Search

A growing body of evidence suggests that miR-5189-3p plays a critical role in multiple diseases. This study aimed to investigate the function of miR-5189-3p in laryngeal squamous cell carcinoma (LSCC) and explore its underlying mechanisms. qRT-PCR was designed to determine the expression levels of miR-5189-3p and eukaryotic translation initiation factor 5A2 (EIF5A2), while CCK-8 assay was performed to measure the effects of miR-5189-3p on cell proliferation. Transwell assay was performed to evaluate cell invasion as well as migration, and wound healing assay was applied to demonstrate cell migratory ability. Target gene prediction and luciferase reporter assay were developed to screen the possible target gene of miR-5189-3p, and Western blot was designed to measure EIF5A2 protein expression. MiR-5189-3p was down-regulated in LSCC tissues and cell lines. Up-regulation of miR-5189-3p notably inhibited cell proliferation, invasion, and migration in HEP2 and FADU cells. EIF5A2 was the potential downstream gene of miR-5189-3p, and overexpression of miR-5189-3p apparently reduced EIF5A2 expression. Moreover, reintroduction of EIF5A2 rescued the tumor suppressive effects of miR-5189-3p. MiR-5189-3p functions as a tumor inhibitor in LSCC progression via directly regulating EIF5A2 and may be a potential therapeutic target for LSCC. [ABSTRACT FROM AUTHOR]

Large differences in projected future annual precipitation increases in North America exists across 27 CMIP6 models under four emission scenarios. These differences partly arise from weak representations of land-atmosphere interactions. Here we demonstrate an emergent constraint relationship between annual growth rates of future precipitation and growth rates of historical temperature. The original CMIP6 projections show 0.49% (SSP126), 0.98% (SSP245), 1.45% (SSP370) and 1.92% (SSP585) increases in precipitation per decade. Combining observed warming trends, the constrained results show that the best estimates of future precipitation increases are more likely to reach 0.40–0.48%, 0.83–0.93%, 1.29–1.45% and 1.70–1.87% respectively, implying an overestimated future precipitation increases across North America. The constrained results also are narrow the corresponding uncertainties (standard deviations) by 13.8–31.1%. The overestimated precipitation growth rates also reveal an overvalued annual growth rates in temperature (6.0–13.2% or 0.12–0.37°C) and in total evaporation (4.8–14.5%) by the original models' predictions. These findings highlight the important role of temperature for accurate climate predictions, which is important as temperature from current climate models' simulations often still have systematic errors. [ABSTRACT FROM AUTHOR]

A regional analysis of soil temperature (ST) is essential for improving our understanding of the soil thermal regime and its link with the atmosphere. This study attempts to assess trends in the Poyang Lake Basin (PLB) ST magnitude during 1960–2016 from station observations at multiple depths. The Mann–Kendall, Thiel-Sen, linear regression, and probability density statistics (PDF) are used for ST trend assessment with a significance level of 95%. The ST seasonal variability shows minimum values in winter (8℃) and maximum in the summer season (32 ℃). On an interannual scale, spring and winter seasons exhibited a significant increase in both land surface temperature (LST) (0.4℃, 0.4℃) and ST (0.3 °C, 0.15℃) magnitude than summer (LST − 0.1℃, ST 0.2℃) and autumn seasons (LST 0.3℃, ST 0.2℃). The northern basin exhibited a significant increase in LST, and ST magnitude, especially during the cold seasons (spring, winter) than the warm seasons. The maximum and minimum temperature trend and their diurnal difference infer an increase in the minimum temperature, especially during the summer, autumn, and winter seasons. The PDF further inferred that extreme cold events' frequency decreased, and a significant increase in extreme warm events is obvious in the recent decade. The increasing trend in soil temperature magnitude is more in the northern basin than the high-altitude southern basin. Large-scale global warming and regional water and energy cycle changes can be the leading factors of such a warming trend. [ABSTRACT FROM AUTHOR]

Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Correction to: Long-term changes in observed soil temperature over Poyang Lake Basin, China, during 1960-2016 Dan Lou SP 2 sp - Xiao Shi SP 1,3 sp - Waheed Ullah SP 4 sp - Dawei Shi SP 5 sp - Chao Li SP 6 sp - Yuanfang Chai SP 7 sp - Xu Jinping SP 8 sp - Hao Zhou SP 9 sp 1 China Meteorological Administration Transportation Meteorology Key Laboratory, Nanjing 210008, China 2 Glarun Technology Co., ltd., Nanjing 211100, China 3 Jiangsu Meteorological Bureau, Meteorological Services Center, Nanjing, China 4 Defense and Security, Rabdan Academy, Abu Dhabi 114646, United Arab Emirates 5 Lianyungang Meteorological Bureau, Lianyungang 222000, China 6 Jiangsu Meteorological Observatory, Nanjing 210008, China 7 Department of Earth Sciences, V.U. University Amsterdam, Amsterdam, Netherlands 8 Anji Meteorological Bureau, Anji 313300, China 9 Peixian Meteorological Bureau, Xuzhou 221000, China The original article has been corrected. [Extracted from the article]

