Recent advances in the development of Rho kinase inhibitors (2015-2021).

Rho-associated coiled-coil kinases (ROCKs) are key downstream effectors of small GTPases. ROCK plays a central role in diverse cellular events with accumulating evidence supporting the concept that ROCK is important in tumor development and progression. Numerous ROCK inhibitors have been investigated for their therapeutic potential in the treatment of cancers. In this article, we review recent research progress on ROCK inhibitors, especially those with potential for the treatment of cancers, reported in the literature from 2015 to 2021. Most ROCK inhibitors show potent in vitro and in vivo antitumor activities and have potential in the treatment of cancers.

First Evidence of the Bioaccumulation and Trophic Transfer of Tire Additives and Their Transformation Products in an Estuarine Food Web.

The discovery of the significant lethal impacts of the tire additive transformation product N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) on coho salmon has garnered global attention. However, the bioaccumulation and trophic transfer of tire additives and their transformation products (TATPs) within food webs remain obscure. This study first characterized the levels and compositions of 15 TATPs in the Pearl River Estuary, estimated their bioaccumulation and trophic transfer potential in 21 estuarine species, and identified priority contaminants. Our observations indicated that TATPs were prevalent in the estuarine environment. Eight, six, seven, and 10 TATPs were first quantified in the shrimp, sea cucumber, snail, and fish samples, with total mean levels of 45, 56, 64, and 67 ng/g (wet weight), respectively. N,N'-Diphenyl-p-phenylenediamine (DPPD) and N,N'-bis(2-methylphenyl)-1,4-benzenediamine (DTPD) exhibited high bioaccumulation. Significant biodilution was only identified for benzothiazole, while DPPD and DTPD displayed biomagnification trends based on Monte Carlo simulations. The mechanisms of bioaccumulation and trophodynamics of TATPs could be explained by their chemical hydrophobicity, molecular mass, and metabolic rates. Based on a multicriteria scoring technique, DPPD, DTPD, and 6PPD-Q were characterized as priority contaminants. This work emphasizes the importance of biomonitoring, particularly for specific hydrophobic tire additives.

Bioaccumulation and Trophic Transfer of Organophosphate Flame Retardants and Their Metabolites in the Estuarine Food Web of the Pearl River, China.

The accumulation and trophodynamics of organophosphate flame retardants (OPFRs) and their metabolites were investigated in the estuarine food web of the Pearl River, China. The mean ∑OPFR concentration among the investigated species increased in the following order: fish [431 ± 346 ng/g lipid weight (lw)] < snail (1310 ± 621 ng/g lw) < shrimp (1581 ± 1134 ng/g lw) < crab (1744 ± 1397 ng/g lw). The di-alkyl phosphates (DAPs) of di-(n-butyl) phosphate (DNBP), bis(2-butoxyethyl) phosphate (BBOEP), and diphenyl phosphate (DPHP) were the most abundant metabolites, with concentrations same as or even higher than their corresponding parent compounds. The log bioaccumulation factors for most OPFRs were lower than 3.70, and significant biomagnification was only found for trisphenyl phosphate [TPHP, with the trophic magnification factors (TMFs) > 1]. The TMFs of OPFRs, except for TPHP and tributyl phosphate had a positive correlation with lipophilicity (log KOW, p ≤ 0.05) and a negative correlation with the biotransformation rate (log KM, p ≤ 0.05). The mean TMF > 1 was observed for all of the OPFR metabolites based on the bootstrap regression method. The "pseudo-biomagnification" of OPFR metabolites might be attributed to the biotransformation of OPFRs in organisms at high trophic levels.

Brand-Specific Toxicity of Tire Tread Particles Helps Identify the Determinants of Toxicity.

