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The age of the Silurian “Lower Red Beds” (LRBs), which occur widely in South China, has long been controversial because of the scarcity of index fossils. Here, we report a fauna with abundant trilobites from the LRBs in Wuhan, Middle Yangtze region, consisting of Aulacopleura (Paraaulacopleura) pijiazhaiensis, ‘Encrinuroides’ yichangensis, Gaotania hubeiensis, Hyrokybe gaotanensis, Japonoscutellum yichangense, Latiproetus latilimbatus, and Ptilillaenus lojopingensis. These trilobites are common in the Leijiatun, upper Xiangshuyuan, Shihniulan, and Lojoping formations in the Upper Yangtze region, and belong to the middle to upper Aeronian Ptilillaenus or ‘Encrinuroides’–Ptilillaenus–Latiproetus assemblages. The discovery of this trilobite assemblage suggests that the LRBs are probably partly of middle–late Aeronian age in the Middle Yangtze region. Thus, the lower boundary of the LRBs is likely diachronous in the Yangtze region, ranging from the middle–late Aeronian to the early Telychian. The discovery of the Ptilillaenus assemblage in the Wuhan LRBs expands the paleogeographic distribution of this assemblage and provides evidence of deeper depositional environment of the LRBs in the study area versus shallow waters in other areas of the Yangtze region.

The Hongguleleng Formation, the highest and most important Devonian marine carbonate horizon in western Junggar, contains an endemic shallow-water Icriodus–Polygnathus conodont fauna with rare palmatolepids and other genera. The conodont faunas from the Bulongguoer and the Wulankeshun sections are similar, with high abundance (about 40%) of endemic taxa (13 taxa), indicating isolation of the Junggar Basin during early Famennian. Non-endemic species in the faunas suggest that the Lower Member of the Hongguleleng Formation is assignable to the Pa. rhomboidea Zone to the Pa. marginifera marginifera Zone of early Famennian, not including the Frasnian–Famennian boundary. The Upper Member may be of late Famennian–early Tournaisian in age on the basis of our preliminary faunal analysis.

A new genus of Eugaleaspidiformes (Galeaspida, Agnatha), Jiangxialepis gen. nov., is described from the Llandovery (Silurian) Fentou Formation from Wuhan, Hubei, South China. The new genus belongs ...

To explore the genomic profiles of Chinese patients with castration sensitive prostate cancer and those with metastatic castration resistant prostate cancer via germline and circulating tumor DNA sequencing.A hybridization capture based next-generation sequencing assay was used to identify germline and somatic alterations in 50 genes including androgen receptor pathway genes, DNA damage repair pathway genes,We successfully sequenced DNA from 396 blood samples and 32 matched tumor tissue samples from 396 patients. We observed a similar frequency of deleterious germline alterations between patients with castration sensitive prostate cancer and metastatic castration resistant prostate cancer (8.9% vs 9.8%, p0.05). There was a high consistency (90.9%) between metastatic tumor tissue and matched circulating tumor DNA. Among patients who were circulating tumor DNA positive we observed significantly higher alteration frequencies ofThrough genomic profiling of prostate cancer across clinical states we identified a similar frequency of deleterious germline alterations between patients with castration sensitive prostate cancer and metastatic castration resistant prostate cancer. We explored the genomic diversity of androgen receptor and DNA damage repair pathway genes between patients with metastatic castration sensitive prostate cancer and metastatic castration resistant prostate cancer. Higher alteration frequencies of

The percentage of filter-feeder species in benthic ostracod assemblages shows evident changes during the Late Devonian Frasnian–Famennian (F–F) transition with two sharp rises in the event stratal interval based on materials collected from the Yangdi section, South China. Neither anoxia nor oligotrophy, eustasy should have been the only primary cause of filter-feeders signal in the F–F event. The sea level fall and rise would create deteriorative environmental conditions such as lower oxygenation and less nutrients, which altogether reduced the diversity and abundance of the benthic ostracods in the F–F transition. The percentage of filter-feeders showed a decrease during the regression, and vice-versa. Therefore, the filter-feeders may be potentially an indicator of sea level changes in the F–F event.

Arthrodira is the most widely distributed and diversified subgroup of Placodermi, which itself is the most diverse major group of the Devonian jawed vertebrates. Arthrodires were traditionally divided into the basal, paraphyletic “Dolichothoraci” and the highly nested monophyletic Brachythoraci, the latter of which displays reduction of body armor. Among brachythoracids, the Coccosteomorphi and Pachyosteomorphi further form a nested monophyletic Eubrachythoracidi. The sister group relationship between Coccosteomorphs and Pachyosteomorphs has been supported by most phylogenetic analyses, but the basal members and their interrelationships in these two groups are still unstable. Coccosteomorphs and pachyosteomorphs are the most diverse arthrodires in the Middle and Late Devonian. Among them, coccosteomorphs are found in strata of the lacustrine and littoral-neritic facies, while the pachyosteomorphs are mostly marine. Selenosteidae, one of the most well-known families in Pachyosteomorphi, are found in marine strata of Europe, North America, and North Africa. Junqing Wang found the nuchal plate of suspected Selenosteidae in the Xiejingsi Formation (early Famennian, Late Devonian) in Hunan Province, China, but due to the lack of identification features of the material, its exact systematic position awaits further determination. The Zhulumute Formation is a lithological unit in western Junggar, Xinjiang of northwest China and is mainly composed of conglomerates, pebbly sandstones and medium- to coarse-grained sandstones, with typical braided stream lithofacies. Channel-fill deposits are thick, with well-developed parallel bedding, scour structure, and large-scale trough, wedge and tabular cross-beddings. This part contains a large number of plant stem fossils in fragment. The fine-grained floodplain deposits are thin, with horizontal beddings and small sand ripple beddings; fine fragments of plant stems or leaves can be seen in the siltstones. These characteristics indicate that the Zhulumute Formation in the Bulongguoer area was formed in the braided stream environment. At the same time, according to the preserved plant fossil Leptophloeum rhombicum , its age is limited to the early Famennian. Here we report on a new selenosteid genus Bulongosteus , collected from the upper part of the Zhulumute Formation. The diagnostic characters of the new genus include: (1) A triangular nuchal plate with convex front edge, concave back edge and bilateral micro concave, and the side edge is overlaid with paranuchal plate; (2) the posterior margin of the paranuchal plate longer than that of the nuchal plate, and two sensory tubes were developed; (3) the preorbital plate enlarged to form the anterolateral margin of the orbit, with dense tumor spots on the surface; (4) the anterior edge of the marginal plate thickened to form the posterior margin of the orbit, and the three sensory tubes in the shape of “Y”; (5) a slender posterior ventrolateral plate. Pachyosteus , Rhinosteus , Melanosteus , and Walterosteu are similar to Bulongosteu s in Selenosteidae. In Rhinosteus , there are a few tumor spots on the surface of the bone and the distribution of the sensory tubes of the paranuchal plate is different from Bulongosteus . The posterior margin of Walterosteu is wider than Bulongosteus , and the distribution of the sensory tubes of the paranuchal plate is different. The characteristics of Pachyosteus and Melanosteus are the most similar to Bulongosteus , but the distribution of the sensory tubes in their paranuchal plate is different from Bulongosteus . And Pachyosteus has less tumor spots in the nuchal plate and has a trapezoid rostral plate. Melanosteus has some tumor spots in the preorbital and suborbital plate. Bulongosteu s is the first arthrodire reported from Xinjiang of northwest China, and also the first relatively complete aspinothoracid reported in China. Strikingly, Bulongosteu s is the first aspinothoracid arthrodire found in the continental strata in the world. The discovery of the new material significantly expands the geographical and ecological distribution of aspinothoracid arthrodires, and also shows that aspinothoracids, like many fishes in the Late Devonian, are euryhaline.

