The transcription factor HNF1 beta has several domains involved in nephrogenesis and partially rescues Pax8/lim1 induced kidney malformations

The tissue-specific transcription factors, HNF1 alpha and HNF1 beta, are two closely related homeodomain proteins that are conserved throughout vertebrate evolution. Heterozygous mutations in the human HNF1beta and HNF1alpha genes are linked to maturity onset diabetes of the young (MODY), but mutated HNF1beta is also associated with kidney malformations. Consistent with this, it has been demonstrated that overexpression of HNF1beta in Xenopus embryos leads to defective pronephric development and agenesis of the pronephros, while HNF1alpha has no effect on kidney development. The regions in the HNF1beta protein responsible for this functional difference were defined in transfected HeLa cells as well as in injected Xenopus embryos. Using domain swapping experiments a nuclear localization signal was localized in the POUH domain of HNF1beta. The POUS and POUH domains of HNF1beta also were responsible for the most of the transactivation activity in transfected cells. In injected Xenopus embryos, three HNF1beta domains are involved in nephrogenesis. These include the dimerization domain, the 26 aa segment specific for splice variant A as well as the POUH domain. HNF1beta together with Pax8 and lim1 constitute the earliest regulators in the pronephric anlage. Overexpression of lim1 together with Pax8 in Xenopus embryos led to an enlarged pronephros with ectopic pronephric structures. In an effort to evaluate whether HNFbeta antagonizes the nephrogenic effect of lim1 and Pax8, all three transcription factors were coinjected into Xenopus embryos. The data shown here that HNF1beta can overcome the enlargement and the induction of an ectopic pronephros mediated by overexpression of Pax8 and lim1. But the phenotype induced by Pax8 and lim1 overexpression and characterized by cyst-like structures and thickening of the pronephric tubules was not altered by HNF1beta overexpression. Taken together, HNF1beta acts antagonistically to Pax8 and lim1 in only some processes during nephrogenesis, and a simple antagonistic relationship does not completely describe the functions of these genes. I conclude that HNF1beta has some distinct morphogenetic properties during nephrogenesis

PM2.5 Pollution and Inhibitory Effects on Industry Development: A Bidirectional Correlation Effect Mechanism

In this paper, a vector autoregression (VAR) model has been constructed in order to analyze a two-way mechanism between PM2.5 pollution and industry development in Beijing via the combination of an impulse response function and variance decomposition. According to the results, long-term equilibrium interconnection was found between PM2.5 pollution and the development of primary, secondary, and tertiary industries. One-way Granger causalities were found in the three types of industries shown to contribute to PM2.5 pollution, though the three industries showed different scales of influences on the PM2.5 pollution that varied for about 1–2 years. The development of the primary and secondary industries increased the emission of PM2.5, but the tertiary industry had an inhibitory effect. In addition, PM2.5 pollution had a certain inhibitory effect on the development of the primary and secondary industries, but the inhibition of the tertiary industry was not significant. Therefore, the development of the tertiary industry can contribute the most to the reduction of PM2.5 pollution. Based on these findings, policy-making recommendations can be proposed regarding upcoming pollution prevention strategies

PM2.5 Pollution: Health and Economic Effect Assessment Based on a Recursive Dynamic Computable General Equilibrium Model

At present particulate matter (PM₂.₅) pollution represents a serious threat to the public health and the national economic system in China. This paper optimizes the whitening coefficient in a grey Markov model by a genetic algorithm, predicts the concentration of fine particulate matter (PM₂.₅), and then quantifies the health effects of PM₂.₅ pollution by utilizing the predicted concentration, computable general equilibrium (CGE), and a carefully designed exposure–response model. Further, the authors establish a social accounting matrix (SAM), calibrate the parameter values in the CGE model, and construct a recursive dynamic CGE model under closed economy conditions to assess the long-term economic losses incurred by PM₂.₅ pollution. Subsequently, an empirical analysis was conducted for the Beijing area: Despite the reduced concentration trend, PM₂.₅ pollution continued to cause serious damage to human health and the economic system from 2013 to 2020, as illustrated by various facts, including: (1) the estimated premature deaths and individuals suffering haze pollution-related diseases are 156,588 (95% confidence intervals (CI): 43,335–248,914)) and six million, respectively; and (2) the accumulated labor loss and the medical expenditure negatively impact the regional gross domestic product, with an estimated loss of 3062.63 (95% CI: 1,168.77–4671.13) million RMB. These findings can provide useful information for governmental agencies to formulate relevant environmental policies and for communities to promote prevention and rescue strategies

Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis

Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation of PU.1, a pioneer factor, which in turn binds and opens chromatin regions of downstream effector genes. PU.1 increases histone acetylation at the DPP4 locus. Precise epigenetic silencing by CRISPR/dCas9KRAB or CRISPR/dCas9HDAC revealed that individual PU.1-remodeled regulatory elements collectively modulate DPP4 expression and liver metastasis growth. Genetic silencing or pharmacological inhibition of each factor along this chromatin remodeling axis strongly suppressed liver metastasis. Therefore, microenvironment-induced epimutation is an important mechanism for metastatic tumor cells to grow in their new niche. This study presents a potential strategy to target chromatin remodeling in metastatic cancer and the promise of repurposing drugs to treat metastasis

