African Suid Genomes Provide Insights into the Local Adaptation to Diverse African Environments.

African wild suids consist of several endemic species that represent ancient members of the family Suidae and have colonized diverse habitats on the African continent. However, limited genomic resources for African wild suids hinder our understanding of their evolution and genetic diversity. In this study, we assembled high-quality genomes of a common warthog (Phacochoerus africanus), a red river hog (Potamochoerus porcus), as well as an East Asian Diannan small-ear pig (Sus scrofa). Phylogenetic analysis showed that common warthog and red river hog diverged from their common ancestor around the Miocene/Pliocene boundary, putatively predating their entry into Africa. We detected species-specific selective signals associated with sensory perception and interferon signaling pathways in common warthog and red river hog, respectively, which contributed to their local adaptation to savannah and tropical rainforest environments, respectively. The structural variation and evolving signals in genes involved in T-cell immunity, viral infection, and lymphoid development were identified in their ancestral lineage. Our results provide new insights into the evolutionary histories and divergent genetic adaptations of African suids.

Mechanistic insights into the amelioration effects of lipopolysaccharide-induced acute lung injury by baicalein: An integrated systems pharmacology study and experimental validation.

BACKGROUND: Acute lung injury is an acute progressive respiratory failure caused by several of non-cardiogenic factors which involves in excessive amplification or uncontrolled inflammatory response. OBJECTIVES: In this study, we investigated the protective effect of baicalein against acute lung injury induced by LPS and explored the underlying mechanisms. METHODS: Forty-eight SPF male C57BL/6 mice were randomly divided into normal group, model group, dexamethasone group and baicalein low-dose, medium-dose and high-dose groups. After 5 days of adaptive feeding, the mice were intraperitoneally injected with LPS and dissected after 12 h. Hematoxylin-eosin staining, ELISA assay, immunofluorescence assay and Western-Blot were applied to appraise microstructural changes and protein expressions of lung tissues. Systems pharmacology study was used to evaluate the protection of baicalein on acute lung injury. FINDINGS: The results showed that baicalein administration could significantly inhibit LPS-induced lung morphological changes, inhibit inflammatory response and pyroptosis. A total of forty-three potential targets of baicalein and acute lung injury were obtained. And PI3K-Akt, TNF and NF-κB were mainly signaling pathways. It is worth mentioning that this experiment also confirmed that NLRP3, caspase-1 and other inflammasome are involved in pyroptosis. CONCLUSION: Baicalein has protected against LPS-induced lung tissues injury via inhibiting inflammatory response and pyroptosis.

OrthReg: a tool to predict cis-regulatory elements based on cross-species orthologous sequence conservation.

Cis-regulatory elements play an important role in the development of traits and disease in organisms (Ma et al., 2020; Woolfe et al., 2005) and their annotation could facilitate genetic studies. The Encyclopedia of DNA Elements (ENCODE) (Davis et al., 2018) and Functional Annotation of Animal Genomes (FAANG) (FAANG Consortium et al., 2015) offer pioneering data on regulatory elements in several species. Currently, however, regulatory element annotation data remain limited for most organisms. In this study, we developed a tool (OrthReg) for annotating conserved orthologous cis-regulatory elements in targeted genomes using an annotated reference genome. Cross-species validation of this annotation tool using human and mouse ENCODE data confirmed the robustness of this strategy. To explore the efficiency of the tool, we annotated the pig genome and identified more than 28 million regulatory annotation records using the reference human ENCODE data. With this regulatory annotation, some putative regulatory non-coding variants were identified within domestication sweeps in European and East Asian pigs. Thus, this tool can utilize data produced by ENCODE, FAANG, and similar projects, and can be easily extended to customized experimental data. The extensive application of this tool will help to identify informative single nucleotide polymorphisms (SNPs) in post-genome-wide association studies and resequencing analysis of organisms with limited regulatory annotation data.

Maternal genomic variability of the wild boar (Sus scrofa) reveals the uniqueness of East-Caucasian and Central Italian populations.

The phylogeography of the European wild boar was mainly determined by postglacial recolonization patterns from Mediterranean refugia after the last ice age. Here we present the first analysis of SNP polymorphism within the complete mtDNA genome of West Russian (n = 8), European (n = 64), and North African (n = 5) wild boar. Our analyses provided evidence of unique lineages in the East-Caucasian (Dagestan) region and in Central Italy. A phylogenetic analysis revealed that these lineages are basal to the other European mtDNA sequences. We also show close connection between the Western Siberian and Eastern European populations. Also, the North African samples were clustered with the Iberian population. Phylogenetic trees and migration modeling revealed a high proximity of Dagestan sequences to those of Central Italy and suggested possible gene flow between Western Asia and Southern Europe which was not directly related to Northern and Central European lineages. Our results support the presence of old maternal lineages in two Southern glacial refugia (i.e., Caucasus and the Italian peninsula), as a legacy of an ancient wave of colonization of Southern Europe from an Eastern origin.

