Progress on functional mechanisms of colorectal cancer causal SNPs in post-GWAS.

Colorectal cancer (CRC) is caused by genetic and environmental factors, and the genetic component plays a significant role in CRC development. Currently, genome-wide association studies (GWAS) have identified a large number of genetic loci associated with CRC risk. In the post-GWAS era, more and more efforts focus on deciphering the biological mechanisms behind these potential causal variants by using multi-omics data and functional experiments. Many analyses have revealed that most risk single nucleotide polymorphisms (SNPs) are located in non-coding regions and these variants may regulate the expression of target genes by altering the transcription factor-binding motif, epigenetic modification, chromatin accessibility or 3D genome conformation. Results obtained from post-GWAS era have highlighted the possibility of moving from association to function. In this review, we summarize the current status of CRC post-GWAS studies and discusses the clinical application as well as future directions of CRC GWAS, in order to better gain insight into the molecular basis of CRC and provide evidence for prevention.

Efficacy of bioactive compounds of Chaihu () on glaucomatous optic atrophy through interleukin-6/hypoxia inducible factor-1α signal pathway.

OBJECTIVE: To investigate the bioactive compounds of Chaihu (Radix Bupleuri Chinensis) (RB) on glaucomatous optic atrophy (GOA), and to study the pharmacological mechanism. METHODS: We collected information on the bioactive compounds of RB from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to bioactive compounds and GOA were also obtained. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analyses were performed to investigate the potential mechanism of RB against GOA. Subsequently, the main bioactive compounds of RB and targets of GOA were docked by Autodock software. Moreover, a GOA model of retinal ganglion cells (RGCs) induced by cobalt chloride was established to verify the effect of RB on GOA. RESULTS: There were 17 main bioactive compounds and 46 key targets were screened as potential players in GOA. The compound-target network mainly contained 17 compounds and 46 corresponding targets, and the key targets consisted of interleukin-6 (IL-6), hypoxia inducible factor-1α (HIF1A), Caspase-3, estrogen receptor alpha (ESR1), MYC proto-oncogene (MYC), and vascular endothelial growth factor A (VEGFA). Forty-nine significantly enriched GO terms, and 134 KEGG signaling pathways were identified (P < 0.05), including HIF-1, tumor necrosis factor, VEGF, prolaction, and other signaling pathways. Molecular docking results showed that the main bioactive compounds of RB exhibited the strongest binding activity with IL-6. Furthermore, experimental validation showed that the RB extract inhibited the activity and promoted apoptosis of RGCs in a dose-dependent manner. The RB extract also suppressed the expression of Bax, Caspase-3, and Caspase-9 and regulated malonaldehyde, superoxide dismutase, and glutathione peroxide by inhibiting the IL-6/HIF-1α signaling pathway. CONCLUSIONS: The present study provided insights into the mechanism of RB on GOA. RB mainly reverses GOA by inhibiting the IL-6/HIF-1α signaling pathway.

Practice audits to reduce caesareans in a tertiary referral hospital in south-western China.

OBJECTIVE: To assess the effectiveness of a three-stage intervention to reduce caesarean deliveries in a Chinese tertiary hospital. METHODS: A retrospective study was conducted to assess whether educating staff, educating patients and auditing surgeon practices (introduced in 2005) had reduced caesarean delivery rates. Multiple logistic regression was used to check for a potential association between caesarean rates and rates of admission to the neonatal intensive care unit (NICU). FINDINGS: The caesarean delivery rate ranged from 53.5% to 56.1% in 2001-2004 and from 43.9% to 36.1% in 2005-2011. When 2001-2004 and 2005-2011 were treated as "before" and "after" periods to evaluate the intervention's impact on the mean caesarean section rate, a significant reduction was noted: from 54.8% to 40.3% (odds ratio, OR: 0.56; 95% confidence interval, CI: 0.52-0.59; χ(2) test: P < 0.001). The overall drop in the caesarean section rate was significant (χ(2) test: P < 0.001) and inversely correlated with the years (Spearman's ρ: -0.096; P < 0.001). Although complicated pregnancies increased after 2004, the primary caesarean section rate decreased annually by 20% on average in 2005-2011, after practice audits were implemented. Multiple logistic regression showed a positive association between the caesarean delivery rate and the rate of admission to the NICU (adjusted OR: 1.26; 95% CI: 1.14-1.40). CONCLUSION: Patient and staff education and practice audits reduced the Caesarean section rate in a tertiary referral hospital without an increase in admissions to the NICU.

