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Dipsaci Radix is one of the commonly used Chinese medicinal materials in China, with a long history. It has the medicinal activities of nourishing liver and kidney, recovering from broken sinews, and treating bone fracture. Triterpenoid saponins are the main functional ingredients of Dipsacus asper. β-Amyrin synthases(β-AS) as a superfamily of oxidosqualene cyclases(OSCs) can catalyze the construction of the skeleton structure of oleanane-type triterpenoid saponins. There are only a few studies about the β-AS in D. asper, and the catalytic mechanism of this enzyme remains to be explored. To enrich the information of β-AS, according to the transcriptome sequencing results, we cloned DaWβ-AS gene from D. asper into a specific vector for heterologous expression in Escherichia coli. In the meantime, real-time PCR was performed to analyze the relative expression of DaWβ-AS in four different tissues of D. asper. The results of RT-qPCR showed DaWβ-AS had the highest expression level in leaves. Bioinformatics results indicated that DaWβ-AS had a conserved domain of PLN03012 superfamily, belonging to the cl31551 superfamily. There was no transmembrane domain or signal peptide in DaWβ-AS. This study provides a scientific basis for revealing the biological pathways of triterpenoid saponins in D. asper, which will facilitate the biosynthesis of the associated saponins and afford reference for the cultivation and development of high-quality resources of D. asper.

Dexmedetomidine is commonly used in hysteroscopy surgery due to its analgesia and sedation without respiratory depression. Many studies have shown that dexmedetomidine can reduce the consumption of sevoflurane. However, the optimal end-tidal concentration of sevoflurane when it is co-administered with dexmedetomidine has not been established. The primary purpose of this study was to investigate the minimal alveolar concentration (MAC) of sevoflurane for cervical dilatation combined with different doses of dexmedetomidine in patients with hysteroscopy surgery.One-hundred patients undergoing hysteroscopy surgery were enrolled in this clinical trial. All the patients were randomly assigned into four groups (C, DThe calculated MAC of sevoflurane using up-and-down method of Dixon and Mood in patients with hysteroscopy surgery was (1.90 ± 0.13)%, (1.23 ± 0.16)%, (1.03 ± 0.10)% and (0.93 ± 0.08)% in groups C, DThe administration of dexmedetomidine can significantly decrease the MAC of sevoflurane for hysteroscopy surgery. However, a ceiling effect of the reduction was observed when the dose of dexmedetomidine was higher than 0.8 μg/kg.

Hua-Feng Yin,1,2 Chun-Ming Yin,3 Ting Ouyang,4 Shu-Ding Sun,1 Wei-Guo Chen,1 Xiao-Lin Yang,5 Xin He,6 Chun-Feng Zhang1 1School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, People’s Republic of China; 2Jiangxi QingFeng Pharmaceutical Co., Ltd, Ganzhou, 341000, Jiangxi, People’s Republic of China; 3Emergency Department, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, People’s Republic of China; 4School of Chinese Materia Medical, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 6School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of ChinaCorrespondence: Xin HeSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, People’s Republic of ChinaTel +852-54445989Email xhe06@qub.ac.ukChun-Feng ZhangSchool of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of ChinaTel +86-25-86185129Email zhangchunfeng67@163.comPurpose: The aim of the present study was to develop an optimized Genkwanin (GKA)-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation to enhance the solubility, intestinal permeability, oral bioavailability and anti-colitis-associated colorectal cancer (CAC) activity of GKA.Methods: We designed a SNEDDS comprised oil phase, surfactants and co-surfactants for oral administration of GKA, the best of which were selected by investigating the saturation solubility, constructing pseudo-ternary phase diagrams, followed by optimizing thermodynamic stability, emulsification efficacy, self-nanoemulsification time, droplet size, transmission electron microscopy (TEM), drug release and intestinal permeability. In addition, the physicochemical properties and pharmacokinetics of GKA-SNEDDS were characterized, and its anti-colitis-associated colorectal cancer (CAC) activity and potential mechanisms were evaluated in AOM/DSS-induced C57BL/6J mice model.Results: The optimized nanoemulsion formula (OF) consists of Maisine CC, Labrasol ALF and Transcutol HP in a weight ratio of 20:60:20 (w/w/w), in which ratio the OF shows multiple improvements, specifically small mean droplet size, excellent stability, fast release properties as well as enhanced solubility and permeability. Pharmacokinetic studies demonstrated that compared with GKA suspension, the relative bioavailability of GKA-SNEDDS was increased by 353.28%. Moreover, GKA-SNEDDS not only significantly prevents weight loss and improves disease activity index (DAI) but also reduces the histological scores of inflammatory cytokine levels as well as inhibiting the formation of colon tumors via inducing tumor cell apoptosis in the AOM/DSS-induced CAC mice model.Conclusion: Our results show that the developed GKA-SNEDDS exhibited enhanced oral bioavailability and excellent anti-CAC efficacy. In summary, GKA-SNEDDS, using lipid nanoparticles as the drug delivery carrier, can be applied as a potential drug delivery system for improving the clinical application of GKA.Keywords: insoluble herbal drug, nanoparticle-based drug delivery system, intestinal permeability, pharmacokinetics, anticancer efficacy

