Evolution and Function of the Notch Signaling Pathway: An Invertebrate Perspective.

The highly conserved Notch signaling pathway affects embryonic development, neurogenesis, homeostasis, tissue repair, immunity, and numerous other essential processes. Although previous studies have demonstrated the location and function of the core components of Notch signaling in various animal phyla, a more comprehensive summary of the Notch core components in lower organisms is still required. In this review, we objectively summarize the molecular features of the Notch signaling pathway constituents, their current expression profiles, and their functions in invertebrates, with emphasis on their effects on neurogenesis and regeneration. We also analyze the evolution and other facets of Notch signaling and hope that the contents of this review will be useful to interested researchers.

System dynamics simulation of occupational health and safety management causal model based on NetLogo.

The occupational health and safety management factors of construction enterprises are critical influencing factors in their training management, and their causal principles are topics that warrant profound exploration. Drawing upon the conventional five factors, this study initially posited and authenticated a causal model among them, subsequently employing system dynamics on the NetLogo platform to dynamically simulate the model, and ultimately scrutinizing the interrelations and dynamic influence degree among the factors. The results show that the direct causes of management factors include human factors (weight coefficient of 0.583) and method factors (weight coefficient of 0.405), and environmental factors directly affect human factors (weight coefficient of 0.994), whereas material factors directly affect method factors (weight coefficient of 0.918). At the same time, it can be seen from the dynamic simulation results that the influence of human factors and method factors on management factors increases sharply in the nascent phase of the simulation cycle (the highest slope is .90), gradually decreases in the intermediary phase (the slope of the inflection point is .11), and is relatively stable in the final phase (the slope is less than 0.11). Three main conclusions have been drawn from this. Firstly, management factors are directly and positively affected by human factors and method factors respectively. Secondly, the interplay between diverse factors evinces a confluence of periodicity and exponential attributes. Thirdly, in each management cycle (set at 381 steps), the main focus is on controlling the causal factors in the early stages of management, with pivotal control points in steps 25 and 100, and the principal management factors comprising the management organization, operating procedures, and protective measures.

DjFARP Contributes to the Regeneration and Maintenance of the Brain through Activation of DjRac1 in Dugesia japonica.

FERM, RhoGEF, and Pleckstrin domain protein (FARP) mediated RhoGTPase pathways are involved in diverse biological processes, such as neuronal development and tumorigenesis. However, little is known about their role in neural regeneration. We uncovered for the first time that FARP-Rac1 signaling plays an important role in neural regeneration in Dugesia japonica, a planarian that possesses unparalleled regenerative capacities. The planarian FARP homolog DjFARP was primarily expressed in both intact and regenerating brain and pharynx tissue. Functional studies suggested that downregulation of DjFARP with dsRNA in Dugesia japonica led to smaller brain sizes, defects in brain lateral branches, and loss of cholinergic, GABAergic, and dopaminergic neurons in both intact and regenerating animals. Moreover, the Rho GTPase DjRac1 was shown to play a similar role in neural regeneration and maintenance. Rac1 activation assay showed that DjFARP acts as a guanine nucleotide exchange factor (GEF) for DjRac1. Together, these findings indicate that the brain defects seen in DjFARP knockdown animals may be attributable to DjRac1 inactivation. In conclusion, our study demonstrated that DjFARP-DjRac1 signaling was required for the maintenance and proper regeneration of the brain in Dugesia japonica.

Construction safety: an analysis of the cross-influence of economic, construction, and accident death factors.

To explore the relations between the number of accident deaths (NCD) and various factors in construction safety, a multiple linear regression model was established, based on the panel data of economy, construction labor, and the number of accident deaths in 31 provinces (regions) of China from 2009 to 2018. The results show that the average total profits and taxes (TPAT), and the death rate of ten thousand people (DR) are positively correlated with NCD, while the labor productivity (LP) is negatively correlated with it. Under the condition that other factors remain unchanged, NCD increases by 0.02 per a hundred million CNY. However, if DR increases by one ten thousand, NCD will increase by 8.66 on average. On the contrary, when LP increases by a hundred million CNY per ten thousand people, NCD decreases by 0.19. The model also predicts NCD in different provinces and cities from 2019 to 2020 with the method of quadratic exponential smoothing. As well, practice results show that the model is effective and practical.

