Phylogenomic discovery of deleterious mutations facilitates hybrid potato breeding.

Hybrid potato breeding will transform the crop from a clonally propagated tetraploid to a seed-reproducing diploid. Historical accumulation of deleterious mutations in potato genomes has hindered the development of elite inbred lines and hybrids. Utilizing a whole-genome phylogeny of 92 Solanaceae and its sister clade species, we employ an evolutionary strategy to identify deleterious mutations. The deep phylogeny reveals the genome-wide landscape of highly constrained sites, comprising ∼2.4% of the genome. Based on a diploid potato diversity panel, we infer 367,499 deleterious variants, of which 50% occur at non-coding and 15% at synonymous sites. Counterintuitively, diploid lines with relatively high homozygous deleterious burden can be better starting material for inbred-line development, despite showing less vigorous growth. Inclusion of inferred deleterious mutations increases genomic-prediction accuracy for yield by 24.7%. Our study generates insights into the genome-wide incidence and properties of deleterious mutations and their far-reaching consequences for breeding.

Plant 22-nt siRNAs mediate translational repression and stress adaptation.

Small interfering RNAs (siRNAs) are essential for proper development and immunity in eukaryotes1. Plants produce siRNAs with lengths of 21, 22 or 24 nucleotides. The 21- and 24-nucleotide species mediate cleavage of messenger RNAs and DNA methylation2,3, respectively, but the biological functions of the 22-nucleotide siRNAs remain unknown. Here we report the identification and characterization of a group of endogenous 22-nucleotide siRNAs that are generated by the DICER-LIKE 2 (DCL2) protein in plants. When cytoplasmic RNA decay and DCL4 are deficient, the resulting massive accumulation of 22-nucleotide siRNAs causes pleiotropic growth disorders, including severe dwarfism, meristem defects and pigmentation. Notably, two genes that encode nitrate reductases-NIA1 and NIA2-produce nearly half of the 22-nucleotide siRNAs. Production of 22-nucleotide siRNAs triggers the amplification of gene silencing and induces translational repression both gene specifically and globally. Moreover, these 22-nucleotide siRNAs preferentially accumulate upon environmental stress, especially those siRNAs derived from NIA1/2, which act to restrain translation, inhibit plant growth and enhance stress responses. Thus, our research uncovers the unique properties of 22-nucleotide siRNAs, and reveals their importance in plant adaptation to environmental stresses.

Interfacial Cherenkov radiation from ultralow-energy electrons.

Cherenkov radiation occurs only when a charged particle moves with a velocity exceeding the phase velocity of light in that matter. This radiation mechanism creates directional light emission at a wide range of frequencies and could facilitate the development of on-chip light sources except for the hard-to-satisfy requirement for high-energy particles. Creating Cherenkov radiation from low-energy electrons that has no momentum mismatch with light in free space is still a long-standing challenge. Here, we report a mechanism to overcome this challenge by exploiting a combined effect of interfacial Cherenkov radiation and umklapp scattering, namely the constructive interference of light emission from sequential particle-interface interactions with specially designed (umklapp) momentum-shifts. We find that this combined effect is able to create the interfacial Cherenkov radiation from ultralow-energy electrons, with kinetic energies down to the electron-volt scale. Due to the umklapp scattering for the excited high-momentum Bloch modes, the resulting interfacial Cherenkov radiation is uniquely featured with spatially separated apexes for its wave cone and group cone.

Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease.

