structure, but with the longest 2A region in the reported picornaviruses so far. Importantly, the clinical symptoms were successfully observed by artificially infecting ducks with DERSV, even in the contact exposed ducks, which suggested that DERSV transmitted among ducks by direct contact. The antibody levels of DERSV were correlated with the emergence of the egg-reducing syndromes in ducks in field. These results indicate that DERSV is a novel emerging picornavirus causing egg-reducing syndrome in ducks.

Associations of Four sensitization patterns revealed by Latent Class Analysis with Clinical symptoms: A multi-center study of China.

Background: Because of the significant regional differences in the distribution of allergens, the relationship between anaphylaxis and allergic sensitization is complex in China. Using this large-scale epidemiologic survey, we explore the potential patterns of sensitization to common allergens in mainland China and investigate their relationship with various clinical symptoms. Method: The participants were recruited from 13 medical centers in mainland China from October 2019 to June 2021. Skin prick test (SPT) results that cover 18 common allergens were utilized to diagnose atopic sensitization. The demographic characteristics and clinical information were collected through questionnaires during routine medical follow-up. Latent class analysis (LCA) was conducted to determine the optimal sensitization patterns. The logistic regression was used to assess the associations of different sensitization patterns with allergy symptoms. Findings: A total of 1089 patients who had a positive SPT to at least one of 18 allergens were included for formal analysis. An optimal LCA model with 4 classes was obtained in this study, and the corresponding labels were as follows: Class1, house dust mite sensitization; Class2, low pollen sensitization; Class3, middle pollen sensitization; Class4, high pollen sensitization. The prevalence of different classes varied widely in geographical distribution, which was characterized by Class1 being very common in south and east as well as Class2 in north and west of China. Compared with patients in Class1, those in middle and high pollen sensitization clusters had the higher odds ratios (ORs) of allergic rhinitis and allergic conjunctivitis when controlling for other confounders. However, there was no significant difference between low pollen sensitization and house dust mite sensitization groups in the risks for various clinical performances except dermatitis. Additionally, the adjusted ORs (95% confidence interval) of allergic conjunctivitis and dermatitis for participants in pollen sensitization clusters (Class2, 3 and 4) were 1.56 (1.18, 2.06) and 1.43 (1.09, 1.88) respectively compared with those in Class1. Interpretation: In this study, we identified four sensitization clusters with specific risks of various clinical symptoms using common allergens by adopting LCA. Our findings may contribute to improved diagnosis and potential immunotherapy approaches to allergy in mainland China. Funding: This study was supported by the National Natural Science Foundation of China (81802076 and 81871736), the Guangzhou Science and Technology Foundation (202102010327), the Foundation of SKLRD (MS-2019-06 and Z-2022-09), and the Foundation of GYYY (ZH201904) and ZNSA-2020012.

Three-dimensional building morphology impacts on PM2.5 distribution in urban landscape settings in Zhejiang, China.

Three-dimensional (3D) urban landscape patterns and building morphology are crucial for urban planning and essential for urban landscape functions. In this study, fixed and mobile monitoring sites were used to determine the spatial distribution of PM2.5 concentrations in Hangzhou. Six 3D metrics were selected to analyze the response of PM2.5 pollution to landscape patterns and building morphology, while their two-dimensional (2D) counterparts' metrics were also analyzed to contrast the differences. A variance partitioning analysis (VPA) was performed to measure the combined and relative contribution of 3D and 2D metrics to the changes in PM2.5 concentrations. The results showed that: (1) on the 3D scale, forming a building pattern with a combination of different building heights can eliminate the accumulation of PM2.5; (2) on the 2D scale, fragmentation and decentralization of landscapes and building patches alleviate PM2.5 pollution; and (3) 3D building morphology indicators have the highest explanatory power (40.94%) for the changes of PM2.5 concentrations. It turns out that the explanatory power of 3D metrics for PM2.5 concentrations changes is much greater than that of 2D metrics. In addition, when compared to building morphology indicators from a single dimension, the combination of 2D and 3D metrics is better able to reflect urban PM2.5 pollution. The results of this study expand our understanding of how PM2.5 pollution responds to 2D and 3D metrics and provide useful information for urban planning.

