Age-, season- and gender-specific reference intervals of serum 25-hydroxyvitamin D3 for healthy children (0 ~ 18 years old) in Nanning area of China.

Establishing specific reference intervals (RIs) of serum 25-hydroxyvitamin D3 [25(OH)D] for children is essential for improving the accuracy of diagnosis and prognosis monitoring of diseases such as rickets and growth retardation. The study including 6,627 healthy children was conducted to establish specific RIs of 25(OH)D for children in Nanning area of China. The results showed that there were statistically significant differences among age, season, and gender of serum 25(OH)D levels, and the age-specific RIs of serum 25(OH)D were 20.3 ~ 53.6 ng/mL for 0 ~ ≤ 1 year and 18.9 ~ 49.6 ng/mL for 2 ~ ≤ 3 years. The age-, season-specific RIs of serum 25(OH)D for 4 ~ ≤ 6 years in spring-summer and autumn-winter were 15.8 ~ 42.6 ng/mL and 15.2 ~ 37.7 ng/mL, respectively. The age-, gender-specific RIs of serum 25(OH)D for 7 ~ ≤ 18 years for males and females were 12.1 ~ 36.1 ng/mL and 10.8 ~ 35.3 ng/mL, respectively. This study successfully established the RIs of serum 25(OH)D, which may help to improve disease diagnosis and monitoring for children in the Nanning area of China.

Oral Administration of the Antimicrobial Peptide Mastoparan X Alleviates Enterohemorrhagic Escherichia coli-Induced Intestinal Inflammation and Regulates the Gut Microbiota.

The gut microbiota plays an important role in intestinal immune system development and in driving inflammation. Antibiotic administration for therapeutic purposes causes an imbalance in the gut microbiota. Antimicrobial peptides can regulate the gut microbiota and maintain intestinal homeostasis. The aim of this study was to investigate the anti-inflammatory effects and regulation of the gut microbiota by the orally administered antimicrobial peptide mastoparan X (MPX). In this study, Escherichia coli was used to induce intestinal inflammation, and the results showed that MPX+ E. coli alleviated weight loss and intestinal pathological changes in necropsy specimens of E. coli-infected mice. MPX+ E. coli reduced the serum levels of the inflammation-related proteins interleukin-2, interleukin-6, tumour necrosis factor-α, myeloperoxidase, and lactate dehydrogenase on days 7 and 28. Furthermore, MPX+ E. coli increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum and colon post infection. Scanning electron microscopy and transmission electron microscopy results showed that MPX could improve the morphology of jejunum villi and microvilli and increase tight junction protein levels. 16S rRNA sequencing analysis of caecal content samples showed that the species diversity and richness were lower in the E. coli-infected group. At the genus level, MPX+ E. coli significantly reduced the abundance of Bacteroidales and Alistipes and enhanced the relative abundance of Muribaculaceae. Alpha-diversity analyses (Shannon index) showed that MPX significantly increased the microbial diversity of mice. Overall, this study is the first to investigate the effects of oral administration of MPX on intestinal inflammation and the gut microbiota, providing a new perspective regarding the prevention of enteritis and maintenance of intestinal homeostasis.

Antimicrobial peptide MPX attenuates LPS-induced inflammatory response and blood-testis barrier dysfunction in Sertoli cells.

