Anemoside B4 Exerts Hypoglycemic Effect by Regulating the Expression of GLUT4 in HFD/STZ Rats.

Anemoside B4 (B4) is a saponin that is extracted from Pulsatilla chinensis (Bge.), and Regel exhibited anti-inflammatory, antioxidant, antiviral, and immunomodulatory activities. However, its hypoglycemic activity in diabetes mellitus has not been evaluated. Here, we explored the effect of B4 on hyperglycemia and studied its underlying mechanism of lowering blood glucose based on hyperglycemic rats in vivo and L6 skeletal muscle cells (L6) in vitro. The rats were fed a high-fat diet (HFD) for one month, combined with an intraperitoneal injection of 60 mg/kg streptozotocin (STZ) to construct the animal model, and the drug was administrated for two weeks. Blood glucose was detected and the proteins and mRNA were expressed. Our study showed that B4 significantly diminished fasting blood glucose (FBG) and improved glucose metabolism. In addition, B4 facilitated glucose utilization in L6 cells. B4 could enhance the expression of glucose transporter 4 (GLUT4) in rat skeletal muscle and L6 cells. Mechanistically, B4 elevated the inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. Furthermore, we confirmed the effect of B4 on glucose uptake involved in the enhancement of GLUT4 expression in part due to PI3K/AKT signaling by using a small molecule inhibitor assay and constructing a GLUT4 promoter plasmid. Taken together, our study found that B4 ameliorates hyperglycemia through the PI3K/AKT pathway and promotes GLUT4 initiation, showing a new perspective of B4 as a potential agent against diabetes.

Enhancing the insecticidal activity of new Bacillus thuringiensis X023 by copper ions.

BACKGROUND: A new Bacillus thuringiensis X023 (BtX023) with high insecticidal activity was isolated in Hunan Province, China. The addition of metals (Cu, Fe, Mg and Mn) to the medium could influence the formation of spores and/or insecticidal crystal proteins (ICPs). In previous studies, Cu ions considerably increased the synthesis of ICPs by enhancing the synthesis of poly-ß-hydroxy butyrate. However, the present study could provide new insights into the function of Cu ions in ICPs. RESULTS: Bioassay results showed that wild strain BtX023 exhibited high insecticidal activity against Plutella xylostella. The addition of 1 × 10-5 M Cu2+ could considerably increase the expression of cry1Ac and vip3Aa, and the insecticidal activity was enhanced. Quantitative real-time polymerase chain reaction (qRT-PCR) and proteomic analyses revealed that the upregulated proteins included amino acid synthesis, the glyoxylate pathway, oxidative phosphorylation, and poly-ß-hydroxy butyrate synthesis. The Cu ions enhanced energy metabolism and primary amino acid synthesis, will providing abundant raw material accumulation for ICP synthesis. CONCLUSION: The new strain BtX023 exerted a strong insecticidal effect on P. xylostella by producing ICPs. The addition of 1 × 10-5 M Cu2+ in the medium could considerably enhance the expression of the cry1Ac and vip3Aa genes, thereby further increasing the toxicity of BtX023 to Helicoverpa armigera and P. xylostella by enhancing energy synthesis, the glyoxylate cycle, and branched-chain amino acids synthesis, but not poly-ß-hydroxy butyrate synthesis.

Comprehensive study of dexamethasone on albumin biogenesis during normal and pathological renal conditions.

