Dgcr8 functions in the secondary heart field for outflow tract and right ventricle development in mammals.

The DGCR8 gene, encoding a critical miRNA processing protein, maps within the hemizygous region in patients with 22q11.2 deletion syndrome. Most patients have malformations of the cardiac outflow tract that is derived in part from the anterior second heart field (aSHF) mesoderm. To understand the function of Dgcr8 in the aSHF, we inactivated it in mice using Mef2c-AHF-Cre. Inactivation resulted in a fully penetrant persistent truncus arteriosus and a hypoplastic right ventricle leading to lethality by E14.5. To understand the molecular mechanism for this phenotype, we performed gene expression profiling of the aSHF and the cardiac outflow tract with right ventricle in conditional null versus normal mouse littermates at stage E9.5 prior to morphology changes. We identified dysregulation of mRNA gene expression, of which some are relevant to cardiogenesis. Many pri-miRNA genes were strongly increased in expression in mutant embryos along with reduced expression of mature miRNA genes. We further examined the individual, mature miRNAs that were decreased in expression along with pri-miRNAs that were accumulated that could be direct effects due to loss of Dgcr8. Among these genes, were miR-1a, miR-133a, miR-134, miR143 and miR145a, which have known functions in heart development. These early mRNA and miRNA changes may in part, explain the first steps that lead to the resulting phenotype in Dgcr8 aSHF conditional mutant embryos.

Crk and Crkl Are Required in the Endocardial Lineage for Heart Valve Development.

Background Endocardial cells are a major progenitor population that gives rise to heart valves through endocardial cushion formation by endocardial to mesenchymal transformation and the subsequent endocardial cushion remodeling. Genetic variants that affect these developmental processes can lead to congenital heart valve defects. Crk and Crkl are ubiquitously expressed genes encoding cytoplasmic adaptors essential for cell signaling. This study aims to explore the specific role of Crk and Crkl in the endocardial lineage during heart valve development. Methods and Results We deleted Crk and Crkl specifically in the endocardial lineage. The resultant heart valve morphology was evaluated by histological analysis, and the underlying cellular and molecular mechanisms were investigated by immunostaining and quantitative reverse transcription polymerase chain reaction. We found that the targeted deletion of Crk and Crkl impeded the remodeling of endocardial cushions at the atrioventricular canal into the atrioventricular valves. We showed that apoptosis was temporally increased in the remodeling atrioventricular endocardial cushions, and this developmentally upregulated apoptosis was repressed by deletion of Crk and Crkl. Loss of Crk and Crkl also resulted in altered extracellular matrix production and organization in the remodeling atrioventricular endocardial cushions. These morphogenic defects were associated with altered expression of genes in BMP (bone morphogenetic protein), connective tissue growth factor, and WNT signaling pathways, and reduced extracellular signal-regulated kinase signaling activities. Conclusions Our findings support that Crk and Crkl have shared functions in the endocardial lineage that critically regulate atrioventricular valve development; together, they likely coordinate the morphogenic signals involved in the remodeling of the atrioventricular endocardial cushions.

Crk/Crkl regulates early angiogenesis in mouse embryos by accelerating endothelial cell maturation.

Rationale: Ubiquitously expressed cytoplasmic adaptors CRK and CRKL mediate multiple signaling pathways in mammalian embryogenesis. They are also associated with cardiovascular defects occurring in Miller-Dieker syndrome and 22q11.2 deletion syndrome, respectively. The embryonic mesoderm contributes to the formation of the cardiovascular system, yet the roles that Crk and Crkl play there are not understood on a single cell level. Objectives: To determine functions of Crk and Crkl in the embryonic mesoderm during early mouse vascular development. Secondly, we will examine the molecular mechanisms responsible for early embryonic endothelial cell (EC) defects by performing single cell RNA-sequencing (scRNA-seq) and in vivo validation experiments. Methods and Results: Inactivation of both Crk and Crkl together using Mesp1 Cre resulted embryonic lethality with severe vascular defects. Although vasculogenesis appeared normal, angiogenesis was disrupted both in the yolk sac and embryo proper, leading to disorganized vascular networks. We performed scRNA-seq of the Mesp1 Cre mesodermal lineage and found that there was upregulation of a great number of angiogenesis and cell migration related genes in ECs in the mutants, including NOTCH signaling genes such as Dll4 and Hey1 . Further bioinformatic analysis of EC subpopulations identified a relative increase in the number of more differentiated angiogenic ECs and decrease in EC progenitors. Consistent with this, we identified an expansion of Dll4 expressing cells within abnormal arteries, in vivo . Also, our bioinformatic data indicates that there is dysregulated expression of lineage genes that promote EC differentiation causing accelerated cell fate progression during EC differentiation. Conclusions: Our results show that Crk and Crkl are crucial for regulating early embryonic angiogenesis. Combined inactivation of Crk/Crkl caused precocious EC maturation with an increase of atypical differentiated angiogenic ECs and failed vascular remodeling. This is in part due to increased NOTCH signaling and altered expression of cell migration genes.

Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS.

Congenital heart disease (CHD) affecting the conotruncal region of the heart, occurs in 40-50% of patients with 22q11.2 deletion syndrome (22q11.2DS). This syndrome is a rare disorder with relative genetic homogeneity that can facilitate identification of genetic modifiers. Haploinsufficiency of TBX1, encoding a T-box transcription factor, is one of the main genes responsible for the etiology of the syndrome. We suggest that genetic modifiers of conotruncal defects in patients with 22q11.2DS may be in the TBX1 gene network. To identify genetic modifiers, we analyzed rare, predicted damaging variants in whole genome sequence of 456 cases with conotruncal defects and 537 controls, with 22q11.2DS. We then performed gene set approaches and identified chromatin regulatory genes as modifiers. Chromatin genes with recurrent damaging variants include EP400, KAT6A, KMT2C, KMT2D, NSD1, CHD7 and PHF21A. In total, we identified 37 chromatin regulatory genes, that may increase risk for conotruncal heart defects in 8.5% of 22q11.2DS cases. Many of these genes were identified as risk factors for sporadic CHD in the general population. These genes are co-expressed in cardiac progenitor cells with TBX1, suggesting that they may be in the same genetic network. The genes KAT6A, KMT2C, CHD7 and EZH2, have been previously shown to genetically interact with TBX1 in mouse models. Our findings indicate that disturbance of chromatin regulatory genes impact the TBX1 gene network serving as genetic modifiers of 22q11.2DS and sporadic CHD, suggesting that there are some shared mechanisms involving the TBX1 gene network in the etiology of CHD.

[Cost-benefit analysis on the intervention of application iron-fortified soy sauce for anemia in Deqing 15-54 years women, Zhejiang].

OBJECTIVE: To make a cost-benefit analysis on anemia intervention with iron-fortified soy sauce in 15-54 years old women. METHODS: The study was conducted in Deqing county, Zhejiang province in 2012-2013. A total 585 women as sampling size were estimated with statistical model and randomly selected by probability proportionate to size sampling. Hemoglobin were measured before intervention and after 15 months. The cost of the intervention project were collected with manpower, communication and other invest. The benefit was estimated with profiling model. RESULTS: After the intervention, the anemia prevalence of sampled women decreased from 31.1% to 21.9%(P<0.01). The major cost of the project was 156 400 RMB, and total benefits result ing from projects were 1 448 485 RMB. The cost-benefit ratio of the project is 1∶9.49. If investing one yuan can produce economic benefits of nearly 9.49 yuan, therefore, the intervention projectis worth to be scaling up. Sensitivity analysis showed the result of this study was stable. CONCLUSION: The intervention can significantly reduce the prevalence of anemia in women, and reduce the economic burden of the diseases. .

A reference-guided TILLING by amplicon-sequencing platform supports forward and reverse genetics in barley.