Orchitis accounts for a high proportion of male animal reproductive disorders. Hence, it is urgent to identify drugs for the prevention and treatment of orchitis. Antimicrobial peptides (AMPs) are currently recognized as one of the most promising alternatives to antibiotics. However, the protective effects of AMPs on lipopolysaccharide (LPS)-induced orchitis have not been reported. In this study, we developed an LPS-induced orchitis model in which primary bovine Sertoli cells were used as model cells. MPX was indicated to effectively reduce the inflammatory response of Sertoli cells. MPX attenuated the gene expression of the proinflammatory cytokines TNF-α, IL-6 and IL-1ß by suppressing the MAPK pathway, especially the phosphorylation of p38 and ERK. MPX also decreased the oxidative stress response caused by LPS and upregulated Occludin and Claudin-1 expression, thereby maintaining the integrity of the blood-testis barrier. Moreover, we found that MPX inhibited apoptosis in Sertoli cells. In a mouse model, we found that MPX significantly inhibited the disruptive effects of LPS, reducing seminiferous epithelium damage, vacuolations, hyperplasia, and apoptosis in spermatogenic cells and rescuing spermatogenesis. In addition, the expression of inflammatory factors such as IL-1ß, IL-18, IL-6 and TNF-α was decreased after MPX treatment in the mouse testes. MPX had no effect on other organs in mice, indicating its safety. This study was undertaken to investigate how MPX regulates the inflammatory response in Sertoli cells and provide a reference for the clinical prevention and treatment of male animal orchitis.

Survivable potential of germ cells after trehalose cryopreservation of bovine testicular tissues.

Germplasm preservation of livestock or endangered animals and expansion of germline stem cells are important. The purpose of this study is to investigate whether supplementation of trehalose to the freezing medium (FM) reduces tissular damage and improves the quality of testicular cells in the cryopreserved bovine testicular tissues. We herein established an optimized protocol for the cryopreservation of bovine testicular tissues, and the isolation as well as culture of bovine germ cells containing spermatogonial stem cells (SSCs) from these tissues. The results showed that FM containing 10% dimethyl sulfoxide (Me2SO/DMSO), 10% knockout serum replacement (KSR) and 20% trehalose (FM5) combined with the uncontrolled slow freezing (USF) procedures has the optimized cryoprotective effect on bovine testicular tissues. The FM5 + USF protocol reduced the cell apoptosis, maintained high cell viability, supported the structural integrity and seminiferous epithelial cohesion similar to that in the fresh tissues. Viable germ cells containing SSCs were effectively isolated from these tissues and they maintained germline marker expressions in the co-testicular cells and co-mouse embryonic fibroblasts (MEF) feeder culture systems respectively, during the short-term culture. Additionally, upregulated transcriptions of spermatogenic differentiation marker C-KIT and meiotic marker SYCP3 were detected in these cells after retinoic acid-induced differentiation. Together, FM5 + USF is suitable for the cryopreservation of bovine testicular tissues, with benefits of reducing the apoptosis, maintaining the cell viability, supporting the testicular structure integrity, and sustaining the survival and differentiation potential of bovine germ cells containing SSCs.

[Therapeutic effect of baicalin in treatment of renal interstitial fibrosis in rats with unliateral ureteral obstruction and related mechanisms].

OBJECTIVE: To investigate the therapeutic effect of baicalin at different doses administered for different periods of time in the treatment of renal interstitial fibrosis in rats with unliateral ureteral obstruction (UUO) and related mechanisms. METHODS: Sixty-four Sprague-Dawley rats were randomly divided into sham-operation, model, low-dose baicalin, and high-dose baicalin groups, and each group was further randomly divided into 7-day and 14-day groups (n=8 each). Left ureteral ligation was used to establish the rat model of UUO. Hematoxylin and eosin staining was used to observe the pathological changes in the kidney. ELISA was used to measure the serum levels of transforming growth factor-ß1 (TGF-ß1), Notch1, and Jagged1. Immunohistochemistry was used to measure the expression of TGF-ß1 and Notch1. The Pearson correlation analysis was used for correlation analysis. RESULTS: Hematoxylin and eosin staining showed inflammatory cell infiltration and edema in renal interstitium, tubular dilation and structure disorder, degeneration and necrosis of renal tubular epithelial cells, and a basically normal structure of the glomeruli on days 7 and 14 in the model group, and these lesions were alleviated in the low- and high-dose baicalin groups. Compared with the sham-operation group, the model group had a significantly higher serum level of TGF-ß1 and a significantly higher number of TGF-ß1-positive cells in renal tissues on days 7 and 14 (P<0.05). Compared with the model group at the same time points, the high- and low-dose baicalin groups had a significantly lower serum level of TGF-ß1 and a significantly lower number of TGF-ß1-positive cells in renal tissues on days 7 and 14 (P<0.05). The serum level of Jagged1 showed no significant differences between any two groups on days 7 and 14 (P>0.05). The serum level of TGF-ß1 was positively correlated with that of Notch1 (r=0.650, P<0.01), and the serum level of Notch1 was positively correlated with that of Jagged1 (r=0.727, P<0.01). TGF-ß1 level in renal tissues was also positively correlated with the number of Notch1-positive cells (r=0.743, P<0.01). CONCLUSIONS: Baicalin can alleviate renal interstitial fibrosis in UUO rats, probably by inhibiting Notch1 signaling pathway and the expression of TGF-ß1.

