Evolution of olfactory receptor superfamily in bats based on high throughput molecular modelling.

The origin of flight and laryngeal echolocation in bats is likely to have been accompanied by evolutionary changes in other aspects of their sensory biology. Of all sensory modalities in bats, olfaction is perhaps the least well understood. Olfactory receptors (ORs) function in recognizing odour molecules, with crucial roles in evaluating food, as well as in processing social information. Here we compare OR repertoire sizes across taxa and apply a new pipeline that integrates comparative genome data with protein structure modelling and then we employ molecular docking techniques with small molecules to analyse OR functionality based on binding energies. Our results suggest a sharp contraction in odorant recognition of the functional OR repertoire during the origin of bats, consistent with a reduced dependence on olfaction. We also compared bat lineages with contrasting different ecological characteristics and found evidence of differences in OR gene expansion and contraction, and in the composition of ORs with different tuning breadths. The strongest binding energies of ORs in non-echolocating fruit-eating bats were seen to correspond to ester odorants, although we did not detect a quantitative advantage of functional OR repertoires in these bats compared with echolocating insectivorous species. Overall, our findings based on molecular modelling and computational docking suggest that bats have undergone olfactory evolution linked to dietary adaptation. Our results from extant and ancestral bats help to lay the groundwork for targeted experimental functional tests in the future.

Evolution and expression patterns of the neo-sex chromosomes of the crested ibis.

Bird sex chromosomes play a unique role in sex-determination, and affect the sexual morphology and behavior of bird species. Core waterbirds, a major clade of birds, share the common characteristics of being sexually monomorphic and having lower levels of inter-sexual conflict, yet their sex chromosome evolution remains poorly understood. Here, by we analyse of a chromosome-level assembly of a female crested ibis (Nipponia nippon), a typical core waterbird. We identify neo-sex chromosomes resulting from fusion of microchromosomes with ancient sex chromosomes. These fusion events likely occurred following the divergence of Threskiornithidae and Ardeidae. The neo-W chromosome of the crested ibis exhibits the characteristics of slow degradation, which is reflected in its retention of abundant gametologous genes. Neo-W chromosome genes display an apparent ovary-biased gene expression, which is largely driven by genes that are retained on the crested ibis W chromosome but lost in other bird species. These results provide new insights into the evolutionary history and expression patterns for the sex chromosomes of bird species.

iORbase: A database for the prediction of the structures and functions of insect olfactory receptors.

Insect olfactory receptors (iORs) with atypical 7-transmembrane domains, unlike Chordata olfactory receptors, are not in the GPCR protein family. iORs selectively bind to volatile ligands in the environment and affect essential insect behaviors. In this study, we constructed a new platform (iORbase, https://www.iorbase.com) for the structural and functional analysis of iORs based on a combined algorithm for gene annotation and protein structure prediction. Moreover, it provides the option to calculate the binding affinities and binding residues between iORs and pheromone molecules by virtual screening of docking. Furthermore, iORbase supports the automatic structural and functional prediction of user-submitted iORs or pheromones. iORbase contains the well-analyzed results of approximately 6 000 iORs and their 3D protein structures identified from 59 insect species and 2 077 insect pheromones from the literature, as well as approximately 12 million pairs of simulated interactions between functional iORs and pheromones. We also built 4 online modules, iORPDB, iInteraction, iModelTM, and iOdorTool to easily retrieve and visualize the 3D structures and interactions. iORbase can help greatly improve the experimental efficiency and success rate, identify new insecticide targets, or develop electronic nose technology. This study will shed light on the olfactory recognition mechanism and evolutionary characteristics from the perspectives of omics and macroevolution.

Focus on the Analysis of the Effect of Solving the Nursing Mode on the Time of the Production Time of the First Maternity and the Subjective Happiness of the Postpartum.

Objective: Focusing to solve the significance of the nursing mode for preliminary maternity care. Methods: Selected 116 first mothers produced in our hospital from January 2010 to January 2022, which were divided into the control group and research group. The two groups each paid conventional care and focused on solving the nursing mode care. Analyze the two groups of pregnancy endings, self-efficacy, negative emotions, subjective happiness, and analgesics. Results: The vaginal delivery rate of the research group was higher than that of the control group, and the cesarean section rate, hospitalization time, and delivery process were lower than the control group (P < 0.05); the amount of bleeding in the postpartum groups increased, but compared with the control group, the increase in bleeding in the research group was smaller (P < 0.05); the research group objective, subjective support, self-evaluation, and subjective happiness index were higher than the control group (P < 0.05). Conclusion: Focusing to solve the nursing model can help the maternal tension relief, the maternal can quickly enter the role, and it plays an important role in establishing a good nursing relationship.

