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.

Liver transcriptomic and proteomic analyses provide new insight into the pathogenesis of liver fibrosis in mice.

BACKGROUND: Liver fibrosis (LF) is a kind of progressive liver injury reaction. The goal of this study was to achieve a more detailed understanding of the molecular changes in response to CCl4-induced LF through the identification of a differentially expressed liver transcriptomic and proteomic. RESULTS: A total of 1224 differentially expressed genes (DEGs) and 302 differentially expressed proteins (DEPs) were significantly identified at the transcriptomic and proteomic level, respectively, and 69 genes (hereafter "cor-DEGs-DEPs" genes) were detected at both levels. Pathway enrichment analysis showed that these cor-DEGs-DEPs genes were significantly enriched in 133 pathways. Importantly, among the cor-DEGs-DEPs genes, Gstm1, Gstm3, Ephx1 and Gstp1 were shown to be associated with metabolic pathways, and confirmed by RT-qPCR and parallel reaction monitoring (PRM) verification. CONCLUSIONS: Through the combined analysis of transcriptomic and proteomic data, this study provides valuable insights into the potential mechanism of the pathogenesis of LF, and lays a theoretical foundation for the further development of targeted therapy for LF.

A case report of solitary fibrous tumor of the thyroid gland and literature review.

RATIONALE: A solitary fibrous tumor (SFT) is an uncommon soft tissue tumor that was first discovered in the pleura. Although SFTs have been documented in other extra-pleural sites, an SFT in the thyroid gland is highly unusual. An SFT of the thyroid gland can be difficult to diagnose, and there is little information about their Underlying biological behavior. PATIENT CONCERNS: We present a case of a 63-year-old man with a progressively growing left-neck mass detected 1 month ago, which was pathologically confirmed to be a benign SFT of the thyroid gland. DIAGNOSIS: Postoperative pathological examination of the tumor revealed an SFT. Immunopathological examination was consistent with the diagnosis of an SFT. INTERVENTIONS: The patient underwent surgical resection of the SFT. OUTCOMES: The patient was recurrence-free during 1.5 years of follow-up. LESSONS: Surgical excision is beneficial in SFTs that show no histological signs of malignancy, such as pleomorphism, enhanced mitotic activity, necrosis, bleeding, or capsular invasion. However, because the biologic activity remains unknown, meticulous long-term monitoring is required.

High-Throughput Sequencing Reveals N6-Methyladenosine-modified LncRNAs as Potential Biomarkers in Mice with Liver Fibrosis.

BACKGROUND: N6-methyladenosine (m6A) is the most frequent internal modification in eukaryotic RNA. Long noncoding RNAs (lncRNAs) are a new type of noncoding regulatory molecule with multiple cellular functions. Both are closely related to the occurrence and development of liver fibrosis (LF). However, the role of m6A-methylated lncRNAs in the progression of LF remains largely unknown. METHODS: In this study, HE and Masson staining were used to observe pathological changes in the liver, m6A-modified RNA immunoprecipitation sequencing (m6A-seq) was performed to systematically evaluate the m6A modification level of lncRNAs in LF mice, meRIP-qPCR and RT-qPCR were used to detect the m6A methylation level and RNA expression level of the target lncRNAs. RESULTS: A total of 415 m6A peaks were detected in 313 lncRNAs in liver fibrosis tissues. There were 98 significantly different m6A peaks in LF, which were located on 84 lncRNAs, of which 45.2% of the lncRNA length was between 200-400 bp. At the same time, the first three chromosomes of these methylated lncRNAs were chromosomes 7, 5 and 1. RNA sequencing identified 154 differentially expressed lncRNAs in LF. The joint analysis of m6A-seq and RNA-seq found that there were three lncRNAs with significant changes in m6A methylation and RNA expression levels: lncRNA H19, lncRNA Gm16023 and lncRNA Gm17586. Subsequently, the verification results showed that the m6A methylation levels of lncRNA H19 and lncRNA Gm17586 were significantly increased, while that of lncRNA Gm16023 was significantly decreased, and the RNA expression of three lncRNAs was significantly decreased. Through the establishment of a lncRNA-miRNA-mRNA regulatory network, the possible regulatory relationships of lncRNA H19, lncRNA Gm16023 and lncRNA Gm17586 in LF were revealed. CONCLUSION: This study revealed the unique m6A methylation pattern of lncRNAs in LF mice, suggesting that the m6A methylation modification of lncRNAs is related to the occurrence and development of LF.

Quantitative phosphoproteomic analysis of mice with liver fibrosis by DIA mass spectrometry analysis with PRM verification.

