van der Waals Decoration of Ultra-High-Q Silica Microcavities for χ(2)-χ(3) Hybrid Nonlinear Photonics.

Optical nonlinear processes are indispensable in a wide range of applications, including ultrafast lasers, microscopy, and quantum information technologies. Among the diverse nonlinear processes, second-order effects usually overwhelm the higher-order ones, except in centrosymmetric systems, where the second-order susceptibility vanishes to allow the use of the third-order nonlinearity. Here we demonstrate a hybrid photonic platform whereby the balance between second- and third-order susceptibilities can be tuned flexibly. By decorating ultra-high-Q silica microcavities with atomically thin tungsten diselenide, we observe cavity-enhanced second-harmonic generation and sum-frequency generation with continuous-wave excitation at a power level of only a few hundred microwatts. We show that the coexistence of second- and third-order nonlinearities in a single device can be achieved by carefully choosing the size and location of the two-dimensional material. Our approach can be generalized to other types of cavities, unlocking the potential of hybrid systems with controlled nonlinear susceptibilities for novel applications.

Heterostructured Pt-PbS Nanobelt Achieves Remarkable Direct Formic Acid Oxidation Catalysis.

Developing efficient and CO-tolerant platinum (Pt)-based anodic catalysts is challenging for a direct formic acid fuel cell (DFAFC). Herein, we report heterostructured Pt-lead-sulfur (PtPbS)-based nanomaterials with gradual phase regulation as efficient formic acid oxidation reaction (FAOR) catalysts. The optimized Pt-PbS nanobelts (Pt-PbS NBs/C) display the mass and specific activities of 5.90 A mgPt-1 and 21.4 mA cm-2, 2.2/1.2, 1.5/1.1, and 36.9/79.3 times greater than those of PtPb-PbS NBs/C, Pt-PbSO4 NBs/C, and commercial Pt/C, respectively. Simultaneously, it exhibits a higher membrane electrode assembly (MEA) power density (183.5 mW cm-2) than commercial Pt/C (40.3 mW cm-2). This MEA stably operates at 0.4 V for 25 h, demonstrating a competitive potential of device application. The distinctive heterostructure endows the Pt-PbS NBs/C with optimized dehydrogenation steps and resisting the CO poisoning, thus presenting the remarkable FAOR performance. This work paves an effective avenue for creating high-performance anodic catalysts for fuel cells and beyond.

Accidental ingestion of multiple magnetic beads by children and their impact on the gastrointestinal tract: a single-center study.

OBJECTIVE: In this study, we aimed to enhance the treatment protocols and help understand the harm caused by the accidental ingestion of magnetic beads by children. METHODS: Data were collected from 72 children with multiple gastrointestinal perforations or gastrointestinal obstructions. The 72 pediatric patients were divided into a perforation and a non-perforation group. The data collected for the analysis included the gender, age, medical history, place of residence (rural or urban), and symptoms along with the educational background of the caregiver, the location and quantity of any foreign bodies discovered during the procedure, whether perforation was confirmed during the procedure, and the number of times magnetic beads had been accidentally ingested. RESULTS: The accuracy rate of preoperative gastrointestinal perforation diagnosis via ultrasound was 71%, while that of the upright abdominal X-ray method was only 46%. In terms of symptoms, the risk of perforation was 13.844 and 12.703 times greater in pediatric patients who experienced vomiting and abdominal pain with vomiting and abdominal distension, respectively, compared to patients in an asymptomatic state. There were no statistical differences between the perforation and the non-perforation groups in terms of age, gender, medical history, and the number of magnetic beads ingested (P > 0.05); however, there were statistical differences in terms of white blood cell count (P = 0.048) and c-reactive protein levels (P = 0.033). A total of 56% of cases underwent a laparotomy along with perforation repair and 19% underwent gastroscopy along with laparotomy. All pediatric patients recovered without complications following surgery. CONCLUSION: Abdominal ultrasonography and/or upright abdominal X-ray analyses should be carried out as soon as possible in case of suspicion of accidental ingestion of magnetic beads by children. In most cases, immediate surgical intervention is required. Given the serious consequences of ingesting this type of foreign body, it is essential to inform parents and/or caregivers about the importance of preventing young children from using such products.

