FibROAD: a manually curated resource for multi-omics level evidence integration of fibrosis research.

Organ fibrosis represents a vital health threat that substantially contributes to yearly mortality rates. While a considerable amount of research has been conducted on fibrosis, these reports have only focused on specific organs as affected within distinct disorders. Accordingly, results from such studies have been unable to provide a comprehensive understanding of the pathological processes involved. Here, we describe the development of FibROAD, an open-access database that integrates evidence from fibrosis-associated disorders as obtained from both the literature and multi-omics data. This resource will greatly assist both researchers and clinicians in the comprehension and treatment of this condition. FibROAD currently involves an assembly of 232 strong evidence-based fibrosis-related genes (FRGs) as garnered from 909 PubMed publications and contains lists of multi-omics data from > 4000 samples including RNA-seq, single-cell RNA-seq, miRNA-seq, ChIP-seq, ATAC-seq MeDIP-seq and MBD-seq as obtained from 17 different organs in 5 species. Results from integrative analyses as obtained using FibROAD have demonstrated that FRGs can be indicators for a wide range of organ fibrosis and reveal potential pro-fibrotic candidate genes for fibrosis research. In conclusion, FibROAD serves as a convenient platform where researchers can acquire integrated evidence and a more comprehensive understanding of fibrosis-related disorders. Database URL  https://www.fibroad.org.

[Development and model of health education and health promotion for schistosomiasis control in mountainous and hilly endemic areas].

Transmission control and interruption of schistosomiasis has been gradually achieved in the mountainous and hilly endemic areas with the implementation of the schistosomiasis control programmes, which are moving towards the progress of schistosomiasis elimination. As an important measure of schistosomiasis control, health education is experiencing new challenges and problems in the new situation, and conventional health education of schistosomiasis control has already failed to meet the needs of socioeconomic and cultural development and the increasing changes of human production and life styles in the endemic areas. Therefore, a precision health education model for schistosomiasis control is of great need to be established to highly effectively promote the implementation of schistosomiasis control measures. This review summarizes the important role of health education in schistosomiasis control in mountainous and hilly endemic areas, and describes the new health education model based on optimization of the policy environment and creation of the community atmosphere according to the changes in the endemic situation of schistosomiasis and requirements of the schistosomiasis control target, so as to promote the precision and sustainable implementation of health education and health promotion in schistosomiasis control.

[Application and effect of integrated control model of schistosomiasis interruption in mountainous and hilly endemic regions].

OBJECTIVE: To explore the integrated schistosomiasis control model in mountainous and hilly endemic regions, so as to provide insights into the development of the schistosomiasis elimination strategy. METHODS: Five hilly and mountainous areas endemic for schistosomiasis were selected as the integrated control demonstration areas in Sichuan Province from 2011 to 2015. According to the epidemic characteristics, economic levels and overall development planning of the demonstration areas, the goals, strategies and measures were developed, and the effectiveness of schistosomiasis control was evaluated following implementation of the integrated control. RESULTS: The support system of the integrated schistosomiasis control model was built in the integrated control demonstration areas in Sichuan Province from 2011 to 2015, and five ecological, industrialized and sustainable development models of integrated schistosomiasis control were developed, including integration of balancing rural and urban development, systematic ecological improvement, intensified ecological agriculture, scientific management and health education of schistosomiasis control and ecological ethnic circular economy. Since the implementation of the integrated schistosomiasis control model, the snail habitats were completely changed. Until 2015, 92.0% of all historical areas with snails were managed, the coverage of safe drinking water was 100.0%, and more than 95.0% of the livestock were fenced. The coverage of sanitary toilets increased by 93.0%, 96.8%, 78.8%, 87.1% and 82.0% from 2011 to 2015, respectively, and the farmers'mean yearly income increased by 32.7% in the demonstration areas. From 2011 to 2015, the seroprevalence of human Schistosoma japonicum infections reduced from 3.1% in 2011 to 1.6% in 2015 in the demonstration areas, and no egg-positives were identified. In addition, the number of fenced bovines reduced year by year, and no egg-positives were detected. The areas of snail habitats were 398.7, 108.2 hm2 and 52.9 hm2 in the demonstration areas from 2011 to 2013, with no infected snails found, and no snails were detected since 2014. The awareness of schistosomiasis control knowledge and percentage of correct behavior formation increased year by year among residents in the demonstration areas from 2011 to 2015. CONCLUSIONS: The five integrated schistosomiasis control models meet the needs of the current schistosomiasis control activities in mountainous and hilly endemic areas of Sichuan Province, and achieve the goals of controlling the sources of S. japonicum infections, economic development, social progress and improving the ecological environment, which provides new insights into schistosomiasis elimination in the country.