Effect of Occupational Health and Safety Training for Chinese Construction Workers Based on the CHAID Decision Tree.

Background: Occupational health and safety (OHS) training is an important way to prevent construction safety risks. However, the effectiveness of OHS training in China is questionable. In this study, the CHAID (chi-squared automatic interaction detection) decision tree, chi-square analysis, and correlation analysis were used to explore the main, secondary, weak, unrelated, and expectation factors affecting the effectiveness of training. It is the first to put forward the "five-factor method" of training effectiveness. It is found that training effectiveness is positively correlated with job responsibilities, OHS training, and job satisfaction. It is also significantly related to job certificate, training time, training method, and working time. However, the effectiveness of training has nothing to do with personal age, marital status, educational level, job type, and whether or not they have experienced industrial accidents. And the workers on site expect the enterprise to provide security and opportunities such as physical safety, training and learning, and future career development. The results show that OHS system training should be strengthened in the construction industry, and classified training should be carried out according to post responsibility, training methods, job satisfaction, and working hours.

miR-8b is involved in brain and eye regeneration of Dugesia japonica in head regeneration.

MicroRNAs (miRNAs) are a class of evolutionarily conserved small non-coding RNAs that regulate gene expression at the translation level in cell growth, proliferation and differentiation. In addition, some types of miRNAs have been proven to be key modulators of both CNS development and plasticity, such as let-7, miR-9 and miR-124. In this research, we found miR-8b acts as an important regulator involved in brain and eyespot regeneration in Dugesia japonica. miR-8b was highly conserved among species and was abundantly expressed in central nervous system. Here, we detected the expression dynamics of miR-8b by qPCR during the head regeneration of D. japonica. Knockdown miR-8b by anti-MIRs method caused severe defects of eyes and CNS. Our study revealed the evolutionary conserved role of miR-8b in the planarian regeneration process, and further provided more research ideas and available information for planarian miRNAs.

Different classes of small RNAs are essential for head regeneration in the planarian Dugesia japonica.

BACKGROUND: Planarians reliably regenerate all body parts after injury, including a fully functional head and central nervous system. But until now, the expression dynamics and functional role of miRNAs and other small RNAs during the process of head regeneration are not well understood. Furthermore, little is known about the evolutionary conservation of the relevant small RNAs pathways, rendering it difficult to assess whether insights from planarians will apply to other taxa. RESULTS: In this study, we applied high throughput sequencing to identify miRNAs, tRNA fragments and piRNAs that are dynamically expressed during head regeneration in Dugesia japonica. We further show that knockdown of selected small RNAs, including three novel Dugesia-specific miRNAs, during head regeneration induces severe defects including abnormally small-sized eyes, cyclopia and complete absence of eyes. CONCLUSIONS: Our findings suggest that a complex pool of small RNAs takes part in the process of head regeneration in Dugesia japonica and provide novel insights into global small RNA expression profiles and expression changes in response to head amputation. Our study reveals the evolutionary conserved role of miR-124 and brings further promising candidate small RNAs into play that might unveil new avenues for inducing restorative programs in non-regenerative organisms via small RNA mimics based therapies.

A novel RhoA-related gene, DjRhoA, contributes to the regeneration of brain and intestine in planarian Dugesia japonica.

A small GTPase, RhoA, plays a variety of functions in the regulation of cellular and developmental events via its downstream effectors, including cytokinesis, cell migration, and phagocytosis. In this study, a novel RhoA-related gene from the planarian Dugesia japonica, DjRhoA, was cloned and characterized. The full-length cDNA of DjRhoA is 869 bp, and the open reading frame encodes a poly-peptide of 194 amino acids. Phylogenetic analysis revealed that DjRhoA clustered with another RhoA-related protein, DjRho2, and located on the base of phylogenetic tree. Whole-mount in situ hybridization results indicated that DjRhoA was expressed in the brain primordia and intestine during regeneration. Knockdown of DjRhoA induces defects in the brain and intestine. These results suggested that DjRhoA was responsible for the regeneration of brain and intestine in Dugesia japonica.