A finite element analysis of a low-profile femoral neck system of screws in sleeves in a vertical femoral neck fracture model.

BACKGROUND: Femoral neck system (FNS) has exhibited some drawbacks, such as non-fit of the plate with the lateral femoral cortex, postoperative pain, and the potential risk of subtrochanteric fractures. We have developed a low-profile FNS system that addresses some compatibility issues in FNS. In this study, we conducted finite element analysis on the 1-hole FNS (1 H-FNS), 2-holes FNS (2 H-FNS), and low-profile FNS (LP-FNS) and compared their biomechanical performance. METHODS: After the mesh convergence analysis, we established three groups of 1 H-FNS, 2 H-FNS, and LP-FNS. The interfragmentary gap, sliding distance, shear stress, and compressive stress and the bone-implant interface compression stress, stiffness, and displacement were determined under the neutral, flexion, or extension conditions of the hip joint, respectively. The stress and displacement of the femur after the implant removal were also investigated. RESULTS: (1) There were no obvious differences among the three FNS groups in terms of the IFM distance. However, the LP-FNS group showed less rotational angle compared with conventional FNS (neutral: 1 H-FNS, -61.64%; 2 H-FNS, -45.40%). Also, the maximum bone-implant interface compression stress was obviously decreased under the neutral, flexion, or extension conditions of the hip joint (1 H-FNS: -6.47%, -20.59%, or -4.49%; 2 H-FNS: -3.11%, 16.70%, or -7.03%; respectively). (2) After the implant removal, there was no notable difference in the maximum displacement between the three groups, but the maximum von Mises stress displayed a notable difference between LP-FNS and 1 H-FNS groups (-15.27%) except for the difference between LP-FNS and 2 H-FNS groups (-4.57%). CONCLUSIONS: The LP-FNS may not only provide the same biomechanical stabilities as the 1 H-FNS and 2 H-FNS, but also have more advantages in rotational resistance especially under the neutral condition of the hip joint, in the bone-implant interface compression stress, and after the implant removal. In addition, the 1 H-FNS and 2 H-FNS have similar biomechanical stabilities except for the maximum von Mises stress after the implant removal. The femur after the LP-FNS removal not only is subjected to relatively little stress but also minimizes stress concentration areas.

Residue analysis and dietary risk assessment of abamectin in fresh corn, bitter melon, and Fritillaria.

To clarify the residue behavior and possible dietary risk of abamectin in fresh corn, bitter melon, and Fritillaria, a method was developed for the simultaneous determination of abamectin residues in fresh corn, bitter melon, and Fritillaria by QuEChERS (quick, easy, cheap, effective, rugged, safe) ultra-performance liquid chromatography-tandem mass spectrometry. The mean recovery of abamectin in fresh corn, bitter melon, and Fritillaria was 86.48%-107.80%, and the relative standard deviation was 2.07%-10.12%. The detection rates of abamectin residues in fresh corn, bitter melon, and Fritillaria were 62.50%, 87.50%, and 80.00%, respectively. The residues of abamectin in fresh corn, bitter melon, and Fritillaria were not more than 0.020, 0.019, and 0.087 mg/kg, respectively. Based on these results, dietary risk assessment showed that the risk content of abamectin residues in long- and short-term dietary exposure for Chinese consumers was 61.57% and 0.41%-1.11%, respectively, indicating that abamectin in fresh corn, bitter melon, and Fritillaria in the market would not pose a significant risk to consumers.

Residue analysis and dietary risk assessment of picoxystrobin in potato (Solanum tuberosum), citrus fruit (Citrus reticulata Blanco), and Dendrobium officinale Kimura et Migo.

