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.

Identification of STAT3 as a biomarker for cellular senescence in liver fibrosis: A bioinformatics and experimental validation study.

BACKGROUND: Cellular senescence is associated with a dysregulated inflammatory response, which is an important driver of the development of liver fibrosis (LF). This study aimed to investigate the effect of cellular senescence on LF and identify potential key biomarkers through bioinformatics analysis combined with validation experiments in vivo and in vitro. METHODS: The Gene Expression Omnibus (GEO) database and GeneCards database were used to download the LF dataset and the aging-related gene set, respectively. Functional enrichment analysis of differential genes was then performed using GO and KEGG. Hub genes were further screened using Cytoscape's cytoHubba. Diagnostic values for hub genes were evaluated with a receiver operating characteristic (ROC) curve. Next, CIBERSORTx was used to estimate immune cell types and ratios. Finally, in vivo and in vitro experiments validated the results of the bioinformatics analysis. Moreover, molecular docking was used to simulate drug-gene interactions. RESULTS: A total of 44 aging-related differentially expressed genes (AgDEGs) were identified, and enrichment analysis showed that these genes were mainly enriched in inflammatory and immune responses. PPI network analysis identified 6 hub AgDEGs (STAT3, TNF, MMP9, CD44, TGFB1, and TIMP1), and ROC analysis showed that they all have good diagnostic value. Immune infiltration suggested that hub AgDEGs were significantly associated with M1 macrophages or other immune cells. Notably, STAT3 was positively correlated with α-SMA, COL1A1, IL-6 and IL-1ß, and was mainly expressed in hepatocytes (HCs). Validation experiments showed that STAT3 expression was upregulated and cellular senescence was increased in LF mice. A co-culture system of HCs and hepatic stellate cells (HSCs) further revealed that inhibiting STAT3 reduced HCs senescence and suppressed HSCs activation. In addition, molecular docking revealed that STAT3 was a potential drug therapy target. CONCLUSIONS: STAT3 may be involved in HCs senescence and promote HSCs activation, which in turn leads to the development of LF. Our findings suggest that STAT3 could be a potential biomarker for LF.

A Network Pharmacology Approach to Explore the Mechanisms of Shugan Jianpi Formula in Liver Fibrosis.

PURPOSE: We explored the mechanism of Shugan Jianpi Formula (SGJPF) and its effective components for the treatment of liver fibrosis (LF). MATERIALS AND METHODS: We collected the active ingredients in SGJPF through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and screened the effective components by absorption, distribution, metabolism, and excretion. Herb-associated target proteins were predicted and screened based on the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine and Search Tool for Interactions of Chemicals databases. LF-associated target proteins were predicted and screened based on the Online Mendelian Inheritance in Man® Database and Comparative Toxicogenomics Database. Common genes with LF and herbs were selected, and Cytoscape 3.5.1 software was used to construct an herb pathway and component-LF common target network. The Search Tool for the Retrieval of Interacting Genes/Proteins was used to build a protein-protein interaction, and quantitative PCR was used to verify the related target genes. Finally, clusterProfiler was applied for the analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. RESULTS: The pharmacological network contained 252 active compounds (e.g., Astragaloside A, saikosaponin, linoleic acid, and Poria acid A), 84 common target genes, and 94 significant signaling pathways. Among them, interleukin 6 (IL-6), tumor protein 53 p53 (TP53), prostaglandin-endoperoxide synthase 2 (PTGS2), AKT1, IL-1ß, and the nucleotide-binding and oligomerization domain-like receptor and Janus kinase-signal transducer and activator of transcription signaling pathways were selected as the critical target gene and critical signal pathway, respectively. CONCLUSION: The mechanisms of SGJPF in protecting against LF include the regulation of multiple targets such as IL-6, TP53, PTGS2, and AKT1. These target proteins affect LF through various signal transduction pathways.

Determining the Age of Terrace Formation Using Luminescence Dating-A Case of the Yellow River Terraces in the Baode Area, China.

