Forecasting groundwater level of karst aquifer in a large mining area using partial mutual information and NARX hybrid model.

Predicting the groundwater level of karst aquifers in North China Coalfield is essential for early warning of mine water hazards and regional water resources management. However, the dynamic changes of strata structure and hydrogeological parameters driven by coal mining activity cause challenges to the process-oriented groundwater model. In order to achieve accurate prediction of groundwater level in large mining areas, this study was the first to use the data-driven Nonlinear Autoregressive with External Input (NARX) model to predict the groundwater level of six karst aquifer observation wells in Pingshuo Mining Area. Three variable input scenarios were set up, solely considering meteorological factors, anthropogenic disturbance factors, and considering both meteorological and anthropogenic disturbance factors. The novel partial mutual information (PMI) screening algorithm was adopted to determine optimized input variables in each scenario. The input and feedback delay coefficients of NARX model were determined by using Seasonal-trend Decomposition Procedure Based on Loess (STL) algorithm and auto- and cross-correlation functions. The results showed that PMI algorithm can effectively screen out the optimal input variables for predicting groundwater level, the NSE coefficients of the PMI-NARX models under the three scenarios were 38.81%, 4.26% and 41.46% higher than those of the corresponding control experiments, respectively. In addition, the prediction performance of the PMI-NARX built on the basis of meteorological factors is poor (NSE <0.63). However, in scenarios which solely use anthropogenic disturbance factors and both use meteorological and anthropogenic disturbance factors, the PMI-NARX coupling models exhibit good prediction performance (NSE and R2 are all greater than 0.8). Especially under solely considering anthropogenic disturbance factors scenario, the model still exhibited good prediction accuracy with a negligible number of input variables. The results can provide technical and theoretical support for the prediction of groundwater level in other mining areas.

Vibsanin B preferentially targets HSP90ß, inhibits interstitial leukocyte migration, and ameliorates experimental autoimmune encephalomyelitis.

Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation-associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz-enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90ß. At the molecular level, inactivation of HSP90 can mimic vibsanin B's effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leukocyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90ß and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases.

miR-142-3p acts as an essential modulator of neutrophil development in zebrafish.

Neutrophils play critical roles in vertebrate innate immune responses. As an emerging regulator in normal myelopoiesis, the precise roles of microRNA in the development of neutrophils have yet to be clarified. Using zinc-finger nucleases, we have successfully generated heritable mutations in miR-142a and miR-142b and showed that hematopoietic-specific miR-142-3p is completely deleted in miR-142 double mutant zebrafish. The lack of miR-142-3p resulted in aberrant reduction and hypermaturation of neutrophils in definitive myelopoiesis, as well as impaired inflammatory migration of neutrophils in the fetal stage. Furthermore, the adult myelopoiesis in the miR-142-3p-deficient zebrafish was also affected, producing irregular hypermature neutrophils with increased cell size and a decreased nucleocytoplasmic ratio. Additionally, miR-142-3p-deficient zebrafish are expected to develop a chronic failure of myelopoiesis with age. Transcriptome analysis showed an aberrant activation of the interferon γ (IFN-γ) signaling pathway in myelomonocytes after miR-142-3p deletion. We found that the reduced number and hypermaturation of neutrophils caused by loss of miR-142-3p was mainly mediated by the abnormally activated IFN-γ signaling, especially the upregulation of stat1a and irf1b. Taken together, we uncovered a novel role of miR-142-3p in maintaining normal neutrophil development and maturation.

Setdb2 controls convergence and extension movements during zebrafish gastrulation by transcriptional regulation of dvr1.

