Search

Background: Neurodevelopmental disorders (NDDs) are a group of diseases that severely affect the physical and mental health of children. The PPP2R5D gene encodes B56δ, the regulatory subunit of protein phosphatase 2A (PP2A). NDDs related to the PPP2R5D gene have recently been defined as Houge–Janssens syndrome 1. Methods: Clinical/whole exome sequencing was performed on approximately 3000 patients with NDDs from 2017 to 2023. In vitro experiments were performed to assess the impairment of variants to protein expression and the assembly of PP2A holoenzyme. The genetic information and phenotypes of the reported patients, as well as patients in this study, were summarized, and the genotype–phenotype relationship was analyzed. The probability of pathogenic missense variants in PPP2R5D was predicted using AlphaMissense (AM), and the relationship between certain phenotype and 3D protein structural features were analyzed. Results: Thirteen new patients carrying twelve PPP2R5D gene variants were detected, including five novel missense variants and one novel frameshift variant. In vitro experiments revealed that the frameshift variant p.H463Mfs*3 resulted in a ~50 kDa truncated protein with lower expression level. Except for E420K and T536R, other missense variants impaired holoenzyme assembly. Furthermore, we found that pathogenic/likely pathogenic (P/LP) variants that have been reported so far were all missense variants and clustered in three conserved regions, and the likelihood of P/LP mutations located in these conserved regions was extremely high. In addition, the macrocephaly phenotype was related to negatively charged residues involved in substrate recruitment. Conclusions: We reported thirteen new patients with PPP2R5D gene variants and expanded the PPP2R5D variant spectrum. We confirmed the pathogenicity of novel variants through in vitro experiments. Our findings in genotype–phenotype relationship provide inspiration for genetic counseling and interpretation of variants. We also provide directions for further research on the mechanism of macrocephaly phenotype.

Global crises have created unprecedented challenges for communities and economies across the world, triggering turmoil in global finance and economy. This study adopts the dynamic conditional correlation multiple generalized autoregressive conditional heteroskedasticity (DCC–MGARCH) model to explore contagion effects across financial markets in crisis. The main findings are as follows: (1) the financial crisis and COVID-19 pandemic intensified the connection between the Chinese and US stock markets in the short term; (2) the dynamic conditional correlations (DCCs) during the COVID-19 pandemic are higher than those during the 2008 financial crisis owing to the further opening of the Chinese capital market, and financial institutions’ investments in the European market are higher than those in the American markets; (3) a stepwise increase is observed in the dynamic conditional correlation between the returns on the S&P 500 Index and SSEC during and after the onset of a destructive crisis; and (4) a unidirectional contagion effect exists between the Chinese market and US market, and the Hong Kong stock market contributes to the risk spillover. Effective transmission channels of external negative shocks may be investors’ sentiments, financial institutions, and the RMB exchange rate in the stock markets. This study provides useful suggestions to authorities formulating financial regulations and investors diversifying risk investments.

Fraxinellone (FRA), a major active component from Cortex Dictamni, produces hepatotoxicity via the metabolization of furan rings by CYP450. However, the mechanism underlying the hepatotoxicity of FRA remains unclear. Therefore, zebrafish larvae at 72 h post fertilization were used to evaluate the metabolic hepatotoxicity of FRA and to explore the underlying molecular mechanisms. The results showed that FRA (10–30 μM) induced liver injury and obvious alterations in the metabolomics of zebrafish larvae. FRA induces apoptosis by increasing the level of ROS and activating the JNK/P53 pathway. In addition, FRA can induce cholestasis by down-regulating bile acid transporters P-gp, Bsep, and Ntcp. The addition of the CYP3A inhibitor ketoconazole (1 μM) significantly reduced the hepatotoxicity of FRA (30 μM), which indicated that FRA induced hepatotoxicity through CYP3A metabolism. Targeted metabolomics analysis indicates the changes in amino acid levels can be combined with molecular biology to clarify the mechanism of hepatotoxicity induced by FRA, and amino acid metabolism monitoring may provide a new method for the prevention and treatment of DILI from FRA.

The visible and infrared scanning radiometer (VIRR) onboard the Fengyun-3C (FY-3C) meteorological satellite has 11 μm and 12 μm channels, which are capable of sea surface temperature (SST) observations. This study is based on atmospheric radiative transfer modeling (RTM) by applying Bayesian cloud detection theory and optimal estimation (OE) to obtain sea surface skin temperature (SSTskin) from VIRR in the Northwest Pacific. The inter-calibration of FY-3C/VIRR 11 μm and 12 μm brightness temperature (BT) is carried out using the Moderate Resolution Imaging Spectroradiometer (MODIS) as the reference sensor. Bayesian cloud detection and OE SST retrieval with the calibration BT data is performed to obtain SSTskin. The SSTskin retrievals are compared with the buoy SST with a temporal window of 1 h and a spatial window of 0.01°. The bias is −0.12 °C, and the standard deviation is 0.52 °C. Comparisons of the retrieved SSTskin with the AVHRR (Advanced Very High Resolution Radiometer) SSTskin from European Space Agency Sea Surface Temperature Climate Change Initiative (ESA SST CCI) project show the bias of 0.08 °C and the standard deviation of 0.55 °C. The results indicate that the VIRR SSTskin are consistent with AVHRR SSTskin and buoy SST.

