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Significant heterogeneity has been observed among different ecosystem services (ES). Understanding the trade-offs and synergies among ES and delineating ecological functional zones is crucial for formulating regional management policies that improve human well-being and sustainably develop and maintain ecosystems. In this study, we used the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) and Carnegie–Ames–Stanford Approach (CASA) models to evaluate the spatial distribution patterns of nine ES (food supply, raw material supply, water resource supply, water connotation, climate regulation, soil conservation, water purification, habitat quality, and entertainment tourism) in the Qilian Mountains from 2000 to 2018. We also investigated the trade-offs and synergistic relationships among ES through Spearman correlation analysis, identified ES hotspots through exploratory spatial data analysis, and identified ES bundles (ESB) using K-means clustering. Our results revealed that water purification and habitat quality remained relatively stable, while food supply, raw material supply, water resource supply, water conservation, climate regulation, soil conservation, and entertainment tourism increased by 1038.83 Yuan·ha−1, 448.21 Yuan·ha−1, 55.45 mm, 7.80 mm, 0.60 tc·ha−1, 40.01 t·ha−1 and 4.82, respectively. High-value areas for water resource supply were mainly concentrated in the high-altitude mountainous area, whereas high-value areas for soil conservation were found in the western and eastern parts of the study area. The low-value areas of water purification were primarily located in the east, while the remaining six services were highly distributed in the east and were less common in the west. Correlation analysis showed that water resource supply, water conservation, and soil conservation exhibited a synergistic relationship in the Qilian Mountains. Moreover, food supply, raw material supply, climate regulation, habitat quality, and entertainment tourism showed synergistic relationships. However, there were trade-offs between food supply and water purification as well as water resource supply, and habitat quality showed a tradeoff with water resource supply, water conservation, and soil conservation. We identified four ESB. The food supply bundle consisted mainly of farmland ecosystems, while the windbreak and sand fixation and ecological coordination bundles were dominant in the Qilian Mountains. Notably, the area of the water conservation bundle increased significantly. Our comprehensive findings on ES and ESB can provide a theoretical foundation for the formulation of ecological management policies and the sustainable development of ecosystems in the Qilian Mountains.

Dopa-responsive dystonia (DRD), also known as Segawa syndrome, is a rare neurotransmitter disease. The decrease in dopamine caused by tyrosine hydroxylase (TH) gene mutation may lead to dystonia, tremor and severe encephalopathy in children. Although the disease caused by recessive genetic mutation of the tyrosine hydroxylase (TH) gene is rare, we found that the clinical manifestations of seven children with tyrosine hydroxylase gene mutations are similar to dopa-responsive dystonia. To explore the clinical manifestations and possible pathogenesis of the disease, we analyzed the clinical data of seven patients. Next-generation sequencing showed that the TH gene mutation in three children was a reported homozygous mutation (c.698G>A). At the same time, two new mutations of the TH gene were found in other children: c.316_317insCGT, and c.832G>A (p.Ala278Thr). We collected venous blood from four patients with Segawa syndrome and their parents for real-time quantitative polymerase chain reaction analysis of TH gene expression. We predicted the structure and function of proteins on the missense mutation iterative thread assembly refinement (I-TASSER) server and studied the conservation of protein mutation sites. Combined with molecular biology experiments and related literature analysis, the qPCR results of two patients showed that the expression of the TH gene was lower than that in 10 normal controls, and the expression of the TH gene of one mother was lower than the average expression level. We speculated that mutation in the TH gene may clinically manifest by affecting the production of dopamine and catecholamine downstream, which enriches the gene pool of Segawa syndrome. At the same time, the application of levodopa is helpful to the study, diagnosis and treatment of Segawa syndrome.

The reconstruction of regional moisture and climate changes during the Holocene has been intensively carried out over the NE Tibetan Plateau, based on different geological archives. However, owing to either the lack of robust independent chronology or ambiguous interpreting of climate proxies as well as complex geographic settings within the plateau, the nature of Holocene environmental changes and their influence factors remain controversial, particularly on whether the optimal climate condition (effective moisture peak) has prevailed during the early- or mid-Holocene. In this study, we reported a new well-dated sand dune accumulation record from the Shawotou sand field in the Babao River drainage area in the southeast Qilian Mountains, to unravel the late glacial and Holocene moisture variation history. The robust chronologies of aeolian sands and palaeosols from two sections were established based on densely collected 49 samples using post-infrared (IR) IR-stimulated luminescence dating of coarse-grained K-feldspar. Based on stratigraphic investigation of the sand dune/palaeosol sections, the results show that the climatic condition was very dry during the late glacial and early Holocene (14–8 ka), characterized by sand dune formation, and then the moisture peaked in the middle Holocene (8–4 ka) with the strongest pedogenesis, followed by a relatively dry condition in the late Holocene (since 4 ka). The regional comparison suggested that the Holocene moisture variation pattern seems synchronous over the NE Tibetan Plateau, that is, the dry early Holocene and late Holocene but with peaked moisture in the middle Holocene, which is likely attributed to the precipitation changes of the East Asian summer monsoon.