Dating fluvial terraces has long been a challenge for geologists and geomorphologists, because terrace straths and treads are not usually directly dated. In this study, the formation ages of the Yellow River terraces in the Baode area in China were determined by dating fluvial deposits overlying bedrock straths using optically stimulated luminescence (OSL) dating techniques. Seven terraces (from the lowest terrace T1 to the highest terrace T7) in the study area were recognized, and they are characterized by thick fluvial terrace deposits overlaid by loess sediments. Twenty-five samples from nine terrace sections were dated to about 2-200 ka. The OSL ages (120-190 ka) of the fluvial samples from higher terraces (T3-T6) seem to be reliable based on their luminescence properties and stratigraphic consistency, but the geomorphologic and stratigraphic evidence show that these ages should be underestimated, because they are generally similar to those of the samples from the lower terrace (T2). The formation ages of the terrace straths and treads for the T1 terrace were deduced to be about 44 ka and 36 ka, respectively, based on the deposition rates of the fluvial terrace deposits, and the T2 terrace has the same strath and tread formation age of about 135 ka. The incision rate was calculated to be about 0.35 mm/ka for the past 135 ka, and the uplift rate pattern suggests that the Ordos Plateau behaves as a rigid block. Based on our previous investigations on the Yellow River terraces and the results in this study, we consider that the formation ages of terrace straths and treads calculated using deposition rates of terrace fluvial sediments can overcome problems associated with age underestimation or overestimation of strath or fill terraces based on the single age of one fluvial terrace sample. The implication is that, for accurate dating of terrace formation, terrace sections should be systematically sampled and dated.

Late Middle Pleistocene Levallois stone-tool technology in southwest China.

Levallois approaches are one of the best known variants of prepared-core technologies, and are an important hallmark of stone technologies developed around 300,000 years ago in Africa and west Eurasia1,2. Existing archaeological evidence suggests that the stone technology of east Asian hominins lacked a Levallois component during the late Middle Pleistocene epoch and it is not until the Late Pleistocene (around 40,000-30,000 years ago) that this technology spread into east Asia in association with a dispersal of modern humans. Here we present evidence of Levallois technology from the lithic assemblage of the Guanyindong Cave site in southwest China, dated to approximately 170,000-80,000 years ago. To our knowledge, this is the earliest evidence of Levallois technology in east Asia. Our findings thus challenge the existing model of the origin and spread of Levallois technologies in east Asia and its links to a Late Pleistocene dispersal of modern humans.

Metabolic characterization of the early stage of hepatic fibrosis in rat using GC-TOF/MS and multivariate data analyses.

The aim of this study was to explore the changes in the urine metabolic spectrum in rats with the early stage of liver fibrosis using gas chromatography-time of flight/mass spectrometry (GC-TOF/MS), try to search for potential biomarkers and elucidate the probably metabonomic pathogenesis. The early stage of liver fibrosis was established with a single subcutaneous injection of carbon tetrachloride twice each week for 4 weeks continuously. At the end of the experiment, GC-TOF/MS technology with multivariate statistical approaches such as principal component analysis, partial least squares-discriminant analysis and orthogonal partial least squares-discriminant analysis was used to analyze the changes in the metabolic spectrum trajectory and identify potential biomarkers. Twelve potential biomarkers in the model group, such as succinic acid, threonine and lactose, were selected, which indicate that the metabonomic pathogenesis of the early stage of liver fibrosis may be related to disorders of energy metabolism, amino acid metabolism and fatty acid metabolism.

Optically stimulated luminescence dating of cave deposits at the Xiaogushan prehistoric site, northeastern China.

The Xiaogushan cave site is one of the most important prehistoric sites in North China. The stone and bone artifacts found in the cave are similar to European contemporaneous artifacts. Cave deposits consist of five layers that have been dated from 46,353 ± 1179 to 4229 ± 135 cal. yr BP, using radiocarbon dating techniques on charcoal and bone samples collected from Layers 2-5. In this paper, optically stimulated luminescence (OSL) techniques were applied to date six samples taken from Layers 1-3. The luminescence properties of the fine-grained and coarse-grained quartz extracts indicate that the materials are suitable for OSL dating using a single-aliquot regeneration-dose (SAR) protocol. The OSL ages obtained are broadly consistent with the stratigraphy and the associated calibrated radiocarbon ages. The dating results show that the cave was first occupied by humans about 70 ka. The human occupation of the cave may be related to climate change. An occupation hiatus is inferred to between ∼ 17 to ∼ 10 ka. The stone and bone artifacts found in Layers 2 and 3 may indicate the Middle to Upper Paleolithic transitions in the region.