BACKGROUND: Sickle cell disease is characterized by the painful recurrence of vaso-occlusive events. Gene therapy with the use of LentiGlobin for sickle cell disease (bb1111; lovotibeglogene autotemcel) consists of autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified ß-globin gene, which produces an antisickling hemoglobin, HbAT87Q. METHODS: In this ongoing phase 1-2 study, we optimized the treatment process in the initial 7 patients in Group A and 2 patients in Group B with sickle cell disease. Group C was established for the pivotal evaluation of LentiGlobin for sickle cell disease, and we adopted a more stringent inclusion criterion that required a minimum of four severe vaso-occlusive events in the 24 months before enrollment. In this unprespecified interim analysis, we evaluated the safety and efficacy of LentiGlobin in 35 patients enrolled in Group C. Included in this analysis was the number of severe vaso-occlusive events after LentiGlobin infusion among patients with at least four vaso-occlusive events in the 24 months before enrollment and with at least 6 months of follow-up. RESULTS: As of February 2021, cell collection had been initiated in 43 patients in Group C; 35 received a LentiGlobin infusion, with a median follow-up of 17.3 months (range, 3.7 to 37.6). Engraftment occurred in all 35 patients. The median total hemoglobin level increased from 8.5 g per deciliter at baseline to 11 g or more per deciliter from 6 months through 36 months after infusion. HbAT87Q contributed at least 40% of total hemoglobin and was distributed across a mean (±SD) of 85±8% of red cells. Hemolysis markers were reduced. Among the 25 patients who could be evaluated, all had resolution of severe vaso-occlusive events, as compared with a median of 3.5 events per year (range, 2.0 to 13.5) in the 24 months before enrollment. Three patients had a nonserious adverse event related or possibly related to LentiGlobin that resolved within 1 week after onset. No cases of hematologic cancer were observed during up to 37.6 months of follow-up. CONCLUSIONS: One-time treatment with LentiGlobin resulted in sustained production of HbAT87Q in most red cells, leading to reduced hemolysis and complete resolution of severe vaso-occlusive events. (Funded by Bluebird Bio; HGB-206 ClinicalTrials.gov number, NCT02140554.).

Preparation and Wettability Analysis of Metal Biofunctional Surfaces Based on the Microquadrangular Structure.

Improving the hydrophobic properties of aluminum alloys is crucial for industry. In previous reports, researchers prepared superhydrophobic surfaces by fabricating micro-nanostructures on the metal surface with a nanosecond laser. However, no researchers have formed microquadrangular groove structures on the metal surface. In this article, inspired by the bamboo leaf, a microquadrangular structure is designed and processed using nanosecond laser technology to form a superhydrophobic functional surface. The effects of laser processing parameters, such as laser power, scanning speed, scanning time, defocus and fill spacing on the size, surface morphology features, and wettability of the microquadrangular structure, are investigated by a single-factor experimental method. The experimental results show the optimal size of the processed microquadrangular structure obtained from the experiment with an error of 1.28% from the design size, where the fill spacing has the greatest effect on the size and the scanning time, defocus, and fill spacing have great influence on the surface morphology. The contact angle of water drops on the surface can reach 154.7°, and the power has the greatest influence on the wettability. Laser parameters have distinct effects on the properties of the materials. Therefore, by regulation of the laser parameters, the formation of the microstructure can be availably controlled and the result of hydrophobicity can be achieved.

Bayesian compositional generalized linear models for analyzing microbiome data.

The crucial impact of the microbiome on human health and disease has gained significant scientific attention. Researchers seek to connect microbiome features with health conditions, aiming to predict diseases and develop personalized medicine strategies. However, the practicality of conventional models is restricted due to important aspects of microbiome data. Specifically, the data observed is compositional, as the counts within each sample are bound by a fixed-sum constraint. Moreover, microbiome data often exhibits high dimensionality, wherein the number of variables surpasses the available samples. In addition, microbiome features exhibiting phenotypical similarity usually have similar influence on the response variable. To address the challenges posed by these aspects of the data structure, we proposed Bayesian compositional generalized linear models for analyzing microbiome data (BCGLM) with a structured regularized horseshoe prior for the compositional coefficients and a soft sum-to-zero restriction on coefficients through the prior distribution. We fitted the proposed models using Markov Chain Monte Carlo (MCMC) algorithms with R package rstan. The performance of the proposed method was assessed by extensive simulation studies. The simulation results show that our approach outperforms existing methods with higher accuracy of coefficient estimates and lower prediction error. We also applied the proposed method to microbiome study to find microorganisms linked to inflammatory bowel disease (IBD). To make this work reproducible, the code and data used in this article are available at https://github.com/Li-Zhang28/BCGLM.