Out of southern East Asia: the natural history of domestic dogs across the world.

The origin and evolution of the domestic dog remains a controversial question for the scientific community, with basic aspects such as the place and date of origin, and the number of times dogs were domesticated, open to dispute. Using whole genome sequences from a total of 58 canids (12 gray wolves, 27 primitive dogs from Asia and Africa, and a collection of 19 diverse breeds from across the world), we find that dogs from southern East Asia have significantly higher genetic diversity compared to other populations, and are the most basal group relating to gray wolves, indicating an ancient origin of domestic dogs in southern East Asia 33 000 years ago. Around 15 000 years ago, a subset of ancestral dogs started migrating to the Middle East, Africa and Europe, arriving in Europe at about 10 000 years ago. One of the out of Asia lineages also migrated back to the east, creating a series of admixed populations with the endemic Asian lineages in northern China before migrating to the New World. For the first time, our study unravels an extraordinary journey that the domestic dog has traveled on earth.

[Chemical Constituents from Mallotus paniculatus (II)].

OBJECTIVE: To study the chemical constituents of Mallotus paniculaus radix. METHODS: The compounds were isolated with column chromatography. The chemical structures were identified by spectral and spectroscopic technology. RESULTS: Seven compounds were isolated from the n-BuOH extract and identified as scopoletin(1), isoscopletin(2), erythordiol(3), apigenin(4), 4-methoxybenzoic acid(5), acetylaleuritolic acid(6) and ß-daucosterol (7). CONCLUSION: compounds 2 - 6 are isolated from this plant for the first time.

Ancient inland human dispersals from Myanmar into interior East Asia since the Late Pleistocene.

Given the existence of plenty of river valleys connecting Southeast and East Asia, it is possible that some inland route(s) might have been adopted by the initial settlers to migrate into the interior of East Asia. Here we analyzed mitochondrial DNA (mtDNA) HVS variants of 845 newly collected individuals from 14 Myanmar populations and 5,907 published individuals from 115 populations from Myanmar and its surroundings. Enrichment of basal lineages with the highest genetic diversity in Myanmar suggests that Myanmar was likely one of the differentiation centers of the early modern humans. Intriguingly, some haplogroups were shared merely between Myanmar and southwestern China, hinting certain genetic connection between both regions. Further analyses revealed that such connection was in fact attributed to both recent gene flow and certain ancient dispersals from Myanmar to southwestern China during 25-10 kya, suggesting that, besides the coastal route, the early modern humans also adopted an inland dispersal route to populate the interior of East Asia.

Genomic Analyses Reveal Potential Independent Adaptation to High Altitude in Tibetan Chickens.

Much like other indigenous domesticated animals, Tibetan chickens living at high altitudes (2,200-4,100 m) show specific physiological adaptations to the extreme environmental conditions of the Tibetan Plateau, but the genetic bases of these adaptations are not well characterized. Here, we assembled a de novo genome of a Tibetan chicken and resequenced whole genomes of 32 additional chickens, including Tibetan chickens, village chickens, game fowl, and Red Junglefowl, and found that the Tibetan chickens could broadly be placed into two groups. Further analyses revealed that several candidate genes in the calcium-signaling pathway are possibly involved in adaptation to the hypoxia experienced by these chickens, as these genes appear to have experienced directional selection in the two Tibetan chicken populations, suggesting a potential genetic mechanism underlying high altitude adaptation in Tibetan chickens. The candidate selected genes identified in this study, and their variants, may be useful targets for clarifying our understanding of the domestication of chickens in Tibet, and might be useful in current breeding efforts to develop improved breeds for the highlands.