CONTEXT: Dexamethasone (DXM) has an anti-immunoinflammatory effect, and is often used in acute kidney injury (AKI). However, the effects of DXM on albumin (ALB) have not been fully studied. OBJECTIVE: To investigate the effects of DXM on ALB production and renal function. MATERIALS AND METHODS: Male Wistar rats were divided into normal and DXM groups (0.25, 0.5, 1 mg/kg for 5 days) (n = 15) for a dose-dependent study. Rats were divided into normal group and DXM groups (0.5 mg/kg for 3, 5, 7 days) (n = 9) for a time-dependent study. In AKI experiment, rats were divided into normal (saline), cisplatin (CP, 5 mg/kg, i.v.), CP + DXM groups (0.25, 0.5 and 1 mg/kg, i.m.) (n = 16). The blood and the organs were isolated for analysis. RESULTS: In normal, serum ALB (sALB) and serum total protein (sTP) increased in DXM group with sALB increased 19.8-32.2% (from small to large dosages); and 30.2-32.5.6% (from 3 to 7 days of DXM); sTP 15.7-22.6% and 14.2-24.3%; urine ALB (uALB) 31.5-392.3%, and 1047.2-1390.8%; urine TP (uTP) 0.68-173.1% and 98.0-504.9%, compared with normal groups. DXM increased the mRNA expression of Cebp and Hnf, suppressing podocin. In AKI, DXM decreased serum BUN (53.7%), serum Cre (73.4%), sALB (30.0%), sTP (18.7%), uALB (74.5%), uTP (449.3%), rescuing the suppressed podocin in kidney. CONCLUSIONS: DXM acts on Cebp and Hnf and promotes ALB production. This finding helps to evaluate the rationale of DXM for kidney injury.

[Study on therapeutic effect and its related mechanism of anemoside B4 on ischemia reperfusion injury induced by renal artery and vein ligation in rats].

The aim of this paper was to investigate the effect and mechanism of anemoside B4 on renal ischemia reperfusion injury in rats. A total of 50 rats were randomly divided into the model group(NS) and anemoside B4 low-dose(1.25 mg·kg~(-1)), medium-dose(2.5 mg·kg~(-1)) and high-dose(5 mg·kg~(-1)) groups after the right kidney was removed and the left kidney was ligated to make the ischemia reperfusion model. Another 10 rats were selected as sham operation group only for normal control group(NS, received normal saline). Automatic biochemical analyzer was used to measure serum blood urea nitrogen(BUN), creatinine(Cre), cerebrospinal fluid(CSF) and urinemicroalbumin(mALB) levels after 5 days of tail vein injection treament. Total urine protein and total urinary albu-min were calculated and kidney samples were collected. Histopathological changes of renal tissues were observed by PAS staining. Western blot analysis was performed to detect the protein expressions of TLR4 and NF-κB in renal inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway. The results showed that the levels of BUN, Cre, urinary total protein and urinary total albumin in the model group were significantly increased(P<0.01), with severe renal tubule injury was serious, manifested by obvious expansion of renal tubules, more serious tubular proteins, and some tubular epithelial cells were exfoliated. At the same time, the expression of inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway increased significantly(P<0.01 or P<0.05). The levels of BUN, Cre were reduced in different doses of anemoside B4(P<0.05). The levels of total urinary protein and total urinary albumin were decreased in the low and high dose groups of anemoside B4.The level of total urinary albumin in the high-dose group of anemoside B4 was significantly reduced(P<0.05).Renal tubular injury was alleviated, tubular epithelial cell exfoliation was reduced, and the expression of related inflammatory factors was reduced in different degrees(P<0.01 or P<0.05). This study showed that anemoside B4 could alleviate renal ischemia-reperfusion injury in rats. And its mechanism may be related to the inhibition of inflammatory factors related to response mediated by NLRP3 pathway and TLR4/NF-κB pathway by anemoside B4.

Comparison of the TLR4/NFκB and NLRP3 signalling pathways in major organs of the mouse after intravenous injection of lipopolysaccharide.

