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Per- and polyfluoroalkyl substances (PFASs) can disrupt lipid metabolism, and changes in cord blood fatty acid composition have been observed in small newborns. Emerging evidence suggests that exposure to PFASs during pregnancy is linked to decreased newborn size, although the evidence is not consistent. The modifying effect of fatty acids on the associations of gestational PFAS exposure with newborn size is still unknown. Here we show that the nutritional status of the fetus, as indicated by the level of fatty acids in the cord blood, mitigates the adverse effects of gestational PFAS exposure on the size of the newborn. Our study confirms the adverse developmental effects of PFASs and identifies emerging short-chain PFASs as the primary drivers of reduced newborn size, despite their lower exposure burden compared to legacy PFASs. Additionally, we find the protective role of cord blood fatty acids, suggesting potential strategies for mitigating the detrimental effects of emerging environmental exposures on human health. Our findings provide new evidence of the potential toxicity of emerging PFASs and call for further toxicity evaluations of these pollutants for regulatory purposes. Future studies should consider the complex interaction between exposure and nutrition within the human body, particularly during the first thousand days of life, to promote lifelong health.

Human exposure to per- and polyfluoroalkyl substances (PFASs) has received considerable attention, particularly in pregnant women because of their dramatic changes in physiological status and dietary patterns. Predicting internal PFAS exposure in pregnant women, based on external and relevant parameters, has not been investigated. Here, machine learning (ML) models were developed to predict the serum concentrations of PFOA and PFOS in a large population of 588 pregnant participants. Dietary exposure characteristics, demographic parameters, and in particular, serum fatty acid (FA) data were used for the model development. The fitting results showed that the inclusion of FAs as covariates significantly improved the performance of the ML models, with the random forest (RF) model having the best predictive performance for PFOA (R2 = 0.33, MAE = 1.51 ng/mL, and RMSE = 1.89 ng/mL) and PFOS (R2 = 0.12, MAE = 2.65 ng/mL, and RMSE = 3.37 ng/mL). The feature importance analysis revealed that serum FAs greatly affected PFOA concentration in the pregnant women, with saturated FAs being associated with decreased PFOA levels and unsaturated FAs with increased levels. Comparison with one-compartment pharmacokinetic model further demonstrated the advantage of the ML models in predicting PFAS exposure in pregnant women. Our models correlate for the first time blood chemical concentrations with human FA status using ML, introducing a novel perspective on predicting PFAS levels in pregnant women. This study provides valuable insights concerning internal exposure of PFASs generated from external exposure, and contributes to risk assessment and management in pregnant populations.

Under international advocacy for a low-carbon and healthy lifestyle, ambient PM2.5 pollution poses a dilemma for urban residents who wish to engage in outdoor exercise and adopt active low-carbon commuting. In this study, an Urban Air Health Navigation System (UAHNS) was designed and proposed to assist users by recommending routes with the least PM2.5 exposure and dynamically issuing early risk warnings based on topologized digital maps, an application programming interface (API), an eXtreme Gradient Boosting (XGBoost) model, and two-step spatial interpolation. A test of the UAHNS’s functions and applications was carried out in Wuhan city. The results showed that, compared with trained random forest (RF), LightGBM, Adaboost models, etc., the XGBoost model performed better, with an R2 exceeding 0.90 and an RMSE of approximately 15.74 μg/m3, based on data from national air and meteorological monitoring stations. Further, the two-step spatial interpolation model was adopted to dynamically generate pollution distribution at a spatial resolution of 300 m*300 m. Then, an exposure comparison was performed under randomly selected commuting routes and times in Wuhan, showing the recommended routes for lower PM2.5 exposure made effectively help. And the route difference ratios of about 14.9 % and 16.9 % for riding and walking, respectively. Finally, the UAHNS platform was integrally realized for Wuhan, consisting of a real-time PM2.5 query, a one-hour PM2.5 prediction function at any location, health navigation on city map, and a personalized health information query.