The Shear-Accelerated II-I Phase Transition of Isotactic Poly(1-Butene).

The II-I phase transition of isotactic poly(1-butene) (iPBu) leads to improved mechanical performance. However, this will take several weeks and increase storage and processing costs. In this work, shear forces are introduced into the supercooled iPBu melt, and the effects of isothermal crystallization temperature (Tc) and shear temperature (Tshear) on crystallization and phase transition are explored. Shear-induced transcrystalline morphology of Form II with a significantly shortened crystallization induction period can be observed at relatively high Tc (105 °C). Besides, the shear-induced Form II can transit to Form I faster than the unsheared one. In addition, the phase transition rate increases as the Tshear decreases, with the fastest rate occurring at Tshear of 120 °C. The half transition time (t1/2) is measured as 6.3 h when Tc = 105 °C, Tshear = 120 °C, which is much shorter than the 20.7 h required for unsheared samples. The accelerated phase transition of iPBu can be attributed to the stretching of molecular chains, resulting from shear treatment. This study provides a quantitative analysis of the influence of the shear treatment and the Tshear on the II-I phase transition rate. It also presents a cost-effective and straightforward approach for expediting the phase transition process.

Developing a competency model for Chinese general practitioners: a mixed-methods study.

BACKGROUND: The Chinese government has formulated a series of policies and strengthened training of general practitioners (GPs) to support their role as "gatekeepers" of residents' health. This study aimed to explore the core competencies of Chinese GPs and develop a competency framework in line with China's actual conditions, which can provide a more scientific basis for the education, training, and evaluation of GPs. METHODS: Literature analysis and behaviour event interviews were conducted to build the competency dictionary and the initial version of the competency model. Two rounds of Delphi were performed to gain consensus on the final model. The questionnaire survey was carried out in 10 provinces (municipalities, autonomous regions) of China, and GPs were invited to score the importance of each competency item. The total sample was randomly divided into two groups. One group was for exploratory factor analysis (EFA), and the other was for confirmatory factor analysis (CFA) to examine the scale's reliability and validity. RESULTS: The dictionary of general practitioners' competency including 107 competency items was constructed. After two rounds of Delphi, a consensus was reached on 60 competencies in 6 domains. A total of 1917 valid questionnaires were obtained in the nationwide survey. The average importance score of all second-level indicators is 4.53 ± 0.45. The Cronbach's α coefficient is 0.984. The results of the five factors extracted by EFA showing the 68.16% cumulative explained variance variation is considered to be consistent with the six dimensions obtained by Delphi after thorough discussion. The model fitness indexes obtained by CFA were acceptable (χ2/df = 4.909, CFI = 0.869, NFI = 0.841, RMSEA = 0.065). The values of the composite reliability (CR) of the six dimensions were all greater than 0.7 (0.943, 0.927, 0.937, 0.927, 0.943, 0.950), and the average of variance extracted (AVE) were all greater than 0.5 (0.562, 0.613, 0.649, 0.563, 0.626, 0.635). The results showed that the model has good reliability and validity. CONCLUSION: A competency model for GPs suited to China has been developed, which may offer guidance for future training and medical licensing examinations of GPs.

Chitosan alleviates ovarian aging by enhancing macrophage phagocyte-mediated tissue homeostasis.

