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Abstract Objective A rapid and accurate forecast for the early prognosis of ICH patients is challenging. This study investigated whether heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) could prognosticate poor neurological outcomes in ICH patients. Methods Between November 2020 and November 2021, we studied 92 spontaneous ICH patients in the First Affiliated Hospital of Nanjing Medical University. Glasgow Outcome Scale (GOS) score at 2 weeks after the ICH was used to categorize patients into good and poor outcome groups. The modified Rankin Scale (mRS) assessed patients' ability to live independently for 1 year. We utilized a portable high‐frequency electrocardiogram (ECG) recording system to record the HRV and SKNA information in ICH patients and control participants. Results 77 patients were eligible for the prediction of neurological outcome and were allocated into the good (n = 22) or poor (n = 55) outcome groups based on the GOS grade. In univariate logistic regression analysis, significant variables that could differentiate the outcomes were age, hypertension, tracheal intubation, Glasgow Coma Scale (GCS) score, existing intraventricular hemorrhage, white blood cells, neutrophil, lnVLF, lnTP, and aSKNA. Variables in the best fit multivariable logistic regression model were age, hypertension, GCS score, neutrophils, and aSKNA. The GCS score was the only independent risk factor for poor outcomes. At 30 days and 1 year of follow‐up, patients with lower aSKNA had poor outcomes. Interpretation ICH patients had reduced aSKNA, which could be a prognostic indicator. A lower aSKNA suggested a worse prognosis. The present data indicate that ECG signals could be helpful for prognosticating ICH patients.

Abstract The limited availability of long‐term historical dust records has impeded comprehension of the mid‐latitude atmospheric circulation and underlying mechanisms of dust activities in arid Central Asia. We present a well‐dated 2,800‐year peat record from the northeastern Qinghai‐Tibet Plateau and identified the aeolian origin of archived particles by comparing grain‐size distribution and strontium isotope with those of modern dusts. We show that the reconstructed dust input was enhanced during warming periods, which also coincides with the variation of Westerlies, total solar irradiance, and North Atlantic Oscillation. We propose that warming climate may have contributed to a significant impact on the moisture balance and wind strength, and predict that this region may experience more frequent dust activity in the future. These findings contrast with meteorological observations of decreasing dust activities during the last 40 years despite a warming trend, suggesting different effects of natural processes versus anthropogenic impact on global warming.

Heart-on-chip emerged as a potential tool for cardiac tissue engineering, recapitulating key physiological cues in cardiac pathophysiology. Controlled electrical stimulation and the ability to provide directly analyzed functional readouts are essential to evaluate the physiology of cardiac tissues in the heart-on-chip platforms. In this scenario, a novel heart-on-chip platform integrating two soft conductive hydrogel pillar electrodes was presented here. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cardiac fibroblasts were seeded into the apparatus to create 3D human cardiac tissues. The application of electrical stimulation improved functional performance by altering the dynamics of tissue structure and contractile development. The contractile forces that cardiac tissues contract was accurately measured through optical tracking of hydrogel pillar displacement. Furthermore, the conductive properties of hydrogel pillars allowed direct and non-invasive electrophysiology studies, enabling continuous monitoring of signal changes in real-time while dynamically administering drugs to the cardiac tissues, as shown by a chronotropic reaction to isoprenaline and verapamil. Overall, the platform for acquiring contractile force and electrophysiological signals in situ allowed monitoring the tissue development trend without interrupting the culture process and could have diverse applications in preclinical drug testing, disease modeling, and therapeutic discovery.

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 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.

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 (

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.

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.

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 G>A) 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.

We generated an iPSCs line from the peripheral blood mononuclear cells (PBMCs) collected from a patient with long QT syndrome type 1 (LQT1) via a non-integrating system. We identified and verified a missense mutation in the KCNQ1 gene (c.773A > T) by whole-exome sequencing and Sanger sequencing. The established iPSC line was tested for pluripotency, differentiation potential, and karyotype. This cell-based model can help study the molecular mechanism and develop personalized drug therapies for LQT1.

Background: Autonomic nervous regulation plays a critical role in end-stage kidney disease (ESKD) patients with cardiovascular complications. However, studies on autonomic regulation in ESKD patients are limited to heart rate variability (HRV) analysis. Skin sympathetic nerve activity (SKNA), which noninvasively reflects the sympathetic nerve activity, has not been used in ESKD patients.Methods: Seventy-six patients on maintenance hemodialysis (MHD) treatment (a 4-h HD session, three times a week) were enrolled. Utilizing a noninvasive, single-lead, high-frequency recording system, we analyzed the dynamic change in HRV parameters and SKNA during HD. The different characteristics between the subgroups divided based on interdialytic weight gain (IDWG,

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.

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.

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.

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.

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.

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 and SCN1B c.590C>T) identified from two BrS patients, we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B, compared their structures and electrophysiology, and evaluated the safety of quinidine in patient-specific iPSCderived 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 or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events. [ABSTRACT FROM AUTHOR]

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 ∼1.5 cal. kyr BP. These arid conditions might be affected by the decreased moisture content of the Westerlies. [ABSTRACT FROM AUTHOR]

Sand wedges, formed mainly in a Late Pleistocene alluvial gravel in the Hexi Corridor are described in detail in this paper. 14C ages of the infilling eolian sand indicate that the sand wedges were products of the Last Ice Age. During the period of formation, the mean annual air temperature in the Hexi Corridor was about −5.3 °C, i.e. 12.6–14.6 °C lower than that of the present day. This estimated value is coincident with the fall in mean air temperature of 13 °C, which is predicated from a mirabilite (Na2SO4·10H2O) sedimentary layer, 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 100–200 mm, about 100 mm more than at present. [Copyright &y& Elsevier]