The contamination of water by arsenic (As) has emerged as a significant environmental concern due to its well-documented toxicity. Environmentally relevant concentrations of As have been reported to pose a considerable threat to fish. However, previous studies mainly focused on the impacts of As at environmentally relevant concentrations on adult fish, and limited information is available regarding its impacts on fish at early life stage. In this study, zebrafish embryos were employed to evaluate the environmental risks following exposure to different concentrations (0, 25, 50, 75 and 150 μg/L) of pentavalent arsenate (AsV) for 120 hours post fertilization. Our findings indicated that concentrations ≤ 150 μg/L AsV did not exert significant effects on survival or aberration; however, it conspicuously inhibited heart rate of zebrafish larvae. Furthermore, exposure to AsV significantly disrupted mRNA transcription of genes associated with cardiac development, and elongated the distance between the sinus venosus and bulbus arteriosus at 75 μg/L and 150 μg/L treatments. Additionally, AsV exposure enhanced superoxide dismutase (SOD) activity at 50, 75 and 150 μg/L treatments, and increased mRNA transcriptional levels of Cu/ZnSOD and MnSOD at 75 and 150 μg/L treatments. Concurrently, AsV suppressed metallothionein1 (MT1) and MT2 mRNA transcriptions while elevating heat shock protein70 mRNA transcription levels in zebrafish larvae resulting in elevated malondialdehyde (MDA) levels. These findings provide novel insights into the toxic effects exerted by low concentrations of AsV on fish at early life stage, thereby contributing to an exploration into the environmental risks associated with environmentally relevant concentrations.

Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (β = −0.18, 95%CI: −0.29 – −0.07, P = 0.002) and progressive motility (β = −0.27, 95%CI: −0.43 – −0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: β = 0.26, 95%CI: 0.01 – −0.51, Pinteraction = 0.047; progressive motility: β = 0.64, 95%CI: 0.23 – 1.05, Pinteraction = 0.003). Co-exposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.

Berberine has growth-promoting and lipid-lowering effects potentially through the regulation of intestinal microbiota and bile acid profiles. This experiment aimed to investigate the effect of dietary berberine on the intestinal microbiota-bile acid-farnesoid X receptor (FXR) axis in yellow catfish (Pelteobagrus fulvidraco). Fish (initial weight: 1.32 ± 0.26 g) were fed a control diet or a diet supplemented with 100 mg/kg (BBR100) or 400 mg/kg berberine (BBR400) for 60 days. The BBR400 group showed significant improvements in growth performance, hepatic antioxidant enzyme activities, intestinal lysozyme activity, cholic acid, ethylchenodeoxycholic acid, and hydroguinone carboxylic acid contents, along with significantly lower intestinal immunoglobulin M, complement 3, complement 4, serum total cholesterol (TCH), and triglyceride (TG) contents, compared to the control group (P

This experiment aimed to investigate the protective effects of berberine on copper-induced liver and gill toxicities in freshwater grouper (Acrossocheilus fasciatus). Fish (initial weight 1.56 ± 0.10 g) were randomly distributed into 12 tanks (80 L, 20 fish per tank) and divided into four experimental groups: The control group, exposed to 0.02 mg/L Cu2+ (Cu group), exposed to 0.02 mg/L Cu2+ and fed 100 mg/kg berberine (BBR100 group), and exposed to 0.02 mg/L Cu2+ and fed 400 mg/kg berberine (BBR400 group). After a 30-day experiment, the results showed that berberine significantly increased the activities of catalase and glutathione peroxidase in the liver, gills, and serum inhibited by Cu2+ exposure (P

Corydalis bungeana Turcz. (CBT) is frequently used to treat inflammatory illnesses, the mechanisms underlying its use to ulcerative colitis (UC) remain unclear. A dextran sulfate sodium (DSS)-induced UC mice model was established. The disease activity index (DAI), colonic length, histological inspection by hematoxylin-eosin staining, the cytokines levels in the colon, proteomics and intestinal flora in mice were investigated to evaluate the effect of CBT. The results showed that CBT can significantly reduce the DAI, increase the length of colon, improve the pathological injury of colon tissue, decrease the level of TNF-α, IL-6, IL-1β and increase the level of IL-10 in UC mice. Gut microbe sequencing showed that CBT could enhance the abundance of the intestinal microbiome, decrease possibly harmful bacteria and promote potentially helpful microbes. Proteomics investigation showed that 20 overlapping differentially expressed proteins (DEPs) were discovered in the control, model, and CBT administration groups. The DEPs in the CBT administration group were connected to biological procedures mainly involving detoxification. Extracellular matrix (ECM) receptor-associated proteins such as Col6a1 and CD36 may be important targets for CBT treatment of UC. Overall, this integrated methodology identified a comprehensive multi-omics network, composed of a certain set of gut microbiota and proteins, which may be potential targets for CBT treatment with UC.