As the primary driving forces of gastrulation, convergence and extension (C&E) movements lead to a medio-lateral narrowing and an anterior-posterior elongation of the embryonic body axis. Histone methylation as a post-translational modification plays a critical role in early embryonic development, but its functions in C&E movements remain largely unknown. Here, we show that the setdb2-dvr1 transcriptional cascade plays a critical role in C&E movements during zebrafish gastrulation. Knockdown of Setdb2, a SET domain-containing protein possessing a potential histone H3K9 methyltransferase activity, induced abnormal C&E movements, resulting in anterior-posterior shortening and medio-lateral expansion of the embryonic axis, as well as abnormal notochord cell polarity. Furthermore, we found that Setdb2 functions through fine-tuning the expression of dvr1, a ligand of the TGF-ß superfamily, to an appropriate level to ensure proper C&E movements in a non-cell-autonomous manner. In addition, both overexpression and knockdown of Dvr1 at the one-cell stage resulted in defects at epiboly and C&E. These data demonstrate that Setdb2 is a novel regulator for C&E movements and acts by modulating the expression level of dvr1, suggesting that Dvr1 acts as a direct and essential mediator for C&E cell movements.

Phospholipase C gamma-1 is required for granulocyte maturation in zebrafish.

The regulation of hematopoiesis is generally evolutionarily conserved from zebrafish to mammals, including hematopoietic stem cell formation and blood cell lineage differentiation. In zebrafish, primitive granulocytes originate at two distinct regions, the anterior lateral plate mesoderm (A-LPM) and the intermediate cell mass (ICM). Few studies in the zebrafish have examined genes specifically required for the granulocytic lineage. In this study, we identified the responsible gene for a zebrafish mutant that has relatively normal hematopoiesis, except decreased expression of the granulocyte-specific gene mpx. Positional cloning revealed that phospholipase C gamma-1 (plcg1) was mutated. Deficiency of plcg1 function specifically affected development of granulocytes, especially the maturation process. These results suggested that plcg1 functioned specifically in zebrafish ICM granulopoiesis for the first time. Our studies suggest that specific pathways regulate the differentiation of the hematopoietic lineages.

Cannabinoid receptor 2 suppresses leukocyte inflammatory migration by modulating the JNK/c-Jun/Alox5 pathway.

BACKGROUND: The role of cannabinoid receptor type 2 (Cnr2) in regulating immune function had been widely investigated, but the mechanism is not fully understood. RESULTS: Cnr2 activation down-regulates 5-lipoxygenase (Alox5) expression by suppressing the JNK/c-Jun activation. CONCLUSION: The Cnr2-JNK-Alox5 axis modulates leukocyte inflammatory migration. SIGNIFICANCE: Linking two important regulators in leukocyte inflammatory migration and providing a potential therapeutic strategy for treating human inflammation-associated diseases. Inflammatory migration of immune cells is involved in many human diseases. Identification of molecular pathways and modulators controlling inflammatory migration could lead to therapeutic strategies for treating human inflammation-associated diseases. The role of cannabinoid receptor type 2 (Cnr2) in regulating immune function had been widely investigated, but the mechanism is not fully understood. Through a chemical genetic screen using a zebrafish model for leukocyte migration, we found that both an agonist of the Cnr2 and inhibitor of the 5-lipoxygenase (Alox5, encoded by alox5) inhibit leukocyte migration in response to acute injury. These agents have a similar effect on migration of human myeloid cells. Consistent with these results, we found that inactivation of Cnr2 by zinc finger nuclease-mediated mutagenesis enhances leukocyte migration, while inactivation of Alox5 blocks leukocyte migration. Further investigation indicates that there is a signaling link between Cnr2 and Alox5 and that alox5 is a target of c-Jun. Cnr2 activation down-regulates alox5 expression by suppressing the JNK/c-Jun activation. These studies demonstrate that Cnr2, JNK, and Alox5 constitute a pathway regulating leukocyte migration. The cooperative effect between the Cnr2 agonist and Alox5 inhibitor also provides a potential therapeutic strategy for treating human inflammation-associated diseases.

Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation.