Whole-genome sequence of the Tibetan frog Nanorana parkeri and the comparative evolution of tetrapod genomes.

The development of efficient sequencing techniques has resulted in large numbers of genomes being available for evolutionary studies. However, only one genome is available for all amphibians, that of Xenopus tropicalis, which is distantly related from the majority of frogs. More than 96% of frogs belong to the Neobatrachia, and no genome exists for this group. This dearth of amphibian genomes greatly restricts genomic studies of amphibians and, more generally, our understanding of tetrapod genome evolution. To fill this gap, we provide the de novo genome of a Tibetan Plateau frog, Nanorana parkeri, and compare it to that of X. tropicalis and other vertebrates. This genome encodes more than 20,000 protein-coding genes, a number similar to that of Xenopus. Although the genome size of Nanorana is considerably larger than that of Xenopus (2.3 vs. 1.5 Gb), most of the difference is due to the respective number of transposable elements in the two genomes. The two frogs exhibit considerable conserved whole-genome synteny despite having diverged approximately 266 Ma, indicating a slow rate of DNA structural evolution in anurans. Multigenome synteny blocks further show that amphibians have fewer interchromosomal rearrangements than mammals but have a comparable rate of intrachromosomal rearrangements. Our analysis also identifies 11 Mb of anuran-specific highly conserved elements that will be useful for comparative genomic analyses of frogs. The Nanorana genome offers an improved understanding of evolution of tetrapod genomes and also provides a genomic reference for other evolutionary studies.

[Chemical constituents of n-BuOH extract from Phyllanthus matsumurae].

OBJECTIVE: To study the chemical constituents of n-BuOH extract from Phyllanthus matsumurae. METHODS: Column chromatography was used for the isolation and purification. Spectroscopic methods including H-NMR, 13C-NMR and MS were used for the identification of structures. RESULTS: Six compounds were isolated from the n-BuOH extract of 75% alcohol extract of the whole plant and identified as ellagic acid (1), phyllanthuspermin B (2), phyllanthuspermin C (3), xanthoxylin (4), hesperetin-7-O-[6-O-(alpha-L-rhamnopy ranosyl)] -beta-D-glucopyranoside (5) and 4-O-methylgallic acid (6). CONCLUSION: Compounds 2 - 6 are obtained from this plant for the first time.

Genetic convergence in the adaptation of dogs and humans to the high-altitude environment of the tibetan plateau.

The high-altitude hypoxic environment represents one of the most extreme challenges for mammals. Previous studies of humans on the Tibetan plateau and in the Andes Mountains have identified statistical signatures of selection in different sets of loci. Here, we first measured the hemoglobin levels in village dogs from Tibet and those from Chinese lowlands. We found that the hemoglobin levels are very similar between the two groups, suggesting that Tibetan dogs might share similar adaptive strategies as the Tibetan people. Through a whole-genome sequencing approach, we have identified EPAS1 and HBB as candidate genes for the hypoxic adaptation on the Tibetan plateau. The population genetic analysis shows a significant convergence between humans and dogs in Tibet. The similarities in the sets of loci that exhibit putative signatures of selection and the hemoglobin levels between humans and dogs of the same environment, but not between human populations in different regions, suggests an extraordinary landscape of convergent evolution between human beings and their best friend on the Tibetan plateau.

Cell microenvironment stimuli-responsive controlled-release delivery systems based on mesoporous silica nanoparticles.

