Evolutionary and biomedical insights from a marmoset diploid genome assembly.

The accurate and complete assembly of both haplotype sequences of a diploid organism is essential to understanding the role of variation in genome functions, phenotypes and diseases1. Here, using a trio-binning approach, we present a high-quality, diploid reference genome, with both haplotypes assembled independently at the chromosome level, for the common marmoset (Callithrix jacchus), an primate model system that is widely used in biomedical research2,3. The full spectrum of heterozygosity between the two haplotypes involves 1.36% of the genome-much higher than the 0.13% indicated by the standard estimation based on single-nucleotide heterozygosity alone. The de novo mutation rate is 0.43 × 10-8 per site per generation, and the paternal inherited genome acquired twice as many mutations as the maternal. Our diploid assembly enabled us to discover a recent expansion of the sex-differentiation region and unique evolutionary changes in the marmoset Y chromosome. In addition, we identified many genes with signatures of positive selection that might have contributed to the evolution of Callithrix biological features. Brain-related genes were highly conserved between marmosets and humans, although several genes experienced lineage-specific copy number variations or diversifying selection, with implications for the use of marmosets as a model system.

Platypus and echidna genomes reveal mammalian biology and evolution.

Egg-laying mammals (monotremes) are the only extant mammalian outgroup to therians (marsupial and eutherian animals) and provide key insights into mammalian evolution1,2. Here we generate and analyse reference genomes of the platypus (Ornithorhynchus anatinus) and echidna (Tachyglossus aculeatus), which represent the only two extant monotreme lineages. The nearly complete platypus genome assembly has anchored almost the entire genome onto chromosomes, markedly improving the genome continuity and gene annotation. Together with our echidna sequence, the genomes of the two species allow us to detect the ancestral and lineage-specific genomic changes that shape both monotreme and mammalian evolution. We provide evidence that the monotreme sex chromosome complex originated from an ancestral chromosome ring configuration. The formation of such a unique chromosome complex may have been facilitated by the unusually extensive interactions between the multi-X and multi-Y chromosomes that are shared by the autosomal homologues in humans. Further comparative genomic analyses unravel marked differences between monotremes and therians in haptoglobin genes, lactation genes and chemosensory receptor genes for smell and taste that underlie the ecological adaptation of monotremes.

Plasmon-modulated bistable second-harmonic generation in a nonlinear microcavity coupled to a metallic nanoparticle.

Multiple nonlinear effects with second-harmonic (SH) generation and optical bistability (OB) are highly desired but rather rare due to insufficient intrinsic nonlinearity in most nonlinear media. Here, a nonlinear microcavity coupled to a metallic nanoparticle (MNP) is suggested to realize the bistable SH generation. When two counterpropagating driving fields are injected into the cavity, a traditional SH pathway is constructed via the two-photon process of fundamental-harmonic (FH) photons. In addition, we report the coexistence between the SH and OB effects under the condition that the strong excitation and the detuning management for the driving fields boost system nonlinear responses. In the presence of a control field toward the MNP, our calculation finds that the traditional and plasmon-induced SH pathways in the present system allow enhancing the SH conversion efficiency and reducing the OB thresholds simultaneously. With the control field intensity increasing, a linear growth rate for the SH efficiency maximum is achieved. Furthermore, the relative phase between the driving and control fields has profound effects on modulating the bistable SH efficiency, the bistable interval and the thresholds.

Providing or receiving alloparental care promote partner preference and alter central oxytocin and dopamine systems in adult mandarin voles.

