The demise of the giant ape Gigantopithecus blacki.

The largest ever primate and one of the largest of the southeast Asian megafauna, Gigantopithecus blacki1, persisted in China from about 2.0 million years until the late middle Pleistocene when it became extinct2-4. Its demise is enigmatic considering that it was one of the few Asian great apes to go extinct in the last 2.6 million years, whereas others, including orangutan, survived until the present5. The cause of the disappearance of G. blacki remains unresolved but could shed light on primate resilience and the fate of megafauna in this region6. Here we applied three multidisciplinary analyses-timing, past environments and behaviour-to 22 caves in southern China. We used 157 radiometric ages from six dating techniques to establish a timeline for the demise of G. blacki. We show that from 2.3 million years ago the environment was a mosaic of forests and grasses, providing ideal conditions for thriving G. blacki populations. However, just before and during the extinction window between 295,000 and 215,000 years ago there was enhanced environmental variability from increased seasonality, which caused changes in plant communities and an increase in open forest environments. Although its close relative Pongo weidenreichi managed to adapt its dietary preferences and behaviour to this variability, G. blacki showed signs of chronic stress and dwindling populations. Ultimately its struggle to adapt led to the extinction of the greatest primate to ever inhabit the Earth.

Probiotics and Prebiotics in Subclinical Hypothyroidism of Pregnancy with Small Intestinal Bacterial Overgrowth.

Evaluating efficacy of probiotics combined with prebiotics in small intestinal bacterial overgrowth (SIBO) in subclinical hypothyroidism (SCH) in the second trimester. We collected data from 78 pregnant women with SCH (SCH group) and 74 normal pregnant women (control group) in second trimester, compare the differences in high sensitivity C-reactive protein (hsCRP), result of lactulose methane-hydrogen breath test and gastrointestinal symptoms assessed by GSRS scale between two groups. In SCH group, 32 patients with SIBO were selected as intervention group. Treatment with probiotics + prebiotics for 21 days; The differences of lipid metabolism, hsCRP, thyroid function level, methane-hydrogen breath test results and GSRS scores before and after treatment were compared to evaluate the therapeutic effect. (1) The positive rate of SIBO and methane, hsCRP levels in SCH group were higher than those in control group (P < 0.05), the total score of GSRS scale, mean score of indigestion syndrome, and constipation syndrome in SCH group were higher (P < 0.05). (2) The mean abundance of hydrogen and methane were higher in SCH group. (3) After treatment, serum levels of thyrotropin(TSH), total cholesterol(TC), triglyceride(TG), low-density lipoprotein (LDL), and hsCRP in intervention group were decreased, and high-density lipoprotein (HDL) was increased compared with before treatment (P < 0.05). (4) After treatment, methane positive rate, total score of GSRS scale, mean score of diarrhea syndrome, dyspepsia syndrome, and constipation syndrome were decreased (P < 0.05). (5) The average abundance of methane and hydrogen were lower. Probiotics combined with prebiotics are effective in the treatment of SIBO in pregnant SCH patients.Clinical Trial Registration Number: ChiCTR1900026326.

Exosomal miR-146a-5p derived from human umbilical cord mesenchymal stem cells can alleviate antiphospholipid antibody-induced trophoblast injury and placental dysfunction by regulating the TRAF6/NF-κB axis.

Exosomes originating from human umbilical cord mesenchymal stem cells (hucMSC-exos) have become a novel strategy for treating various diseases owing to their ability to regulate intercellular signal communication. However, the potential of hucMSC-exos to improve placental injury in obstetric antiphospholipid syndrome and its underlying mechanism remain unclear. Our objective was to explore the potential application of hucMSC-exos in the treatment of obstetric antiphospholipid syndrome and elucidate its underlying mechanism. In our study, hucMSC-exos ameliorated the functional impairment of trophoblasts caused by antiphospholipid antibodies in vitro and attenuated placental dysfunction in mice with obstetric antiphospholipid syndrome by delivering miR-146a-5p. Exosomal miR-146a-5p suppressed the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibited the activation of NF-κB signaling, leading to the down-regulation of IL-1ß and IL-18 to rescue inflammation and modulation of Cleaved-CASP3, BAX, and BCL2 to inhibit apoptosis in HTR8/SVneo cells and mice placenta. This study identified the potential molecular basis of how hucMSC-exos improved antiphospholipid antibody-induced placental injury and highlighted the functional importance of the miR-146a-5p/TRAF6 axis in the progression of obstetric antiphospholipid syndrome. More importantly, this study provided a fresh outlook on the promising use of hucMSC-exos as a novel and effective treatment approach in obstetric antiphospholipid syndrome.