The widespread occurrence of tire tread particles (TPs) has aroused increasing concerns over their impacts. However, how they affect the soil fauna remains poorly understood. Here, based on systematically assessing the toxicity of TPs on soil model speciesEnchytraeus crypticusat environmentally relevant concentrations through both soil and food exposure routes, we reported that TPs affected gut microbiota, intestinal histopathology, and metabolites of the worms both through particulate- and leachate-induced effects, while TP leachates exerted stronger effects. The dominant role of TP leachates in TP toxicity was further explained by the findings that worms did not ingest TPs with a particle size of over 150 µm and actively avoided consuming TP particles. Moreover, by comparing the effects of different brands of TPs as well as new and aged TPs, we demonstrated that it was mainly TP leachates that resulted in the ubiquity of the disturbance in the worm's gut microbiota among different brands of TPs. Notably, the large variations in leachate compositions among different brands of TPs provided us a unique opportunity to identify the determinants of TP toxicity. These results provide novel insights into the toxicity of TPs to soil fauna and a reference for toxicity reduction of tires.

Role of Gastrointestinal Microbiota from Crucian Carp in Microbial Transformation and Estrogenicity Modification of Novel Plastic Additives.

Ingestion is a major exposure route for hydrophobic organic pollutants in fish, but the microbial transformation and estrogenic modification of the novel plastic additives by the gut microbiota of fish remain obscure. Using an in vitro approach, we provide evidence that structure-related transformation of various plastic additives by the gastric and intestinal (GI) microbiota from crucian carp, with the degradation ratio of bisphenols and triphenyl phosphate faster than those of brominated compounds. The degradation kinetics for these pollutants could be limited by oxygen and cometabolic substrates (i.e., glucose). The fish GI microbiota could utilize the vast majority of carbon sources in a Biolog EcoPlate, suggesting their high metabolic potential and ability to transform various organic compounds. Unique microorganisms associated with transformation of the plastic additives including genera of Citrobacter, Klebsiella, and some unclassified genera in Enterobacteriaceae were identified by combining high-throughput genetic analyses and metagenomic analyses. Through identification of anaerobic transformation products by high-resolution mass spectrometry, alkyl-cleavage was found the common transformation mechanism, and hydrolysis was the major pathway for ester-containing pollutants. After anaerobic incubation, the estrogenic activities of triphenyl phosphate and bisphenols A, F, and AF declined, whereas that of bisphenol AP increased.

Knockdown of NF-κB activating protein promotes pancreatic cancer growth and metastasis through mTOR signaling pathway.

BACKGROUND: NF-κB activating protein (NKAP) acts as a transcriptional suppressor in the Notch signaling pathway, It plays a role in hematopoiesis maintenance, immune cell development, maturation, and functional competency acquisition. NKAP has been found to act as an oncogene in many tumors, but it has not been reported in PAAD.The purpose of this study was to investigate the effect of NKAP on the growth and metastasis of pancreatic adenocarcinoma(PAAD). METHODS AND RESULTS: In this study, western blot and qRT-PCR showed that highly expressed NKAP was found in PAAD cell lines, and small interfering RNA (siRNA) was employed to reduce the expression of NKAP in PAAD cell lines. The results of CCK-8, clony formation, Transwell and flow cytometry showed that knockdown of NKAP significantly inhibited biological function of PAAD cells, and increased cell apoptosis. Study also observed that knockdown of NKAP inhibited the expression levels of apoptosis proteins and cyclin in PAAD cells. In addition, mTOR's degree of phosphorylation and the expression of its downstream target p70S6K can both be activated by NKAP. This effect was also confirmed in salvage experiments performed with Rapamycin(RaPa), an inhibitor of mTOR. At the end of the experiment, It was investigated how NKAP affected the drug sensitivity of gemcitabine used to treat PAAD. The results showed that knocking down NKAP could increase the drug sensitivity of gemcitabine. CONCLUSIONS: NKAP as an oncogene regulates the development of PAAD cells. The research found that the mTOR signaling pathway is engaged in the oncogenic role of NKAP in PAAD for the first time.

Effect of levothyroxine treatment on fetal growth among women with mild subclinical hypothyroidism and thyroid peroxidase antibody negative: a cohort study.