Dopa-responsive dystonia (DRD), also known as Segawa syndrome, is a rare neurotransmitter disease. The decrease in dopamine caused by tyrosine hydroxylase (

Background: Autonomic nerve system (ANS) plays an important role in regulating cardiovascular function and cerebrovascular function. Traditional heart rate variation (HRV) and emerging skin sympathetic nerve activity (SKNA) analyses from ultra-short-time (UST) data cannot fully reveal neural activity, thereby quantitatively reflect ANS intensity.Methods: Electrocardiogram and SKNA from sixteen patients (seven cerebral hemorrhage (CH) patients and nine control group (CO) patients) were recorded using a portable device. Ten derived HRV (mean, standard deviation and root mean square difference of sinus RR intervals (NNmean, SDNN and RMSSD), ultra-low frequency (Results: The validation results of HRV and VG features in discriminating CH from CO showed that VG features were more clearly distinguishable between the two groups than HRV features. For effectiveness evaluation of analyzing ANS on UST segment, the NNmean, SDNN, RMSSD, LF, HF and LF/HF in HRV features and the CC, Trans, Dia and GE of VG features remained stable in both activated and inactivated segments across all data lengths. The capability of HRV and VG features in quantifying ANS-Load were evaluated and compared under different ANS-Load, the results showed that most HRV features (SDNN, LFHF, RMSSD, vLF, LF and HF) and almost all VG features were correlated to sympathetic nerve activity intensity.Conclusions: The proposed autonomic nervous activity analysis method based on VG and SKNA offers a new insight into ANS assessment in UST segments and ANS-Load quantification.

The iPSC line was generated from the peripheral blood mononuclear cells (PBMCs) from a 53-year-old female patient carrying the LMNA gene mutation (c.1304_1307dup) diagnosed with atrial fibrillation and paroxysmal ventricular tachycardia. Through comprehensive detection, it was verified that the cell line had the LMNA gene mutation, normal karyotype, and the potential to differentiate into the three germ layers. This cell line may reveal potential therapeutic targets for atrial and ventricular arrhythmias caused by LMNA mutations.

Lake shoreline beach ridges and their sediments have often been investigated as paleoenvironmental indicators in arid northern China. Robust chronology is crucial to utilize this archive for paleoenvironmental reconstruction and interpretation. In this study, we reported a robust chronology for the highest wave-built beach ridge around Jinchang paleolake at the northeast (NE) margin of the Tibetan Plateau, using a combined quartz and K-feldspar luminescence dating technique, together with radiocarbon dating. The consistent quartz and K-feldspar ages suggested the sufficient reset of luminescence signals before deposition for the investigated sediments. Both kinds of luminescence ages were in agreement with three independent 14C ages, further corroborating the robustness of these obtained luminescence ages. Our results demonstrated that the investigated beach ridge was formed around 8.5–6.9 ka, suggesting a distinct period of lake highstand which has been identified in other lakes nearby. This highstand event may implicate an increased regional moisture condition, which is likely caused by the increased Asian summer monsoon precipitation.

Epilepsy of infancy with migrating focal seizures (EIMFS) is a kind of epileptic encephalopathy with high genetic heterogeneity. The most common pathogenic gene for EIMFS is potassium sodium-activated channel subfamily T member 1 (KCNT1). Using Sendai virus-mediated reprogramming, we established an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a five-month-old Chinese girl with heterozygous missense mutation (c.2800 GA) in the KCNT1 gene. The iPSCs were stable during amplification, expressed pluripotent genes, maintained a normal karyotype, and showed characteristics of the three germs layers in an in vitro differentiation assay.

Ancient cities are excellent spatiotemporal indicators for the study of historical human activities and environmental change. The ancient city of Sanchahe is located at the southern margin of the Mu Us Desert, China. It is an ideal location for studying the complex relationships between historical desertification and human activities. Field observations of the ancient city walls, a well, and a spring, as well as 14C dating, grain size, spatial analysis of archaeological sites, and analyses of historical seismicity, indicated that neotectonics may have contributed to crustal uplift and accelerated fluvial incision of the Wuding River. This rapid incision caused a decline in groundwater levels, which is an important reason for the irreversible environmental degradation around Sanchahe city over the past 800 yr. This study provides new evidence for such environmental degradation and may contribute to a better understanding of historical desertification in the Mu Us Desert.

NE Asia has experienced Significant extensional events in the Early Cretaceous, including related volcanic rocks, extensional basins, metamorphic core complexes (MCCs), and low-angle detachment fau...

