[Characteristics of anion and cation in rhizosphere soil of saline grassland in North China under different nitrogen addition levels]. / ä¸åŒæ°´å¹³æ°®æ·»åŠ ä¸‹åŽåŒ—ç›æ¸åŒ–è‰åœ°æ ¹é™ åœŸå£¤é˜´é˜³ç¦»å­ç‰¹å¾.

We investigated the effects and mechanisms of nitrogen additions (0, 1, 2, 4, 8, 16, 24, 32 g N·m-2·a-1) on contents of anion and cation in rhizosphere soil, bulk soil, and mixed rhizosphere and bulk soil in the heavily salinized grassland in the agro-pastoral ecotone of North China. The results showed that pH of rhizosphere, mixed and bulk soils decreased significantly with the increases of nitrogen addition levels. Moreover, pH of three soil types under the 32 g N·m-2·a-1 treatment decreased by 1.2, 0.9, and 0.6, respectively, while pH of rhizosphere soil decreased by 0.44 compared with the bulk soil. Na+ content of rhizosphere, mixed and bulk soils significantly decreased, while the NO3- content significantly increased. The proportion of Na+ content in total soluble salt content in rhizosphere soil decreased by 14% and that in bulk soil decreased by 12% after the 32 g N·m-2·a-1 addition. NO3- content increased by 29% in rhizosphere soil and by 26% in bulk soil. There was significant negative correlation between pH and NO3- content, and significant positive correlation between pH and Na+ content. The total soluble salt content of rhizosphere soil under the 32 g N·m-2·a-1 treatment was significantly reduced by 31.5%. Collectedly, nitrogen deposition could reduce soil pH and total soluble salt content of rhizosphere soil and alleviate saline-alkali stress.

Effects of nitrogen addition on rhizosphere soil properties in a salinized grassland.

We explored the impacts of nitrogen (N) inputs and the rhizosphere effect on the properties of rhizosphere and bulk soils in a salinized grassland in Northern Shanxi under N addition rates of 0, 1, 2, 4, 8, 16, 24 and 32 g N·m-2·a-1. The results showed that N addition significantly decreased soil pH, but significantly increased Ca2+, NO3--N and inorganic nitrogen contents in rhizosphere and bulk soil. With the increases of N addition rates, the contents of Ca2+, NO3--N, inorganic nitrogen in rhizosphere and bulk soils and total nitrogen in rhizosphere soil increased gradually, whereas the contents of Na+, K+, Mg2+, NH4+-N and amino acid in rhizosphere soil, and total nitrogen in bulk soil first increased and then decreased. Results of the principal component analysis showed that the responses of soil properties to low (≤8 g·m-2·a-1) and high nitrogen addition rates (>8 g·m-2·a-1) were significantly different. Compared with bulk soil, soil pH, the contents of organic acids and amino acids in rhizosphere soil were significantly lower by 0.71 units, 44.3% and 9.8%, respectively, while the contents of K+, Ca2+, Mg2+, NH4+-N, inorganic nitrogen, total carbon and total nitrogen in rhizosphere soil were significantly higher by 51.0%, 47.6%, 20.8%, 215.5%, 139.3%, 31.7% and 65.3%, respectively. These results indicated that rhizosphere effect on soil properties was stronger than that of nitrogen addition.

Global progress in peptide radiopharmaceutical research and China's opportunities / 药学学报

Radiopharmaceutical is an essential component of nuclear medicine and molecular imaging, as well as a key component of precision medicine. The United States Food and Drug Administration (FDA) has recently approved the marketing of several peptide-based radiopharmaceuticals, sparking a global trend of research in this area and propelling nuclear medicine into the precision theranostic era. This has created a new wave of technological competition in the field of nuclear medicine. It is the responsibility of Chinese scientists in the radiopharmaceutical field to capitalize on this opportunity, leverage the momentum, and strengthen their independent innovation capability in order to stay ahead in the future global nuclear science and technology competition. This review provides an overview of the remarkable progress made in the research, development, and translation of global peptide-based radiopharmaceuticals. It examines the advantages of peptide-based radiopharmaceuticals and outlines the current hot targets and progress in drug development in this field. Additionally, it proposes six opportunities for China to overtake others in the field of peptide-based radiopharmaceuticals and achieve technological self-reliance, based on interdisciplinary collaboration and independent innovation. Lastly, the future prospect of peptide-based radiopharmaceuticals is discussed.