Advances in the immunology have identified that interleukin (IL)-17 and IL-35 are cytokines with diverse functions, serving important roles in autoimmune diseases and chronic inflammation. Checkpoint inhibitor pneumonitis (CIP) is focal or diffuse lung inflammation induced by immune checkpoint inhibitors and the underlying pathogenesis has not been fully explored. The aim of the present study was to investigate the roles of IL-17A and IL-35, and the correlation between their levels and different T cell subsets in CIP. The levels of IL-17A and IL-35 in peripheral blood and bronchoalveolar lavage fluid (BALF) were measured in patients with non-small cell lung cancer (NSCLC) with CIP, and the corresponding controls. The percentages of helper T lymphocyte (Th)1, Th2 and Th17 cells, and regulatory T cells (Tregs) in the peripheral blood were synchronically detected. Serum levels of IL-17A and IL-35 were significantly increased at the time of CIP diagnosis compared with the baseline, and significantly decreased upon clinical recovery or improvement. IL-17A and IL-35 were also increased in the BALF during the development of CIP compared with the baseline. Serum levels of IL-17A were positively correlated with the percentages of Th1 and Th17 cells as well as the ratio of Th17 to Tregs, but negatively associated with the frequency of Tregs in CIP. Serum levels of IL-35 were positively correlated with the percentages of Th1 and Tregs, and with the ratio of Th1 to Th2 cells in CIP. A higher frequency of Th1 and Th17 cells, as well as higher ratios of Th17 to Tregs and Th1 to Th2 cells were detected upon development of CIP comparing with the baseline. These data suggested that the activation of Th1 and Th17 cells, as well as Treg inhibition contributed to the imbalanced ratios of Th1 to Th2 and Th17 to Tregs, which resulted in increased secretion of IL-17A and IL-35 in the plasma and BALF; this may present a valuable index to monitor the development and severity of CIP in patients with NSCLC receiving immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Allele-specific DNA methylation (ASM) describes genomic loci that maintain CpG methylation at only one inherited allele rather than having coordinated methylation across both alleles. The most prominent of these regions are germline ASMs (gASMs) that control the expression of imprinted genes in a parent of origin-dependent manner and are associated with disease. However, our recent report reveals numerous ASMs at non-imprinted genes. These non-germline ASMs are dependent on DNA methyltransferase 1 (DNMT1) and strikingly show the feature of random, switchable monoallelic methylation patterns in the mouse genome. The significance of these ASMs to human health has not been explored. Due to their shared allelicity with gASMs, herein, we propose that non-traditional ASMs are sensitive to exposures in association with human disease. Results: We first explore their conservancy in the human genome. Our data show that our putative non-germline ASMs were in conserved regions of the human genome and located adjacent to genes vital for neuronal development and maturation. We next tested the hypothesized vulnerability of these regions by exposing human embryonic kidney cell HEK293 with the neurotoxicant rotenone for 24 h. Indeed,14 genes adjacent to our identified regions were differentially expressed from RNA-sequencing. We analyzed the base-resolution methylation patterns of the predicted non-germline ASMs at two neurological genes, HCN2 and NEFM, with potential to increase the risk of neurodegeneration. Both regions were significantly hypomethylated in response to rotenone. Conclusions: Our data indicate that non-germline ASMs seem conserved between mouse and human genomes, overlap important regulatory factor binding motifs, and regulate the expression of genes vital to neuronal function. These results support the notion that ASMs are sensitive to environmental factors such as rotenone and may alter the risk of neurological disease later in life by disrupting neuronal development. [ABSTRACT FROM AUTHOR]

Objective: The inflammatory bowel disease disability index (IBD‐DI) has been used to evaluate functional status for patients with inflammatory bowel diseases (IBD). The study aimed to develop a reliable Chinese version of IBD‐DI (C‐IBD‐DI). Methods: Consecutive patients with IBD and healthy controls were recruited from June 2016 to July 2017 in the First Affiliated Hospital, College of Medicine, Zhejiang University (Hangzhou, Zhejiang Province, China) to complete an inflammatory bowel disease questionnaire‐32 (IBDQ‐32), Hamilton's anxiety rating scale (HAMA) and Hamilton's depression rating scale‐24 items (HAMD‐24). The validation process included item reduction, reliability and validity tests. Results: Altogether 122 patients with IBD completed the validation process. Factor analysis reduced the C‐IBD‐DI to 13 items. Cronbach's α coefficient was 0.90. The C‐IBD‐DI scores were correlated with IBDQ‐32 score (r = −0.79, P < 0.001), HAMA (r = 0.78, P < 0.001) and HAMD‐24 (r = 0.81, P < 0.001). The total score of C‐IBD‐DI was significantly higher in patients with active IBD than in those in remission. The intraclass correlation coefficient was 0.83 in the stable IBD group, representing a good test–retest reliability. Those with improved disease activity had a significantly lower C‐IBD‐DI score at the follow‐up visit than at baseline. Patients with IBD had worse disability levels and quality of life than the controls, and were more likely to be anxious and depressed, especially those with active IBD. Conclusions: The validated C‐IBD‐DI comprising 13 questions has highly acceptable reliability and validity. Multicenter studies including large sample sizes are needed to further confirm our results. [ABSTRACT FROM AUTHOR]

Tan Re Qing (TRQ), a traditional Chinese medicine formula, is composed of Scutellariae Radix and other four herbs (bear bile powder, Caprae Hircus Cornu, Lonicerae japonicae Flos and Forsythiae Fructus) used for the treatment of bronchitis and upper respiratory infection. Chemical constituents in the herb always changed in content during processing. So, in this study, the ingredient change was monitored from three froms of Scutellariae Radix, including original herb, intermediate and product (TRQ capsules) with the same batch by HPLC MS/MS. A total of 98 compounds, including 69 flavonoids, 5 phenylethanoid glucosides, 6 other compounds and 18 unknown components, were tentatively identified in Scutellariae Radix. Most minor components in Scutellariae Radix were disappeared during preparation process, and only 17 of these compounds were detected in TRQ capsules. 5,2'-Dihydroxy-7,8-dimethoxyflavone and one unknown compound were detected in the original herb and intermediate, but disappeared in the TRQ capsules. These findings indicated the productive process control is vital for risk assessment and chemical material basis, as well as the basis for quality control of TRQ capsules. [ABSTRACT FROM AUTHOR]

The South Asian high (SAH) location and intensity are linked with the latent heating of the Tibetan Plateau (TP) and Yangtze River basin. The relationship between SAH variability and its impact on South Asian monsoon (SAM) onset is rarely linked with TP soil moisture. This study uses remotely sensed soil moisture and reanalysis products to quantify the relationship between the TP spring (April–June) soil moisture with SAH and SAM onset during 1988–2008. The results show that the TP spring soil moisture and monsoon onset indices are negatively correlated (R < −0.65), whereas the SAH exhibits a significant positive correlation (R ≥ 0.70) with TP soil moisture. The monsoon onset shows a difference of 20–25 days between the early- and late-onset composites. Significant positive (negative) soil moisture anomalies persist over the TP during the early (late) onset followed by positive (negative) LH (SH) anomalies during early (late)-onset composites. The TP thermal forcing exhibited positive anomalies during the early (late)-onset composites implying significant soil moisture control over the diabatic heating, which favors vertical ascent over the eastern plateau. Such a pattern leads to an earlier formation and movement of the SAH toward the Bay of Bengal (BOB) and southwestward of the TP. Before the early and late monsoon onset composites, the SAH pentad evolution drives the lower-tropospheric westerlies/easterlies toward continental SA. In the Indian Ocean the wind shear and transition from prevailing easterlies into westerlies during the pre-onset, onset, and post-onset pentad results in strong/weak ascent affecting the onset timing over the Arabian Sea and continental SA with less influence over the BOB monsoon onset. Significance Statement: The Tibetan Plateau heating is one of the key drivers of the Asian monsoon precipitation in the surrounding regions, which has been previously studied in detail. This study explored the Tibetan Plateau spring soil moisture's effect on South Asian monsoon onset timing. The monsoon onset timing is calculated using changes in wind direction, atmospheric temperature, and relative precipitation magnitude. Results found that the spring soil moisture substantially affects the TP thermal heating and the SA monsoon onset timing and highlights the physical processes leading to changes in the monsoon onset timing. The inclusion of soil moisture in estimating the monsoon onset timing can provide a tangible way of improving our understanding of the monsoon and associated water resources management practices. [ABSTRACT FROM AUTHOR]