Mega-dunes in the lake group area of the Badain Jaran Sand Sea, China, are generally taller than dunes in the non-lake group area. This spatial distribution of dune heights may provide a new perspective on the controversy regarding the dunes’ formation mechanism. In this study, we calculated the relative heights and slopes of individual dunes based on a digital elevation model, and we confirmed the height distribution of abnormally tall dunes in the lake group area of the sand sea. It was also found that slopes of more than 10° in the lake group area are more common than those in the non-lake group area. Based on meteorological observations, coupled with the measurement of water content in the sand layers, we propose a conceptual model demonstrating that moisture exchange between the lakes and soil via non-rainfall water will humidify dune slopes and form a more favorable accumulation environment for aeolian sand, thus increasing dune heights. Although long-term observations are yet to be carried out, the present study can be used as evidence for understanding the basis of dune formation in the lake group area and assessing groundwater utilization in deserts.

Atrial fibrillation (AF) is an important cardiovascular disease that causes a great burden of disease. However, there is limited evidence of a link between air pollution exposure and AF. This study aimed to explore the short-term association between air pollution and AF. We obtained daily hospitalization of AF in two major hospitals of Yancheng, China from May, 2015 to May, 2020. Generalized additive models with quasi-Poisson regression were used to assess the associations between six criteria air pollutants and AF hospitalization. We explored the lag patterns, and visualized the concentration-response relationships. The robustness of the association was tested by two-pollutant model, and we explored potential effect modification by age, sex and season. A total of 15,171 inpatients from two hospitals were collected in this study with an average daily count of eight patients. We observed consistent and significant associations between six air pollutants and AF on lag 0–4 days. A 10 ug/m3 increase in PM2.5 was associated with 2.81% (95%CI: 1.44%, 4.20%) changes in AF, and the effect estimate was 1.67% (95%CI: 0.77%, 2.59%) for PM10, 4.90% (95%CI: 1.69%, 8.22%) for NO2, 6.81% (95%CI: 0.46%, 13.57%) for SO2, 1.82% (95%CI: 0.60%, 3.06%) for O3; a 0.1 mg/m3 increase in CO was associated with 2.55% (95%CI: 0.91%, 4.21%) increments in AF. Associations of PM2.5 and PM10 were robust after adjusting for SO2, NO2, CO, and O3, but not vice versa. Female patients and those aged less 70 years had larger risk of AF associated with air pollution exposure. The concentration-response curves of the six pollutants were almost linear and increasing with no obvious thresholds. This time-series study in Yancheng demonstrated increased risk of AF and a delayed effect over lag 0–4 days. Our findings suggested need of prevention and protection against these environmental risk factors for AF in health departments.

The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G>A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A>C (p.Q381P). The splicing mutation c.393+1G>A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A>C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14–15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G>A, missense mutation c.1A>C (p.Q381P), and COLQ exon 14–15 deletion could cause CMS.

Mental retardation, X-linked 21/34 (MRX21/34), is a rare intellectual disability disease caused by mutations in the IL1RAPL1 (Interleukin-1 Receptor Accessory Protein-Like 1) gene. Using Sendai virus-mediated reprogramming, we established an induced pluripotent stem cell (iPSC) line from PBMCs collected from a ten-year-old boy with MRX21/34. The iPSCs showed stable amplification, expressed pluripotent genes, displayed a normal karyotype, and had characteristics of trilineage differentiation potential in an in vitro differentiation assay.

Aeolian sediments are widely distributed in the Lake Qinghai basin of the northeastern Tibetan Plateau (TP), but the history of aeolian activities in the basin is indistinct, and the underlying impacting factors are still poorly understood. In this study, depositional history of a mega-dune from the eastern Lake Qinghai basin was determined by optically stimulated luminescence (OSL) dating. The results show that nearly 30 m thick of sands accumulated during the interval of 7-6 ka, followed by soil formation during the last ∼5 ka. Together with previously published OSL ages of aeolian sediments, the Holocene aeolian activity in the Lake Qinghai basin was reconstructed as following: (1) The temporary aeolian activity appears to be characterized with a pattern of strengthened intensity during the first half of Holocene but relatively lowered intensity with a gradual decreasing trend afterward; (2) The interval of 7-6 ka in the middle Holocene witnessed a transition from dune activation towards stabilization; (3) A very low sand accumulation rate during the period of 5-3 ka and the contemporaneous extensive palaeosol development imply the least aeolian activity at that period. We inferred that the Holocene aeolian activity in the Lake Qinghai basin was mainly controlled by sediment supply, which was in turn modulated by the lake-level change of Lake Qinghai. Large amounts of sand were available, when the lake level dropped and then beach sands could exposure for deflation.

Human-induced pluripotent stem cell (hiPSC) technology and directed cardiac differentiation technology can provide a continuous supply of cells for disease modeling, drug screening, and cell therapy. However, two-dimensional (2D) cells often fail to faithfully reflect the physiological structure and function of the heart. Considering the contractile function is the most critical and easy-to-understand function of cardiomyocytes, the engineered cardiac tissues (ECT) with mechanical properties may serve as an appropriate three-dimensional (3D) platform for drug evaluation. At present, there are various methods to generate ECTs, some of which are quite costly. In the present study, we proposed that human foreskin fibroblast (HFF) cells, as a cost-effective and accessible cell source, can promote the compaction and remodeling of ECTs. The HFFs derived ECTs displayed stable structural and functional characteristics with a higher performance-to-price ratio. Moreover, both ECTs made from atrial and ventricular cardiomyocytes showed an excellent drug response, demonstrating that the ECT with HFFs as an easy and reliable platform for drug evaluation.

