•This study estimated groundwater storage information of China.•The groundwater storage was certificated to be reliable and accurate.•The causes of groundwater storage changes in different basins ...were analyzed.
As an important freshwater resource, groundwater is of great significance to agriculture, industry, and daily life. The investigation of groundwater storage (GWS) in different regions of China is critical for water resource management and conservation. However, previous studies used different methods and data to monitor GWS in different regions of China, which made their results difficult to compare and cross validate. Here, we used a unified method by the Gravity Recovery and Climate Experiment (GRACE) satellite data and global models to study the variations of GWS in 10 major basins in China from April 2002 to December 2016. Results showed that GWS in the i) Songhua River basin (SRB), Liao River basin (LRB), Haihe River basin (HRB), Yellow River basin (YRB), Huaihe River basin (HHRB), and southeast basin (SEB) exhibited decreasing trends, ii) Yangtze River basin (YZRB) and Pearl River basin (PRB) presented increasing trends, and iii) southwest basin (SWB) and continental basin (CB) displayed both decreasing and increasing trends during the study period. These results were validated by comparing them with a large number of previous studies, which revealed that they were accurate and reliable. Comparing with the climate data and bulletin data, the analysis of causes for these trends indicated that drought and irrigation water-use led to a decline in GWS in several basins of northern China. The decreasing trend of GWS in the SEB was related to water use for production, whereas groundwater recharge from precipitation drove the increasing trends of GWS in the YZRB and PRB. In contrast, the wide geographical areas and complex factors of the SWB and CB led to the increasing–decreasing trends of GWS. This study enriches the GWS for China over the past decade, especially for SEB, PRB, and CB with rare GWS information. It will be helpful for the country’s groundwater resource management and systematic water conservation.
Results of a five-year research project and several industrial collaborations have produced tools that model the individual effects and complex dynamic interactions between an IT system's application ...workload and resource contention at multiple levels in the execution environment. An evaluation shows significant resource efficiency gains without sacrificing the performance specified in service-level agreements.
Cholestatic liver diseases comprise a variety of disorders of bile formation and/or flow which generally result in progressive hepatobiliary injury. Regulation of bile acid (BA) synthesis and ...homeostasis is a promising strategy for the treatment of cholestatic liver disease. Limb expression 1-like protein (LIX1L) plays an important role in post-transcriptional gene regulation, yet its role in cholestatic liver injury remains unclear.
LIX1L expression was studied in patients with primary sclerosing cholangitis (PSC) or primary biliary cholangitis (PBC), and 3 murine models of cholestasis (bile duct ligation BDL, Mdr2 knockout Mdr2-/-, and cholic acid CA feeding). Lix1l knockout mice were employed to investigate the function of LIX1L in cholestatic liver diseases. Chromatin immunoprecipitation assays were performed to determine whether Egr-1 bound to the Lix1l promoter. MiRNA expression profiling was analyzed by microarray. An adeno-associated virus (AAV)-mediated hepatic delivery system was used to identify the function of miR-191-3p in vivo.
LIX1L expression was increased in the livers of patients with PSC and PBC, and in the 3 murine models, as well as in BA-stimulated primary mouse hepatocytes. BA-induced Lix1l upregulation was dependent on Egr-1, which served as a transcriptional activator. LIX1L deficiency attenuated cholestatic liver injury in BDL and Mdr2-/- mice. MiR-191-3p was the most reduced miRNA in livers of WT-BDL mice, while it was restored in Lix1l-/--BDL mice. MiR-191-3p targets and downregulates Lrh-1, thereby inhibiting Cyp7a1 and Cyp8b1 expression. AAV-mediated hepatic delivery of miR-191-3p significantly attenuated cholestatic liver injury in Mdr2-/- mice.
LIX1L deficiency alleviates cholestatic liver injury by inhibiting BA synthesis. LIX1L functions as a nexus linking BA/Egr-1 and miR-191-3p/LRH-1 signaling. LIX1L and miR-191-3p may be promising targets for the treatment of BA-associated hepatobiliary diseases.
Bile acid homeostasis can be impaired in cholestatic liver diseases. Our study identified a novel mechanism of positive feedback regulation in cholestasis. LIX1L and miR-191-3p represent potential therapeutic targets for cholestatic liver diseases.
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•LIX1L was upregulated in cholestatic liver specimens from both patients and mouse models.•Bile acids triggered upregulation of Egr-1, which induced LIX1L expression.•LIX1L deficiency alleviated cholestatic liver injury by inhibiting bile acid synthesis.•Overexpression of miR-191-3p using AAV protected against cholestatic liver injury in mouse models.
