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Abstract The Caucasus region is key for understanding early human dispersal and evolution in Eurasia, and characterizing the environmental contrast between Last Glacial Maximum and Holocene is crucial for investigating human adaptation strategies to large climatic shifts. However, a paucity of high-resolution paleoclimate records leave this context largely unknown for early human populations in the Caucasus region. Based on our model-proxy comparison of high- and low-resolution records of 24 stalagmites from three caves, we find spatially distinct changes in vegetation and seasonality of precipitation, especially under glacial conditions. Supported by modern oxygen-isotope data and climate modeling, we identify a supraregional cold-season temperature control for oxygen isotopes in Black Sea speleothems, which previously had been interpreted as a local moisture-source signal. Carbon-isotope and trace-element data further suggest disproportionate changes in vegetation cover and soil dynamics at high altitudes, which would have resulted in a reduction but not a disappearance of human refugia during the Last Glacial Maximum, relative to the current interglacial. Our findings imply that abrupt climatic pressures from harsh conditions were overcome by adaptive strategies in the past.

Abstract 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-1β 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. Graphical Abstract

Abstract 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.

Abstract There is a general agreement that Northern Hemisphere temperatures have cooled over the past two millennia, culminating in the Little Ice Age. However, this understanding partly relies on the compilation of existing proxy records, the majority of which carry a warm season bias such that there is an underrepresentation of cold-season temperatures. Here we report a unique cold-season temperature record based on the alkenone paleothermometer from the northeastern Tibetan Plateau that spans the last two millennia. In contrast to the regional- and hemisphere-scale summer cooling, our reconstruction shows a long-term warming through the Medieval Climate Anomaly into Little Ice Age. We attribute these opposing temperature trends to combined effects of seasonally divergent insolation and North Atlantic subpolar gyre circulation. Our study indicates that the cold season during the Little Ice Age was not the coldest period of the last two millennia at least on the northeastern Tibetan Plateau.

The carbon isotopic composition of dissolved organic carbon (δ13CDOC) in speleothems, based on high-precision U-Th ages, has great potential to reconstruct past ecology, microbial activity, and carbon cycling. Identifying the reliability of the pretreatment and measurement of speleothem δ13CDOC is therefore essential to putting it into practice. Actually, we have previously verified the reliability of the method for speleothem δ13CDOC measurements. However, it was only based on the final δ13CDOC values of homogeneous speleothem powder and is unable to evaluate the effects of different experimental conditions and the impacts of adding acid on δ13CDOC if using speleothem as the study samples. In this study, we used an organic reagent (potassium sorbate) as the study sample and designed a conditional experiment that simulates the protocols for speleothem δ13CDOC analysis and presented the resulting data to inspect the effects of the experimental processes on the analysis of δ13CDOC. The results show that the standard deviation of duplicate samples is 0.1‰, which is close to that of the previous work for organic reagents and water samples, and the results were not affected by different experimental conditions and operation steps (such as adding orthophosphoric acid, digestion time, and storage duration of resulting CO2 in storage vessels), suggesting that this method is robust to detect the speleothem δ13CDOC. Considering the range and standard deviation of results, we proposed that the δ13CDOC record could be used in various studies when the amplitudes of the δ13CDOC record are larger than 0.1‰, especially greater than 0.4‰.

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.

Abstract Contrary to global warming projections, northern mid‐latitude continents have suffered from an increased frequency of unusually cold winters during the last few decades. However, a lack of longer‐term cold‐season temperature records from mid‐latitudes hampers our understanding of the forcing mechanisms of this temperature variability. Here we report a Group 1 alkenone‐based high‐resolution record of cold‐season temperatures extending to the pre‐industrial era (since 1700 CE) from Lake Luming in northeastern China. By comparing with the instrumental and historical records in the region, we verify the high efficacy of Group 1 alkenones as recorders of cold‐season temperature variability. Our record shows pre‐industrial warmth between 1750 and 1850 CE relative to anthropogenic industrial period (since 1850 CE), which is largely driven by variability of the Arctic Oscillation, with a negligible contribution from anthropogenic greenhouse‐gas forcing. Our results highlight the importance of internal atmospheric circulation in driving cold‐season temperatures in northeastern China.

New cave records from monsoon regions improve the Greenland ice core chronological framework around the Heinrich Stadial 2 by an order of magnitude, suggesting a more active role of low-latitude hydroclimate in millennial-scale climate oscillations.