Heart failure (HF) is a global public health problem of increasing importance. The association between acute exposure to air pollution and HF has been well established in developed countries, but little evidence is available in developing countries where air pollution levels are much higher. To explore the associations between PM2.5 and HF hospitalizations in Yancheng, China. In this time-series study, daily HF hospitalizations admitted in three major hospitals in Yancheng from May 1, 2015 to Apr 30, 2020 were collected. We used a generalized additive model with quasi-Poisson regression to investigate the association between PM2.5 and HF hospitalizations. The robustness of the associations was tested using two-pollutant models, and we examined the potential effect modification by age, gender, and season via stratification analyses. Lastly, we pooled the concentration-response curves. A total of 10,466 HF hospitalizations were recorded, with a daily average of 6 cases. We observed the most robust estimates on lag 0 day, and the associated increment in HF was 1.28% (95% CI 0.45%, 2.11%) for a 10-μg/m3 increase of PM2.5. The association remained after adjustment of O3, but not for NO2, CO, and SO2. The PM2.5-HF associations were positive in females, patients aged ≥ 65 years, and in cold season. The C-R relationship curve was generally increasing below 30 μg/m3. This study provided evidence on the association of PM2.5 with acute exacerbation of chronic heart failure, which may benefit future prevention strategy and policymaking.

Aeolian sediments are widely distributed in the Qinghai Lake basin on the northeastern Tibetan Plateau (TP), and have been extensively investigated for the palaeoclimate reconstruction. However, due to the relatively scanty of dating materials and applicable techniques, and also the commonly existed hiatus in aeolian sequences, the details of the Holocene aeolian activities in the Qinghai Lake basin remain unclear. In this study, we applied the optically stimulated luminescence (OSL) dating technique to a 3.6 m thick loess-palaeosol sequence (QH-18) located on the southern bank of the Qinghai Lake to establish a high-resolution chronology of the aeolian accumulation history. The quartz OSL chronology demonstrated that the loess accumulation commenced since the last deglaciation and continued during the Holocene (∼14.6–0.5 ka), characterized with a remarkably low sedimentation rate period from 6 ka to 2 ka. Similar phenomenon has been recorded in previously investigated aeolian sequences not only in the Qinghai Lake basin but also across the northeastern TP, which was likely owing to the optimal environment conditions that have suppressed the dust emission from the source areas in the extensive arid and semiarid areas. The end-member (EM) analysis of grain-size distribution in QH-18 yielded an optimal model with three EMs, i.e., EM1 (6 μm, background dust), EM2 (56 μm, fraction of medium or long-distance transportation) and EM3 (447 μm, fraction from proximal or local source). The EM3 fraction can only be transported with saltation process in short distances that derived from proximal or local sources. In addition to the regional climatic conditions, according to the variation and contribution of the EMs, we consider that the Holocene aeolian activity in the Lake Qinghai basin was also modulated by the lake-level fluctuations of Lake Qinghai, in the way of changing the supply of sandy materials.

Background: Brugada syndrome (BrS) is an autosomal dominant disorder that causes a high predisposition to sudden cardiac death. Several genes have been reported to be associated with BrS. Considering that the heterogeneity in clinical manifestations may result from genetic variations, the application of patient-specific induced pluripotent stem (iPS) cell-derived cardiomyocytes (CMs) may help to reveal cell phenotype characteristics resulting from different genetic backgrounds. The present study was to compare the structural and electrophysiological characteristics of sodium channel subunits with different genetic variations and evaluate the safety of quinidine for use with BrS patient-specific iPSC-derived cardiomyocytes.Methods: Two BrS patient-specific iPS cell lines were constructed that carried missense mutations in SCN5A and SCN1B. One iPS cell line from a healthy volunteer was used as a control. The differentiated cardiomyocytes from the three groups were evaluated by flow cytometry, immunofluorescence staining, electron microscopy, as well as calcium transient and patch clamp analyses to assess different pathological phenotypes. Finally, we evaluated the drug responses to varying concentrations of quinidine by measuring the action potential.Results: Compared to the control group, BrS-CMs showed a significant reduction in sodium current, prolonged action potential duration and varying degrees of decreased Vmax, but no structural difference was observed. After applying different concentrations of quinidine, the disease-specific groups and the control group had a downward trend in maximal upstroke velocity, resting membrane potential and action potential amplitude, and exhibited prolonged action potential duration without increasing incidence of arrhythmic events.Conclusion: Both patient-specific iPSC-CMs recapitulated the BrS phenotype at the cellular level. Although the SCN5A variation led to a markedly lower sodium current than what was observed with the SCN1B variation, their responses to quinidine were quite similar. The present study provides an advantageous platform for exploring disease mechanisms and evaluating drug safety in vitro.