The Wnt/Ca2+ signaling pathway is essential for the regeneration of GABAergic neurons in planarian Dugesia japonica.

The growth and differentiation of neurons are critical events in the establishment of proper neuron connectivity and function. Planarians have a remarkable ability to completely regenerate a functional nervous system from a pluripotent stem cell population. Thus, planarians provide a powerful model to identify genes required for neuronal differentiation in vivo. The Wnt/Ca2+ signaling pathway is crucial for cancer development, arousing inflammatory responses, and neurodegeneration. We analyzed the expression patterns and RNAi phenotypes for members of the Wnt/Ca2+ signaling pathway in the planarian, Dugesia japonica. The expression of DjWnt5a, DjPLC-ß, DjCamKII, and DjCaln during regeneration was surprisingly similar and revealing in the regenerated brain. RNAi knockdown of DjWnt5a, DjPLC-ß, DjCamKII, and DjCaln led to defects in regenerated brains including brain partial deletions, incompact phenotypes at the posterior of the new brain, and lateral branches, which could not regenerate. Furthermore, the expressions of GAD and the number of GABAergic neurons decreased. Together, these results suggest that the Wnt/Ca2+ signaling pathway is required for GABAergic neuron regeneration.

Extreme Environmental Stress-Induced Biological Responses in the Planarian.

Planarians are bilaterally symmetric metazoans of the phylum Platyhelminthes. They have well-defined anteroposterior and dorsoventral axes and have a highly structured true brain which consists of all neural cell types and neuropeptides found in a vertebrate. Planarian flatworms are famous for their strong regenerative ability; they can easily regenerate any part of the body including the complete neoformation of a functional brain within a few days and can survive a series of extreme environmental stress. Nowadays, they are an emerging model system in the field of developmental, regenerative, and stem cell biology and have offered lots of helpful information for these realms. In this review, we will summarize the response of planarians to some typical environmental stress and hope to shed light on basic mechanisms of how organisms interact with extreme environmental stress and survive it, such as altered gravity, temperature, and oxygen, and this information will help researchers improve the design in future studies.

Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs.

The discovery of RNAs (for example, messenger RNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function by delivering additional paternal information aside from solely providing the DNA 1 . Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress2,3 and metabolic disorders4-6. How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat-diet-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m5C, m2G) in sperm 30-40 nt RNA fractions that are induced by a high-fat diet. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs and rRNA-derived small RNAs, which might be essential in composing a sperm RNA 'coding signature' that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m5C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.

14-3-3 α and 14-3-3 ζ contribute to immune responses in planarian Dugesia japonica.

14-3-3 proteins are a family of highly conserved acidic proteins that regulate cellular processes. They act as a kind of important signaling molecules taking part in many crucial decisions throughout the development process. We have isolated and characterized two members of the 14-3-3 family, namely, Dj14-3-3 α and Dj14-3-3 ζ in the planarian Dugesia japonica. The Dj14-3-3 α and ζ genes encode polypeptides of 260 and 255 amino acids respectively. We have proved that the Dj14-3-3 α and ζ genes were especially expressed in the pharynx in adult and regenerating planarians by in situ hybridization and they were not involved in regeneration process. Besides, Dj14-3-3 α and ζ genes can compensate each other in planarians by RNA interference. The Dj14-3-3 α and ζ were significantly up-regulated expression when planarians were stimulated with the pathogen-associated molecular patterns including lipopolysaccharide (LPS), peptidoglycan (PGN), ß-Glu and Poly (I:C), indicating that the Dj14-3-3 α and ζ may be involved in the immune responses.

Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.

Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.

Hormonal regulation of ovarian bursa fluid in mice and involvement of aquaporins.

