This study investigates the identification and inference of quantile treatment effects (QTEs) in a fuzzy regression discontinuity (RD) design under rank similarity. Unlike Frandsen et al. (2012, Journal of Econometrics 168, 382–395), who focus on QTEs only for the compliant subpopulation, our approach can identify QTEs and average treatment effect for the whole population at the threshold. We derived a new set of moment restrictions for the RD model by imposing a local rank similarity condition, which restricts the evolution of individual ranks across treatment status in a neighborhood around the threshold. Based on the moment restrictions, we derive closed-form solutions for the estimands of the potential outcome cumulative distribution functions for the whole population. We demonstrate the functional central limit theorems and bootstrap validity results for the QTE estimators by explicitly accounting for observed covariates. In particular, we develop a multiplier bootstrap-based inference method with robustness against large bandwidths that applies to uniform inference by extending the recent work of Chiang et al. (2019, Journal of Econometrics 211, 589–618). We also propose a test for the local rank similarity assumption. To illustrate the estimation approach and its properties, we provide a simulation study and estimate the impacts of India’s 40-billion-dollar national rural road construction program on the reallocation of labor out of agriculture.

Placental trophoblastic cells play important roles in placental development and fetal health. However, the mechanism of trophoblastic cell fusion is still not entirely clear. The level of Tspan5 in the embryo culture medium was detected using enzyme-linked immunosorbent assay (ELISA). Fusion of BeWo cells was observed by immunofluorescence. Cell fusion-related factors and EMT-related factors were identified by qRT-PCR and western blotting. Notch protein repressor DAPT was used to verify the role of Tspan5 in BeWo cells. The expression of Tspan5 was significantly increased in embryo culture medium. The fusion of BeWo cells was observed after treatment with forskolin (FSK). Cell fusion-related factors (i.e. β-hCG and syncytin 1/2) and Tspan5 were significantly increased after FSK treatment. In addition, FSK treatment promoted EMT-related protein expression in BeWo cells. Knockdown of Tspan5 inhibited cell fusion and EMT-related protein levels. Notch-1 and Jagged-1 protein levels were significantly upregulated, and the EMT process was activated by overexpression of Tspan5 in FSK-treated BeWo cells. Interestingly, blocking the Notch pathway by the repressor DAPT had the opposite results. These results indicated that Tspan5 could promote the EMT process by activating the Notch pathway, thereby causing cell fusion. These findings contribute to a better understanding of trophoblast cell syncytialization and embryonic development. Tspan5 may be used as a therapeutic target for normal placental development.

This paper studies the sustainability of plastrons on superhydrophobic (SHPo) surfaces made of longitudinal micro-trenches covered by nano-grass with the main interest on hydrodynamic friction drag reduction in high-speed flows of open water, which represent the operating conditions of common watercraft. After revising the shear-driven drainage model to address the air diffusion for SHPo surfaces, the existing theories are combined to reveal the trends of how the immersion depth, air saturation level and shear stress affect the maximum attainable plastron length. Deviations from the theories by the dynamic effect at the two ends of the trench, the interfacial contaminations and turbulent fluctuation are also discussed. A combinatorial series of well-defined SHPo trench surfaces (4 cm × 7 cm in size with varying trench widths, depths, lengths and roughnesses) is microfabricated and attached underneath a 4 m long motorboat on seawater in turbulent flows up to 7.2 m s−1 (shear rate ∼83 000 s−1 and friction Reynolds number ∼5500). Because the plastron can provide a substantial slip only while its air–water interfaces are pinned (or only slightly depinned) at the trench top, two underwater cameras are employed to differentiate the pinned (and slightly depinned) interfaces from the depinned (and no) interfaces. In addition to achieving pinned plastrons on 6 cm long trenches aligned to high-speed flows in open water, the experimental results corroborate the theoretical estimations, supporting the design of SHPo surfaces for field applications.