High-performance heterostructure Na0.7MnO2.05-Na0.91MnO2 as a lithium-free cathode for lithium-ion batteries.

In this investigation, a lithium-free cathode material, Na0.7MnO2.05-Na0.91MnO2, was synthesized by the solid phase method. The intercalation mechanism and partial phase transformation mechanism of NMO600 were clarified by in situ X-ray diffraction and impedance. The design of the heterostructure is favourable for improving the lithium ion storage of NMO600, which can deliver a discharge capacity of 83.12 mA h g-1 at 1 A g-1 and keep 61.71 mA h g-1 after 700 cycles.

Holocene climate change in southern Oman deciphered by speleothem records and climate model simulations.

Qunf Cave oxygen isotope (δ18Oc) record from southern Oman is one of the most significant of few Holocene Indian summer monsoon cave records. However, the interpretation of the Qunf δ18Oc remains in dispute. Here we provide a multi-proxy record from Qunf Cave and climate model simulations to reconstruct the Holocene local and regional hydroclimate changes. The results indicate that besides the Indian summer monsoon, the North African summer monsoon also contributes water vapor to southern Oman during the early to middle Holocene. In principle, Qunf δ18Oc values reflect integrated oxygen-isotope fractionations over a broad moisture transport swath from moisture sources to the cave site, rather than local precipitation amount alone, and thus the Qunf δ18Oc record characterizes primary changes in the Afro-Asian monsoon regime across the Holocene. In contrast, local climate proxies appear to suggest an overall slightly increased or unchanged wetness over the Holocene at the cave site.

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.

Supermolecular nanovehicles co-delivering TLR7/8-agonist and anti-CD47 siRNA for enhanced tumor immunotherapy.

Cancer immunotherapy is the most promising method for tumor therapy in recent years, among which the macrophages play a critical role in the antitumor immune response. However, tumor-associated macrophages (TAMs) usually display the tumor-promoting M2 phenotype rather than the tumor-killing M1 phenotype. Moreover, the over-expressed CD47 on tumor cells severely hinders the function of macrophages by blocking the CD47/SIRPα pathway. Herein, a nano-assembly system of CHTR/siRNA was constructed through the host-guest interaction of a hyperbranched amino-functionalized ß-cyclodextrin and immune agonist imiquimod (R848), while CD47 siRNA was loaded inside through electrostatic interaction. The Toll-like receptor (TLR) 7/8 agonist R848 can "re-educate" macrophages from the protumoral M2 phenotype to antitumoral M1 phenotype, while CD47 siRNA can down-regulate the "don't eat me" CD47 signal on the surface of cancer cells and enhance the phagocytosis of cancer cells by macrophages. Through the dual regulation of TAMs, the immunosuppressive tumor microenvironment was relieved, and the host-guest drug-carrying system resulted in synergistic immunotherapy effect on tumors and inhibited tumor growth. The facile self-assembly of nanodrug offers a new strategy in co-delivery of multiple therapeutic agents for cascade cancer immunotherapy.

Correlation between the intestinal microflora and peripheral blood Th1/Th2 balance in hypothyroidism during the first half of pregnancy.