Allan-Herndon-Dudley syndrome (AHDS) is a rare, X-chromosome-linked inherited disorder that affects brain development and is caused by a mutation in SLC16A2. Herein, we generated an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells of a one-year-old male infant with AHDS using Sendai-virus-mediated reprogramming. These iPSCs exhibited stable amplification, expressed pluripotent markers, and differentiated spontaneously into three germ layers in vitro. Additionally, this iPSC line was found to maintain a normal karyotype and retain the pathogenic mutation in SLC16A2, facilitating the study of disease mechanisms and development of new therapies of AHDS.

Mitochondrial DNA depletion syndrome-13 (MTDPS13) is a rare autosomal recessive mitochondrial disease caused by mutations in the FBXL4 (F-box and leucine-rich repeat protein 4) gene. Using Sendai virus-mediated reprogramming, we established an induced pluripotent stem cell (iPSC) line from PBMCs collected from a one-year-old female patient with MTDPS13. The iPSCs were stable during amplification, expressed pluripotent genes, maintained a normal karyotype, and showed characteristics of the three germs layers in an in vitro differentiation assay.

Mediator complex subunit 12 (MED12)-related disorders are recessive-X-linked intellectual disabilities present primarily in male patients. We came across a female patient with a heterozygous mutation (c.1249-1G > C) related to MED12-related syndrome. MED12 expression was significantly lower than that in her parents, and another X chromosome was inactive. We established an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) of a 1-year old Chinese girl with a heterozygous mutation (c.1249-1G > C) in MED12. PBMCs were reprogrammed using nonintegrative Sendai viral vectors. The iPSCs showed stable amplification, pluripotency-related gene expression, trilineage differentiation potential, and a normal karyotype.

BACKGROUND This study aimed to clarify the diagnosis and expand the understanding of dopa-responsive dystonia (DRD). MATERIAL AND METHODS Relevant data from clinical diagnoses and genetic mutational analyses in 3 Han Chinese patients with sporadic DRD were collected and analyzed. Protein structure/function was predicted. RESULTS One novel mutation of c.679A>G (p.T227A) in GCH1 and 3 known mutations of c.457C>T (p.R153X), c.739G>A (p.G247S), and c.698G>A (p.R227H) in tyrosine hydroxylase (TH) have been found and predicted to be damaging or deleterious. All of the mutations were localized in conserved sequences. The iterative threading assembly refinement (I-TASSER) server generated three-dimensional (3D) atomic models based on protein sequences from the novel nonsense mutation of c.679A>G (p.T227A) in GCH1, which showed that residue 227 was located in the GCH1 active site. CONCLUSIONS Patients carrying different non-synonymous variants had remarkable variation in clinical phenotype. This study expands the spectrum of genotypes and phenotypes of DRD in the Han Chinese ethnicity, provides new insights into the molecular mechanism of DRD, and helps the diagnosis and treatment of DRD.

Arid central Asia (ACA) is one of the largest arid (desert) areas in the world, and its climate is dominated by the westerlies. In this study, we examined sand dune evolution from the Bayanbulak Basin in the Tian Shan (Xinjiang, NW China), aiming to infer the Holocene moisture history of the ACA. Combined with stratigraphic observation and environmental proxies analysis (grain size, magnetic susceptibility and total organic content), large numbers of luminescence ages from multiple sites (eight sections, 79 samples) were applied to reconstruct the evolution of the sand dune accumulation in the study basin. The overall results imply very dry conditions characterized by sand dune accumulation at ∼12–6.5 ka, a wet interval between ∼6.5 and 0.8 ka when soil formation occurred, and decreased moisture during the last 0.8 ka. This moisture variation pattern is generally consistent with that inferred from many lacustrine records in the core zone of ACA, suggesting a widespread dry period in the early-to-middle Holocene and relatively wet middle-to-late Holocene. Thus, the moisture history derived from the current sand dune system contrasts with that in Asian monsoon areas, which are characterized by a strong monsoon (high precipitation) in the early and mid-Holocene and a weak monsoon (low precipitation and dry climate) during the late Holocene. Our results strongly suggest that the winter solar insolation and the external boundary conditions such as atmospheric CO2 concentration, ice sheets, and meltwater fluxes, have been major influential factors triggering the Holocene moisture evolution in the core zone of ACA.

Brugada syndrome (BrS) is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death. Considering that its heterogeneity in clinical manifestations may result from genetic background, the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) may help to reveal cell phenotype characteristics underlying different genetic variations. Here, to verify and compare the pathogenicity of mutations (SCN5A c.4213G>A andSCN1B c.590C>T) identified from two BrS patients, we generated two novel BrS iPS cell lines that carried missense mutations inSCN5A or SCN1B, compared their structures and electrophysiology, and evaluated the safety of quinidine in patient-specific iPSC-derived CMs. Compared to the control group, BrS-CMs showed a significant reduction in sodium current, prolonged action potential duration, and varying degrees of decreased Vmax, but no structural difference. After applying different concentrations of quinidine, drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration (ETPC). The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A orSCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.