In this study, the length scaling for the boundary layer separation induced by two incident shock waves is experimentally and analytically investigated. The experiments are performed in a Mach 2.73 flow. A double-wedge shock generator with two deflection angles ($\alpha _1$ and $\alpha _2$) is employed to generate two incident shock waves. Two deflection angle combinations with an identical total deflection angle are adopted: ($\alpha _1 = 7^\circ$, $\alpha _2 = 5^\circ$) and ($\alpha _1 = 5^\circ$, $\alpha _2 = 7^\circ$). For each deflection angle combination, the flow features of the dual-incident shock wave–turbulent boundary layer interactions (dual-ISWTBLIs) under five shock wave distance conditions are examined via schlieren photography, wall-pressure measurements and surface oil-flow visualisation. The experimental results show that the separation point moves downstream with increasing shock wave distance ($d$). For the dual-ISWTBLIs exhibiting a coupling separation state, the upstream interaction length ($L_{int}$) of the separation region approximately linearly decreases with increasing $d$, and the decrease rate of $L_{int}$ with $d$ increases with the second deflection angle under the condition of an identical total deflection angle. Based on control volume analysis of mass and momentum conservations, the relation between $L_{int}$ and $d$ is analytically determined to be approximately linear for the dual-ISWTBLIs with a coupling separation region, and the slope of the linear relation obtained analytically agrees well with that obtained experimentally. Furthermore, a prediction method for $L_{int}$ of the dual-ISWTBLIs with a coupling separation region is proposed, and the relative error of the predicted $L_{int}$ in comparison with the experimental result is $\sim$10 %.

Childhood maltreatment has been suggested to have an adverse impact on neurodevelopment, including microstructural brain abnormalities. Existing neuroimaging findings remain inconsistent and heterogeneous. We aim to explore the most prominent and robust cortical thickness (CTh) and gray matter volume (GMV) alterations associated with childhood maltreatment. A systematic search on relevant studies was conducted through September 2022. The whole-brain coordinate-based meta-analysis (CBMA) on CTh and GMV studies were conducted using the seed-based d mapping (SDM) software. Meta-regression analysis was subsequently applied to investigate potential associations between clinical variables and structural changes. A total of 45 studies were eligible for inclusion, including 11 datasets on CTh and 39 datasets on GMV, consisting of 2550 participants exposed to childhood maltreatment and 3739 unexposed comparison subjects. Individuals with childhood maltreatment exhibited overlapped deficits in the median cingulate/paracingulate gyri simultaneously revealed by both CTh and GM studies. Regional cortical thinning in the right anterior cingulate/paracingulate gyri and the left middle frontal gyrus, as well as GMV reductions in the left supplementary motor area (SMA) was also identified. No greater regions were found for either CTh or GMV. In addition, several neural morphology changes were associated with the average age of the maltreated individuals. The median cingulate/paracingulate gyri morphology might serve as the most robust neuroimaging feature of childhood maltreatment. The effects of early-life trauma on the human brain predominantly involved in cognitive functions, socio-affective functioning and stress regulation. This current meta-analysis enhanced the understanding of neuropathological changes induced by childhood maltreatment.

Little effort has been made to integrate developmental cascades with maternal/paternal parenting in a single investigation. The present study seeks to test cascading effects among academic and internalizing/externalizing symptoms and their associations with maternal/paternal parenting across three time points from 8 to 10 years. Data for this investigation came from a nationally representative prospective cohort study of children born in April through July of 2008 in South Korea who were followed up annually. The sample included 1,598 families (48.5% girls). Parents rated their parenting and teachers rated children’s internalizing/externalizing problems and academic performance. Structural equation modeling showed that externalizing problems were negatively related to academic performance. Academic performance was negatively related to internalizing problems and positively related to maternal/paternal authoritative parenting, which in turn led to children’s higher academic performance. Bidirectional relations were found between academic performance and externalizing problems and between paternal authoritative parenting and children’s internalizing problems. Findings suggested cascading effects and their associations with parenting were not attributable to child gender, intelligence, or socioeconomic differences. These findings lend support to adjustment erosion and academic incompetence models and underscore the need for greater attention to the role that fathering may play in children’s development and mothering.

Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.

The low maturation rate of oocytes is an important reason for female infertility and failure of assisted pregnancy. The germinal vesicle breakdown (GVBD) is a landmark event of oocyte maturation. In our previous studies, we found that zona pellucida 3 (ZP3) was strongly concentrated in the nuclear region of germinal vesicle (GV) oocytes and interacted with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) and lamin A to promote GVBD. In the current study, we found that lamin A is mainly concentrated in the nuclear membrane. When ZP3 is knocked down, lamin A will be partially transferred to the nucleus of oocytes. The prelamin A is increased in both the nuclear membrane and nucleus, while phosphorylated lamin A (p-lamin A) is significantly reduced. AIPL1 was also proved to accumulate in the GV region of oocytes, and ZP3 deletion can significantly inhibit the aggregation of AIPL1 in the nuclear region. Similar to ZP3 knockdown, the absence of AIPL1 resulted in a decrease in the occurrence of GVBD, an increase in the amount of prelamin A, and a significant decrease in p-lamin A in oocytes developed in vitro. Finally, we propose the hypothesis that ZP3 can stabilize farnesylated prelamin A on the nuclear membrane of AIPL1, and promote its further processing into mature lamin A, therefore promoting the occurrence of GVBD. This study may be an important supplement for the mechanism of oocyte meiotic resumption and provide new diagnostic targets and treatment clues for infertility patients with oocyte maturation disorder.