Trace fossils are special objects in the study of predator–prey interactions in the fossil record. Here we report on diverse morphological types of the gnathostome fish hunting trace Osculichnus from the Upper Devonian of South China. The studied Osculichnus specimens occur as groups of bilobate mounds on the sole of fine- to medium-grained quartz sandstones from the estuarine-embayment depositional system of the Upper Devonian Wutong Formation in Wuhan city. The fish feeding trace Osculichnus is closely associated with the highly regular, branched sinuous trace Sinusichnus sinuosus on the bedding plane. Previously, Sinusichnus sinuosus has been typically reported from Late Cretaceous to Miocene marginal-marine sediments, with two records in the Lower and Middle Triassic of South China, and is generally regarded as the burrows of decapod crustaceans. The discovery of Sinusichnus sinuosus in the Upper Devonian, though of relatively small diameter (0.4–4.3 mm) than its Mesozoic and Cenozoic counterparts, extends its stratigraphical distribution and is suggestive of some primitive, small-sized decapod crustacean producers. The Osculichnus makers possibly preyed upon the Sinusichnus makers or other small invertebrates in the sediments. The overall shape and morphological details of the Late Devonian Osculichnus suggest lungfish as candidate trace makers. The fish hunting traces and associated trace fossils from South China thus provide unique insights into the palaeoecology of Late Devonian fishes.

In this study, systematic conodont biostratigraphy and cyclostratigraphy are carried out on Ordovician sections from the North China and South China blocks. The Liangjiashan section, situated on the North China Block margin, accumulated shallow marine carbonate during the Early Ordovician. The Huanghuachang section (GSSP for the Dapingian Stage), situated on the South China Block margin, accumulated thinly bedded carbonates and minor clastics in a deep shelf environment. Conodont biostratigraphy and 405-kyr long-eccentricity cycles interpreted from the Liangjiashan and Huanghuachang sections are used to establish an Astronomical Time Scale (ATS) for the Early–Middle Ordovician period. The ATS indicates that the duration of the Floian Stage is 7.08 ± 0.405 Myr. The temporal ranges of Lower–Middle Ordovician conodont biozones are also estimated: the durations of the Serratognathus bilobatus, Serratognathus extensus, Oepikodus communis, Oepikodus evae, and Baltoniodus triangularis zones are 1.0 Myr, 5.1 Myr, 0.2 Myr, 0.8 Myr, and 0.2 Myr, respectively. The evolution of the ratio of obliquity to total power and short-eccentricity power to total power depicts periodicities of 1 Myr for the s4–s3 term, and 1.9 Myr shifting to 1 Myr for the g4–g3 term. The shift in the g4–g3 term may indicate a chaotic transition in the Mars and Earth orbital motions from a (s4–s3)–2(g4–g3) to (s4–s3)–(g4–g3) resonance state during the Early Ordovician.

This study focuses on the Late Devonian ostracods and their responses to the F—F (Frasnian-Famennian) event based on abundant materials collected from the Yangdi and Nandong sections in South China. More than half (53%) of the benthic ostracod species disappeared at the F—F boundary in the Yangdi section of slope facies, whereas most benthic ostracod species survived the F—F crisis in the Nandong section of basinal facies, with the extinction of some pelagic entomozooidea. In view of a higher extinction rate (more than 65%) of ostracod species in the shallow-water Xikuangshan section, we deduce that ostracods in varied environments responded to the F—F event differently. Namely, from the carbonate platform, slope, to basinal settings, the extinction rate of benthic ostracods at the F—F transition decreased with increasing water depth. Nevertheless, the F—F event caused substantial loss among pelagic entomozooidea lineages. The extinction pattern of benthic and pelagic ostracods in F—F event in South China is similar to the situation in Europe. But the extinction rates of benthic ostracods in shallow water and slope in Europe seems to be higher than that in the same situation in South China. The abundance and diversity of ostracods decreased and some species even disappeared in anoxic environments across the F—F boundary in South China, when there were rapid changes in the palaeotemperature of surface sea water.

Background: The incidence of treatment-induced neuroendocrine prostate cancer (t-NEPC) has been greatly increasing after the usage of second-generation androgen receptor (AR) pathway inhibitors (ARPIs). Neuroendocrine differentiation (NED) is closely associated with ARPI treatment failure and poor prognosis in prostate cancer (PCa) patients. However, the molecular mechanisms of NED are not fully understood. Methods: TRIM59 expression was evaluated in PCa samples from patients at first diagnosis or at relapse stage post ARPI treatment by immunohistochemistry; in vitro effects of TRIM59 were determined by cell proliferation, sphere formation and cell migration assays; while in vivo analysis was performed using subcutaneous tumor model. Western blot, qPCR assay, dual luciferase assessment, chromatin immunoprecipitation and RNA sequencing were applied for mechanistic exploration.Results: Here we report that upregulation of TRIM59, a TRIM family protein, is strongly correlated with ARPI treatment mediated NED and shorter patient survival in PCas. AR binds to TRIM59 promoter and represses its transcription. ARPI treatment leads to a reversal of repressive epigenetic modifications on TRIM59 gene and the transcriptional restraint on TRIM59 by AR. Upregulated TRIM59 then drives the NED of PCa by enhancing the degradation of RB1 and P53 and upregulating downstream lineage plasticity-promoting transcription factor SOX2. Conclusion: Altogether, TRIM59 is negatively regulated by AR and acts as a key driver for NED in PCas. Our study provides a novel prognostic marker for PCas and shed new light on the molecular pathogenesis of t-NEPC, a deadly variant of PCa.

Objectives To investigate the roles of chemokine (C-C motif) ligand 8 (CCL8) in periodontal ligament during orthodontic tooth movement (OTM). Methods Bioinformatics analyzed 100 genes in human periodontal ligament cells that were most upregulated after 48 hours of mechanical stress, and these genes were classified through GO and KEGG databases. Nickel-titanium closed-coil springs were placed between right first molar and incisors to produce 20 cN of orthodontic force in eight-week-old male SD rats for 1 and 2 days, followed by immunohistochemical staining of CCL8. Human periodontal ligament fibroblasts (hPDLFs) were stimulated by 14% cyclic tension force (Flexcell FX-5000 T Tension System) or hypoxia conditions to mimic OTM for 1 and 2 days, then the resulting CCL8 were examined through ELISA. Scratching assay was performed by treating hPDLFs with different concentrations of CCL8 (1 ng/ml, 10 ng/ml, 100 ng/ml). The migration, proliferation, and adhesion abilities of 100 ng/ml CCL8-treated hPDLFs were also examined. qRT-PCR and western blot detected matrix metalloproteinase 3, periostin, and osteoprotegrin expressions of hPDLFs under 100 ng/ml CCL8. Results Bioinformatic analysis demonstrated that CCL8 was upregulated after applying mechanical stress for 48 hours. CCL8 secretion showed upregulation after 24 hours of OTM applicationsin vivo and in vitro. CCL8-treated hPDLFs showed significant positive effects on cell proliferation and matrix metalloproteinase 3. It also inhibited periostin and osteoprotegrin expressions. Conclusions CCL8 was upregulated in periodontal ligament during initial stage of OTM. Although CCL8 in human periodontal ligaments showed no significant effects on cell migration ability, it did enhance cell proliferation and osteoclastogenesis.

The Late Devonian Frasnian–Famennian (F–F) event, consisting of the Lower and Upper Kellwasser events, had a severe impact on shallow-water ecosystems, while the effect on deep-water ecosystems is ambiguous. In order to recognize the Kellwasser events and to evaluate their influences on the deep-water ecosystems, a newly refined conodont biostratigraphic framework spanning the Lower Palmatolepis rhenana Zone to the Pa. delicatula platys Zone has been established in the Nandong section (basinal facies), Guangxi, South China. The Upper Devonian Lower and Upper Kellwasser horizons (LKH and UKH) have been recognized in the deep-water facies on the basis of lithological variations, biological turnovers, and positive carbon isotope (δ13Ccarb) excursions. The LKH is characterized by the enrichment of marine nektonic communities (e.g. conodonts, homoctenids, and entomozoacean ostracods), whereas the top of the UKH is barren of fossil organisms, suggesting that the Upper Kellwasser event had a more severe effect on nekton than the Lower Kellwasser event. The Upper Kellwasser (UK) δ13Ccarb positive excursion lags behind the enrichment of Cu, Ni, Mo and V, indicating that the UK δ13Ccarb positive excursion was probably related to elevated primary productivity, which induced oxygen depletion in the water column. The UK δ13Ccarb positive excursion peak prior to the F–F boundary indicates a more limited effect of riverine influx on the deep-water setting, which suggests that the regional palaeogeographic configuration played an important role in the carbon cycle.