Interstitial loss of all or part of the long arm of chromosome 5, or del(5q), is a frequent clonal chromosomal abnormality in human myelodysplastic syndrome (MDS, a preleukemic disorder) and acute myeloid leukemia (AML), and is thought to contribute to the pathogenesis of these diseases by deleting one or more tumor-suppressor genes. Although a major commonly deleted region (CDR) has been delineated on chromosome band 5q31.1 (refs. 3-7), attempts to identify tumor suppressors within this band have been unsuccessful. We focused our analysis of gene expression on RNA from primitive leukemia-initiating cells, which harbor 5q deletions, and analyzed 12 genes within the CDR that are expressed by normal hematopoietic stem cells. Here we show that the gene encoding alpha-catenin (CTNNA1) is expressed at a much lower level in leukemia-initiating stem cells from individuals with AML or MDS with a 5q deletion than in individuals with MDS or AML lacking a 5q deletion or in normal hematopoietic stem cells. Analysis of HL-60 cells, a myeloid leukemia line with deletion of the 5q31 region, showed that the CTNNA1 promoter of the retained allele is suppressed by both methylation and histone deacetylation. Restoration of CTNNA1 expression in HL-60 cells resulted in reduced proliferation and apoptotic cell death. Thus, loss of expression of the alpha-catenin tumor suppressor in hematopoietic stem cells may provide a growth advantage that contributes to human MDS or AML with del(5q).

Dominant-negative C/ebpα and polycomb group protein Bmi1 extend short-lived hematopoietic stem/progenitor cell life span and induce lethal dyserythropoiesis.

The primitive hematopoietic stem/progenitor cells (HSPCs) during embryonic hematopoiesis are thought to be short-lived (SL) with limited self-renewal potential. The fate and consequence of these short-lived HSPCs, once reprogrammed into "long-lived" in a living animal body, remain unknown. Here we show that targeted expression of a dominant-negative C/ebpα (C/ebpαDN) in the primitive SL-HSPCs during zebrafish embryogenesis extends their life span, allowing them to survive to later developmental stage to colonize the definitive hematopoietic sites, where they undergo a proliferative expansion followed by erythropoietic dysplasia and embryonic lethality because of circulation congestion. Mechanistically, C/ebpαDN binds to a conserved C/EBP-binding motif in the promoter region of bmi1 gene, associated with a specific induction of bmi1 transcription in the transgenic embryos expressing C/ebpαDN. Targeted expression of Bmi1 in the SL-HSPCs recapitulates nearly all aberrant phenotypes induced by C/ebpαDN, whereas knockdown of bmi1 largely rescues these abnormalities. The results indicate that Bmi1 acts immediately downstream of C/ebpαDN to regulate the survival and self-renewal of HSPCs and contribute to the erythropoietic dysplasia.

Sumoylation of CCAAT/enhancer-binding protein α promotes the biased primitive hematopoiesis of zebrafish.

Hematopoiesis is evolutionarily conserved from zebrafish to mammals, and this includes both primitive and definitive waves during embryogenesis. Primitive hematopoiesis is dominated by erythropoiesis with limited myelopoiesis. Protein sumoylation, a ubiquitination-like posttranslational protein modification, is implicated in a variety of biochemical processes, most notably in transcriptional repression. We show here that the loss of 6 small ubiquitin-related modifier (SUMO) paralogs triggers a sharp up-regulation of the myeloid-specific marker mpo and down-regulation of the erythroid-specific marker gata1 in myelo-erythroid progenitor cells (MPCs) in the intermediate cell mass (ICM) during primitive hematopoiesis. Accordingly, in transgenic zebrafish lines, hyposumoylation expands myelopoiesis at the expense of erythropoiesis. A SUMO-CCAAT/enhancer-binding protein α (SUMO-C/ebpα) fusion restores the normal myelopoiesis/erythropoiesis balance, suggesting that sumoylation status of C/ebpα contributes to myelo-erythroid lineage determination. Our results therefore implicate sumoylation in early lineage determination and reveal the possible molecular mechanism underlying the puzzling biased primitive hematopoiesis in vertebrates.

Two functional microRNA-126s repress a novel target gene p21-activated kinase 1 to regulate vascular integrity in zebrafish.