Context: Lipopolysaccharide (LPS) is often used to induce immunoinflammatory reactions. TLR4/NFκB and NLRP3 signalling are major factors for inflammation. Dexamethasone (DXM) has an anti-immunoinflammatory effect. Objective: To investigate the inflammatory reaction in pathological changes of organs and the expression of inflammatory signalling during LPS infection. Materials and methods: ICR mice were divided into control group (n = 9), LPS group (n = 15) and LPS + DXM group (n = 14). LPS (10 mg/kg) was injected intravenously in LPS group and LPS + DXM group, normal saline was injected to the control group; DXM (0.5 mg/kg) was given by intragastric administration. 12 h after LPS, the blood was collected and the organs were isolated for biochemical analysis, protein expression, and morphological examination. Results: The results showed that BUN, Cre, ALT, AST in the LPS group increased distinctly by 81.42, 67.84, 40.53 and 36.05%, respectively, and CK, ALP, TP and ALB decreased by 71.37, 60.6, 12.57 and 19.73%, respectively, compared with the control group. In the morphologic observation, local necrosis in the liver, arterial vasodilation in the heart and kidney, alveolar secretions and pulmonary interstitial in the lungs, and mucosal shedding in the small and large intestines, the expression of TLR4-NFκB signalling were up-regulated distinctly whereas NLRP3 signalling was less broadly affected. DXM can decrease BUN and Cre, downregulate the expression of TLR4-NFκB signalling, but has no effect on the organ damage based on morphology. Conclusion: Acute injuries induced by LPS are extensive. The inflammatory damage in small and large intestines, liver and kidney was more severe than other organs. TLR4-NFκB signalling was the major response to LPS stress.

[Study on acute kidney injury model induced by renal ischemia-reperfusion in rats].

In this study,in-depth systematic evaluation of rat of acute kidney injury(AKI) caused by renal arteriovenous ligation was conducted to better master and apply this model for drug research. Male SD rats of 2-3 months old were employed in this study.The left kidney was removed,and the right kidney received ligation for 40 min and reperfusion for 24 h. Serum creatinine(Crea),urea nitrogen(BUN) and the renal tissue sections were assayed as the basic indicators to evaluate their renal function. The mRNA expression of inflammatory necrosis factors and apoptotic factors was used to evaluate the mechanism of molecular pathophysiological changes. The results showed that the serum Crea and BUN caused by ligation of both renal arteries and veins were significantly higher than those of rats with renal artery ligation. After renal arteriovenous ligation for 40 min and reperfusion for 24 h in rats,the serum Crea of the rats varied from less than 100 µmol·L-1 to more than 430 µmol·L-1. Among them,5 rats showed less than 100 µmol·L-1 serum Crea,20 rats with 100-200 µmol·L-1 serum Crea and 12 rats with more than 430 µmol·L-1. Rats with serum Crea between 300-430 µmol·L-1 accounted for 66.3%(122/184) of the total number of the experiment rats. After 72 h reperfusion,serum Crea in the group of Crea 370-430 µmol·L-1 continued to increase,while the serum Crea in the group of Crea 200-300 µmol·L-1 and the group of Crea 300-370 µmol·L-1 recovered quickly. No matter serum Crea was elevated or decreased,the renal tubules showed pathological changes such as vacuolar degeneration or even necrosis. The mRNA expression levels of Toll-like receptor(TLR4),tumor necrosis factor(TNF-α) and interleukin(IL-6) in renal tissueswere significantly up-regulated,and the effect was most obvious in the group of serum Crea 370-430 µmol·L-1. The study indicated that the model for AKI caused by renal arteriovenous ligation and reperfusion is easy to operate,and the serum Crea and BUN have the characteristics of continuous increase,beneficial to the observation of drug effects. This acute kidney injury is mainly related to the pathophysiological response of inflammatory necrosis.

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution.

Shenmai injection (SMI) is a Chinese patent-protected injection, which was mainly made of Red Ginseng and Radix Ophiopogonis and widely used for treating coronary heart disease and tumors by boosting Qi and nourishing Yin. In this study we examined whether SMI could produce direct synergetic effects on the cytoxicity of adriamycin (ADR) and paclitaxel (PTX) in colorectal cancers in vivo and in vitro, and explored the underlying pharmacokinetic mechanisms. BALB/c nude mice with LoVo colon cancer xenografts were intraperitoneally injected with ADR (2 mg·kg-1·3d-1) or PTX (7.5 mg·kg-1·3d-1) with or without SMI (0.01 mL·g-1·d-1) for 13 d. Co-administration of SMI significantly enhanced the chemotherapeutic efficacy of ADR and PTX, whereas administration of SMI alone at the given dosage did not produce visible anti-cancer effects, The chemosensitizing action of SMI was associated with increased concentrations of ADR and PTX in the plasma and tumors. In Caco-2 and LoVo cells in vitro, co-treatment with SMI (2 µL/mL) significantly enhanced the cytotoxicity of ADR and PTX, and resulted in some favorable pharmacokinetic changes in the subcellular distribution of ADR and PTX. In addition, SMI-induced intracellular accumulation of ADR was closely correlated with the increased expression levels of P-glycoprotein in 4 colon cancer cell lines (r2=+0.8558). SMI enhances the anti-cancer effects of ADR and PTX in colon cancers in vivo and in vitro by improving the subcellular distributions of ADR and PTX.

