Morphological and morphometric analyses of a late Middle Pleistocene hominin mandible from Hualongdong, China.

Excavations in Hualongdong (HLD), East China, have yielded abundant hominin fossils dated to 300 ka. There is a nearly complete mandible that fits well with a partial cranium, and together they compose the skull labeled as HLD 6. Thus far, detailed morphological description and comparisons of the mandible have not been conducted. Here we present a comprehensive morphological, metric, and geometric morphometric assessment of this mandible and compare it with both adult and immature specimens of Pleistocene hominins and recent modern humans. Results indicate that the HLD 6 mandible exhibits a mosaic morphological pattern characterized by a robust corpus and relatively gracile symphysis and ramus. The moderately developed mental trigone and a clear anterior mandibular incurvation of the HLD 6 mandible are reminiscent of Late Pleistocene hominin and recent modern human morphology. However, the weak expression of all these features indicates that this mandible does not possess a true chin. Moreover, a suite of archaic features that resemble those of Middle Pleistocene hominins includes pronounced alveolar planum, superior transverse torus, thick corpus, a pronounced endocondyloid crest, and a well-developed medial pterygoid tubercle. The geometric morphometric analysis further confirms the mosaic pattern of the HLD 6 mandible. The combination of both archaic and modern human features identified in the HLD 6 mandible is unexpected, given its late Middle Pleistocene age and differs from approximately contemporaneous Homo members such as Xujiayao, Penghu, and Xiahe. This mosaic pattern has never been recorded in late Middle Pleistocene hominin fossil assemblages in East Asia. The HLD 6 mandible provides further support for the high morphological diversity during late Middle Pleistocene hominin evolution. With these findings, it is possible that modern human morphologies are present as early as 300 ka and earlier than the emergence of modern humans in East Asia.

A computerized facial approximation method for Homo sapiens based on facial soft tissue thickness depths and geometric morphometrics.

Facial approximation (FA) provides a promising means of generating the possible facial appearance of a deceased person. It facilitates exploration of the evolutionary forces driving anatomical changes in ancestral humans and can capture public attention. Despite the recent progress made toward improving the performance of FA methods, a limited understanding of detailed quantitative craniofacial relationships between facial bone and soft tissue morphology may hinder their accuracy, and hence subjective experience and artistic interpretation are required. In this study, we explored craniofacial relationships among human populations based upon average facial soft tissue thickness depths (FSTDs) and covariations between hard and soft tissues of the nose and mouth using geometric morphometrics. Furthermore, we proposed a computerized method to assign the learned craniofacial relationships to generate a probable facial appearance of Homo sapiens, reducing human intervention. A smaller resemblance comparison (an average Procrustes distance was 0.0258 and an average Euclidean distance was 1.79 mm) between approximated and actual faces and a greater recognition rate (91.67%) tested by a face pool indicated that average dense FSTDs contributed to raising the accuracy of approximated faces. Results of partial least squares (PLS) analysis showed that nasal and oral hard tissues have an effect on their soft tissues separately. However, relatively weaker RV correlations (<0.4) and greater approximation errors suggested that we need to be cautious about the accuracy of the approximated nose and mouth soft tissue shapes from bony structures. Overall, the proposed method can facilitate investigations of craniofacial relationships and potentially improve the reliability of the approximated faces for use in numerous applications in forensic science, archaeology, and anthropology.

Diet of the earliest modern humans in East Asia.

Reconstructing diet can offer an improved understanding toward the origin and evolution of modern humans. However, the diet of early modern humans in East Asia is poorly understood. Starch analysis of dental calculus is harmless to precious fossil hominins and provides the most direct evidence of plant food sources in early modern human dietary records. In this paper, we examined the starch grains in dental calculus from Fuyan Cave hominins in Daoxian (South China), which were the earliest modern humans in East Asia. Our results reveal the earliest direct evidence of a hominin diet made of acorns, roots, tubers, grass seeds, and other yet-unidentified plants in marine isotope stage 5 between 120 and 80 ka. Our study also provides the earliest evidence that acorns may have played an important role in subsistence strategies. There may have been a long-lasting tradition of using these plants during the Late Pleistocene in China. Plant foods would have been a plentiful source of carbohydrates that greatly increased energy availability to human tissues with high glucose demands. Our study provides the earliest direct consumption of carbohydrates-rich plant resources from modern humans in China for the first time. In addition, it also helps elucidate the evolutionary advantages of early modern humans in the late Middle and early Upper Pleistocene.