The complete chloroplast genome of Bothriochloa ischaemum.

Bothriochloa ischaemum (Linn.) 1936 is a high-quality perennial forage in Loess Plateau of China. In this study, we sequenced and characterized the complete chloroplast genome of B. ischaemum, which was a circular DNA of 138,316 bp in length, including a large single copy (LSC) region of 80,226 bp, a small single copy (SSC) region of 12,526 bp, and the circular DNA was separated by a pair of identical inverted repeat regions (IRs) of 22,782 bp each. A total of 134 genes were identified, including 87 protein-coding genes, 39 tRNA genes, and eight rRNA genes. Phylogenetic tree showed that B. ischaemum was closer to B. decipiens and B. alta, genus Bothriochloa was closely related to genus Pseudanthistiria. Our findings will be helpful for better understanding of genetic diversity of Bothriochloa plants.

Whole-body PET tracking of a d-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors

Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the in vivo fate of d-peptides is limited. This highlights the need for whole-body, quantitative tracking of d-peptides to better understand how they interact with the living body. Here, we used mouse models to track the movement of a programmed death-ligand 1 (PD-L1)-targeting d-dodecapeptide antagonist (DPA) using positron emission tomography (PET). More specifically, we profiled the metabolic routes of [64Cu]DPA and investigated the tumor engagement of [64Cu/68Ga]DPA in mouse models. Our results revealed that intact [64Cu/68Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [64Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the in vivo fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.

The complete chloroplast genome of Medicago ruthenica cv. 'Taihang' (Fabaceae) from Shanxi, China.

Medicago ruthenica is an important perennial forage with multiple characteristics of resistance. In this study, we sequenced and characterized the complete chloroplast genome of M. ruthenica 'Taihang', which is 124, 254 bp in length. A total of 108 genes were identified, including 74 protein-coding, 30 tRNA, and four rRNA genes. Phylogenetic analysis based on 27 chloroplast genomes showed that M. ruthenica 'Taihang' has a close relationship with M. ruthenica from Qinghai Province, China. The data are useful in better understanding the genetic diversity and stress resistance of Medicago and contribute to the phylogenetic study of Trifolieae.

Effects of precipitation change and nitrogen addition on soil net N mineralization in a saline-alkaline grassland of Northern Shanxi Province, China.

To explore the responses of soil net nitrogen (N) mineralization rate to precipitation varia-tion and nitrogen deposition in salinized grassland, we set precipitation manipulation and nitrogen addition experiments in the typical agro-pastoral ecotone saline-alkaline grassland of Northern Shanxi Province, China. The in situ soil net N mineralization rate was determined by top-cover buried PVC cylinder from May to September in 2019. The results showed that there were seasonal dynamics in soil net N mineralization rate. Soil net N mineralization rate was not affected by increase/decrease precipitation (±50%), nitrogen addition (10 g·m-2·a-1) or the combination of nitrogen addition and increase 50% precipitation treatments. The combination of nitrogen addition and 50% reduction of precipitation significantly improved soil net nitrification rate and net N mine-ralization rate by 10.8 and 8.6 times, respectively. Soil net nitrogen mineralization rate was positively related to soil water content, and negatively related to soil pH. The effects of nitrogen addition on soil nitrogen mineralization rate were dependent on precipitation conditions. Soil water content and pH were important factors regulating soil net nitrogen mineralization rate in the saline-alkaline grassland of Northern Shanxi Province. Therefore, to roundly assess the response model of soil N mine-ralization process to global change, it is necessary to consider the interaction of precipitation changes and nitrogen addition, and the soil physical and chemical properties of salinized grassland.