Experiences and insomnia-associated factors in Chinese breast cancer survivors: a qualitative study.

AIMS AND OBJECTIVES: This study aimed to explore the experiences and factors associated with insomnia in Chinese breast cancer survivors. BACKGROUND: Insomnia is a common and significant symptom in breast cancer survivors. Quantitative studies are unable to describe the experience of insomnia and the sleep-associated factors from a personal point of view. A profound understanding of the experience of insomnia in breast cancer survivors can provide information for health workers and caregivers to allow them to provide more effective support. DESIGN: A descriptive qualitative research was adopted. METHODS: In-depth interviews were conducted with 22 insomniac breast cancer survivors. A qualitative content analysis was used to analyse the data. RESULTS: Three themes emerged concerning the experiences of insomnia, including sleep neglect, insomnia perception and insomnia anxiety. Participants reported their own opinions on three insomnia-associated factors, including factors associated with hospitalisation, factors associated with breast cancer and the therapies and too much attention placed on sleep. CONCLUSIONS: Survivors would neglect their sleep problems in the early stage after diagnosis. When they became aware of their sleep problems, they were inclined to worry too much and sought help from traditional Chinese medicine. Anticipatory sleep anxiety, excessive negative cognitive activities and insomnia became a vicious circle for insomniac breast cancer survivors. RELEVANCE TO CLINICAL PRACTICE: The findings provide detailed information to help nurses understand the experiences of breast cancer survivors with insomnia. Nurses could provide proper care to help prevent insomnia or improve sleep.

Optimization of Maximum Light Use Efficiency in Inner Mongolian Steppe.

For the case that the value of the maximum light use efficiency (MLUE) is not optimized for different steppes, we simulated the MLUE for meadow steppe, typical steppe and desert steppe in Inner Mongolia based on the field observed NPP and CASA ecosystem model, and analyzed the spatial and temporal pattern of the LUE and net primary productivity (NPP) in Inner Mongolia. The result indicate that the MLUE is optimized to be 0.654，0.553 and 0.511 gC·MJ-1 for meadow steppe, typical steppe and desert steppe in Inner Mongolia, respectively, with an average of 0.573 gC·MJ-1. Compared to the result that used same value of 0.541 gC·MJ-1 for MLUE, the correlation coefficient and relative mean square error was improved 0.024 and 2.62 gC·(m2·month-1)-1, respectively after optimization. Affected by the hydrothermal condition and distribution of grassland types, the LUE and NPP in Inner Mongolia decreased from northeast to southwest, and showed one crest shape. However, the maximum value of LUE and NPP was appeared in August and July. This difference could be attributed to the difference in the maximum value between absorbed photosynthetically active radiation and LUE. The LUE and NPP decreased by meadow steppe, typical steppe and desert steppe.

Posttraumatic growth and psychological distress in Chinese early-stage breast cancer survivors: a longitudinal study.