In rodent species, the ovary and the end of oviduct are encapsulated by a thin membrane called ovarian bursa. The biological functions of ovarian bursa remain unexplored despite its structural arrangement in facilitating oocytes transport into oviduct. In the present study, we observed a rapid fluid accumulation and reabsorption within the ovarian bursa after ovarian stimulation (PMSG-primed hCG injection), suggesting that the ovarian bursa might play an active role in regulating local fluid homeostasis around the timing of ovulation. We hypothesized that the aquaporin proteins, which are specialized channels for water transport, might be involved in this process. By screening the expression of aquaporin family members (Aqp1-9) in the ovarian tissue and isolated ovarian bursa (0, 1, 2 and 5 h after hCG injection), we found that AQP2 and AQP5 mRNA showed dynamic changes after hCG treatment, showing upregulation at 1-2 h followed by gradually decrease at 5 h, which is closely related with the intra-bursa fluid dynamics. Further immunofluorescence examinations of AQP2 and AQP5 in the ovarian bursa revealed that AQP2 is specifically localized in the outer layer (peritoneal side) while AQP5 localized in the inner layer (ovarian side) of the bursa, such cell type specific and spatial-temporal expressions of AQP2 and 5 support our hypothesis that they might be involved in efficient water transport through ovarian bursa under ovulation related hormonal regulation. The physiological significance of aquaporin-mediated water transport in the context of ovarian bursa still awaits further clarification.

Occurrence of endocrine-disrupting compounds in reclaimed water from Tianjin, China.

Continuous disposal of endocrine-disrupting compounds (EDCs) into the environment can lead to serious human health problems and can affect plants and aquatic organisms. The determination of EDCs in water has become an increasingly important activity due to our increased knowledge about their toxicities, even at low concentration. The EDCs in water samples from the reclaimed water plant of Tianjin, northern China, were identified by gas chromatography (GC)-mass spectrometry (MS). Important and contrasting EDCs including estrone (E1), 17beta-estradiol (E2), 17alpha-ethynylestradiol (EE2), 4-tert-octylphenol (OP), 4-nonylphenol (NP), bisphenol A (BPA), di-n-butyl phthalate (DnBP), diisobutyl phthalate (DIBP), and di(2-ethylhexyl)phthalate (DEHP) were selected as the target compounds. Concentrations of steroid hormones, alkylphenolic compounds and phthalates ranged from below the limit of detection (LOD) to 8.1 ng L(-1), from

Occurrence and distribution of polycyclic aromatic hydrocarbons in reclaimed water and surface water of Tianjin, China.

Persistent organic pollutants (POPs) such as polycyclic aromatic hydrocarbons (PAHs) are of great concern due to their persistence, bioaccumulation and toxic effects. In this work, 16 PAHs included in the US Environmental Protection Agency's (EPA) priority pollutant list were analyzed using solid-phase extraction-gas chromatography-mass spectrometry (SPE-GC-MS) with a selected ion monitoring (SIM) mode. Reclaimed water and surface water sampling was undertaken in Tianjin, northern China. Total PAH concentrations varied from 1800 to 35,000 ng/L in surface waters (main rivers, tributaries, ditches, etc.) with mean value of 14,000 ng/L and from 227 to 600 ng/L in reclaimed water with mean value of 352 ng/L, respectively. The PAH profiles were dominated by low molecular weight PAHs (two- and three-ring components) in reclaimed water samples and surface water samples. These indicated that PAHs in reclaimed water and surface water might origin from oil or sewage contamination (petrogenic input). To elucidate sources, molecular indices based on indices among phenanthrene versus anthracene and fluoranthene versus pyrene were used to evaluate the possible source (pyrogenic and petrogenic sources, respectively) of PAH contamination in reclaimed water and surface water. The collected data showed that petrogenic input was predominant at almost all the stations investigated. To discriminate pattern differences and similarities among samples, principal component analysis (PCA) was performed using a correlation matrix. PCA revealed the latent relationships among all the surface water stations investigated and confirmed our analytical results. The analysis results of the ratios and PCA in this study showed that the ratios and PCA could be applied to the surface water investigation to some extent.

[Distribution of tributyltin between water and liposome].

Distribution of the tributyltin (TBT) between egg-phosphatidylcholine membranes (liposome) and water under different pH and a comparison between the partition of TBT into lipid membranes and into octanol were studied. The distribution of this compound into both lipid membranes and octanol increased with pH. The major difference was that at lower pH, where ionized TBT dominated distribution was greater into lipid membranes compared to that of octanol. At high pH, where TBT predominates as neutral species, the distribution ratios were very similar in the octanol and the liposome-water system. These differences can be attributed to the properties of the biomembrane. The results indicated that the liposome-water partition model appears to be a better molecular descriptor for ionogenic organic compounds.