In the Asian monsoon margin of northwest China, millennial-scale precipitation and effective moisture changes during the Holocene differ from those observed in the primary monsoon area. Whether these differences were caused by a change in precipitation or other hydroclimate factors remains controversial. We selected Huahai Lake, located in the western portion of the Hexi Corridor, at the northwest margin of the Asian monsoon area, to address this question. Using paleoclimate proxies (mineralogical assemblages and immobile elements) and results from a previous study, we inferred hydroclimate changes in this area during the early and middle Holocene (10.5–5.5 cal ka BP). Heavy precipitation and abundant runoff occurred during the early Holocene (10.5–8.8 cal ka BP). Proxies (carbonate content, total organic carbon and C/N) for precipitation minus evaporation (P − E) in the same section, however, revealed low P − E during the early Holocene and highest P − E in the middle Holocene (8.8–5.5 cal ka BP). Therefore, on a millennial timescale, precipitation amount and effective moisture changes were asynchronous during the early and middle Holocene. The precipitation and effective moisture pattern in the study area during that time span was different from patterns in both the Asian monsoon and westerly wind-influenced areas, suggesting an interplay between the two climate features. High precipitation during the early Holocene corresponded to a strengthened Asian monsoon. Highest P − E in the study area occurred during the middle Holocene and may have been caused by low evaporation, rather than high precipitation.

Calcareous root tubes or rhizoliths have a strong potential for paleoenvironmental studies, especially in reconstructing paleoenvironmental conditions and paleovegetation. Previous studies suggested that the effectivity of the moisture level affects the formation of calcareous root tubes in the deserts of the Alashan Plateau, Northwest China. However, it remains unclear whether the temporal distribution of calcareous root tubes can be used to reconstruct paleo-effective moisture in this area. In this study, based on conventional 14C dating results of 34 Holocene calcareous root tube samples collected from the Badain Jaran Desert, the Tengger Desert and the Ulan Buh Desert in the Alashan Plateau of northwestern China, millennial-scale changes in paleo-effective moisture during the Holocene in this area were reconstructed. The frequency of the 14C dating results demonstrates that ~ 62% of the Holocene samples were dated to 7–5 cal kyr BP, and ~ 38% of the Holocene samples were dated to 4–2 cal kyr BP, indicating an arid period during the early Holocene (before 8.0 cal kyr BP), a humid period during the mid-Holocene (8.0–5.0 cal kyr BP) and a humid to arid period during the late Holocene (after 5.0 cal kyr BP). The reconstruction results were consistent with other previous reconstruction results from lake sediments and aeolian sand–lacustrine sequences, which indicated that temporal distribution of calcareous root tubes can reflect millennial-scale changes in paleo-effective moisture in this area. However, a single sample could indicate local environmental changes that may differ from the overall desert environmental changes. Hence, the relatively humid environmental record obtained from the presence of calcareous root tubes is a local signal or a regional signal that should be noted.

Understanding past human-environment interactions over a long time-scale offers an analogue to predict, adapt and mitigate the environmental issues caused by global change and human activities in the future. The transient existence of historical cities from arid northern China can provide a valuable reference for this issue. In this study, we investigated a set of sand dunes which accumulated alongside the city wall of South Heishuiguo ancient city (SHC) from the middle Hexi Corridor in arid northern China. Dating these dune sands can provide the timing of both desertification and city abandonment. A series of sand samples (a total of 20) were collected, and their ages were determined by luminescence dating of K-feldspar fraction. The results suggest an abrupt sand dune accumulation between 0.40 ± 0.03 ka and 0.25 ± 0.02 ka, corresponding to 1590–1790 CE. This study confirms a phase of desertification between the late 16th century and the late 18th century in the Hexi Corridor, and the abandonment of the SHC at the ~17th century. In order to assess the anthropogenic influences on desertification, we also reconstructed the population history of the Hexi Corridor over the last 2000 years based on historical literature as a quantitative index of human activity intensity. By comparison of the timing of onset of desertification around the SHC with robust paleoclimate and historical population reconstructions, we conclude that (1) the desertification of 1590–1790 CE was likely the result of considerably enhanced human activities between the late Ming and the early Qing Dynasties, as this period was dominated by a relatively moist climate and could restrain the sand deflation; and (2) the desertification in turn caused abandonment of SHC as the impact of environmental changes on people.