Barley is a diploid species with a genome smaller than those of other members of the Triticeae tribe, making it an attractive model for genetic studies in Triticeae crops. The recent development of barley genomics has created a need for a high-throughput platform to identify genetically uniform mutants for gene function investigations. In this study, we report an ethyl methanesulfonate (EMS)-mutagenized population consisting of 8525 M3 lines in the barley landrace "Hatiexi" (HTX), which we complement with a high-quality de novo assembly of a reference genome for this genotype. The mutation rate within the population ranged from 1.51 to 4.09 mutations per megabase, depending on the treatment dosage of EMS and the mutation discrimination platform used for genotype analysis. We implemented a three-dimensional DNA pooling strategy combined with multiplexed amplicon sequencing to create a highly efficient and cost-effective TILLING (targeting induced locus lesion in genomes) platform in barley. Mutations were successfully identified from 72 mixed amplicons within a DNA pool containing 64 individual mutants and from 56 mixed amplicons within a pool containing 144 individuals. We discovered abundant allelic mutants for dozens of genes, including the barley Green Revolution contributor gene Brassinosteroid insensitive 1 (BRI1). As a proof of concept, we rapidly determined the causal gene responsible for a chlorotic mutant by following the MutMap strategy, demonstrating the value of this resource to support forward and reverse genetic studies in barley.

Facile Synthesis of Pd and PdPtNi Trimetallic Nanosheets as Enhanced Oxygen Reduction Electrocatalysts.

While bimetallic 2D metallic nanomaterials are widely synthesized and used as electrocatalysts with enhanced performance, trimetallic 2D structures are less commonly reported. In this work, a facile wet chemical method for synthesizing Pd nanosheets and PdPtNi trimetallic alloy nanosheets is developed. Without the introduction of gaseous CO and pressurized equipment, Pd nanosheets with a thickness of ≈2.85 nm and sizes in the range of 1-2 µm can be obtained. The facile synthesis conditions allow for a comprehensive study of the nanosheet growth mechanism. It is found that 2D growth is closely related to the product of solvent decomposition and the additive ligand diethylenetriamine. Further, by depositing Pt and Ni onto the Pd nanosheets, trimetallic nanosheets with tunable compositions can be obtained and applied as oxygen reduction reaction electrocatalysts. Typically, the Pd9 Pt1 Ni1 nanosheets have the highest half-wave potential of 0.928 V (vs reversible hydrogen electrode), which is 34 mV higher than that of commercial Pt/C and 28 mV higher than that of Pd/C, and also have high durability.

Crk and Crkl have shared functions in neural crest cells for cardiac outflow tract septation and vascular smooth muscle differentiation.

CRK and CRKL encode cytoplasmic adaptors that contribute to the etiology of congenital heart disease. Neural crest cells (NCCs) are required for cardiac outflow tract (OFT) septation and aortic arch formation. The roles of Crk/Crkl in NCCs during mouse cardiovascular development remain unknown. To test this, we inactivated Crk and/or Crkl in NCCs. We found that the loss of Crk, rather than Crkl, in NCCs resulted in double outlet right ventricle, while loss of both Crk/Crkl in NCCs resulted in severe defects with earlier lethality due to failed OFT septation and severe dilation of the pharyngeal arch arteries (PAAs). We found that these defects are due to altered cell morphology resulting in reduced localization of NCCs to the OFT and failed integrity of the PAAs, along with reduced expression of Integrin signaling genes. Further, molecular studies identified reduced differentiation of vascular smooth muscle cells that may in part be due to altered Notch signaling. Additionally, there is increased cellular stress that leads to modest increase in apoptosis. Overall, this explains the mechanism for the Crk/Crkl phenotype.

Combination Therapy of Metastatic Castration-Recurrent Prostate Cancer: Hyaluronic Acid Decorated, Cabazitaxel-Prodrug and Orlistat Co-Loaded Nano-System.