Juveniles of cooperative breeding species usually remain in the natal area and provide care to younger siblings, a behavior considered one form of alloparenting in the natural condition. Previous studies have demonstrated the effects of providing or receiving alloparental care on adult behaviors, including anxiety-like behavior, social interaction, and parental behavior, but little is known about the influences on species-typical bonding behaviors, such as pair-bond formation. In this study, we explored this concept using socially monogamous mandarin voles (Lasiopodomys mandarinus). As the oxytocin (OT) and dopamine systems are involved in alloparental and pair-bonding behaviors, we also examined the levels of central OT and tyrosine hydroxylase (TH), as well as OT receptor (OTR) and dopamine D1-type and D2-type receptors (D1R and D2R) mRNA expression in the nucleus accumbens (NAcc) and amygdala to investigate the underlying mechanisms. Our results show that mandarin voles providing alloparental care to younger siblings displayed facilitation of partner preference formation, lower levels of OT expression in the paraventricular nucleus of the hypothalamus (PVN) and lateral hypothalamus (LH), and increased OTR and D2R mRNA expression in the NAcc compared to controls. Individuals receiving alloparental care also demonstrated facilitation of partner preference formation in adult voles. Additionally, alloparental care enhanced OT expression in the PVN, anterior medial preoptic nucleus (MPOAa), medial amygdala (MeA), and TH expression in the ventral tegmental area (VTA) and zona incerta (ZI). Furthermore, males displayed decreased D1R mRNA expression in the NAcc, whereas females showed slightly increased D2R expression in the amygdala. These results demonstrate that providing or received alloparental care can promote partner preference formation in monogamous species and that these changes are associated with altered OT and dopamine levels and their receptors in specific brain regions.

Expression and clinical significance of CXCL17 and GPR35 in endometrial carcinoma.

Endometrial carcinoma is one of the most common gynecologic malignancies. CXCL17-CXCR8 (GPR35) axis is reported to play an indispensability role in tumors. Our purpose is to screen possible prognostic and immune-related factors in endometrial carcinoma by detecting the mRNA and protein expression of CXCL17 and CXCR8. We use the qRT-PCR method to test the mRNA expression of CXCL17 and CXCR8 in 35 pairs of endometrial carcinoma and adjacent tissue. The protein expression of CXCL17 and CXCR8 in 30 cases of normal proliferative endometrium, 30 cases of endometrial atypical hyperplasia and 50 cases of endometrial carcinoma was detected by tissue microarray immunohistochemistry. There was no significant difference in the positive expression rate between endometrial adenocarcinoma tissue and endometrial atypical hyperplasia tissue (P > 0.05). But significantly better than normal proliferative tissue (P < 0.001). Correlation analysis of CXCR8 and CXCL17 in endometrial carcinoma showed a positive correlation (r = 0.9123, P < 0.0001). For patients with endometrial cancer, the overall survival (OS) of patients with high CXCL17 expression was significantly higher than that low CXCL17 expression (log-rank test, P < 0.0001), whereas CXCR8 had no statistical significance. But the expression of CXCR8 is an independent prognostic factor of OS in endometrial carcinoma patients. Our study showed that CXCL17 and CXCR8 may be involved in the occurrence and development of endometrial cancer. High expression of CXCL17 may be used as a biomarker for predicting survival. Because CXCL17 and CXCL18 are related to lymphocytes and immune regulation, they are expected to become potential targets for immunotherapy.

Practical application of European biological variation combined with Westgard Sigma Rules in internal quality control.

OBJECTIVES: Westgard Sigma Rules is a statistical tool available for quality control. Biological variation (BV) can be used to set analytical performance specifications (APS). The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) regularly updates BV data. However, few studies have used robust BV data to determine quality goals and design a quality control strategy for tumor markers. The aim of this study was to derive APS for tumor markers from EFLM BV data and apply Westgard Sigma Rules to establish internal quality control (IQC) rules. METHODS: Precision was calculated from IQC data, and bias was obtained from the relative deviation of the External quality assurance scheme (EQAS) group mean values and laboratory-measured values. Total allowable error (TEa) was derived using EFLM BV data. After calculating sigma metrics, the IQC strategy for each tumor marker was determined according to Westgard Sigma Rules. RESULTS: Sigma metrics achieved for each analyte varied with the level of TEa. Most of these tumor markers except neuron-specific enolase reached 3σ or better based on TEamin. With TEades and TEaopt set as the quality goals, almost all analytes had sigma values below 3. Set TEamin as quality goal, each analyte matched IQC muti rules and numbers of control measurements according to sigma values. CONCLUSIONS: Quality goals from the EFLM BV database and Westgard Sigma Rules can be used to develop IQC strategy for tumor markers.