Objective The chemical finger printing-based methods for evaluating TCMs quality can report partial of TCMs quality without linking to effective constituents. In this study, a mathematical model was established for the quality evaluation of total saponins of Panax japonicus (TSPJ), a folk medicine in China and Japan for treating diseases, through coupling the dynamic changes of chemical constitutions with corresponding activities. Methods High-performance liquid chromatography (HPLC) fingerprints were applied to establish the chromatographic database of TSPJ. The associated hypolipidemic activity database was determined by TG assay using HepG2 cell model. Correlation analyses of two databases were performed by partial least squares (PLS) for calculating regression coefficients, and the interval value of YZL value (the ratio of positive and negative peak-to-peak area coefficient) closely related to hypolipidemic activity was refined by the formula of Norminv function to value the quality of TSPJ. Results In this study, the chromatographic data of 16 common peaks were obtained from 20 batches of TSPJ. After the estimate by this mathematical evaluation model, seven peaks were positively correlated with hypolipidemic activity, and nine peaks were negatively correlated with hypolipidemic activity. When the YZL value was less than 0.7861, the quality of sample was inferior, while YZL value was more than 6.6992, and the quality of samples was superior. The quality of another ten batches of TSPJ was further assessed to verify this method. Conclusion These results indicated that the established model could be usefully applied to evaluate the quality of TSPJ in the hypolipidemic activity.

In this work, an immersion freezing system was proposed to shorten the total freezing time and improve the quality of frozen food. The thermal performance of the refrigerant liquid prepared for using in the immersion freezing system was evaluated. A three-dimensional model (3D) was developed to investigate the dynamic characteristics of food freezing process. The effects of the refrigerant liquid inlet flow rate, inlet temperature, total freezing time and freezing rate of chicken breast, velocity and temperature distribution in the immersion freezing system were investigated. In addition, the freezing rates of food using traditional air-blast freezing and the proposed immersion freezing were evaluated. The results showed that the freezing rate of food in immersion freezing was approximately 12.85 times higher than that of the traditional air-blast freezing. When the flow rate increased from 0.11 kg·s-1 to 0.63 kg·s-1, the total freezing time shortened by 36.9%. When the temperature decreased from -25 ºC to -40 ºC, the total freezing time shortened by 35.5%. However, the temperature of the refrigerant liquid should not be too low, which will lead to high viscosity of the liquid, thus resulting in increasing in the overall power consumption of the proposed system.

Both bone mineral density (BMD) and lean body mass (LBM) are important physiological measures with strong genetic determination. Besides, BMD and LBM might have common genetic factors. Aiming to identify pleiotropic genomic loci underlying BMD and LBM, we performed bivariate genome-wide association study meta-analyses of femoral neck bone mineral density and LBM at arms and legs, and replicated in the large-scale UK Biobank cohort sample. Combining the results from discovery meta-analysis and replication sample, we identified three genomic loci at the genome-wide significance level (p < 5.0 × 10(−8)): 2p23.2 (lead SNP rs4477866, discovery p = 3.47 × 10(−8), replication p = 1.03 × 10(−4)), 16q12.2 (rs1421085, discovery p = 2.04 × 10(−9), replication p = 6.47 × 10(−14)) and 18q21.32 (rs11152213, discovery p = 3.47 × 10(−8), replication p = 6.69 × 10(−6)). Our findings not only provide useful insights into lean mass and bone mass development, but also enhance our understanding of the potential genetic correlation between BMD and LBM.

BACKGROUND: Fat mass and lean mass are two biggest components of body mass. Both fat mass and lean mass are under strong genetic determinants and are correlated. METHODS: We performed a bivariate genome-wide association meta-analysis of (lean adjusted) leg fat mass and (fat adjusted) leg lean mass in 12,517 subjects from 6 samples, and followed by in silico replication in large-scale UK biobank cohort sample (N = 370 097). RESULTS: We identified four loci that were significant at the genome-wide significance (GWS, α = 5.0 × 10(−8)) level at the discovery meta-analysis, and successfully replicated in the replication sample: 2q36.3 (rs1024137, p(discovery) = 3.32 × 10(−8), p(replication) = 4.07 × 10(−13)), 5q13.1 (rs4976033, p(discovery) = 1.93 × 10(−9), p(replication) = 6.35 × 10(−7)), 12q24.31 (rs4765528, p(discovery) = 7.19 × 10(−12), p(replication) = 1.88 × 10(−11)) and 18q21.32 (rs371326986, p(discovery) = 9.04 × 10(−9), p(replication) = 2.35 × 10(−95)). The above four pleiotropic loci may play a pleiotropic role for fat mass and lean mass development. CONCLUSIONS: Our findings further enhance the understanding of the genetic association between fat mass and lean mass and provide a new theoretical basis for their understanding.