BACKGROUND: Age-related changes in the ovarian microenvironment are linked to impaired fertility in women. Macrophages play important roles in ovarian tissue homeostasis and immune surveillance. However, the impact of aging on ovarian macrophage function and ovarian homeostasis remains poorly understood. METHODS: Senescence-associated beta-galactosidase staining, immunohistochemistry, and TUNEL staining were used to assess senescence and apoptosis, respectively. Flow cytometry was employed to evaluate mitochondrial membrane potential (MMP) and apoptosis in granulosa cells lines (KGN), and macrophages phagocytosis. After a 2-month treatment with low molecular weight Chitosan (LMWC), ovarian tissues from mice were collected for comprehensive analysis. RESULTS: Compared with the liver and uterus, the ovary displayed accelerated aging in an age-dependent manner, which was accompanied by elevated levels of inflammatory factors and apoptotic cells, and impaired macrophage phagocytic activity. The aged KGN cells exhibited elevated reactive oxygen species (ROS) and apoptotic levels alongside decreased MMP. H2O2-induced aging macrophages showed reduced phagocytosis function. Moreover, there were excessive aging macrophages with impaired phagocytosis in the follicular fluid of patients with diminished ovarian reserve (DOR). Notably, LMWC administration alleviated ovarian aging by enhancing macrophage phagocytosis and promoting tissue homeostasis. CONCLUSIONS: Aging ovarian is characterized by an accumulation of aging and apoptotic granulosa cells, an inflammatory response and macrophage phagocytosis dysfunction. In turn, impaired phagocytosis of macrophage contributes to insufficient clearance of aging and apoptotic granulosa cells and the increased risk of DOR. Additionally, LMWC emerges as a potential therapeutic strategy for age-related ovarian dysfunction.

The mop1 mutation affects the recombination landscape in maize.

Meiotic recombination is a fundamental process that generates genetic diversity and ensures the accurate segregation of homologous chromosomes. While a great deal is known about genetic factors that regulate recombination, relatively little is known about epigenetic factors, such as DNA methylation. In maize, we examined the effects on meiotic recombination of a mutation in a component of the RNA-directed DNA methylation pathway, Mop1 (Mediator of paramutation1), as well as a mutation in a component of the trans-acting small interference RNA biogenesis pathway, Lbl1 (Leafbladeless1). MOP1 is of particular interest with respect to recombination because it is responsible for methylation of transposable elements that are immediately adjacent to transcriptionally active genes. In the mop1 mutant, we found that meiotic recombination is uniformly decreased in pericentromeric regions but is generally increased in gene rich chromosomal arms. This observation was further confirmed by cytogenetic analysis showing that although overall crossover numbers are unchanged, they occur more frequently in chromosomal arms in mop1 mutants. Using whole genome bisulfite sequencing, our data show that crossover redistribution is driven by loss of CHH (where H = A, T, or C) methylation within regions near genes. In contrast to what we observed in mop1 mutants, no significant changes were observed in the frequency of meiotic recombination in lbl1 mutants. Our data demonstrate that CHH methylation has a significant impact on the overall recombination landscape in maize despite its low frequency relative to CG and CHG methylation.

Functionalized graphene oxide as a nanocarrier for delivering oridonin to improve anti-breast cancer cell activity.

In this study, a targeted nanocarrier was developed by functionalizing graphene oxide with polyethyleneimine and folic acid, intended for loading oridonin. The nanocarrier was successfully synthesized and characterized using an ultraviolet spectrum, Fourier transform infrared spectroscopy and scanning electron microscopy. The nanocarrier demonstrated a remarkable oridonin loading capacity, reaching 424.8 µg/mg, as determined by ultra-high performance liquid chromatography. In vitro drug release experiments exhibited a pH-dependent release profile, with a higher cumulative release in an acidic environment. The release mechanism followed the Ritger-Peppas equation model. Cytotoxicity assays indicated minimal toxicity of the nanocarrier. Enhanced cellular uptake by MCF7 cells was observed for carriers functionalized with folate and polyethyleneimine. These findings highlight the potential of functionalized graphene oxide as a promising carrier for oridonin delivery in biomedical applications.

A highly sensitive fluorescence biosensor for aflatoxins B1 detection based on polydiacetylene liposomes combined with exonuclease III-assisted recycling amplification.