Environmental and sensitization variations among asthma and/or rhinitis patients between 2008 and 2018 in China.

BACKGROUND: Little is known about the changes in allergen sensitization in China secondary to the environmental variations over the past decade. We aimed at investigating the variations in sensitization among asthma and/or rhinitis patients in China between 2008 and 2018. METHODS: This study analyzed cross-sectional data from national surveys conducted in China in 2008 and 2018. After finishing the questionnaire, participants underwent serum specific IgE measurements. A total of 2322 and 2798 patients were enrolled in 2008 and 2018, respectively. The significance of differences in sensitization rates among four regions of China were assessed. Correlation analysis was used to identify the associations of sensitization with climate change and planting of Artemisia desertorum between the two surveys. RESULTS: Compared with 2008, the general sensitization rate to mites significantly increased in 2018, which ranked highest among all tested allergens. Sensitization to pollens, especially Artemisia vulgaris, showed the greatest increase in the north. The annual mean temperature, rainfall and relative humidity in all four regions, and the Artemisia desertorum coverage in the northeastern area, increased significantly in 2018 as compared with 2008. From 2008 to 2018, an increase in Dermatophagoides pteronyssinus sensitization was significantly associated with an increase in relative humidity (r = 0.54, p = 0.037). The increase in A. vulgaris sensitization was significantly associated with the increase in the A. desertorum planting area (r = 0.67, p = 0.006) and with a decrease in rainfall (r = -0.59, p = 0.021). CONCLUSIONS: House dust mites remain the most important allergen in Chinese individuals with asthma and/or rhinitis. Pollen sensitization dramatically increased in northern China. Increases in sensitization to dust mites and Artemisia were related to the increases in humidity and planting area of A. desertorum.

Efficacy of a recombinant turkey herpesvirus (H9) vaccine against H9N2 avian influenza virus in chickens with maternal-derived antibodies.

Although vaccines have been widely used for many years, they have failed to control H9N2 avian influenza virus (AIV) in the field in China. The high level of maternal-derived antibodies (MDAs) against H9N2 virus contributes to the H9N2 influenza vaccine failure in poultry. The study aimed to generate a new vaccine to overcome MDAs interference in H9N2 vaccination in chickens. We used turkey herpesvirus (HVT) as a vaccine vector to express H9 hemagglutinin (HA) proteins. The recombinant HVT expressing H9 HA proteins (rHVT-H9) was successfully generated and characterized in primary chicken embryonic fibroblasts (CEFs). Western blot and indirect immunofluorescence assay (IFA) showed that the rHVT-H9 consistently expressed HA proteins. In addition, the rHVT-H9 had similar growth kinetics to the parent HVT. Preliminary animal experiments showed that compared to the conventional inactivated whole virus (IWV) vaccine, the rHVT-H9 stimulated robust humoral immunity in chickens with passively transferred antibodies (PTAs) that were used to mimic MDAs. Transmission experiments showed that the rHVT-H9 induced both humoral and cellular immunity in chickens with PTAs. Furthermore, we used mathematical models to quantify the vaccine's efficacy in preventing the transmission of H9N2 AIV. The results showed that the rHVT-H9 reduced the virus shedding period and decreased the reproduction ratio (R) value in chickens with PTAs after homologous challenge. However, the vaccination in this trial did not yet bring R < 1. In summary, we generated a new rHVT-H9 vaccine, which stimulated strong humoral and cellular immunity, reducing virus shedding and transmission of H9N2 AIV even in the presence of PTAs in chickens.

A Multicenter Study Assessing Risk Factors and Aeroallergens Sensitization Characteristics in Children with Self-Reported Allergic Rhinitis in China.