Homo bodoensis and why it matters.

In our original paper, we proposed a new species, Homo bodoensis, to replace the problematical taxa Homo heidelbergensis and Homo rhodesiensis, with the goal of streamlining communication about human evolution in the Chibanian. We received two independent responses. Given their substantial overlap, we provide one combined reply. In this response: (1) we are encouraged that the primary proposal in our paper, to discontinue the use of H. heidelbergensis (as a junior synonym to Homo neanderthalensis) due to its' nomenclatural problems, is acknowledged. (2) we provide additional clarification about the rules governing taxonomic nomenclature as outlined by the International Code of Zoological Nomenclature and join the growing calls for a revision to these rules. (3) we discuss further why H. rhodesiensis should be abandoned, particularly in light of the current sensitivity to using culturally inappropriate names. We conclude that H. bodoensis is a better solution than the proposed alternatives.

Hominin evolution and diversity: a comparison of earlier-Middle and later-Middle Pleistocene hominin fossil variation in China.

Historical views of Asia as an evolutionary 'backwater' are associated with the idea that Homo erectus experienced long periods of stasis and ultimately went extinct. However, recent discoveries of well-dated Middle Pleistocene hominin fossils in China have considerably challenged these ideas and provide sufficient data to propose a testable model that explains the patterning of variation in Middle Pleistocene China, and why it changed over time. A series of hominin fossil studies comparing earlier-Middle and later-Middle Pleistocene groups confirm that the expressions of certain traits shift around 300 ka. Fossils from the later Middle Pleistocene are more variable with a mix of archaic traits as well as ones that are common in Western Eurasian early Homo sapiens and Neanderthals. The period around 300 ka appears to have been a critical turning point for later-Middle Pleistocene morphological changes in China. It coincides with a phase of climatic instability in the Northern Hemisphere between Marine Isotope Stages 12 and 10 that would have led to changes in gene flow patterning, and regional population survival/extinction. This localized and testable model can be used for future explorations of hominin evolution in later Pleistocene eastern Eurasia. This article is part of the theme issue 'The impact of Chinese palaeontology on evolutionary research'.

Evolution of cranial capacity revisited: A view from the late Middle Pleistocene cranium from Xujiayao, China.

The Late Middle Pleistocene hominin fossils from the Xujiayao site in northern China have been closely studied in light of their morphological variability. However, all previous studies have focused on separated cranial fragments. Here, we report the first reconstruction of a fairly complete posterior cranium, Xujiayao 6 (XJY 6), confidently dated to ∼200-160 ka, which facilitated an assessment of its overall cranial size. XJY 6 was reconstructed from three of the original fragments-the PA1486 (No.7/XJY 6a) occipital bone, PA1490 (No.10/XJY 6b) right parietal bone, and PA1498 (No.17/XJY 15) left temporal bone-which originated from the same young adult individual. The XJY 6 endocranial capacity, estimated by measuring endocranial volume, was estimated using multiple regression formulae derived from ectocranial and endocranial measurements on select samples of Pleistocene hominins and recent modern humans. The results indicate that the larger pooled sample of both Pleistocene and recent modern humans was more robust for the endocranial capacity estimate. Based on the pooled sample using the ectocranial and endocranial measurements, we conservatively estimate the XJY 6 endocranial volume to be ∼1700 cm3 with a 95% confidence interval of 1555-1781 cm3. This is close to Xuchang 1, which dates to 125-105 ka and whose endocranial volume is ∼1800 cm3. Thus, XJY 6 provides the earliest evidence of a brain size that falls in the upper range of Neanderthals and modern Homo sapiens. XJY 6, together with Xuchang 1, Homo floresiensis, Homo luzonensis, and Homo naledi, challenge the general pattern that brain size gradually increases over geological time. This study also finds that hominin brain size expansion occurred at different rates across time and space.