A fluorescence biosensor for determination of aflatoxin B1 (AFB1) based on polydiacetylene (PDA) liposomes and exonuclease III (EXO III)-assisted recycling amplification was developed. The AFB1 aptamer partially hybridizes with complementary DNA (cDNA), which is released upon recognition of AFB1 by the aptamer. Subsequently, the cDNA hybridizes with hairpin H to form double-stranded DNA that undergoes digestion by EXO III, resulting in the cyclic release of cDNA and generation of capture DNA for further reaction. The capture DNA then hybridizes with probe modified on PDA liposomes, leading to aggregation of liposomes and subsequent fluorescence production. This strategy exhibited a limit of detection of 0.18 ng/mL within the linear range 1-100 ng/mL with a determination coefficient > 0.99. The recovery ranged from 92.81 to 106.45%, with relative standard deviations (RSD) between 1.73 and 4.26%, for corn, brown rice, peanut butter, and wheat samples. The stability, accuracy, and specificity of the method demonstrated the applicability for real sample analysis.

PSMOT: Online Occlusion-Aware Multi-Object Tracking Exploiting Position Sensitivity.

Models based on joint detection and re-identification (ReID), which significantly increase the efficiency of online multi-object tracking (MOT) systems, are an evolution from separate detection and ReID models in the tracking-by-detection (TBD) paradigm. It is observed that these joint models are typically one-stage, while the two-stage models become obsolete because of their slow speed and low efficiency. However, the two-stage models have naive advantages over the one-stage anchor-based and anchor-free models in handling feature misalignment and occlusion, which suggests that the two-stage models, via meticulous design, could be on par with the state-of-the-art one-stage models. Following this intuition, we propose a robust and efficient two-stage joint model based on R-FCN, whose backbone and neck are fully convolutional, and the RoI-wise process only involves simple calculations. In the first stage, an adaptive sparse anchoring scheme is utilized to produce adequate, high-quality proposals to improve efficiency. To boost both detection and ReID, two key elements-feature aggregation and feature disentanglement-are taken into account. To improve robustness against occlusion, the position-sensitivity is exploited, first to estimate occlusion and then to direct the post-process for anti-occlusion. Finally, we link the model to a hierarchical association algorithm to form a complete MOT system called PSMOT. Compared to other cutting-edge systems, PSMOT achieves competitive performance while maintaining time efficiency.

Tri-frequency simultaneous ultrasound pickling for the acceleration of the NaCl content and quality improvement of pork (longissimus dorsi).

BACKGROUND: The pickling process with NaCl is an essential step for pork preservation. This study aimed to investigate the effect of different ultrasonic intensities of tri-frequency simultaneous ultrasound (TSIU) pickling on the NaCl content and quality of pork (longissimus dorsi). After 30 min pickling, the NaCl content, moisture content, pickling yield, cooking loss, textural properties, color, pH, moisture migration and distribution as well as microstructure of pork were assessed. RESULTS: Results showed that among all the ultrasonic treatment intensities (85-150 W L-1), the NaCl content of the sample pickled by an intensity of 101.3 W L-1 was higher than that of other intensities. TSIU 101.3 W L-1 showed 59.95% higher NaCl content than the control sample. In addition, the sample treated with TSIU of 101.3 W L-1 had higher pickling yield and moisture content, better textural properties of pork (including hardness and chewiness), and less cooking loss. The results of the low-field nuclear magnetic resonance showed that, compared with the control group, the relaxation time T21 of the ultrasound-assisted pickling samples increased, while the proportion of T22 (A22) reduction ranged from 175.0% to 379.9%. The microstructure designated that the ultrasonic treatment could facilitate changes in meat texture. CONCLUSION: Ultrasound marination of different intensities promoted the diffusion of NaCl and affected the quality of pork tenderloins. The TSIU at 101.3 W L-1 could better accelerate NaCl transport and homogeneous distribution on meat, thereby improving the sample quality. © 2024 Society of Chemical Industry.

Current advances of chlorinated organics degradation by bioelectrochemical systems: a review.