Antibacterial peptide can be easily degraded by protease and has the lethal effect on the host Escherichia coli. In order to solve these problems and further improve the expression ability of the Escherichia coli system, the antimicrobial peptide Spinosan-C of Paa spinosa was studied. First, the codon of Spinosan-C was optimized according to E. coli codon usage frequency. Then, the 8 multimeric Spinosan-C gene (8×Spinosan-C) was synthesized and cloned into prokaryotic expression vector pET-28a. The fusion antimicrobial peptide 8×Spinosan-C was further highly expressed in Escherichia coli strain Rosetta. The recombinant 8×Spinosan-C protein was then purified and cleaved specially by formic acid to generate the Spinosan-C monomer. Antibacterial test in vitro suggested that the cleaved Spinosan-C monomer had antibacterial bioactivity against the test bacteria. This study provides a technical reference for the largescale preparation of frog antimicrobial peptides.为克服抗菌肽易被蛋白酶降解及对宿主大肠杆菌的杀伤作用，并进一步提高大肠杆菌系统的表达能力，以棘胸蛙Paa spinosa 抗菌肽Spinosan-C 为研究对象，按照大肠杆菌密码子利用频率进行密码子优化，设计合成8 拷贝的串联8×Spinosan-C 基因，将合成的串联基因克隆到大肠杆菌表达载体pET-28a，利用大肠杆菌感受态细胞Rosetta 进行原核表达，获得高效表达的串联8×Spinosan-C 重组蛋白，用甲酸专一性切割得到抗菌肽Spinosan-C单体。体外抑菌试验表明，切割后的抗菌肽Spinosan-C 单体对测试菌生长具有抑制作用，为蛙类抗菌肽的规模化制备提供了参考。.

Calcareous root tubes are widely distributed across the Badain Jaran Desert and the Tengger Desert of the Alashan Plateau in northwest China. However, the reliability of their 14 C dating results and their environmental significance remain unclear. In this study, the conventional 14 C ages of 31 calcareous root tube samples and one aquatic mollusc shell sample, which were all collected from the Badain Jaran Desert and the Tengger Desert, were measured. The results reveal that nine of the 14 calcareous root tube samples from the Badain Jaran Desert were from Marine Isotope Stage (MIS) 3, while two samples were from MIS 2. The other three samples were dated to the mid-Holocene, one of which is consistent with the aquatic mollusc shell sample collected from the shoreline of Zhunzhahanjilin Lake in the Badain Jaran Desert. Moreover, the 17 calcareous root tube samples from the Tengger Desert were all dated to the mid- and late-Holocene, most of which were from the mid-Holocene. The results demonstrate that calcareous root tubes can be used as

Background/aim: Multiple sclerosis (MS) is a chronic and debilitating inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelinated axons in the CNS. Incomplete remissions occur more commonly with increasing duration of disease. Intravenous immunoglobulin (IVIg) has various functions as an immune modulator via macrophage activation. Clinical trials of immunoglobulin demonstrated remarkable clinical effects in several types of MS, especially in relapsing-remitting type. It is an approved method for the treatment of relapsing-remitting MS that can be used as a supportive therapy. Our study involves the case of a ten year old female patient with relapsing-remitting MS. This study was undertaken to examine the effects of IVIg used almost every 6 months in a patient with relapsing-remitting MS. Results: This case study demonstrated that treatments of IVIg used almost every 6 months in a patient with relapsing-remitting MS have potent therapeutic actions with early beneficial responses. Conclusion: IVIg used almost every 6 months shows a potential positive therapeutic treatment for relapsing-remitting MS and more large-scale clinical studies are required.

The pattern of Holocene environmental changes in the Asian monsoon margin on a millennial timescale remains controversial. Based on lithological characteristics and sedimentological proxies, we reconstructed Holocene-effective humidity changes and the lake evolution of Huahai Lake in the marginal area of the Asian monsoon in the Hexi Corridor of NW China. Our results show that alluvial and aeolian deposition before 10.4 cal ka BP indicate an arid environment, that lacustrine deposition from 10.4 to 8.8 cal ka BP indicates a transition from an arid to a humid environment, and that lacustrine deposition from 8.8 to 5.5 cal ka BP occurred during the most humid conditions, indicated by proxy records (grain size, carbonate, TOC, and C/N). After 5.5 cal ka BP, a depositional hiatus implicates an arid environment in the late Holocene. Holocene environmental changes on millennial timescales in Huahai Lake imply that climate was arid to humid in the early Holocene, most humid in the mid-Holocene and arid in the late Holocene. These moisture changes were influenced by the Asian monsoon, particularly the transportation of water vapor by the Indian monsoon. In addition, these moisture changes could have been affected by westerly winds that could have contributed to the water vapor supply to this region during the mid-Holocene. The most humid conditions that occurred in the study area during the mid-Holocene may have been caused by strong westerlies and low levels of evaporation.

Over the Tibetan Plateau and adjacent regions, numerous 14C-based lake records revealed a ubiquitous wet climatic period during 40–25 ka (late MIS 3), which is in contradiction with the global pattern of generally cold and dry climates. This paper focuses on OSL dating results of a large set of sand dunes and alluvial sediments (50 OSL ages) from the Qinwangchuan (QWC) Basin at the northeast edge of the Tibetan Plateau, with the aim to test the validity of the anomalous wet condition for the late MIS 3 interval, evidenced by numerous lake highstands. The abrupt sand dune accumulation as indication of increased aridity in the study area was OSL dated to ~40–13 ka. This dry climatic inference of the sand dune system from QWC apparently shows no wet MIS 3a event. Thus, the anomalous wet conditions revealed by high lake levels for the late MIS 3 phase may not be a universal phenomena across entire western China.