[Understanding of needle-knife medicine on ashi point].

The concept of ashi point and the understanding of modern acupoint research on ashi points were analyzed. According to the bowstring mechanics anatomy of needle-knife medicine and mesh theory, it was believed ashi point was the warning of mechanical imbalance of bowstring mechanics anatomy. Ashi points were mainly distributed in the joint part of bowstring or stress concentration of string; the acupotomy could compensate for the subjectivity and arbitrariness of point selection of ashi, which also emphasized the importance of ashi point anatomy.

[Anatomical basis and clinical application of "two points" acupotomology surgery program in treating cubital tunnel syndrome].

OBJECTIVE: To explore an effective acupotomology surgery program in treating cubital tunnel syndrome. METHODS: According to pathogenic factors and elbow anatomy, a "two points" acupotomology surgery program was designed, which could loose the attachment point of arcuate ligament on medial border of olecroanon and medial epicondyle of humerus. Twenty-one cases of cubital tunnel syndrome were treated with acupotmology, then the efficacy was obsered. RESULTS: After one year postoperative visit, 21 patients with ulnar nerve area skin numbness were cured, claw hand deformity and medial hand muscle atrophy recovered significantly. Results of function evaluation were excellent in 17 cases, good in 2 cases, fair in 2 cases and poor in 0 cases, the good rate was 90.5%. CONCLUSION: The acupotomology surgery program which could cut the starting and ending points of osborne's ligament and solve the problem of ulnar nerve entrapment is an easy, little-traumatic and effective minimally invasive surgery which also conforms to the anatomical structure.

Toward immunosuppressive effects on liver transplantation in rat model: tacrolimus loaded poly(ethylene glycol)-poly(D,L-lactide) nanoparticle with longer survival time.

In this study, tacrolimus (FK506) was encapsulated into a biodegradable poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PLA) block copolymer using a double emulsion-solvent evaporation technique. Drug loading (DL) and encapsulation efficiency (EE) can be changed by varying the mass ratio of FK506/MPEG-PLA. Furthermore, transmission electron microscope (TEM) and Malvern Zetasizer were used to investigate the properties of FK506/MPEG-PLA nanoparticles (DL=9.5%), which were monodisperse (PDI=0.100 ± 0.023) with a mean particle size of 90.5 ± 1.5 nm. Compared with FK506 capsule, in vitro release profile showed that FK506/MPEG-PLA nanoparticles exhibited sustained release. Meanwhile, the higher concentration and longer retention time in plasma were also confirmed in vivo. We further preliminarily evaluated immunosuppressive effect on liver transplantation in rat model. The survival time of the rat administrated FK506/MPEG-PLA nanoparticles was obviously prolonged than that of the control group administrated FK506 capsule.

Polymeric micelles, a promising drug delivery system to enhance bioavailability of poorly water-soluble drugs.

Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs) can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1) protection of the loaded drug from the harsh environment of the GI tract, (2) release of the drug in a controlled manner at target sites, (3) prolongation of the residence time in the gut by mucoadhesion, and (4) inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained.

Oral administration of heparin or heparosan increases the Lactobacillus population in gut microbiota of rats.

Heparin and heparosan have been confirmed to be effective blockers in inhibiting adhesion of pathogens in vitro. However, their effects on gut microbiota in vivo remain unknown. Here we have studied the effects of oral administration of heparin or heparosan on gut microbiota in rats by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Results showed that the predominant bacterial communities in the feces of heparin- or heparosan-treated animals were different from those of the saline-treated animals, with increased Lactobacillus spp. and decreased Enterococcus sp. Different DGGE banding patterns were also observed for the subpopulations of Lactobacillus and Bacteroides groups. In conclusion, heparin or heparosan may be used as an effective gut microbiota modulator by increasing the subpopulation of Lactobacillus.

Intra-articular injection of xanthan gum reduces pain and cartilage damage in a rat osteoarthritis model.