OBJECTIVE: To describe the dynamic changes in posttraumatic growth (PTG) and psychological distress in hospitalized early-stage breast cancer (BC) survivors over a 6-month period. METHODS: A longitudinal study design was adopted. The PTG inventory (PTGI) and distress management screening measure were used 3 months after diagnosis, then again at 6 and 9 months after diagnosis. For baseline data, 155 BC patients who were receiving chemotherapy were selected from four first-class tertiary hospitals in Beijing from April 2010 to March 2011 using a purposive sampling method. Of these, 120 BC patients completed the follow-up investigation. A repeated measures analysis of variance, followed by least significant difference post-hoc analysis, was used to compare PTG and psychological distress. RESULTS: The total score of the PTGI was 62.72 ± 14.66 in BC survivors at 3 months after diagnosis.There was a weak negative relationship between PTG and psychological distress (r = ­0.282, p<0.001).PTG increased and psychological distress decreased from 3 to 9 months after diagnosis. The PTGI scores were 63.24 ± 14.21, 68.26 ± 15.29, and 70.29 ± 16.07 at 3, 6, and 9 months after diagnosis, respectively, with distress thermometer scores of 3.62 ± 1.98, 2.59 ± 2.00, and 2.51 ± 1.00, respectively. CONCLUSIONS: At 3 months after diagnosis, BC survivors develop PTG at a low level while they are receiving chemotherapy. PTG showed a weak negative association with psychological distress. The level of PTG shows an increasing tendency, whereas the degree of psychological distress exhibits a downward trend in the 9 months after diagnosis.

Precise prediction of phase-separation key residues by machine learning.

Understanding intracellular phase separation is crucial for deciphering transcriptional control, cell fate transitions, and disease mechanisms. However, the key residues, which impact phase separation the most for protein phase separation function have remained elusive. We develop PSPHunter, which can precisely predict these key residues based on machine learning scheme. In vivo and in vitro validations demonstrate that truncating just 6 key residues in GATA3 disrupts phase separation, enhancing tumor cell migration and inhibiting growth. Glycine and its motifs are enriched in spacer and key residues, as revealed by our comprehensive analysis. PSPHunter identifies nearly 80% of disease-associated phase-separating proteins, with frequent mutated pathological residues like glycine and proline often residing in these key residues. PSPHunter thus emerges as a crucial tool to uncover key residues, facilitating insights into phase separation mechanisms governing transcriptional control, cell fate transitions, and disease development.

Postmarketing studies on safety of Dengfeng shenmai injection.

OBJECTIVE: To systematically research the postmarketing safety of Dengfeng shenmai injection, identify potential risk factors, and ensure its clinical safety. METHODS: We investigated a comprehensive series of studies on the production process, quality standards, pharmacology, postmarketing clinical studies, and safety evaluation of Shenmai injection, including literature analysis of adverse drug reaction (ADR) case analysis and systematic review. Data from the hospital information system (HIS) and spontaneous reporting system (SRS) were also analyzed. RESULTS: The approximate dosage leading to death in dogs is 45.0-67.5 g raw drug/kg and the toxic reactions are restlessness, skin irritation, salivation, and vomiting. The results of chronic toxicity tests in mice and dogs, and the other tests such as 6-month toxicity, drug safety, genetic toxicity, and reproductive toxicity of rats and dogs, were positive or qualified. Patient ADR history and ADR family history were closely associated with itching based on the data analysis from SRS. There was no damage to renal function from Shenmai injection use at a dosage and a treatment course outside the recommended dosage and treatment course as specified based on data analysis from HIS. The most common ADR from Shenmai injection are difficulty breathing, facial flushing, nausea, vomiting, chest tightness, skin itching, rash, and back pain. CONCLUSION: This study includes complete information on Shenmai injection ADR incidence rate. We found that Shenmai injection is safe and this study can provide clinical, research, and production institutions with an objective, reliable, and scientific basis for use of Shenmai injection.

Protective effects of GuanXinNing tablet (GXNT) on diabetic encephalopathy in zucker diabetic obesity (ZDF) rats.