[Construction and application of the surveillance system for schistosomiasis transmission risk in Sichuan Province].

OBJECTIVE: To build a schistosomiasis transmission risk surveillance system in Sichuan Province, so as to provide technical support for facilitating the progress towards schistosomiasis elimination in the province. METHODS: The surveillance sites for schistosomiasis transmission risk were assigned in 63 endemic counties (districts) of 11 cities (prefectures) in Sichuan Province. During the period from 2015 through 2018, wild feces contamination, the sources of Schistosoma japonicum infections (fever patients, livestock and wild animals), water infectivity in key settings, snail distribution in key settings, and snail breeding risk (snail importation and spread, floating debris carrying snails and snail breeding in ecological wetlands) were monitored in the surveillance sites. RESULTS: From 2015 to 2018, a total of 1 636 wild faces were detected in Sichuan Province, and 3 faces were positive for S. japonicum, with a 0.18% positive rate; among 3 995 livestock and 59 wild mice monitored, no S. japonicum infection was detected. A total of 49 414 fever patients were monitored in 2018, and 493 were seropositive for S. japonicum infection; then, 445 seropositives were subjected to stool examinations, and no egg-positives were found. From 2010 to 2018, a total of 93 sentinel sites were assigned, and 3 994 sentinel mice were placed for monitoring the water infectivity, with one S. japonicum-infected mouse detected. Between 2015 and 2018, a total of 4 156 key settings were investigated covering an area of 1 998.46 hm2, and 668 settings were detected with snails (16.07%), covering an area of 193.26 hm2; 497 suspected settings with a likelihood of snail importation with plant introduction were monitored from 2017 to 2018, and 65 settings with snails were found with 2 673 snails captured; 593 sites were assigned to collect the floating debris from 2017 to 2018, and 9 191.39 kg floating debris were collected with 186 snails captured; 4 wetlands were monitored for the risk of schistosomiasis transmission from 2013 to 2015, and snail breeding was found in 2 wetlands. No S. japonicum infection was identified in snails captured from all surveillance sites. CONCLUSIONS: A sensitive and effective schistosomiasis transmission risk surveillance system has been successfully established in Sichuan Province. There is still a risk of schistosomiasis transmission risk in local areas of Sichuan Province. Therefore, the integrated schistosomiasis control measures with emphasis on the control of the source of S. japonicum infections should be further intensified, and snail monitoring and control and monitoring and control of schistosomiasis in wetlands should be also intensified.

[Surveillance of epidemic factors of schistosomiasis in wetlands in Sichuan Province].

OBJECTIVE: To investigate the epidemic factors of schistosomiasis in wetlands in Sichuan Province, so as to provide scientific evidence for the prevention and control of schistosomiasis in wetlands. METHODS: The artificial and natural wetlands were selected from Sichuan Province, and the relevant data regarding wetlands were collected. Routine snail survey, investigation on human morbidity due to schistosomiasis, snail diffusion experiments, questionnaire survey, determination of water infectivity and retrospective survey were conducted. RESULTS: In Sichuan Province, the mean densities of living snails were 0.003 snails/0.1 m2 and 2.033 snails/0.1 m2 in the upper and lower reaches of the Meiwan Reservoir wetlands, 0.08 snails/0.1 m2 in the Jinyan Lake of Guanghan City, 0.21 snails/0.1 m2 in Muhe River of Guanghan City, and 0.02 snails/0.1 m2 prior to the construction of Qiong-hai wetland park in Xichang City in 2015. Artificial simulation experiments showed that the largest distance of snail diffusion in water was 2 000 m. There were 8.80% (41/466) of subjects that lived neighboring wetlands, worked in wetlands and visited wet-lands having infested water contact behaviors. A total of 690 sentinel mice were assigned, and no Schistosoma japonicum infection was detected in the 677 mice dissected. Retrospective survey showed that the construction of the Meiwan Reservoir caused the spread of schistosomiasis in Dailing County, and snails were found in the ditches entering the Jinyan Lake and in Jinyan Lake areas 5 years following the construction of the Jinyan Lake in Guanghan City, with S. japonicum -infected snails detected in the ditches entering the Jinyan Lake. CONCLUSIONS: O. hupensis snails are found in some wetlands in Sichuan Province. Protection of wetlands and snail control with environmental improvements are recommended for the prevention of snail importation in natural wetlands, while in artificial wetlands, thorough snail control is recommended during the construction of the wetlands because of the likelihood of snail importation via water systems. In addition, both natural and artificial wetlands require long-term systematic surveillance of schistosomiasis.