Resolving the "muddle in the middle": The case for Homo bodoensis sp. nov.

Recent developments in the field of palaeoanthropology necessitate the suppression of two hominin taxa and the introduction of a new species of hominins to help resolve the current nebulous state of Middle Pleistocene (Chibanian) hominin taxonomy. In particular, the poorly defined and variably understood hominin taxa Homo heidelbergensis (both sensu stricto and sensu lato) and Homo rhodesiensis need to be abandoned as they fail to reflect the full range of hominin variability in the Middle Pleistocene. Instead, we propose: (1) introduction of a new taxon, Homo bodoensis sp. nov., as an early Middle Pleistocene ancestor of the Homo sapiens lineage, with a pan-African distribution that extends into the eastern Mediterranean (Southeast Europe and the Levant); (2) that many of the fossils from Western Europe (e.g. Sima de los Huesos) currently assigned to H. heidelbergensis s.s. be reassigned to Homo neanderthalensis to reflect the early appearance of Neanderthal derived traits in the Middle Pleistocene in the region; and (3) that the Middle Pleistocene Asian fossils, particularly from China, likely represent a different lineage altogether.

Newborn screening with targeted sequencing: a multicenter investigation and a pilot clinical study in China.

Different newborn screening (NBS) programs have been practiced in many countries since the 1960s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing (NESTS) program to screen 11,484 babies in 8 Women and Children's hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85% (902/11,484). With 45.89% (414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07% (50/414), estimating an average of 0.95% (7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.

First Report of Bacteremia Caused by Clostridium cadaveris in China.

BACKGROUND: Bacteremia caused by C. cadaveris is an extremely rare infection that accounts for 0.5-2% of all positive blood cultures. C. cadaveris is an opportunistic agent that is highly lethal in immunocompromised or epithelial barrier disruption hosts. CASE PRESENTATION: A 74-year-old woman was admitted to our hospital with a high fever. The patient was diagnosed with an abdominal infection after a bowel invasion and recurrence of an ovarian tumor after surgery. Blood sample culturing yielded transparent, smooth, moist, slightly raised colonies without a hemolytic ring. C. cadaveris was identified by gram staining and MALDI-TOF MS. 16S rRNA gene sequencing confirmed a sequence homologous to C. cadaveris in the GenBank database. Drug susceptibility testing showed that C. cadaveris was sensitive to cefoxitin, clindamycin, imipenem, meropenem, metronidazole, and vancomycin. After treatment, the patient's body temperature was normal and she was discharged from the hospital. CONCLUSION: This is the first case report of bacteremia caused by C. cadaveris in China and also the first report of identifying C. cadaveris in clinical specimens by MALDI-TOF MS. This case study could increase the awareness of these infections in China.

Morphological description and evolutionary significance of 300 ka hominin facial bones from Hualongdong, China.

Late Middle Pleistocene hominins in Africa displaying key modern morphologies by 315 ka are claimed as the earliest Homo sapiens. Evolutionary relationships among East Asian hominins appear complex due to a growing fossil record of late Middle Pleistocene hominins from the region, reflecting mosaic morphologies that contribute to a lack of consensus on when and how the transition to modern humans transpired. Newly discovered 300 ka hominin fossils from Hualongdong, China, provide further evidence to clarify these relationships in the region. In this study, facial morphology of the juvenile partial cranium (HLD 6) is described and qualitatively and quantitatively compared with that of other key Early, Middle, and Late Pleistocene hominins from East Asia, Africa, West Asia, and Europe and with a sample of modern humans. Qualitatively, facial morphology of HLD 6 resembles that of Early and Middle Pleistocene hominins from Zhoukoudian, Nanjing, Dali, and Jinniushan in China, as well as others from Java, Africa, and Europe in some of these features (e.g., supraorbital and malar regions), and Late Pleistocene hominins and modern humans from East Asia, Africa, and Europe in other features (e.g., weak prognathism, flat face and features in nasal and hard plate regions). Comparisons of HLD 6 measurements to group means and multivariate analyses support close affinities of HLD 6 to Late Pleistocene hominins and modern humans. Expression of a mosaic morphological pattern in the HLD 6 facial skeleton further complicates evolutionary interpretations of regional morphological diversity in East Asia. The prevalence of modern features in HLD 6 suggests that the hominin population to which HLD 6 belonged may represent the earliest pre-modern humans in East Asia. Thus, the transition from archaic to modern morphology in East Asian hominins may have occurred at least by 300 ka, which is 80,000 to 100,000 years earlier than previously recognized.