BACKGROUND: Up to now, epidemiological studies on allergy rhinitis (AR) have primarily focused on determining the risk of disease in Chinese adults, with the majority of them designed by single centers, while cross-sectional and epidemiological data describing allergic sensitization in children with self-reported AR are scarce. OBJECTIVE: This study was estimating of the latest information about the sensitization patterns and risk factors of clinical AR to develop effective strategies for the prevention and treatment of AR. METHODS: We conducted a cross-sectional survey between January 2020 and June 2021 involving children from seven cities in China who reported AR. A total of 762 children participated in this survey. To evaluate the risk factors and specific sensitization patterns of clinical AR through questionnaires and specific immunoglobulin E to 11 aeroallergens. RESULTS: Of the 762 patients, 593 (77.8%) had at least one positive IgE level. Aged 7-14 years (OR 1.503, (95% CI 1.058-2.136), P = 0.023); With allergic conjunctivitis (OR 1.843, (95% CI 1.297-2.620), P = 0.001) and living in the Eastern (OR 1.802, (95% CI 1.263-2.573), P = 0.001) all elevated the risk of clinical AR associated with aeroallergens. The sensitization rates of D. pteronyssinus and D. farinae were higher than those of other allergens in the 0-6 and 7-14 years old age groups. The most common aeroallergens among self-reported children with AR in the eastern were D. farinae (74.9%) and D. pteronyssinus (74.3%), while in the western were mugwort (60.0%) and marguerite (56.6%). Majority of sIgE-positive subjects were sensitized to three or more of the tested pollen allergens in the Western (52.1%), compared with 5.7% in the Eastern. CONCLUSION: There was an apparent geographic variation in childhood allergies in China. Age factors also had strong impacts on the allergen sensitization rate of children, but these impacts differed across regions.

RBC-derived vesicles as a systemic delivery system of doxorubicin for lysosomal-mitochondrial axis-improved cancer therapy.

Introduction: Chemotherapeutic drugs are the main intervention for cancer management, but many drawbacks impede their clinical applications. Nanoparticles as drug delivery systems (DDSs) offer much promise to solve these limitations. Objectives: A novel nanocarrier composed of red blood cell (RBC)-derived vesicles (RDVs) surface-linked with doxorubicin (Dox) using glutaraldehyde (glu) to form Dox-gluRDVs was investigated for improved cancer therapy. Methods: We investigated the in vivo antineoplastic performance of Dox-gluRDVs through intravenous (i.v.) administration in the mouse model bearing subcutaneous (s.c.) B16F10 tumor and examined the in vitro antitumor mechanism and efficacy in a panel of cancer cell lines. Results: Dox-gluRDVs can exert superior anticancer activity than free Dox in vitro and in vivo. Distinct from free Dox that is mainly located in the nucleus, but instead Dox-gluRDVs release and efficiently deliver the majority of their conjugated Dox into lysosomes. In vitro mechanism study reveals the critical role of lysosomal Dox accumulation-mediated mitochondrial ROS overproduction followed by the mitochondrial membrane potential loss and the activation of apoptotic signaling for superior anticancer activity of Dox-gluRDVs. Conclusion: This work demonstrates the great potential of RDVs to serve a biological DDS of Dox for systemic administration to improve conventional cancer chemotherapeutics.

The legacy effects of PM2.5 depositon on Nerium Oleander L.

Green plants have the capability to retain atmospheric particulate matter (PM) on their leaves, which can effectively reduce PM pollution, especially in the urban settings. Some studies reported that the periodic PM pollution could change plant retaining PM capacity, which, indeed, was the reason of physiological responses. In advancing the previous studies, we selected Nerium oleander L. to measure PM retention on leaf surface in a controlled environment by the following periods: initial pollution period (S1), recovery period (R), and secondary pollution period (S2) for a total of 12 weeks. The experimental design was one elevated pollution treatment (166 µg m-3) and one ambient control (28 µg m-3) with three replications. Results showed that during S2, the total retention decreased by 8.87 µg cm-2, which was about 10.4% significant lower than in S1. During the third week, the ascorbic acid content (ASA) in S1 was 6.71 mg g-1 significantly lower than that in S2 in the treatment. The total chlorophyll (Chl T) of the treatment decreased continuously and significantly by 33.8% in S1, but showed no similar trend in S2. The net photosynthetic rate of the treatment was significantly lower than that of the control, and the plants in the treatment showed a consistently high dark respiration rate than that in the control. The correlations between PM retention and ASA, Chl T and RWC were weaker in S1 than that in S2. In addition, air pollution tolerance index (APTI) showed a significant decline in plant pollution tolerance in the treatment during the third week.

Associations of pre-pregnancy impaired fasting glucose and body mass index among pregnant women without pre-existing diabetes with offspring being large for gestational age and preterm birth: a cohort study in China.