Population Genomics Analysis Revealed Origin and High-altitude Adaptation of Tibetan Pigs.

Tibetan pig is native to the Qinghai-Tibet Plateau and has adapted to the high-altitude environmental condition such as hypoxia. However, its origin and genetic mechanisms underlying high-altitude adaptation still remain controversial and enigmatic. Herein, we analyze 229 genomes of wild and domestic pigs from Eurasia, including 63 Tibetan pigs, and detect 49.6 million high-quality variants. Phylogenomic and structure analyses show that Tibetan pigs have a close relationship with low-land domestic pigs in China, implying a common domestication origin. Positively selected genes in Tibetan pigs involved in high-altitude physiology, such as hypoxia, cardiovascular systems, UV damage, DNA repair. Three of loci with strong signals of selection are associated with EPAS1, CYP4F2, and THSD7A genes, related to hypoxia and circulation. We validated four non-coding mutations nearby EPAS1 and CYP4F2 showing reduced transcriptional activity in Tibetan pigs. A high-frequency missense mutation is found in THSD7A (Lys561Arg) in Tibetan pigs. The selective sweeps in Tibetan pigs was found in association with selection against non-coding variants, indicating an important role of regulatory mutations in Tibetan pig evolution. This study is important in understanding the evolution of Tibetan pigs and advancing our knowledge on animal adaptation to high-altitude environments.

Extrarenal Wilms' Tumor of the Female Genital System: A Case Report and Literature Review.

Extrarenal Wilms' Tumors (ERWTs) are rare. There have been only 25 cases of ERWT arising from the female genital system reported in the literature. In this paper, we report a 60-year-old woman with a complaint of vaginal bleeding and a polypoid mass in the uterine cavity by sonography that was demonstrated as ERWT by pathology after resection. The pathological characteristics, histological origination, diagnosis, therapy and prognosis of ERWT in female reproductive system are discussed in this paper in the purpose of improving the diagnosis and therapy of this rare tumor.

Association of TLR4 Gene rs2149356 polymorphism with primary gouty arthritis in a case-control study.

BACKGROUND: The toll-like receptor (TLR)4-interleukin1ß (IL1ß) signaling pathway is involved in the monosodium urate (MSU)-mediated inflammation. The aim of this present study was to determine whether the TLR4 gene rs2149356 SNP is associated with gouty arthritis (GA) susceptibility and whether rs2149356 SNP impacts the TLR4-IL1ß signaling pathway molecules expression. METHODS AND FINDINGS: The rs2149356 SNP was detected in 459 GA patients and 669 control subjects (containing 459 healthy and 210 hyperuricemic subjects). Peripheral blood mononuclear cells (PBMCs) TLR4 mRNA and serum IL1ß were measured in different genotype carriers, and correlations between TLR4 gene SNP and TLR4 mRNA, IL1ß were investigated. The frequencies of the genotype and allele were significantly different between the GA and control groups (P<0.01, respectively). The TT genotype was associated with a significantly increased risk of GA (OR = 1.88); this finding was not influenced by making adjustments for the components of possible confounders (adjusted OR = 1.96). TLR4 mRNA and IL1ß were significantly increased in the TT genotype from acute GA patients (P<0.05, respectively), and lipids were significantly different among three genotypes in the GA patients (P<0.05, respectively). CONCLUSIONS: The TLR4 gene rs2149356 SNP might be associated with GA susceptibility, and might participate in regulating immune, inflammation and lipid metabolism. Further studies are required to confirm these findings.

No evidence for involvement of the toll-like receptor (TLR) 4 gene Asp299Gly and Thr399Ile polymorphisms in susceptibility to primary gouty arthritis.

Previous studies demonstrated that toll-like receptor (TLR) 4 was involved in the development of autoinflammatory disease including gouty arthritis (GA). TLR4 functional gene Asp299Gly and Thr399Ile polymorphisms play a role in some autoinflammatory disease susceptibility. We undertook this study to analyze the association between the genetic polymorphisms within TLR4 gene and the susceptibility to GA in Chinese Han people. Two functional variants, Asp299Gly and Thr399Ile, in the TLR4 gene were genotyped using 5' exonuclease TaqMan technology from 218 male GA patients and 226 ethnically matched controls. None polymorphisms of Asp299Gly and Thr399Ile were detected in all GA cases and controls, which indicates that there is no evidence for involvement of the TLR4 gene Asp299Gly and Thr399Ile polymorphisms in susceptibility to primary GA in the Chinese Han population. Further studies with extended single nucleotide polymorphisms should be performed.

[Studies on the polysaccharide SGPS2 from the fruits of Siraitia grosvenorii].