SUMMARY: Aiming to identify pleiotropic genomic loci for bone mineral density and bone size, we performed a bivariate GWAS in five discovery samples and replicated in two large-scale samples. We identified 2 novel loci at 2q37.1 and 6q26. Our findings provide insight into common genetic architecture underlying both traits. INTRODUCTION: Bone mineral density (BMD) and bone size (BS) are two important factors that contribute to the development of osteoporosis and osteoporotic fracture. Both BMD and BS are highly heritable and they are genetically correlated. In this study, we aim to identify pleiotropic loci associated with BMD and BS. METHODS: We conducted a bivariate genome-wide association (GWA) analysis of hip BMD and hip BS in 6180 participants from 5 samples, followed by in silico replication in the UK Biobank study of BMD (N = 426,824) and the deCODE study of BS (N = 28,954), respectively. RESULTS: SNPs from 2 genomic loci were significant at the genome-wide significance (GWS) level (p lt; 5 × 10(−8)) in the discovery samples and were successfully replicated in the replication samples (2q37.1, lead SNP rs7575512, discovery p = 1.49 × 10(−10), replication p = 0.05; 6q26, lead SNP rs1040724, discovery p = 1.95 × 10(−8), replication p = 0.03). Functional annotations suggested functional relevance of the identified variants to bone development. CONCLUSION: Our findings provide insight into the common genetic architecture underlying BMD and BS, and enhance our understanding of the potential mechanism of osteoporosis fracture.

Energetic X-ray radiations emitted from various accretion systems are widely considered to be produced by Comptonization in the hot corona. The corona and its interaction with the disc play an essential role in the evolution of the system and are potentially responsible for many observed features. However many intrinsic properties of the corona are still poorly understood, especially for the geometrical configurations. The traditional spectral fitting method is not powerful enough to distinguish various configurations. In this paper we intent to investigate the possible configurations by modeling the polarization properties of X-ray radiations. The geometries of the corona include the slab, sphere and cylinder. The simulations are implemented through the publicly available code, LEMON, which can deal with the polarized radiative transfer and different electron distributions readily. The results demonstrate clearly that the observed polarizations are dependent on the geometry of the corona heavily. The slab-like corona produces the highest polarization degrees, the following are the cylinder and sphere. One of the interesting things is that the polarization degrees first increase gradually and then decrease with the increase of photon energy. For slab geometry there exists a zero point where the polarization vanishes and the polarization angle rotates for $90^\circ$. These results may potentially be verified by the upcoming missions for polarized X-ray observations, such as $IXPE$ and $eXTP$., Comment: 29 pages, 12 figures, RAA accepted. The source code can be downloaded from \url{https://bitbucket.org/yangxiaolinsc/corona_geometry/src/main/}

Background Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults, with pathological mechanisms remaining to be fully elucidated. Fibroblast Growth Factor 13 (FGF13) encodes an intracellular protein involved in microtubule stabilization and regulation of voltage-gated sodium channels (VGSCs) function. FGF13 mutation has been identified in patients with inherent seizure, suggesting a potential association between FGF13 and the etiology of TLE. Here, we set to explore the pathological role of FGF13 in the etiology of TLE. Results We found that the expression of FGF13 was increased in the cortical lesions and CA1 region of sclerotic hippocampus and correlated with the seizure frequency in TLE patients. Also, Fgf13 expression was increased in the hippocampus of chronic TLE mice generated by kainic acid (KA) injection. Furthermore, Fgf13 knockdown or overexpression was respectively found to attenuate or potentiate the effects of KA on axonal length, somatic area and the VGSCs-mediated current in the hippocampal neurons. Conclusions Taken together, these findings suggest that FGF13 is involved in the pathogenesis of TLE by modulating microtubule activity and neuronal excitability.

The level of serum lipids is associated with bone mineral density (BMD), an important skeletal trait. Yet the causality has not been determined. Here we performed a Mendelian randomization (MR) analysis to test potential causal links between BMD and lipid profile, i.e., low-density lipoprotein cholesterol (LDC-c), total cholesterol (TC), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-c). We observed causal effect of LDL-c, TC and TG to BMD, and reversely the effect of BMD to HDL-c. We further explored the effect of body mass index (BMI) in these causalities and found that the effect of LDL-c, TC and TG to BMD is independent of BMI. Our findings provided useful information in the clinical relevance of blood lipids on BMD variation and osteoporosis risk.