Picoxystrobin is a systemic fungicide widely used on potato, citrus fruit, and Dendrobium officinale. To provide information for the risk assessment of potato, citrus, and Dendrobium officinale, field experiments combined with QuEChERS and HPLC-MS/MS were performed to detect picoxystrobin. Picoxystrobin had good linearity (R2 > 0.99), the average recovery rate was 75 - 102%, and the relative standard deviation was 1 - 11%. Picoxystrobin was utilized as the test agent in field experiments, and samples were evaluated and analyzed at various times after the final application utilizing random sampling. The results showed that picoxystrobin residuals in potato and citrus (orange meat) were ˂ 0.01 mg kg-1, whereas those in citrus whole fruit, D. officinale (fresh), and D. officinale (dried) were < 0.05 - 0.084, 0.16 - 3.82, and 0.34 - 9.05 mg kg-1, respectively. Based on these results, both the acute risk quotient (2.77%) and chronic risk quotient (8.7%) were ˂100%, and the dietary risk assessment indicated that the intake of picoxystrobin residues in potato, citrus fruit, and D. officinale did not pose a health risk. This study can guide the reasonable use of picoxystrobin in potato, citrus fruit, and D. officinale.

Evidence of solvent-mediated proton transfer during H2O2 activation in titanosilicate-catalyzed oxidation systems.

The catalytic performance of titanosilicates involving hydrogen peroxide (H2O2) as the oxidant is strongly influenced by the solvents. Until now, there is still a lack of a universal principle that can guide the choice of a solvent. Herein, the kinetics of H2O2 activation catalyzed by various titanosilicates in different solvents is investigated, and an isokinetic compensation effect is concluded. This indicates that the solvent participates in the H2O2 activation process for the formation of a Ti-OOH species. Additionally, the results of isotopically labeled infrared spectra preliminarily confirm that the solvent acts as the mediator to promote the proton transfer during the H2O2 activation process. The catalytic activities of a series of TS-1 catalysts toward 1-hexene epoxidation are compared, which include Ti(OSi)3OH species with a range of densities but a constant total Ti content. This reveals that the solvent effect is closely related to the Ti active sites of these TS-1 catalysts. Based on these results, a principle for the rational choice of solvent for this catalytic process is proposed. ROH is found to be the mediator for Ti(OSi)4 sites, and methanol, which has a strong proton-donating ability, is the best solvent for these sites. However, for the Ti(OSi)3OH sites, water (H2O) is the mediator, and a weaker hydrogen bonding between H2O molecules promotes proton transfer more effectively. The solvent influences the catalytic performance by perturbing the hydrogen bonds between the H2O molecules, and aprotic acetonitrile, which has a strong ability to break the hydrogen bonding network between H2O molecules, is the best solvent for Ti(OSi)3OH sites. This study provides experimental evidence that the solvent promotes the catalytic performance of titanosilicates by assisting the proton transfer during the catalytic H2O2 activation process, which will pave the way toward the rational choice of solvent for the titanosilicate-catalyzed oxidation systems.

Xenon-lamp simulated sunlight-induced photolysis of pyriclobenzuron in water: Kinetics, degradation pathways, and identification of photolysis products.

Pyriclobenzuron 1(PBU) is a novel molluscicide developed to control Pomacea canaliculate, and little information on its environmental fate has been published. In this study, the photolysis of PBU in an aqueous environment was simulated using a xenon lamp. Results showed that the photolysis of PBU in water followed first-order kinetics, exhibiting a t0.5 of 95.1 h and 83.6 h in Milli-Q water and river water, respectively. Two main photolysis products 2(PPs) were detected by HPLC-UV and identified by UPLC-Q/TOF MS, which were formed via the hydroxylation and photocatalytic hydro-dehalogenation of PBU, respectively. The initial relative abundance of photolysis product 1 3(PP-1) in Milli-Q water was 1.55 times higher than that in river water. PP-1 was detected at 26.5 % and 76.8 % of the maximum relative abundance in the river water and Milli-Q water after 720 h, respectively. Photolysis product 2 4(PP-2) was stable in water because of its weak hydrophilicity. The PP-2 detected after 720 h in Milli-Q water and river water was 93.7 % and 93.5 % of the maximum relative abundance, respectively. Finally, ECOSAR software was used to evaluate the acute aquatic toxicity of PBU and its PPs, revealing that the PPs had lower toxicity levels to non-target aquatic organisms.