Soil moisture is a key variable in terrestrial water cycle, playing a key role in the exchange of water and energy in the land-atmosphere interface. The spatiotemporal variations of soil moisture from multiple sources during 1988–2010 are evaluated against in situ observations in the Yellow River basin, China, including the Essential Climate Variable satellite’s passive microwave product (SMECV), ERA-Interim reanalysis (SMERA), the National Centers for Environmental Prediction/Department of Energy’s Reanalysis-2 (SMNCEP), and the Variable Infiltration Capacity model products (SMVIC). The seasonal soil moisture dynamics of SMECV and SMVIC appear to be consistent with SMin  situ, with significant soil drying in spring and wetting in summer. SMERA and SMNCEP, however, fail to capture the soil drying before rainy seasons. Remarkably, SMECV shows large agreement with SMin  situ in terms of the interannual variations and the long-term drying trends. SMVIC captures the interannual variations but fails to have the long-term trends in SMin  situ. As for SMERA and SMNCEP, they fail to capture both the interannual variations and the long-term soil drying trends in SMin  situ. [ABSTRACT FROM AUTHOR]

Epidemiological studies have revealed that environmentally relevant low levels of paraquat (PQ) exposure is listed on the etiology of neurological disorders such as Parkinson’s disease (PD). The behavioral effects of PQ are of current interest, especially when exposure occurs in the period of early stage of life. To characterize whether and how age affects neurobehavioral performances of mice after PQ exposure, 21 days postnatal (PN21) and adult male C57BL/6 mice were daily administrated by oral gavage with 0 mg/kg (saline, control), 5 mg/kg or 10 mg/kg of PQ for 28 consecutive days. Survival rate and body weight were analyzed. Subsequently, mice were subjected to Morris water maze tests (MWM). The results showed that mice exposed to PQ had significantly longer latencies than those in the control group, with a dose-dependent manner. Furthermore, PN21 mice tended to have longer latencies than adult mice in the same dose group. Our data suggested that PQ exposure induced significant learning and memory impairment and more severely in PN21 mice when compared with adult mice. [ABSTRACT FROM PUBLISHER]

Paraquat (PQ) exposure influences central nervous system and results in serious neurotoxicity in vitro and in vivo. However, the role of PQ exposure in the development of CNS remains unclear. In present study, we investigated microRNAs (miRNAs) expression profiling and cell differential status following PQ treatment in human neural progenitor cells (hNPCs) as well as involved mechanism. Microarray profiling of miRNAs expression of PQ treated cell line and their corresponding control was determined. Differentially expression miRNAs were confirmed by quantitative real time PCR. Neural cell differentiation was performed with immunocytochemical analysis. Predicated target of miRNA was identified with luciferase reports and quantitatively analyzed using western blotting. Our results found PQ dramatically suppressed neural cell differentiation ability. 43 differentially expressed miRNAs were identified in PQ treated cells. The expression levels were over expressed in 25 miRNAs, whereas 18 miRNAs were suppressed. More importantly, we observed that miR-200a expression level to be lower in PQ treated cells. Luciferase assay and protein expression results confirmed the direct binding effect between CTNNB1 and miR-200a following PQ exposure. Collectively, our data suggested that down regulation of miR-200a in the PQ treated neural stem cell significantly participated in the differentiation processes and subsequently resulting in decreased cell viability, increased epithelial-mesenchymal transition process and the inhibited differential through CTNNB1 pathway. [ABSTRACT FROM AUTHOR]

An ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method was developed and validated to determine acetaminophen (AAP) and dihydrocodeine (DHC) in human plasma simultaneously. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard midazolam were separated on an Acquity UPLC BEH C18 column and mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m / z 151.2 → 110.0 and m / z 302.3 → 199.2 were used to quantify for AAP and DHC, respectively. The linearity of this method was found to be within the concentration range of 50–10000 ng/mL for AAP, and 1–100 ng/mL for DHC in human plasma, respectively. The lower limit of quantification (LLOQ) was 50 ng/mL and 1 ng/mL for AAP and DHC in human plasma, respectively. The relative standard deviations (RSD) of intra and inter precision were less than 10% for both AAP and DHC. The analysis time of per sample was 1.0 min. The developed and validated method was successfully applied to a pharmacokinetic study of AAP (500 mg) with DHC (20 mg) capsule in Chinese healthy volunteers ( N = 20). [ABSTRACT FROM AUTHOR]

The article discusses the highlights of a Virtual Reality (VR) Hackfest held by the eLibrary team at the Palo Alto City Library. Topics covered include how VR technology might change people's lives, an exhibit of the participants' VR scenes, and how to use A-Frame code to render 3D scenes that can be experienced through a web browser or VR headset.

Abstract: The broad application of paraquat (PQ) has given rise to wide public concern over its potential to damage the nigrostriatal dopaminergic system because its chemical structure closely resembles that of the well-known dopaminergic neurotoxicant MPP+. However, little is known about the relevance of dopamine homeostasis changes in response to PQ exposure as the underlying mechanism of the neurotoxicity. We used the PC12 cell, a popular in vitro cell model system for characterizing the dopaminergic neuron to examine the effects of PQ on dopamine homeostasis. After 24h treatment with different concentrations of PQ (from 0 to 1000μmol/l), MTT tests showed that cell viability decreased with increasing PQ concentrations. Flow cytometry analysis also showed that PQ induced cell apoptosis in a dose-dependent manner. An enzyme-linked immunosorbent assay revealed that the intracellular dopamine content increased after PQ treatment. The mRNA expression of genes associated with dopamine synthesis (TH), storage (VMAT2), transportation (DAT and D2R) and degradation (MAO) was assessed using real-time PCR. Results showed that the expression of TH and COMT were unaffected while the expression of MAO was suppressed after PQ treatment. In addition, exposure to PQ reduced the expression of VMAT2 but up-regulated the expression of D2R. Moreover, the expression of DAT was up-regulated at a lower dose of PQ, and then decreased at a higher dose. These alterations of gene expression of MAO, D2R and DAT are consistent with an increase of intracellular dopamine content. Together, these findings suggest that PQ exposure can influence dopamine homeostasis, which may be partly related to the neurotoxicity of PQ. [Copyright &y& Elsevier]