Liver fibrosis (LF), commonly associated with chronic liver diseases, is a major public health problem worldwide. Protein phosphorylation is not only an important form of protein modification in organisms but also the most important mechanism to regulate and control the activity and function of proteins, affecting the occurrence and development of many diseases. However, comprehensive phosphoproteomic profiling in LF has not been fully elucidated. In this study, data-independent acquisition (DIA) was used to analyse the phosphoproteomics of mice with LF. A total of 553 phosphopeptides (representing 440 phosphoproteins) had significant phosphorylation levels. Among these phosphoproteins, 49 were upregulated and 401 were downregulated, and 5 phosphoserine (P-Ser) motifs and 2 phosphothreonine (P-Thr) motifs were conserved in LF. GO and KEGG pathway enrichment analyses identified 769 significant GO terms and 49 significant KEGG pathways. Four phosphorylated proteins were selected for parallel reaction monitoring (PRM) verification, and the results were consistent with DIA data. Together, there were significantly different phosphoproteomic profiles in LF, suggesting that protein phosphorylation was related to the occurrence and progression of LF, which could pave the way for further investigation into the related regulatory mechanisms. SIGNIFICANCE: LF is a necessary stage in the development of chronic liver disease to liver cirrhosis and has attracted wide attention. To the best of our knowledge, there are few reports on the phosphorylated proteomics of LF. In this study, DIA and PRM techniques were used to study the liver tissue of mice induced by CCl4. The results showed that phosphorylation had a significant effect on the activity and function of proteins, and the PRM results were consistent with the trend observed in DIA analysis. This study will help to better reveal the relationship of phosphorylated proteins in LF and lay a foundation for further study of related regulatory mechanisms.

Review of research on migration, distribution, biological effects, and analytical methods of microfibers in the environment.

Microplastics have been proven to be one of the critical environmental pollution issues. Moreover, microfibers, the most prominent form of microplastics in the environment, have likewise attracted the attention of various countries. With the increase in global population and industrialization, the production and use of fibers continue to increase yearly. As a result, a large number of microfibers are formed. If fiber products are not used or handled correctly, it will cause direct/indirect severe microfiber environmental pollution. Microfibers will be further broken into smaller fiber fragments when they enter the natural environment. Presently, researchers have conducted extensive research in the identification of microfibers, laying the foundation for further resourcefulness research. This work used bibliometric analysis to review the microfiber contamination researches systematically. First, the primary sources of microfibers and the influencing factors are analyzed. We aim to summarize the influence of the clothing fiber preparation and care processes on microfiber formation. Then, this work elaborated on the migration in/between water, atmosphere, and terrestrial environments. We also discussed the effects of microfiber on ecosystems. Finally, microfibers' current and foreseeable effective treatment, disposal, and resource utilization methods were explained. This paper will provide a structured reference for future microfiber research.

Fucosylated Chondroitin Sulfate against Parkinson's Disease through Inhibiting Inflammation Induced by Gut Dysbiosis.

Growing evidence for the importance of the gut-brain axis in Parkinson's disease (PD) has attracted researchers' interest in the possible application of microbiota-based treatment approaches. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, we looked into the prospect of treating PD with fucosylated chondroitin sulfate obtained from sea cucumbers Isostichopus badionotus (fCS-Ib). We showed that giving fCS-Ib polysaccharide orally greatly reduced the motor deficits, dopamine depletion, and alpha-synuclein increase caused by MPTP in the substantia nigra (SN). It appears that the anti-PD action of fCS-Ib polysaccharide could be attained by squelching inflammation. Glial cell hyperactivation in SN and overproduction of proinflammatory substances in serum could both be suppressed by fCS-Ib polysaccharide injection. The bacterial DNA in fresh colonic feces was submitted to 16S rRNA and untargeted metabolic analyses to confirm the participation of the microbiota-gut-brain axis in the aforementioned interpretation. The findings showed that the MPTP treatment-induced decrease in norank_f_Muribaculaceae and the increase in Staphylococcus were reversed by the administration of fCS-Ib polysaccharide. The NF-κB signaling pathway was shown to be involved in the fCS-Ib polysaccharide-induced anti-inflammation. In conclusion, our research demonstrated for the first time how fCS-Ib polysaccharide combats PD by reducing inflammation caused by gut microbial dysbiosis.

Effect of traditional Chinese exercise combined with massage on pain and disability in patients with lumbar disc herniation: A multi-center, randomized, controlled, assessor-blinded clinical trial.