Hormone-sensitive lipase (HSL) is one of the rate-determining enzymes in the hydrolysis of TAG, playing a crucial role in lipid metabolism. However, the role of HSL-mediated lipolysis in systemic nutrient homoeostasis has not been intensively understood. Therefore, we used CRISPR/Cas9 technique and Hsl inhibitor (HSL-IN-1) to establish hsla-deficient (hsla-/-) and Hsl-inhibited zebrafish models, respectively. As a result, the hsla-/- zebrafish showed retarded growth and reduced oxygen consumption rate, accompanied with higher mRNA expression of the genes related to inflammation and apoptosis in liver and muscle. Furthermore, hsla-/- and HSL-IN-1-treated zebrafish both exhibited severe fat deposition, whereas their expressions of the genes related to lipolysis and fatty acid oxidation were markedly reduced. The TLC results also showed that the dysfunction of Hsl changed the whole-body lipid profile, including increasing the content of TG and decreasing the proportion of phospholipids. In addition, the systemic metabolic pattern was remodelled in hsla-/- and HSL-IN-1-treated zebrafish. The dysfunction of Hsl lowered the glycogen content in liver and muscle and enhanced the utilisation of glucose plus the expressions of glucose transporter and glycolysis genes. Besides, the whole-body protein content had significantly decreased in the hsla-/- and HSL-IN-1-treated zebrafish, accompanied with the lower activation of the mTOR pathway and enhanced protein and amino acid catabolism. Taken together, Hsl plays an essential role in energy homoeostasis, and its dysfunction would cause the disturbance of lipid catabolism but enhanced breakdown of glycogen and protein for energy compensation.

Instrument delivery is critical part in vascular intervention surgery. Due to the soft-body structure of instruments, the relationship between manipulation commands and instrument motion is non-linear, making instrument delivery challenging and time-consuming. Reinforcement learning has the potential to learn manipulation skills and automate instrument delivery with enhanced success rates and reduced workload of physicians. However, due to the sample inefficiency when using high-dimensional images, existing reinforcement learning algorithms are limited on realistic vascular robotic systems. To alleviate this problem, this paper proposes discrete soft actor-critic with auto-encoder (DSAC-AE) that augments SAC-discrete with an auxiliary reconstruction task. The algorithm is applied with distributed sample collection and parameter update in a robot-assisted preclinical environment. Experimental results indicate that guidewire delivery can be automatically implemented after 50k sampling steps in less than 15 h, demonstrating the proposed algorithm has the great potential to learn manipulation skill for vascular robotic systems.

Microtubule-severing proteins (MTSPs) play important roles in mitosis and interphase. However, to the best of our knowledge, no previous studies have evaluated the role of MTSPs in female meiosis in mammals. It was found that FIGNL1, a member of MTSPs, was predominantly expressed in mouse oocytes and distributed at the spindle poles during meiosis in the present study. FIGNL1 was co-localized and interacted with γ-tubulin, an important component of the microtubule tissue centre (MTOC). Fignl1 knockdown by specific small interfering RNA caused spindle defects characterized by an abnormal length:width ratio and decreased microtubule density, which consequently led to aberrant chromosome arrangement, oocyte maturation and fertilization obstacles. In conclusion, the present results suggested that FIGNL1 may be an essential factor in oocyte maturation by influencing the meiosis process via the formation of spindles.

The association between alcohol intake and the risk of glioma has been widely studied, but these results have yielded conflicting findings. Therefore, we conducted this systematic review and updated meta-analysis to systematically evaluate the association between alcohol intake and the risk of glioma. A systematic literature search of relevant articles published in PubMed, Web of Science, CNKI and Wan fang databases up to December 2021 was conducted. Pooled estimated of relative risk (RR) and 95 % CI were calculated using fixed-effects models. A total of eight articles with three case–control studies involving 2706 glioma cases and 2 189 927 participants were included in this meta-analysis. A reduced risk of glioma was shown for the low–moderate alcohol drinking v. non-drinking (RR = 0·87; 95 % CI (0·78, 0·97); P = 0·014). In addition, there was no evidence of an increased risk of glioma in the heavy alcohol drinking compared with non-drinking (RR = 0·89; 95 % CI (0·67, 1·18); P = 0·404). The findings suggest an inverse association between low–moderate alcohol drinking and the risk of glioma, in the absence, however, of a dose–response relationship. More prospective studies are needed to provide further insight into the association between alcohol drinking and glioma risk.