Radially polarized cosine non-uniformly correlated beams and their propagation properties.

We introduce a kind of radially polarized partially coherent (RPPC) beam with a prescribed non-uniform correlation function, called a radially polarized cosine non-uniformly correlated (RPCNUC) beam. Based on the extended Huygens-Fresnel principle, we study the propagation properties in free space and in a turbulent atmosphere. Unlike RPPC beams with uniform coherence, RPCNUC beams possess the invariance of dark hollow cores and radial polarization, and exhibit self-focusing properties. In a turbulent atmosphere, the intensity distribution demonstrates self-healing properties over a certain propagation distance. We also investigate how to adjust the beam parameters to reduce the turbulence-induced degradation in detail.

Ppm-level oxygen detection system based on deep-ultraviolet-absorption spectroscopy.

Oxygen is a gas essential to human life and industrial processes. Here, we developed a highly sensitive oxygen gas sensor based on deep ultraviolet absorption spectroscopy between 180 and 200 nm. The implemented method relies on differential absorption spectra extracted from the obtained high-resolution absorption spectra. The detection capability was greatly improved (six-fold) by eliminating air from the open optical path, achieved by purging the entire system with pure nitrogen. A linear relationship was obtained between the optical parameter and the oxygen concentration with a slope of 0.107 and determination coefficient of 0.999. A detection limit of 24 ppm per meter was determined with a response time of 25 s. Good repeatability (standarddeviation=16ppm) and stability were confirmed. We demonstrated that this system can detect ppm oxygen levels with high sensitivity and low uncertainty.

Circ_0072995 drives cervical cancer development by regulating the miR-29a/WDR5 axis.

Circular RNA_0072995 (Circ_0072995) is involved in the pathogenesis of cancers; however, no study has investigated its role in cervical cancer. Therefore, we aimed to investigate the function of circ_0072995 in cervical cancer. Normal human cervical epithelial cells (hCECs), HeLa cells, and forty female nude BALB/c mice were used. Immunohistochemistry, invasion assays, flow cytometric analysis, luciferase assays, and tumour volume measurements were performed to explore the potential mechanism. Circ_0072995 was significantly up-regulated in cancer tissues, and its level was markedly correlated with the International Federation of Gynecology and Obstetrics system (FIGO) staging. In vitro studies revealed that circ_0072995 interacts with miR-29a to induce WD repeat domain 5 (WDR5) expression and promotes the proliferation and invasion of cells, but inhibits apoptosis of cells. Knockdown of circ_0072995 or WDR5, or overexpression of miR-29a significantly inhibited tumour growth in vivo. In conclusion, circ_0072995 promoted cervical cancer development by inducing miR-29a-mediated WDR5 expression.Impact statementWhat is already known on this subject? Global Cancer Statistics 2020 estimated that there were 1 021,494 new cases of cervical cancer and 439 201 deaths from cervical cancer. Circ_0072995 was first shown to promote breast cancer development in 2018. Subsequent studies have revealed that circ_0072995 is also involved in the development of other cancers, including epithelial ovarian cancer and hepatocellular carcinoma. However, no studies have explored the association between circ_0072995 and cervical cancer.What do the results of this study add? We hypothesized that circ_0072995 drives cervical cancer development by sponging miRNAs and inducing the expression of key factors involved in tumorigenesis. Based on this hypothesis, we investigated the role of circ_0072995 in cervical cancer and paracancerous tissues and explored the underlying mechanism in both in vitro and in vivo studies.What are the implications of these findings for clinical practice and/or further research? For the first time, our study revealed the key role of WDR5 in cervical cancer progression regulated by circ_0072995. We first reported the promoting effects of circ_0072995 in cervical cancer development by inducing miR-29a mediated WDR5 expression and also revealed the therapeutic potential of circ_0072995, miR-29a, and WDR5 in cervical cancer.

Mesh Denoising via Adaptive Consistent Neighborhood.