Chlorinated organic compounds (COCs) are typical refractory organic compounds, having high biological toxicity. These compounds are a type of pervasive pollutants that can be present in polluted soil, air, and various types of waterways, such as groundwater, rivers, and lakes, posing a significant threat to the ecological environment and human health. Bioelectrochemical systems (BESs) are an effective strategy for the degradation of bio-refractory compounds. BESs improve the waste treatment efficiency through the application of weak electrical stimulation. This review discusses the processes of BESs configurations and degradation performances in different environmental media including wastewater, soil, waste gas and groundwater. In addition, the degradation mechanisms and performance-enhancing additives are summarized. The future challenges and perspectives on the development of BES for COCs removal are briefly discussed.

Hypoxia-mediated chemotaxis and residence of macrophage in decidua by secreting VEGFA and CCL2 during normal pregnancy.

In brief: Hypoxia is vital for the establishment of the maternal-fetal interface during early pregnancy. This study shows that decidual macrophages (dMφ) could be recruited and reside in decidua under the regulation of hypoxia/VEGFA-CCL2 axis. Abstract: Infiltration and residence of decidual macrophages (dMφ) are of great significance to pregnancy maintenance for their role in angiogenesis, placental development, and inducing immune tolerance. Besides, hypoxia has now been acknowledged as an important biological event at maternal-fetal interface in the first trimester. However, whether and how hypoxia regulates biofunctions of dMφ remain elusive. Herein, we observed increased expression of C-C motif chemokine ligand 2 (CCL2) and residence of macrophages in decidua compared to secretory-phase endometrium. Moreover, hypoxia treatment on stromal cells improved the migration and adhesion of dMφ. Mechanistically, these effects might be mediated by upregulated CCL2 and adhesion molecules (especially ICAM2 and ICAM5) on stromal cells in the presence of endogenous vascular endothelial growth factor-A (VEGFA) in hypoxia. These findings were also verified by recombinant VEGFA and indirect coculture, indicating that the interaction between stromal cells and dMφ in hypoxia condition may facilitate dMφ recruitment and residence. In conclusion, VEGFA derived from a hypoxic environment may manipulate CCL2/CCR2 and adhesion molecules to enhance the interactions between dMφ and stromal cells and thus contribute to the enrichment of macrophages in decidua early during normal pregnancy.

Low-Velocity-Favored Transition Radiation.

When a charged particle penetrates through an optical interface, photon emissions emerge-a phenomenon known as transition radiation. Being paramount to fundamental physics, transition radiation has enabled many applications from high-energy particle identification to novel light sources. A rule of thumb in transition radiation is that the radiation intensity generally decreases with the decrease of particle velocity v; as a result, low-energy particles are not favored in practice. Here, we find that there exist situations where transition radiation from particles with extremely low velocities (e.g., v/c<10^{-3}) exhibits comparable intensity as that from high-energy particles (e.g., v/c=0.999), where c is the light speed in free space. The comparable radiation intensity implies an extremely high photon extraction efficiency from low-energy particles, up to 8 orders of magnitude larger than that from high-energy particles. This exotic phenomenon of low-velocity-favored transition radiation originates from the interference of the excited Ferrell-Berreman modes in an ultrathin epsilon-near-zero slab. Our findings may provide a promising route toward the design of integrated light sources based on low-energy electrons and specialized detectors for beyond-standard-model particles.

Biallelic mutations of TTC12 and TTC21B were identified in Chinese patients with multisystem ciliopathy syndromes.