ObjectiveThis 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.MethodsThe 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.ResultsC-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.ConclusionA 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.

Precipitation in southeastern China exhibits strong seasonal variability, which significantly impacts local agricultural production and social development. However, the reconstruction of precipitation seasonality has been limited by the lack of precisely dated high-resolution paleoclimatic records. This study presents seasonal-scale multi-proxy records (trace elements: Mg/Ca, Sr/Ca Ba/Ca and stable isotopes: δ18O and δ13C) of a modern (1810–2009 AD) annually laminated stalagmite (EM1) from E’Mei Cave, Jiangxi Province in southeastern China. Comparative analysis of observation data with meteorological and simulation data shows that the seasonal variation of EM1 δ18O, derived from precipitation δ18O, is mainly controlled by the large-scale circulation and precipitation seasonality on an interannual timescale. The seasonal EM1 δ18O variation is controlled by the seasonal precipitation δ18O, however, the most negative values of EM1 δ18O are higher than those of simulated calcite δ18O and the average amplitude of the seasonal variation of EM1 δ18O (∼1.93‰) is much smaller than that of simulated calcite δ18O (∼9.72‰) because of evaporation and mixing of waters in the epikarst system. On the decadal timescales, variations of δ13C, Mg/Ca, Sr/Ca, and Ba/Ca were found to be strongly correlated, consistent with the variation of the local dry/flood index, indicating a common influencing factor of local hydroclimate change. However, their seasonal phase relationships vary between strong and weak summer monsoon conditions. We find a strong covariation between Mg/Ca and δ13C with Sr/Ca and Ba/Ca during the strong monsoon period (1951–1976), and they are in antiphase with seasonal δ18O variation. However, the seasonal variations of Sr/Ca and Ba/Ca transformed to dominantly antiphase with Mg/Ca and δ13C during the weak monsoon period (1977–1991 AD). Therefore, we suggest that Mg/Ca and δ13C are dominantly controlled by the local hydroclimate changes on seasonal timescales but Sr/Ca and Ba/Ca might have been affected by complex processes in the epikarst under different hydrothermal configuration conditions. The findings indicate the potential of the variation of the seasonal phase relationships between multi-proxy records in reconstructing precipitation seasonality changes under different hydrothermal backgrounds.

Abstract The complexity of processes affecting soil organic carbon (SOC) turnover on spatio‐temporal scales often hinders the extrapolation of results from specific sites to larger scales. This study presents Holocene speleothem U‐Th ages paired with 14C ages of carbonate and dissolved organic carbon (DOC) through three caves located on a north‐south transect through China. The deviations of speleothem 14CDOC ages from the U‐Th ages show clearly spatial variability, and they are positively correlated with mean ages of modern SOC and soil turnover time, suggesting that deviations can be used to infer the SOC turnover. We further demonstrate that slow SOC turnover (large deviation) was associated with weak monsoon (low temperature/less precipitation) on temporal scales. Our findings reveal that climate dominates the speleothem 14CDOC ages and SOC turnover. As global warming likely will intensify, the accelerated turnover of SOC, particularly at higher latitude areas, may partially offset the existing soil carbon stock.

Abstract The 8.2 ka event has been extensively studied, whereas its structure is ambiguous in North China. Here we present a high‐resolution (∼1 year) δ18O record from annual laminated speleothem from Beijing to characterize the detailed variability across this event in North China. Our record indicates a dry 8.2 ka event spanning 8.254–8.107 ka BP with a two‐stage structure superimposed by three prominent high δ18O excursions. The identical structure of speleothem δ18O records between North and central China during the event suggests a common forcing/response in East China, whereas the progressively increased offset between their average values may reflect changes in moisture source or rainout effect. A close comparison with the Greenland ice core records suggests a strong linear response of the Asian summer monsoon to the North Atlantic climate changes across the early and middle stages of the event, but a different mechanism in the termination processes.

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.

Severe cooling at high northern latitudes, which marked the onset of Heinrich Stadial 4, was synchronous with changes in tropical monsoon systems and preceded Antarctic warming by around 300 years, according to a compilation of speleothem and ice core records.

Abstract 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.

ObjectiveTo 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.ConclusionProbiotics 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.

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.