CUX1 Facilitates the Development of Oncogenic Properties Via Activating Wnt/ß-Catenin Signaling Pathway in Glioma.

Background: Homeobox cut like 1 (CUX1), which often presents aberrated expression in many cancer cells, exerts a crucial role in tumorigenesis. Evidence describing CUX1 in gliomagenesis is scarce, and the effects of CUX1 on the Wnt/ß-catenin pathway have not been reported. Our study aimed to explore the biological functions and molecular mechanisms involved in CUX1 activity in glioma. Methods: Datasets for bioinformatics analysis were obtained from the GEO, TCGA, CGGA, GTEX and CCLE databases. qRT-PCR, western blotting (WB), and immunohistochemistry (IHC) assays were used to investigate the expression patterns of CUX1 among glioma and brain tissues. CUX1 knockdown and overexpression vectors were transfected into glioma cell lines, the CCK-8, clone formation assay, wound healing, Transwell assay, and flow cytometry were performed to detect changes in cell viability, invasiveness, and the cell cycle. WB and immunofluorescence (IF) assays were used to explore changes in cell cycle-related and Wnt/ß-catenin signaling protein levels. Results: Overexpression of CUX1 was identified in glioma tissues, and especially in glioblastoma (GBM), when compared to normal controls and correlated with poor prognosis. In comparison with untreated cells, TJ905 glioma cells overexpressing CUX1 showed higher proliferation and invasion abilities and S phase cell-cycle arrest, while the knockdown of CUX1 suppressed cell invasive ability and induced G1 phase arrest. Active Wnt/ß-catenin signaling was enriched and clustered in a CUX1-associated GSEA/GSVA analysis. IF and WB assays indicated that CUX1 regulated the distribution of Axin2/ß-catenin in glioma cells and regulated the expression of proteins downstream of the Wnt/ß-catenin signaling pathway, suggesting that CUX1 served as an upstream positive regulator of the Wnt/ß-catenin pathway. Finally, the knockdown of Axin2 or ß-catenin could reverse the tumor-promoting effects caused by CUX1 overexpression, suggesting that CUX1 induced gliomagenesis and malignant phenotype by activating the Wnt/ß-catenin signaling pathway. Conclusion: Our data suggested that the transcription factor CUX1 could be a novel therapeutic target for glioma with gene therapy.

TROAP regulates cell cycle and promotes tumor progression through Wnt/ß-Catenin signaling pathway in glioma cells.

AIMS: Experimental evidence demonstrated a crucial role of TROAP (Trophinin-associated protein) in regulating the cell proliferation of multiple tumors, while TROAP expression and function were largely unknown in glioma. We aimed to investigate the oncogenic role of TROAP and its potential mechanisms in gliomagenesis. METHODS: Four gene expression databases (GEO, TCGA, GTEx and CCLE) were enrolled in our study and used for TROAP expression and survival analysis. TROAP expression was quantified by qRT-PCR, western blot and immunohistochemistry assays in glioma tissues and cell lines. TROAP knockdown and overexpression vector were constructed and transfected into glioma cells. CCK-8, colony formation, transwell, and wound healing assays were used to evaluate cell viability, migration and invasion, flow cytometry to determine cell cycle arrest. Gene set enrichment analysis (GSEA) was conducted to screen the pathway involved in TROAP-high phenotype. The expression of cell cycle and Wnt/ß-Catenin signaling proteins were analyzed by immunofluorescence and western blot. RESULTS: Based on the bioinformatic analysis and a series of functional assays, we found the TROAP was enriched in glioma tissues and cell lines, its overexpression was correlated with the clinicopathologic characteristics and poor prognosis. TROAP knockdown inhibited cell proliferation, migration, invasion, and G1/S cell cycle arrest compared with control group in glioma. Mechanism analysis revealed that TROAP activated Wnt/ß-Catenin pathway and upregulated its downstream targets expression, while silencing ß-Catenin or Axin2 could reverse the tumor-promoting effects caused by TROAP, confirming that TROAP-induced malignant phenotype and tumorigenesis via Wnt/ß-Catenin signaling pathway. CONCLUSION: The present study found that TROAP accelerated the progression of gliomagenesis through Wnt/ß-Catenin pathway, and TROAP might be considered as a novel target for glioma therapy.