The Study of Influence of Sound on Visual ERP-Based Brain Computer Interface

The performance of the event-related potential (ERP)-based brain–computer interface (BCI) declines when applying it into the real environment, which limits the generality of the BCI. The sound is a common noise in daily life, and whether it has influence on this decline is unknown. This study designs a visual-auditory BCI task that requires the subject to focus on the visual interface to output commands and simultaneously count number according to an auditory story. The story is played at three speeds to cause different workloads. Data collected under the same or different workloads are used to train and test classifiers. The results show that when the speed of playing the story increases, the amplitudes of P300 and N200 potentials decrease by 0.86 μV (p = 0.0239) and 0.69 μV (p = 0.0158) in occipital-parietal area, leading to a 5.95% decline (p = 0.0101) of accuracy and 9.53 bits/min decline (p = 0.0416) of information transfer rate. The classifier that is trained by the high workload data achieves higher accuracy than the one trained by the low workload if using the high workload data to test the performance. The result indicates that the sound could affect the visual ERP-BCI by increasing the workload. The large similarity of the training data and testing data is as important as the amplitudes of the ERP on obtaining high performance, which gives us an insight on how make to the ERP-BCI generalized

Research on the scale effects of solute transport in a bended karst conduit

Research on the scale effect of solute transport in karst conduits is very important for the correct interpretation of breakthrough curves (BTCs), but the scale effect of solute transport in a bended conduit has not been examined. In this paper, a karst conduit and a pool developed within the conduit are generalized into the transparent hose and cubic pool, respectively. Based on the previously established pool-pipe system, the bended pipes with different lengths are arranged downstream of the pool, and the tracer experiments are conducted to study the effect of the transport scale on the BTCs in conduits. We use the transient storage model to simulate the experimental curves. The results show that with the increasing pipe length downstream the pool, the peak concentration gradually decreases slowly, the rising slope of the BTCs does not change significantly, and the BTC tails gradually shorten, indicating that the longer transport distance exerts a larger effect on solute transport than the conduit bend. The coefficient of skewness (CSK), breakthrough time of posterior solute plume (tre) and breakthrough time of solute plume (td) are well negatively correlated with the length of the pipe system (R2>0.96). When the length of the pipe system with the symmetrical or asymmetrical pool increases to 154.5 m and 164.3 m, respectively, the CSK is close to zero, and the BTC is nearly symmetrical. The dispersion coefficient (D), cross-sectional area of the storage zones (As) and exchange coefficient (α) have a good negative correlation with the length of the pipe system. When the length of the pipe system with the symmetrical or asymmetrical pool increases to 159.9 m and 178.1 m, respectively, the As is close to zero. Then, the solute retention caused by the pool basically disappears. The results have certain indications for the interpretation of the BTCs in field karst conduits

Comparative analysis of miRNAs and their target transcripts between a spontaneous late-ripening sweet orange mutant and its wild-type using small RNA and degradome sequencing

Fruit ripening in citrus is not well understood at the molecular level. Knowledge of the regulatory mechanism of citrus fruit ripening at the post-transcriptional level in particular is lacking. Here, we comparatively analyzed the miRNAs and their targeted genes in a spontaneous late-ripening mutant, ‘Fengwan’ sweet orange (MT) (Citrus sinensis L. Osbeck), and its wild-type counterpart ('Fengjie 72-1', WT). Using high-throughput sequencing of small RNAs and RNA degradome tags, we identified 107 known and 21 novel miRNAs, as well as 225 target genes. A total of 24 miRNAs (16 known miRNAs and 8 novel miRNAs) were shown to be differentially expressed between MT and WT. The expression pattern of several key miRNAs and their target genes during citrus fruit development and ripening stages was examined. Csi-miR156k, csi-miR159 and csi-miR166d suppressed specific transcription factors (GAMYBs, SPLs and ATHBs) that are supposed to be important regulators involved in citrus fruit development and ripening. In the present study, miRNA-mediated silencing of target genes was found under complicated and sensitive regulation in citrus fruit. The identification of miRNAs and their target genes provide new clues for future investigation of mechanisms that regulate citrus fruit ripening

Exploring the Tribophysics and Tribochemistry of MoS2 by Sliding MoS2/Ti Composite Coating Under Different Humidity

The MoS2 coatings were prepared by unbalanced magnetron sputtering system. Ti was used as the dopant to improve its mechanical properties and oxidation resistance. The microstructure of the coatings changed from coarse columnar platelet structure at low Ti content (0-1.8 at.%) to a denser columnar microstructure at increased Ti content. The hardness and elastic modulus of the MoS2/Ti composite coatings gradually increase as the Ti content increases. The tribological properties of the coatings were evaluated against a GCr15 ball under different relative humidity atmosphere to verify the oxidation resistance. The results show that doping of Ti can significantly improve the oxidation resistance of the coatings. Particularly, the friction coefficient for the composite coating with 10.8 at.% Ti exhibited almost the same friction coefficient under three different humidity. However, excessive Ti induced high brittleness and the coatings flaking easily from the substrate; therefore, the coatings show poor wear resistances under both dry and humidity atmospheres