Inter-annual variation patterns in the carbon footprint of farmland ecosystems in Guangdong Province, China.

Carbon sequestration in farmland ecosystems is an important link in the world carbon cycle and plays an important role in regional carbon reduction. Guangdong, a major industrial and economic province in China, was used as the study area, and the period 2001-2020 was taken as the study period. The carbon emissions, sequestration, and footprint of farmland ecosystems in Guangdong were estimated using carbon emission factors for agricultural inputs that are closer to the actual situation in China. The study showed that: (1) Carbon average emissions from farmland in Guangdong during the study period was 3.7624 million t a-1, with a balanced overall trend of change, and that nitrogen fertilize applications was the main factor contributing to carbon emissions. (2) The carbon sink capacity of Guangdong farmland ecosystems showed an overall decreasing trend of 10.32%, with an average annual carbon sink of 19.0363 million t a-1. Paddy and sugar cane cultivations were the main factor of carbon sink in farmland. (3) The average annual carbon footprint of Guangdong's farmland ecosystems was 531,100 ha a-1, which was in a carbon surplus. Carbon surplus and footprint showed a decreasing trend year by year. The paper results provide a theoretical basis for the formulation of carbon emission reduction policies and industrial restructuring in Guangdong and provinces with the same industrial structure.

In vitro study on human cytomegalovirus affecting early pregnancy villous EVT's invasion function.

BACKGROUND: Human cytomegalovirus (HCMV) is the most common pathogen in uterus during pregnancy, which may lead to some serious results such as miscarriage, stillbirth, cerebellar malformation, fetus developmental retardation, but its pathogenesis has not been fully explained. The hypofunction of extravillous cytotrophoblast (EVT) invasion is the essential pathologic base of some complications of pregnancy. c-erbB-2 is a kind of oncogene protein and closely linked with embryogenesis, tissue repair and regeneration. Matrix metalloproteinase (MMP) is one of the key enzymes which affect EVT migration and invasion function. The expression level changes of c-erbB-2, MMP-2 and MMP-9 can reflect the changes of EVT invasion function. RESULTS: To explore the influence of HCMV on the invasion function of EVT, we tested the protein expression level changes of c-erbB-2, MMP-2 and MMP-9 in villous explant cultured in vitro infected by HCMV, with the use of immunohistochemistry SP method and western blot. We confirmed that HCMV can reproduce and spread in early pregnancy villus; c-erbB-2 protein mainly expressed in normal early pregnancy villous syncytiotrophoblast (ST) remote plasma membrane and EVT, especially remote EVT cell membrane in villous stem cell column, little expressed in ST proximal end cell membrane and interstitial cells; MMP-2 protein primarily expressed in early pregnancy villous EVT endochylema and rarely in villous trophoblast (VT), ST and interstitial cells; MMP-9 protein largely expressed in early pregnancy villous mesenchyme, EVT and VT endochylema. Compared with control group, the three kinds of protein expression level in early pregnancy villus of virus group significantly decreased (P < 0.05). CONCLUSION: HCMV can infect villus in vitro and cause the decrease of early pregnancy villous EVT's invasion function.

Field monitoring of Helicoverpa armigera (Lepidoptera: Noctuidae) Cry1Ac insecticidal protein resistance in China (2005-2017).

BACKGROUND: Bt cotton expressing Cry1Ac can efficiently control Helicoverpa armigera, but field-evolved Bt resistance reduces its efficacy. Susceptibility of H. armigera field populations to Cry1Ac protein has been monitored since Bt cotton was commercialized in 1997 in China. Here we report the results of our continued monitoring from 2005 to 2017 to provide important guidelines for sustainably growing cotton. RESULTS: From 13 provinces and regions, 221 populations were sampled and measured. IC50 values (concentration producing 50% inhibition of larval development to third instar) among different strains ranged from 0.004 to 0.212 µg mL-1 , the percentage survival at a diagnostic concentration (IC99 , 1.0 µg mL-1 ) (SUR) ranged from 0% to 22.2%, and the percentage of field populations yielding survivors at diagnostic concentration (PSD) increased from 0 in 2006 and 2007 to 80% in 2015. CONCLUSIONS: Compared to resistance level from 1998 to 2004 and the geographic baseline in different places of China in 1997, Bt resistance of H. armigera field populations to Cry1Ac protein has increased significantly, but failure of Bt cotton has not yet been detected. © 2018 Society of Chemical Industry.