The machine learning algorithms application in atmospheric sciences along the Earth System Models has the potential of improving prediction, forecast, and reconstruction of missing data. In the current study, a combination of two machine learning techniques namely K-means, and decision tree (C4.5) algorithms, are used to separate observed precipitation into clusters and classified the associated large-scale circulation indices. Observed precipitation from the Chinese Meteorological Agency (CMA) during 1961–2016 for 83 stations in the Poyang Lake basin (PLB) is used. The results from K-Means clusters show two precipitation clusters splitting the PLB precipitation into a northern and southern cluster, with a silhouette coefficient ~0.5. The PLB precipitation leading cluster (C1) contains 48 stations accounting for 58% of the regional station density, while Cluster 2 (C2) covers 35, accounting for 42% of the stations. The interannual variability in precipitation exhibited significant differences for both clusters. The decision tree (C4.5) is employed to explore the large-scale atmospheric indices from National Climate Center (NCC) associated with each cluster during the preceding spring season as a predictor. The C1 precipitation was linked with the location and intensity of subtropical ridgeline position over Northern Africa, whereas the C2 precipitation was suggested to be associated with the Atlantic-European Polar Vortex Area Index. The precipitation anomalies further validated the results of both algorithms. The findings are in accordance with previous studies conducted globally and hence recommend the applications of machine learning techniques in atmospheric science on a sub-regional and sub-seasonal scale. Future studies should explore the dynamics of the K-Means, and C4.5 derived indicators for a better assessment on a regional scale. This research based on machine learning methods may bring a new solution to climate forecast. [ABSTRACT FROM AUTHOR]

Abstract: We closely mimicked the in vivo setting in which sporadic hepatocarcinoma occurs by establishing a transgenic mouse model carrying regulatable SV40 early sequences under the control of the regulatory sequences of the human antithrombin III gene that confer hepatic expression. In this system, floxed dormant oncogenic sequences became functional after excision due to adenoviral expression of Cre recombinase or the stable transgenic expression in liver of a tamoxifen-inducible Cre. Hepatic oncogene expression was switched on by both methods, leading to the development of hepatocellular carcinoma. This model could be useful for investigating the key steps of the preneoplastic process, to identify suitable targets for the testing of new therapies. [Copyright &y& Elsevier]

Triptolide (TP) is a diterpene epoxide component extracted from Tripterygium wilfordii and has been shown to possess an impressive anticancer effect. However, TP has not yet entered any clinic trials due to the severe adverse effects that resulted from the off-target absorption and distribution found in animal studies. In this study, we designed and synthesized three amino acids (tryptophan, valine, and lysine) based TP prodrugs to target ATB0,+ which are highly expressed in pancreatic cancer cells for more effective pancreatic cancer therapy. The stability, uptake profiles, uptake mechanism, and cancer-killing ability were studied in vitro. All three prodrugs showed increased uptake and enhanced cytotoxicity in pancreatic cancer cells, but not in normal pancreatic cells. The difference in killing effect on normal and cancer cells was attributed to pancreatic cancer over-expressed ATB0,+-mediated uptake. Specifically, tryptophan-conjugated TP prodrug (TP-Trp) showed the highest uptake and the best cancer cell killing effect, considered as the best candidate. The present study provided the proof-of-concept of exploiting TP prodrug to target ATB0,+ for pancreatic cancer-selective delivery and treatment. [ABSTRACT FROM AUTHOR]

Aims/Introduction: To investigate the genetic etiology and evaluate the diagnostic application of next‐generation sequencing for diabetes/persistent hyperglycemia in children and adolescents. Materials and Methods: Patients with diabetes/persistent hyperglycemia, presenting with at least one other clinical manifestation (other than diabetes) or with a family history of diabetes, were recruited. The clinical and laboratory characteristics of the patients were recorded. Next‐generation sequencing was carried out, and candidate variants were verified by Sanger sequencing. Variant pathogenicity was further evaluated according to the American College of Medical Genetics and Genomics guidelines. Results: This study included 101 potential probands, 36 of whom were identified as positive by genetic testing. A further 51.2 and 20.9% of variants were determined to be pathogenic or likely pathogenic, respectively. Variants associated with the disease were primarily identified in 21 genes and three regions of copy number variants. Among the 39 variants in 21 genes, 61.5% (24/39) were novel. The genetic diagnosis of 23 patients was confirmed based on genetic evidence and associated clinical manifestations. We reported GCK variants (21.7%, 5/23) as the most common etiology in our cohort. Different clinical manifestations were observed in one family with WFS1 variants. Conclusions: Our findings support the use of next‐generation sequencing as a standard method in patients with diabetes/persistent hyperglycemia and provide insights into the etiologies of these conditions. [ABSTRACT FROM AUTHOR]

COVID-19 caused by SARS-CoV-2 is a great threat to public health. We present the safety and immunogenicity data from a phase I trial in China of an mRNA vaccine (LVRNA009). In the single-centre, double-blind, placebo-controlled and dose-escalation study, 72 healthy unvaccinated adults aged 18–59 years were randomized (3:1) to receive LVRNA009 with one of three vaccine dosage (25, 50 and 100 μg) or placebo, to evaluate for the safety, tolerability and immunogenicity of LVRNA009. All these participants received two injections 28 days apart. No adverse events higher than grade 2 were reported during the study. A total of 30 participants (42 %) reported solicited adverse reactions during the first 14 days after vaccinations. Of the events reported, fever (n = 11, 15 %) was the most common systemic adverse reaction, and pain at the injection site (n = 17, 24 %) was the most frequent solicited local adverse reaction. Anti-S-protein IgG and neutralising antibodies were observed to have been induced 14 days after the first dose, significantly increased 7 days after the second dose, and remained at a high level 28 days after the second dose. Specific T-cell responses peaked 7 days and persisted 28 days after second vaccination. LVRNA009 has demonstrated promising results in safety and tolerability at all three dose levels among Chinese adults. LVRNA009 at three dose levels could rapidly induce strong humoral and cellular immune responses, including binding and neutralising antibody production and IFN- γ secretion, which showed good immunogenicity. Clinical trial registration number: Clinicaltrials.gov NCT05364047; Chictr.org.cn ChiCTR2100049349. [ABSTRACT FROM AUTHOR]