Trace fossils are important evidence of benthic activity and proxies of bottom and interstitial water oxygen content, making them a promising tool to understand the oceanic redox evolution and extinction patterns during the end-Permian mass extinction (EPME). Detailed bed-by-bed ichnologic studies were performed at a high-resolution scale from two uppermost Permian sections (Shangsi and Dongpan) in South China, documenting the presence of Chondrites targionii, Chondrites isp., Nereites isp., Planolites isp. A, Planolites isp. B, Palaeophycus isp., Phycosiphon incertum, Thalassinoides isp., and Zoophycos isp. The uppermost Permian strata at the Shangsi section mainly comprise siliceous limestone interbedded with illite-montmorillonite claystone and shale, recording a deep shelf setting. The uppermost Permian strata at the Dongpan section consist of mixed chert, mudstone and claystone, formed in a slope environment. Bioturbation index in uppermost Permian strata is mostly 1–2, but with thin intervals reaching 3–4. Fluctuating bioturbation intensities, ichnofaunal composition (Thalassinoides, Planolites, Zoophycos) and ethologies, as well as the ratio of highly reactive iron to total iron (FeHr/FeT) and the proportion of the highly reactive iron pool in the form of pyrite (Fepy/FeHR) suggest that bottom and interstitial oxygen levels were not permanently anoxic/euxinic, but were interrupted by brief periods of aerobic conditions during the latest Permian. Three bioturbation phases in the EPME are identified. Phase I is characterized by the absence of typical pascichnia ichnotaxa (e.g. Nereites isp.) and relatively large fodinichnia burrow (e.g., Planolites isp. B; Zoophycos isp.). Phase II mainly consists of smaller Planolites isp. A, Thalassinoides isp. and Chondrites isp., recording a transition from softground to firmground. Only occasional smaller Planolites isp. A occur in Phase III without any associated vertical burrows. Ichnodiversity and bioturbation index from Phase I to Phase III show a step by step decline, corresponding to the two-stage extinction patterns. Long-term environmental stress (e.g., oceanic anoxia, volcanic winter, global warming, ocean acidification, hypercapnia) may have played major role in the collapse of the infaunal ecospace and only facies-crossing, highly tolerant, opportunistic organisms may have persisted in otherwise vacant ecological niches in the aftermath of the extinction.

The impact of climate change on biodiversity has been the focus of studies on the Phanerozoic biotic crises. However, it is still controversial whether climate change has caused the Frasnian–Famennian (F–F) biotic crisis since there is no unequivocal view on the global climate change during this critical period. In order to reconstruct palaeotemperatures during the F–F transition in South China (eastern Palaeotethys), a high-resolution oxygen isotope ( δ 18 O PO 4 ) record was obtained based on 104 measurements of conodont apatite from the Yangdi section. The oxygen isotope record based on mono-generic samples reveals an increase in δ 18 O PO 4 by 0.7‰ in the Lower Kellwasser horizon (LKH) and 1.4‰ in the Upper Kellwasser horizon (UKH), translating into low-latitude surface water cooling of ∼3 °C and ∼6 °C, respectively. These two δ 18 O PO 4 shifts agree well with the time-equivalent δ 18 O PO 4 records from the western Palaeotethys, suggesting that two climate cooling pulses in conjunction with the deposition of the Kellwasser horizons are a global signal during the F–F transition. The positive shift of δ 18 O PO 4 coincides with positive excursion in carbon isotope of carbonates ( δ 13 C carb ) in the UKH, indicating that enhanced burial of organic carbon resulted in a drop in atmospheric p CO 2 and thus global climate cooling. Cooling started immediately before the Upper Kellwasser biotic crisis, with the lowest temperature documented at the top of the UKH. Climate cooling during the deposition of the LKH is observed in conjunction with the sharp decline in metazoan reefs. The coincidence of cooling and the Kellwasser biotic crisis suggests that global cooling played a major role in the collapse of ecosystems.

Thirty-seven ostracod species belonging to 25 genera from the Devonian-Carboniferous (D/C) transition in Dushan of Guizhou, South China are identified and figured. The stratigraphical distribution of ostracods in the Baihupo section suggests that the D/C boundary should be fixed in the basal part of the Tangbagou Formation, which is also the boundary between Gelaohe and Tangbagou formations. The ostracod assemblages from the Gelaohe Formation belong to the Eifelian Mega-Assemblage, incorporating palaeocopid and smooth-podocopid associations, which implies a nearshore-offshore palaeoenvironment, while the ecological assemblages of ostracods from the Tangbagou Formation correspond to a smooth-podocopid association that indicates an offshore palaeoenvironment. There was probably a transgression during the D/C transition when Gelaohe and Tangbagou formations were being deposited in Dushan of Guizhou.

Wangshangkia, a new genus of Ostracoda, from the Late Devonian in Dushan of Guizhou, South China, is described. This genus belongs to the family Bairdiocyprididae Shaver, 1961 and includes two new species, i.e. Wangshangkia dushaniensis and W. bailouiensis. The new genus is characterized by a wide ventral carina with radial striae. It is reported from the Famennian of South China and disappeared just below the Devonian-Carboniferous boundary. Wangshangkia is essentially a benthic crawler and is restricted to the shallow-marine depositional environment with a low hydrodynamic condition.Wangshangkia: urn:lsid:zoobank.org:act:34BF01D4-D202-492D-8E27-BC508EF7EFFBW. dushaniensis: urn:lsid:zoobank.org:act:D267C362-7510-4D19-996B-EA1848D7D025W. bailouiensis: urn:lsid:zoobank.org:act:FE988AA0-7363-4D9E-A5AB-1526C8DBCDD9

Palynological investigations have been carried out on samples from the Upper Devonian Hongguleleng Formation of Western Junggar, Xinjiang, NW China. In total, 26 miospore species belonging to 19 genera and 28 acritarch species assigned to 19 genera have been recognized from the lower member of the Hongguleleng Fm. in the Bulongguoer section. The palynofloral assemblages, in particular the miospore taxa, are similar to those from the eastern European early Famennian Corbulispora vimineus–Geminospora vasjamica (VV) and Cyrtospora cristifer–Diaphanospora zadonica (CZ) miospore biozones, albeit quantitatively and qualitatively depauperate. The miospore assemblage zone is also consistent with the previous zonal schemes in light of brachiopod and conodont fauna assemblages, as well as carbon isotope geochemistry, that indicates a correspondence to the Palmatolepis crepida conodont Biozone. Part of the earliest Famennian Corbulispora vimineus–Geminospora vasjamica (VV) (more or less equivalent to the Palmatolepis triangularis conodont Biozone) miospore Biozone is most likely to be missing in the Hongguleleng Fm. of the Bulongguoer section. The palynostratigraphy and sedimentary sequence in Western Junggar are very similar to those from some other regions of western and eastern Europe, which increases the knowledge of the evolution of the paleoclimate, paleogeography and regional sedimentary environment of the Central Asian Orogenic Belt (CAOB), Eastern European Platform, and Laurussia.

The Late Devonian is considered as a crucial climatic transition from the Devonian greenhouse to Carboniferous icehouse. Published Late Devonian marine palaeotemperature records are mainly based on conodont δ18Oapatite data from the Rheic Ocean. In order to reconstruct palaeotemperature variations in the eastern Palaeotethys, oxygen isotopes were measured on the latest Givetian to latest Famennian conodonts from the Lali section (South China). Assuming constant seawater δ18O, the early to middle Frasnian is marked by a warming trend (−1.5‰ shift in δ18Oapatite), with warmest temperatures reconstructed in FZ 11 (FZ = Frasnian Zonation). Late Devonian cooling during the middle to late Famennian (velifer to ultimus Zone) is documented by a long-term positive δ18Oapatite shift of +2‰. This increase corresponds to a similar δ18Oapatite increase in the Rheic Ocean and can be explained by cooling as well as the formation of ice masses as evidenced by the occurrence of glacial sediments in Gondwana and Euramerica during the late Famennian. The Late Devonian δ18Oapatite record largely matches 2nd-order T-R cycles. The δ18Oapatite record from the Lali section shows several short-term positive excursions coinciding with Late Devonian bio-events as the Middlesex (+0.5‰ δ18Oapatite), Lower Kellwasser (+1‰ δ18Oapatite) and Upper annulata (+0.8‰ δ18Oapatite) events. However, due to the lower sampling resolution of the F-F (Frasnian-Famennian) boundary interval, we did not recognize a positive shift in δ18Oapatite for the Upper Kellwasser event as reported from other sections.