Short-term effects of grazing intensity on soil stoichiometric characteristics of typical grassland in the agro-pastoral ecotone of northern China.

Grazing is the dominant land use way for natural grasslands. Different grazing intensities could affect soil stoichiometry in grasslands by influencing the selective feeding by livestock, litter input, and microbial community structure. In this study, a grazing experiment was carried out in a grassland of agro-pastoral ecotone in Northern China for three years (2017-2019). The concentrations of total carbon (TC), total nitrogen (TN), dissolved organic carbon (DOC), dissolved nitrogen (DN), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) in soils were measured. We analyzed the stoichiometric characteristics of those parameters. The results showed that different grazing intensities (1, 2, 4 sheep·0.2 hm-2) had no significant effect on soil TC after three years. The moderate grazing intensity significantly reduced soil TN in 10-20 cm layer in 2019. The light, moderate, and heavy grazing intensities significantly increased soil C/N at 10-20 cm layer, while grazing intensities did not affect soil DOC, DN and DOC/DN. The soil DOC and DN content showed a decreasing trend with the increase of grazing intensity in 2019. It indicated that continuous high intensity grazing might reduce soil dissolved nutrients. The light grazing inten-sity increased soil MBC, while heavy grazing intensity reduced soil MBC significantly, with the increase of grazing year. Different grazing intensities did not affect soil MBN and MBC/MBN.

Development of a highly-specific

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified

Recent developments on PET radiotracers for TSPO and their applications in neuroimaging

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.

Pharmacokinetic/pharmacodynamic models of anti-tumor agents in xenograft mice: historical review, recent advances, and application in drug development / 药学学报

Xenograft mice are preclinical animal models of tumors and are widely utilized in anti-tumor research. PK/PD modeling of anti-tumor agents is an approach that can capture the time profile of the "dose-plasma concentration-biomarker level-tumor volume" process based on experimental data from xenograft mice using a non-linear mixed-effect model. PK/PD modeling can help optimize the dosing regimen for anti-tumor therapy, evaluate any synergistic effect and help identify an optimal schedule for combination therapy, as well as providing a preliminary estimate of a drug's efficacy and anti-tumor potency in the human body. PK/PD modeling can also help by quantitatively explaining the mechanism of the tumor-inhibitory effect as indicated by changes in biomarker levels after a drug acts on its target. This article provides a systematic summary of the background, application range, and limitations of the mainstream anti-tumor agent PK/PD models. Recent advances in model structure development are reviewed in detail. Finally, we discuss promising applications of PK/PD models in anti-tumor medicine development from the perspective of a drug's mechanism of action, optimization of combination therapy schedules, and their clinical translation.

Developing native peptide-based radiotracers for PD-L1 PET imaging and improving imaging contrast by pegylation.

Herein, a PD-L1 targeted native peptide was developed for PET imaging. 18F and 64Cu were utilized to label the peptide. To improve the pharmacokinetics and biodistribution of the tracers, the peptide was further pegylated to form star-like tetramers. Consequently, four tracers were synthesized with acceptable radiochemical characteristics and their in vivo pharmacokinetics and PD-L1 imaging capability were systematically evaluated. This proof-of-principle study may provide new possibilities for PD-L1 PET imaging in cancers.

[Short-term Effects of Different Grazing Intensities on Greenhouse Gas Fluxes in Semi-arid Grassland].