Abstract Both epidemiological investigations and animal studies have linked arsenic-contaminated water to cancers, including skin, liver and lung cancers. Besides genotoxicity, arsenic exposure-related pathogenesis of disease is widely considered through epigenetic mechanisms; however, the underlying mechanism remains to be determined. Herein we explore the initial epigenetic changes via acute sodium arsenite (As) exposures of mouse embryonic fibroblast (MEF) cells and histone H3K79 methyltransferase Dot1L knockout (Dot1L−/−) MEF cells. Our RNA-seq and Western blot data demonstrated that, in both cell lines, acute As exposure abolished histone acetyltransferase p300 at the RNA level and subsequent protein level. Consequently, p300-specific main target histone H3K27ac, a marker separating active from poised enhancers, decreased dramatically as validated by both Western blot and ChIP-qPCR/seq analyses. Concomitantly, H3K4me1 as another well-known marker for enhancers also showed significant decreases, suggesting an underappreciated crosstalk between H3K4me1 and H3K27ac involved in As exposure. Significantly, As exposure-reduced H3K27ac and H3K4me1 inhibited the expression of genes including EP300 itself and Kruppel Like Factor 4(Klf4) that both are tumor suppressor genes. Collectively, our investigations identified p300 as an internal bridging factor within cells to sense external environmental As exposure to alter chromatin, thereby changing gene transcription for disease pathogenesis. Highlights • Acuate arsenite exposure abolished histone acetyltransferase p300. • A crosstalk between H3K4me1 and H3K27ac involved in arsenite exposure. • Attenuated H3K27ac and H3K4me1 repressed the expression of tumor suppressor genes upon arsenite exposure. [ABSTRACT FROM AUTHOR]

In recent years, remote sensing has become one newest technology for deriving soil moisture at large scales. Using a radiative transfer algorithm, we have derived soil moisture over the Tibetan Plateau from the brightness temperature of the microwave radiometer imager (MWRI) onboard China’s Fengyun 3B (FY3B) satellite. The derived FY3B soil moisture data are evaluated with in situ observations, the ERA-Interim reanalysis and the retrievals from microwave imager (TMI) onboard the Tropical Rainforest Measuring Mission (TRMM). The FY3B and the TMI data are found to have both overestimated the soil moisture magnitudes against in situ observations. The FY3B data significantly outperform the TMI retrievals and particularly the ERA-Interim data with respect to their temporal dynamics, which is more important in soil moisture applications. This finding suggests the promising potential for using FY3B microwave brightness temperature to derive soil moisture over the Tibetan Plateau. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CPF) is one of the organophosphorus pesticides widely used around the world, especially in China. Acetylcholinesterase inhibition is the main effect of organophosphorus insecticides exposure. Studies showed that CPF may also interfere with the metabolism of monoamine transmitters. To investigate the effects of CPF on dopaminergic pathway, the dopamine content, gene expression of catechol-O-methyl- transferase (COMT), vesicular monoamine transporter-2 (VMAT-2), and monoamine oxidase (MAO) and its activity in PC12 cells exposed to CPF was determined. Results showed that cell viability was decreased and total dopamine concentration was increased with CPF administration in a dose-dependent pattern. Gene of MAO was significantly downregulated in PC12 cells, while genes of COMT and VMAT-2 in PC12 cells did not show any change after CPF exposure. The MAO activity was decreased following incubation exposed to CPF. These results suggest that CPF may interfere with dopaminergic pathway through inhibition on gene and protein expression of MAO in vitro. [ABSTRACT FROM AUTHOR]

Hereditary hemochromatosis is a prevalent genetic disorder of iron hyperabsorption leading to hyperferremia, tissue iron deposition and complications including cirrhosis, hepatocarcinoma, cardiomyopathy and diabetes. Most individuals affected with hereditary hemochromatosis are homozygous with respect to a missense mutation that disrupts the conformation of HFE, an atypical HLA class I molecule (ref. 1; OMIM 235200). Mice lacking Hfe[SUP2-4] or producing a C282Y mutant Hfe protein[SUP3] develop hyperferremia and have high hepatic iron levels. In both humans and mice, hereditary hemochromatosis is associated with a paucity of iron in reticuloendothelial cells. It has been suggested that HFE modulates uptake of transferrin-bound iron by undifferentiated intestinal crypt cells, thereby programming the absorptive capacity of enterocytes derived from these cells[SUP5,6]; however, this model is unproven and controversial[SUP7,8]. Hepcid in, a peptide hormone (HAMP; OMIM 606464), seems to act in the same regulatory pathway as HFE. Although expression of mouse Hamp is normally greater during iron overload, Hfe[SUP-/-] mice have inappropriately low expression of Hamp. We crossed Hfe[SUP-/-] mice with transgenic mice overexpressing Hamp and found that Hamp inhibited the iron accumulation normally observed in the Hfe[SUP-/-] mice. This argues against the crypt programming model and suggests that failure of Hamp induction contributes to the pathogenesis of hemochromatosis, providing a rationale for the use of HAMP in the treatment of this disease. [ABSTRACT FROM AUTHOR]

Deviations in South Asian Summer Monsoon (SASM) precipitation affect the regional floods and drought patterns. In the current study, in-situ observations from Pakistan Meteorological Department (PMD), remotely sensed precipitation data from Climate Hazard Infrared Precipitation with Station data (CHIRPS), reanalysis data from ERA5, and National Center for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) during 1981–2018 are used to explore the atmospheric circulation patterns during above and below-normal precipitation episodes. In a statistical sense, two methods, namely the Empirical Orthogonal Function (EOF) and Percent Normal (PN) indices are used to derive dominant spatial patterns and temporal evolution of extreme monsoon precipitation episodes. Results inferred 60% of the variance to the leading EOF mode depicting a similar spatial pattern of eigenvectors across the region. The leading principal component (PC) and PN index together depicted similar deviations, complementing the extreme flooding and drought years. From the composites, an anomalous increase (decrease) in seasonal precipitation magnitude was observed. The possible mechanism suggests an active control of atmospheric and sea-surface temperature (SST) forcing by altering the wind ascent (descent). The jet streams (200 hPa) intensification of Rossby waves high (low) pressure provides favorable frontal boundaries between polar cold and tropical warm air masses. The westerlies and easterlies are intensified (suppressed) during the above (below) normal precipitation composites, affecting the moisture transport. The enhanced (reduced) convective activities in the Indian Ocean as a primary source affected precipitation in the region during each composite. • Significant differences in precipitation magnitude exist during above- and below normal precipitation composites. • South-westerlies from the Indian Ocean and easterlies from Pacific Ocean convergence produce above-normal precipitation. • An active control of atmospheric and sea-surface temperature (SST) forcing modify the regional wind ascent. [ABSTRACT FROM AUTHOR]