Objectives: Aiming to uncover the genetic basis of abdominal obesity, we performed a genome-wide association study (GWAS) meta-analysis of trunk fat mass adjusted by trunk lean mass (TFMadj) and followed by a series of functional investigations. Subjects: A total of 11,569 subjects from 6 samples were included into the GWAS meta-analysis. Methods: Meta-analysis was performed by a weighted fixed-effects model. In silico replication analysis was performed in the UK-Biobank (UKB) sample (N=331,093) and in the GIANT study (N up to 110,204). Cis-expression QTL (cis-eQTL) analysis, dual-luciferase reporter assay and electrophoresis mobility shift assay (EMSA) were conducted to examine the functional relevance of the identified SNPs. At last, differential gene expression analysis (DGEA) was performed. Results: We identified an independent SNP rs12409479 at 1p21 (MAF=0.07, p=7.26×10−10), whose association was replicated by the analysis of TFM in the UKB sample (one sided p=3.39×10−3), and was cross-validated by the analyses of BMI (one-sided p=0.03) and WHRadj (one-sided p=0.04) in the GIANT study. Cis-eQTL analysis demonstrated that allele A at rs12409479 was positively associated with PTBP2 expression level in subcutaneous adipose tissue (N=385, p=4.15×10−3). Dual-luciferase reporter assay showed that the region repressed PTBP2 gene expression by downregulating PTBP2 promoter activity (p

The method to efficiently design a sparse near-field focusing sparse array antenna is introduced here. First, the calculation model and analysis method of three array topologies including the square grid, the circular grid, and the regular triangular grid are established. The evaluation criterion is the lowest sparsity under the condition that the focusing performance of the sparse array approaches to that of a referenced focusing array with the element spacing of a half of one wavelength. After comparing the focusing performance of these array antennas with different grids, the circular-grid array is the optimal one and selected to further discuss the influence of different topology parameters. The optimal sparse near-field focusing array should have the constant distance between two adjacent rings and increase three elements compared with the last ring. Finally, the method based on the proposed selection criteria is employed to design a sparse near-field focusing sparse array. The correctness of the method has been validated by the full-wave simulated results.

Managing the complex demands on available energy, food and water is a fundamental challenge for a world with increasingly tenuous resource pools. The North China Plain’s groundwater crisis has become increasingly serious due to decades-long over-exploitation for irrigation to pursue high grain yield. This combined challenge motivated investigation of ways to mitigate the groundwater table decline while fostering the use of renewable bioenergy resources. To provide insights about tradeoffs among water, food and energy, we performed a six-year experiment from 2010 to 2015 in the North China Plain where groundwater use, biomass and biofuel production and water use efficiency were compared for four cropping systems. They are winter wheat-summer maize (WM, grains, 1-year cycle), ryegrass–sweet sorghum (RS, forage plus bioenergy crops, 1-year cycle), winter wheat–summer maize→ ryegrass–sweet sorghum (WMRS, forage, bioenergy plus grain crops, 2-year cycle), and perennial switchgrass (SG, bioenergy crop). Actual evapotranspiration (ETa) and recharge to groundwater were calculated and validated using observed soil moisture contents. Results showed ETa of the cropping systems were statistically similar ranging from 694 to 730 mm yr−1 with the exception of switchgrass which was significantly less at 504 mm yr-1. The water table was projected to decline by about 1.3 m yr-1 for all three multi-crop rotations and 0.4 m yr-1 for switchgrass. In terms of bioethanol production per unit land and per unit ETa, the ryegrass-sweet sorghum (RS) rotation performed best with 25.0 m3 ha-1 and 5.7 L m-3 outperforming the yearly winter wheat–summer maize (WM) rotation (11.7 m3 ha-1 and 3.3 L m-3) and switchgrass (11.4 m3 ha-1 and 2.6 L m-3). The multiple year rotation of winter wheat–summer maize→ ryegrass–sweet sorghum (WMRS) yielded 16.9 m3 bioethanol per hectare and 4.3 L m-3 bioethanol per m3 ETa. When optimizing bioethanol against net groundwater depletion, RS and switchgrass outperformed the two grain-based rotations with 15.5 L and 14.4 L of bioethanol per m3 of depleted groundwater, ahead of WMRS at 10.9 L m-3 and WM at 9.1 L m-3. These results are significant for setting governmental policies on sustainable use of groundwater by various crop mixes.

Bone mineral density (BMD) at various skeletal sites have shared genetic determinants. In the present study, aiming to identify shared loci associated with BMD, we conducted a joint association study of a genomewide association study (GWAS) and a meta-analysis of BMD at different skeletal sites: (i) a single GWAS of heel BMD in 142,487 individuals from the UK Biobank, and (ii) a meta-analysis of 30 GWASs of total body (TB) BMD in 66,628 individuals from the Genetic Factors for Osteoporosis (GEFOS) Consortium. The genetic correlation coefficient of the two traits was estimated to be 0.57. We performed joint association analysis with a recently developed statistical method multi-trait analysis of GWAS (MTAG) to account for trait heterogeneity and sample overlap. The joint association analysis combining samples of up to 209,115 individuals identified 18 novel loci associated with BMD at the genomewide significance level (α = 5.0 × 10-8 ), explaining an additional 0.43% and 0.60% of heel-BMD and TB-BMD heritability, respectively. The vast majority of the identified lead SNPs or their proxies exerted local expression quantitative trait loci (cis-eQTL) activity. Credible risk variants, defined as those SNPs located within 500 kilobases (kb) of the lead SNP and with p values within two orders of magnitude of the lead SNP, were enriched in transcription factor binding sites (p = 3.58 × 10-4 ) and coding regions (p = 5.71 × 10-4 ). Fifty-six candidate genes were prioritized at these novel loci using multiple sources of information, including several genes being previously reported to play a role in bone biology but not reported in previous GWASs (PPARG, FBN2, DEF6, TNFRSF19, and NFE2L1). One newly identified gene, SCMH1, was shown to upregulate the expression of several bone biomarkers, including alkaline phosphatase (ALP), collagen type 1 (COL-I), osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2), in mouse osteoblastic MC3T3-E1 cells, highlighting its regulatory role in bone formation. Our results may provide useful candidate genes for future functional investigations. © 2019 American Society for Bone and Mineral Research.

