Disruption of Gastrulation and Heparan Sulfate Biosynthesis in EXT1-Deficient Mice

AbstractMutations in the EXT1 gene are responsible for human hereditary multiple exostosis type 1. The Drosophila EXT1 homologue, tout-velu, regulates Hedgehog diffusion and signaling, which play an important role in tissue patterning during both invertebrate and vertebrate development. The EXT1 protein is also required for the biosynthesis of heparan sulfate glycosaminoglycans that bind Hedgehog. In this study, we generated EXT1-deficient mice by gene targeting. EXT1 homozygous mutants fail to gastrulate and generally lack organized mesoderm and extraembryonic tissues, resulting in smaller embryos compared to normal littermates. RT-PCR analysis of markers for visceral endoderm and mesoderm development indicates the delayed and abnormal development of both of these tissues. Immunohistochemical staining revealed a visceral endoderm pattern of Indian hedgehog (Ihh) in wild-type E6.5 embryos. However, in both EXT1-deficient embryos and wild-type embryos treated with heparitinase I, Ihh failed to associate with the cells. The effect of the EXT1 deletion on heparan sulfate formation was tested by HPLC and cellular glycosyltransferase activity assays. Heparan sulfate synthesis was abolished in EXT1 −/− ES cells and decreased to less than 50% in +/− cell lines. These results indicate that EXT1 is essential for both gastrulation and heparan sulfate biosynthesis in early embryonic development

A Novel CRYBB2

Congenital cataract is the most common cause of the visual disability and blindness in childhood. This study aimed to identify gene mutations responsible for autosomal dominant congenital cataract (ADCC) in a Chinese family using next-generation sequencing technology. This family included eight unaffected and five affected individuals. After complete ophthalmic examinations, the blood samples of the proband and two available family members were collected. Then the whole exome sequencing was performed on the proband and Sanger sequencing was applied to validate the causal mutation in the two family members and control samples. After the whole exome sequencing data were filtered through a series of existing variation databases, a heterozygous mutation c.499T<G (p.E167X) in CRYBB2 gene was found. And the results showed that the mutation cosegregated with the disease phenotype in the family and was absolutely absent in 1000 ethnicity-matched control samples. Thus, the heterozygous mutation c.499T<G (p.E167X) in CRYBB2 was the causal mutation responsible for this ADCC family. In conclusion, our findings revealed a novel stopgain mutation c.499T<G (p.E167X) in the exon 6 of CRYBB2 which expanded the mutation spectrum of CRYBB2 in Chinese congenital cataract population and illustrated the important role of CRYBB2 in the genetics research of congenital cataract

Does the economic growth target overweight induce more polluting activities? Evidence from China.

In China, official promotion evaluation based on economic performance motivates local governments to develop high economic growth targets, which has played an active role in boosting China's economic growth in the past decades, whereas its environmental consequences have not been fully exploited. This paper finds that the economic growth target overweight has a stronger positive impact on the output of high-polluting industries than on the output of low-polluting industries, thus inducing more polluting activities. To deal with the issues of reverse causality and omitted variables bias, we take an instrumental variable approach. Examining mechanisms, we show that economic growth target overweight promotes polluting activities through the deregulation of the polluting activities in high-polluting industries. We also find an increase in the impact of the economic growth target overweight after the 2008 global economic crisis. Our study provides new evidence for explaining the dual presence of rapid economic growth and heavy environmental pollution in China

Characteristics of Newly Increased and Deceased Patients with Severe Mental Illness in a Community in Beijing from 2011 to 2021