Grazing is one of the most important ways for managing grassland in northern China. Different studies have focused on the effects of grazing on the structure and function of ecosystems. Grazing affects the structure and function of soil via biological and physical processes, such as animal trampling, feeding, and excretion, which further affects N2O emissions. However, there is less research on greenhouse gases (GHGs) emissions by grazing intensities in semi-arid grassland ecosystems in northern China. In this study, four different grazing intensities were considered in the semi-arid grassland ecosystem of the typical agro-pastoral ecotone in northern China (Youyu, Shanxi). The influence of different grazing intensities on GHG fluxes was studied by measuring GHGs fluxes in the growing season with an opaque static chamber. The results showed that ① Grazing had no effect on CO2 and N2O fluxes during the first year of grazing treatment. ② However, grazing decreased soil water content (P<0.05), moderate grazing intensity decreased microbial biomass carbon (P<0.05), and moderate and heavy grazing intensities reduced microbial biomass nitrogen (P<0.05). ③ Significant positive correlations between CO2 flux and soil temperature and soil moisture were observed. The correlation between temperature and CO2 emissions was increased by grazing. ④ There was a significant positive correlation between soil temperature, soluble nitrogen, soil microbial biomass nitrogen, CO2 flux, and N2O flux. Our results indicated that GHG, regulated by soil microorganisms, was affected by soil temperature and moisture.

Suppression of hepatocellular carcinoma invasion and metastasis by Rho-kinase inhibitor Fasudil through inhibition of BTBD7-ROCK2 signaling pathway / 中南大学学报(医学版)

Objective: To explore the eff ect of Fasudil on the invasion and metastatic abilities of human high metastatic liver cancer cells (HCCLM3) and the underlying mechanisms. Methods: HCCLM3 cells were incubated with 100 μmol/L Fasudil. Fluorescence staining forF-actin and Transwell assay were performed to observe the invasion ability of HCCLM3 cells. HCCLM3 cells were divided into 3 groups: a negative control group, a Fasudil group and a BTB/POZ domain containing 7 (BTBD7)-siRNA group. Western blot assay was performed to detect the expression levels of BTBD7, ras homolog family member C (RhoC) and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2), matrix metalloproteinases 2 (MMP2) and MMP9. Zymogram analysis method was performed to detect the expression activities of MMP2 and MMP9. hTe BTBD7-siRNA group was served as a positive control. Results: In HCCLM3 cells treated with Fasudil, the invasion ability was significant decreased compared with the control group, concomitant with the down-regulated expression levels of BTBD7, RhoC and ROCK2 protein as well as the decreased activities of MMP2 and MMP9. Conclusion: Fasudil plays an important role in interfering BTBD7-ROCK2 signaling pathway and suppressing the invasion and metastasis of hepatocellular carcinoma.

Improvement of carbon tetrachloride drug-induced liver injury model in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To establish an ideal CCl4 drug-induced liver injury model in vitro.</p><p><b>METHOD</b>Traditional method and improved method were adopted for preparing CCl4 injury liquid and drug-induced human liver HepG2 cell injury. Cell morphological change was observed under a bright-field microscope. The level of alanine aminotransferase (ALT) in supernatant was detected by biochemical method. 4-Methyl-tetrazolium (MTT) chromatometry was adopted for determining cell activity.</p><p><b>RESULT</b>The improved method showed better CCl4-induced injury effect than the traditional method. With the increase in the concentration of CCl4 injury liquid, the ALT level significantly increased, whereas the cell activity notably decreased. Particularly, 70% CCl4 injury liquid use for 4 hours could achieve the best injury effect.</p><p><b>CONCLUSION</b>The improved method could be used to establish an ideal CCl4 drug-induced liver injury model in vitro, which can lay foundation for further in vitro studies.</p>

Effects of feeding salt-tolerant forage cultivated in saline-alkaline land on rumen fermentation, feed digestibility and nitrogen balance in lamb.