Dry eye disease (DED) is a multifactorial ocular surface disease. The commonest treatment is artificial tears. A novel artificial tears is urgently required to treat DED pathophysiologically, more than symptoms relief. In this study, a novel artificial tears with highly purified recombinant human lysozyme (rhLYZ), high homologous with natural tear, was obtained for DED treatment on a established rabbit DED model. 36 models were divided into 6 groups (n = 6), and treated with different concentration of novel artificial tears 180µl of drops daily, continuously for 4 weeks. To evaluate pathophysiologic therapeutic effect of the novel artificial tears, rabbit eyes were performed to the schirmer I test, tear ferning test, and corneal fluorescein staining test in 0, 1, 2, 3 and 4 weeks post-administration, respectively. The sacrificed models' corneas in 4 weeks were performed by pathological section staining. In the project, the quality of the artificial tears including rhLYZ was up to the quality standards of pharmacopoeia. RhLYZ eye drops, especially in the medium (0.15% of rhLYZ) and the high(0.30% of rhLYZ) concentration, enable to improve dry eye symptoms effectively, benefit to anti-inflammatory function and promote corneal repair. The novel artificial tears is a promising pathophysiological therapeutic agent in DED treatment.

To investigate the effects of different plasma target concentrations of remifentanil on the minimum alveolar concentration (MAC) for blocking adrenergic response (BAR) of sevoflurane in children with laparoscopic herniorrhaphy.Seventy-five children with 3-7 years old scheduled for laparoscopic herniorrhaphy were randomly divided into group RA total of 52 child patients were used among the anticipated 75 patients. In groups RRemifentanil by target-controlled infusion can effectively reduce the MACThe trial was registered at http://www.chictr.org.cn ( ChiCTR1800019393 , 8, Nov, 2018).

Background Age at natural menopause (ANM) is an important index for women’s health. Either early or late ANM is associated with a series of adverse outcomes later in life. Despite being an inheritable trait, its genetic determinant has not yet been fully understood. Methods Aiming to better characterize the genetic architecture of ANM, we conducted genome-wide association study (GWAS) meta-analyses in European-specific as well as trans-ancestry samples by using GWAS summary statistics from the following 3 large studies: the Reproductive Genetics Consortium (ReproGen; N = 69 626), the UK Biobank cohort (UKBB; N = 111 593) and the BioBank Japan Project (BBJ; N = 43 861), followed by a series of bioinformatical assessments and functional annotations. Results By integrating the summary statistics from the 3 GWAS of up to 225 200 participants, this largest meta-analysis identified 49 novel loci and 3 secondary signals that were associated with ANM at the genome-wide significance level (P < 5 × 10−8). No population specificity or heterogeneity was observed at most of the associated loci. Functional annotations prioritized 90 candidate genes at the newly identified loci. Among the 26 traits that were genetically correlated with ANM, hormone replacement therapy (HRT) exerted a causal relationship, implying a causal pattern by which HRT was determined by ANM. Conclusion Our findings improved our understanding of the etiology of female menopause, as well as shed light on potential new therapies for abnormal menopause.

Appendicular lean mass (ALM) is a heritable trait associated with loss of lean muscle mass and strength, or sarcopenia, but its genetic determinants are largely unknown. Here we conducted a genome-wide association study (GWAS) with 450,243 UK Biobank participants to uncover its genetic architecture. A total of 1059 conditionally independent variants from 799 loci were identified at the genome-wide significance level (p, Here, the authors report a genome-wide association study for appendicular lean mass using more than 450,000 participants in the UK Biobank Study. They identify 799 loci at genome-wide significance, explaining over 15% of phenotypic variance and >25% of the heritability, allowing the authors to uncover the genetic architecture of this sarcopenia-related trait.