Deposits from the Huahai ancient lake in the Hexi Corridor were dated using conventional and AMS 14C. A 2500a “carbon storage effect” was defined at 9.25 m depth according to the 14C age difference between a plant macrofragment and detrital organic matter from the same layer. The chronology of this strata indicated that the mirabilite layer at the depth of 8.05 m–9.15 m had formed during the Younger Dryas (YD) event. The formation of the mirabilite layer indicated that the mean annual temperature in the Hexi Corridor dropped by 11 C° during the YD event compared with today. The lowest cold event occurred early in the YD, which is consistent with what has been revealed by other high-resolution records, such as those of Arctic ice cores and stalagmites in mid-latitude regions.

Li, Y., Wang, N., Cheng, H., Long, H. & Zhao, Q.: Holocene environmental change in the marginal area of the Asian monsoon: a record from Zhuye Lake, NW China. Boreas, 10.1111/j.1502-3885.2008.00063.x. ISSN 0300-9843. This article examines Holocene environmental change in Zhuye Lake in the marginal area of the Asian monsoon, NW China. Holocene environment records were obtained for the QTH01 and QTH02 sections in Zhuye Lake. The fluctuations in grain size, pollen, total organic carbon content and C/N ratios record notable environmental variation. The early Holocene (11.0 to 7.4 cal. kyr BP) was relatively arid, while vegetation coverage was sparse and primary productivity low. The optimal environment prevailed during the mid-Holocene (7.4 to 4.7 cal. kyr BP). Vegetation coverage was the densest and primary productivity the highest during the mid-Holocene. During the late Holocene (4.7 to 0 cal. kyr BP), the environment became arid, as shown by low lake level and sparse vegetation coverage. After 1.6 cal. kyr BP another strong aridification occurred. In this area, the environment was likely to have been influenced by both the Westerlies and the East Asian monsoon during the Holocene. During the early Holocene, the relatively arid environment lay in the background of the increasing East Asian monsoon and dry westerly wind. During the mid-Holocene, central Asia was controlled by the humid Westerlies, while a strong East Asian monsoon prevailed in Central China. The mid-Holocene optimum in this area benefited from an expanded East Asian monsoon and the humid Westerlies. Weakening of the East Asian monsoon caused aridification of the environment during the late Holocene. Intensification of this aridification after 1.6 cal. kyr BP might be correlated with appearance of the arid environments in the Westerly domain after similar to 1.5 cal. kyr BP. These arid conditions might be affected by the decreased moisture content of the Westerlies.

This paper contributes to an understanding of the relationship between pollen assemblages and grain-size in north-west China. Based on the relationship, we have reconstructed the environmental and vegetation history from sediments from Zhuye Lake, located in the marginal area of the Asian monsoon. During the Late Glacial (before ~ 13 cal ka BP), the high content of sand is correlated with low pollen concentrations, which implies an arid environment and low vegetation cover in the drainage. The relatively high percentages of Pinus and Quercus pollen, derived from nearby high elevations, may indicate particularly low vegetation cover in the lower part of the watershed. Between 13 and 7.7 cal ka BP, increasing silt content is correlated with high percentages of Picea pollen. Fluvial flow and effective humidity at high elevations, as well as lake-level, all increase. Following this, an abrupt environmental change which is likely caused by some change in lake geomorphology persists for about 300 years. The Holocene Optimum is between 7.4 and 4.7 cal ka BP in this region. Pollen concentrations reach their highest values in the section. The abundant herb pollen reflects the high vegetation cover in the lower part of the watershed. The silt and the fine components in the sediments are high and stable indicating optimal moisture conditions. Between 4.7–1.5 cal ka BP the lake-level fell and silty peat was formed at the site. The pollen concentration decreased in contrast to the high pollen concentration in the Holocene Optimum. In the last 1500 years the lake-level fell while terrestrial sediments were deposited at the site. In this phase Chenopodiaceae, Nitraria and Ephedra reach their highest values in the section reflecting an arid environment. In Zhuye Lake and the surrounding area environmental changes are mainly controlled the combined effects of the East Asian monsoon and the Westerlies since the Late Glacial. In the last ~ 1.5 cal ka BP the intensive arid trend may be correlated with changes in the Westerlies.

Sand wedges in the Hexi Corridor mainly formed in an alluvial gravel stratum of the late Pleistocene and the radiocarbon ages of the eolian sand infilling wedge prove that they were a product of the last ice age. During their period of formation, the mean annual air temperature in the Hexi Corridor was about −5.3°C., i.e. about 13°C lower than that of the present. This estimated value is coincident with the decrease in air temperature predicated from mirabilite (Na2SO4 · 10H2O) sedimentary layer in study area, and also agrees with research on the estimated amplitude of air temperature lowering in middle and high latitudes of the Northern Hemisphere during the last glacial period. The annual precipitation in the Western Hexi Corridor at that time was probably about 100–200 mm, i.e. about 100 mm more than at present.