BACKGROUND: Some clinicians used levothyroxine (LT4) treatment for mild subclinical hypothyroidism (SCH) pregnant women (2.5 < thyroid-stimulating hormone (TSH) ≤ the pregnancy-specific reference range with normal free thyroxine (FT4) level) with thyroid peroxidase antibody negative (TPOAb-), although the recent clinical guideline did not recommend it. It is unknown whether LT4 treatment for pregnant women with mild SCH and TPOAb- have impact on fetal growth. Therefore, the aim of the study was to investigate the effect of LT4 treatment on fetal growth and birth weight among mild SCH pregnant women with TPOAb-. METHODS: This was a birth cohort study including 14,609 pregnant women between 2016 and 2019 in Tongzhou Maternal and Child Health Hospital of Beijing, China. Pregnant women were divided into 3 groups as follows: Euthyroid (n = 14,285, 0.03 ≤ TSH ≤ 2.5mIU/L, normal FT4), TPOAb-; Untreated mild SCH with TPOAb- (n = 248, 2.5 < TSH ≤ 2.9mIU/L, normal FT4, without LT4 treatment); Treated mild SCH with TPOAb- (n = 76, 2.5 < TSH ≤ 2.9mIU/L, normal FT4, with LT4 treatment). The main outcome measures were Z-scores of fetal growth indicators (abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), head circumference (HC), estimated fetal weight (EFW)), fetal growth restriction (FGR) and birth weight. RESULTS: There was no difference in fetal growth indicators and birth weight between the untreated mild SCH women with TPOAb- and the euthyroid pregnant women. But the HC Z-score was lower in the LT4 treated mild SCH women with TPOAb-, compared with the euthyroid pregnant women (ß = -0.223, 95%CI: -0.422, -0.023). The LT4 treated mild SCH women with TPOAb- had lower fetal HC Z-score (ß = -0.236, 95%CI: -0.457, -0.015), compared with the untreated mild SCH women with TPOAb-. CONCLUSIONS: We observed that LT4 treatment for mild SCH with TPOAb- was associated with decreased fetal HC, which was not observed for untreated mild SCH women with TPOAb-. The adverse effect of LT4 treatment for mild SCH with TPOAb- provided new evidence for the recent clinical guideline.

Bidirectional spillover between maladaptive parenting and peer victimization and the mediating roles of internalizing and externalizing problems: A within-person analysis among Chinese early adolescents.

Parenting practices and relationships with peers are crucial aspects of youth socialization. Although theoretically expected reciprocal associations between changes in maladaptive parenting and adolescent peer victimization exist, there is a lack of studies that examine this link and address the mediating mechanisms at the within-person level. This longitudinal study examined reciprocal relations between peer victimization and two types of maladaptive parenting including harsh punishment and psychological control, and the potential mediating roles of internalizing and externalizing problems within these relations, by disentangling between- and within-person effects. A total of 4,731 Chinese early adolescents (44.9% girls; M age = 10.91 years, SD = 0.72) participated in a four-wave longitudinal study with 6-month intervals. The results of random intercept cross-lagged panel modeling showed: (a) harsh punishment did not directly predict peer victimization, and vice versa; (b) psychological control directly predicted peer victimization, and vice versa; (c) psychological control indirectly predicted peer victimization via internalizing problems, and peer victimization also indirectly predicted psychological control via internalizing problems. These findings provide evidence of a bidirectional spillover effect between psychological control and peer victimization at the within-person level, suggesting Chinese early adolescents may become caught in a vicious cycle directly or indirectly via their internalizing problems.

Novel Brominated Flame Retardants (NBFRs) in a Tropical Marine Food Web from the South China Sea: The Influence of Hydrophobicity and Biotransformation on Structure-Related Trophodynamics.