Background We report five patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), four of whom presented with precocious puberty and one with growth hormone deficiency (GHD. Our five children ...add to the growing endocrine data base of MRKHS. Case presentation We retrospectively reviewed clinical data of 5 MRKHS patients from 2017 to 2020. The clinical features, hormonal profiles, radiological imaging and genetic analyses were collated. The age range of the 5 patients at diagnosis was 6.7-9.1 years. Four presented with premature thelarche, and one presented with short stature. External genitalia were normal in all patients. Gonadotropin-releasing hormone stimulation tests for the 5 patients revealed peak luteinizing hormone and follicular stimulating hormone levels of 3.57, 6.24, 11.5, 4.44 and 4.97 IU/L and 9.41, 16.7, 13.8, 14.2 and 10.3 mIU/mL, respectively. Growth hormone stimulation for one patient with short stature was consistent with GHD with a peak level of GH was 7.30 ng/mL. Imaging disclosed advanced bone age in four patients and no skeletal abnormalities in any of the patients. Ultrasonography of the abdomen revealed bilateral polycystic kidneys in one patient. Pelvic magnetic resonance imaging confirmed no uterus in five patients. All of the patients had a normal karyotype (46, XX). In one patient, whole-exome sequencing detected a deletion of 17q12(chr17:36,046,434-36,105,050, hg19) encompassing the HNF1B gene. Conclusions We report the unusual co-occurrence of precocious puberty and GHD in patients with MRKHS, highlighting that abnormal puberty and growth development may represent initial unexplained manifestations. Whether the deletion of 17q 22 begat GHD is unclear. Keywords: Mayer-Rokitansky-kuster-Hauser syndrome, Children, Precocious puberty, Growth hormone deficiency, Case report
ALT-803, a complex of an interleukin (IL)-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein, was found to exhibit significantly stronger in vivo biologic activity on NK and T ...cells than IL-15. In this study, we show that a single dose of ALT-803, but not IL-15 alone, eliminated well-established 5T33P and MOPC-315P myeloma cells in the bone marrow of tumor-bearing mice. ALT-803 treatment also significantly prolonged survival of myeloma-bearing mice and provided resistance to rechallenge with the same tumor cells through a CD8(+) T-cell-dependent mechanism. ALT-803 treatment stimulated CD8(+) T cells to secrete large amounts of IFN-γ and promoted rapid expansion of CD8(+)CD44(high) memory T cells in vivo. These memory CD8(+) T cells exhibited ALT-803-mediated upregulation of NKG2D (KLRK1) but not PD-1 (PDCD1) or CD25 (IL2RA) on their cell surfaces. ALT-803-activated CD8(+) memory T cells also exhibited nonspecific cytotoxicity against myeloma and other tumor cells in vitro, whereas IFN-γ had no direct effect on myeloma cell growth. ALT-803 lost its antimyeloma activity in tumor-bearing IFN-γ knockout mice but retained the ability to promote CD8(+)CD44(high) memory T-cell proliferation, indicating that ALT-803-mediated stimulation of CD8(+)CD44(high) memory T cells is IFN-γ-independent. Thus, besides well-known IL-15 biologic functions in host immunity, this study shows that IL-15-based ALT-803 could activate CD8(+)CD44(high) memory T cells to acquire a unique innate-like phenotype and secrete IFN-γ for nonspecific tumor cell killing. This unique immunomodulatory property of ALT-803 strongly supports its clinical development as a novel immunotherapeutic agent against cancer and viral infections.
This study aimed to test the mediating role of knowledge sharing, which includes two central processes of knowledge collecting and knowledge donating, in the relationship of psychological capital and ...innovative work behavior (IWB). The proposed theoretical framework was based on the theory of reasoned action and social exchange theory. In a field study, using a research sample of 345 valid leader-subordinate matching data, we tested three competitive models to explore the different mediating effects of knowledge collecting and donating. Results indicated that knowledge donating and knowledge collecting played a chain mediating role between psychological capital and IWB, and the independent mediating effect of knowledge collecting was also significant. From the perspective of knowledge sharing, the present study deeply analyzes the psychological processing mechanism of psychological capital on IWB, confirms the positive significance of knowledge donating at the individual level, and provides a new perspective for organizations to promote employees' knowledge sharing and stimulate their IWB.