To develop novel tumor cell microenvironment stimuli-responsive smart controlled-release delivery systems is one of the current common interests of materials science and clinical medicine. Meanwhile, mesoporous silica nanoparticles as a promising drug carrier have become the new area of interest in the field of biomedical application in recent years because of their unique characteristics and abilities to efficiently and specifically entrap cargo molecules. This review describes the more recent developments and achievements of mesoporous silica nanoparticles in drug delivery. In particular, we focus on the stimuli-responsive controlled-release systems that are able to respond to tumor cell environmental changes, such as pH, glucose, adenosine-5'-triphosphate (ATP), glutathione (GSH), and H(2)O(2).

[Chemical constituents of Mallotus paniculatus].

OBJECTIVE: To study the chemical constituents of Mallotus paniculatus. METHODS: Column chromatography were used for the isolation and purification. Spectroscopic methods including 1H-NMR, 13C-NMR and MS were used for the identification of structures. RESULTS: Six compounds were isolated from the CHCl3 extract of 75% alcohol extract of the whole plant and identified to be quercetin( 1), kaempherol(2), hesperetin (3), 7,3'-O-dimethylluteolin (4), p-sitosterol (5) and syringaresinol (6). CONCLUSION: All the compounds above were isolated from this plant for the first time.

Origin of Chinese goldfish and sequential loss of genetic diversity accompanies new breeds.

BACKGROUND: Goldfish, Carassius auratus, have experienced strong anthropogenic selection during their evolutionary history, generating a tremendous extent of morphological variation relative to that in native Carassius. To locate the geographic origin of goldfish, we analyzed nucleotide sequences from part of the control region (CR) and the entire cytochrome b (Cytb) mitochondrial DNA genes for 234 goldfish and a large series of native specimens. Four important morphological characteristics used in goldfish taxonomy-body shape, dorsal fin, eye shape, and tailfin-were selected for hypothesis-testing to identify those that better correspond to evolutionary history. PRINCIPAL FINDING: Haplotypes of goldfish rooted in two sublineages (C5 and C6), which contained the haplotypes of native C. a. auratus from southern China. Values of F(ST) and N(m) revealed a close relationship between goldfish and native C. a. auratus from the lower Yangtze River. An extraordinary, stepwise loss of genetic diversity was detected from native fish to goldfish and from Grass-goldfish relative to other breeds. Significantly negative results for the tests of Tajima's D and Fu and Li's D* and F* were identified in goldfish, including the Grass breed. The results identified eye-shape as being the least informative character for grouping goldfish with respect to their evolutionary history. Fisher's exact test identified matrilineal constraints on domestication. CONCLUSIONS: Chinese goldfish have a matrilineal origin from native southern Chinese C. a. auratus, especially the lineages from the lower Yangtze River. Anthropogenic selection of the native Carassius eliminated aesthetically unappealing goldfish and this action appeared to be responsible for the stepwise decrease in genetic diversity of domesticated goldfish, a process similar to that reported for the domestication of pigs, rice, and maize. The three-breed taxonomy--Grass-goldfish, Egg-goldfish, and Wen-goldfish--better reflected the history of domestication.

Porous iron molybdate nanorods: in situ diffusion synthesis and low-temperature H2S gas sensing.

In the paper, we developed an in situ diffusion growth method to fabricate porous Fe2(MoO4)3 nanorods. The average diameter and the length of the porous nanorods were 200 nm and 1.2-4 µm, respectively. Moreover, many micropores existed along axial direction of the Fe2(MoO4)3 nanorods. In terms of nitrogen adsorption-desorption isotherms, calculated pore size was in the range of 4-115 nm, agreeing well with the transmission electron microscope observations. Because of the uniquely porous characteristics and catalytic ability at low temperatures, the porous Fe2(MoO4)3 nanorods exhibited very good H2S sensing properties, including high sensitivity at a low working temperature (80 °C), relatively fast response and recovery times, good selectivity, and long-term stability. Thus, the porous Fe2(MoO4)3 nanorods are very promising for the fabrication of high-performance H2S gas sensors. Furthermore, the strategy presented here could be expended as a general method to synthesize other hollow/porous-type transition metal molybdate nanostructures by rational designation in nanoscale.