The reconstruction of Asian summer monsoon (ASM) changes during the last glacial period is of great significance for better understanding monsoon dynamics. The phase relationship between the Indian summer monsoon (ISM) and East Asian summer monsoon (EASM) subsystems on different timescales is still unclear. The comparative analysis of speleothem records in the ISM region, EASM region, and central China helps to clarify the relationship between the ISM and EASM. Based on the well-dated isotope records of stalagmite DDH-B15 from the Didonghe (DDH) Cave in Hanzhong, Shaanxi, we reconstructed ASM changes during the past 34–13 thousand years before the present (kyr BP). The small average error (61 years) of 18 uranium-series ages enables a precise comparison of the stalagmite δ18O record with other well-dated records from the orbital to the millennial timescales. The δ18O signal of the DDH-B15 stalagmite is controlled by changes of the low latitude northern hemisphere summer insolation (NHSI) on the orbital timescale. It records cold Heinrich Stadial (HS) and Dansgaard–Oeschger (DO) cycles which are originated from the northern high latitude on the millennial time scale. The δ18O changes of stalagmites from the three regions are similar on the millennial and centennial timescales. But on the orbital-suborbital timescale, stalagmite δ18O changes during the last glacial cycle have different characteristics. The stalagmite δ18O values in eastern China became gradually negative, and the stalagmite δ18O values in the Indian monsoon domain showed a increasing trend, but the stalagmite δ18O values in Central China adopted an intermediate state between the EASM and ISM. Then we argued that the δ18O value of stalagmites in Central China is a mixed signal of the ISM and EASM, which indicates a change of the water vapor source as an important influence on the Chinese stalagmite δ18O record.

ObjectiveTo investigate the association of differential metabolites with small intestinal microflora and maternal outcomes in subclinical hypothyroidism (SCH) during pregnancy.MethodsThe plasma of pregnant women in the SCH group and control group was analyzed by liquid chromatography-mass spectrometry (LC-MS), obtaining differential metabolites. Then, methane and hydrogen breath tests were performed in both groups, and basic clinical data and maternal outcome information were collected. Finally, differential metabolites were analyzed for small intestinal bacterial overgrowth (SIBO) and pregnancy outcomes using Spearman correlation analysis.Results(1) Multivariate statistics: There were 564 different metabolites in positive ion mode and 226 different metabolites in negative ion mode. (2) The positive rate of the methane hydrogen breath test in the SCH group was higher than that in the control group (p

ObjectiveTo investigate the lipid profiles and intestinal microflora in pregnant patients with hypothyroidism and their correlation with pregnancy outcomes.MethodsIn total, 27 pregnant women with hypothyroidism (study case) and 28 normal pregnant women (control group) were enrolled in this study. The lipid profiles and intestinal microflora in the two groups were compared using untargeted liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA amplicon sequencing, respectively. The association among the differential metabolites, intestinal microflora, serological indicators and pregnancy outcomes was further analyzed.ResultsPatients in study case had higher C-reactive protein (CRP) levels (P = 0.025) and lower birth weight (P=0.005) than the control group. A total of 42 differential lipid metabolites and 7 enrichment KEGG pathways were obtained between the two groups (VIP ≥ 1, P < 0.05). Ten lipid metabolites can be used as characteristic metabolites of study case, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM). The richness and diversity of intestinal microflora in study case were lower than those in the control group (P>0.05). LEfSe analysis revealed that patients in study case had higher abundance of Prevotella and Haemophilus and lower abundance of Blautia than the control group (P < 0.05). Blautia was positively correlated with SM and negatively correlated with PC and PE; the CRP level and Prevotella were positively correlated; the neonatal weight and PC level were negatively correlated (P < 0.05).ConclusionThe lipid profile and intestinal microflora of pregnant women with hypothyroidism significantly differed from those of normal pregnant women and were associated with adverse pregnancy outcomes. The interaction between lipid metabolism and intestinal microflora may be a potential target for further studies investigating the pathogenesis of hypothyroidism during pregnancy.

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.