In this paper, we propose a novel guided normal filtering followed by vertex updating for mesh denoising. We introduce a two-stage scheme to construct adaptive consistent neighborhoods for guided normal filtering. In the first stage, we newly design a consistency measurement to select a coarse consistent neighborhood for each face in a patch-shift manner. In this step, the selected consistent neighborhoods may still contain some features. Then, a graph-cut based scheme is iteratively performed for constructing different adaptive neighborhoods to match the corresponding local shapes of the mesh. The constructed local neighborhoods in this step, known as the adaptive consistent neighborhoods, can avoid containing any geometric features. By using the constructed adaptive consistent neighborhoods, we compute a more accurate guide normal field to match the underlying surface, which will improve the results of the guide normal filtering. With the help of the adaptive consistent neighborhoods, our guided normal filtering can preserve geometric features well, and is robust against complex shapes of surfaces. Intensive experiments on various meshes show the superiority of our method visually and quantitatively.

Influence of flocculation conditioning on environmental risk of heavy metals in dredged sediment.

This study comprehensively analyzes the environmental risk of heavy metals (HMs) in the dewatering process of dredged sediment. First, the toxicity leaching capacity, total content, and chemical speciation of the HMs (As, Cd, Co, Cr, Cu, Hg, Mo, Pb, Sb, Sr, Tl, Zn) in dewatered sediment were determined using toxicity characteristic leaching procedure and modified Community Bureau of Reference sequential extraction procedure. The ecotoxicity and environmental risk of the HMs were then evaluated based on sediment quality guidelines, geo-accumulation index, enrichment factor, potential ecological risk, and risk assessment code. The results showed that flocculants reduced the ecological risk of Hg and Mo in sediment, and promoted the transformation of Mo, Sb, and Tl from the biologically active fraction to the more stable fraction. The transformation percentages of Mo, Sb, and Ti were 45.15%, 50.59% and 76.44%, respectively, after chitosan (CTS) treatment, and 64.55%, 31.75% and 99.90%, respectively, after cationic polyacrylamide (CPAM) treatment. CTS reduced the potential risks of bioavailable As, Cr, Cu, Mo, Sb, and Hg by (at most) 46.28%, 45.92%, 43.01%, 100.00%, 44.45%, and 39.69%, respectively, whereas CPAM decreased the ecotoxicity of bioavailable Cd, Co, and Zn by (at most) 27.49%, 16.10%, and 20.89%, respectively. According to the result of principal component analysis, the main factors affecting the environmental risk of HMs in sediment dewatering were nitrogenous organic compounds (mainly protein substances), fulvic acid substances, and minerals. The most essential factor was nitrogenous organic compounds, which accounted for 89.52% of the total variance. Chemical speciation was apparently more suitable for environmental risk assessment of sediment dewatering than total content. This study provides an important basis for controlling the environmental risk of HMs caused by sediment dewatering.

Systematic assessment of dredged sludge dewaterability improvement with different organic polymers based on analytic hierarchy process.

Organic polymeric flocculants are commonly used in improving dredged sludge dewaterability, but less attention has been paid to residual water quality. In this paper, the effects of cationic etherified starch (CS) and poly-dimethyl diallyl ammonium chloride (PDDA) on dredged sludge dewatering efficiency and residual water quality of Baiyangdian lake were comprehensively investigated and evaluated by analytic hierarchy process (AHP). The results indicated that PDDA had stronger electrical effect and flocculation performance compared with CS, resulting in more efficient dewatering performance. PDDA can reduce the pollutants of discharged residual water, while CS significantly promoted the increase of NH4+-N and NO3--N in the residual water. The increase of NH4+-N in the residual water of CS was due to the release of dredged sludge, while the increase of NO3--N was introduced by CS leaching. AHP showed that PDDA performed better in flocculation treatment of dredged sludge than other organic polymers. This work provides a method for optimization of flocculation treatment for dredged sludge dewaterability.

Multi-hyperbolic sine-correlated beams and their statistical properties in turbulent atmosphere.