INTRODUCTION: Associations of pre-pregnancy impaired fasting glucose (IFG) and body mass index (BMI) with large for gestational age (LGA) and preterm birth (PTB) have been poorly understood. We aimed to investigate the associations of maternal BMI, separately and together with pre-pregnancy IFG, with LGA and PTB in Chinese population. We also aimed to quantify these associations by maternal age. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study of women from the National Free Preconception Health Examination Project with singleton birth from 121 counties/districts in 21 cities of Guangdong Province, China, from January 1, 2013 to December 31, 2017. Women were included if they did not have pre-existing chronic diseases (diabetes, hypertension, etc). Participants were divided into eight groups according to their BMI (underweight (BMI <18.5 kg/m2), normal weight (18.5-23.9 kg/m2), overweight (24.0-27.9 kg/m2), and obesity (≥28.0 kg/m2)) and pre-pregnancy fasting glucose status (normoglycemia (fasting glucose concentration <6.1 mmol/L) and IFG (6.1-7.0 mmol/L)). Adjusted incidence risk ratios (aIRRs) and 95% CIs of LGA, severe LGA, PTB and early PTB were estimated. RESULTS: We included 634 030 women. The incidences of LGA, severe LGA, PTB and early PTB for the study population were 7.1%, 2.5%, 5.1% and 1.1%, respectively. Compared with normal weight mothers with normoglycemia, overweight and obese mothers irrespective of IFG had a higher risk of LGA (eg, obesity with IFG aIRR 1.85 (1.60-2.14)) and severe LGA (eg, obesity with IFG 2.19 (1.73-2.79)). The associations of BMI and pre-pregnancy fasting glucose status with LGA were similar found among women of all age groups. Underweight with normoglycemia had 6.0% higher risk of PTB (1.06 (1.03-1.09)) and 8.0% higher risk of early PTB (1.08 (1.02-1.17)), underweight with IFG had 14.0% higher risk of PTB (1.14 (1.02-1.27)), and obese mothers with IFG had 45.0% higher risk of PTB (1.45 (1.18-1.78)). The associations of BMI and pre-pregnancy fasting glucose status with PTB differed by maternal age. CONCLUSION: Overweight and obesity regardless of IFG were associated with an increased risk of LGA, and these associations were similarly observed among mothers of all age groups. Underweight regardless of IFG, and obesity with IFG were associated with an increased risk of PTB, but the associations differed by maternal age. Findings from this study may have implications for risk assessment and counselling before pregnancy.

CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration.

Tetraspanin CD9 is widely expressed on various cell types, such as cancer cells and mesenchymal stem cells (MSCs), and/or cell-released exosomes. It has been reported that exosomal CD9 plays an important role in intercellular communications involved in cancer cell migration and metastasis. However, reports on the effect of the CD9 of MSCs or MSC-derived exosomes on cancer cell migration are still lacking. In this study, using a transwell migration assay, we found that both dextran-coated iron oxide nanoparticles (dex-IO NPs) and ionomycin stimulated exosomal CD9 expression in human MSCs (hMSCs); however, hMSCs could not deliver them to melanoma cells to affect cell migration. Interestingly, a reduced migration of melanoma cell line was observed when the ionomycin-incubated hMSC-conditioned media but not dex-IO NP-labeled hMSC-conditioned media were in the bottom chamber. In addition, we found that dex-IO NPs decreased cellular CD9 expression in hMSCs but ionomycin increased this. Simultaneously, we found that ionomycin suppressed the expression and secretion of the chemokine CCL21 in hMSCs. The silencing of CD9 demonstrated an inhibitory role of cellular CD9 in CCL21 expression in hMSCs, suggesting that ionomycin could upregulate cellular CD9 to decrease CCL21 expression and secretion of hMSCs, which would reduce the migration of B16F10, A549 and U87MG cancer cell lines due to chemoattraction reduction of CCL21. The present study not only highlights the important role of bone marrow-derived hMSCs' CD9-mediated CCL21 regulation in cancer bone metastasis but also suggests a new distinct pharmaceutical strategy for prevention or/and therapy of cancer metastasis.