Background: Using epigenetic markers and fragmentomics of cell-free DNA for cancer detection has been proven applicable. Methods: We further investigated the diagnostic potential of combining two features (epigenetic markers and fragmentomic information) of cell-free DNA for detecting various types of cancers. To do this, we extracted cfDNA fragmentomic features from 191 whole-genome sequencing data and studied them in 396 low-pass 5hmC sequencing data, which included four common cancer types and control samples. Results: In our analysis of 5hmC sequencing data from cancer samples, we observed aberrant ultra-long fragments (220–500 bp) that differed from normal samples in terms of both size and coverage profile. These fragments played a significant role in predicting cancer. Leveraging the ability to detect cfDNA hydroxymethylation and fragmentomic markers simultaneously in low-pass 5hmC sequencing data, we developed an integrated model that incorporated 63 features representing both fragmentomic features and hydroxymethylation signatures. This model achieved high sensitivity and specificity for pan-cancer detection (88.52% and 82.35%, respectively). Conclusion: We showed that fragmentomic information in 5hmC sequencing data is an ideal marker for cancer detection and that it shows high performance in low-pass sequencing data.

Perfluorohexyl sulfonate (PFHxS) is the third most abundant per- and polyfluoroalkyl substances and its developmental toxicity remains very poorly understood. Here, pregnant mice exposed to PFHxS at human relevant dose showed increased fetal death incidence in the high-dose PFHxS-H group (P

Chinese cities contributes a large amount of CO2 emissions. Reducing CO2 emissions through urban governance is an important issue. Despite the increasing attention paid on the CO2 emission prediction, few studies consider the collective and complex influence of governance element system. To predict and regulate CO2 emissions through comprehensive urban governance elements, this paper use the random forest model through the data from 1903 Chinese county-level cities in 2010, 2012 and 2015, and establish a CO2 forecasting platform based on the effects of urban governance elements. The results are as follows: (1) The municipal utility facilities element, the economic development & industrial structure element, and the city size &structure and road traffic facilities elements are crucial for residential, industrial and transportation CO2 emissions, respectively; (2) Governance elements have nonlinear relationship with CO2 emissions and most of the relations present obvious threshold effects; (3) Random forest can be used to predict CO2 emissions more accurately than can other predictive models. These findings can be used to conducts the CO2 scenario simulation and help government formulate active governance measurements.

Objectives: To explore the relationship between acceptance of illness and quality of life (QOL), and factors associated with acceptance of illness among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). Methods: Three hundred and one MSM were recruited from an HIV clinic between August and December 2018. The battery of measurements consisted of the Acceptance of Illness Scale, World Health Organization Quality of Life Questionnaire for HIV brief version, HIV Cognitive Appraisal Scale and a self-designed questionnaire used to collect general information. Pearson correlation test was used to examine the relationship between acceptance of illness and QOL. Univariate and multivariate ordinal logistic regression analyses were used to examine whether the general data (demographic and HIV-related clinical data) and HIV cognitive appraisal were associated with acceptance of illness levels. Results: Descriptive analysis showed the acceptance level among MSM living with HIV was moderate (Mean = 26.29, SD = 5.28). Those with a better acceptance of illness had a better QOL (r = 0.69, P

Nanomaterials have been used in improving the performance of construction materials due to their compacting micro-structure effect and accelerating cement hydration reaction. Considering the brittle characteristic of fiber reinforced polymer (termed as FRP) tube encased concrete and inferior properties of recycled concrete, nanoparticles were used in FRP tube encased recycled aggregate concrete. The axial compressive performance of FRP tube used in recycled concrete treated with nanoparticles strengthening, termed as FRP-NPRC, were investigated by axial compression experiments and theoretical analysis. Five experimental variables were considered including (1) the dosages and (2) varieties of nanoparticles (i.e. 1% and 2% of nanoSiO2, 1% and 2% of nanoCaCO3), (3) replacement ratios of recycled coarse aggregates (termed as RCAs) (0%, 50%, 70% and 100%) the RCAs were mainly produced from the waste cracked bricks, (4) the number of glass FRP (GFRP) tube layers (2, 4 and 6-layer) and (5) the mixing methods of concrete. Results indicate that the combination of FRP confinement and nanoparticle modification in recycled concrete exhibited up to 76.2% increase in compressive strength and 7.62 times ductility improvement. Furthermore, a design-oriented stress–strain model on the basis of the ultimate condition analysis were executed to evaluate the stress–strain property of this strengthened component.