We introduce a partially coherent beam, called a multi-hyperbolic sine-correlated (MHSC) beam, by employing a multi-hyperbolic sine function to modulate the spectral degree of coherence. Based on the extended Huygens-Fresnel principle and second-order moments of the Wigner distribution function, we derive the analytical expressions for the spectral intensity, the root-mean-square (rms) angular width and the M2 factor in turbulent atmosphere. Numerical results show that the intensity profile, which keeps the dark-hollow invariant in free space, will be gradually destroyed by the turbulence along the propagation distance. We believe that the MHSC beams have significant advantage over the hyperbolic sine-correlated beams for reducing the turbulence-induced degradation, especially for the MHSC beams with a higher beam order N. The effects of the beams parameters and the turbulent atmosphere on the beam quality are analyzed in detail.

Propagation properties of radially polarized multi-Gaussian Schell-model beams in oceanic turbulence.

By utilizing the extended Huygens-Fresnel principle, we derive the analytical formulas for the cross-spectral density matrix elements of a radially polarized multi-Gaussian Schell-model (RPMGSM) beam propagating in oceanic turbulence. Effects of beam parameters and oceanic turbulence parameters on the propagation properties of RPMGSM beams are investigated in detail by numerical simulation. Our results show that the RPMGSM beam with larger beam order M has an advantage over the radially polarized Gaussian Schell-model beam for reducing turbulence-induced degradation. Compared with temperature-induced turbulence fluctuation, the salinity-induced turbulence fluctuation makes a greater contribution to the influence on propagation properties of RPMGSM beams.

Customized design and efficient fabrication of two freeform aluminum mirrors by single point diamond turning technique.

The precision single point diamond turning technique has been a promising technology for generating small and medium-sized freeform optical elements with high surface quality. In this paper, we present an extremely off-axis freeform optical system with a large 10.0 mm pupil diameter and a low 3.0 F-number over a wide 28° field of view. It is composed of two freeform aluminum mirrors, which are fabricated efficiently by the single point diamond turning machine. The manufacturing strategy and parameters are estimated rationally and comprehensively, based on the freeform surface characters. The freeform aluminum mirror surface can reach submicron surface accuracy and achieve nanometer surface roughness. The final assembled prototype of the off-axis two-mirror freeform display optical system has the advantages of compactness, a broad spectrum, and good display imaging performance.

Parent-offspring cohabitation after weaning inhibits partner preference and alters central oxytocin and dopamine systems in adult mandarin vole.

In some mammals, offspring may live with their parents for a very long time after weaning, but little is known about the effect of post-weaning parent-offspring cohabitation on the behavioral and neurobiological development of offspring. Here, we explored the effect of this experience on partner preference in adult mandarin vole (Microtus mandarinus). Levels of central oxytocin (OT), tyrosine hydroxylase (TH), as well as OT receptor (OTR), dopamine D1-type and D2-type receptors (D1R and D2R) mRNA expression in the nucleus accumbens (NAcc) and medial amygdala (MeA) were also measured. Our data showed that post-weaning living with parents inhibited the preference to partner over an unfamiliar opposite-sex conspecific. Voles with this experience possessed more OT-but less TH-immunoreactive neurons as compared to the control. Additionally, males with this experience had less D2R and OTR mRNA expression in the NAcc than the control while females had less D2R mRNA expression in the NAcc, but more OTR mRNA expression in the MeA. These findings demonstrate that post-weaning parent-offspring cohabitation inhibits the partner preference formation at adulthood, and these changes may be associated with alterations in the levels of central OT and DA, and their receptor mRNA expression in specific brain regions.

Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel.

Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Although a capsaicin-bound channel structure was previously resolved by cryo-EM at 4.2- to 4.5-Å resolution, capsaicin was registered as a small electron density, reflecting neither its chemical structure nor specific ligand-channel interactions--important details required for mechanistic understanding. We obtained the missing atomic-level details by iterative computation and confirmed them by systematic site-specific functional tests. We observed that the bound capsaicin takes a 'tail-up, head-down' configuration. The vanillyl and amide groups form specific interactions to anchor its bound position, while the aliphatic tail may sample a range of conformations, making it invisible in cryo-EM images. Capsaicin stabilizes TRPV1's open state by 'pull-and-contact' interactions between the vanillyl group and the S4-S5 linker. Our study provides a structural mechanism for the agonistic function of capsaicin and its analogs, and demonstrates an effective approach to obtain atomic-level information from cryo-EM structures.