The objective of this study was to evaluate the alleviative effect of intra-articular (IA) injection of xanthan gum (XG) on pain and cartilage degradation in a model of monosodium iodoacetate (MIA)-induced knee osteoarthritis (OA). The rheological study and hyaluronidase (HAse) degradation analysis of XG injection were presented. The effect of pain relief was determined by measurements of paw withdrawal threshold and weight bearing by hind limbs. The protective effect on the cartilage was evaluated by gross morphological observation and histological evaluation of knee joints. The effect was investigated in two protocols: a therapeutic treatment protocol, and a prophylactic treatment protocol. Our results showed that HAse had no effect on the rheological properties of XG injection. Local XG administration in both protocols could reduce OA pain and alleviate the joint cartilage degradation induced by MIA. IA injection of XG might be an effective method for OA treatment in human.

The protective effect of xanthan gum on interleukin-1ß induced rabbit chondrocytes.

We have previously shown that intra-articular injection of xanthan gum (XG) could protect the joint cartilage and reduce osteoarthritis progression. In this study, we investigated the preliminary cytotoxicity of XG on chondrocytes, evaluated the effects of XG on the proliferation and the protein expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinase-1 (TIMP-1) in interleukin-1ß (IL-1ß)-induced rabbit chondrocytes. Primary rabbit chondrocytes were cultured. After treatment with various concentrations of XG with or without 10 ng/mL IL-1ß, the proliferation of chondrocytes was evaluated using the MTT assay and the expression levels of MMPs and TIMP-1 were evaluated using ELISA. The results showed that XG alone displayed no adverse effects on cell viability and reversed significantly IL-1ß-reduced cell proliferation in a dose-dependent manner. Furthermore, XG showed a dose-dependent inhibition in the IL-1ß-induced release of MMPs while increasing TIMP-1 expression. These results strongly suggest that XG affords protection on IL-1ß induced rabbit chondrocytes.

The aryl hydrocarbon receptor nuclear translocator-interacting protein 2 suppresses the estrogen receptor signaling via an Arnt-dependent mechanism.

We explored whether modulation of the estrogen receptor (ER) signaling is possible through an aryl hydrocarbon receptor nuclear translocator (Arnt)-dependent mechanism. We utilized the Arnt-interacting protein 2 (Ainp2) to examine whether the presence of Ainp2 in MCF-7 cells would interfere with the Arnt-mediated ER signaling. We found that Arnt increased the 17 beta-estradiol (E2)-dependent luciferase activity and Ainp2 significantly suppressed this Arnt-mediated luciferase activity. Ainp2 significantly suppressed 25% of the E2- and Arnt-dependent up-regulation of the GREB1 message. No suppression of the ER target gene expression by Ainp2 was detected in Arnt-knockdown MCF-7 cells and in Arnt-independent ER signaling. Although Ainp2 did not interact with ER alpha and ER beta, it suppressed the ER alpha::Arnt interaction and reduced the E2-driven recruitment of Arnt to the GREB1 promoter. We concluded that Ainp2 suppresses the ER signaling by not allowing Arnt to participate in the ER-dependent, Arnt-mediated activation of gene transcription.

Beta tubulin affects the aryl hydrocarbon receptor function via an Arnt-mediated mechanism.

We have been studying the requirement for the aryl hydrocarbon receptor nuclear translocator (Arnt)-dependent DNA complex formation, which precedes the activation of gene transcription. Using DEAE chromatography, we have obtained a Sf9 insect fraction F5 that is highly enriched with beta-tubulin. F5 inhibits the formation of the AhR gel shift complex and this inhibition is sensitive to protease, suggesting that proteins that are present in this F5 fraction are responsible for the inhibition. Additional experiments have revealed that this inhibition is less pronounced in the presence of anti-beta-tubulin IgG and beta-tubulin enriched fraction from pig brain also inhibits the AhR gel shift formation. Sf9 beta-tubulin interacts with Arnt and suppresses the binding of the AhR/Arnt heterodimer to its corresponding enhancer. Human beta4-tubulin, which shares high sequence identity with Sf9 beta-tubulin, suppresses the AhR-dependent luciferase expression by reducing the nuclear Arnt content and retaining Arnt in the cytoplasm. Fluorescence studies using the GFP fusion of human beta4-tubulin have revealed that beta4-tubulin prevents the localization of Arnt in Sf9 cells. Here we have provided evidence suggesting that beta-tubulin may regulate the physiological content of Arnt.