Objective: This study aimed to investigate the relationship between intestinal microflora characteristics and the peripheral blood T helper cell (Th)1/Th2 balance in patients with hypothyroidism during the first half of pregnancy. Methods: The Th1/Th2 ratios in the peripheral blood of pregnant women in the hypothyroidism and control groups were determined using flow cytometry. The cytometric bead array assay was used to determine the serum levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Moreover, 16S rRNA amplicon sequencing was used to determine the intestinal microbial composition in the two groups. Finally, the relationships between intestinal microflora, Th1/Th2 cells, cytokines, and clinical indicators were analyzed. Results: C-reactive protein levels were higher in the hypothyroidism group than in the control group. In contrast to the control group, the hypothyroidism group showed an increase in Th1 cells and the Th1/Th2 ratio, and a decrease in Th2 cells. The hypothyroidism group had higher serum IL-2, TNF-α, and IFN-γ levels, and lower IL-10 levels, than the control group. The richness of the intestinal microflora in the hypothyroidism group increased whereas the diversity decreased. The linear discriminant analysis effect size revealed that the hypothyroidism group had a higher abundance of Prevotella and Faecalibacterium, but a lower abundance of Bacteroides, compared to the control group. Prevotella was positively correlated with Th1 cells, the Th1/2 ratio, and TNF-α. Bacteroides was positively correlated with Th2 cells and IL-10, but negatively correlated with Th1 cells, the Th1/2 ratio, TNF-α, and IFN-γ. The thyroid peroxidase antibody level was directly proportional to TNF-α. Conclusion: A Th1/Th2 imbalance occurs in patients with hypothyroidism during the first half of pregnancy. Disorders of the intestinal microflora may lead to hypothyroidism during pregnancy by affecting the Th1/Th2 balance.

Preparation and Electrochemical Performance of Na2-xLixFePO4F/C Composite Cathode Materials with Different Lithium/Sodium Ratios.

With their advantages of abundant raw material reserves, safety, and low toxicity and cost, sodium-ion batteries (SIBs) have gained increasing attention in recent years. Thanks to a high theoretical specific capacity (124 mAh g-1), a high operating voltage (about 3.2 V), and a very stable three-dimensional layered structure, sodium ferric fluorophosphate (Na2FePO4F, NFPF) has emerged as a strong candidate to be used as a cathode material for SIBs. However, applications are currently limited due to the low electronic conductivity and slow ion diffusion rate of NFPF, which result in a low actual specific capacity and a high rate performance. In this study, the authors used a high-temperature solid-phase technique to produce Na2-xLixFePO4F/C (0 ≤ x ≤ 2) and evaluated the impact on electrode performance of materials with different Na+ and Li+ contents (values of x). Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were also used to analyze the material's crystal structure and nanostructure. The results show that the material had the best room-temperature performance when x = 0.5. At a charge-discharge rate of 0.1 C, the first discharge-specific capacity of the resulting Na1.5Li0.5FePO4F/C cathode material was 122.9 mAh g-1 (the theoretical capacity was 124 mAh g-1), and after 100 cycles, it remained at 118 mAh g-1, representing a capacity retention rate of 96.2% and a Coulomb efficiency of 98%. The findings of this study demonstrate that combining lithium and sodium ions improves the electrochemical performance of electrode materials.

Milankovitch theory and monsoon.

The widely accepted "Milankovitch theory" explains insolation-induced waxing and waning of the ice sheets and their effect on the global climate on orbital timescales. In the past half century, however, the theory has often come under scrutiny, especially regarding its "100-ka problem." Another drawback, but the one that has received less attention, is the "monsoon problem," which pertains to the exclusion of monsoon dynamics in classic Milankovitch theory even though the monsoon prevails over the vast low-latitude (∼30° N to ∼30° S) region that covers half of the Earth's surface and receives the bulk of solar radiation. In this review, we discuss the major issues with the current form of Milankovitch theory and the progress made at the research forefront. We suggest shifting the emphasis from the ultimate outcomes of the ice volume to the causal relationship between changes in northern high-latitude insolation and ice age termination events (or ice sheet melting rate) to help reconcile the classic "100-ka problem." We discuss the discrepancies associated with the characterization of monsoon dynamics, particularly the so-called "sea-land precession-phase paradox" and the "Chinese 100-ka problem." We suggest that many of these discrepancies are superficial and can be resolved by applying a holistic "monsoon system science" approach. Finally, we propose blending the conventional Kutzbach orbital monsoon hypothesis, which calls for summer insolation forcing of monsoons, with Milankovitch theory to formulate a combined "Milankovitch-Kutzbach hypothesis" that can potentially explain the dual nature of orbital hydrodynamics of the ice sheet and monsoon systems, as well as their interplays and respective relationships with the northern high-latitude insolation and inter-tropical insolation differential.