[Application of "major scientific issues and engineering technology difficulties in traditional Chinese medicine(2019-2021)" in national science and t echnology layout].

In order to judge the future development trend of science and technology, plan ahead and lay out the frontier technology fields and directions, China Association of Chinese Medicine(CACM) has launched consultation projects for collecting "major scienti-fic issues and engineering technology difficulties in traditional Chinese medicine(TCM)" for the industry for three consecutive years since 2019. Up to now, 18 projects have been selected as major issues for research, and some experience and achievements have been made. These projects have been applied in important scientific and technological work such as scientific and technological planning and deployment at all levels of national, local, and scientific research institutions, the selection and cultivation of major national scientific and technological projects, and the construction of innovation bases, giving full play to the role of the think tank advisory committee of CACM. This study reviewed the selection of major issues for the first time, systematically combed its application in the national layout of science and technology, and put forward the existing problems and improvement suggestions, aiming to provide new ideas for further improving the selection of major issues and research direction, providing a theoretical basis and decision support for the national scientific and technological layout in the field of TCM, and promoting scientific and technological innovation to facilitate the high quality development of TCM.

Evaluation of single-cell classifiers for single-cell RNA sequencing data sets.

Single-cell RNA sequencing (scRNA-seq) has been rapidly developing and widely applied in biological and medical research. Identification of cell types in scRNA-seq data sets is an essential step before in-depth investigations of their functional and pathological roles. However, the conventional workflow based on clustering and marker genes is not scalable for an increasingly large number of scRNA-seq data sets due to complicated procedures and manual annotation. Therefore, a number of tools have been developed recently to predict cell types in new data sets using reference data sets. These methods have not been generally adapted due to a lack of tool benchmarking and user guidance. In this article, we performed a comprehensive and impartial evaluation of nine classification software tools specifically designed for scRNA-seq data sets. Results showed that Seurat based on random forest, SingleR based on correlation analysis and CaSTLe based on XGBoost performed better than others. A simple ensemble voting of all tools can improve the predictive accuracy. Under nonideal situations, such as small-sized and class-imbalanced reference data sets, tools based on cluster-level similarities have superior performance. However, even with the function of assigning 'unassigned' labels, it is still challenging to catch novel cell types by solely using any of the single-cell classifiers. This article provides a guideline for researchers to select and apply suitable classification tools in their analysis workflows and sheds some lights on potential direction of future improvement on classification tools.

Evolutionary origin of pathogenic GJB2 alleles in China.

The frequency of the pathogenic allele of the autosomal recessive deafness gene GJB2 varies among different populations in the world, and accumulates to a sufficiently high frequency in certain population. The purpose of this study is to investigate the origin and evolution of GJB2 pathogenic alleles in Chinese deaf patients. Children with non-syndromic hearing loss, and their parents, from 295 families were recruited. Customized capture probes targeted at 943 single nucleotide polymorphisms (SNPs) related to GJB2 gene were designed for sequencing of genomic DNA in blood samples. Haplotypes carrying pathogenic allele were analyzed through linkage disequilibrium block building, ancestry tracing, and extended haplotype heterozygosity calculation. Two pathogenic GJB2 alleles, c.235delC (18.41%) and c.109G > A (15.57%), were observed in 867 donors. For c.235delC allele, three different core haplotypes with one major haplotype (97.32%) were found, and their core SNPs were 100% conserved. For c.109G > A allele, six different haplotypes with one major haplotype (93.28%) were found and the major c.109G > A allele evolved from a specific ancestral haplotype. Geographical origins of donors carrying GJB2 c.109G > A and c.235delC core haplotypes centered between Qinghai and Neimenggu. GJB2 c.235delC has long-range linkage disequilibrium. No positive selection signature was found for GJB2 c.235delC or c.109G > A in the studied population. In conclusion, we discovered a single origin of GJB2 c.235delC allele and multiple independent origins of GJB2 c.109G > A allele. Alternative to positive selection or multiple independent recurrent mutation event, population bottleneck effect might account for the observed high population frequency of these pathogenic alleles.