This study develops a data-driven modification scheme for a commonly used soil moisture retrieval algorithm by introducing a vegetation density-related single scattering albedo based on in situ and Fengyun-3B passive microwave observations. The Jiangxi province in China's mainland is one of the most challenging regions for soil moisture retrievals due to its complex topography, open water, and vegetation conditions. However, it has a very dense in situ soil moisture observation network which makes it a suitable test-bed to examine the performance of the modification scheme. The development of this new scheme consists of two steps. In a first step, the model is initialized using the most recently developed algorithm configuration. In the second step, these initial outcomes are used as input to determine the vegetation density related single scattering albedo which is solely based on observational data and used as the final algorithm configuration over our study area. We start by comparing the two most recent algorithm configurations against the in situ soil moisture network and demonstrate an overall improvement in terms of correlations coefficient for the most recent version. Then, the observational data- driven modification scheme was proposed and evaluated against the in situ soil moisture network with further improvements after its implementation. We furthermore applied the vegetation density-based scattering albedo in soil moisture retrievals over all grid cells in Jiangxi, and found that soil moisture data with the newly developed configuration significantly improved (up to 30%) compared to the preceding algorithm configurations. The two existing algorithm configurations were also evaluated over all grid cells and all results indicate consistent improvements between the successive algorithm versions. [ABSTRACT FROM AUTHOR]

Land surface temperature (LST) plays an essential role in the energy exchanges between land and atmosphere. It reflects the changes of available terrestrial energy in the context of global warming, and thus can serve as an indicator of regional climate change. The recently developed HIRS (High‐resolution infrared radiation sounder onboard NOAA satellites) LST product is among the longest LST records. We have analysed the HIRS LST against ground measurements from 66 stations in the Poyang Lake basin, China, considering the temporal variations at daily and interannual time scales during 1980–2009. The error metrics of correlation coefficient, Bias and unbiased Root Mean Square Deviation (ubRMSD) are used, together with the long‐term linear trends. The two data sets have considerable agreement with respect to daily variations. Their correlation coefficients are higher than 0.95 for all stations; and those for daily anomalies range from 0.73 to 0.85 across the basin. The Bias and the ubRMSD have indicated that the HIRS data have generally underestimated the LST across the basin, mainly because of its large underestimation of the occurrences of temperature higher than 35 °C. Nevertheless, the HIRS LST has largely overestimated the occurrences of summer days with temperature ranging 20–30 °C. The Bias and the ubRMSD appear to be smaller in the cropped plains and much larger in the afforested mountain areas. As for the interannual variations, the HIRS LST shows highest correlations with ground measurement in spring; they are lowest in summer, possibly due to the interference of monsoonal precipitation. Both the HIRS LST and ground measurements show significant increasing trends with similar patterns in spring and winter. However, the long‐term trends are significantly overestimated across the basin in summer, but underestimated in autumn in the HIRS LST data. Normalized probability density function of the HIRS LST and ground measurements in (a) NGB and (b) SGB regions. [ABSTRACT FROM AUTHOR]

Abstract Mitochondrial dysfunction is considered as a critical mechanism in the pathogenesis of Parkinson's disease (PD). Increasing evidence supports the notion of mitochondria-associated membranes (MAMs) in mitochondrial dysfunction; yet little is known about the role of MAMs-related proteins in the pathogenesis of PD. Herein we exposed the nematode Caenorhabditis elegans to 0.5–10.0 μM rotenone (RO) or 0.2–1.6 mM paraquat (PQ) for 3 days. Our results showed that both RO and PQ induced similar Parkinsonism including motor deficits and dopaminergic degeneration. RO/PQ caused mitochondrial damages characterized by the increase of vacuole areas and autophagy vesicles, but the decrease of mitochondrial cristae. RO/PQ-impacted mitochondrial function was also demonstrated by the decrease of ATP level and mitochondrial membrane potential. Additionally, the attachment or surrounding of endoplasmic reticulum to the damaged mitochondria indicates ultrastructural alterations in MAMs. Using fluorescently labeled transgenic nematodes, we further found that the expression of tomm-7 and genes of Complex I, II and III was reduced, whereas the expression of pink-1 was increased in the exposed animals. To determine MAMs in toxicity toward PD, we investigated the mutants of hop-1 and pink-1 , encoding presenilin and PTEN-induced putative kinase 1 (PINK1) in mitochondria-associated membranes, respectively. Results demonstrated that the mutation of both hop-1 and pink-1 reduced the vulnerability of lethal, behavioral, and mitochondrial toxicity induced by RO/PQ. These findings suggest that presenilin and PINK1 play important roles in the RO/PQ-induced neurotoxicity through the mechanisms involved in mitochondria-associated membranes. Highlights • Rotenone (RO) and paraquat (PQ) induced Parkinsonism in Caenorhabditis elegans. • RO/PQ caused mitophagy and mitochondria-associated membrane (MAM) damages. • RO/PQ reduced tomm-7 and Complex I, II, III gene, but increased pink-1 expression. • Mutation of hop-1 and pink-1 reduced vulnerability of RO/PQ-induced toxicity. • Presenilin and PINK1 play key roles in Parkinsonism-related toxicity through MAMs. [ABSTRACT FROM AUTHOR]

The availability of reliable long-term and large scale soil moisture observation datasets over the Tibetan Plateau has been of more concern in recent years. It is therefore necessary to verify any such data to have a better guide to their usage. In this study, we have compared satellite soil moisture retrievals of the Special Sensor Microwave Imager (SSM/I), with ERA-Interim/Land and Global Land Data Assimilation System (GLDAS-1) soil moisture products over the Tibetan Plateau. They are found to be largely different from each other regarding the soil moisture magnitudes in spring, summer and autumn, with those of the ERA-Interim/Land particularly higher than the other datasets in the eastern plateau. The SSM/I and the ERA-Interim/Land data are in good agreement considering their seasonal dynamics, which are however considerably different from the GLDAS-1 models (CLM, Noah, Mosaic and VIC). For interannual variations, it is striking to find strong negative correlations (R < − 0.6) between the SSM/I and the ERA-Interim/Land data in spring and autumn, especially over the central plateau. The SSM/I data is found to have also strong negative correlations (R < − 0.4) with data of the four GLDAS-1 models in the eastern plateau in spring; and such negative correlations appear in central and western plateau in autumn. In summer, the SSM/I data appears to be positively correlated with the ERA-Interim/Land and all the GLDAS-1 data over the plateau. The negative correlations indicate these data have quite different temporal dynamics for their interannual variations, especially in spring and autumn. A look at the spatial variations revealed that the SSM/I data shows a north-south seesaw pattern in all seasons. The GLDAS-1 Mosaic, Noah and CLM data are able to represent this seesaw pattern principally, which however, can hardly be seen in the ERA-Interim/Land and the GLDAS-1 VIC data. Our results have indicated significant uncertainties in the soil moisture data from remote sensing and reanalysis sources; and we have to use such data with great care. [ABSTRACT FROM AUTHOR]