Wild animals are vulnerable to environmental noise. In wetlands, wintering waterbirds are easily disturbed by ship noises; however, the behavioral changes of waterbirds in response to different levels of noise are unclear. We simulated the acoustic environment created by ship movement to investigate the effects of ship noise on foraging, vigilance, and flight behaviors of the wintering bean goose (Anser fabalis). In particular, we used a noise playback method to simulate the acoustic environment created by ship operations at various noise levels (i.e., background noise N ≤ 30) were more sensitive to noise interference. As the noise level increased, the frequency of foraging behavior decreased and the frequencies of vigilance and flight behaviors increased, particularly above 70 dB. For noises >70 dB at short disturbance distances and >80 dB at medium disturbance distances, flight behavior increased significantly. These findings suggested that ships should keep a distance of more than 200 m from waterbirds to reduce noise interference.

Increasing arsenic (As) pollution is posing potential endangerment to mangrove wetland ecosystems. Mangrove phytoextraction, translocation, and responses to As exposure must be urgently addressed. In this study, the growth and physiological response of Kandelia obovata seedlings were examined after addition of 25−200 mg kg−1 As under sediment culture conditions. Results showed that the seedling morphological variations were not significant below 100 mg kg−1 compared to the control group, indicating superoxide dismutase, peroxidase, and catalase synergetic interaction to resist the As exposure. High As concentrations (150–200 mg kg−1) inhibited the seedling growth accompanied by a significant increase in malondialdehyde content and decrease in activities of antioxidant enzymes. Toxicity symptoms and mortality appeared in 200 mg kg−1 As, presumably because the plant reached the limit of As tolerance. Besides, As accumulated mainly in roots, accounting for 87.04–97.85% of the total As, and the bioaccumulation factor (BCF) was >100%. However, the BCF and translocation factor (TF) in stems and leaves were below unity, illustrating a weak capacity of transferring As to aerial parts of the seedlings. Overall, K. obovata is a potential remediated species in polluted coastal wetlands due to high phytoextraction capacity and high tolerance to As exposure.

Fengyun-3C (FY-3C) is a second-generation meteorological satellite of China that was launched on 23 September 2013. The on board Visible and Infrared Radiometer (VIRR) can be used to observe global sea surface temperature (SST). In this paper, the VIRR SST products are compared with MODIS SST products and buoy measurements from 2015 to 2019. The collocations of VIRR, MODIS, and buoy SST are generated separately during the day and night with the spatial window of 0.05° × 0.05°. The comparison results show that the biases of VIRR SST minus buoy SST during the day and night are −0.21 and −0.13 °C with a corresponding robust standard deviation (RSD) of 0.58 and 0.59 °C, respectively. The mean differences between VIRR and MODIS are −0.10 and 0.08 °C with RSDs of 0.53 and 0.58 °C for the daytime and nighttime, respectively. The consistency of VIRR SST accuracy from 2015 to 2019 and the dependence of VIRR SST error on SST and latitude are also investigated.

Material properties affect the surface finishing in ultra-precision diamond cutting (UPDC), especially for aluminum alloy 6061 (Al6061) in which the cutting-induced temperature rise generates different types of precipitates on the machined surface. The precipitates generation not only changes the material properties but also induces imperfections on the generated surface, therefore increasing surface roughness for Al6061 in UPDC. To investigate precipitate effect so as to make a more precise control for the surface quality of the diamond turned Al6061, it is necessary to confirm the compositions and material properties of the precipitates. Previous studies have indicated that the major precipitate that induces scratch marks on the diamond turned Al6061 is an AlFeSi phase with the composition of Al86.1Fe8.3Si5.6. Therefore, in this paper, to study the material properties of the AlFeSi phase and its influences on ultra-precision machining of Al6061, an elastoplastic-damage model is proposed to build an elastoplastic constitutive model and a damage failure constitutive model of Al86.1Fe8.3Si5.6. By integrating finite element (FE) simulation and JMatPro, an efficient method is proposed to confirm the physical and thermophysical properties, temperature-phase transition characteristics, as well as the stress–strain curves of Al86.1Fe8.3Si5.6. Based on the developed elastoplastic-damage parameters of Al86.1Fe8.3Si5.6, FE simulations of the scratch test for Al86.1Fe8.3Si5.6 are conducted to verify the developed elastoplastic-damage model. Al86.1Fe8.3Si5.6 is prepared and scratch test experiments are carried out to compare with the simulation results, which indicated that, the simulation results agree well with those from scratch tests and the deviation of the scratch force in X-axis direction is less than 6.5%.

Aluminum alloy 6061(Al6061), an Al-Mg-Si alloy, is a precipitation-hardened alloy. The generation of precipitate affects its mechanical properties, and induces a worse surface finish during diamond cutting. The friction coefficients of the tool-chip and tool-workpiece interfaces influence temperature rise, and are therefore important predictors of tool wear and surface integrity during the diamond cutting of Al6061. This study investigated the relationship between precipitate generation and the friction coefficients of Al6061. Groups of experiments were conducted to study the influence of temperature and heating time on the number of precipitates and the friction coefficients. The results show that the generation of AlFeSi particles induces cracks, scratch marks and pits on diamond-machined Al6061 and affects the cutting forces. Moreover, the variation trend of the friction coefficient of Al6061 under different heating conditions agrees well with that of the number of AlFeSi particles. This implies that, during ultra-precision machining of precipitation-hardened alloys, cutting-induced heat causes precipitates to form on the chips and machined surface, changing their material properties. This affects the tool-workpiece and tool−chip contact conditions and the mechanisms of chip formation and surface generation in ultra-precision machining.