Background and objective Epithelial-mesenchymal transition (EMT) has been proved to occur in drug-induced gingival overgrowth. However, the specific pathogenic mechanism remains uncertain. The aim of this study is to examine the expression of EMT markers in cyclosporine A (CsA)-induced gingival overgrowth in rat models. Material and methods Thirty-six rats were randomly divided into two groups. The experimental group received CsA therapy subcutaneously in a daily dose of 10 mg/kg, and the other group was used as a control. Six rats per group were sacrificed at 20, 40 and 60 days, and the gingivae were obtained. The expression of TGF-β1, E-Cadherin, ZEB1, ZEB2, and Snail1 were examined by quantitative real time PCR (qRT-PCR), western blotting, and immunohistochemistry. In addition, a group of microRNAs associated with EMT and fibrosis were also detected in gingival tissue by qRT-PCR. Results The mRNA and protein levels of TGF-β1, ZEB1, and ZEB2 in gingivae were significantly upregulated after 40 and 60 days of CsA administration. Conversely, the levels of E-cadherin were significantly downregulated in overgrowth sample at day 40 and 60. Intense immunohistochemmical staining for TGF-β1 were observed in the samples from CsA group at day 40 and 60. Concomitantly, the densities of E-cadherin were gradually decreased in the basal layers of epithelium with time. Three members of miR–200 s (miR-200a, miR-200b and miR-200c) were significantly downregulated in CsA-treated rats at 40 and 60 days, while miR-9, miR-23a and miR-155 were significantly upregulated when compared with those of the control group. Conclusions The process of EMT in CsA-induced rat gingival overgrowth is associated with increased expression of TGF-β1, ZEB1, and ZEB2, and decreased expression of E-cadherin.

An exceptionally preserved biota is described from the middle Telychian (Llandovery, Silurian) Fentou Formation of Wuhan, Central China, which preserves nontrilobite arthropods, cnidarians, echinoderms, sponges, fish, and algae as well as abundant shelly fossils and trace fossils in the Skolithos-Cruziana ichnofacies. This biota can be divided into two assemblages on the basis of the biological characteristics, fossil-bearing strata, and their sedimentary environments. Assemblage 1 comprises nonbiomineralized phyllocarids, Sphenothallus, conulariids, complete crinoids and stelleroids, and Burgess Shale–type sponges as well as some uncertain fossils in taxonomy and abundant marine shelly fossils. Assemblage 2 consists of numerous eurypterids, agnathans, chondrichthyes, and a few conulariids, algae, as well as shelly euryhaline fossils. Discoveries of the Fentou biota expand the temporospatial distribution and sedimentary environment of the exceptionally preserved Silurian biota and advances a deepe...

The cephalon of the trilobite Phacopidae was usually separated from the thorax during moulting, and abandoned near the trunk. We statistically evaluated the distribution pattern of the cephala of Omegops cornelius, and found that near 70% of the total cephala were displaced on the right side, from the Upper Devonian deposits of the western Junggar in Northwest China. Omegops cornelius might have actively pushed the cephalon to the right of its body during moulting, indicating their preference to move counterclockwise. This preferred movement direction manifested the behavioural asymmetry in trilobites. A different type of asymmetry has been observed in Phacopidae Plagiolaria nandanensis from the Lower Devonian of Guangxi in South China, where about 67% of the cephala were found on the left side of the trilobite trunks. So the behavioural asymmetry may be diverse (or opposite) in different species of trilobites, and the reasons for the asymmetric moulting and movement patterns of the above two trilobites are likely related to their body structures, or their living environments. These new materials provide evidence for studying the origin and evolution of behavioural asymmetry.

Trace fossils are unique evidence of the body plan and behavioural complexity of animals. Major radiation periods in the Phanerozoic were associated with not only changes in biodiversity, biomass, and ecosystems but also transformations in the relatively implicit, behavioural world. Here we report on a diverse ichnoassemblage from the Middle–Upper Ordovician deep-marine deposits of Inner Mongolia, North China, totalling 24 ichnogenera (including two undetermined forms). They include Alcyonidiopsis, Bifasciculus, Bifungites, Chondrites, Circulichnis, ?Cochlichnus, Dendrorhaphe, Diplocraterion, Halopoa, Gyrophyllites, Monofungites, Multina, Nereites, Paleodictyon, Phymatoderma, Ptychoplasma, Rhizocorallium, Sinusichnus, Taenidium, Thalassinoides, Trichichnus, Zoophycos, bag-like trace, and closed ring trace. Highly regular and complex burrow systems have been discovered, i.e., the branched circular pattern of Circulichnis sinensis, elaborate radial graphoglyptid tunnel system Dendrorhaphe racemosa ichnosp. nov., sinusoid mazework Sinusichnus sinuosus, and the boxwork bag-like trace consisting of highly symmetric horizontal galleries and numerous semi-equidistant vertical shafts. The occurrence of these complex trace fossils suggests distinct behavioural complication and novelty in deep-sea communities during the Middle–Late Ordovician. We speculate that along with the onshore–offshore displacement of ichnofauna and significant expansion of deposit-feeding structures possibly driven by accelerated competition in the shallow-marine niches and aided by ameliorated deep-sea benthic food level, there was underlying behavioural evolution towards more delicate, geometric, and efficient feeding patterns. The Late Ordovician may represent the early peak not only in ichnodiversity but also in ichnodisparity and behavioural complexity of deep-sea ichnofauna, which probably reflect the complex interplay of biodiversity, biomass, and ecological changes during the Ordovician Radiation.

A global Late Devonian ostracod database is constructed, incorporating new materials from South China and Northwest China. Four palaeobiogeographical units (Cathaysia, North America, Europe and peri-Gondwana) are recognized during the Frasnian and five palaeobiogeographical units (Cathaysia, North America, Europe, Siberia and Australia) in the Famennian. Three controlling factors (climatic zonation, geographical isolation and global sea-level changes) are identified to have played roles in shaping the palaeogeographical regionalization of ostracod faunas in the Late Devonian. The ostracod palaeobiogeography in the Frasnian was mainly influenced by climatic zonation, while rapid changes in tectonic configuration in the Famennian drastically altered the global palaeobiogeography of ostracods. The palaeobiogeographical regionalization of ostracod faunas suggests that Laurussia and Gondwana continued to draw near during the Late Devonian, with the first collision occurring in Southern Central Europe in the Famennian. The South China plate drifted northward to the Kazakhstan plate away from the Australian plate, which gradually became isolated during the Famennian Stage.

Late Devonian to Early Carboniferous deep-sea deposits of the western Junggar, NW China contain 21 ichnotaxa: Arenituba verso (Chamberlain), Chondrites cf. intricatus (Brongniart), Chondrites targionii (Brongniart), ? Chondrites isp., Gordia marina Emmons, Halopoa imbricata Torell, Helminthoidichnites isp., Helminthopsis cf. hieroglyphica Wetzel and Bromley, Laevicyclus isp., Lophoctenium comosum Richter, ? Multina isp., Nereites missouriensis (Weller), Phycodes cf. bilix (Ksiązkiewicz), Phycosiphon incertum Fischer-Ooster, ? Phycosiphon isp., Planolites isp., cf. Taenidium , Thalassinoides isp., Zoophycos isp., undetermined short ridges, and undetermined tubular structures. They form three typical ichnoassemblages, i.e. the Helminthopsis–Helminthoidichnites–Arenituba ichnoassemblage characteristic of upper-bathyal, probably hyperpycnal-flow-influenced deposits, Zoophycos–Nereites–Phycosiphon ichnoassemblage in typical slope deposits, and the Phycosiphon–Nereites ichnoassemblage featuring bottom-current-influenced, lower slope or basin floor muddy deposits. They can be ascribed to the Cruziana , Zoophycos , and the Nereites ichnosubfacies respectively. Comparison with contemporaneous deep-water facies (foremost the Kulm facies in Western and Central Europe) reveals significant loss in the western Junggar of otherwise common element Dictyodora liebeana (Geinitz). Combining the global Palaeozoic tectonic evolution, we propose that Dictyodora was probably originated from peri-Gondwana terranes and the larvae/juveniles of Dictyodora producers hadn't migrated to the northern palaeolatitudes (open ocean Kazakhstan “archipelago”) in the Early Carboniferous. The relatively global distribution of the Phycosiphon–Nereites association indicates efficient larval dispersal of their producers. Intensive bioturbation in deposits dominated by the Phycosiphon–Nereites ichnoassemblage implies a high level of food supply at certain stratigraphic levels, most likely related to surface blooms and enhanced plant detritus input. The monsoonal palaeoclimatic model is integrated with the archipelagic palaeogeography to account for the deep-sea ichnofauna in the western Junggar during the Late Devonian to Early Carboniferous. The most important factors include seasonal climatic perturbations, such as monsoon-derived upwelling events and enhanced primary production, and efficient food/nutrients transport in the dotted island scenario.