Background: Sleep quality and the associated factors in professional nurses have been extensively investigated. However, as an important part of the workforce in hospitals, sleep quality and influencing factors among in-hospital nursing assistants is rarely investigated. Aim: This study aimed to assess the sleep quality and the associated factors of in-hospital nursing assistants in general hospital. Methods: A cross-sectional survey study was conducted in a tertiary general hospital. Data were collected from 187 in-hospital nursing assistants using convenience sampling from June to July 2018. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate participants’ sleep quality. A multiple linear regression was performed to identify associated factors with sleep quality. Results: This study revealed a mean PSQI score of 5.96 ± 3.64 among all participants, of which 62.3% (114/187) participants suffered from impaired sleep quality. In-hospital nursing assistants with significant medical condition, low monthly income, irregular diet and high family burden reported more worse sleep quality. Conclusion: The study showed that poor sleep quality is a highly prevalent issue among Chinese in-hospital nursing assistants in general hospital. Measures to enhance nursing assistants’ wellbeing status (health and burden) and improve their salary (monthly income) are recommended.

Transport properties of liquid are the necessary data for thermodynamic cycle design and optimization, and most of them could be measured by experiments. Molecular dynamic simulation provides an effective way to predict these transport properties in some limited condition that cannot be measured experimentally. In this work, NEMD (nonequilibrium molecular dynamics) method has been applied to calculate the thermal conductivity and RNEMD (reverse nonequilibrium molecular dynamics) method has been used to calculate the viscosity of alcohols. The calculated results are in good agreement with experimental values. The results prove the feasibility of the two simulation methods and provide a new way to calculate the thermal conductivity and viscosity of other organic liquids in some limited conditions.

Objectives: Although effective antiretroviral therapy (ART) has been used for more than two decades, HIV-associated neurocognitive disorder remains prevalent. Thus, whether ART can improve neurocognitive impairment is controversial. This review aims to explore the effects of ART on cognitive impairment in people living with HIV (PLWH). Methods: A systematic literature search was conducted in eight databases (PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, China Biology Medicine disc, and WanFang) to identify studies that compare cognitive function between study groups who are administered and not administered ART. We searched for articles published up to April 2019. Article evaluation and data extraction were independently conducted by two reviewers. Results: Sixteen articles (6,694 participants)—14 cross-sectional studies and 2 cohort studies—were included in this meta-analysis. The cross-sectional studies demonstrated that ART group did not perform better than the non-ART group (OR = 1.16; 95% CI, 1.03–1.30). However, the cohort studies reported a significant improvement in cognitive function at three months (OR = 4.01; 95% CI, 2.35–6.85) and six months (OR = 9.24; 95% CI, 1.71–49.96) after ART initiation compared with the baseline data. No significant cognitive improvement was found in participants younger than 55 years old, but the two cross-sectional studies showed that ART may improve cognitive function in PLWH under 65 years old with poor physical condition and immune status. Conclusions: ART could improve cognitive function in PLWH with poor physical condition and immune status, but it does not considerably improve cognition in the entire PLWH population.

Recently, biodiesel is considered as a biodegradable, renewable and high-potential fuel which could be used directly in tradition internal combustion engines. Fuel’ transport properties in high pressure are required to model the process of fuel spray, atomization and combustion accurately. This work, three ethyl esters’ liquid thermal conductivity (biodiesel compounds) in the liquid phase was measured by an experiment system which is established based on a transient hot-wire method with a bare platinum hot wire. The measurements were conducted at the temperatures ranging from 292 K to 372 K and pressure up to 15 MPa. The combined expanded uncertainty of the measurement was estimated to be ±2.0% (in the 0.95 confidence level). For interpolation, the relationship between measured results with temperature and pressure were correlated as a polynomial function, and the maximum deviation of correlations were less than 0.30%.