Association of maternal pre-pregnancy low or increased body mass index with adverse pregnancy outcomes.

This study investigated the association between pre-pregnancy body mass index (BMI) and adverse pregnancy outcomes among women participated in the National Free Preconception Health Examination Project in Guangdong Province, China, and explored these associations according to maternal age. Pre-pregnancy BMI was classified into underweight (BMI < 18.5 kg/m2), healthy weight (18.5-23.9 kg/m2), overweight (24.0-27.9 kg/m2), and obesity (≥ 28.0 kg/m2) according to Chinese criteria. Outcomes were preterm birth (PTB, delivery before 37 weeks of gestation), large for gestational age (LGA, birthweight above the 90th percentile for gestational age by infants' sex), small for gestational age (SGA, birthweight below the 10th percentile for gestational age by infants' sex), primary caesarean delivery, shoulder dystocia or birth injury, and stillbirth. Adjusted incidence risk ratios (aIRR) were calculated for underweight, overweight and obesity, respectively. Compared with healthy weight, underweight was associated with increased risk of PTB (aIRR 1.06, 95%CI 1.04-1.09) and SGA (1.23, 1.22-1.26) but inversely associated with LGA (0.83, 0.82-0.85), primary caesarean delivery (0.88, 0.87-0.90) and stillbirth (0.73, 0.53-0.99). Overweight was associated with increased risk of LGA (1.17, 1.14-1.19), primary caesarean delivery (1.18, 1.16-1.20) and stillbirth (1.44, 1.03-2.06), but inversely associated with SGA (0.92, 0.90-0.95) and shoulder dystocia or birth injury (0.86, 0.79-0.93). Obesity was associated with increased risk of PTB (1.12, 1.05-1.20), LGA (1.32, 1.27-1.37), primary caesarean delivery (1.45, 1.40-1.50), but inversely associated with SGA (0.92, 0.87-0.97). The aIRRs for underweight, overweight and obesity in relation to these adverse pregnancy outcomes ranged from 0.65 to 1.52 according to maternal age. In Chinese population, maternal pre-pregnancy BMI was significantly associated with the risk of adverse pregnancy outcomes and the risk differs according to maternal age. Further investigation is warranted to determine whether and how counselling and interventions for women with low or increased BMI before pregnancy can reduce the risk of adverse pregnancy outcomes.

Catalytic prior distributions with application to generalized linear models.

A catalytic prior distribution is designed to stabilize a high-dimensional "working model" by shrinking it toward a "simplified model." The shrinkage is achieved by supplementing the observed data with a small amount of "synthetic data" generated from a predictive distribution under the simpler model. We apply this framework to generalized linear models, where we propose various strategies for the specification of a tuning parameter governing the degree of shrinkage and study resultant theoretical properties. In simulations, the resulting posterior estimation using such a catalytic prior outperforms maximum likelihood estimation from the working model and is generally comparable with or superior to existing competitive methods in terms of frequentist prediction accuracy of point estimation and coverage accuracy of interval estimation. The catalytic priors have simple interpretations and are easy to formulate.

ZnO Nanoparticles Induced Caspase-Dependent Apoptosis in Gingival Squamous Cell Carcinoma through Mitochondrial Dysfunction and p70S6K Signaling Pathway.

Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in sunscreens, food additives, pigments, rubber manufacture, and electronic materials. Several studies have shown that ZnO-NPs inhibit cell growth and induce apoptosis by the production of oxidative stress in a variety of human cancer cells. However, the anti-cancer property and molecular mechanism of ZnO-NPs in human gingival squamous cell carcinoma (GSCC) are not fully understood. In this study, we found that ZnO-NPs induced growth inhibition of GSCC (Ca9-22 and OECM-1 cells), but no damage in human normal keratinocytes (HaCaT cells) and gingival fibroblasts (HGF-1 cells). ZnO-NPs caused apoptotic cell death of GSCC in a concentration-dependent manner by the quantitative assessment of oligonucleosomal DNA fragmentation. Flow cytometric analysis of cell cycle progression revealed that sub-G1 phase accumulation was dramatically induced by ZnO-NPs. In addition, ZnO-NPs increased the intracellular reactive oxygen species and specifically superoxide levels, and also decreased the mitochondrial membrane potential. ZnO-NPs further activated apoptotic cell death via the caspase cascades. Importantly, anti-oxidant and caspase inhibitor clearly prevented ZnO-NP-induced cell death, indicating the fact that superoxide-induced mitochondrial dysfunction is associated with the ZnO-NP-mediated caspase-dependent apoptosis in human GSCC. Moreover, ZnO-NPs significantly inhibited the phosphorylation of ribosomal protein S6 kinase (p70S6K kinase). In a corollary in vivo study, our results demonstrated that ZnO-NPs possessed an anti-cancer effect in a zebrafish xenograft model. Collectively, these results suggest that ZnO-NPs induce apoptosis through the mitochondrial oxidative damage and p70S6K signaling pathway in human GSCC. The present study may provide an experimental basis for ZnO-NPs to be considered as a promising novel anti­tumor agent for the treatment of gingival cancer.