The increasing discharge and ubiquitous occurrence of novel brominated flame retardants (NBFRs) in aquatic environments have initiated intense global concerns; however, little information is available regarding their structure-related trophodynamics in marine food webs. In this study, a tropical marine food web including 29 species (18 fish and 11 invertebrate species) was collected from coral reef waters of the Xisha Islands, the South China Sea, for an analysis of 11 representative NBFRs. The mean ∑NBFR concentrations generally increased in the following sequence: sea cucumbers (0.330 ng/g lw) < crabs (0.380 ng/g lw) < shells (2.10 ng/g lw) < herbivorous fishes (2.30 ng/g lw) < carnivorous fishes (4.13 ng/g lw), with decabromodiphenyl ethane (DBDPE) and hexabromobenzene (HBB) as the predominant components. Trophic magnification was observed for all of the investigated NBFRs, with trophic magnification factors (TMFs) ranging from 1.53 (tetrabromobisphenol A bis(dibromopropyl ether)) to 5.32 (HBB). Significant negative correlations were also found between the TMFs and the tested in vitro transformation clearance rates (CLin vitro) for the target NBFRs except for bis(2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate (TBPH) (p < 0.05). Multiple linear regression analysis confirmed that the transformation rate is a more powerful predictor for TMFs than the hydrophobicity of NBFRs in this marine food web.

The relationship between online courses and mental health among Chinese children.

BACKGROUND: Previous studies on the association of online courses and mental health were mainly conducted in universities, and no study investigated the relationship between characteristics of online courses and children's mental health in primary and secondary school. This study aimed to explore the association of online courses and children's mental health in primary and secondary school. METHODS: A cross-sectional study was conducted through an online survey among 540 primary and secondary school students and their parents in the eastern, central and western region of China from April to May in 2020. Children's mental health was assessed by the Strengths and Difficulties Questionnaire (SDQ). Borderline mental health problems (SDQ total difficulties score ≥ 16) and mental health problems (SDQ total difficulties score ≥ 20) were defined according to Goodman's standard. Multivariable linear and logistic regression models were used to examine the association between online courses and children's mental health. RESULTS: Compared with those who did not have problems of online courses, children having the difficulty in understanding the content of online courses had a higher SDQ total difficulties score [ß = 1.80, 95% confidence interval (CI): 0.89, 2.71] and a higher risk of borderline mental health problems [odds ratio (OR) = 1.93, 95%CI: 1.07, 3.49], while device or internet connection problems were not significantly associated with children's mental health. Compared with children who had live courses, those having video-recorded courses had a higher SDQ total difficulties score (ß = 0.90, 95%CI: 0.01, 1.80). Children who spent more than 4 h on online courses had a higher SDQ total difficulties score than those of less than or equal to 4 h (ß = 0.95, 95%CI: 0.09, 1.81). CONCLUSION: We found that online courses with inappropriate characteristics were associated with children's mental health. The findings called for the efforts to optimize the online courses and improve children's mental health.

Release of the additive metals from 3 commonly used plastics during the degradation under the treatment of UV irradiation.

Additive metals are continuously released into the environment during the photo-degradation of plastics into microplastics, but this phenomenon has not been reported by many studies. Herein, we investigated the surface morphology changes along with the release of additive metals (Cr, Mn, Fe, Co, Cu, Zn, and Pb) during the degradation of three types of plastics, i.e., polypropylene (PP), polyethylene terephthalate (PET) and polyvinyl chloride (PVC), under UV light irradiation. FTIR results showed that 168 days of UV-irradiation led to the primary degradation of each plastic sample. The metal release could be found after 70 days UV-irradiation. The rate of metal release for the three plastics showed the following order: PP > PET ≈ PVC. In addition, the distribution and concentrations of the metals in the plastic could influence the release characteristics of each metal. Low release rate of Fe symbolized by the total metal release in the range of 4.28 ~10.27% as evident from the results of the primary degradation experiment, indicated the release of Fe occurring in the late stage of the plastic degradation or even in the microplastics-formation stage. As for the release of Co from PP, it was far lower than that of the other elements (0.35%), showing the same release characteristics as that of Fe. On the contrary, the release ratio of Pb from PP was 78.89% and was mainly concentrated in the early stage of the plastic degradation. The results help understanding the release behavior of the additive metals during the degradation of typical plastics under ultraviolet light irradiation.

