New Late Pleistocene age for the Homo sapiens skeleton from Liujiang southern China.

The emergence of Homo sapiens in Eastern Asia is a topic of significant research interest. However, well-preserved human fossils in secure, dateable contexts in this region are extremely rare, and often the subject of intense debate owing to stratigraphic and geochronological problems. Tongtianyan cave, in Liujiang District of Liuzhou City, southern China is one of the most important fossils finds of H. sapiens, though its age has been debated, with chronometric dates ranging from the late Middle Pleistocene to the early Late Pleistocene. Here we provide new age estimates and revised provenience information for the Liujiang human fossils, which represent one of the most complete fossil skeletons of H. sapiens in China. U-series dating on the human fossils and radiocarbon and optically stimulated luminescence dating on the fossil-bearing sediments provided ages ranging from ~33,000 to 23,000 years ago (ka). The revised age estimates correspond with the dates of other human fossils in northern China, at Tianyuan Cave (~40.8-38.1 ka) and Zhoukoudian Upper Cave (39.0-36.3 ka), indicating the geographically widespread presence of H. sapiens across Eastern Asia in the Late Pleistocene, which is significant for better understanding human dispersals and adaptations in the region.

Initial Upper Palaeolithic material culture by 45,000 years ago at Shiyu in northern China.

The geographic expansion of Homo sapiens populations into southeastern Europe occurred by ∼47,000 years ago (∼47 ka), marked by Initial Upper Palaeolithic (IUP) technology. H. sapiens was present in western Siberia by ∼45 ka, and IUP industries indicate early entries by ∼50 ka in the Russian Altai and 46-45 ka in northern Mongolia. H. sapiens was in northeastern Asia by ∼40 ka, with a single IUP site in China dating to 43-41 ka. Here we describe an IUP assemblage from Shiyu in northern China, dating to ∼45 ka. Shiyu contains a stone tool assemblage produced by Levallois and Volumetric Blade Reduction methods, the long-distance transfer of obsidian from sources in China and the Russian Far East (800-1,000 km away), increased hunting skills denoted by the selective culling of adult equids and the recovery of tanged and hafted projectile points with evidence of impact fractures, and the presence of a worked bone tool and a shaped graphite disc. Shiyu exhibits a set of advanced cultural behaviours, and together with the recovery of a now-lost human cranial bone, the record supports an expansion of H. sapiens into eastern Asia by about 45 ka.

Innovative ochre processing and tool use in China 40,000 years ago.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1-4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5-7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8-10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11.

Technological innovations at the onset of the Mid-Pleistocene Climate Transition in high-latitude East Asia.

The interplay between Pleistocene climatic variability and hominin adaptations to diverse terrestrial ecosystems is a key topic in human evolutionary studies. Early and Middle Pleistocene environmental change and its relation to hominin behavioural responses has been a subject of great interest in Africa and Europe, though little information is available for other key regions of the Old World, particularly from Eastern Asia. Here we examine key Early Pleistocene sites of the Nihewan Basin, in high-latitude northern China, dating between ∼1.4 and 1.0 million years ago (Ma). We compare stone-tool assemblages from three Early Pleistocene sites in the Nihewan Basin, including detailed assessment of stone-tool refitting sequences at the ∼1.1-Ma-old site of Cenjiawan. Increased toolmaking skills and technological innovations are evident in the Nihewan Basin at the onset of the Mid-Pleistocene Climate Transition (MPT). Examination of the lithic technology of the Nihewan sites, together with an assessment of other key Palaeolithic sites of China, indicates that toolkits show increasing diversity at the outset of the MPT and in its aftermath. The overall evidence indicates the adaptive flexibility of early hominins to ecosystem changes since the MPT, though regional abandonments are also apparent in high latitudes, likely owing to cold and oscillating environmental conditions. The view presented here sharply contrasts with traditional arguments that stone-tool technologies of China are homogeneous and continuous over the course of the Early Pleistocene.

The Paleolithic in the Nihewan Basin, China: Evolutionary history of an Early to Late Pleistocene record in Eastern Asia.