PURPOSE: Prostate cancer (PCa) is the second leading cause of cancer-related death among men in developed countries. Cabazitaxel (CBZ) is recommended as one of the most active chemotherapy agents for PCa. This study aimed to develop a hyaluronic acid (HA) decorated, cabazitaxel-prodrug (HA-CBZ) and orlistat (ORL) co-loaded nano-system against the prostate cancer in vitro and in vivo. METHODS: Cabazitaxel-prodrug was firstly synthesized by conjugating HA with CBZ through the formation of ester bonds. HA contained ORL and CBZ prodrug co-loaded lipid-polymer hybrid nanoparticles (ORL/HA-CBZ/LPNs) were constructed and characterized in terms of particle size, zeta potential, drug loading capacity and stability. The antitumor efficiency and systemic toxicity of LPNs were evaluated in vitro and in vivo. RESULTS: The resulting ORL/HA-CBZ/LPNs were 150.9 nm in particle size with narrow distribution and high entrapment efficiency. The minimum combination index of 0.57 was found at a drug ratio of 1:2 (ORL:HA-CBZ, w/w) in the drug co-loaded formulations, indicating the strongest synergism effect. ORL/HA-CBZ/LPNs demonstrated an enhanced in vitro and in vivo antitumor effect compared with single drug loaded LPNs and free drug formulations. CONCLUSION: ORL/HA-CBZ/LPNs showed remarkable synergism cytotoxicity and the best tumor inhibition efficiency in mice with negligible systemic toxicity. ORL/HA-CBZ/LPNs can be highly useful for targeted prostate cancer therapy.

Electric field controlled type-I and type-II conversion of BP/SnS van der Waals heterostructure.

Type-I heterostructure, in which electrons and holes are confined in same region, is widely used in light emitting diodes and semiconductor lasers. Type-II heterostructure is widely used in photovoltaic devices because of its excellent spatial separation property of electrons and holes. Can we integrate photovoltaic, photoelectric properties with luminescent property in one device? Here we report a van der Waals heterostructure formed by black phosphorus (BP) and SnS monolayers. It is expected to realize these functions in one device. By first-principles methods, the structural stability, electronic properties and optical properties are investigated. It was found that the BP/SnS bilayer is type-II heterostructure with an indirect bandgap of 0.56 eV. Thep-like character of the band edge in BP/SnS vdW heterostructure makes it to be an excellent optoelectronic material. The type-II stability of the system can be improved by applying a negative electric field. However, when the positive electric field is bigger than 0.1 V Å-1, the system begins to transform from type-II to type I. Therefore, by adding a gate voltage the bandgap and band alignment of this system can be controlled. The photovoltaic and photoelectric properties can be integrated in one device based on this heterostructure.

BiNV bond: A hole-transfer bridge for high-efficient separation and transfer of carriers.

Addressing the inherent holes transport limitation of BiVO4 photoanode is crucial to achieve efficient photoelectrochemical (PEC) water splitting. The construction of the hole-transfer bridge between co-catalysts and BiVO4 photoanode could be an effective way to overcome sluggish hole-transfer kinetics of BiVO4 photoanode. Herein, CxNy/BiVO4 photoanode was prepared by coupling carbon nitride hydrogel (CNH) containing unsaturated N on the BiVO4 photoanode during annealing. CxNy/BiVO4 photoanode exhibited excellent PEC performance and stability. Photoelectrochemical tests proved that the coupling of CxNy accelerated holes transfer and enhanced oxygen evolution kinetics. X-ray photoelectron spectroscopy (XPS) and theoretical calculations confirmed the existence of the BiNV bond between BiVO4 photoanode and CxNy, which could serve as the hole-transfer bridge to significantly accelerate separation and transfer of carriers driven by the interfacial electric field. Moreover, it was found that the coupling of CxNy effectively inhibited the dissociation of metal ions through changing their coordination environment, resulting in the excellent stability of CxNy/BiVO4 photoanode. This result provides unique insights into vital roles of the interfacial structure, which might have a significant impact on the construction of PEC devices.

Widely tunable direct bandgap of two-dimensional GeSe.

Bulk GeSe is an indirect bandgap semiconductor. However, direct bandgap semiconductor of two-dimensional GeSe can be obtained by applying strain along armchair direction, and the direct bandgap can be tuned in a wide energy range from 0.86 eV to 0.00 eV by electric field. The bandgap modulation mechanism is studied in detail by first-principle calculations. The calculations of phonon spectra show that the crystal structure is relatively stable under the strain and electric field. Therefore, 2D GeSe is a promising material in frequency adjustable electronic and optical devices.