RATIONALE: MicroRNAs (miRNAs) are key regulators of vascular development and diseases. The function and underlying mechanism of endothelial miRNAs have not been fully defined. OBJECTIVE: To investigate the role of endothelial miR-126 in zebrafish vascular development. METHODS AND RESULTS: Two homologs of miR-126, miR-126a (namely miR-126 in previous literature) and miR-126b, with only 1 nucleotide difference in their mature sequences, were identified in zebrafish genome. In vitro analysis showed that both precursors could sufficiently produce mature functional miRNAs. Expression analyses by Northern blot and quantitative RT-PCR showed that both miR-126s accumulated significantly 12 hours after fertilization and were specifically expressed in endothelial cells of zebrafish. Inhibition of miR-126a or miR-126b with specific morpholinos caused cranial hemorrhage, and simultaneous inhibition of both miR-126s resulted in a pronounced hemorrhage in higher percentage of embryos. Bioinformatics prediction showed that the targets of miR-126a/b partially overlapped but essentially differed. p21-activated kinase1 (pak1) was identified as a novel target of miR-126a/b, and pak1 3' untranslated region was differently regulated by these 2 miRNAs. Quantitative RT-PCR, in situ hybridization, and Western blot analyses showed that the level of pak1 was reduced when miR-126a/b were overexpressed. Notably, pak1 expression in endothelial cells was increased when miR-126a/b were knocked down. Furthermore, overexpression of the active form of human pak1 caused cranial hemorrhage, and knockdown pak1 effectively rescued the hemorrhage caused by inhibiting miR-126a/b. CONCLUSIONS: Two functional endothelial cell-specific miRNAs, miR-126a and miR-126b, synergistically regulate zebrafish vascular integrity, and pak1 is a critical target of miR-126a/b in vascular development.

Setdb2 restricts dorsal organizer territory and regulates left-right asymmetry through suppressing fgf8 activity.

Dorsal organizer formation is one of the most critical steps in early embryonic development. Several genes and signaling pathways that positively regulate the dorsal organizer development have been identified; however, little is known about the factor(s) that negatively regulates the organizer formation. Here, we show that Setdb2, a SET domain-containing protein possessing potential histone H3K9 methyltransferase activity, restricts dorsal organizer development and regulates left-right asymmetry by suppressing fibroblast growth factor 8 (fgf8) expression. Knockdown of Setdb2 results in a massive expansion of dorsal organizer markers floating head (flh), goosecoid (gsc), and chordin (chd), as well as a significant increase of fgf8, but not fgf4 mRNAs. Consequently, disrupted midline patterning and resultant randomization of left-right asymmetry are observed in Setdb2-deficient embryos. These characteristic changes induced by Setdb2 deficiency can be nearly corrected by either overexpression of a dominant-negative fgf receptor or knockdown of fgf8, suggesting an essential role for Setdb2-Fgf8 signaling in restricting dorsal organizer territory and regulating left-right asymmetry. These results provide unique evidence that a SET domain-containing protein potentially involved in the epigenetic control negatively regulates dorsal organizer formation during early embryonic development.

Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling.

HYPB is a human histone H3 lysine 36 (H3K36)-specific methyltransferase and acts as the ortholog of yeast Set2. This study explored the physiological function of mammalian HYPB using knockout mice. Homozygous disruption of Hypb impaired H3K36 trimethylation but not mono- or dimethylation, and resulted in embryonic lethality at E10.5-E11.5. Severe vascular defects were observed in the Hypb(-/-) embryo, yolk sac, and placenta. The abnormally dilated capillaries in mutant embryos and yolk sacs could not be remodeled into large blood vessels or intricate networks, and the aberrantly rounded mesodermal cells exhibited weakened interaction with endothelial cells. The embryonic vessels failed to invade the labyrinthine layer of placenta, which impaired the embryonic-maternal vascular connection. These defects could not be rescued by wild-type tetraploid blastocysts, excluding the possibility that they were caused by the extraembryonic tissues. Consistent with these phenotypes, gene expression profiling in wild-type and Hypb(-/-) yolk sacs revealed that the Hypb disruption altered the expression of some genes involved in vascular remodeling. At the cellular level, Hypb(-/-) embryonic stem cell-derived embryonic bodies, as well as in vitro-cultured human endothelial cells with siRNA-mediated suppression of HYPB, showed obvious defects in cell migration and invasion during vessel formation, suggesting an intrinsic role of Hypb in vascular development. Taken together, these results indicate that Hypb is required for embryonic vascular remodeling and provide a tool to study the function of H3K36 methylation in vasculogenesis/angiogenesis.