In this study, a flexible polymer (polysiloxane) containing SiOSi molecular chains and epoxy groups (EPSE) was prepared. The effect of EPSE on the cryogenic mechanical properties of epoxy matrix and carbon fiber (CF) reinforced epoxy composite laminate was investigated in detail. At RT, with an EPSE content of 8 wt%, the failure strain and fracture toughness KIC value of epoxy resin was improved by 69.4% and 10.4%, respectively. At cryogenic temperature, the tensile strength, failure strain and KIC value of EPSE-epoxy reached a maximum of 207 MPa, 3.13%, and 2.60 MPa·m1/2, respectively. Micro-morphology of the fracture surface indicated that the incorporation of EPSE improved the resistance to crack growth. The flexural strength of CF/EPSE-epoxy laminate at 77 K was 17.2% higher than that of CF/neat epoxy laminate, which mainly attributed to the flexible SiOSi molecular chains in EPSE reducing the CF/matrix interface thermal stress. The transition of failure mode resulted in the jagged-shape load fluctuations in the load-displacement curves of laminates at 77 K. Thermal cycling affecting the flexural strength of CF/EPSE-epoxy laminate was mainly ascribed to the release of part of thermal residual stress and the formation of interface debonding.

Studies have begun to emerge showing the protumor effects of tumor-associated neutrophils (TANs) in tumorigenesis, which may involve dysfunction of NK cells. However, the mechanism through which these rebellious neutrophils modulate NK cell immunity in tumor-bearing state remains unclear. In the present study, we demonstrate that neutrophils can impair the cytotoxicity and infiltration capability of NK cells, and downregulate CCR1 resulting in the weakened infiltration capability of NK cells. Moreover, neutrophils can decrease the responsiveness of NK-activating receptors, NKp46 and NKG2D. Mechanistically, enhanced PD-L1 on neutrophils and PD-1 on NK cells, and subsequent PD-L1/PD-1 interactions were the main mechanisms determining the suppression of neutrophils in NK cell immunity. G-CSF/STAT3 pathway was responsible for PD-L1 upregulation on neutrophils, while IL-18 was essential for PD-1 enhancement on NK cells. The crosstalk between neutrophils and NK cells was cell-cell interaction-dependent. These findings suggest that neutrophils can suppress the antitumor immunity of NK cells in tumor-bearing status through the PD-L1/PD-1 axis, highlighting the importance of PD-L1/PD-1 in the inhibitory effect of neutrophils on NK cells. Targeting G-CSF/STAT3 and IL-18 signaling pathway may be potential strategies to inhibit residual tumor in tumor therapy.

Purpose: This study was designed to compare the clinical efficacy of “8” and “0” wire fixation systems combined with double-head cannulated compression screws or Kirschner wires for the treatment of transverse patellar fractures. Methods: From September 2011 to September 2018, patients with closed transverse patellar fractures treated with a double-head compression screw or Kirschner wire were included and analyzed retrospectively. Patients with patellar fractures combined with distal femoral fractures, tibial plateau fracture or preoperative lower limb dysfunction were excluded. The patients treated with the “8” tension band wire fixation system and Kirschner wire were taken as Group A; those treated with the “0” fixation system and Kirschner wire were taken as Group B; those treated with the “8” fixation system and double-head cannulated compression screw were taken as group C; and those treated with the “0” fixation system and double-head cannulated compression screw were taken as group D. Six weeks and one year after the operation and every month from the third month after the operation until the fractures healed, an X-ray examination was performed to identify fracture healing. The time of fracture healing and postoperative complications of the four groups were compared. One year after the operation, knee function was evaluated by Bostman’s score. Results: During the study period, 168 patients with patellar fractures were treated by operations, and 88 patients were excluded because the fracture type did not meet the requirements or because there were combined fractures of the distal femur or tibial plateau. As a result, 80 patients were included in this study, 20 in each group. All the patients were followed up for an average period of 12.2 months. Compared with Group A, patients in Group D presented less postoperative discomfort in the prepatellar region, quicker fracture healing, less fixation failure and better postoperative knee function scores (all p < 0.05). The incidence of internal fixation failure in Group (B+D) was lower than that in Group (A+C) (p > 0.05). Conclusion: The “0” wire fixation system combined with a double-head cannulated compression screw seems to be more beneficial than the other three fixation systems for the treatment of transverse patellar fractures.