Exercise preconditioning is a simple and effective way to prevent ischemia. This paper further provided the mechanism in hemodynamic aspects at the cellular level. To study the anti-apoptotic effects of fluid mechanics preconditioning, Cultured rats brain microvascular endothelial cells were given fluid intervention in a parallel plate flow chamber before oxygen glucose deprivation. It showed that fluid mechanics preconditioning could inhibit the apoptosis of endothelial cells, and this process might be mediated by the shear stress activation of Tie-2 on cells membrane surface and Bcl-2 on the mitochondria surface. [ABSTRACT FROM AUTHOR]

Little is known about the physiological or pharmacological properties of alarin, a new neuropeptide belonging to the galanin family. We previously showed that alarin has an antidepressant-like effect and is associated with a decrease in the hyperactivity of hypothalamic–pituitary–adrenal (HPA) axis that is observed in patients with depression using unpredictable chronic mild stress (UCMS) mouse model of depression. However, the mechanisms underlying these effects have not been uncovered. Inflammatory cytokines are reportedly associated with depression. Animal studies and cytokine immune therapy in humans suggest that pro-inflammatory cytokines induce depressive symptomatology and potently activate the HPA axis, whereas anti-inflammatory cytokines may decrease activation. Thus, we first determined the levels of inflammatory cytokines in the blood and brain to evaluate whether the antidepressant-like effect of alarin in UCMS-treated mice is related to its regulation of these inflammatory cytokines. Pro-inflammatory cytokines disrupt the function and/or expression of glucocorticoid receptors (GRs), which mediate the negative feedback of glucocorticoids on the HPA axis to keep it from being overactivated. We next explored the expression level of GRs in the brains of mice subjected to UCMS and to the administration of alarin. We found that intracerebroventricular administration of alarin significantly ameliorated depression-like behaviors in the UCMS-treated mice. Alarin restored the UCMS-induced an increase in the levels of the pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α and a decrease in the anti-inflammatory cytokine IL-10 level in the blood, prefrontal cortex, hippocampus and hypothalamus. Alarin also reversed the UCMS-induced down-regulation of GR expression in these brain regions. Thus, the antidepressant-like effects of alarin may be mediated by restoring altered pro-inflammatory and anti-inflammatory cytokine levels and GR expression to decrease HPA axis hyperactivity. Our findings provide additional knowledge to interpret the pathophysiology of depression. [ABSTRACT FROM AUTHOR]

Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an orphan nuclear receptor involved in the control of numerous functions in various organs (organogenesis, differentiation, metabolic homeostasis, etc.). The aim of the present work was to characterize the regulation and contribution of COUP-TFII in the control of hepatic fatty acid and glucose metabolisms in newborn mice. Our data show that postnatal increase in COUP-TFII mRNA levels is enhanced by glucagon (via cAMP) and PPARa. To characterize COUP-TFII function in the liver of suckling mice, we used a functional (dominant negative form; COUP-TFII-DN) and a genetic (shRNA) approach. Adenoviral COUP-TFII-DN injection induces a profound hypoglycemia due to the inhibition of gluconeogenesis and fatty acid oxidation secondarily to reduced PEPCK, Gl-6-Pase, CPT I, and mHMG-CoA synthase gene expression. Using the crossover plot technique, we show that gluconeogenesis is inhibited at two different levels: 1) pyruvate carboxylation and 2) trioses phosphate synthesis. This could result from a decreased availability in fatty acid oxidation arising cofactors such as acetyl-CoA and reduced equivalents. Similar results are observed using the shRNA approach. Indeed, when fatty acid oxidation is rescued in response to Wy-14643-induced PPARa target genes (CPT I and mHMG-CoA synthase), blood glucose is normalized in COUP-TFII-DN mice. In conclusion, this work demonstrates that postnatal increase in hepatic COUP-TFII gene expression is involved in the regulation of liver fatty acid oxidation, which in turn sustains an active hepatic gluconeogenesis that is essential to maintain an appropriate blood glucose level required for newborn mice survival. [ABSTRACT FROM AUTHOR]

• Vegetation growth contributes 85.4–90.5% of the increased water consumption. • 94.3–98.8% of global vegetation land are sustainable due to rising precipitation. • Unsustainable regions will continuously expand due to the greening world. The global vegetation cover is increasing and is expected continue increasing till 2100, owing to CO 2 fertilisation and afforestation. This greening phenomenon may create conflicting demands for water between ecosystems, atmosphere, and humans, and has aroused a series of controversies. For exploring the effects of greening phenomenon on terrestrial water availability, we estimated the balance between water supply (precipitation and snowmelt runoff) and water consumption (evaporation, human water use, transpiration, and interception losses) in the global vegetation land based on the outputs of 30 models from the Coupled Model Intercomparison Project Phase 6. Water consumption showed an increasing trend in most regions of global vegetation land for the period 1982–2016 as well as 2040–2100, mainly driven by the increased transpiration and interception losses for vegetation growth (contributing 85.4–90.5%). Although the greening phenomenon widely exacerbates water shortages, 94.3–98.8% of the global vegetation land was still found to be sustainable during 1982–2100, due to the water supply exceeding the total water consumption. More attention should be paid to the unsustainable regions where the total water consumption exceeded the total water supply. Such areas were continuously found to increase from 2.1–5.3% (1982–2016) to 5.4–5.7% (2040–2100) of the global vegetation land. We predict that Oceania, Northern India, the southern coastal regions of North America will be transformed from sustainable regions in 1982–2016 to unsustainable regions in 2040–2100. [ABSTRACT FROM AUTHOR]