Correlation between hand and total body bone density in normal Chinese children.

Hand bone mineral density (BMD) in adults was found to be significantly correlated with various skeletal sites, including the total body. However, the relationships between hand and total body bone measurements have yet to be explored for children. We conducted a cross-sectional study of 892 normal Chinese children (511 males, 381 females) aged 5-14 years by measuring the BMD and bone mineral content (BMC) at the total hand, upper limb, subtotal body, and total body using dual-energy X-ray absorptiometry (DXA). We found that hand BMD and BMC increased with age for both genders. Female children had significantly higher hand BMD and BMC than males. Age explained more variance in hand BMD for females (R2=0.727) than for males (R2=0.596). For both genders, hand BMD and BMC correlated highly with age, weight, height, total body lean mass, and BMD and BMC at the upper limb, subtotal body, and total body (r=0.730-0.965, p<0.001) and moderately with body mass index and total body fat mass (r=0.525-0.701, p<0.001). Therefore, the hand DXA scan can potentially be a new tool for the clinical assessment of bone health in children.

Effects of chitosan and heparin on early extension of burns.

Chitosan, a naturally occurring high-molecular glycosaminoglycan (GAG), has been widely used in wound healing, including burns. Heparin is also a highly used glycosaminoglycan in burns. To evaluate the effects of chitosan and heparin alone and the mixture of chitosan and heparin on early extension of burn wound, deep partial-thickness burns were performed on the dorsum of rats. Then chitosan and heparin powder and the mixture of chitosan and heparin were applied, respectively, on the burn wounds. After 72 h, histological examination of the burn wounds was performed. Outcome showed that the burn degree of chitosan group was less severe than control group and chitosan greatly prevented the extension of burns in early phase. However, heparin had no protective effect on the early extension of burns. Use of chitosan and heparin together attenuated chitosan's protective effect.

Normal reference for bone density in healthy Chinese children.

An ethnicity- and gender-specific normal reference database is necessary for the clinical dual-energy X-ray absorptiometry (DXA) assessment of skeletal status in Chinese children. We used a Lunar Prodigy DXA densitometer to measure bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) at total body and subcranial skeleton for 877 healthy Chinese children (505 boys, 372 girls) aged 5-13 yr. The height-for-age, BA-for-height, and BMC-for-BA percentile curves were developed using the LMS method (L, power in Box-Cox transformation; M, median; S, coefficient of variation). We found that total body BMD and subcranial skeleton BMD were highly correlated (r=0.701-0.949), and that total body BMD was significantly higher than subcranial skeleton BMD for each gender and age group (p<0.001). No gender differences in total body and subcranial skeleton BMD were found. Total body lean mass correlated highly with total body BMC and subcranial skeleton BMD and BMC (boys: r=0.888-0.953, girls: r=0.917-0.967) and moderately with total body BMD (boys: r=0.684, girls: r=0.777). The head region accounted for 16-52% and 16-49% of the total body BMC in boys and girls, respectively, and the percentages were negatively correlated with age (boys: r=-0.824, girls: r=-0.864) and height (boys: r=-0.911, girls: r=-0.922). Regression analyses showed that age explained more variance in subcranial skeleton BMD (boys: R(2)=0.641, girls: R(2)=0.685) than in total body BMD (boys: R(2)=0.387, girls: R(2)=0.472). In summary, we have presented an ethnicity- and gender-specific densitometric normal reference database for Chinese children aged 5-13 yr. It should allow for an appropriate clinical assessment of total body bone density in Chinese children as measured by the Lunar Prodigy DXA densitometer.

Bilateral femoral bone mineral density measurements in Chinese women and men.

The aim of this study was to assess the contralateral femoral bone mineral density (BMD) difference as measured by dual-energy X-ray absorptiometry (DXA) in mainland Chinese women and men. We measured bilateral proximal femora (i.e., total hip, femoral neck, upper femoral neck, and trochanter) using DXA in 1101 subjects (284 males, 817 females), among whom 504 were postmenopausal. Data were analyzed by descriptive statistics, Student's t-tests, and Pearson's correlation coefficients (r). With bilateral femur measurements and the acquisition of the mean BMD, precision error could be significantly reduced at the total hip, the femoral neck, and the upper femoral neck. Contralateral femoral BMD was highly correlated at all measuring sites (r=0.879-0.964). For the male group and for the postmenopausal subgroup, no significant differences in contralateral femoral BMDs were found. In the postmenopausal women, the percentage of subjects with discordance in classification (i.e., normal, osteopenia, and osteoporosis) for the left and right femora declined from 16.9% to 8.1% with precision adjustment. From a population perspective, since there may still be a considerable number of misdiagnosed cases, we therefore suggest that bilateral femur measurements may be justified for postmenopausal Chinese women.