Speleothem calcite stable oxygen isotope (δ18OC) is one of the most widely used proxies in paleoclimate research, and understanding its seasonal-annual variability is very significant for palaeoclimate reconstruction. Five-year precipitation and karst cave water from 2016 to 2021 were monitored in Shennong cave, Jiangxi Province, Southeast China. The local meteoric water line (LMWL) is δD = 8.20 × δ18O + 13.34, which is similar to the global meteoric water line. The stable hydrogen and oxygen isotope (δD and δ18O) characteristics of precipitation and cave water were studied. δ18O and δD of precipitation and cave water show obvious seasonal variations. Lower precipitation δ18O and δD generally occur during summer and autumn compared with higher δ18O and δD values during winter and spring. Meanwhile, low precipitation δ18O values do not only appear in June–July when precipitation is the highest of the year but also appear in August–September when precipitation is limited. The back-trajectory analysis of monsoon precipitation moisture sources shows that the moisture uptake regions vary little on inter-annual scales; the water vapor of rainfall in June–July comes from the South China Sea and the Bay of Bengal, while the moisture source in August–September is mainly from the West Pacific and local area. The El Niño-Southern Oscillation is an important factor affecting the value of δ18O by modulating the percentage of summer monsoon precipitation in the annual precipitation and moisture source. The relationship between amount-weighted monthly mean precipitation δ18O and Niño-3.4 index shows that the East Asian summer monsoon (EASM) intensifies during La Niña phases, resulting in more precipitation in monsoon season (May to September, MJJAS) and lower δ18O values, and vice versa during El Niño phases.

ObjectiveTo evaluate the small intestinal bacterial overgrowth (SIBO) of subclinical hypothyroidism of pregnant women, and explore their possible relevance.MethodsIn total, 224 pregnant women with subclinical hypothyroidism during pregnancy (study group) and 196 pregnant women whose thyroid function was normal (control group) were enrolled in this study. Lactulose-based hydrogen and methane breath test was performed to evaluate the growth of intestinal bacteria. The serum-free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), body mass index (BMI) and gastrointestinal symptoms were detected and recorded.ResultsThe positive rates of SIBO were 56.7% and 31.6% in study group and control group, respectively. The levels of C response protein (CRP), abdominal distension and constipation in study group were higher than those in the control group. The risk of abdominal distension and constipation in SIBO-positive pregnant women were higher than that in SIBO-negative pregnant women, and the BMI of SIBO-positive patients in the two groups was lower than that of SIBO-negative patients in each group. In addition, the TPOAb-positive rate and TSH levels were higher but the FT4 level was lower in SIBO-positive patients compared to SIBO-negative patients in study group.ConclusionThe occurrence of subclinical hypothyroidism is related to SIBO, and the excessive growth of small intestinal bacteria may affect gastrointestinal symptoms.Clinical Trialhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR1900026326.

Abstract Mountainous depocentres are often the single available archives in intracontinental areas. As such, the investigation of their sedimentary dynamics is the only way to reconstruct palaeoenvironmental evolution in these peculiar regions. Here, the basin‐scale sedimentary dynamics of the Agadir‐Tissint Feija (i.e. feija is the local name for lowlands) are discussed together with new palaeoenvironmental information on the late Quaternary in the north‐western Sahara margin. The succession consists of up to ca 40 m thick fluvio‐lacustrine deposits subdivided into three depositional sequences (S1–S3) that were deposited between ca 75 ka and ca 10 ka. S1 and S2 reflect the evolution of a palaeolake intercalated by carbonate‐rich palustrine to alluvial plain environments, while S3 shows the transition to an entirely clastic alluvial plain environment. The three sequences are genetically associated with three pulses of tufa buildups at the outlet of the depocentre. Each pulse of tufa buildup is attributed to wet conditions, while each interruption is associated with drier conditions. The wet–dry alternation at the origin of S1 fits with summer insolation fluctuation suggesting that precession parameters may have paced long‐term climate variability in the area. Superimposed on wet–dry cycles, submillennial‐scale (750–900 year) shorter‐term lake fluctuations are identified in S1 and S2; their origins may be related to North Atlantic Oscillation mechanisms. Furthermore, the sudden increase in clastic sediment supply in S3 evidences a change in sediment production in the catchment area attributed to lower temperatures established during the last glacial period. Finally, this newly identified continental archive is unique at the northern Sahara margin; it enables reconstructions of the local and regional hydrological conditions during the last glacial cycle. Even if a more systematic investigation of palaeoclimate forcing is still necessary, the Agadir‐Tissint Feija will potentially bring important information to understand past and anticipate future regional climate change.