Conodont faunas from the Wulankeshun section in the northwestern Junggar Basin of Xinjiang, NW China, are characterized by shallow-water assemblages with many endemic taxa. This study presents separate local icriodid and polygnathid conodont zonations for the Lower Member of the Hongguleleng Formation, which can only roughly be correlated with the pelagic “standard zonation”. The basal beds of the Hongguleleng Formation are assigned to a low diverse Icriodus praealternatus ferus n. ssp. Zone, which possibly includes latest Frasnian strata but it continues into the basal Famennian. At present, the Frasnian/Famennian boundary cannot be defined unequivocally by conodonts and there are no obvious Upper Kellwasser equivalents. However, the carbon isotope data are comparable with the Bulongguor Reservoir stratotype, where the top-Frasnian lies within the basal Hongguleleng Formation. In the early Famennian, partly endemic icriodid lineages provide successive Icriodus cornutus , I. stenoancylus junggarensis n. ssp., and I. plurinodosus n. sp. (sub)zones. The basal Famennian is possibly marked by the oldest, endemic species of Neopolygnathus , Neo. huijunae n. sp. It is followed by local Neo. communis communis , “ Polygnathus ” pomeranicus , Po. cf. szulczewskii , and “ Po. ” pseudocommunis n. sp. zones. The new local conodont zonations provide a high biostratigraphic resolution for further future studies. The Wulankeshun shallow-water conodont faunas show restricted similarities with contemporaneous faunas from eastern Europe, Kazakhstan, and Iran. There are a few taxa that were originally described from other distant regions, such as NW Canada and eastern Australia. The local high number of endemic taxa (17 (sub)species, 46%) points to a significant plate tectonic isolation of the Junggar Basin in the early Famennian.

The Frasnian–Famennian (F–F) event may be recognized in various facies areas in South China. In the pelagic cherty basin facies, both Lower and Upper Kellwasser events can seemingly be recognized. In the deeper water carbonate facies, the F–F event level is well controlled in light of conodont biostratigraphy. In the shallow water carbonate and mixed carbonate-shale facies, the F–F boundary may be defined by clear taxonomic distinction in benthic fossils (articulate brachiopods and corals) as well as evidence from minor pelagic fossils. Post-extinction recovery rate of benthic organisms differs in different facies settings and different taxonomic groups. In open shallow water platform to inter-platform depression areas, brachiopods seem to recover quickly, probably in the Middle Pa. triangularis Zone; benthic ostracodes seem to recover at a later stage; recovery of rugose corals did not happen until the uppermost Famennian. Three steps of the F–F mass extinction are postulated: 1) extinction of diverse brachiopods (including most atrypids); 2) extinction of pelagic conodonts; 3) extinction of both benthic faunas (very abundant and diverse rugose corals and ostracodes) and pelagic conodonts. Evidence of an end-Frasnian regression in South China is clear, particularly in shallow water settings. However, in deeper water settings, the picture is complicated, with evidence of both sea level rise and fall in the latest Frasnian. It may be assumed from overall data so far known that crustal evolution itself and associated multiple volcanic/hydrothermal activities may have mainly caused frequent and rapid climatically warming-cooling alterations and sea level changes as well as marine ecologic collapse (eutrophication, microbial blooming, seawater acidification, and anoxia), which may explain the F–F extinction pattern in South China.

Continuous centimeter-scale sampling for conodonts with microfacies and carbon isotope analysis has been carried out across the Frasnian–Famennian (F–F) transition at the Yangdi section, Guangxi, South China. The newly revised conodont biostratigraphy reveals a succession of six zones, ranging from the upper Palmatolepis rhenana zone to lower Palmatolepis crepida zone in ascending order. Based on a detailed analysis of conodont abundance and diversity changes through the section, two intervals involving significant conodont faunal changes were recognized in the uppermost Palmatolepis linguiformis zone at the Yangdi section. The first conodont change occurred at the transition between the lower and upper Pa. linguiformis zone and is marked by the disappearance of Pa. linguiformis , accompanied by the successive disappearances of Pa. eureka , Pa. rhenana , Pa. nasuta , Pa. gigas , Ad. ioides , and Ad. nodosa . The second conodont change appeared in a horizon equivalent to the uppermost Upper Kellwasser Horizon (UKH) and is indicated by the elimination of nearly all Frasnian palmatolepids, ancyrodellids, and polygnathids. Furthermore, the second conodont change is coincident with the decimation of ostracods and tentaculitids and is synchronous with the turnovers of conodont biofacies. In addition, the onset of the δ 13 C carb perturbation is a little earlier than the second conodont change, with the maximum amplitude of excursion right at the start of the Famennian. Therefore, we conclude that the second conodont change represents the F–F mass extinction based on the temporal correlation among δ 13 C carb excursions, pelagic faunal changes, and conodont biofacies turnovers during the F–F boundary interval. According to the high-resolution conodont biostratigraphy together with cyclostratigraphy, the uppermost UKH and whole UKH contain 1 and 12 bundle cycles, respectively. Thus, the time span of the mass extinction and the entire Upper Kellwasser crisis lasted 16–18 kyr and ~ 200 kyr, respectively.

Two sections of the Late Devonian to Early Carboniferous Hongguleleng Formation in the Sha'erbuerti and Xiemisitai mountains of western Junggar, NW China were logged in detail and studied with particular reference to their trace fossil content and sedimentary features. The Hongguleleng Formation is composed essentially of shallow marine deposits formed in a volcanic arc-related setting. It contains trace fossils including indeterminate ellipsoid structures, indeterminate shallow-pit structures, Chondrites intricatus, Chondrites targionii, Chondrites isp., Dolopichnus gulosus,?Multina isp., Nereites missouriensis, Nereites isp., Palaeophycus tubularis, ?Phycosiphon isp., ?Phymatoderma isp., Rhizocorallium commune, Rosselia cf. socialis, Teichichnus rectus, Teichichnus ispp., Thalassinoides isp., and Zoophycos ispp. These ichnofossils and related bioturbation structures constitute five distinct groups of ichnofabrics: Chondrites–?Phymatoderma, Rhizocorallium commune, anemone dwelling/burrowing, Teichichnus, and Zoophycos ichnofabrics, conforming to an upward trend from the Cruziana to Zoophycos ichnofacies. The volcanic arc setting provides a natural laboratory to investigate the colonisation styles of benthic faunas during the Devonian, especially for environments with widespread and relatively frequent depositional events disturbing background deposition. The distal event beds are especially suitable for the distinction of the relationship between background and post-event ichnofaunas. Simple and composite ichnofabrics have been distinguished. The simple ichnofabrics are typified by the indeterminate ellipsoid “ichnofabric” made by sea anemones, representing short colonisation event and in situ death and burial resulted from relatively high sedimentation rates even during the periods between volcanic explosions. The composite ichnofabrics are characterised by the Chondrites–?Phymatoderma, ?Multina–Zoophycos and multi-tier Zoophycos ichnofabrics, representing vertical migration of benthic faunas in pace with either distal event deposition or steadily accreted sea floor. The colonisation window in the arc-related setting is closely related to sedimentation rates and frequency of depositional events, determining the completeness of burrow system structure and maturity of benthic communities.