The Nihewan Basin of China preserves one of the most important successions of Paleolithic archeological sites in Eurasia. Stratified archeological sites and mammalian fossils, first reported in the 1920s, continue to be recovered in large-scale excavation projects. Here, we review key findings from archeological excavations in the Nihewan Basin ranging from ~1.66 Ma to 11.7 ka. We place particular emphasis on changes in stone tool technology over the long term. Though Pleistocene lithic industries from East Asia are often described as simple in character, re-evaluation of the stone tool evidence from the Nihewan Basin demonstrates significant, though periodic, innovations and variability in manufacturing techniques through time, indicating adaptive and technological flexibility on the part of hominins. Synthesis of paleoenvironmental and archeological data indicate changes in hominin occupation frequency in the Nihewan Basin, with chronological gaps suggesting that continuous presence in high, seasonal latitudes was not possible prior to the Late Pleistocene.

ClC-5 alleviates renal fibrosis in unilateral ureteral obstruction mice.

Renal fibrosis is the major feature of end-stage renal disease with high mortality. Chloride (Cl-) moving along Cl- channels has been suggested to play to an important role in renal function. This study aims to investigate the role of ClC-5 in renal fibrosis in unilateral ureteral occlusion (UUO) mice. C57BL/6 mice received UUO surgery followed by delivery of adeno-associated virus encoding ClC-5 cDNA (AAVClC-5). Western blotting, real-time PCR and histological analysis were used to investigate the effects of ClC-5 on renal fibrosis and underlying mechanisms. The expression of ClC-5 was significantly decreased in renal cortex of UUO mice and transforming growth factor-ß1 (TGF-ß1)-stimulated HK2 cells. Overexpression of ClC-5 in vivo markedly ameliorated UUO-induced renal injury and fibrosis. The increased expressions of plasminogen activator inhibitor type 1, connective tissue growth factor, collagen III and collagen IV were also inhibited by ClC-5 upregulation. Moreover, UUO-induced immune cell infiltration and inflammatory cytokines release were attenuated in mice infected with AAVClC-5. In addition, the in vivo and in vitro results showed that ClC-5 overexpression prevented epithelial-to-mesenchymal transition (EMT), concomitantly with a restoration of E-cadherin expression and a decrease of vimentin, α-SMA and S100A4 expressions. Furthermore, ClC-5 overexpression inhibited UUO- or TGF-ß1-induced increase in nuclear factor kappa B (NF-κB) acetylation and matrix metalloproteinases-9 (MMP-9) expression. However, downregulation of ClC-5 in HK2 cells further potentiated TGF-ß1-induced EMT and increase in NF-κB acetylation and MMP-9 expression. ClC-5 upregulation ameliorates renal fibrosis via inhibiting NF-κB/MMP-9 pathway signaling activation, suggesting that ClC-5 may be a novel therapeutic target for treating renal fibrosis and chronic kidney disease.

Hominin occupation of the Chinese Loess Plateau since about 2.1 million years ago.

Considerable attention has been paid to dating the earliest appearance of hominins outside Africa. The earliest skeletal and artefactual evidence for the genus Homo in Asia currently comes from Dmanisi, Georgia, and is dated to approximately 1.77-1.85 million years ago (Ma)1. Two incisors that may belong to Homo erectus come from Yuanmou, south China, and are dated to 1.7 Ma2; the next-oldest evidence is an H. erectus cranium from Lantian (Gongwangling)-which has recently been dated to 1.63 Ma3-and the earliest hominin fossils from the Sangiran dome in Java, which are dated to about 1.5-1.6 Ma4. Artefacts from Majuangou III5 and Shangshazui6 in the Nihewan basin, north China, have also been dated to 1.6-1.7 Ma. Here we report an Early Pleistocene and largely continuous artefact sequence from Shangchen, which is a newly discovered Palaeolithic locality of the southern Chinese Loess Plateau, near Gongwangling in Lantian county. The site contains 17 artefact layers that extend from palaeosol S15-dated to approximately 1.26 Ma-to loess L28, which we date to about 2.12 Ma. This discovery implies that hominins left Africa earlier than indicated by the evidence from Dmanisi.