The association between maternal fat-soluble vitamin concentrations during pregnancy and infant birth weight in China.

Fat-soluble vitamins during pregnancy are important for fetal growth and development. The present study aimed at exploring the association between vitamin A, E and D status during pregnancy and birth weight. A total of 19 640 women with singleton deliveries from a retrospective study were included. Data were collected by the hospital electronic information system. Maternal serum vitamin A, E and D concentrations were measured during pregnancy. Logistic regression was performed to estimate the association between the vitamin status and low birth weight (LBW) or macrosomia. Women with excessive vitamin E were more likely to have macrosomia (OR 1·30, 95 % CI 1·07, 1·59) compared with adequate concentration. When focusing on Z scores, there was a positive association between vitamin E and macrosomia in the first (OR 1·07, 95 % CI 1·00, 1·14), second (OR 1·27, 95 % CI 1·11, 1·46) and third (OR 1·28, 95 % CI 1·06, 1·54) trimesters; vitamin A was positively associated with LBW in the first (OR 1·14, 95 % CI 1·01, 1·29), second (OR 1·31, 95 % CI 1·05, 1·63) and third (OR 2·00, 95 % CI 1·45, 2·74) trimesters and negatively associated with macrosomia in the second (OR 0·79, 95 % CI 0·70, 0·89) and third (OR 0·77, 95 % CI 0·62, 0·95) trimesters. The study identified that high concentrations of vitamin E are associated with macrosomia. Maintaining a moderate concentration of vitamin A during pregnancy might be beneficial to achieve optimal birth weight. Further studies to explore the mechanism of above associations are warranted.

High-precision visual localization based on an improved shape-based matching algorithm.

To deal with the requirement of high-precision localization of large-size workpieces in an industrial environment, an improved shape-based matching algorithm is proposed based on the phase stretching transformation and the iterative closest point algorithms. Basler industrial cameras are used to collect images of large-size workpieces, such as glass. The experimental results show that the average localization error is 0.05±0.013mm, which can meet the requirements of practical applications. This algorithm can effectively and accurately achieve high-precision localization of different positions of multi-directionally transformed objects in industrial environments.

Characteristics of expanded polystyrene microplastics on island beaches in the Pearl River Estuary: abundance, size, surface texture and their metals-carrying capacity.

While expanded polystyrene (EPS) microplastics have been widely recognized as one of the most important components of plastic litter in the intertidal zones of the global ocean, our understanding of their environmental fate on island beaches is insufficient. In this study, we intended to reveal that the latest EPS microplastic pollution status on 5 island beaches in the Pearl River Estuary, China, by comprehensively assessing the abundance, distribution, size, surface texture and carrying capacity of heavy metals (Cd, As, Cr, Ni, Cu, Pb, Mn, Fe, Al). High level of EPS microplastic abundance ranged from 328 to 82,276 particles m-2 was found, with the highest abundance at Guishan Island and the lowest at Dong'ao Island. Spatial distribution of EPS microplastic abundance was significantly different among different islands. EPS microplastics in the size range of 1-2 mm were the most abundant. The content of heavy metals in EPS microplastics collected on the beaches was greater than that in the new EPS products. The average concentrations of heavy metals in EPS microplastics from 5 islands are Cd (0.27 ± 0.19 µg g-1), As (5.50 ± 3.84 µg g-1), Cr (14.9 ± 8.25 µg g-1), Cu (15.0 ± 7.66 µg g-1), Ni (17.2 ± 17.6 µg g-1), Pb (24.8 ± 7.39 µg g-1), Mn (730 ± 797 µg g-1), Fe (8340 ± 4760 µg g-1), and Al (9624 ± 6187 µg g-1), respectively. The correlation between heavy metals in EPS microplastics and sediments was better than that between heavy metals in EPS microplastics and seawater. The study results indicated that EPS microplastics could act as a carrier for the transport of heavy metals, which might pose a threat to biological and human health.