IL15, a potent stimulant of CD8(+) T cells and natural killer (NK) cells, is a promising cancer immunotherapeutic. ALT-803 is a complex of an IL15 superagonist mutant and a dimeric IL15 receptor ...αSu/Fc fusion protein that was found to exhibit enhanced biologic activity in vivo, with a substantially longer serum half-life than recombinant IL15. A single intravenous dose of ALT-803, but not IL15, eliminated well-established tumors and prolonged survival of mice bearing multiple myeloma. In this study, we extended these findings to demonstrate the superior antitumor activity of ALT-803 over IL15 in mice bearing subcutaneous B16F10 melanoma tumors and CT26 colon carcinoma metastases. Tissue biodistribution studies in mice also showed much greater retention of ALT-803 in the lymphoid organs compared with IL15, consistent with its highly potent immunostimulatory and antitumor activities in vivo. Weekly dosing with 1 mg/kg ALT-803 in C57BL/6 mice was well tolerated, yet capable of increasing peripheral blood lymphocyte, neutrophil, and monocyte counts by >8-fold. ALT-803 dose-dependent stimulation of immune cell infiltration into the lymphoid organs was also observed. Similarly, cynomolgus monkeys treated weekly with ALT-803 showed dose-dependent increases of peripheral blood lymphocyte counts, including NK, CD4(+), and CD8(+) memory T-cell subsets. In vitro studies demonstrated ALT-803-mediated stimulation of mouse and human immune cell proliferation and IFNγ production without inducing a broad-based release of other proinflammatory cytokines (i.e., cytokine storm). Based on these results, a weekly dosing regimen of ALT-803 has been implemented in multiple clinical studies to evaluate the dose required for effective immune cell stimulation in humans.
The novel Graves disease (GD) model was established in BALB/c mice with recombinant adenovirus expressing the full-length human TSHR (Ad-TSHR289) by three times immunizations for nearly three months. ...Reducing the frequency of immunizations may shorten the modeling time to improve the efficiency of the study. In this study, female BALB/c mice were immunized one time with an adenovirus expressing the autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). At the 3, 6, 12, 17 weeks after the immunization, mice were sacrificed. The blood was collected and thyroids were removed. T3, T4, TRAB and thyroid weight/body weight (TW/BW) were tested. Compared with the Normal control (NC) group, the incidence of hyperthyroidism at 3, 6, 12 and 17 weeks after immunization were about 66.67%, 100%, 100%, and 100%. Meanwhile, the incidences of goiter were nearly 50%, 83.33%, 100% and 100% at the same stages. Therefore, modeling rates of GD were about 50%, 83.33%, 100%, 100% at 3, 6, 12 and 17 weeks after immunization. T3 in serum continues to increase from 3 weeks to 17 weeks after immunization. Serum TRAb reached to peak at 6 weeks and remained from 12 weeks after immunization, while T4 and TW/BW had kept steady from 6 weeks. There are positive correlations between T3, T4 and TRAb, TRAb and TW/BW, as well as T3, T4 and TW/BW. GD model can be constructed by primary immunization with Ad-TSHR289, which could be detected at 3 weeks and at least until the 17 weeks after primary immunization. It would improve the efficiency of GD research.
Abstract
Copper powder is prepared by electrolysis, and additives Sodium dodecyl benzene sulfonate (SDBS) and polyvinyl pyrrolidone (PVP) are added to the electrolyte. Through the synergy effect of ...the two additives, the shielding effect between metal atoms is enhanced, and as a consequence the microscopic morphology is changed and it the powder performance is improved. Scanning electron microscopy (SEM), x-ray diffraction (XRD) and Electrochemical Impedance Spectroscopy (EIS) are used to characterize the copper powder. The results show that when the content of SDBS and PVP is 5 g l
−1
and 1.5g l
−1
respectively, the new type of thin and long dendrite copper powder can be obtained by electrolysis.
Primary cilia (PC) are non-motile and microtube-based organelles protruding from the surface of almost all thyroid follicle cells. They maintain homeostasis in thyrocytes and loss of PC can result in ...diverse thyroid diseases. The dysfunction of structure and function of PC are found in many patients with common thyroid diseases. The alterations are associated with the cause, development, and recovery of the diseases and are regulated by PC-mediated signals. Restoring normal PC structure and function in thyrocytes is a promising therapeutic strategy to treat thyroid diseases. This review explores the function of PC in normal thyroid glands. It summarizes the pathology caused by PC alterations in thyroid cancer (TC), autoimmune thyroid diseases (AITD), hypothyroidism, and thyroid nodules (TN) to provide comprehensive references for further study.
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