Widespread oceanic anoxia has been implicated as a killing mechanism during the end-Permian mass extinction (EPME). A high-resolution investigation of pyrite framboids and bioturbation structures in the Shangsi section of South China has revealed repeated and frequent fluctuations of coupled anoxic/euxinic to dysoxic/oxic episodes in the latest Permian, immediately preceding the EPME. Anoxic bottom waters and interstitial water conditions are documented by the smallest pyrite framboids (3–5 μm) and the absence of bioturbation, and dysoxic bottom waters and anoxic interstitial waters are inferred from larger pyrite framboids (6–10 μm) and the occurrence of Zoophycos. In comparison, oxic conditions for both bottom waters and interstitial waters are revealed by a high bioturbation index (BI = 4) and the occurrence of mid-tier Thalassinoides. Fluctuating pyrite framboid sizes and bioturbation structures suggest that bottom and interstitial oxygen levels were neither fully, nor persistently, anoxic/euxinic before the EPME, and instead recorded frequent periodic fluctuations between anoxic/euxinic and dysoxic/oxic conditions. The paleoceanic redox variation appears to correlate with the 405-ka eccentricity cycles in the anhysteretic remanent magnetization (ARM) series, suggesting that fluctuations might have been controlled by Milankovitch cycles. The role of fluctuations between anoxic/euxinic and dysoxic/oxic episodes in the latest Permian to the EPME is unclear, but it seems plausible that they represent a prelude to the highly stressed conditions that are characteristic of the EPME.

The Late Devonian Period was a critical geological interval, affected by numerous significant global bio- and environmental events, including the Kellwasser, annulata and Hangenberg events, and a major climate transition leading to the Carboniferous ice ages. The timing and pattern of these events are unclear due to lack of the precise time scale. In this study, an analysis of calcium concentration series was carried out on the Upper Devonian cyclostratigraphic slope-facies of the Lali section, South China. Objective testing of the section indicates the presence of astronomical forcing: long orbital eccentricity, short eccentricity, obliquity, and precession index. Two independent astrochronologies were developed for the Ca series and compared with spectral analysis. The age of the Devonian–Carboniferous boundary (358.9 ± 0.4 Ma) was selected as an “anchor”, and an Astronomical Time Scale (ATS) was constructed from the late Frasnian to early Tournaisian based on 405-kyr cycles. The ATS indicates a duration of the Famennian Stage of 14.4 ± 0.28 myr, and assigns 373.3 ± 0.49 Ma to the Frasnian–Famennian boundary. The durations of the Famennian conodont zones are also indicated. The timing of Famennian bio- and environmental events also can be established by the ATS. The Upper Kellwasser horizon starts at 373.4 Ma and is constrained to a duration of 100-kyr; a sharp positive carbon isotope excursion CIE, +3‰ recognized across the Frasnian–Famennian boundary lasts 300 kyr. The Lower and Upper annulata events each last 50-kyr with positive CIEs; and the ages of two CIE peaks are 361.7 Ma and 361.3 Ma, respectively. Five transgressive events, including the Nehden, Enkeberg, Dasberg, Strunian, and Hangenberg transgressions occur at 370.6 Ma, 368 Ma, 360.4 Ma, 360.1 Ma, and 358.9 Ma, respectively. Five regressive events i.e., the linguiformis, prima, Condroz, velifer, and Derwer regressions occur at 373.4 Ma, 371 Ma, 369 Ma, 362.3 Ma, and 359.2 Ma, respectively.

Large numbers of densely distributed Rhizocorallium provide a window to understanding the behavioural and functional changes of the trace maker after extreme environmental events. This study focuses on the analysis of Rhizocorallium from the Middle Triassic (Anisian) limestones in the Boyun section, Yunnan Province, Southwest China to investigate the ecological strategies and ethological signatures of its producers before and after storm events. Based on its morphological features, the studied Rhizocorallium is attributed to two ichnospecies Rhizocorallium jenense and R. commune, the latter showing two varieties R. commune var. auriforme and R. commune var. irregulare. In addition to Rhizocorallium, the trace fossil assemblage consists of Arenicolites, Palaeophycus, Planolites and Thalassinoides, which allows assignation to the Cruziana ichnofacies associated with the shallow marine environment. The studied ichnofossil-bearing intervals in the Boyun section are usually high bioturbated, with BPBI (bedding plane bioturbation index) around 5. The ichnoassemblage has a relatively low ichnodiversity and shows high density of Rhizocorallium, which is interpreted as the result of the opportunist strategy when the Rhizocorallium trace makers exploited the quiet, nutrient-rich substrates after storm events. Crosscutting relationships between multiple levels of Rhizocorallium indicate that earlier burrows were reworked by later ones due to successive storm events and erosion of the shallow-tier burrows. Orientation of the marginal tubes of Rhizocorallium jenense shows a bidirectional pattern at 295°NW and 160°SE, which may record the changes of the main flow direction. Diameter measurements support the total recovery of the macrobenthic trace makers during the Middle Triassic (Anisian).

The aim of the present study was to investigate the role of sentrin/small ubiquitin-like modifier (SUMO)-specific protease 5 (SENP5) in oral squamous cell carcinoma (OSCC), as the overexpression of SENP5 has been observed in 31 OSCC tissue specimens. CAL-27 OSCC cells were used for in vitro measurements. The distribution of SENP5 was visualized using immunohistochemistry and H2O2-induced oxidative stress, and the effects of SENP-small interfering RNA on SENP5 were analyzed via western blotting. The apoptotic rates of the CAL-27 cells during oxidative stress and SENP5 silencing were estimated using flow-cytometry, and the mitochondrial structures were analyzed using a mitochondria tracker. The SENP5 protein was localized in the nuclei and cytosols of the CAL-27 cells, and incubation with 100 µm H2O2 for >1 h led to its stabilization. Incubation with H2O2 alone had no effect on the CAL-27 cells, however, a combination of H2O2 and SENP5 silencing led to enhanced apoptotic rates (P

Forty-eight ostracod species belonging to 28 genera from the Late Devonian of Guangxi in South China are described and figured. The ostracod assemblage from the Nandong section can be attributed to the rhenana–linguiformis conodont zones. The ecological assemblages of ostracods from the Yangdi section correspond to a smooth-podocopid association accompanied by some pelagic entomozoids. This mixed assemblage is indicative of an environment of carbonate platform to slope during an ongoing regression. The ostracod faunas from the Nandong section are on the contrary composed of both pelagic and benthic ostracods and pelagic forms dominate in number of specimens suggesting a basin environment.

Abundant perfectly-preserved phosphatic microspherules have been discovered across the Frasnian-Famennian (F-F) transition from the Yangdi section in Guilin, Guangxi, South China. They are mostly spherical or elliptical in shape and about 150 μm in diameter with smooth exterior surfaces. Each microspherule consistently possesses a small dimple on the surface. The internal texture of microspherules consists of concentric light-colored apatite and dark-colored organic matter bands alternating around a central core. Conodonts have also been found preserved together with phosphatic microspherules in the same horizon, and the abundance of the former is obviously higher than that of the latter. Laser Raman spectral studies show close similarities in spectral patterns between the outer shells of phosphatic microspherules and the blade of the conodont genus Palmatolepis sp., as well as between the microspherule nucleus and the platform of the same conodont genus. Furthermore, the statistical results and geochemical data demonstrate that the elevated abundance of phosphatic microspherules roughly coincides with the blooms of bacteria and algae, but is later than the sharp increase of oceanic nutrients. The phosphatic microspherules are interpreted here to be the ‘otoliths’ secreted by conodont animals based on the compositional similarities between phosphatic microspherules and conodonts and their interrelated abundances. In addition, an analogous study reveals morphological and textural similarities between fish otoliths and phosphatic microspherules. The formation of phosphatic microspherules is probably related to seawater eutrophication. We speculate that the explosive growth of bacteria and algae is probably caused by the enrichment of nutrients that is most likely associated with the increase of terrestrial inputs, submarine hydrothermal activities or the upwelling anoxic bottom waters in the late Devonian, which would stimulate the conodont animals to secrete phosphatic microspherules—the ‘otoliths’ of conodont animals. This study reveals the coupling relationship between organisms and environments from the perspective of phosphatic microspherules and provides new evidence for the cause of faunal crisis during the Late Devonian F-F transition.

The Lali section (Guangxi Province, South China) is composed of quiet-water carbonates containing abundant conodonts, which allowed recognition of 12 Frasnian and 20 Famennian biozones. The Kellwasser and annulata events are characterized by transgressive black carbonates, while the Hangenberg Event is represented by black shale deposits. Other transgressive events recognized at Lali include the Middlesex, Nehden, Enkeberg, and Dasberg, as well as the Strunian transgression. Four regressive events were recognized on the basis of lithological and microfacies changes, i.e., the linguiformis regression, Condroz Event, velifer regression, and the Derwer regression. These sea-level change events were of short duration and globally isochronous based on conodont correlations. Microfacies analyses and the abundance of Palmatolepis indicate that the highest Frasnian sea level lies in FZ 12-13 (Upper rhenana Zone), whereas the highest Famennian sea level was in the utahensis Zone.