Coupled atmosphere-ice-ocean dynamics during Heinrich Stadial 2.

Our understanding of climate dynamics during millennial-scale events is incomplete, partially due to the lack of their precise phase analyses under various boundary conditions. Here we present nine speleothem oxygen-isotope records from mid-to-low-latitude monsoon regimes with sub-centennial age precision and multi-annual resolution, spanning the Heinrich Stadial 2 (HS2) - a millennial-scale event that occurred at the Last Glacial Maximum. Our data suggests that the Greenland and Antarctic ice-core chronologies require +320- and +400-year adjustments, respectively, supported by extant volcanic evidence and radiocarbon ages. Our chronological framework shows a synchronous HS2 onset globally. Our records precisely characterize a centennial-scale abrupt "tropical atmospheric seesaw" superimposed on the conventional "bipolar seesaw" at the beginning of HS2, implying a unique response/feedback from low-latitude hydroclimate. Together with our observation of an early South American monsoon shift at the HS2 termination, we suggest a more active role of low-latitude hydroclimate dynamics underlying millennial events than previously thought.

Paleolithic occupation of arid Central Asia in the Middle Pleistocene.

Central Asia is positioned at a crossroads linking several zones important to hominin dispersal during the Middle Pleistocene. However, the scarcity of stratified and dated archaeological material and paleoclimate records makes it difficult to understand dispersal and occupation dynamics during this time period, especially in arid zones. Here we compile and analyze paleoclimatic and archaeological data from Pleistocene Central Asia, including examination of a new layer-counted speleothem-based multiproxy record of hydrological changes in southern Uzbekistan at the end of MIS 11. Our findings indicate that Lower Palaeolithic sites in the steppe, semi-arid, and desert zones of Central Asia may have served as key areas for the dispersal of hominins into Eurasia during the Middle Pleistocene. In agreement with previous studies, we find that bifaces occur across these zones at higher latitudes and in lower altitudes relative to the other Paleolithic assemblages. We argue that arid Central Asia would have been intermittently habitable during the Middle Pleistocene when long warm interglacial phases coincided with periods when the Caspian Sea was experiencing consistently high water levels, resulting in greater moisture availability and more temperate conditions in otherwise arid regions. During periodic intervals in the Middle Pleistocene, the local environment of arid Central Asia was likely a favorable habitat for paleolithic hominins and was frequented by Lower Paleolithic toolmakers producing bifaces.

Efficacy evaluation of probiotics combined with prebiotics in patients with clinical hypothyroidism complicated with small intestinal bacterial overgrowth during the second trimester of pregnancy.