LFM: A Lightweight LCD Algorithm Based on Feature Matching between Similar Key Frames.

Loop Closure Detection (LCD) is an important technique to improve the accuracy of Simultaneous Localization and Mapping (SLAM). In this paper, we propose an LCD algorithm based on binary classification for feature matching between similar images with deep learning, which greatly improves the accuracy of LCD algorithm. Meanwhile, a novel lightweight convolutional neural network (CNN) is proposed and applied to the target detection task of key frames. On this basis, the key frames are binary classified according to their labels. Finally, similar frames are input into the improved lightweight feature matching network based on Transformer to judge whether the current position is loop closure. The experimental results show that, compared with the traditional method, LFM-LCD has higher accuracy and recall rate in the LCD task of indoor SLAM while ensuring the number of parameters and calculation amount. The research in this paper provides a new direction for LCD of robotic SLAM, which will be further improved with the development of deep learning.

Dual-Arm Coordinated Control Strategy Based on Modified Sliding Mode Impedance Controller.

To meet the high-accuracy position/force control requirements of dual-arm robots for handling a target object, a control algorithm for dual-arm robots based on the modified sliding mode impedance controller MSMIC(tanh) is proposed. First, the combinative kinematics equation of the dual-arm robots and the unified dynamics model combining the manipulated object is established. Second, according to the impedance control motion model for the object, the desired joint angular accelerations of the manipulators are obtained, and the sliding mode controller based on the hyperbolic tangent function as the switch function is introduced to design the coordinated control strategy for dual-arm robots. The stability and convergence of the designed controller are proved according to the Lyapunov function theory. Finally, the operation tasks of the coordinated transport the target object for dual-arm robots are carried out in the simulated experiment environment. Simulation results show that the proposed control scheme can stably output the required internal force and achieve a high-precision trajectory tracking effect while reducing the periodic torque and joint chattering amplitude generated in the conventional sliding mode control algorithm.

Evidence for complex sources of persistent halogenated compounds in birds from the south China sea.

Persistent halogenated compounds (PHCs), including dichlorodiphenyltrichloroethane and its metabolites (DDTs), polybrominated diphenyl ethers (PBDEs), alternative brominated flame retardants (ABFRs), and dechlorane plus (DP), were analyzed in muscle of six bird species from the South China Sea. DDTs, with concentrations up to 19,000 ng/g lipid weight (lw), were the dominant contaminants contributing to 66-99% of PHCs in birds. Concentrations of PBDEs, ABFRs, and DP ranged from 1.1 to 130, 0.73-40, and 0.21-2.5 ng/g lw, respectively. Historically pollution of DDTs and flame retardants in surrounding Asian lands were the main sources for PHCs in birds. BDE 209 was the primary PBDE congener in all birds. 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) and decabromodiphenyl ethane (DBDPE) were the main ABFRs. Anti-DP and p,p'-DDE were the dominating compounds of DP and DDTs, respectively. Only concentrations of BDEs 153, 203, 196, and 207, p,p'-DDE, and p,p'-DDD showed significant and positive correlations with δ15N values in samples. The resident birds, red-footed booby (Sula sula), had much lower levels of p,p'-DDE and most of PBDEs than those in migratory birds from the South China Sea. Results of stable isotope ratios of carbon suggest the highly variable food items for the five migratory bird species. The abundance of DBDPE in red-footed booby might be related with the ingestion of plastic debris, which still warrants further verification.

The individual and joint effects of maternal 25(OH)D deficiency and gestational diabetes on infant birth size.