[Hydrochemical Characteristics and Control Factors of Groundwater in the Northwest Salt Lake Basin].

Taking the Tugeligaole sub-basin of the Jilantai Salt Lake Basin in Inner Mongolia as the typical study area, the groundwater samples of 22 points were collected, and their main characteristic indexes were tested during the wet season and the dry season separately in 2021. Mathematical statistics, Piper triangular diagrams, a Gibbs plot, ionic relations, and factor analysis were used to analyze and discuss the hydrochemical characteristics and formation mechanism of groundwater in different periods. Based on the evaluation of the groundwater quality using the water quality index(WQI) method, the potential risks of groundwater Cr6+ and F- were evaluated using the health risk evaluation model. The results showed that the groundwater was overall weakly alkaline; the dominant anions and cations during the different periods were Cl- and Na+, and the water chemistry type was mainly Cl--Na+; the groundwater quality was generally good, and the difference in water quality between the wet season and the dry season was not significant; adults and children had higher carcinogenic health risks in the dry season than that in the wet season, and the health risks of children were significantly higher than those in adults. The maximum carcinogenic health risk of drinking water exposure to Cr6+ in adults and children was higher than the maximum acceptable risk level(5×10-5). The chemical evolution of groundwater was mainly affected by evaporative concentration, evaporative salt rock dissolution, and cation exchange, and the main control factors were evaporative concentration(contribution rate of 54.19%), native geological environment factors(contribution rate of 12.99%), and carbonate rock dissolution(contribution rate of 11.66%). The study results have significance to some degree to the sustainable exploitation and utilization of groundwater resources and environmental protection of the salt lake basin.

[Water Chemical Isotope Characteristics and Water Transformation Relationship in Mongolian Section of the Yellow River Basin].

The Yellow River in Inner Mongolia was selected as the study area in this study. In July (wet season) and October (dry season) of 2021, the acquisition of seasonal rivers, the Yellow River tributaries and precipitation, the Yellow River, Wuliangsuhai, Lake Hasuhai, Lake Daihai, an irrigation canal system, and underground water and sea water samples were collected to test the water chemical composition and hydrogen and oxygen isotopic values of different water types. Using the Piper triplot, Gibbs plot, ion ratio, and MixSIAR model methods, the evolution of water chemistry in the Mongolian section of the Yellow River Basin was analyzed, and the transformation relationship between precipitation, surface water, and groundwater was revealed. The results showed that both groundwater and surface water in the study area were slightly alkaline; the dominant anion in water was Cl-, and the dominant cation was Na+. The main hydrochemical types of surface water were Cl·SO4-Na·Mg and SO4·HCO3-Na·Mg, whereas those of groundwater were Cl·SO4-Na·Mg and SO4·HCO3-Na·Ca. Groundwater Ca2+ and Mg2+ were primarily derived from the dissolution of silicate and evaporite, and surface water Ca2+ and Mg2+ were primarily derived from carbonate karst dissolution and carbonate and sulfuric acid in water participating in the dissolution process of carbonate and sulfide minerals. Na+ and Cl- in different water bodies were all affected by anthropogenic pollution sources. Owing to the seasonal effect, δD and δ18O of surface water and groundwater were higher in the wet season than in the dry season. The results showed that surface water was affected by evaporative fractionation after receiving precipitation recharge, and the groundwater recharge sources were complex. The MixSIAR model revealed that surface water was the main recharge source of groundwater, accounting for 52.4%-62.2% of the total recharge, and atmospheric precipitation was the main recharge source of surface water, accounting for 85.4%-97.1% of the total recharge.

[Risk Assessment of Heavy Metals in Dust Fall Around Reservoirs in Typical Ecologically Fragile Areas and Traceability Based on APCS-MLR Model].