The parasite Fasciola hepatica is an important zoonotic parasite. The development of an animal model of F. hepatica's life cycle is critical for studying the biological characteristics of the parasite in snails and mammals. Eggs of F. hepatica of bovine origin were cultured, and metacercariae were obtained after infection of Galba pervia snails. The life cycle system of F. hepatica was initiated in 2 different animals by orally infecting rabbits, SD rats and Kunming mice with the metacercariae. The animals' survival after infection, parasite migration in the animals and pathological damage to the liver were observed. We discovered that rabbits died due to acute suppurative hepatitis 60–69 days after infection, and eggs were found in the feces on day 63 of infection. The liver of SD rats showed punctate lesions on day 3 of infection, and further changes occurred as the infection progressed. However, liver repair was observed at week 9. SD rats survived for more than a year after infection and continued the F. hepatica life cycle. The liver lesions in Kunming mice after infection were similar but more severe than those in SD rats. Death was observed on the 31st post-infection day. We discovered that while rabbits, SD rats and Kunming mice can all be used as animal models of F. hepatica, SD rats are more suitable experimental animals in terms of tolerance and pathological response.

Listeriosis is a rare but serious foodborne disease caused by Listeria monocytogenes. This matched case–control study (1:1 ratio) aimed to identify the risk factors associated with food consumption and food-handling habits for the occurrence of sporadic listeriosis in Beijing, China. Cases were defined as patients from whom Listeria was isolated, in addition to the presence of symptoms, including fever, bacteraemia, sepsis and other clinical manifestations corresponding to listeriosis, which were reported via the Beijing Foodborne Disease Surveillance System. Basic patient information and possible risk factors associated with food consumption and food-handling habits were collected through face-to-face interviews. One hundred and six cases were enrolled from 1 January 2018 to 31 December 2020, including 52 perinatal cases and 54 non-perinatal cases. In the non-perinatal group, the consumption of Chinese cold dishes increased the risk of infection by 3.43-fold (95% confidence interval 1.27–9.25, χ2 = 5.92, P = 0.02). In the perinatal group, the risk of infection reduced by 95.2% when raw and cooked foods were well-separated (χ2 = 5.11, P = 0.02). These findings provide important scientific evidence for preventing infection by L. monocytogenes and improving the dissemination of advice regarding food safety for vulnerable populations.

External modulation on thermal convection has been studied extensively to achieve the control of flow structures and heat-transfer efficiency. In this paper, we carry out direct numerical simulations on Rayleigh–Bénard convection accounting for both the modulation of wall shear and roughness over the Rayleigh number range $1.0 \times 10^6 \le Ra \le 1.0 \times 10^8$, the wall shear Reynolds number range $0 \le Re_w \le 5000$, the aspect-ratio range $2 \le \varGamma \le 4{\rm \pi}$, and the dimensionless roughness height range $0 \le h \le 0.2$ at fixed Prandtl number $Pr = 1$. Under the combined actions of wall shear and roughness, with increasing $Re_w$, the heat flux is initially enhanced in the buoyancy-dominant regime, then has an abrupt transition near the critical shear Reynolds number $Re_{w,cr}$, and finally enters the purely diffusion regime dominated by shear. Based on the crossover of the kinetic energy production between the buoyancy-dominant and shear-dominant regimes, a physical model is proposed to predict the transitional scaling behaviour between $Re_{w,cr}$ and $Ra$, i.e. $Re_{w,cr} \sim Ra^{9/14}$, which agrees well with our numerical results. The reason for the observed heat-transport enhancement in the buoyancy-dominant regime is further explained by the fact that the moving rough plates introduce an external shear to strengthen the large-scale circulation (LSC) in the vertical direction and serve as a conveyor belt to increase the chances of the interaction between the LSC and secondary flows within cavities, which triggers more thermal plumes, efficiently transports the trapped hot (cold) fluids outside cavities.

The internal electric field of a 2D P-N junction of a semiconductor is mapped out by two techniques: measuring the deflection of the transmitted beam in micro-STEM mode with acquisition and data fitting of an un-scattered beam image, and through the derivative of electrostatic potential maps by dual lens electron holography. Comparable results of the P-N junction internal electric field measured with these two techniques are reported.