BACKGROUND: Diabetic encephalopathy (DE) is a complication of diabetes that leads to cognitive and behavioral decline. Utilizing safe and effective complementary and alternative medications for its management is a wise choice. Previous studies have shown that GuanXinNing Tablet (GXNT), an oral preparation primarily derived from two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., exerts a beneficial neuroprotective effect. In this study, we explored the protective effects of GXNT on DE in male Zucker diabetic fatty (ZDF) rats induced by a high-fat diet, aiming to ascertain its significance and potential mechanisms. METHODS: ZDF rats were induced to develop type 2 diabetes (T2DM) with DE by a high-fat diet and treated with GXNT for 8 weeks until they were 20 weeks old. Throughout the experiment, the animals' vital parameters, such as body weight, were continuously monitored. Cognitive function was evaluated using the Y maze test. Biochemical kits were employed to analyze blood glucose, lipids, and vascular endothelial-related factors. Cerebrovascular lesions were assessed using magnetic resonance angiography (MRA) imaging. Brain lesions were evaluated using hematoxylin and eosin (H&E) staining and ultrastructure observation. IgG and albumin (ALB) leakage were detected using immunofluorescence. RESULTS: GXNT demonstrated an enhancement in the overall well-being of the animals. It notably improved cognitive and behavioral abilities, as demonstrated by extended retention time in the novel heterogeneous arm during the Y-maze test. GXNT effectively regulated glucose and lipid metabolism, reducing fasting and postprandial blood glucose, glycated hemoglobin (HbA1c), and total cholesterol (TC) levels. Additionally, it exhibited a protective effect on the vascular endothelium by reducing the serum TXB2/PGI2 ratio while elevating NO and PGI2 levels. Moreover, GXNT ameliorated stenosis and occlusion in cerebral vessel branches, increased the number of microvessels and neurons around the hippocampus, and improved microvascular occlusion in the cerebral cortex, along with addressing perivascular cell abnormalities. Immunofluorescence staining showed a decrease in the fluorescence intensity of IgG and ALB in the cerebral cortex. CONCLUSIONS: GXNT demonstrated a highly satisfactory protective effect on DE in ZDF rats. Its mechanism of action could be based on the regulation of glucolipid metabolism and its protective effect on the vascular endothelium.

Low-dose lipopolysaccharide inducing continuous and obvious increase in urinary protein in hyperglycemic rats and the underlying mechanism.

Proteinuria is an important hallmark of diabetic nephropathy models, however it takes a long time for the proteinuria and is not stable. Therefore, low-dose lipopolysaccharide (LPS) was investigated in this work to induce rapid and stable proteinuria in hyperglycemic rats and the underlying mechanism was studied. Hyperglycemia rats was induced by high-fat feeding combined with intraperitoneal injection of streptozotocin (STZ). After 21 days, the model rats received a subinjury dose of 0.8 mg / kg LPS intraperitoneally (i.p.). We detected related biochemical indexes at different time periods after LPS injection and examined the expression of glomerular podocyte-associated proteins. Simultaneously, we measured expression of inflammatory factors, apoptotic proteins and albumin (ALB) in the renal cortex and renal medulla, respectively. PAS (Periodic Acid Schiff) staining was used to observe renal pathology. After LPS injection, urinary microalbumin (umALB) increased significantly and lasted longer. The expression of Nephrin, Podocin and necroptosis factor kappa B (NF-κB) in rennal cortex and Interleukin 18 (IL-18), Caspase-1, NF-κB and ALB in the renal medulla was significantly changed. Pathologically, the glomerular basement membrane was observed to be significantly thickened, the renal tubules were dilated, and the epithelial cells fell off in a circle. LPS promoted the continuous increase in urinary microalbumin in hyperglycemic rats, which was related to the damage to the glomerular basement membrane and renal tubular epithelial cells and to the inflammatory reaction in the kidney involved in NF-κB signaling, and this pathological damage can help to establish a stable model of diabetic nephropathy with increased proteinuria.

Clonal Propagation and Assessment of Biomass Production and Saponin Content of Elite Accessions of Wild Paris polyphylla var. yunnanensis.

Paris polyphylla var. yunnanensis is an endangered medicinal plant endemic to China with great economic importance for the pharmaceutical industry. Two significant barriers to its commercial development are the long duration of its seed germination and the frequency of interspecific hybridization. We developed a method for clonal propagation of Paris polyphylla var. yunnanensis and successfully applied it to selected elite wild plants, which could become cultivar candidates based on their biomass production and saponin content. In comparison to the traditional method, somatic embryogenesis produced an average of 63 somatic embryos per gram of callus in just six weeks, saving 12 to 15 months in plantlet production. The produced in vitro plantlets were strong and healthy and 94% survived transplanting to soil. Using this method, four candidate cultivars with diverse morphologies and geographic origins were clonally reproduced from selected elite wild accessions. In comparison to those obtained with the traditional P. polyphylla propagation technique, they accumulated higher biomass and polyphyllin levels in rhizomes plus adventitious roots during a five-year period. In conclusion, somatic embryogenesis-based methods offer an alternate approach for the rapid and scaled-up production of P. polyphylla, as well as opening up species conservation options.