Bisphenol A is a newly discovered endocrine disrupting chemical found in the environment that has estrogenic properties. With the extensive use of plastic products, the diffusion of bisphenol A from these products has caused serious environmental contamination. The present study investigated the synthesis of bisphenol-A antigen and polyclonal antibodies in order to develop a rapid method for the detection of bisphenol A in water. A carboxyl group was introduced into bisphenol A to create a novel hapten capable of coupling with proteins. A rabbit polyclonal antibody with good specificity was prepared by using the novel synthetic antigen. The obtained antibody had a low cross-reaction with other steroid substances. The half inhibitory concentration of the established method was 1.92 ± 0.06 μg L−1, with the lowest limit of detection being 0.10 μg L−1 and the coefficient of variation being less than 10%. The standard recovery rate of water samples was 95.5–105.0%. The method established in this study is an easy, rapid and specific method used for the quantitative detection of bisphenol A in water samples. [ABSTRACT FROM AUTHOR]

Highlights: [•] Paraquat (PQ) can directly affect human neural progenitor cells by reducing the viability of hNPCs. [•] Oxidative stress plays an important role in PQ-induced cytotoxicity. [•] PQ-induced cytotoxicity is associated with increased apoptosis. [Copyright &y& Elsevier]

Abstract: Rab GTPases, which belong to the Ras superfamily, represent a group of small molecular weight GTP binding proteins that are involved in various steps along the exocytic and endocytic pathways. We first identified mRabL5 (GenBank Accession No. NP_080349), a novel Mus musculus Rab-like protein, present as a Golgi-associated protein. Here we presented the results of the cloning, prokaryotic expression, purification, and polyclonal antibody production of the novel Rab-like protein. In order to obtain a specific antibody against mRabL5, we prepared two GST fusion proteins, full-length mRabL5 GST fusion protein and mRabL5 C terminus GST fusion protein, to immunize rabbits. Western blot analysis showed that both antibodies prepared against full length of mRabL5 and its C terminus, respectively, can recognize mRabL5 protein. Immunofluorescence of mRabL5 in NIH3T3 cells using the two antibodies showed its perinuclear clustering distribution pattern. The polyclonal antibodies preparation against mRabL5 provided a good tool for us to study the functional involvement of mRabL5. [Copyright &y& Elsevier]

Recently, mutations causing juvenile hemochromatosis have been identified in a novel gene, hemojuvelin (HJV), located on chromosome 1. Mouse models of this disease have now been developed by 2 groups, Huang et al. and Niederkofler et al., through targeted disruption of the Hjv gene (see the related articles beginning on pages 2180 and 2187). These mutant mice will allow further investigation into the role of HJV in the regulation of iron homeostasis, a role that to date remains elusive. [ABSTRACT FROM AUTHOR]

Drought severity still remains a serious concern across Sub-Saharan Africa (SSA) due to its destructive impact on multiple sectors of society. In this study, the interannual variability and trends in the changes of the self-calibrating Palmer Drought Severity Index (scPDSI) based on the Penman–Monteith (scPDSIPM) and Thornthwaite (scPDSITH) methods for measuring potential evapotranspiration (PET), precipitation (P), normalized difference vegetation index (NDVI), and sea surface temperature (SST) anomalies were investigated through statistical analysis of modeled and remote sensing data. It was shown that scPDSIPM and scPDSITH differed in the representation of drought characteristics over SSA. The regional trend magnitudes of scPDSI in SSA were 0.69 (scPDSIPM) and 0.2 mm/decade (scPDSITH), with a difference in values attributed to the choice of PET measuring method used. The scPDSI and remotely sensed-based anomalies of P and NDVI showed wetting and drying trends over the period 1980–2012 with coefficients of trend magnitudes of 0.12 mm/decade (0.002 mm/decade). The trend analysis showed increased drought events in the semi-arid and arid regions of SSA over the same period. A correlation analysis revealed a strong relationship between the choice of PET measuring method and both P and NDVI anomalies for monsoon and pre-monsoon seasons. The correlation analysis of the choice of PET measuring method with SST anomalies indicated significant positive and negative relationships. This study has demonstrated the applicability of multiple data sources for drought assessment and provides useful information for regional drought predictability and mitigation strategies. [ABSTRACT FROM AUTHOR]

Soil moisture is an important parameter in land surface processes, which can control the surface energy and water budgets and thus affect the air temperature. Studying the coupling between soil moisture and air temperature is of vital importance for forecasting climate change. This study evaluates this coupling over China from 1980–2013 by using an energy-based diagnostic method, which represents the momentum, heat, and water conservation equations in the atmosphere, while the contributions of soil moisture are treated as external forcing. The results showed that the soil moisture–temperature coupling is strongest in the transitional climate zones between wet and dry climates, which here includes Northeast China and part of the Tibetan Plateau from a viewpoint of annual average. Furthermore, the soil moisture–temperature coupling was found to be stronger in spring than in the other seasons over China, and over different typical climatic zones, it also varied greatly in different seasons. We conducted two case studies (the heatwaves of 2013 in Southeast China and 2009 in North China) to understand the impact of soil moisture–temperature coupling during heatwaves. The results indicated that over areas with soil moisture deficit and temperature anomalies, the coupling strength intensified. This suggests that soil moisture deficits could lead to enhanced heat anomalies, and thus, result in enhanced soil moisture coupling with temperature. This demonstrates the importance of soil moisture and the need to thoroughly study it and its role within the land–atmosphere interaction and the climate on the whole. [ABSTRACT FROM AUTHOR]

Various state-of-the-art gridded satellite precipitation products (GPPs) have been derived from remote sensing and reanalysis data and are widely used in hydrological studies. An assessment of these GPPs against in-situ observations is necessary to determine their respective strengths and uncertainties. GPPs developed from satellite observations as a primary source were compared to in-situ observations, namely the Climate Hazard group Infrared Precipitation with Stations (CHIRPS), Multi-Source Weighted-Ensemble Precipitation (MSWEP), Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks-Climate Data Record (PERSIANN-CDR) and Tropical Rainfall Measuring Mission (TRMM) multi-satellite precipitation analysis (TMPA). These products were compared to in-situ data from 51 stations, spanning 1998–2016, across Pakistan on daily, monthly, annual and interannual time scales. Spatiotemporal climatology was well captured by all products, with more precipitation in the north eastern parts during the monsoon months and vice-versa. Daily precipitation with amount larger than 10 mm showed significant (95%, Kolmogorov-Smirnov test) agreement with the in-situ data, especially TMPA, followed by CHIRPS and MSWEP. At monthly scales, there were significant correlations (R) between the GPPs and in-situ records, suggesting similar dynamics; however, statistical metrics suggested that the performance of these products varies from north towards south. Temporal agreement on an interannual scale was higher in the central and southern parts which followed precipitation seasonality. TMPA performed the best, followed in order by CHIRPS, MSWEP and PERSIANN-CDR. [ABSTRACT FROM AUTHOR]