OBJECTIVE: To study the structure of the polysaccharides constituents in the fruits of Siraitia grosvenorii (Swingle) C. Jeffrey. METHODS: SGPS2 was purified by DEAE-cellulose and Sephadex G-200 column chromatography, the component and structure of SGPS2 were analyzed on the basis of spectral and chemical studies by HPLC, IR analysis, partial hydrolysis with acid, methylation analysis, GC and 13C-NMR. RESULTS: The molecular weight of SGPS2 was 650 000. Polysaccharide was composed of L- made up of (1 --> 2, 4) linked rhamnose, (1 --> 4) linked rhamnose residues in main chain; and (1 --> 2) linked rhamnose, (1 --> 3) linked rhamnose in side chains. Terminal residues attached main chain to rhamnose. CONCLUSION: SGPS2 was composed of rhamnose and curonic acid.

A new dilactone from the seeds of Gaultheria yunnanensis.

Gaultheriadiolide (1), a new compound, together with the known dauosterol (2), ginkgetin (3), myricetin (4), 6-ethyl-5-hydroxy-2,7-dimethoxy-1,4-naphthoquinone (5), ursolic acid (6), methyl salicylate 2-O-beta-D-xylosyl(1-->6)beta-D-glucopyranoside (7), and methyl salicylate 2-O-beta-D-glucopyranoside (8) were isolated from Gaultheria yunnanensis. The structure was elucidated on the basic of spectral analysis, especially 1D and 2D NMR. Primary bioassays showed that compound 1 had medium cytotoxic activity against HEp-2 and HepG2 Cells, with IC(50) of 23.337 microM and 29.4497 microM, respectively.

[Study on the prevalence rate and risk factors of chronic obstructive pulmonary disease in rural community population in Hubei province].

OBJECTIVE: To explore the prevalence of chronic obstructive pulmonary disease (COPD) and its risk factors in rural area in the southern part of Hubei province and to provide evidence for prevention and treatment. METHODS: Using uniform scheme, procedures and questionnaire, a multistage survey for 1883 people in rural area in southern part of Hubei province was performed, and physical examinations and lung function tests were conducted for every participant. RESULTS: In this survey, 186 COPD cases were identified with a overall prevalence of 9.88%. The prevalence for male was 13.68% while in female it was 6.46%. The prevalence was higher in males than in females (chi2 = 27.48, P< 0.001) and higher with the increase of age (chi2 = 79.22, P<0.001). Factors associated with COPD were identified in one-way variance model as follows: sex, age, smoking, time for cooking, using biomass fuels for in-door cooking, family history, frequent cough before age 14, low body index and having house remodelling in the last five years. Results from multivariate logistic regression analysis showed that sex (OR= 1.3010), age (OR = 1.8506), smoking (OR= 3.0118), cooking time (OR= 1.7651), family history (OR = 1.5278), frequent cough before age 14 (OR = 2.8965) were risk factors. CONCLUSION: The prevalence of COPD in the southern part of Hubei province was high, suggesting that comprehensive intervention measures should be taken.

[Effects of adrenomedullin regulating inducible nitric oxide synthase on proliferation and apoptosis in hypoxic pulmonary artery smooth muscle cells].

AIM: To investigate the effects of hypoxia on the proliferation and apoptosis of PASMC, to evaluate the role of iNOS protein expression and ADM on the hypoxic pulmonary hypertension (HPH) pathogenesis. METHODS: To culture rat pulmonary artery smooth muscle cell (PASMC), cultured PASMC cells were grouped into: normoxic group; hypoxic group; hypoxia + L-NAME group; hypoxia+ ADM group. Proliferation of PASMC were investigated by MTT and PCNA. Apoptosis of PASMC were examined by flow-cytometry. Westen blot was used to measure protein expression of iNOS induced by hypoxia. RESULTS: (By MTT, the value of 24 h hypoxia was significantly higher than that in the normoxic group (P < 0.01), the value of the hypoxia + ADM was significantly lower than that in hypoxia group, the value of the hypoxia + L-NAME was significantly higher than those of hypoxic group and normoxic group (P < 0.01). (2) By immunohistochemistry, PCNA was poorly positive in PASMC, whereas positive after 24 h hypoxia (P < 0.01), ADM inhibited the expression of PCNA significantly (P < 0.01), whereas L-NAME increased the expression of PCNA significantly (P < 0.01). (3) By FCM, apoptosis index was not significantly different between the normoxic group, hypoxic group, hypoxia + L-NAME and hypoxia + ADM (P > 0.05). (4) By Western blot, iNOS expression was poorly positive in control group, positive after 4 h hypoxia (P < 0.01), increasing as the hypoxia environment continued (P < 0.01). L-NAME had no effect on iNOS protein, ADM promoted iNOS expression (P < 0.01). CONCLUSION: (1) Hypoxia stimulates the proliferation of PASMC, and has no obvious effects on the apoptosis of PASMC. (2) Hypoxia induces the expression of iNOS, ADM can increase expression of iNOS, ADM and INOS plays a role of protection in HPH pathogenesis.