Ab Initio Calculation of Ground- and Low-Excited-State Spectroscopic Data and Transition Properties of SBr.

In this paper, potential energy curves of Λ-S and Ω states of SBr+ are reported for the first time, and the spectrum data of some low excited bound states are obtained. The differences in the spectrum properties of main-group molecules and SBr+ were compared and analyzed, providing a sufficient theoretical basis for the subsequent study of main-group molecules. The avoided crossing that occurs in the Ω state is analyzed, and finally it is concluded that this phenomenon mainly occurs in the energy region between 20,000 and 40,000 cm-1 that is relative to the minimum energy value. Potential transitions in the Ω state capable of achieving laser cooling of SBr+ are explored. The Franck-Condon factor, radiation lifetime, and Einstein coefficient between X3Σ0+- and b1Σ0++ are calculated. From the calculation results, we concluded that direct laser cooling of SBr+ is not feasible. What we have studied in this paper provides a theoretical basis for subsequent computational exploration of the spectrum properties of SBr+.

Should cannulated screws be removed after a femoral neck fracture has healed, and how? A finite element analysis of the femur before and after cannulated screw removal.

PURPOSE: The removal of three inverted triangular parallel cannulated screws after the femoral neck fracture healing is sometimes accompanied by osteonecrosis of the femoral head (ONFH) or its refracture. The purpose of this study was to determine the biomechanical changes of the femur before and after the screw removal using a finite element analysis. METHODS: The CT data of the femurs were obtained from a 69-year-old healthy female to establish the femur models. The established finite element models consisted of N, C, and R groups: N group, the normal femur; C group (to simulate the femoral neck fracture healing after the internal fixation), the normal femur with three inverted triangular parallel cannulated screws (C1) or with two upper parallel screws (C2). For the R1 or R2 groups, the screws in the model of the C1 or C2 individuals were gradually removed in seven or three types of different screw combinations, respectively. The stresses and displacements of the femur were determined. RESULTS: (1) Compared with the N group, a uniform stress distribution was stopped by the addition of three screws in the C1 group; in contrast, all screw removals resulted in the stress concentration on the screw holes and the disappearance of stress shielding. Moreover, the average stress of the femoral head in C1 group increased by 37.85%, while that of the femoral neck decreased by 23.03%. (2) Compared with the C1 group, while only the lowest femoral calcar screw was removed, there was a similar stress distribution in the proximal femur, and the average stress of the femoral head increased only by 0.35% although that of the femoral neck increased by 63.62%; however, removal by any other means resulted in a significant stress concentration in the proximal femur and a significant increase in the average stresses of the femoral head and neck (5.96-40.95% and 12.82-75.46%, respectively). (3) Compared with the N or C1 group, there was a significant stress concentration on the screws and its surrounding proximal femur in the C2 group. (4) Compared with the C2 group, the simultaneous removal of two upper screws not only did not cause a significant stress concentration on the proximal femur but also significantly reduced the average stresses of the femoral head and neck by 87.49% and 65.51% respectively. On the contrary, the gradual removal of two screws caused a significant stress concentration on the screw and its surrounding proximal femur although the average stresses of the femoral head and neck decreased by 88.79-89.06% and 67.00-67.22%, respectively. (5) Compared with the N group, the average displacements of the femoral head and neck in the C1 group increased only by 3.12% and 3.37%, respectively. Additionally, compared with the C1 group, while three, two, or one screw was simultaneously removed, the average displacements of the femoral head and neck only fluctuated - 5.51-1.65% and 1.78-9.03%, respectively. CONCLUSIONS: Residual internal fixation after femoral neck fracture healing may lead to stress concentration on screws and stress shielding around screws. The first removal of the lowest femoral calcar screw and then the second removal of two upper residual screws have a minimum effect on the stress concentration on the proximal femur and the average stress on the femoral head. The incorrect screw removal and resulting femoral load may well be closely related to occurrence in ONFH or its refracture.

