[Mechanism of melatonin-mediated antihyperglycemic effect of transcutaneous auricular vagus nerve stimulation].

OBJECTIVE: To observe the effects of transcutaneous auricular vagus nerve stimulation （taVNS） on plasma melatonin （MLT） content and insulin receptor expression in the liver, the skeletal muscles, and the pancreas of Zucker diabetic fatty （ZDF） rats, so as to explore the hypoglycemic mechanism of taVNS. METHODS: Thirty male ZDF rats were randomly divided into model group, taVNS group and sham-taVNS group, with 10 rats in each group； besides, 10 male Zucker lean rats of the same strain were collected for the blank control group. ZDF rats were fed with high-fat diet to induce type 2 diabetes mellitus （T2DM） rat model. In the taVNS group, HANS-100A electroacupuncture instrument was used to stimulate the cavum conchae of both sides. The stimulation sites of rats in the sham-taVNS were the same as the taVNS group, but without electricity delivered. The above interventions were performed 30 min each time, once daily, lasting for 6 weeks. Fasting blood glucose （FBG） was measured weekly in each group, the plasma metatonin （MLT） content was detected by ELISA, and the insulin receptor expression level in the liver, the skeletal muscle and the pancreas was determined by Western blot. RESULTS: Compared with the blank control group, the level of FBG of rats were increased （P<0.01）, the plasma MLT content was decreased （P<0.01） and the insulin receptor expression level in the pancreatic tissue was decreased （P<0.01） in the model group. In the taVNS gruop, FBG was decreased （P<0.05, P<0.01）, the plasma MLT content was increased （P<0.01）, and the insulin receptor expression level in the liver, the skeletal muscle and the pancreas was increased （P<0.05, P<0.01, P<0.001） when compared with the model group. Compared with the taVNS group, FBG was increased （P<0.05, P<0.01）, the plasma MLT content was decreased （P<0.01）, and the expression level of insulin receptors in the skeletal muscle and the pancreas was decreased （P<0.01, P<0.001） in the sham-taVNS group. CONCLUSION: The taVNS can improve the insulin resistance and ultimately obtain the antihyperglycemic effect through regulating MLT concentration.

Proprioceptive Acuity Assessment in Multiple Directions Across Multiple Joints in the Upper Limb.

Proprioception is essential for precise movement as it helps the body transmit important data about its surroundings to the central nervous system for maintaining body posture and position. This study aimed to investigate the effect of direction and joint angle on upper limb proprioception. Thirty individuals (all males) completed a position reproduction activity in 13 directions and three joint angles. It was discovered that upper limb proprioception is dependent on joint angle, direction, and range of motion. The position reproduction error was found to be dependent on the direction, which had a significantly lower accuracy in the direction with a larger range of motion. In addition, upper limb repositioning errors increased at greater limb elevation angles. Our findings also showed that the joint angle did not significantly affect the absolute error of elbow flexion. With an increase in the elbow flexion, the increase of the gravitational moment of the upper arm and hand coupled with the increase of the muscle arm of the biceps brachii possibly causes slight changes in muscle length perceived by spindles or muscular force perceived by Golgi tendon organs.

[Temporal and Spatial Variation Characteristics of Carbon Storage in the Source Region of the Yellow River Based on InVEST and GeoSoS-FLUS Models and Its Response to Different Future Scenarios].

Regional land use change is the main cause of carbon storage changes in ecosystems. Predicting the impact of future land use changes on carbon storage is of great significance for the sustainable development of carbon storage functions. In recent years, under the combined action of natural and human factors, the land use in the source region of the Yellow River has changed significantly, and its carbon storage function has also changed accordingly. This study combined InVEST and GeoSoS-FLUS models to evaluate land use change and its impact on carbon storage in the source region of the Yellow River from 2000 to 2020 and from 2020 to 2040 under different scenarios. The results showed that:① from 2000 to 2020, the carbon storage in the source region of the Yellow River showed an overall upward trend, with a total increase of 11.59×106 t. ② Over the past 20 years, the land use changes in the source region of the Yellow River included mainly the increase in the area of low-coverage grassland, construction land, and wetland and the decrease in the area of high-coverage grassland, medium-coverage grassland, and unused land, as well as the large-scale reduction of unused land and the reduction of grassland. The increase in the area of wetlands was the main reason for the increase in carbon storage. ③ Under the natural change scenario in 2040, the ecosystem carbon storage in the source region of the Yellow River was 871.34×106 t, an increase of 3.92×106 t compared with that in 2020. Under the ecological protection scenario, carbon storage increased significantly, with an increase of 13.53×106 t compared with that in 2020. The results of this study can provide a scientific reference for the decision-making of land use management and the sustainable development of carbon storage function in the source region of the Yellow River.