Objective: To explore the effect of probiotics combined with prebiotics on clinical hypothyroidism during pregnancy combined with small intestinal bacterial overgrowth. Methods: (1) In total, 441 pregnant women were included in this study. A total of 231 patients with clinical hypothyroidism during the second trimester of pregnancy and 210 normal pregnant women were enrolled in the lactulose methane-hydrogen breath test. The positive rate of intestinal bacterial overgrowth (SIBO), gastrointestinal symptoms, thyroid function and inflammatory factors were compared between the two groups by chi-square test and two independent sample t-test. (2) SIBO-positive patients in the clinical hypothyroidism group during pregnancy (n=112) were treated with probiotics combined with prebiotics based on conventional levothyroxine sodium tablets treatment. The changes in the methane-hydrogen breath test, gastrointestinal symptoms, thyroid function and inflammatory factors were compared before treatment (G0) and 21 days after treatment (G21) by chi-square test and paired sample t test. Results: (1) The positive rates of SIBO in pregnant women in the clinical hypothyroidism group and control group were 48.5% and 24.8%, respectively. (2) The incidence of abdominal distention and constipation in the clinical hypothyroidism group was significantly higher than that in the control group, and the risk of abdominal distention and constipation in SIBO-positive pregnant women was higher than that in SIBO-negative pregnant women. (3) The serum levels of hypersensitive C-reactive protein (hsCRP), IL-10, IL-6, TNF-α, low-density lipoprotein (LDL), total cholesterol (TC), free fatty acids (FFAs) and apolipoprotein B (ApoB) in the hypothyroidism group during pregnancy were higher than those in the control group. (4) After 21 days of probiotics combined with prebiotics, the incidence of pure methane positivity in the methane-hydrogen breath test in the G21 group was significantly reduced, and the average abundance of hydrogen and methane at each time point in the G21 group was lower than that in the G0 group. (5) The incidence of constipation in the G21 group was significantly lower than before treatment. (6) The levels of serum TSH, hsCRP, IL-6, TNF-α, TC and LDL in pregnant women after probiotics combined with prebiotics were lower than those before treatment. Conclusion: Probiotics combined with prebiotics are effective in the treatment of pregnant patients with clinical hypothyroidism complicated with SIBO, providing a new idea to treat pregnant patients with clinical hypothyroidism complicated with SIBO.

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.

Nitrogen self-doped carbon with super high-rate and long cycle life as anode materials for lithium-ion batteries.

Nitrogen self-doped carbon was synthesized by hydrothermal and microwave calcination using polyacrylonitrile as a carbon source and nitrogen source. This method dramatically reduces the material preparation time while improving the electrochemical performance of amorphous carbon. X-ray photoelectron spectroscopy (XPS) analyses reveal that the pyridine nitrogen content is increased and the graphitized nitrogen disappeared in an amorphous carbon block. This indicates that the nitrogen doping sites of the amorphous carbon block can be modulated by the hydrothermal method. Microscopic observations show that the nitrogen self-doped carbon is nano-carbon spheres and carbon micron block. The self-doped nitrogen micron carbon block exhibits excellent cyclability and ultra-high rate capacity. When cycled at 0.5 A g-1, the discharge capacity remains 356.6 mA h g-1 after 1000 cycles. Even cycled at 5 A g-1, the rate capacity was maintained at 183.3 mA h g-1 after 300 cycles. The defects produced by self-doped pyridine nitrogen, not only improved the reactivity and electronic conductivity but also enhanced lithium-ion diffusion kinetics.

Speleological and environmental history of Lida Ajer cave, western Sumatra.

Some of the earliest evidence for the presence of modern humans in rainforests has come from the fossil deposits of Lida Ajer in Sumatra. Two human teeth from this cave were estimated to be 73-63 thousand years old, which is significantly older than some estimates of modern human migration out of Africa based on genetic data. The deposits were interpreted as being associated with a rainforest environment based largely on the presence of abundant orangutan fossils. As well as the main fossil-bearing chamber, fossil-bearing passages are present below a sinkhole, although the relationship between the different fossil deposits has only been tenuously established. Here, we provide significant new sedimentological, geochronological and palaeoecological data aimed at reconstructing the speleological and environmental history of the cave and the clastic and fossil deposits therein. Our data suggest that the Lida Ajer fossils were deposited during Marine Isotope Stage 4, with fossils from the lower passages older than the main fossil chamber. Our use of stable carbon and oxygen isotope analyses of mammalian tooth enamel demonstrates that early humans probably occupied a closed-canopy forest very similar to those present in the region today, although the fossil orangutans may have occupied a slightly different niche. This article is part of the theme issue 'Tropical forests in the deep human past'.

T follicular helper cells improve the response of patients with chronic hepatitis B to interferon by promoting HBsAb production.