Quantitative assessment of the effects of climate, vegetation, soil and groundwater on soil moisture spatiotemporal variability in the Mongolian Plateau.

Soil moisture (SM) is a key parameter regulating the hydrothermal balance of global terrestrial ecosystems and plays an important role in local ecological environment, particularly in arid and semiarid areas. However, current studies have so far obtained insufficient knowledge of SM spatiotemporal variability and its primary control factors, which limits our understanding of the feedback effects of SM on surface vegetation and hydrothermal activity. Here, we chose the ecologically fragile Mongolian Plateau (MP) as the study area to quantitatively reveal the soil moisture spatiotemporal variability (SMSTV) and the influence of control factors (climate, vegetation, soil and groundwater) with the help of empirical orthogonal functions (EOFs) and geographical detector models. The results indicated that a significant trend of decreasing SM and one dominant spatial structure (EOF1) of SM was found in the MP from 1982 to 2019, which explained over 54% of the spatial variability in SM, and as the soil depth increased, the EOF1 interpretation capacity increased. In addition, EOF1 is high in the north and east and low in the south and west of the MP and that vegetation cover is also relatively greater in the high-value areas. Overall, groundwater has the greatest influence on SMSTV in the MP (q = 0.89); however, precipitation and potential evapotranspiration remain the main control factors for SMSTV for different ecological zones, while the influence of vegetation elements (NDVI and GPP) cannot be ignored, and soil textures (clay, sand, silt) have the least influence. Meanwhile, SMSTV is explained to a greater extent by the interaction of the factors rather than by a single factor. However, there are differences in the influence mechanisms of each factor on SMSTV. This study provides strong evidence that meteorological forcing is not the only factor that dominates SMSTV and that the dominant factors may vary considerably between ecological zones.

Systematic evaluation and meta-analysis of Chinese medicine in the treatment of centrally mediated abdominal pain syndrome.

BACKGROUND: This study aimed to evaluate the clinical efficacy of Chinese medicine for the treatment of centrally mediated abdominal pain syndrome (CAPS) using a meta-analysis system. METHODS: Six databases, including China National Knowledge Infrastructure, Vendor Information Pages, Chinese Biomedical Database, Wanfang, PubMed, and Embase were searched for randomized controlled trials related to the treatment of CAPS with traditional Chinese medicine. The bias risk assessment tool and RevMan5.3 software (Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration) were used to conduct quality assessment and meta-analysis, and the GRADE grading system was used to evaluate the quality of evidence for outcome indicators. RESULTS: Fifteen articles were included in this study. Meta-analysis results showed that the treatment group was more effective in terms of the total effective rate (relative risk = 1.27; 95% confidence interval [CI], 1.19-1.34; P < .00001), Behavioral Rating Scale-6 pain score (mean difference [MD] = -0.79; 95% CI, -0.99 to -0.59; P < .00001), and traditional Chinese medicine (TCM) symptom score (MD = -1.74; 95% CI, -2.23 to -1.26; P < .00001) than the control group (P < .05). However, in terms of numerical rating scale pain score (MD = 0.79; 95% CI, -1.70 to 0.12; P = .09), the efficacy was comparable between the 2 groups, and the difference was not statistically significant (P > .05). In terms of verbal rating scale pain, depression, and anxiety scores, the data could not be combined due to inconsistent scoring criteria, and only descriptive analysis was performed. The results showed that the treatment group was slightly better than the control group in terms of relieving verbal rating scale pain and improving anxiety and depression (P < .05). CONCLUSION: Chinese medicine can effectively improve the pain and TCM clinical symptoms of patients with CAPS and relieve patients' anxiety and depression with fewer adverse effects, which has certain therapeutic advantages. However, because of the low methodological quality assessment of the included literature, the quality of GRADE evidence for outcome indicators is of mostly low and very low quality, the strength of recommendation is weak, and the credibility of the conclusion is average. More rigorous, larger sample, and higher-quality clinical trials are required to provide a higher level of evidence-based medicine for the development of TCM treatment standards for CAPS.