Background: Herniation of the nucleus pulposus caused by disc degeneration and other reasons can cause low back pain and disability. In China, traditional Chinese exercises (TCEs) and traditional Chinese massage (TCM) are widely used to improve symptoms of pain and disability in patients with lumbar disc herniation (LDH). The safety and efficacy of combination therapy have not been studied. Objectives: To assess the effect of traditional Chinese exercise combined with massage vs. traditional Chinese massage alone on pain, disability, lumbar mobility and gait performance in patients with LDH. Methods: Multi-center, randomized clinical trial conducted at 4 hospitals in China and enrolling 272 patients with LDH. Participants were randomly assigned to TCEs plus TCM group or TCM alone group. The combined therapy group received 18 Tai Chi training sessions (30-min sessions 3 times a week) and regular TCM treatments over 6 weeks. The control group received TCM therapy alone and was instructed to maintain their usual daily physical activity. Outcome variables measured included Visual Analog Scale (VAS), Short Form of McGill Pain Questionnaire (SF-MPQ), Oswestry Disability Index (ODI), lumbar spine range of motion (ROM) and gait performance. Results: Among the 272 randomized participants, 259 completed the study. The mean VAS score was 51.77 mm at baseline in the TCEs plus TCM group, and 50.93 mm for the TCM alone group. The reduction in the VAS score at week 6 was greater in the TC group than in the TCM group with a mean difference of 4.05 (95% CI, 2.15-5.95; P < 0.001), and the ODI score with between-group differences of 3.57 points (95% CI, 2.84-4.30 points; P < 0.001). Similar significantly different results were observed in SF-MPQ, walking speed, cadence, and lumbar ROM. No serious adverse events were reported throughout the study period. Conclusion: Compared with TCM alone, TCEs combined with TCM treatment performed better in reducing pain and improving disability. The combination therapy could be considered a valuable treatment option for LDH patients, with potential therapeutic utility for middle-aged and elderly patients with LDH.

Comprehensive Analysis of the Transcriptome-Wide m6A Methylation Modification Difference in Liver Fibrosis Mice by High-Throughput m6A Sequencing.

N6-Methyladenosine (m6A), a unique and common mRNA modification method in eukaryotes, is involved in the occurrence and development of many diseases. Liver fibrosis (LF) is a common response to chronic liver injury and may lead to cirrhosis and even liver cancer. However, the involvement of m6A methylation in the development of LF is still unknown. In this study, we performed a systematic evaluation of hepatic genome-wide m6A modification and mRNA expression by m6A-seq and RNA-seq using LF mice. There were 3,315 genes with significant differential m6A levels, of which 2,498 were hypermethylated and 817 hypomethylated. GO and KEGG analyses illustrated that differentially expressed m6A genes were closely correlated with processes such as the endoplasmic reticulum stress response, PPAR signaling pathway and TGF-ß signaling pathway. Moreover, a total of 90 genes had both a significant change in the m6A level and mRNA expression shown by joint analysis of m6A-seq and RNA-seq. Hence, the critical elements of m6A modification, including methyltransferase WTAP, demethylases ALKBH5 and binding proteins YTHDF1 were confirmed by RT-qPCR and Western blot. In an additional cell experiment, we also observed that the decreased expression of WTAP induced the development of LF as a result of promoting hepatic stellate cell (HSC) activation. Therefore, this study revealed unique differential m6A methylation patterns in LF mice and suggested that m6A methylation was associated with the occurrence and course of LF to some extent.

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.

Reconstruction and analysis of competitive endogenous RNA network reveals regulatory role of long non­coding RNAs in hepatic fibrosis.

Hepatic fibrosis (HF), one of the leading global health problems, is defined as aberrant and excess production of extracellular matrix components. The pathogenesis of HF is complex and poorly understood. Long non­coding RNAs (LncRNAs) can interact with microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs) to regulate the expression of target genes, which play a significant role in the initiation and progression of HF. In the present study, the LncRNA­associated ceRNA network was reconstructed based on LncRNA, miRNA and mRNA expression profiles that were downloaded from National Center for Biotechnology Information Gene Expression Omnibus. Bioinformatics assessments including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed with Database for Annotation, Visualization and Integration Discovery. The ceRNA network was composed of 220 LncRNA nodes, 24 miRNA nodes, 164 mRNA nodes and 1,149 edges. Functional assays identified that a total of 338 GO terms and 25 pathways, including regulation of cytokine and collagen, and the transforming growth factor­ß and Toll­like receptor signaling pathways, were significantly enriched. In addition, 4 LncRNAs (NONMMUT036242, XR_877072, XR_378619 and XR_378418) were highly related to HF and thereby chosen as key LncRNAs. The present study uncovered a ceRNA network that could further the understanding of the mechanisms underlying HF development and provide potential novel markers for clinical diagnosis and targets for treatment.

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.

Enhanced methane production of vinegar residue by response surface methodology (RSM).