Background: Study shows the metabolite, hexafluoroisopropanol (HFIP) from sevoflurane, has a strong inhibition on the central nervous system. This study aims to compare the level of free HFIP in the blood after inhaled a same concentration of sevoflurane in patients with normal liver function versus grade B liver dysfunction and observe its effect on patients’ recovery quality.Methods: Twenty four patients with normal liver function and twenty four patients with grade B liver dysfunction undergoing elective abdominal surgery were selected and assigned to group A and group B, respectively. All patients were inhaled sevoflurane (1.5MAC) for anesthesia about 3 h. The free HFIP concentration was determined at the time points of 0.5 h, 1 h, 2 h, 3 h after inhaled sevoflurane and 0.5 h, 1 h, 2 h, 4 h after discontinuation of sevoflurane, respectively. Patients’ eyes opening time, orientation recovery time, command response time and extubation time were observed after operation. The visual analogue scale (VAS) and Ramsay sedation score (RSS) were also evaluated at different time points after extubation. Results: Although the peak time of free HFIP in group B was 1 h later than that in group A, no significant differences were found in the peak concentration and other corresponding time points’ free HFIP concentrations between the two groups (PPPConclusion: The status of patients with grade B liver dysfunction does not affect the degree of sevoflurane metabolism. However, it can significantly prolong the peak time of free HFIP when compared with normal liver function.Trial registry number: Identified as ChiCTR 2000028901at http://www.chictr.org.cn/

Recent studies have demonstrated the important role played by gut microbiota in regulating bone development, but the evidence of such causal relationship is still sparse in human population. The aim of this study is to assess the causal relationship from gut microbiota to bone development and to identify specific causal bacteria taxa via a Mendelian randomization (MR) approach. A genome-wide association study (GWAS) summary statistic based two-sample MR analysis was performed. Summary statistics of microbiome GWAS (MGWAS) in 1126 twin pairs of the TwinsUK study was used as discovery sample, and the MGWAS in 984 Dutch participants from the LifeLines-DEEP cohort was used as replication sample. Estimated heel bone mineral density (eBMD) GWAS in 426,824 participants from the UK biobank (UKB) cohort was used as outcome. Bacteria were grouped into taxa features at both order and family levels. In the discovery sample, a total of 25 bacteria features including 9 orders and 16 families were analyzed. Fourteen features (5 orders + 9 families) were nominally significant, including 5 orders (Bacteroidales, Clostridiales, Lactobacillales, Pasteurellales and Verrucomicrobiales) and 9 families (Bacteroidaceae, Clostridiaceae, Lachnospiraceae, Mogibacteriaceae, Pasteurellaceae, Porphyromonadaceae, Streptococcaceae, Verrucomicrobiaceae and Veillonellaceae). One order Clostridiales and its child taxon, family Lachnospiraceae, were successfully replicated in the replication sample (Clostridiales Pdiscovery = 3.32 × 10−3 Preplication = 7.29 × 10−3; Lachnospiraceae Pdiscovery = 0.03 Preplication = 7.29 × 10−3). Our findings provided evidence of causal relationship from microbiota to bone development, as well as identified specific bacteria taxa that regulated bone mass variation, thus providing new insights into the microbiota mediated bone development mechanism.

BACKGROUND Keratitis is a complex condition in humans and is the second most common cause of legal blindness worldwide. MATERIAL AND METHODS To reveal the genomic loci underlying keratitis, we performed functional annotations of SNP-based and gene-based genome-wide association studies of keratitis in the UK Biobank (UKB) cohort with 337 199 subjects of European ancestry. RESULTS The publicly available SNP-based association results showed a total of 34 SNPs, from 14 distinct loci, associated with keratitis in the UKB. Gene-based association analysis identified 2 significant genes: IQCF3 (p=2.0×10⁻⁶) and SOD3 (p=2.0×10⁻⁶). Thirty-two candidate genes were then prioritized using information from multiple sources. The overlap of IQCF3 in these 2 analyses resulted in a total of 33 hub genes. Functional annotation of hub genes was performed and transcriptional factors of IQCF3 and SOD3 were predicted. CONCLUSIONS A total of 34 SNPs from 14 distinct loci were identified as being associated with keratitis, and 32 candidate genes were then prioritized. In addition, IQCF3 and SOD3 were identified by their p values through gene-based tests on the basis of individual SNP-based tests. The functional relationship between these suspect genes and keratitis suggest that IQCF3 and SOD3 are candidate genes underlying keratitis.

Bone mineral density (BMD) and lean body mass (LBM) not only have a considerable heritability each, but also are genetically correlated. However, common genetic determinants shared by both traits are largely unknown. In the present study, we performed a bivariate genome-wide association study (GWAS) meta-analysis of hip BMD and trunk lean mass (TLM) in 11,335 subjects from 6 samples, and performed replication in estimated heel BMD and TLM in 215,234 UK Biobank (UKB) participants. We identified 2 loci that nearly attained the genome-wide significance (GWS, p < 5.0 × 10(−8)) level in the discovery GWAS meta-analysis and that were successfully replicated in the UKB sample: 11p15.2 (lead SNP rs12800228, discovery p = 2.88 × 10(−7), replication p = 1.95 × 10(−4)) and 18q21.32 (rs489693, discovery p = 1.67 × 10(−7), replication p = 1.17 × 10(−3)). The above 2 pleiotropic loci may play a pleiotropic role for hip BMD and TLM development. So our findings provide useful insights that further enhance our understanding of genetic interplay between BMD and LBM.