Correction: The lithic assemblages of Donggutuo, Nihewan basin: Knapping skills of Early Pleistocene hominins in North China.

[This corrects the article DOI: 10.1371/journal.pone.0185101.].

The lithic assemblages of Donggutuo, Nihewan basin: Knapping skills of early pleistocene hominins in North China.

Donggutuo (DGT) is one of the richest archaeological localities in the Nihewan Basin of North China, thereby providing key information about the technological behaviours of early hominins in eastern Asia. Although DGT has been subject of multiple excavations and technological studies over the past several decades, few detailed studies on the lithic assemblages have been published. Here we summarize and describe the DGT lithic assemblages, examining stone tool reduction methods and technological skills. DGT dates to ca. 1.1 Ma, close to the onset of the mid-Pleistocene climate transition (MPT), indicating that occupations at DGT coincided with increased environmental instability. During this time interval, the DGT knappers began to apply innovative flaking methods, using free hand hard hammer percussion (FHHP) to manufacture pre-determined core shapes, small flakes and finely retouched tools, while occasionally using the bipolar technique, in contrast to the earlier and nearby Nihewan site of Xiaochangliang (XCL). Evidence for some degree of planning and predetermination in lithic reduction at DGT parallels technological developments in African Oldowan sites, suggesting that innovations in early industries may be situational, sometimes corresponding with adaptations to changes in environments and local conditions.

The Lithic Assemblages of Xiaochangliang, Nihewan Basin: Implications for Early Pleistocene Hominin Behaviour in North China.

Xiaochangliang (XCL), located in the Nihewan Basin of North China, is a key archaeological locality for understanding the behavioural evolution of early humans. XCL dates to ca. 1.36 Ma, making it one of the earliest sites in Northeast Asia. Although XCL represents the first excavation of an Early Pleistocene site in the Nihewan Basin, identified and excavated in the 1970's, the lithic assemblages have never been published in full detail. Here we describe the lithic assemblages from XCL, providing information on stone tool reduction techniques and the influence of raw materials on artefact manufacture. The XCL hominins used both bipolar and freehand reduction techniques to manufacture small flakes, some of which show retouch. Bipolar reduction methods at XCL were used more frequently than previously recognized. Comparison of XCL with other Early Pleistocene sites in the Nihewan Basin indicates the variable use of bipolar and freehand reduction methods, thereby indicating a flexible approach in the utilization of raw materials. The stone tools from XCL and the Nihewan sites are classifiable as Mode I lithic assemblages, readily distinguished from bifacial industries manufactured by hominins in Eastern Asia by ca. 800 ka.

Groundwater sapping as the cause of irreversible desertification of Hunshandake Sandy Lands, Inner Mongolia, northern China.

In the middle-to-late Holocene, Earth's monsoonal regions experienced catastrophic precipitation decreases that produced green to desert state shifts. Resulting hydrologic regime change negatively impacted water availability and Neolithic cultures. Whereas mid-Holocene drying is commonly attributed to slow insolation reduction and subsequent nonlinear vegetation-atmosphere feedbacks that produce threshold conditions, evidence of trigger events initiating state switching has remained elusive. Here we document a threshold event ca. 4,200 years ago in the Hunshandake Sandy Lands of Inner Mongolia, northern China, associated with groundwater capture by the Xilamulun River. This process initiated a sudden and irreversible region-wide hydrologic event that exacerbated the desertification of the Hunshandake, resulting in post-Humid Period mass migration of northern China's Neolithic cultures. The Hunshandake remains arid and is unlikely, even with massive rehabilitation efforts, to revert back to green conditions.

Enzyme-promoted regioselective coupling oligomerization of isorhapontigenin towards the first synthesis of (±)-gnetulin.

We report the first synthesis of a natural (±)-gnetulin and an unnatural analogue of (±)-gnemonol M by using the regioselective oxidative coupling reactions of 5-tert-butyl-isorhapontigenin as the key step. Both the effects of different enzyme-catalyzed systems on the structures of coupling products and structural transformations of coupling products in the presence of several Lewis acids were systematically investigated.