A novel polypeptide from shark cartilage with potent anti-angiogenic activity.

Using guanidine-HCl extraction, acetone precipitation, ultra-filtration and chromatography, a novel polypeptide with potent anti-angiogenic activity was purified from cartilage of the shark, Prionace glauca. N-terminal amino acid sequence analysis and SDS-PAGE revealed that the substance is a novel polypeptide with MW 15500 (PG155). The anti-angiogenic effects of PG155 were evaluated using zebrafish embryos model in vivo. Treatment of the embryos with 20 microg/ml PG155 resulted in a significant reduction in the growth of subintestinal vessels (SIVs). A higher dose resulted in almost complete inhibition of SIV growth, as observed by endogenous alkaline phosphatase (EAP) staining assay. An in vitro transwell experiment revealed that the polypeptide inhibited vascular endothelial growth factor (VEGF) induced migration and tubulogenesis of human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs in 20 microg/ml PG155 significantly decreased the density of migrated cells. Almost complete inhibition of cell migration was found when HUVECs were treated with 40-80 microg/ml PG155. PG155 (20 microg/ml) markedly inhibited the tube formation of HUVECs and a dose-dependent effect was also found when treatment of HUVECs with PG155 at the concentration from 20-160 microg/ml.

Oral absorption of hyaluronic acid and phospholipids complexes in rats.

AIM: To prepare a complex of hyaluronic acid (HA) and phospholipids (PL), and study the improvement effect of PL on the oral absorption of HA. METHODS: The complex of HA-PL (named Haplex) was prepared by film dispersion and sonication method, its physico-chemical properties were identified by infrared spectra and differential scanning calorimetry (DSC). The oral absorption of Haplex was studied. Thirty-two healthy rats were divided into 4 groups randomly: (1) a normal saline (NS) control group; (2) an HA group; (3) a mixture group and (4) a Haplex group. After intragastric administration, the concentration of HA in serum was determined. RESULTS: The physico-chemical properties of Haplex were different from HA or PL or their mixture. After Haplex was administered to rats orally, the serum concentration of HA was increased when compared with the mixture or HA control groups from 4 h to 10 h (P<0.05). The DeltaAUC0-12 h of Haplex was also greater than that of the other three groups (P<0.05). CONCLUSION: The method of film dispersion and sonication can prepare HA and PL complex, and PL can enhance the oral absorption of exogenous HA.

Assessment of total body fat percentage from regional spine and femur DXA measurements among Chinese women and men.

This study was aimed at determining the correlation between regional body composition and total body fat percentage (TBF%), as measured by dual-energy X-ray absorptiometry (DXA), among Chinese women and men. Men (n=203) and women (n=630), aged 20-87yr, were assessed for height, weight, and body mass index (BMI) and for total body, lumbar spine (L2-L4), and left and right proximal femur fat percentage using DXA. Based on their BMI, male and female subjects were subdivided into 4 groups. For all groups, the TBF% derived from the total body scan was strongly correlated with spine %fat (r range: 0.60-0.96) and the left and right femur %fat (r range: 0.72-0.80 and 0.69-0.83, respectively), as obtained from regional scans. In stepwise regression, TBF% was best assessed by spine %fat, left femur %fat, age, and BMI for both genders (male: R(2)=0.88; female: R(2)=0.84). Equations with spine %fat, age, and BMI also provided good estimates of TBF% (male: R(2)=0.80; female: R(2)=0.75), whereas android and gynoid %fat were predicted with spine %fat and left femur %fat, respectively, and the predicted fat percentage ratio of android to gynoid (A/G) could be obtained from spine %fat and left femur %fat. The cross-validation results showed that the accuracy of all prediction equations was high in the male group, whereas prediction equations with high-to-moderate accuracy were found in the female group. Therefore, for DXA systems that do not offer total body scan, clinicians can assess TBF% using data obtained from regional scans.