Dissipation, Processing Factors and Dietary Risk Assessment for Flupyradifurone Residues in Ginseng.

The massive use of pesticides has brought great risks to food and environmental safety. It is necessary to develop reliable analytical methods and evaluate risks through monitoring studies. Here, a method was used for the simultaneous determination of flupyradifurone (FPF) and its two metabolites in fresh ginseng, dried ginseng, ginseng plants, and soil. The method exhibited good accuracy (recoveries of 72.8-97.5%) and precision (relative standard deviations of 1.1-8.5%). The field experiments demonstrated that FPF had half-lives of 4.5-7.9 d and 10.0-16.9 d in ginseng plants and soil, respectively. The concentrations of total terminal residues in soil, ginseng plants, dried ginseng, and ginseng were less than 0.516, 2.623, 2.363, and 0.641 mg/kg, respectively. Based on these results, the soil environmental risk assessment shows that the environmental risk of FPF to soil organisms is acceptable. The processing factors for FPF residues in ginseng were 3.82-4.59, indicating that the concentration of residues increased in ginseng after drying. A dietary risk assessment showed that the risk of FPF residues from long-term and short-term dietary exposures to global consumers were 0.1-0.4% and 12.07-13.16%, respectively, indicating that the application of FPF to ginseng at the recommended dose does not pose a significant risk to consumers.

[Research Progress of Ubiquitin Proteasome Inhibitors in Acute Myeloid Leukemia].

Ubiquitin-proteasome system (UPS) plays an essential role in eukaryotic protein cycle,the dysregulation of which can lead to tumorigenesis.Increased activities of UPS have been observed in the patients with cancers including leukemia.UPS inhibitors can kill cancer cells by affecting ubiquitin-ligating enzyme E3,deubiquitinase,and protein degradation active sites of UPS.Therefore,UPS inhibitors have emerged as an important therapy for treating hematological malignancies,while they are rarely applied in the treatment of acute myeloid leukemia.This paper summarizes the research progress in the inhibitors affecting the protein ubiquitination at different stages of acute myeloid leukemia,aiming to provide new clues for the clinical treatment of acute myeloid leukemia.

Dissipation and residue analysis of novel nematicide trifluorocide in ginseng and soil using modified QuEChERS method coupled with HPLC-MS/MS.

In the present study, an analytical method that combined a modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method and high-performance liquid chromatography coupled with tandem mass spectrometry was developed to determine trifluorocide in fresh and dried ginseng roots, plants (stems and leaves), and soil. At three spiked levels (0.01, 0.1, and 1.0 mg kg-1), the mean recoveries (n = 15) of trifluorocide from fresh and dried ginseng roots, plants, and soil were in the range of 95.6 - 109.7%, with relative standard deviations less than 10.0%. The limits of quantitation of different matrices were determined to be 0.01 mg kg-1. Dissipation and residue study of trifluorocide was conducted in ginseng cultivation ecosystems in Northeast China. The t1/2 (half-life) of trifluorocide in ginseng fresh roots, plants, and soil were 8.3-13.1 days, 7.4-10.9 days, and 8.8-10.6 days, respectively. The terminal residues of trifluorocide in ginseng fresh roots were less than 0.01 mg kg-1 after 35 days of trifluorocide application. This study could be beneficial in residue analysis and assist in the scientific application of trifluorocide during ginseng cultivation.

A novel NGS-based microsatellite instability (MSI) status classifier with 9 loci for colorectal cancer patients.