Solving high-temperature plastic mulching film-induced leaf burning in the first week during tobacco cultivation would take much time and effort. In the present study, the growth as well as the leaf sugar and nicotine contents of seedlings with or without leaf burning induced by high-temperature plastic mulching film were tested at two independent sites in 2015 and 2016 to identify the influence of leaf burning on seedling growth. The results showed that the growth of seedlings with leaf burning was improved with increased leaf area, leaf number and plant height compared to those without leaf burning, combined with an increased seedling survival rate at two sites in two years. In seedlings with leaf burning, the contents of fructose and glucose increased and peaked at 11:00 and 13:00 in the leaf and root, respectively, with an increased root nicotine content beginning at 13:00, highlighting the signalling role of sugars. Activities of antioxidant enzymes including peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) were all increased in seedlings with leaf burning. More plant biomass was allocated to roots in seedlings with leaf burning with increased root volume compared to control seedlings, which might facilitate the absorption of water and nutrients from the soil. Our findings demonstrate that high-temperature plastic mulching film-induced leaf burning not inhibited but benefited seedling survival and growth, suggesting that the time and labour-consuming manual plucking of burnt leaves can be avoided during tobacco cultivation.

MicroRNAs (miRNAs) are ~21 nucleotide (nt), endogenous RNAs that regulate gene expression in plants. Increasing evidence suggests that miRNAs play an important role in species-specific development in plants. However, the detailed miRNA profile divergence has not been performed among tomato species. In this study, the small RNA (sRNA) profiles of Solanum lycopersicum cultivar 9706 and Solanum habrochaites species PI 134417 were obtained by deep sequencing. Sixty-three known miRNA families were identified from these two species, of which 39 were common. Further miRNA profile comparison showed that 24 known non-conserved miRNA families were species-specific between these two tomato species. In addition, six conserved miRNA families displayed an apparent divergent expression pattern between the two tomato species. Our results suggested that species-specific, non-conserved miRNAs and divergent expression of conserved miRNAs might contribute to developmental changes and phenotypic variation between the two tomato species. Twenty new miRNAs were also identified in S. lycopersicum. This research significantly increases the number of known miRNA families in tomato and provides the first set of small RNAs in S. habrochaites. It also suggests that miRNAs have an important role in species-specific plant developmental regulation.

In order to determine the potential for haploid induction via in vitro gynogenesis in tomato, the ovules and protoplasts of embryo sacs from the hybrids Zhongza 101 and Zhongza 105 were cultured. An efficient method of ovule isolation was established in this study. Using this method, 100-150 ovules could be isolated from one ovary. Isolated ovules were cultured on three induction media to induce gynogenesis in vitro. During culture, ovules were enlarged markedly, with opaque white color. When observed microscopically, there were cell divisions and cell clumps in embryo sacs. Subsequently, the cell clumps in embryo sacs ceased growth, likely because the integument grew faster than embryo sacs did and hindered the further development of embryo sacs. Therefore, subsequent callus morphogenesis might be originated from the integument. Thousands of calli from the two tomato varieties were obtained. Five diploid plants were regenerated after 15 months of subculturing. To eliminate the hindering effect of integument on embryo sac cells, the protoplasts of embryo sacs were prepared and cultured. After 48 hours of culture, the protoplasts of embryo sacs doubled in size and gradually formed clusters of cells. These results suggested that gynogenesis might be a potential way for haploid induction in tomato.

Panaxadiol is a triterpenoid sapogenin monomeric compound found in the roots of Panax ginseng and has a variety of biological activities such as neuroprotective and anti-tumour functions. However, the mechanisms how panaxadiol exerts the anticancer effects remain unknown. The current study aimed to investigate the potential activity of panaxadiol on programmed cell death-ligand 1 (PD-L1) expression and tumour proliferation in human colon cancer cells and to identify the underlying mechanism. Results showed that panaxadiol showed little cytotoxicity as assessed by a cytotoxicity assay and significantly inhibited PD-L1 expression at the protein and mRNA level in a dose-dependent manner. Furthermore, panaxadiol supressed the hypoxia-induced synthesis of hypoxia-inducible factor (HIF)-1α via the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways without affecting HIF-1α degradation. Simultaneously, panaxadiol inhibited STAT3 activation through the JAK1, JAK2, and Src pathways. Moreover, pre-treatment with panaxadiol enhanced the activity of cytotoxic T lymphocytes (CTL) and regained their capacity of tumour cell killing in a T cell and tumour cell co-culture system. Immunoprecipitation showed that panaxadiol inhibited PD-L1 expression by blocking the interaction between HIF-1α and STAT3. The inhibitory effect of panaxadiol on tumour proliferation was further demonstrated by colony formation and EdU labelling assays. The anti-proliferative effect of panaxadiol was also proved by a xenograft assay in vivo. Taken together, the current work highlights the anti-tumour effect of panaxadiol, providing insights into development of cancer therapeutic through PD-L1 inhibition., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)