Synthesis of highly effective absorbents with waste quenching blast furnace slag to remove Methyl Orange from aqueous solution.

Water quenching blast furnace slag (WQBFS) is widely produced in the blast furnace iron making process. It is mainly composed of CaO, MgO, Al2O3, and SiO2 with low contents of other metal elements such as Fe, Mn, Ti, K and Na. In this study, WQBFS was treated with grinding, hydrochloric acid acidification, filtration, filtrate extraction by alkali liquor and a hydration reaction. Then BFS micropowder (BFSMP), BFS acidified solid (BFSAS) and BFS acid-alkali precipitate (BFSAP) were obtained, which were characterized by X-ray diffraction, scanning electron microscopy, X-ray fluorescence and Brunauer-Emmet-Teller (BET) specific surface area. The decoloration efficiency for Methyl Orange (MO) was used to evaluate the adsorptive ability of the three absorbents. The effects of adsorptive reaction conditions (pH and temperature of solution, reaction time, sorbent dosage and initial concentration) on MO removal were also investigated in detail. The results indicated that BFSAP performed better in MO removal than the other two absorbents. When the pH value of MO solutions was in the range 3.0-13.0, the degradation efficiency of a solution with initial MO concentration of 25mg/L reached 99.97% for a reaction time of 25min at 25°C. The maximum adsorption capacity of BFSAP for MO was 167mg/g. Based on optimized experiments, the results conformed with the Langmuir adsorption isotherm and pseudo-second-order kinetics. Among inorganic anions, SO42- and PO43- had significant inhibitory effects on MO removal in BFSAP treatment due to ion-exchange adsorption.

Propagation factors of multi-sinc Schell-model beams in non-Kolmogorov turbulence.

We derive several analytical expressions for the root-mean-square (rms) angular width and the M(2)-factor of the multi-sinc Schell-model (MSSM) beams propagating in non-Kolmogorov turbulence with the extended Huygens-Fresnel principle and the second-order moments of the Wigner distribution function. Numerical results show that a MSSM beam with dark-hollow far fields in free space has advantage over the one with flat-topped or multi-rings far fields for reducing the turbulence-induced degradation, which will become more obvious with larger dark-hollow size. Beam quality of MSSM beams can be further improved with longer wavelength and larger beam width, or under the condition of weaker turbulence. We also demonstrate that the non-Kolmogorov turbulence has significantly less effect on the MSSM beams than the Gaussian Schell-model beam.

Bilobalide alleviates depression-like behavior and cognitive deficit induced by chronic unpredictable mild stress in mice.

Bilobalide (BB), a unique constituent of Ginkgo biloba, has powerful neuroprotection and stress-alleviating properties. However, whether BB exerts a positive effect on depression and cognitive deficit induced by chronic stress is not known. The present study was designed to investigate the influence of BB on depression and cognitive impairments induced by chronic unpredictable mild stress (CUMS) in mice. During daily exposure to stressors for 5 consecutive weeks, mice were administered BB at the doses of 0, 3, or 6 mg/kg/day intraperitoneally. We replicated the finding that CUMS induced depression-like behavior and cognitive deficits as the CUMS+vehicle (VEH) group showed a significant increase in immobility in the tail suspension test, a decrease in the discrimination index of the novel object recognition task, and increased latency to platform and decreased number of platform crossings in the Morris water maze compared with the control+VEH group. Chronic administration of BB effectively reversed these alterations. In addition, the CUMS+VEH group showed significantly higher levels of baseline serum corticosterone than those of the control+VEH group and BB dose-dependently inhibited this effect. Our results suggest that BB may be useful for inhibition of depression-like behavior and cognitive deficits, and this protective effect was possibly exerted partly through an action on the hypothalamic-pituitary-adrenal axis.