BACKGROUND: With the recent emergence of immune checkpoint inhibitors, microsatellite instability (MSI) status has become an important biomarker for immune checkpoint blockade therapy. There are growing technical demands for the integration of different genomic alterations profiling including MSI analysis in a single assay for full use of the limited tissues. METHODS: Tumor and paired control samples from 64 patients with primary colorectal cancer were enrolled in this study, including 14 MSI-high (MSI-H) cases and 50 microsatellite stable (MSS) cases determined by MSI-PCR. All the samples were sequenced by a customized NGS panel covering 2.2 MB. A training dataset of 28 samples was used for selection of microsatellite loci and a novel NGS-based MSI status classifier, USCI-msi, was developed. NGS-based MSI status, single nucleotide variant (SNV) and tumor mutation burden (TMB) were detected for all patients. Most of the patients were also independently detected by immunohistochemistry (IHC) staining. RESULTS: A 9-loci model for detecting microsatellite instability was able to correctly predict MSI status with 100% sensitivity and specificity compared with MSI-PCR, and 84.3% overall concordance with IHC staining. Mutations in cancer driver genes (APC, TP53, and KRAS) were dispersed in MSI-H and MSS cases, while BRAF p.V600E and frameshifts in TCF7L2 gene occurred only in MSI-H cases. Mismatch repair (MMR)-related genes are highly mutated in MSI-H samples. CONCLUSION: We established a new NGS-based MSI classifier, USCI-msi, with as few as 9 microsatellite loci for detecting MSI status in CRC cases. This approach possesses 100% sensitivity and specificity, and performed robustly in samples with low tumor purity.

Inferring fetal fractions from read heterozygosity empowers the noninvasive prenatal screening.

PURPOSE: Fetal fraction (FF) is the percent of cell-free DNA (cfDNA) in the mother's peripheral blood that is of fetal origin, which plays a pivotal role in noninvasive prenatal screening (NIPS). We present a method that can reliably estimate FFs by examining autosome single-nucleotide polymorphisms (SNPs). METHODS: Even at a very low sequencing depth, there are plenty of SNPs covered by more than one read. At those SNPs, we define read heterozygosity and demonstrate that the percent of read heterozygosity is a function of FF, which allows FF to be inferred. RESULTS: We first demonstrated the effectiveness of our method in inferring FF. Then we used the inferred FF as an informative alternative prior to computing Bayes factors to test for aneuploidy, and observed better power than the Z-test. In analysis of clinical samples, we were able to identify female-male twins thanks to the accurate FF inference. CONCLUSION: Knowing FF improves efficacy of NIPS. It brings a powerful Bayesian method, allows "no call" for samples with small FFs, renders screening for XXY syndrome simpler, and permits an adaptive design to sequence at a higher depth for samples with small FFs.

Correction: Inferring fetal fractions from read heterozygosity empowers the noninvasive prenatal screening.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Identification of a novel melatonin-binding nuclear receptor: Vitamin D receptor.

Previous studies confirmed that melatonin regulates Runx2 expression but the mechanism is unclear. There is a direct interaction between Runx2 and the vitamin D receptor (VDR). Herein, we observed a direct interaction between melatonin and the VDR but not Runx2 using isothermal titration calorimetry. Furthermore, this direct binding was detected only in the C-terminal ligand binding domain (LBD) of the VDR but not in the N-terminal DNA-binding domain (DBD) or the hinge region. Spectrophotometry indicated that melatonin and vitamin D3 (VD3) had similar uptake rates, but melatonin's uptake was significantly inhibited by VD3 until the concentration of melatonin was obviously higher than that of VD3 in a preosteoblastic cell line MC3T3-E1. GST pull-down and yeast two-hybrid assay showed that the interactive smallest fragments were on the 319-379 position of Runx2 and the N-terminus 110-amino acid DBD of the VDR. Electrophoretic mobility shift assay (EMSA) demonstrated that Runx2 facilitated the affinity between the VDR and its specific DNA substrate, which was further documented by a fluorescent EMSA assay where Cy3 labeled Runx2 co-localized with the VDR-DNA complex. Another fluorescent EMSA assay confirmed that the binding of the VDR to Runx2 was significantly enhanced with an increasing concentrations of the VDR, especially in the presence of melatonin; it was further documented using a co-immunoprecipitation assay that this direct interaction was markedly enhanced by melatonin treatment in the MC3T3-E1 cells. Thus, the VDR is a novel melatonin-binding nuclear receptor, and melatonin indirectly regulates Runx2 when it directly binds to the LBD and the DBD of the VDR, respectively.