To assess the health risk status and pollution sources of heavy metals in the atmosphere of ecologically vulnerable areas, the surrounding area of Dahekou Reservoir in Xilingol League was selected as the study area. From 2021 to 2022, 12 monitoring points for atmospheric dust fall were collected for a period of one year. A total of 144 samples were collected to determine the contents of eight types of heavy metals, namely Cr, Ni, Pb, Cu, Zn, Mn, As, and Cd. The potential ecological index (Eri) and health risk assessment model were used to assess the risk level of atmospheric heavy metals on ecological security and human health. The analysis of enrichment factors, principal components, and the model of absolute principal component multiple linear regression (APCS-MLR) receptor were used to analyze the sources of heavy metal pollution qualitatively in the atmosphere of the study area. The results showed that:① the mean value of the comprehensive potential ecological risk of heavy metals in the annual atmospheric dust fall in the study area was at a high ecological risk, and only the Cd value was at a very high risk level among the heavy metals, whereas the remaining were at a slight risk. ② The results of the health risk showed that intake by hand, mouth, and skin contact were the main exposure routes, which led to non-carcinogenic and carcinogenic risks. Children were under non-carcinogenic and acceptable carcinogenic risks in different months. During those months, the main source of the risks was As. ③ Through enrichment factor analysis, principal component analysis, and APCS-MLR receptor model calculation, the results revealed that the proportion of wind-blown sources was the largest, accounting for 37.82%, and the contribution rates of coal combustion and traffic sources to Cu, Cd, Pb, and Zn were 73.01%, 40.22%, 70.31%, and 32.82%, respectively. The contribution rate of mining activities to As was 42.59%, while that of industrial sources of Cd was 22.01%; the contributions of other human activity sources of Cd, As, Pb, and Zn were 21.12%, 34.40%, 23.04%, and 32.15%, respectively.

Spatiotemporal variations of ecosystem security pattern in Horqin sandy dune meadow alternating area, China.

The natural and geographical environment of ecologically fragile areas in northern China is complex. Due to heavy human disturbance and impacts of climate change, the sustainable development of ecosystems is facing serious challenges. Constructing ecological security pattern can provide decision-making basis for ecological environment protection in desertification areas. Based on land use change data of Horqin dune-meadow interphase area from 1985 to 2021, we identified ecological sources with the importance of ecosystem services and ecological sensitivity, and constructed the ecological security pattern using the minimum cumulative resistance model. We further analyzed the ecological security pattern and its development trend in 1985, 1995, 2005, 2015 and 2021, and explored the ecological spatial layout adjustment strategy. The results showed that the proportion of source area in the ecological security pattern of the study area was always small and scattered from 1985 to 2021, the network of ecological corridors was low, and the connectivity between ecological patches was lacking. The ecological security pattern had experienced a trend of deterioration first and then gradually improving. Ecological policies such as returning farmland to forest and grassland and afforestation had significantly improved the environmental security. We optimized the study area by combining the cultivated land suitability evaluation method. The ecological security pattern showed a spatial trend of 'dual-core, scattered and semi-surrounded'. The results could provide references for the construction of county-scale ecological security pattern in ecologically fragile areas and the ecological management of Horqin sands.

[Relationship Between Precipitation, River Water, and Groundwater Conversion in the Upper Reaches of Xilin River During the Rainy Season].

To deeply understand the hydrological cycle process and the transformation mechanism of different water bodies in the grassland inland river basin, the atmospheric precipitation, river water, and groundwater in the Xilin River Basin were taken as the research objects, the hydrogen and oxygen stable isotopes were analyzed, and the multi-scale spatio-temporal characteristics were analyzed to explore the quantitative transformation relationship between different water bodies in the basin. The results showed that:① the Xilin River Basin had an obvious inland semi-arid climate, the atmospheric precipitation was the main source of recharge for the river water and groundwater, and the groundwater and river water experienced different degrees of non-equilibrium evaporation at the same time. ② The isotopic composition of the river water showed the characteristics of depletion in spring and autumn and enrichment in summer and showed a trend of increasing from upstream to downstream in space. The variation in δ18O in shallow and deep groundwater during the growing season was basically the same, and the main difference between the two occurred at the end of the growing season, that is, the former tended to be stable, whereas the latter showed an upward trend, which reflected that the deep groundwater had a lagged response to the infiltration and recharge of atmospheric precipitation and surface water, and both of them were depleted gradually from southeast to northwest in space. ③ Based on the estimation results of the endmember mixing model, the average recharge ratio of atmospheric precipitation and shallow groundwater to river water in summer was 52.69% and 47.31%, respectively, indicating that shallow groundwater was an important recharge source of river water in the inland river basin even during the rainy season. The results of this study provide theoretical guidance for water resource regulation and ecological environment protection in a typical semi-arid grassland inland river basin.