BACKGROUND: Mixing salt-tolerant plants with other plants may affect rumen fermentation, which could result in an increase of feed conversion rate. The objective of this study was to evaluate the effects of partially or entirely replacing the corn stover with a mixture of salt-tolerant forage (Dahurian wildrye grass, weeping alkaligrass and erect milkvetch) in the diet of lambs on ruminal fermentation, feed digestibility and nitrogen (N) balance. Ratios of corn stover to the mixture of salt-tolerant forages in the four experimental diets were 100:0, 67:33, 33:67 and 0:100, respectively, for control, low (LF), medium (MF) and high (HF). RESULTS: Ruminal pH was lower (P = 0.048) with LF and MF than with control and HF diets. Total VFA concentration was consistently higher (P = 0.039) for LF and MF than for control and HF with increasing amount of salt-tolerant forage. Ratio of acetate to propionate was linearly (P = 0.019) decreased due to the decrease in acetate production. Digestibilities of OM, NDF and CP in the whole tract linearly (P < 0.002) decreased with increasing amount of salt-tolerant forage. Similarly, retained N and ratio of retained N to digestible N also linearly (P < 0.005) decreased. CONCLUSION: Feeding salt-tolerant forage cultivated in saline-alkaline land improved rumen fermentation with increased total VFA production, and changed the rumen fermentation pattern to increased butyrate production. However, the decreased feed digestibility in the whole digestive tract of lamb may reduce nutrient availability to animals and thus adversely affect animal productivity. Additionally, feeding salt-tolerant forages may require more protein supplement to meet animal requirements, because of the low protein content and low protein digestibility of the salt-tolerant forages.

Epidemiological investigation of an outbreak of acute gastroenteritis caused by human calicivirus in Lulong County / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To survey an outbreak of acute gastroenteritis in Lulong County and analyze the cause of the disease.</p><p><b>METHODS</b>Epidemiological methods were applied to investigate an outbreak of acute gastroenteritis occurred in June 2000 in Lulong County. Stool specimens were collected from diarrhea patients and were tested for human calicivirus by ELISA and RT-PCR. The products of RT-PCR were cloned and sequenced, then phylogenetic analysis was carried out.</p><p><b>RESULTS</b>In total, 736 farmers were surveyed, among them 134 had acute gastroenteritis, the attack rate was 18.20%, and one elderly patient died. The age of patients was from 1 to 77 years and the incidence of the disease among young people was higher with a peak in June 25 through 30. Six stool specimens were tested for caliciviruses by ELISA and 3 were positives, one of them was confirmed by RT-PCR and belonged to norovirus genotype GI/2. No other pathogens were detected.</p><p><b>CONCLUSION</b>Human calicivirus was confirmed to be the cause of the outbreak of acute gastroenteritis.</p>

Epidemiological study of human caliciviruses among children with acute diarrhea in Lulong county, 1999 - 2001 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the epidemiological characteristus of human caliciviruses (HuCVs) among children under 5 years of age with acute diarrhea and to estimate the disease burden in Lulong county.</p><p><b>METHODS</b>HuCVs were detected by enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). Some PCR amplicons were cloned and sequenced. Phylogenetic tree was constructed for strain characterization. The rate of HuCVs-attributed hospitalization was estimated according to the positive rate of HuCVs detection in fecal specimens collected from hospitalized diarrhea patients.</p><p><b>RESULTS</b>Between July 1999 and June 2001, 708 fecal specimens were collected, of which 393 rotavirus-negative and 5 rotavirus-positive specimens were detected for HuCVs. Thirty-one point six percentage of fecal specimens from patients with diarrhea was HuCVs positive. Among inpatients, HuCVs positive rate was 17.5%. HuCVs detection was mainly distributed in 3 - 17 mouth-old children, in winter. All 11 strains belonged to NLV GII in which 6 strains GII-3, 2 strains GII-4 and 3 strains GII-7, and they shared 55.1% - 100% nucleotide identity. NLV GII-4 and GII-7 were identified in 2000, while NLV GII-3 and GII-7 in 2001. The preliminary estimate of HuCVs-attributed hospitalization rate was 3.6 per thousand.</p><p><b>CONCLUSION</b>Human caliciviruses with different genotypes circulated among children in Lulong county with GII NLVs were the prevalent strains. The disease burden of HuCVs was second to rotavirus.</p>