Evaluation of Zhenwu Decoction Effects on CYP450 Enzymes in Rats Using a Cocktail Method by UPLC-MS/MS.

This thesis is aimed at shedding light on the effects of the Zhenwu decoction (ZWD) on the activities and mRNA expressions of seven CYP450 isoenzymes. In the first step, we determined the main chemical compounds of ZWD by high-performance liquid chromatography (HPLC). Next, 48 male (SD) rats were randomly divided into the normal saline (NS) group and the ZWD low- (2.1875 g/kg), medium- (4.375 g/kg), and high- (8.75 g/kg) dose groups (12 per group). All rats were gavaged once daily for 28 consecutive days. A mixed solution of seven probe drugs was injected into 24 rats through the caudal vein after the last intragastric administration. Lastly, a validated cocktail method and real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) were used to detect pharmacokinetic parameters and mRNA expressions, respectively. Compared with the NS group, ZWD at medium- and high-dose groups could significantly induce CYP2C6 (P < 0.05) activity, while the mRNA expression (P < 0.05) increased only in the high-dose group. Additionally, CYP2C11 activity was induced and consistent with mRNA expression (P < 0.05). Moreover, ZWD could induce the activity of CYP3A1 (P < 0.05), but the mRNA expression showed no significant differences except in high-dose groups. Additionally, ZWD has no effects on CYP1A2, CYP2B1, CYP2C7, and CYP2D2. In conclusion, the significant inductive effects of ZWD on three CYP450 isoenzymes indicated that when ZWD was coadministrated with drugs mediated by these enzymes, not only should the potential herb-drug interactions (HDIs) be observed, but the dosage adjustment and tissue drug concentration should also be considered. Furthermore, the approach described in this article can be applied to study the importance of gender, age, and disease factors to HDI prediction.

Chemosensing properties and logic gate behaviors of graphene quantum dot-appended terpyridine.

Graphene quantum dot-covalently appended terpyridine, GQDs-tpy, was synthesized and characterized by X-ray photoelectron spectroscopy, FTIR spectroscopy and transmission electron microscopy. GQDs-tpy was found to act as multifunctional chemosensors: a highly selective colorimetric chemosensor for Fe2+ as evidenced by an obvious color change from colorless to pink, and a typical fluorescence enhanced probe for Zn2+ over 13 metal cations even in practical water samples. Moreover, two-input XOR, INHIBIT and IMPICATION logic gates as well as four-input OR and NOR logic gates were constructed according to the characteristic responses of GQDs-tpy to a sequence of cations.

[Study on Si-PIN and CdTe Detectors Used in Energy Dispersive X-Ray Fluorescence Measurements].

Semiconductor detector is widely used in energy dispersive X-ray fluorescence measurements due to its excellent performance. In this paper, Si-PIN and CdTe semiconductor detectors were studied, performances of the two detectors were compared in material properties, detection efficiency, energy resolution and other aspects. Focused on the performance of the detectors influenced by the thickness of detector sensitive area, energy of incident X-ray, shaping time of post-stage circuit, and analyzed the differences of energy spectrum caused by escape peaks and hole trailing. Aiming at the problem of incomplete hole collection in detector, a digital multi-channel analyzer (DMCA) based on FPGA with rise-time discriminator was designed, it could reduce the influence of hole trailing effectively and improve energy resolution. The experimentation results indicate that the detection efficiency of Si-PIN and CdTe is roughly equal when energy is below 15 keV while CdTe has much higher detection efficiency than Si-PIN when energy is above 15 keV. The optimum forming time of the Si-PIN detector is about 10 µs, and the CdTe detector is about 2.6 µs, so the CdTe detector is more suitable for the high count rate condition. Si-PIN detector has better energy resolution than CdTe detector for different energy incident X-ray. CdTe detector has obvious hole tailing effect and the energy resolution of CdTe detector is significantly improved by using DMCA with rise-time discrimination.

The mechanism for microsporidian parasite suppression of the hindgut bacteria of the migratory locust Locusta migratoria manilensis.

Locusts aggregate into bands of nymphs and swarms of adults that can pose a major threat to crop. Previous studies have shown that infection by the microsporidian parasite Paranosema locustae prevents locust aggregation behavior and we show that gut bacteria, which produce components of locust aggregation pheromones, are substantially reduced in locusts infected with P. locustae. We found that P. locustae could reduce the diversity, abundance and community composition of Locusta migratoria's gut bacteria. The parasite infection was also shown to interrupt the peroxidase activity of locust hindgut. Genome-wide expression analysis showed that the parasite infection suppressed peroxidase mRNA relative expression of locust hindgut, but had no effects on attacin expression and superoxide dismutase at 16 d post-inoculation with 20,000 P. locustae spores. Our findings reveal the mechanisms by which P. locustae impairs bacterial diversity and community structure of Locusta migratoria's gut bacteria.