Middle Pleistocene human femoral diaphyses from Hualongdong, Anhui Province, China.

OBJECTIVES: The paleontological description and comparative analysis using discrete morphology, morphometrics (linear and geometric) and cross-sectional geometry of three femoral diaphyseal sections from the Middle Pleistocene site of Hualongdong, China. MATERIALS AND METHODS: The material consists of the original Hualongdong femoral fossils and available data on femoral diaphyses from Middle and Late Pleistocene archaic humans and Middle and earlier Upper Paleolithic modern humans. The methods include visual observation, diaphyseal diameters, cross-sectional parameters (transverse areas and second moments of area derived from micro-CT scans), and geometric morphometrics using semilandmark data. RESULTS: The Hualong 11 midshaft section is similar to other Middle and Late Pleistocene archaic humans in being transversely broad and lacking a pilaster despite a prominent linea aspera. It clusters principally with archaic human femora in all measured parameters. The Hualong 15 and 16 subtrochanteric pieces are similar to many Middle Pleistocene and early modern human femora in being transversely broad. In particular, Hualong 15 exhibits a prominent lateral (gluteal) buttress, similar to many Upper Paleolithic femora but also the Lazaret and Krapina archaic ones. In addition, Hualong 15 has a small third trochanter, a common Upper Paleolithic but rare earlier feature. DISCUSSION: The Hualong 11 femoral piece reinforces the general Middle Pleistocene pattern, especially for eastern Eurasia from which archaic human femora are rare. The subtrochanteric proportions of Hualong 15 and 16 reinforce the Early Pleistocene and (generally) Middle Pleistocene pattern of bone distributions, but their subperiosteal contours align them (along with those of the Lazaret and Krapina femora) with Upper Paleolithic ones. It is difficult to account for these proportions from the generally broad pelves of Pleistocene archaic humans.

Isotopic and hydrochemical evidence for the salinity origin in the coastal aquifers of the Pearl River Delta, Guangzhou, China.

To better understand the origin of the saline groundwater in the Pearl River Delta (PRD), China, water samples were collected from local aquifers, rainfall regions and rivers for isotopic and hydrochemical analysis. The hydraulic connections between the aquifers in the study area were tested by analyzing a series of water samples from different months in one hydrological year (January 2017-January 2018). The total dissolved solids (TDS) results show that the highly saline groundwater only occurs in the granites, which indicates that the TDS distribution depends on the permeability of the aquifer material. Variations in the TDS and stable hydrogen and oxygen isotope ratios (δ2H and δ18O, respectively) of the water samples from different months reflect a dynamic balance among evaporation and precipitation in a hydrological year. Additionally, the very old radiocarbon (14C) ages and undetectable amounts of tritium (3H) in most of the groundwater samples suggest that the residence time of the groundwater in the aquifer is high. In general, the saline groundwater (TDS >5 g/L) in the area mainly originated primarily from seawater intrusion in the past. Meanwhile, the water contents of saline groundwater were affected by evaporation and long-term geochemical processes, such as water-rock, sulfate reduction, methanogenesis and ion exchange. The fresh groundwater in the area is from modern meteoric precipitation recharge.