Kruppel-like factor 7 (KLF7) is a member of the KLF family of zinc finger transcription factors, and was the first KLF cloned using complementary DNA and polymerase chain reaction (PCR) techniques with human vascular endothelial cells as a template. In addition, KLF7 is known as the ubiquitous Kruppel-like factor, as it is widely expressed in numerous human tissues at low levels. In the present study, the function of KLF7 in migration and epithelial-mesenchymal transition (EMT), which are associated with tumor progression, was investigated in human oral squamous cell carcinoma (OSCC) cells. Genes that were differentially expressed in normal vs. OSCC tissue were identified in the Gene Expression Omnibus database, which identified upregulation of KLF7 in OSCC. The expression and subcellular location of KLF7 was then analyzed using immunohistochemistry. KLF7 expression was measured in three OSCC cell lines, and the two cell lines with the highest (HN13) and lowest (CAL27) KLF7 expression were selected for further analysis. Subsequently, HN13 cells with reduced KLF7 expression (sh-HN13) and CAL27 cells overexpressing KLF7 (OE-CAL27) were constructed. Transwell migration and wound healing assays were then used to analyze the migration of the cells. In addition, mRNA and protein expression levels of the EMT markers E-cadherin, N-cadherin, vimentin and snail were detected using reverse transcription-quantitative PCR and western blotting. KLF7 overexpression in OSCC was validated using tissue immunohistochemistry, which identified moderate to high cytoplasmic staining of KLF7 in OSCC cells. KLF7 knockdown and overexpression altered the migration ability of sh-HN13 and OE-CAL27 cells, which decreased and increased significantly respectively. Expression of E-cadherin, N-cadherin, vimentin and snail was markedly altered in sh-HN13 and OE-CAL27 cells, indicating changes in EMT status. The results of the present study suggest that KLF7 overexpression changes the migratory behavior of OSCC cells, and induces EMT and lymph node metastasis through the expression of snail.

The pathogenesis of cyclosporine (CsA)-induced gingival overgrowth (GO) is multifactorial. Plaque-induced gingival inflammation has been shown to play a pivotal role in the development of CsA-induced GO (1, 2). CsA may override the inhibitory effect of lipopolysaccharide(LPS) on cell proliferation and maintain a capacity to stimulate fibroblast DNA synthesis (3, 4). In co-cultures of gingival fibroblasts and marcophages, CsA can inhabit the activities of matrix metalloproteinase in the presence of Porphyromonas gingivalis(Pg) LPS, promoting abnormal accumulation of extracellular matrix components in the gingival lamina propria (5). LPS induces the proliferation of periodontal epithelial cells via the CD14 and Toll-like receptor (TLR) signaling pathway (6). CsA positively regulates TLR-mediated inflammatory responses of gingival fibroblasts to microbial components, enhancing the production of pro-inflammatory cytokines and potentially augmenting the proliferation of gingival fibroblasts(7). These results suggest that complex interactions between the LPS signaling pathway and tissue metabolism might be involved in the pathogenesis of CsA-induced GO. CD14, a pattern recognition receptor on monocyte and macrophage, plays a critical role in innate immunity through recognition of bacterial LPS (8). Through interaction with both CD14 and LPS-binding protein, signal transduction on effector cells is then transferred via the TLR/MD-2 signaling complex (9), resulting in the activation of innate immune response and the release of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and transforming growth factor-β1, that act synergistically with CsA in the modulation of gingival fibroblast metabolism (10–12). A -260C>T polymorphism in the CD14 gene promoter results in decreased affinity of DNA/protein interaction at a GC box that contains a binding site for SP proteins and modulates the activity of the promoter(13). Carriage of the TT genotype has been associated with significantly higher serum levels of the soluble CD14 receptor (sCD14) and an increased density of CD14 in monocytes (14). Individuals carrying the TT genotype are more susceptible to developing periodontal infections induced by opportunistic pathogens (15). The carriers of the T-containing genotype of CD14-260(CT+TT) have been shown to have a higher extent of periodontal disease compared to those carrying the CC genotype (16), while other studies did not find associations (17, 18). The concept of periodontal infectogenomics is defined as the relationship between host genetic factors and the composition of the subgingiva microbiota (19). Genetic factors may influence the colonization of pathogenic bacteria, therefore increasing the risk for the initiation and development of periodontal disease. Subjects positive for the composite IL-1 genotype had increased counts of red and orange complex species (20). Other studies also demonstrated an association between IL-6 gene and Fcr gene receptor variants and subgingival detection of Pg and Aggregatibacter actinomycetemcomitans (Aa) (21–24). Therefore, we hypothesized that CD14-260 genotype may influence the composition of subgingival microbiota, contributing to the increase of pro-inflammatory cytokines within gingival tissues and hence be associated with the severityof CsA-induced GO. The aim of this study was to investigate the possible association of CD14-260 polymorphisms, subgingival microbiota, and gingival crevicular fluid (GCF) cytokine levels of IL-1β and sCD14 with CsA-induced GO in renal transplant patients.

Givetian, Frasnian and Famennian limestones from southern China contain microfossils generally regarded as calcified algae and cyanobacteria. These are present in 61 out of 253 sampled horizons in four sections from three widely spaced localities in Guangxi and southern Guizhou. Three of the sections sampled are Givetian-Frasnian-Famennian; one section is Frasnian-Famennian. They include reef and non-reef carbonates of shallow marine platform facies. The following taxa are identified with differing degrees of confidence, and placed in algae, cyanobacteria or microproblematica. Algae: Halysis, ‘solenoporaceans’, Vermiporella. Cyanobacteria: Bevocastria, Girvanella, Hedstroemia, Subtifloria. Microproblematica: ?Chabakovia, Garwoodia, ?Issinella, Izhella, Paraepiphyton, Rothpletzella, Shuguria, ?Stenophycus, Tharama, Wetheredella. As a whole, the abundance of algae, cyanobacteria and microproblematica increases by 34% from Givetian to Frasnian, and declines by 63% in the Famennian. This secular pattern of marked Famennian decrease does not support recognition of them as “disaster forms” in the immediate aftermath of late Frasnian extinction. Nonetheless, their survival into the Famennian could indicate tolerance of environmental stress, independence of changes in food supply, morphologic plasticity, and ability to occupy a range of habitats and depths. Uncertainties concerning the affinities of the problematic taxa hinder assessment of their significance.

Satb2 is a special AT-rich binding transcription factor essential for osteoblast differentiation and bone formation. Specific microRNAs (miRNAs) have been identified to regulate the complex process of osteogenic differentiation. It remains unclear how miRNA expressions is changed in the Satb2-induced osteogenic differentiation of bone marrow stromal cells (BMSCs). From the miRNA expression profile data collected by us from Satb2-induced osteogenic differentiation of mouse BMSCs, we found that miR-27a was significantly down-regulated relative to non-treated cells 7 days post induction. By in silico analysis, we identified Sp7 as a miR-27a targeting gene and verified the findings by Western blot analysis, qRT-PCR, and luciferase reporter assays. We also analyzed the function of miR-27a in osteogenic differentiation by transfection of exogenous miR-27a into BMSCs. Overexpression of miR-27a remarkably inhibited the expression of Sp7 and attenuated Satb2-induced osteogenic differentiation. Our results suggest that expression of Sp7 during the early stage of Satb2-induced osteogenic differentiation of BMSCs is regulated by miR-27a.