The chemical finger printing-based methods for evaluating TCMs quality can report partial of TCMs quality without linking to effective constituents. In this study, a mathematical model was established for the quality evaluation of total saponins ofHigh-performance liquid chromatography (HPLC) fingerprints were applied to establish the chromatographic database of TSPJ. The associated hypolipidemic activity database was determined by TG assay using HepG2 cell model. Correlation analyses of two databases were performed by partial least squares (PLS) for calculating regression coefficients, and the interval value ofIn this study, the chromatographic data of 16 common peaks were obtained from 20 batches of TSPJ. After the estimate by this mathematical evaluation model, seven peaks were positively correlated with hypolipidemic activity, and nine peaks were negatively correlated with hypolipidemic activity. When theThese results indicated that the established model could be usefully applied to evaluate the quality of TSPJ in the hypolipidemic activity.

Optimizing irrigation strategies to increase water utilization efficiency and achieve higher yield is vital for balancing groundwater use and improving food security during water shortage in the North China Plain (NCP). Based on a 16-year field experiment (2003–2018) using seven irrigation schedules from W0M0 to W4M3 (numbers are irrigation times in wheat (W) and maize (M) season, 75 mm each) in the winter wheat–summer maize double cropping system, we analyzed annual total water consumption (ETa) and groundwater table change in terms of net groundwater depletion, annual total grain yield, water productivity (WP), irrigation water productivity (IWP) and marginal benefit of the whole wheat–maize system. Relationship between yield or WP and irrigation or ETa were also revealed. Results showed that (1) total ETa increased as irrigation input increased, ranging from 427.3 mm (Rainfed, W0M0) to 891.0 mm (W4M3). Soil water storage contributed nearly 30% to ETa for winter wheat under water deficit conditions. Pre-sowing soil water storage played an important role in improving the annual yield and WP of both wheat and maize by promoting germination, seedling emergence and root growth; (2) the rainfed treatment (W0M0) was best for mitigating the groundwater table decline (0.1 m yr-1), followed by W1M1 (0.5 m yr-1) and W2M1 (0.8 m yr-1). Groundwater table decline in M2W2 almost overlapped the observed data at the station (1.1 m yr-1). In W3M2, the farmers’ traditional practice, the groundwater table declined by 1.4 m yr-1, obviously over exploitation, while W4M2 and W4M3 declined by almost 2.0 m yr-1; (3) the relationship between total annual yield and irrigation (or ETa) followed a quadratic curve. Total annual yield significantly increased from W0M0 to M1W1 (25%) to M2M1 (5%) and then kept stable. Average annual WP decreased as irrigation increased, from 2.4 kg m-3 (W0M0) to 1.6 kg m-3 (W4M3). Average annual IWP and marginal benefit also declined as irrigation increased. These results over 16 years indicated that the W2M1 is the most balanced irrigation regime for wheat– maize rotation to mitigate groundwater decline, maintain grain production, and improve water use efficiency in the NCP.

Sweet sorghum [Sorghum bicolor (L.) Moench] offers a sustainable and renewable bioenergy resource for feed and biomass production. Two separate field experiments were conducted on arable land at Shangzhuang Station and on saline-alkali land at Quzhou Station in the North China Plain. Three cultivars of sweet sorghum including early- (ZS1) (114 days), medium- (CT2) (138 days), and late-maturity (LN3) (160 days), were sole cropped on arable land in 2006–2007. Using the same cultivars, sweet sorghum based - double cropping systems with winter wheat rotation were analyzed on saline-alkali land in 2009–2011. This study aims to determine the planting potential of three sweet sorghum cultivars and develop an optimized sweet sorghum - based double cropping system on saline-alkali land to maximize the production outputs. The aboveground biomass yield, energy output, theoretical ethanol yield (TEY), and chemical composition of three sweet sorghum cultivars - based cropping systems were assessed. Results indicate that: (1) the annual average dry biomass yield and dry matter content of the three sweet sorghum cultivars showed an overall uptrend with the increasing crop growth length. The average dry biomass yield of three sorghum maturity groups on arable land were 48.9% higher than that on saline-alkali land. (2) Sweet sorghum cultivars of late- (LN3) and medium- maturity (CT2) displayed better chemical composition for both bioenergy utilization (higher starch, soluble sugar, cellulose and hemicellulose and lower ash) and forage quality (better relative feed value (RFV) and lower acid detergent fiber (ADF) and neutral detergent fiber (NDF)). (3) The double cropping system of medium-maturity sweet sorghum (CT2) and winter wheat presented the best total dry biomass yield (24.9 t ha−1), energy output (394.6 GJ ha−1), and theoretical ethanol yield (6857 L ha−1). Therefore, this double cropping system can be recommended for extensive planting in the North China Plain for bioenergy or forage production.