Background & Aims Factors that influence the outcomes after deceased-donor liver transplantation (DDLT) for primary biliary cirrhosis (PBC) are not well known. We aimed to clarify these effects on the outcomes after DDLT. Methods We retrospectively analyzed patients with PBC who underwent DDLT from March 2006 to July 2018 at the organ transplantation center of the First Hospital of Jilin University and the First Central Hospital of Tianjin. Changes in liver function were assessed posttransplantation. Recurrence, survival rate, and complications were recorded at follow-up. The effect of liver transplantation on survival and recurrence was evaluated using univariate and/or multivariate Cox regression analyses. Results In total, 69 patients with PBC undergoing DDLT were included in this study. At 4 weeks posttransplant, all liver function tests were normal. During a median follow-up time of 32 months, 5-year overall survival and recurrence rates were estimated as 95.1% and 21.8%, respectively. A recipient aspartate aminotransferase-to-platelet ratio index (APRI) greater than 2 was negatively associated with survival (P = 0.0018). Multivariate regression analysis demonstrated that age younger than 48 years was an independent risk factor for recurrent PBC in recipients undergoing liver transplantation (hazard ratio 0.028, 95% confidence interval 0.01–0.71, P = 0.03). Posttransplant infections (62%) and biliary tract complications (26%) were the most common complications. Conclusion Liver transplantation is an effective treatment for patients with PBC. Liver function normalizes by 4 weeks posttransplant. Although posttransplant survival rate is high, recurrence is possible. To some extent, survival rate and recurrence rate can be predicted by APRI and age, respectively.

Abstract Background Aberrant microRNA expression has been implicated in metastasis of cancers. MiR-661 accelerates proliferation and invasion of breast cancer and ovarian cancer, while impedes that of glioma. Its role in non small cell lung cancer (NSCLC) and underlying mechanism are worthy elucidation. Methods Expression of miR-661 was measured with real-time PCR in both NSCLC tissues and cell lines. The effects of miR-661 on migration, invasion and metastasis capacity of NSCLC were evaluated using wound healing, transwell assay and animal models. Dual reporter luciferase assay and complementary experiments were performed to validate RB1 as a direct target of miR-661 for participation in the progression of NSCLC. Results MiR-661 was upregulated in NSCLC tissues as compared to paired adjacent tissues and associated with shorter overall survival. Furthermore, miR-661 promoted proliferation, migration and metastasis of NSCLC. Then, we identified RB1 as a direct target of miR-661 through which miR-661 affected EMT process and metastasis of NSCLC. RB1 interacted with E2F1 and both could mediate EMT process in NSCLC. Conclusion MiR-661 promotes metastasis of NSCLC through RB/E2F1 signaling and EMT events, thus may serves as a negative prognostic factor and possible target for treatment of NSCLC patient.

The precipitation variations of Longxi area, northeast margin of the Tibetan Plateau since AD 960 are reconstructed from Chinese historical documentary records. These records show that since AD 960, the precipitation of Longxi decreased and reached the lowest level at the end of the 17th and the 18th centuries. After this period, the precipitation gradually increased. The three short wet periods of Longxi in the last millennium were: from the end of the 10th century to the early years of the 11th century, from the end of the 12th century to the early years of the 13th century and during the first half of the 20th century. The precipitation variations coincide well with variations of the Northern Hemisphere temperature and the atmospheric 14C concentration, as well as the averaged 10Be concentration and the reconstructed solar modulation record which show that solar activity may be an important driving force of the precipitation variations of Longxi on multi-decadal to centennial scales during the last millennium. Solar activity controls the motion of the north edge of the Asian summer monsoon by affecting the Asia summer monsoon intensity, the East Asian winter monsoon intensity and the locations of westerlies, thus further dominating precipitation variations of Longxi. Synchronous variations of Longxi precipitation and Northern Hemisphere temperature may also be ascribed to the same control of solar activity.

Understanding the processes and rates of groundwater recharge in arid and semi-arid areas is crucial for utilizing and managing groundwater resources sustainably. We obtained three chloride profiles of the unsaturated-zone in the desert/loess transition zone of northwestern China and reconstructed the groundwater recharge variations over the last 11, 21, and 37 years, respectively, using the generalized chloride mass balance (GCMB) method. The average recharge rates were 43.7, 43.5, and 45.1 mm yr-1, respectively, which are similar to those evaluated by the chloride mass balance (CMB) or GCMB methods in other semi-arid regions. The results indicate that the annual recharge rates were not in complete linear proportion to the corresponding annual precipitations, although both exhibited descending tendencies on the whole. Comparisons between the daily precipitation aggregate at different intensity and recharge rates reveal that the occurrence of relatively heavy daily precipitation per year may contribute to such nonlinearity between annual precipitation and recharge. The possible influences of vegetation cover alterations following precipitation change cannot be excluded as well. The approximately negative correlation between the average annual recharge and temperature suggests that changes in temperature have had significant influences on recharge.