Using large-scale climate drivers to forecast meteorological drought condition in growing season across the Australian wheatbelt.

Recurring drought has caused large crop yield losses in Australia during past decades. Long-term drought forecasting is of great importance for the development of risk management strategies. Recently, large-scale climate drivers (e.g. El Niño-Southern Oscillation) have been demonstrated as useful in the application of drought forecasting. Machine learning-based models that use climate drivers as input are commonly adopted to provide drought forecasts as these models are easy to develop and require less information compared to physical-based models. However, few machine learning-based models have been developed to forecast drought conditions during growing season across all Australian cropping areas. In this study, we developed a growing season (Apr.-Nov.) meteorological drought forecasting model for each climate gauging location across the Australian wheatbelt based on multiple lagged (past) large-scale climate indices and the Random Forest (RF) algorithm. The Standardized Precipitation Index (SPI) was used as the response variable to measure the degree of meteorological drought. Results showed that the RF model could provide satisfactory drought forecasts in the eastern areas of the wheatbelt with Pearson's correlation coefficient r > 0.5 and normalized Root Mean Square Error (nRMSE) < 23%. Forecasted drought maps matched well with observed drought maps for three representative periods. We identified NINO3.4 sea surface temperature and Multivariate ENSO Index as the most influential indices dominating growing season drought conditions across the wheatbelt. In addition, lagged impacts of large-scale climate drivers on growing season drought conditions were long-lasting and the indices in previous year could also potentially affect drought conditions during current year. As large-scale climate indices are readily available and can be rapidly used to feed data driven models, we believe the proposed meteorological drought forecasting models can be easily extended to other regions to provide drought outlooks which can help mitigate adverse drought impacts.

Polarization-Sensitive Self-Powered Type-II GeSe/MoS2 van der Waals Heterojunction Photodetector.

Polarization-sensitive photodetectors are highly desirable for high-performance optical signal capture and stray light shielding in order to enhance the capability for detection and identification of targets in dark, haze, and other complex environments. Usually, filters and polarizers are utilized for conventional devices to achieve polarization-sensitive detection. Herein, to simplify the optical system, a two-dimensional self-powered polarization-sensitive photodetector is fabricated based on a stacked GeSe/MoS2 van der Waals (vdW) heterojunction which facilitates efficient separation and transportation of the photogenerated carriers because of type-II band alignment. Accordingly, a high-performance self-powered photodetector is achieved with merits of a very large on-off ratio photocurrent at zero bias of currently 104 and a high responsivity (Rλ) of 105 mA/W with an external quantum efficiency of 24.2%. Furthermore, a broad spectral photoresponse is extended from 380 to 1064 nm owing to the high absorption coefficient in a wide spectral region. One of the key benefits from these highly anisotropic orthorhombic structures of layered GeSe is self-powered polarization-sensitive detection with a peak/valley ratio of up to 2.95. This is realized irradiating with a 532 nm wavelength laser with which a maximum photoresponsivity of up to 590 mA/W is reached when the input polarization is parallel to the armchair direction. This work provides a facile route to fabricate self-powered polarization-sensitive photodetectors from GeSe/MoS2 vdW heterojunctions for integrated optoelectronic devices.

Ab initio study of optoelectronic and magnetic properties of Mn-doped ZnS with and without vacancy defects.

The effect of vacancy defects on optoelectronic and magnetic properties of Mn-doped ZnS have been systematically investigated using first principle approaches. A single Mn substitution at Zn site induces a spin-polarized ground state in pure ZnS with total magnetization 5 [Formula: see text]. Our results for magnetic coupling show that the coupling between Mn spins in pure Mn doped ZnS is antiferromagnetic under the super-exchange mechanism. The existence of native defects has a great influence on the magnetic ground state of Mn-doped ZnS. In particular, a p -type defect such as Zn vacancy play a crucial role in stabilizing ferromagnetic ground state while n-type defect, such as S vacancy, has no effect on the magnetic ground state i.e. the interaction between two Mn spins with S-vacancy remain antiferromagnetic. Furthermore, optical properties such as dielectric functions, absorption coeffiecients, reflectivity and transmissitivity for Mn doped systems with and without vacancy defect were also studied, and we found that an absorption peak was obtained in the infrared region which is attributed to the defect states introduced by Zn vacancy in the system. In a S-vacancy defect system, the peaks in the near infrared and visible region are due to donor states introduced by S vacancy defect and these peaks are produced by electrons flipping from a spin up state to a spin down state. Finally, we also correlated the magnetic interactions with the d-d optical transition in pure Mn-doped ZnS and found that the d-d transitions during optical absorptions are red shifted and blue shifted in FM and AFM coupled Mn ions pair, which is in good agreement with the experimental observations. This study may help to understand the behavior of optical and magnetic properties of DMS under vacancy defects.