BACKGROUND AND AIMS: To examine the independent effect of maternal serum 25-hydroxyvitamin D [25(OH)D] deficiency and its joint effect with gestational diabetes mellitus (GDM) on infant birth size. METHODS AND RESULTS: This retrospective cohort study was conducted in 15,724 mother-offspring dyads in Beijing, China between 2016 and 2017. Outcomes included infant birth weight Z-score (adjusted for gestational age and sex) and large for gestational age (LGA). Exposures were maternal 25(OH)D concentrations. Linear and logistic regression models were used to assess the associations of exposures with continuous and binary outcomes, respectively. Exposure-outcome associations were not observed when analyzing 25(OH)D concentrations continuously or in quartiles (P > 0.05); however, mothers with severely deficient 25(OH)D concentrations (n = 307) had a decreased risk of LGA compared with those with sufficient 25(OH)D concentrations (≥30.0 ng/mL; n = 5400) (adjusted odds ratio (OR): 0.63; 95% confidence interval (CI): 0.42, 0.93). Compared to mothers with no 25(OH)D deficiency (≥20.0 ng/mL) and no GDM (n = 7975), those with both 25(OH)D deficiency and GDM (n = 1090) had 0.15 (95% CI: 0.09, 0.21) higher infant birth weight Z-score and a higher risk of LGA (OR: 1.29; 95% CI: 1.09, 1.52). Maternal 25(OH)D deficiency and GDM had additive interaction on the risk of LGA (relative risk due to interaction: 0.18). CONCLUSION: Mothers with severely deficient 25(OH)D might have a decreased risk of LGA. However, the joint effect of maternal 25(OH)D deficiency and GDM might increase the risk of LGA. Our findings have clinical and public health implications and provide potential directions for future studies.

Urinary bisphenol A concentration is correlated with poorer oocyte retrieval and embryo implantation outcomes in patients with tubal factor infertility undergoing in vitro fertilisation.

Bisphenol A (BPA) is a substance ubiquitously present in the environment, and its toxicity on reproductive function has been well characterised in animal models. However, it is still controversy about the effects of BPA exposure on human female reproduction. Therefore, in the present study, the associations of urinary BPA concentration with the outcomes of in vitro fertilisation (IVF) and embryo transfer from fresh and frozen cycles were analysed in the same cohort. 351 women who underwent IVF treatment from September 2013 to October 2016, at the Centre of Reproductive Medicine in the Women's Hospital School of Medicine at Zhejiang University were recruited. Single-spot urine samples were collected on the day of oocyte retrieval to detect BPA using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. A multivariable generalised linear mixed model was used to evaluate the association between the urinary BPA concentration and IVF outcomes. After adjustment for age, body mass index, baseline follicle-stimulating hormone level, baseline oestradiol level, and antral follicle count, a significant decrease in the number of retrieved oocytes and in the rates of clinical pregnancy and implantation was observed in the patients with a high urinary BPA concentration. We concluded that BPA exposure exert negative effects on oocyte retrieval and embryo implantation in women undergoing IVF.

MiR-129-3p favors intracellular BCG survival in RAW264.7 cells by inhibiting autophagy via Atg4b.

Autophagy plays an important role in the fight against Mycobacterium tuberculosis infection. Massive researches proved that miRNAs could be the regulators of autophagy, which implied miRNAs could favor MTB invasion or latent infection. In our study, multiple bioinformatics databases and software were used to seek and lock the miRNAs associating with regulation of autophagy. Notably, a novel miR-129-3p was found and its target gene Atg4b showed grand potential in mediation of autophagy. Moreover, BCG infection triggered miR-129-3p overexpression in RAW264.7 cells. Up-regulation of miR-129-3p decreased mRNA or protein level of Atg4b and resulted in the inhibition of autophagy. The antagomir of miR-129-3p had the opposite impact. The LC3 puncta formation in RAW264.7 cells were also affected after transfection of miR-129-3p mimic or antagomir. The mRFP-GFP-LC3 analysis indicated that mimic of miR-129-3p impaired autophagic flux while antagomir improved autophagy. The CFU assay results showed that miR-129-3p promoted the intracellular survival of BCG in macrophages. Consequently, these data suggested that miR-129-3p could favor MTB survival by inhibiting autophagy via Atg4b.