An evolutionarily conserved PTEN-C/EBPalpha-CTNNA1 axis controls myeloid development and transformation.

Loss of function of tumor suppressor genes, such as PTEN, CEBPAlpha, and CTNNA1 (encoding the alpha-catenin protein), has been found to play an essential role in leukemogenesis. However, whether these genes genetically interact remains largely unknown. Here, we show that PTEN-mammalian target of rapamycin signaling acts upstream to dictate the ratio of wild-type p42 C/EBPalpha to its dominant-negative p30 isoform, which critically determines whether p30 C/EBPalpha (lower p42/p30 ratio) or p42 C/EBPalpha (higher p42/p30 ratio) binds to the proximal promoter of the retained CTNNA1 allele. Binding of p30 C/EBPalpha recruits the polycomb repressive complex 2 to suppress CTNNA1 transcription through repressive H3K27me3 modification, whereas binding of p42 C/EBPalpha relieves this repression and promotes CTNNA1 expression through activating H3K4me3 modification. Loss of Pten function in mice and zebrafish induces myelodysplasia with abnormal invasiveness of myeloid progenitors accompanied by significant reductions in both wild-type C/EBPalpha and alpha-catenin protein. Importantly, frame-shift mutations in either PTEN or CEBPA were detected exclusively in the primary LICs with low CTNNA1 expression. This study uncovers a novel molecular pathway, PTEN-C/EBPalpha-CTNNA1, which is evolutionarily conserved and might be therapeutically targeted to eradicate LICs with low CTNNA1 expression.

[Temporal and spatial variations of annual precipitation and meteorological drought in China during 1951-2018]. / 1951­2018年中国年降水量及气象干旱的时空变异.

Exploring the temporal and spatial variations of precipitation and drought is an important topic in hydro-logy. Based on the precipitation data of 619 meteorological stations in China from 1951 to 2018, we used anomaly percentage method and Morlet wavelet analysis to analyze the temporal and spatial variations of annual precipitation and drought. The results showed that annual precipitation in China showed a stepwise decreasing trend from southeast to northwest during the study period, and that the intensity of annual precipitation change was on the contrary. The precipitation near the boundary of the second and third steps showed a downward trend, and the abrupt change of precipitation occurred mainly in the 1960s and 1970s. The rest region was on the rise, with substantial changes in the 1990s. The main period of precipitation was short in the regions with temperate continental climate and temperate monsoon climate. From 1960s to 2010s, the area of arid land in China had decreased, while that of the semi-arid area and semi-humid area had increased gradually, especially in the recent decade. An aridity boundary was found between 30° N and 40° N, with drought frequency in its north being much more than the south. On the whole, the frequency and scope of drought events showed a decreasing trend and its interdecadal shift direction was from the central part of northwest China to the southern part of North China and then to the northern part of North China.

Mir-144 selectively regulates embryonic alpha-hemoglobin synthesis during primitive erythropoiesis.

Precise transcriptional control of developmental stage-specific expression and switching of alpha- and beta-globin genes is significantly important to understand the general principles controlling gene expression and the pathogenesis of thalassemia. Although transcription factors regulating beta-globin genes have been identified, little is known about the microRNAs and trans-acting mechanism controlling alpha-globin genes transcription. Here, we show that an erythroid lineage-specific microRNA gene, miR-144, expressed at specific developmental stages during zebrafish embryogenesis, negatively regulates the embryonic alpha-globin, but not embryonic beta-globin, gene expression, through physiologically targeting klfd, an erythroid-specific Krüppel-like transcription factor. Klfd selectively binds to the CACCC boxes in the promoters of both alpha-globin and miR-144 genes to activate their transcriptions, thus forming a negative feedback circuitry to fine-tune the expression of embryonic alpha-globin gene. The selective effect of the miR-144-Klfd pathway on globin gene regulation may thereby constitute a novel therapeutic target for improving the clinical outcome of patients with thalassemia.