Abundant normal alkanes, isoprenoid hydrocarbons, terpanes and steranes were detected in 23 samples taken from the carbonate platform to basin facies in the Devonian Frasnian-Famennian (F-F) transition of Guangxi, South China. They were mainly derived from the phytoplankton or bacteria and algae. Molecular stratigraphic parameters, abundant micron gypsums and pyrite framboids show that hypersaline and anoxia prevailed in the F-F transition, the highly stressed environments occurred near the F-F boundary. Orbital cyclostratigraphic studies indicate that the hypersaline and anoxia prevailed in the F-F transition spanned an interval at least from the Palmatolepis linguiformis conodont Zone to the Middle Palmatolepis triangularis conodont Zone and lasted about 1.2 Ma. The Devonian marine ecosystem underwent Early Devonian gradual optimization, Middle Devonian to the F-F transitional stepwise deterioration and late Famennian recovery. A positive feedback among higher surface ocean temperatures, hypersaline, water column anoxia, enhanced nutrient regeneration, phytoplankton productivity and eutrophication was probably substantial in the F-F transition in Guangxi, South China, even in other regions of the world, such as Holy Cross Mountains of Poland, Montagne Noire in southern France, Alberta in Canada. The point that should be emphasized is that the decisive and direct causes of the F-F transitional mass extinction would be the stepwise deterioration of the marine ecosystem since the Middle Devonian other than a bolide impact on the earth. The hypersaline and anoxia prevailed in the F-F transition favor the formation and preservation of hydrocarbon source rocks in South China.

Zoophycos is one of the most complex and enigmatic trace fossils recorded in marine strata from Cambrian to Quaternary worldwide, which is invaluable for the study of Phanerozoic development of organism–environment interactions. Here we address and demonstrate the macroevolution of Phanerozoic Zoophycos by assembling 448 points in constructing the Phanerozoic Zoophycos database based on 291 papers from 1821 to 2015 and 180 specimens from Cambrian to Palaeogene. The comprehensive dataset reveals, for the first time, five peaks and six depressions in Phanerozoic Zoophycos occurrence frequency. Secondly, the palaeogeographical distribution of Zoophycos is closely associated with the supercontinent Pangaea shifting, independent of the latitude. Our data also attest that the bathymetrical shift of Zoophycos from the littoral–neritic to bathyal environments is synchronized with the tiering shift from shallow to deep. By detailed comparison with body fossils, geochemical and palaeogeographical records, we conclude that the macroevolution of Phanerozoic Zoophycos is multi-affected by the global biodiversity expansion, benthic nutrient enhancement and the biotic macroevolution of the Zoophycos-producers. The macroevolution of development evidenced by the morphological changes of Zoophycos and other trace fossils, may have great implications on the behavioural and physiological adaptation of ancient animals to the environments.

In a previous study, we showed that IFN-γ and TNF-α induce bone marrow mesenchymal stem cell (BMMSC) apoptosis and absorption of tissue-engineered cartilage, but the induced regulatory T cells (iTreg) inhibit the function of IFN-γ and TNF-α. In this study, we investigated the effect of iTreg cells on the absorption of tissue-engineered cartilage caused by endogenous IFN-γ and TNF-α.We transfected the TGF-β1 gene into BMMSCs co-cultured with CD4(+) T lymphocytes. Then, we assessed the expression of iTreg cell markers (Foxp3, CD25 and CD 39) and IFN-γ and TNF-α and the level of apoptosis of BMMSCs. In addition, we characterized chondrogenic-committed cells from TGF-β1(+)BMMSCs and explored the role of iTreg cells.IFN-γ and TNF-α were detected in the groups with CD4(+) T cells. In the group in which TGF-β1(+)BMMSCs were co-cultured with CD4(+) T cells, we observed Foxp3(+)Treg/ CD25(+)CD39(+) (17.58 ± 0.45%) cells as well as significant inhibition of BMMSC apoptosis and tissue-engineered cartilage absorption.CD4(+) T cells led to the absorption of tissue-engineered cartilage through the secretion of endogenous IFN-γ and TNF-α, whose inflammatory functions were concomitantly suppressed by iTreg cells converted from CD4(+) T cells. This study is clinically relevant and adds to our understanding of the mechanism of tissue-engineered cartilage absorption.

Special AT-rich sequence-binding protein 2 (SATB2 ) acts as a potent transcription factor to promote osteoblast differentiation and bone regeneration. In this study, we first used lentiviral-mediated gene transfer of Satb2 into mouse bone marrow stromal cells (BMSCs) and investigated the capacity of SATB2 overexpression to promote osteogenic differentiation in vitro and in vivo. We found that LV-Satb2 -transduced BMSCs produced SATB2 protein and underwent rapid and marked osteogenic differentiation, as demonstrated by increased expression of osteoblastic genes, including runt-related transcription factor 2 (Runx2), transcription factor Sp7 (Sp7), activating transcription factor 4 (Atf4), and bone sialoprotein (Bsp), and increased alkaline phosphatase activity and Alizarin Red S staining. To analyze the induction of bone formation in vivo, LV-Satb2-transduced BMSCs were implanted into the hindlimbs of syngeneic mice, with β-tricalcium phosphate as the scaffolding material. Four weeks after implantation, transduction with LV-Satb2 had greatly enhanced the formation of new bone. These data demonstrated the capacity of lentiviral-mediated SATB2 to promote the osteogenic differentiation of BMSCs in vitro and to enhance bone formation through a tissue-engineering technique that may be useful in bone-regenerative medicine.

Satb2 acts as a potent transcription factor to promote osteoblast differentiation and bone regeneration. Recently, microRNAs (miRNA) have been identified as critical regulators of osteogenic differentiation. This study aimed to identify specific miRNAs and their regulatory roles in the process of Satb2-induced osteogenic differentiation. We studied the differentially expressed miRNAs by Satb2 overexpression in murine bone marrow stromal cells using miRNA microarray. Ten down-regulated miRNAs including miR-27a, miR-125a-5p, and miR-466f-3p, and 18 up-regulated miRNAs including miR-17, miR-20a and miR-210 were found to be differentially expressed and their expression were verified by quantitative real time PCR. The differentially expressed miRNAs were further subjected to gene ontology and KEGG analysis. The highly enriched GOs and KEGG pathway showed target genes of these miRNAs were significantly involved in multiple biological processes (mesenchymal cell differentiation, bone formation, and skeletal development), and several osteogenic pathways (TGF-β/BMP, MAPK, and Wnt signaling pathway). Finally, miR-27a was selected for target verification and function analysis. BMP2, BMPR1A, and Smad9, members of the TGF-β/BMP superfamily, which were predicted to be target genes of miR-27a, were confirmed to be significantly up-regulated in Satb2-overexpressing cells by quantitative real time PCR. Overexpression of miR-27a significantly inhibited osteogenesis and repressed BMP2, BMPR1A, and Smad9 expression. In this study, we identified that a number of differentially regulated miRNAs, whose target genes involved in the TGF-β/BMP signaling pathway, play an important role in the early stage of Satb2-induced osteogenic differentiation.

Objective Interleukin-10 (IL-10) is an anti-inflammatory cytokine whose genetic polymorphisms are associated with the production of IL-10 and the susceptibility to periodontal diseases. The aim of this study was to investigate the possible association of IL-10 single nucleotide polymorphisms (SNPs) and cyclosporin A (CsA)-induced gingival overgrowth (GO) in renal transplant patients in a Chinese population, taking into account subgingival microbiota as additional variables. Material and methods A total of 202 patients were dichotomized into two groups: 122 with GO and 80 without GO. The IL-10-1082 SNP, -819 SNP and -592 SNP were measured using an allele-specific PCR method. The levels of subgingival bacteria were measured by real-time PCR. Genotype and allele frequencies were analyzed using the Chi-square test and logistic regression analysis. Results The frequency of IL-10-819TT (-592AA) genotype was statistically higher in patients with GO than that in patients without GO (P

Song, J., Crasquin, S. & Gong, Y., September 2016. Ostracods of the Late Devonian Frasnian/Famennian transition from western Junggar, Xinjiang, NW China. Alcheringa 41, xxx–xxx. ISSN 0311-5518.Ostracods are described for the first time from the Late Devonian of western Junggar in Xinjiang, NW China. Fifty-two species belonging to 30 genera are recognized, and seven are new: Arcuaria hebukesarensis sp. nov., Bairdia shaerbuertiensis sp. nov., Cribroconcha honggulelengensis sp. nov., Microchelinella bulongourensis sp. nov., M. hoxtolgayensis sp. nov., Pribylites wulankeshunensis sp. nov. and P. junggarensis sp. nov. The ostracod fauna indicates a probable late Frasnian age for the lower member of the Hongguleleng Formation, and the Frasnian/Famennian boundary may exist in the basal part of the formation. The ostracod assemblages are referable to the Eifelian Mega-Assemblage, incorporating both the palaeocopid and smooth-podocopid associations. The fauna implies deposition in a nearshore–offshore environment...