Quaternary nanocomposites consisting of graphene, Fe3O4@Fe core@shell, and ZnO nanoparticles: synthesis and excellent electromagnetic absorption properties.

This paper presents for the first time a successful synthesis of quaternary nanocomposites consisting of graphene, Fe(3)O(4)@Fe core/shell nanopariticles, and ZnO nanoparticles. Transmission electron microscopy measurements show that the diameter of the Fe(3)O(4)@Fe core/shell nanoparitcles is about 18 nm, the Fe(3)O(4) shell's thickness is about 5 nm, and the diameter of ZnO nanoparticles is in range of 2-10 nm. The measured electromagnetic parameters show that the absorption bandwidth with reflection loss less than -20 dB is up to 7.3 GHz, and in the band range more than 99% of electromagnetic wave energy is attenuated. Moreover, the addition amount of the nanocomposites in the matrix is only 20 wt %. Therefore, the excellent electromagnetic absorption properties with lightweight and wide absorption frequency band are realized by the nanocomposites.

Lactase persistence may have an independent origin in Tibetan populations from Tibet, China.

Milk consumption is prevalent in daily diets of Tibetans. To digest the milk sugar lactose, lactase persistence (LP) should be required. However, little is known about the genetic basis of LP in Tibetans. We screened 495 Tibetan individuals for five previously reported single-nucleotide polymorphisms (SNPs): -13907C/G (rs41525747), -13910C/T (rs4988235), -13915T/G (rs41380347), -14010G/C and -22018G/A (rs182549), which are associated with the LP in populations from a vast region surrounding Tibet. The five SNPs were nearly absent in Tibetan populations, suggesting LP likely to have an independent origin in Tibetans rather than to be introduced via gene flow from neighboring populations. We identified three novel SNPs (-13838G/A, -13906T/A and -13908C/T) in Tibetans. In particular, -13838G/A might be functional as it is located in the binding motif for HNF4α that acts as a transcription factor for intestinal gene expression. To investigate the potential association of this variant with LP, further detailed studies are required in the future.

Fe2O3/TiO2 tube-like nanostructures: synthesis, structural transformation and the enhanced sensing properties.

The paper describes for the first time the successful synthesis of Fe(2)O(3)/TiO(2) tube-like nanostructures, in which TiO(2) shell is of quasi-single crystalline characteristic and its thickness can be controlled through adjusting the added amount of aqueous Ti(SO(4))(2) solution. The characterization of samples obtained at different stages using transmission electron microscope indicates that the outer TiO(2) shell is changed gradually from amorphous and polycrystalline phase into quasi-single crystal under thermal actions through the Ostwald ripening process, accompanying the corrosion of the central parts of Fe(2)O(3) nanorods, and the formation of small particles separating each other, leading to the special core/shell nanorods. Furthermore, Fe(2)O(3)/TiO(2) tube-like nanostructures can be transformed into Fe(2)TiO(5) nanostructures after they are thermally treated at higher temperatures. Those nanostructures exhibit enhanced ethanol sensing properties with respect to the monocomponent. Our results imply that not only hollow nanostructures, but also a novel type of nanostructures can be fabricated by the present method for nanodevices.

Bioresponsive controlled release using mesoporous silica nanoparticles capped with aptamer-based molecular gate.

This communication describes the design of a novel and general bioresponsive controlled-release mesoporous silica (MS) nanoparticles system based on aptamer-target interactions. In this system, the pores of MS were capped with Au nanoparticles modified with aptamer (ATP aptamer in this case). By a competitive displacement reaction, the Au nanoparticles were uncapped in the presence of ATP molecule, and the cargo was released. Our results demonstrated that the aptamer-target interaction may be a promising route for the design of custom-made controlled-release nanodevices specifically governed by target biomolecules. Since aptamers have been obtained for a broad range of targets, including several cancer biomarkers, we believe that this aptamer-based controlled-release system should have an equally broad spectrum of applications.