The impact of maternal prepregnancy impaired fasting glucose on preterm birth and large for gestational age: a large population-based cohort study.

BACKGROUND: The impact of maternal prepregnancy impaired fasting glucose on preterm birth and large for gestational age has been poorly understood. OBJECTIVES: We aimed to estimate the impact of prepregnancy impaired fasting glucose defined by the World Health Organization cut point on the risk of preterm birth and large for gestational age and to investigate whether the World Health Organization cut point of impaired fasting glucose was appropriate for identifying women at risk of preterm birth and large for gestational age among the Chinese population. STUDY DESIGN: This was a retrospective cohort study of women from the National Free Preconception Health Examination Project with singleton birth from 121 counties/districts in 21 cities of Guangdong Province, China, from Jan. 1, 2013, to Dec. 31, 2017. Women were included if their prepregnancy fasting glucose was less than 7.0 mmol/L. The primary outcomes were preterm birth (gestational age <37 weeks), early preterm birth (gestational age <34 weeks), large for gestational age (birthweight by gestational age >90th percentile based on the international standards in the International Fetal and Newborn Growth Consortium for the 21st Century study), and severe large for gestational age (birthweight by gestational age >97th percentile). We calculated the adjusted risk ratio for impaired fasting glucose and a 1 standard deviation increase in fasting glucose. RESULTS: We included 640,469 women. Of these, 31,006 (4.84%) met the World Health Organization cut point for impaired fasting glucose, 32,640 (5.10%) had preterm birth and 7201 (1.12%) had early preterm birth, 45,532 (7.11%) had large for gestational age birth, and 16,231 (2.53%) had severe large for gestational age birth. Compared with women with normoglycaemia, women with prepregnancy impaired fasting glucose had a 7.0% higher risk of preterm birth (adjusted risk ratio, 1.07, 95% confidence interval, 1.02-1.12), 10.0% had a higher risk of large for gestational age (adjusted risk ratio, 1.10, 95% confidence interval, 1.06-1.14), and 17.0% had a higher risk of severe large for gestational age (adjusted risk ratio, 1.17, 95% confidence interval, 1.10-1.26). No significant association of prepregnancy impaired fasting glucose with early preterm birth was found. The association of prepregnancy impaired fasting glucose with preterm birth and large for gestational age were similar in subgroups of women with various baseline characteristics. Adjusted risk ratio for preterm birth per standard deviation fasting glucose (0.7 mmol/L) was 0.99 (95% confidence interval, 0.98-1.00), for early preterm birth an adjusted risk ratio of 0.99 (confidence interval, 0.97-1.02), for large for gestational age an adjusted risk ratio of 1.04 (confidence interval, 1.03-1.05), and for severe large for gestational age an adjusted risk ratio of 1.03 (confidence interval, 1.01-1.04). CONCLUSION: Our data suggest that maternal prepregnancy impaired fasting glucose increases the risk of preterm birth, large for gestational age, and severe large for gestational age. Data also suggest that the World Health Organization cut point of impaired fasting glucose is too restrictive, and lower levels of fasting glucose also increase the risk of large for gestational age and severe for severe gestational age in the Chinese population. Further investigation is warranted to determine whether and how counseling and interventions for women with prepregnancy impaired fasting glucose could reduce the risk of preterm birth and large for gestational age.