Optoelectronic and magnetic properties of Mn-doped and Mn-C co-doped Wurtzite ZnS: a first-principles study.

In order to meet the requirement of spintronic and optoelectronic, we have systematically investigated the effect of Mn doping and co-doping of Mn with C on the electronic, magnetic and optical properties of wurtzite zinc sulfide (ZnS) using first principle calculations. Our results find that single Mn doping alters the non-magnetic ZnS to a magnetic one and keeps its semiconducting and a semiconductor to half-metal transition is observed for Mn-C co-doping. Furthermore, an antiferromagnetic (AFM) and ferromagnetic (FM) ground states are favorable for Mn-doped and Mn-C co-doped system, respectively. Additionally, the optical properties of our studied configuration have been calculated in terms of real and imaginary parts of the complex dielectric function, absorption coefficient, and reflectivity. The absorption edge shifts slightly toward lower energy and intensity of the main peak become weak for single Mn doping, and a sharp peak at low energy is observed for the Mn-C co-doping. The analysis of optical absorption of Mn ions doped system shows the blue- and red-shifts of the d-d transition in the AFM and FM coupled of Mn ions doped configuration, respectively which is in good agreement with the experimental observations. The improved magnetic and optical properties of Mn-C co-doped ZnS shed light on the future application of such kind of materials in spintronic and optoelectronic devices such as remote sensing and photovoltaics.

Bulked segregant RNA-sequencing (BSR-seq) identified a novel rare allele of eIF4E effective against multiple isolates of BaYMV/BaMMV.

KEY MESSAGE: A novel rare allele of the barley host factor gene eIF4E for BaMMV/BaYMV infection was identified in an Iranian landrace that showed broad resistance to barley yellow mosaic virus disease, and molecular markers facilitating efficient selection were developed. The soil-borne yellow mosaic virus disease caused by different strains of barley yellow mosaic virus (BaYMV) and barley mild mosaic virus (BaMMV) is a major threat to winter barley (Hordeum vulgare) production in Europe and East Asia. However, the exploration of resistant germplasm or casual genes for barley breeding is rather limited in relation to the rapid diversification of viral strains. Here, we identified an Iranian barley landrace 'HOR3298,' which represented complete resistance to BaYMV and BaMMV. In contrast to rym4 and rym5, which act as the predominant source in Europe and East Asia for breeding resistant cultivars over decades and which have been overcome by several virulent isolates, this landrace showed broad-spectrum resistance to multiple isolates of BaYMV/BaMMV in the fields of Germany and China. By employment of bulked segregant RNA sequencing, test for allelism, and haplotype analysis, a recessive resistance gene in 'HOR3298' was genetically mapped coincident with the host factor eukaryotic translation initiation factor 4E (eIF4E, causal gene of rym4 and rym5). The eIF4EHOR3298 allele encoded for a novel haplotype that contained an exclusive nucleotide mutation (G565A) in the coding sequence. The easily handled markers were developed based on the exclusively rare variation, providing precise selection of this allele. Thus, this work provided a novel reliable resistance source and the feasible marker-assisted selection assays that can be used in breeding for barley yellow mosaic virus disease resistance in cultivated barley.

Glucocorticoids and Body Fat Inversely Associate With Bone Marrow Density of the Distal Radius in Healthy Youths.