BACKGROUND AND AIMS: Hepatitis B surface antigen (HBsAg) seroconversion is considered the optimal outcome of the treatment of chronic hepatitis B virus (HBV) infection. In this study, we aimed to determine the cellular and molecular mechanisms by which pegylated interferon alpha (PEG-IFN-α) improves the seroconversion rate in patients with chronic hepatitis B (CHB). METHODS: Flow cytometry was performed using circulating T follicular helper (TFH) cells from 15 healthy individuals and 45 patients with CHB presenting different treatment responses [complete response group (CRG), incomplete response group (ICRG), and nonresponse group (NRG)] to the standard 48-week regimen of PEG-IFN-α monotherapy to examine the significance of circulating TFH cells in the therapeutic response of patients with CHB to PEG-IFN-α. In addition, the capacities of different TFH subsets to activate B cells and stimulate IgG production were assessed by performing coculture experiments. RESULTS: Longitudinal analysis revealed specific and significant increases in the numbers of CD40L+CD4+CXCR5+ TFH cells in the CRG compared with the NRG and ICRG. According to the results of in vitro coculture experiments, blocking CD40-CD40L signaling, but not ICOS-ICOSL signaling, specifically inhibits B-cell activation and IgG production. HBV may impair TFH cell function by enhancing inhibitory regulatory T-cell activity. Transcriptome analysis further revealed the upregulation of CD40L, but not of ICOS, in TFH cells isolated from the CRG. CONCLUSIONS: TFH cells, particularly those with CD40L expression, stimulate B-cell differentiation and improve the HBsAg seroconversion rate in patients with CHB treated with PEG-IFN-α monotherapy.

Collapse of the Liangzhu and other Neolithic cultures in the lower Yangtze region in response to climate change.

The Liangzhu culture in the Yangtze River Delta (YRD) was among the world's most advanced Neolithic cultures. Archeological evidence suggests that the Liangzhu ancient city was abandoned, and the culture collapsed at ~4300 years ago. Here, we present speleothem records from southeastern China in conjunction with other paleoclimatic and archeological data to show that the Liangzhu culture collapsed within a short and anomalously wet period between 4345 ± 32 and 4324 ± 30 years ago, supporting the hypothesis that the city was abandoned after large-scale flooding and inundation. We further show that the demise of Neolithic cultures in the YRD occurred within an extended period of aridity that started at ~4000 ± 45 years ago. We suggest that the major hydroclimatic changes between 4300 and 3000 years ago may have resulted from an increasing frequency of the El Niño­Southern Oscillation in the context of weakened Northern Hemisphere summer insolation.

Differential lipids in pregnant women with subclinical hypothyroidism and their correlation to the pregnancy outcomes.

Subclinical hypothyroidism (SCH) has become a prevalent complication in pregnancy. Recent research links SCH to disturbed thyroid lipid profile; however, it is unclear how lipid metabolism disorders contribute to the pathogenesis of SCH during pregnancy. Thus, we used nontargeted lipidomics to identify and compare the lipids and metabolites expressed by pregnant women with SCH and healthy pregnant women. Multivariate analysis revealed 143 lipid molecules differentially expressed between the SCH group and the control group. Based on fold change, 30 differentially expressed lipid metabolites are potential biomarkers. KEGG pathway enrichment analysis showed that the differentially expressed metabolites participate in several pathways, including response to pathogenic Escherichia coli infection, regulation of lipolysis in adipocytes, metabolic pathways, glycerophospholipid metabolism, and fat digestion and absorption pathways. Correlation analyses revealed sphingomyelin (SM) and phosphatidylcholine (PC) positively correlate to tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6), while phosphatidylglycerol (PG), and phosphatidylinositol (PI) negatively correlate with them. In addition, PG positively correlates to birth weight. Thus, the lipid profile of pregnant women with SCH is significantly different from that of healthy pregnant women. Lipid molecules associated with the differential lipid metabolism, such as SM, phosphatidylethanolamine (PE), and PI, should be further investigated for their roles in the pathogenesis of SCH in pregnancy, as they might be targets for reducing the incidence of adverse pregnancy outcomes.

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.