Background There is a contradiction between a large population with severe mental illness and insufficient capacity to receive and treat them in China. Most of these patients long-termly live in the community, so it is essential for community health institutions to provide this population with timely and effective primary mental health services. Objective To analyze the characteristics of newly increased and decreased patients with severe mental illness in a community in Beijing from 2011 to 2021, so as to provide evidence for the implementation of community-based prevention and treatment of mental illnesses. Methods In January 2022, information of registered patients with severe mental illness (schizophrenia, bipolar disorder, schizoaffective disorder, persistent delusional disorder, mental disorders associated with epilepsy or mental retardation accompanied by mental disorders) in a community of Beijing was obtained through Beijing Municipal Mental Health Information Management System, including demographic characteristics, disease status and the status of file creation. The yearly morbidity, mortality and years of life lost (YLL) rates were calculated for years between 2011 and 2021. With the patient information up to December 31, 2010 as the baseline, the information of newly increased and deceased patients from 2011 to 2021 was counted. Results From 2011 to 2021, the newly increased patients outnumbered the deceased ones, and the prevalence rate increased year by year since 2012, reaching 3.77‰ in 2021. Compared with the baseline, patients with severe mental illness in 2021 presented the following features: higher education level, a higher proportion of employers, a higher proportion of 60-year-olds and older, a lower proportion of schizophrenics, a higher proportion of patients with bipolar disorder, and a shorter duration of non-creation of files, and the differences were statistically significant (P&lt;0.05). During the period, there were 212 newly increased patients, and most of them suffered from schizophrenia (57.08%, 121/212) or bipolar disorder (36.32%, 77/212). The age of the first onset was mostly between 19 and 45 years (65.57%, 139/212). The number of patients with 5 years or less of duration of non-creation of files was the most (40.57%, 86/212), and the average median was 8.5 (15.5) years. Among the 90 deceased cases, schizophrenics accounted for the highest percentage (86.67%, 78/90), and those aged over 60 years accounted for 74.44% (67/90). The top three causes of death were somatic disease (84.44%, 76/90), suicide (7.78%, 7/90), and accidental death (2.22%, 2/90). The YLL rate fluctuated between -0.250‰ and 1.436‰ during the period. Conclusion The period of 2011 to 2021 witnessed more newly increased community residents with severe mental illness than deceased ones, an increased prevalence trend of severe mental illness, a shortened duration of non-creation of files, and the aged as the major deceased group, and somatic diseases as the major cause of death. Targeted measures should be taken to cope with the above changes

Exploration of the common pathogenic link between COVID‐19 and diabetic foot ulcers: An in silico approach

Abstract Background and Aims The Coronavirus Disease‐19 (COVID‐19) is posing an ongoing threat to human health. Patients of diabetic foot ulcer (DFU) are susceptible to COVID‐19‐induced adverse outcomes. Nevertheless, investigations into their mutual molecular mechanisms have been limited to date. In the present work, we tried to uncover the shared pathogenesis and regulatory gene targets of COVID‐19 and DFU. Methods In this study, we chose GSE161281 as the COVID‐19 data set, which contained severe acute respiratory syndrome coronavirus 2 infected human induced embryonic stem cell‐derived peripheral neurons (n = 2) with uninfected controls (n = 2). The GSE134431 designated as the DFU data set, comprising full‐thickness DFU (n = 13) and diabetic foot skin (n = 8) samples from diabetic patients. The differential expressed genes (DEGs) were identified from GSE161281 and GSE134431, and the common DEGs between COVID‐19 and DFU were extracted. Multifactor regulatory network and co‐expression network of the common DEGs were analyzed, along with candidate drug prediction. Results Altogether, six common DEGs (dickkopf‐related protein 1 [DKK1], serine proteinase inhibitor A3 [SERPINA3], ras homolog family member D [RHOD], myelin protein zero like 3 [MPZL3], Claudin‐11 [CLDN11], and epidermal growth factor receptor pathway substrate 8‐like 1 [EPS8L1]) were found between COVID‐19 and DFU. Functional analyses indicated that pathways of apoptotic and Wnt signaling may contribute to progression of COVID‐19. Gene co‐expression network implied the shared pathways of immune regulation and cytokine response participated collectively in the development of DFU and COVID‐19. A multifactor regulatory network was constructed integrating the corresponding microRNAs (miRNAs) and transcription factors. Additionally, we proposed potential drug objects for the combined therapy. Conclusion Our study revealed the shared molecular mechanisms underlying COVID‐19 and DFU. The identified pivotal targets and common pathways can provide new perspectives for further research and assist the development of management strategies in patients of DFU complicated with COVID‐19