CTCF organizes inter-A compartment interactions through RYBP-dependent phase separation.

Chromatin is spatially organized into three-dimensional structures at different levels including A/B compartments, topologically associating domains and loops. The canonical CTCF-mediated loop extrusion model can explain the formation of loops. However, the organization mechanisms underlying long-range chromatin interactions such as interactions between A-A compartments are still poorly understood. Here we show that different from the canonical loop extrusion model, RYBP-mediated phase separation of CTCF organizes inter-A compartment interactions. Based on this model, we designed and verified an induced CTCF phase separation system in embryonic stem cells (ESCs), which facilitated inter-A compartment interactions, improved self-renewal of ESCs and inhibited their differentiation toward neural progenitor cells. These findings support a novel and non-canonical role of CTCF in organizing long-range chromatin interactions via phase separation.

The abrupt pathological deterioration of cisplatin-induced acute kidney injury: Emerging of a critical time point.

Cisplatin (CP), an anticancer drug, often causes kidney damage. However, the mechanism of CP-induced acute kidney injury (AKI) is not completely understood. AKI was induced by intravenous injection (i.v.) of cisplatin at doses of 5, 8, and 10 mg/kg. Anemoside B4 (B4) (20 mg/kg, i.m.) and dexamethasone (DXM) (0.5 mg/kg, i.v.) were used for AKI treatment. Biochemical indicators were assessed using an automatic biochemical analyzer, protein expression was analyzed by western blotting, and morphological changes in the kidney were examined by PAS staining. The serum creatinine (Cre) and blood urea nitrogen (BUN) levels did not change significantly in the first 2 days but abruptly increased on the third day after CP injection. The serum albumin (ALB) and total protein (TP) levels decreased in both a time- and dose-dependent manner. The urine protein level increased, the clearing rate of Cre decreased distinctly, and morphologic changes appeared in a dose-dependent manner. The protein expression of p53/caspase-3, NLRP3, IL-6, and TNF-α was obviously upregulated on day 3; concurrently, nephrin and podocin were downregulated. The expression of LC3II and p62 was upregulated significantly as the CP dose increased. B4 and DXM obviously decreased the BUN and Cre levels after 3 or 5 days of treatment. AKI appeared distinctly in a time-dependent manner at 2 to 5 days after the administration of 5 mg/kg CP and in a dose-dependent manner upon the administration of 5, 8, and 10 mg/kg CP. The third day was a significant time point for renal deterioration, and treatment with B4 and DXM within the first 3 days provided significant protection against AKI.

Azelnidipine and amlodipine: a comparison of their effects and safety in a randomized double-blinded clinical trial in Chinese essential hypertensive patients.

The purpose of this study is to compare the effects and safety of azelnidipine and amlodipine in Chinese essential hypertensive patients. Patients were randomized to receive administration of azelnidipine 8-16 mg/day or amlodipine 2.5-5 mg/day for 8 weeks. The blood pressure and pulse rate were evaluated in an outpatient clinic and by ambulatory blood pressure monitoring. There were 220 patients enrolled to the study. The blood pressure in both groups was decreased significantly (P < 0.001). Compared with amlodipine, the patients received azelnidipine had better response in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (P < 0.01). No significant changes of pulse rate were observed in either group. For the ambulatory blood pressure monitoring, both drugs had stable anti-hypertensive effects over 24 h. The trough/peak ratios of DBP for the azelnidipine and amlodipine groups were, respectively, 46% and 40%. Adverse events occurred at 7.3% and 10.0%, respectively in the azelnidipine and amlodipine groups (P = 0.485). Headache and dizziness were observed at an incidence of more than 1% in both groups. Once-daily administration of azelnidipine effectively controlled blood pressure and had a stable action over 24 h. Azelnidipine had good safety and compliance similar to amlodipine.