BACKGROUND: Abnormalities in cilia ultrastructure and function lead to a range of human phenotypes termed ciliopathies. Many tetratricopeptide repeat domain (TTC) family members have been reported to play critical roles in cilium organization and function. RESULTS: Here, we describe five unrelated family trios with multisystem ciliopathy syndromes, including situs abnormality, complex congenital heart disease, nephronophthisis or neonatal cholestasis. Through whole-exome sequencing and Sanger sequencing confirmation, we identified compound heterozygous mutations of TTC12 and TTC21B in six affected individuals of Chinese origin. These nonsynonymous mutations affected highly conserved residues and were consistently predicted to be pathogenic. Furthermore, ex vivo cDNA amplification demonstrated that homozygous c.1464 + 2 T > C of TTC12 would cause a whole exon 16 skipping. Both mRNA and protein levels of TTC12 were significantly downregulated in the cells derived from the patient carrying TTC12 mutation c.1464 + 2 T > C by real-time qPCR and immunofluorescence assays when compared with two healthy controls. Transmission electron microscopy analysis further identified ultrastructural defects of the inner dynein arms in this patient. Finally, the effect of TTC12 deficiency on cardiac LR patterning was recapitulated by employing a morpholino-mediated knockdown of ttc12 in zebrafish. CONCLUSIONS: To the best of our knowledge, this is the first study reporting the association between TTC12 variants and ciliopathies in a Chinese population. In addition to nephronophthisis and laterality defects, our findings demonstrated that TTC21B should also be considered a candidate gene for biliary ciliopathy, such as TTC26, which further expands the phenotypic spectrum of TTC21B deficiency in humans.

IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/ß-catenin pathway in fetal growth restriction.

Background: Fetal growth restriction (FGR) is characterized by restricted fetal growth and dysregulated placental development. The etiology and pathogenesis still remain elusive. IL-27 shows multiple roles in regulating various biological processes, however, how IL-27 involves in placentation in FGR pregnancy hasn't been demonstrated. Methods: The levels of IL-27 and IL-27RA in FGR and normal placentae were determined by immunohistochemistry, western blot and RT-PCR. HTR-8/SVneo cells and Il27ra-/- murine models have been adopted to evaluate the effects of IL-27 on the bio-functions of trophoblast cells. GO enrichment and GSEA analysis were performed to explore the underlying mechanism. Findings: IL-27 and IL-27RA was lowly expressed in FGR placentae and administration of IL-27 on HTR-8/SVneo could promote its proliferation, migration and invasion. Comparing with wildtypes, Il27ra-/- embryos were smaller and lighter, and the placentae from which were poorly developed. In mechanism, the molecules of canonical Wnt/ß-catenin pathway (CCND1, CMYC, SOX9) were downregulated in Il27ra-/- placentae. In contrast, the expression of SFRP2 (negative regulator of Wnt) was increased. Overexpression of SFRP2 in vitro could impair trophoblast migration and invasion capacity. Interpretation: IL-27/IL-27RA negatively regulates SFRP2 to activate Wnt/ß-catenin, and thus promotes migration and invasion of trophoblasts during pregnancy. However, IL-27 deficiency may contribute to the development of FGR by restricting the Wnt activity.

Preparation, characterization, and pharmacokinetics of oridonin-loaded liposomes.

The aim of this study was to prepare oridonin liposomes and evaluate the physicochemical characteristics and pharmacokinetics in rats. A three-level, three-factor Box-Behnken design was used to optimize the preparation of oridonin liposomes. A highly sensitive high-performance liquid chromatographic quantification method using ultraviolet detection was established and validated for the determination of oridonin in rat plasma. Twelve Sprague-Dawley rats were randomly assigned and injected with 15 mg/kg of oridonin or oridonin liposomes via the tail vein. Pharmacokinetic parameters were estimated using a compartmental modeling approach using PKsolver software. The optimum conditions were as follows: soybean phospholipids/cholesterol ratio, 3.9:1; soybean phospholipids/drug ratio, 8.5:1; and soybean phospholipid concentration, 1.1%. Under these conditions, the mean particle size, polydispersity index, zeta potential, and encapsulation efficiency of oridonin liposomes were 170.5 nm, 0.246, -30.3 mV, and 76.15%, respectively. The pharmacokinetic results showed that liposomes could significantly prolong the elimination half-life (from 2.88 ± 0.55 to 13.67 ± 3.52 h), increase the area under the concentration-time curve (from 1.65 ± 0.17 to 6.22 ± 0.83 µg h/ml), and decrease the clearance (from 6.62 ± 1.38 to 1.96 ± 0.24 L/kg h). The oridonin liposomes increased the elimination half-life and area under the concentration-time curve and provided a reference for the development of drugs with a short half-life.