Community Characteristics and Niche Analysis of Soil Animals in Returning Farmland to Forest Areas on the Loess Plateau

Niche theory is significant for understanding the function of community structure, interspecific relationships, and community dynamic succession. However, there are few studies on the soil animal niche in returning farmland to forest areas on the Loess Plateau, making it challenging to comprehend the utilization of soil animal resources, the stability of the local community, and the succession process in the areas. Therefore, this study collected soil animals in five typical vegetation types: Robinia pseudoacacia (R), Hippophae rhamnoides (H), Populus simonii (P), Pinus tabulaeformis (T), and Armeniaca sibirica x Hippophae rhamnoides (M), with abandoned grassland (G) used as a control group. Then, the number of soil animal taxa, individuals, diversity, and niche were sampled and examined in the study areas during the four seasons of spring, summer, autumn, and winter using the manual sorting method and the Tullgren method. The results revealed that 3872 soil animals from 3 Phyla, 8 Classes, 22 Orders, and 49 Families were captured in the study areas. The dominant groups of soil macrofauna were Diptera larvae, Julidae, and Formicidae, and the dominant groups of meso–micro soil fauna were Oribatida, Protospira, and Collembola juveniles. Soil animals have rich nutritional function groups, with the most saprophytic soil animal groups. The individual density and taxa number of soil animals in G were lower than other vegetation on the whole. H, M, and P had a higher Shannon–Winner index than the other vegetation. Seasonal changes had different effects on macro and meso–micro soil fauna. The diversity of soil macrofauna is higher in spring and summer, and that of meso–micro soil fauna is higher in autumn and winter. Oribatida, Diptera Larvae, and Formicidae had a large niche width in the main taxa of soil animals, with universal adaptability to the environment. Cicadellidae and Culicidae had narrow niche widths and were highly dependent on resources and the environment. There were 67 pairs of highly overlapped (Oik > 0.8) taxa of soil animals and 56 pairs of moderately overlapped (0.6 Oik ≤ 0.8) taxa, accounting for 80.39% of the total number of taxa. Soil animals had high commonality in resource utilization, intense competition, and poor community stability. As a result, we can conclude that the soil animal community in the study areas was in the stage of succession

Experimental Study on Flow Characteristics of Aeolian Sand in Fractures

It is one of the important safety problems in the process of mining shallow coal seams in western China that the rock mass affected by mining stress breaks and forms a penetrating fracture, leading to a sand burst in the working face. The self-developed test system is used to carry out the experimental study on the flow characteristics of Aeolian sand in fractures. The research work is focused on the influence of several parameters, such as the thickness of the Aeolian sand layer, the fracture opening, and the fracture dip angle on the velocity of sand particles in fractures. The results show the following: (1) The influence of fracture opening and fracture angle on sand burst rate is much greater than that of sand thickness. No matter what the fracture angle and fracture opening value are, the influence weight of sand thickness on sand burst rate is almost zero. (2) When other conditions are unchanged, with the increase of fracture dip angle, the sand burst rate increases significantly, and the relationship between the sand burst rate and the fracture dip angle is exponential. (3) The influence weight of fracture opening is the largest. With the increase of fracture opening, the sand burst rate increases logarithmically. Finally, according to the test results, the relation equation which can simultaneously describe the influence of fracture opening and fracture inclination on the rate of the sand burst is fitted. This study can provide a theoretical basis and scientific guidance for the prevention and control of coal mine sand inrush disasters caused by roof cracking in western coal mines