[Study on interventions based on urban - rural integration system construction to consolidate achievements of schistosomiasis control in hilly schistosomiasis endemic areas].

OBJECTIVE: To explore the effectiveness of comprehensive schistosomiasis control interventions based on urban-rural integration system construction to carry out the schistosomiasis control in hilly schistosomiasis endemic areas, so as to offer a new mode to consolidate the achievements of schistosomiasis control in the new situation. METHODS: Shouan Town and Changqiu Township in Pujiang County in hilly schistosomiasis endemic regions were selected as demonstration areas. The comprehensive schistosomiasis control interventions based on urban-rural integration system construction were implemented, including the land consolidation, centralized residence and so on. The effectiveness the interventions was evaluated. RESULTS: In Shouan Town and Changqiu Township, the transformed environments with Oncomelania hupensis snail habitats were 1 330.61 hm2 and 1 456.84 hm2, the areas with snails decreased from 94.31 hm2 and 83.00 hm2 in 2000 to both 0 in 2015, the positive rates of serological tests for schistosomiasis decreased from 11.8% and 7.53% in 2000 to 1.01% and 1.86% in 2015, and the positive rates of parasitological tests decreased from 0.18% and 0.15% in 2000 to both 0 in 2015 respectively. The numbers of cattle decreased from 358 and 368 in 2000 to 4 and 6 in 2015 respectively. In 2000, the schistosome infection rates of cattle were 3.63% and 6.51% in Shouan Town and Changqiu Township respectively, and from 2004, no infected cattle were found. CONCLUSIONS: The comprehensive schistosomiasis control interventions based on urban-rural integration system construction can decrease the schistosome infection rate and area with snails effectively, providing a new mode for schistosomiasis elimination.

Transmembrane helix of novel oncogene with kinase-domain (NOK) influences its oligomerization and limits the activation of RAS/MAPK signaling.

Ligand-dependent or independent oligomerization of receptor protein tyrosine kinase (RPTK) is often an essential step for receptor activation and intracellular signaling. The novel oncogene with kinase-domain (NOK) is a unique RPTK that almost completely lacks an ectodomain, expresses intracellularly and activates constitutively. However, it is unknown whether NOK can form oligomer or what function oligomerization would have. In this study, two NOK deletion mutants were generated by either removing the ectodomain (NOKDeltaECD) or including the endodomain (NOK-ICD). Co-immunoprecipitation demonstrated that the transmembrane (TM) domain of NOK was essential for its intermolecular interaction. The results further showed that NOK aggregated more closely as lower order oligomers (the dimer- and trimer-sized) than either deletion mutant did since NOK could be cross-linked by both Sulfo-EGS and formaldehyde, whereas either deletion mutant was only sensitive to Sulfo-EGS. Removing the NOK TM domain (NOK-ICD) not only markedly promoted higher order oligomerization, but also altered the subcellular localization of NOK and dramatically elevated the NOK-mediated constitutive activation of extracellular signal-regulated kinase (ERK). Moreover, NOK-ICD but not NOK or NOKDeltaECD was co-localized with the upstream signaling molecule RAS on cell membrane. Thus, TM-mediated intermolecular contacting may be mainly responsible for the constitutive activation of NOK and contribute to the autoinhibitory effect on RAS/MAPK signaling.

The carboxyl terminal tyrosine 417 residue of NOK has an autoinhibitory effect on NOK-mediated signaling transductions.

Receptor protein tyrosine kinases (RPTKs) are essential mediators of cell growth, differentiation, migration, and metabolism. Recently, a novel RPTK named NOK has been cloned and characterized. In current study, we investigated the role of the carboxyl terminal tyrosine 417 residue of NOK in the activations of different signaling pathways. A single tyrosine to phenylalanine point mutation at Y417 site (Y417F) not only dramatically enhanced the NOK-induced activation of extracellular signal-regulated kinase (ERK), but also markedly promoted the NOK-mediated activation of both signal transducer and activator of transcription 1 and 3 (STAT1 and 3). Moreover, the proliferation potential of NIH3T3-NOK (Y417F) stable cells were significantly elevated as compared with that of NIH3T3-NOK. Overall, our results demonstrate that the tyrosine Y417 residue at the carboxyl tail of NOK exhibits an autoinhibitory role in NOK-mediated signaling transductions.