Smith fir (Abies georgei var. smithii), which is the timberline constructive tree species in the cool slope of Mt. Sygera in the southeast of Tibet, plays a very important role in maintaining the timberline completeness and indicating global climate change. This study uses the instrumental recorded meteorological data along the altitude from 3600 to 4400 m at every 200 m in the growing season, investigates the smith fir growth biomass from 2006 to 2010 in the same timberline ecotone, and makes a non-linear regression analysis to determine the relationship between the alpine tree growth biomass and its in-situ environment condition. The results showed that the cool and warm slope share different air temperature lapse rates, which were −0.48 °C (100 m)−1 in the warm slope and −0.54 °C (100 m)−1 in the cool slope, respectively. However, the dominant timberline tree species in the warm slope was Sabina saltuaria, and it can reach as high as 4570 m, which is approximately 170 m higher than that in the cool slope. Moreover, the smith fir in the cool slope was only distributed in the range of elevation from approximately 3600 to 4400 m. The altitude of approximately 3800 m was the appropriate altitude for the growing smith fir, where the mean air temperature in the growing season was about 9.0 °C, and the young smith fir tree can form more biomass. The results suggested that alpine forest chose a suitable environment where trees can grow more in the prolonged succession, but not in the warmer or cooler condition, it could be seen as a biological evidence for climate change. Keywords: Abies georgei var. smithii, Growth biomass, Sabina saltuaria, In-situ environment condition, Non-linear regression analysis

Aiming to uncover a shared genetic basis of abdominal obesity and osteoporosis, we performed a bivariate GWAS meta-analysis of femoral neck BMD (FNK-BMD) and trunk fat mass adjusted by trunk lean mass (TFM(adj)) in 11,496 subjects from 6 samples, followed by in silico replication in the large-scale UK Biobank (UKB) cohort. A series of functional investigations were conducted on the identified variants. Bivariate GWAS meta-analysis identified two novel pleiotropic loci 12q15 (lead SNP rs73134637, p = 3.45 × 10(–7)) and 10p14 (lead SNP rs2892347, p = 2.63 × 10(–7)) that were suggestively associated and that were replicated in the analyses of related traits in the UKB sample (osteoporosis p = 0.06 and 0.02, BMI p = 0.03 and 4.61 × 10(–3), N up to 499,520). Cis-eQTL analysis demonstrated that allele C at rs73134637 was positively associated with IFNG expression in whole blood (N = 369, p = 0.04), and allele A at rs11254759 (10p14, p = 9.49 × 10(–7)) was negatively associated with PRKCQ expression in visceral adipose tissue (N = 313, p = 0.04) and in lymphocytes (N = 117, p = 0.03). As a proof-of-principle experiment, the function of rs11254759, which is 235 kb 5′-upstream from PRKCQ gene, was investigated by the dual-luciferase reporter assay, which clearly showed that the haplotype carrying rs11254759 regulated PRKCQ expression by upregulating PRKCQ promoter activity (p = 4.60 × 10(–7)) in an allelic specific manner. Mouse model analysis showed that heterozygous PRKCQ deficient mice presented decreased fat mass compared to wild-type control mice (p = 3.30 × 10(–3)). Mendelian randomization analysis demonstrated that both FNK-BMD and TFM(adj) were causally associated with fracture risk (p = 1.26 × 10(–23) and 1.18 × 10(–11)). Our findings may provide useful insights into the genetic association between osteoporosis and abdominal obesity.

An understanding of biomass yield and quality response to N supply is essential to breeding and cultivation of sorghum ( Sorghum bicolor (L.) Moench) for the production of bioethanol or forage. A two – year field experiment was conducted in 2013 and 2014 on semiarid marginal land in Inner Mongolia (39°10′N, 109°53′E) to determine the effects of N fertilizer rate (0, 60, 120, and 240 kg ha −1 ) on biomass yield and quality of sweet sorghum (GT-8) and biomass sorghum (GN-11), and on soil conditions. Results indicated that (1) biomass yield, leaf/stem ratio, and crude protein (CP), protein yield, theoretical ethanol yield (TEY), and soil net NO 3 − -N accumulation of both sorghum varieties in 2013 and 2014 significantly increased with the increasing N fertilizer rate from 0 to 240 kg ha −1 , whereas dry matter ratio and relative feed value (RFV) varied inversely with the N application rates. (2) Compared to biomass sorghum (GN-11), sweet sorghum (GT-8) demonstrated significant enhancement of forage quality components including CP, dry matter digestibility (DMD), dry matter intake (DMI), total digestible nutrients (TDN), net energy for lactation (NE L ), and RFV, with stems exhibiting higher forage quality than leaves. Biomass sorghum (GN-11) exhibited better performance for bioenergy production, with an average biomass yield of 7.9 t ha −1 and TEY of 3046.7 L ha −1 averaged across all N rates. (3) Annual average amount of net NO 3 − -N accumulation in 0–90 cm layers of two years significantly increased when fertilizer N exceeded 120 kg N ha −1 . In short, N fertilizer of 60 kg ha −1 is recommended to sweet sorghum for the forage production and 120 kg N ha −1 to biomass sorghum for bioenergy feedstock sustainability, respectively, meanwhile to prevent the soil degradation on semiarid marginal lands.