Evaluation of genetic factors for warfarin dose prediction.

OBJECTIVES: Warfarin is a commonly prescribed anticoagulant drug used to prevent thromboses that may arise as a consequence of orthopedic and vascular surgery or underlying cardiovascular disease. Warfarin is associated with a notoriously narrow therapeutic window where small variations in dosing may result in hemorrhagic or thrombotic complications. To ultimately improve dosing of warfarin, we evaluated models for stable maintenance dose that incorporated both clinical and genetic factors. METHOD: A model was constructed by evaluating the contribution to dosing variability of the following clinical factors: age, gender, body surface area, and presence or absence of prosthetic heart valves or diabetes. The model was then sequentially expanded by incorporating polymorphisms of cytochrome P450 (CYP) 2C9; vitamin K 2,3 epoxide reductase complex, subunit 1 (VKORC1); gamma carboxylase; factor VII; and apolipoprotein (Apo) E genes. RESULTS: Of genetic factors evaluated in the model, CYP2C9 and VKORC1 each contributed substantially to dose variability, and together with clinical factors explained 56% of the individual variability in stable warfarin dose. In contrast, gamma carboxylase, factor VII and Apo E polymorphisms contributed little to dose variability. CONCLUSION: The importance of CYP2C9 and VKORC1 to patient-specific dose of warfarin has been confirmed, while polymorphisms of gamma carboxylase, factor VII and Apo E genes did not substantially contribute to predictive models for stable warfarin dose.

Small molecule antagonists of the TGF-beta1/TGF-beta receptor binding interaction.

Excessive and inappropriate action of transforming growth factor (TGF)-beta has been implicated in the pathogenesis of several disease processes, especially cancer and fibrosis. To identify antagonists of the TGF- beta ligand-binding domain that may have therapeutic potential, we screened the National Cancer Institute open access chemical repository for molecules that inhibited binding of TGF-beta to the type II receptor (TbetaRII). About 30,000 molecules were screened resulting in the identification of five structurally related molecules that reduced binding of TGF-beta1 to soluble TbetaRII with an ED50 of approx 10 microM. The chemicals blocked inhibition of Mv1Lu cell growth by TGF-beta, TGF-beta - induced expression of luciferase driven by the TGF-beta response element, and induction of plasminogen inhibitor mRNA detected by Northern blot. In contrast, the chemicals did not block activin-induced inhibition of cell growth. Our results identify a novel chemical group that blocks binding of TGF-beta to its receptor and may result in novel treatment for disease.

Analysis of candidate genes for prostate cancer.

Considerable evidence demonstrates that genetic factors are important in the development and aggressiveness of prostate cancer. To identify genetic variants that predispose to prostate cancer we tested candidate SNPs from genomic regions that show linkage to prostate cancer susceptibility and/or aggressiveness, as well as genes that show a significant difference in mRNA expression level between tumor and normal tissue. Cases had histologically verified prostate cancer. Controls were at least 65 years old, never registered a PSA above 2.5 ng/ml, always had digital rectal examinations that were not suspicious for cancer, and have no known family history of prostate cancer. Thirty-nine coding SNPs and nine non-coding SNPs were tested in up to 590 cases and 556 controls resulting in over 40,000 SNP genotypes. Significant differences in allele frequencies between cases and controls were observed for ID3 (inhibitor of DNA binding), p = 0.05, HPN (hepsin), p = 0.009, BCAS1 (breast carcinoma amplified sequence 1), p = 0.007, CAV2 (caveolin 2), p = 0.007, EMP3 (epithelial membrane protein 3), p < 0.0001, and MLH1 (mutL homolog 1), p < 0.0001. SNPs in three of these genes (BCAS1, EMP3 and MLH1) remained significant in an age-matched subsample.

Genetics of prostate cancer.

Prostate cancer is the most frequently diagnosed visceral cancer of men, responsible for approximately 40,000 deaths in adult males per year. To identify the genetic causes of prostate cancer, we performed a whole genome scan of affected sib pairs, using DNA markers spaced evenly across the human genome. We demonstrated that regions on chromosomes 1, 4, 5, 7, 8, 11, 16 and 19 might harbor genes that predispose individuals to prostate cancer and may affect tumor growth rate and tumor aggressiveness. Here we present DNA sequence analysis of KIAA 0872 and 17-beta hydroxysteroid dehydrogenase that are located on chromosome 16 within the mapped region, and we demonstrate that neither of these genes carries mutations in the protein coding region or their splice junction sites. These results suggest that these genes are less likely to be associated with the cause of familial prostate cancer.