As the by-product of the vinegar production process, a large number of vinegar residue has been abandoned and caused a serious environmental pollution. Anaerobic digestion has been proved to be able to dispose and convert vinegar residue into bioenergy but still need to improve the efficiency. This study applied central composite design of response surface methodology to investigate the influences of feed to inoculum ratio, organic loading, and initial pH on methane production and optimize anaerobic digestion condition. The maximum methane yield of 203.91 mL gVS-1 and biodegradability of 46.99% were obtained at feed to inoculum ratio of 0.5, organic loading of 31.49 gVS L-1, and initial pH of 7.29, which was considered as the best condition. It has a very significant improvement of 69.48% for methane production and 52.02% for biodegradability compared with our previous study. Additionally, a high methane yield of 182.09 mL gVS-1 was obtained at feed to inoculum ratio of 1.5, organic loading of 46.22 gVS L-1, and initial pH of 7.32. And it is more appropriate to apply this condition in industrial application owing to the high feed to inoculum ratio and organic loading. Besides, a significant interaction was found between feed to inoculum ratio and organic loading. This study maximized the methane production of vinegar residue and made a good foundation for further study and future industrial application.

The world's earliest Aral-Sea type disaster: the decline of the Loulan Kingdom in the Tarim Basin.

Remnants of cities and farmlands in China's hyperarid Tarim Basin indicate that environmental conditions were significantly wetter two millennia ago in a region which is barren desert today. Historical documents and age data of organic remains show that the Loulan Kingdom flourished during the Han Dynasty (206 BCE-220 CE) but was abandoned between its end and 645 CE. Previous archaeological, geomorphological and geological studies suggest that deteriorating climate conditions led to the abandonment of the ancient desert cities. Based on analyses of lake sediments from Lop Nur in the eastern Tarim Basin and a review of published records, we show that the Loulan Kingdom decline resulted from a man-made environmental disaster comparable to the recent Aral Sea crisis rather than from changing climate. Lop Nur and other lakes within the Han Dynasty realm experienced rapidly declining water levels or even desiccation whilst lakes in adjacent regions recorded rising levels and relatively wet conditions during the time of the Loulan Kingdom decline. Water withdrawal for irrigation farming in the middle reaches of rivers likely caused water shortage downstream and eventually the widespread deterioration of desert oases a long time before man initiated the Aral Sea disaster in the 1960s.

Study on biomethane production and biodegradability of different leafy vegetables in anaerobic digestion.

Enormous amounts of vegetable residues are wasted annually, causing many environmental problems due to their high moisture and organic contents. In this study, the methane production potential of 20 kinds of typical leafy vegetable residues in China were explored using a unified method. A connection between the biochemical components and the methane yields of these vegetables was well established which could be used to predict biogas performance in practice. A high volatile solid/total solid (VS/TS) ratio and hemicellulose content exhibited a positive impact on the biogas yield while lignin had a negative impact. In addition, three kinetic models were used to describe the methane production process of these agro-wastes. The systematic comparison of the methane production potentials of these leafy vegetables shown in this study will not only serve as a reference for basic research on anaerobic digestion but also provide useful data and information for agro-industrial applications of vegetable residues in future work.

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.

Panax notoginseng saponins ameliorates experimental hepatic fibrosis and hepatic stellate cell proliferation by inhibiting the Jak2/ Stat3 pathways.

OBJECTIVE: To investigate the inhibitory effect of Panax notoginseng saponins (PNS) on liver fibrosis and explore the underlying mechanisms. METHODS: Carbon tetrachloride (CCl4)-treated rats and hepatic stellate cells (HSCs) were used. The effect of PNS on CCl4-induced liver fibrosis was studied with histochemical and biochemical analysis. Transforming growth factor (TGF)-ß1, α-smooth muscle actin (α-SMA), and collagen I mRNA expression were determined by reverse transcripwhile, the protein expression levels of α-SMA, collagen I, phosphorylation-Janus activated kinase signal transducer (p-Jak2)/Jak2, and phosphorylation-activator of transcription (p-Stat)3/Stat3 were determined by immunohistochemistry and/or immunoblotting. RESULTS: PNS treatment significantly improved the liver function of rats as indicated by decreased serum enzymatic activities of alanine aminotransferase and aspartate aminotransferase. Histopathological results indicated that PNS alleviated liver damage and reduced the formation of fibrous septa. Moreover, PNS significantly decreased liver hydroxyproline and significantly attenuated expressions of collagen I, α-SMA, TGF-ß1, p-Jak2 / Jak2, and p-Stat3/Stat3 in the rat liver fibrosis model and HSCs. CONCLUSION: PNS can relieve liver fibrosis by modulating Jak2/Stat3 signaling transduction pathway, which may be one of its mechanisms to suppress hepatic fibrosis.