CONTEXT: Elevated bone marrow adipose tissue (BMAT) is associated with lower bone quality, higher fracture rates, and an unfavorable overall metabolic profile. Apart from age, particularly glucocorticoids (GC), body fat, and diet are discussed to influence BMAT. We hypothesized that already in healthy youths, higher fat intake, higher fat mass index (FMI), and higher GC secretion, still within the normal range, may associate with increased BMAT. DESIGN: In a subsample of healthy 6- to 18-year-old participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study, peripheral quantitative CT of the nondominant proximal forearm was used to determine bone marrow density of the distal radius as an inverse surrogate parameter for BMAT. In those participants (n = 172) who had collected two, 24-hour urines within around one year before bone measurement, major urinary GC metabolites were measured by gas chromatography-mass spectrometry and summed up to assess daily adrenal GC secretion (ΣC21). Dietary intake was assessed by 3-day weighed dietary records. FMI was anthropometrically calculated. Separate multiple linear regression models were used to analyze the relationships of ΣC21, FMI, and fat intake with BMAT. RESULTS: After controlling for confounders, such as age, energy intake, and forearm muscle area, ΣC21 (ß = -0.042) and FMI (ß = -0.002) showed inverse relationships with bone marrow density (P < 0.05), whereas fat intake did not associate significantly. CONCLUSION: Our results indicate that already a moderately elevated GC secretion and higher body fatness during adolescence may adversely impact BMAT, an indicator for long-term bone health.

Whether Syndrome Differentiation Affects Treatment Result: Study Protocol of MaZiRenWan () for Functional Constipation in A Randomized Controlled Trial.

BACKGROUND: Syndrome is one of the most important concepts in Chinese medicine (CM) theory. However, it was not well accounted in most of randomized controlled trials (RCTs). OBJECTIVES: To determine whether CM syndrome differentiation affects the treatment results, functional constipation (FC) was selected as a target disease, and MaZiRenWan (, MZRW), a classic CM formula commonly used for constipation with excessive heat syndrome, was selected for study. METHODS: It is an 18-week prospective double-blinded, doubledummy RCT, including 2-week run-in, 8-week treatment and 8-week post treatment follow-up. A total of 120 FC patients diagnosed as excessive heat syndrome will be recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the Baokang Affiliated Hospital of Tianjin University of Traditional Chinese Medicine. Patients will be randomly allocated into fixed MZRW (f_MZRW) granule group, modified MZRW (m_MZRW) granule group or bisacodyl group. For m_MZRW group, no more than two herbal granules can be added according to the syndrome differentiation for individual participants. The primary end point is the mean of complete spontaneous bowel movements (CSBMs) per week during the treatment period. Secondary end points include mean of CSBMs per week during follow-up, stool form, global symptom improvement, constipation and constipation-related symptoms assessment, CM syndrome change, and reported adverse events. DISCUSSION: This trial is designed to evaluate the effectiveness of these three interventions for FC patients with the CM syndrome of excessive heat, and to determine the change of CM syndrome and the progress of disease during the treatment course. The results are important to explore whether syndrome differentiation is important for the therapeutic effect of a formula on a disease. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-TRC-13003742); protocol version: MZRW/NSFC-81173363 (2015.05.04)].

Dual-Color Lasing Lines from EMPs in Diluted Magnetic Semiconductor CdS:NiI Structure.

Have one ever seen a semiconductor that can issue two-color lasing lines? The diluted magnetic semiconductor (DMS) can do this. Here, we have observed dual lasing lines of 530 nm and 789 nm from a DMS structure of CdS:NiI, in which the excitonic magnetic polaron (EMP) and localized excitonic magnetic polaron (LEMP) are excitations out of ferromagnetic (NiS) x nanocluster and NiI2 nanoclusters within CdS lattice; both of them could lead to the collective EMP state at high excitation and therein produce coherent emission lines simultaneously. This occurrence is due to the superposition of EMP near CdS bandedge and the combination of the charge-transfer band of (NiI) n cluster with the LEMP within CdS lattice by overcoming the strong electron correlation of NiI cluster in a DMS structure, evidenced also by ab initio calculation. This finding opens a way to understand the collective behaviour of spin-coupled excitons in DMS and to find novel applications in the spin-related quantum technology.