Genomic analyses reveal dead-end hybridization between two deeply divergent kiwifruit species rather than homoploid hybrid speciation.

Despite the importance of hybridization in evolution, the evolutionary consequence of homoploid hybridizations in plants remains poorly understood. Specially, homoploid hybridization events have been rarely documented due to a lack of genomic resources and methodological limitations. Actinidia zhejiangensis was suspected to have arisen from hybridization of Actinidia eriantha and Actinidia hemsleyana or Actinidia rufa. However, this species was very rare in nature and exhibited sympatric distribution with its potential parent species, which implied it might be a spontaneous hybrid of ongoing homoploid hybridization. Here, we illustrate the dead-end homoploid hybridization and genomic basis of isolating barriers between A. eriantha and A. hemsleyana through whole genome sequencing and population genomic analyses. Chromosome-scale genome assemblies of A. zhejiangensis and A. hemsleyana were generated. The chromosomes of A. zhejiangensis are confidently assigned to the two haplomes, and one of them originates from A. eriantha and the other originates from A. hemsleyana. Whole genome resequencing data reveal that A. zhejiangensis are mainly F1 hybrids of A. hemsleyana and A. eriantha and gene flow initiated about 0.98 million years ago, implying both strong genetic barriers and ongoing hybridization between these two deeply divergent kiwifruit species. Five inversions containing genes involved in pollen germination and pollen tube growth might account for the fertility breakdown of hybrids between A. hemsleyana and A. eriantha. Despite its distinct morphological traits and long recurrent hybrid origination, A. zhejiangensis does not initiate speciation. Collectively, our study provides new insights into homoploid hybridization in plants and provides genomic resources for evolutionary and functional genomic studies of kiwifruit.

Soft Actuators and Actuation: Design, Synthesis, and Applications.

Soft actuators are one of the most promising technological advancements with potential solutions to diverse fields' day-to-day challenges. Soft actuators derived from hydrogel materials possess unique features such as flexibility, responsiveness to stimuli, and intricate deformations, making them ideal for soft robotics, artificial muscles, and biomedical applications. This review provides an overview of material composition and design techniques for hydrogel actuators, exploring 3D printing, photopolymerization, cross-linking, and microfabrication methods for improved actuation. It examines applications of hydrogel actuators in biomedical, soft robotics, bioinspired systems, microfluidics, lab-on-a-chip devices, and environmental, and energy systems. Finally, it discusses challenges, opportunities, advancements, and regulatory aspects related to hydrogel actuators.

Multi-UAV Collaborative Search and Attack Mission Decision-Making in Unknown Environments.

To address the challenge of coordinated combat involving multiple UAVs in reconnaissance and search attacks, we propose the Multi-UAV Distributed Self-Organizing Cooperative Intelligence Surveillance and Combat (CISCS) strategy. This strategy employs distributed control to overcome issues associated with centralized control and communication difficulties. Additionally, it introduces a time-constrained formation controller to address the problem of unstable multi-UAV formations and lengthy formation times. Furthermore, a multi-task allocation algorithm is designed to tackle the issue of allocating multiple tasks to individual UAVs, enabling autonomous decision-making at the local level. The distributed self-organized multi-UAV cooperative reconnaissance and combat strategy consists of three main components. Firstly, a multi-UAV finite time formation controller allows for the rapid formation of a mission-specific formation in a finite period. Secondly, a multi-task goal assignment module generates a task sequence for each UAV, utilizing an improved distributed Ant Colony Optimization (ACO) algorithm based on Q-Learning. This module also incorporates a colony disorientation strategy to expand the search range and a search transition strategy to prevent premature convergence of the algorithm. Lastly, a UAV obstacle avoidance module considers internal collisions and provides real-time obstacle avoidance paths for multiple UAVs. In the first part, we propose a formation algorithm in finite time to enable the quick formation of multiple UAVs in a three-dimensional space. In the second part, an improved distributed ACO algorithm based on Q-Learning is introduced for task allocation and generation of task sequences. This module includes a colony disorientation strategy to expand the search range and a search transition strategy to avoid premature convergence. In the third part, a multi-task target assignment module is presented to generate task sequences for each UAV, considering internal collisions. This module provides real-time obstacle avoidance paths for multiple UAVs, preventing premature convergence of the algorithm. Finally, we verify the practicality and reliability of the strategy through simulations.

Enhanced Water Adsorption Performance of UiO-66 Modulated with p-Nitrobenzoic or p-Hydroxybenzoic Acid: Introduced Defects and Functional Groups.

Adding appropriate modulators can effectively improve the porosity and adsorption performance of UiO-66. Herein, UiO-66 samples were synthesized with p-nitrobenzoic acid (PNBA) and p-hydroxybenzoic acid (PHBA) as modulators. All samples exhibited good crystallinity and thermal stability. The polar functional groups (-NO2 and -OH) and defects were introduced into UiO-66, which significantly improved its water adsorption performance and applications in adsorption heat transformation. With the addition of six equiv PNBA, the saturated water uptake of UiO-66 increased from 0.40 to 0.58 g/g. Also, 4eqPNBA-UiO-66 exhibited the highest water uptake under low relative pressure, which was almost twice that of "low-defect" LD-UiO-66. The addition of PHBA had little effect on the saturated water absorption. However, its highest water uptake at P/P0 = 0.3 is 0.23 g/g, which is equivalent to that of 4eqPNBA-UiO-66. Ten consecutive adsorption/desorption cycles indicated that these samples had good cycle stability.

Overexpression of miR-210-3p Impairs Extravillous Trophoblast Functions Associated with Uterine Spiral Artery Remodeling.

Hsa-miR-210-3p has been reported to be upregulated in preeclampsia (PE); however, the functions of miR-210-3p in placental development are not fully understood, and, consequently, miR-210-3p's role in the pathogenesis of PE is still under investigation. In this study, we found that overexpression of miR-210-3p reduced trophoblast migration and invasion, extravillous trophoblast (EVT) outgrowth in first trimester explants, expression of endovascular trophoblast (enEVT) markers and the ability of trophoblast to form endothelial-like networks. In addition, miR-210-3p overexpression significantly downregulated the mRNA levels of interleukin-1B and -8, as well as CXC motif ligand 1. These cytokines have been suggested to play a role in EVT invasion and the recruitment of immune cells to the spiral artery remodeling sites. We also showed that caudal-related homeobox transcription factor 2 (CDX2) is targeted by miR-210-3p and that CDX2 downregulation mimicked the observed effects of miR-210-3p upregulation in trophoblasts. These findings suggest that miR-210-3p may play a role in regulating events associated with enEVT functions and its overexpression could impair spiral artery remodeling, thereby contributing to PE.

MicroRNA-218-5p Promotes Endovascular Trophoblast Differentiation and Spiral Artery Remodeling.

Preeclampsia (PE) is the leading cause of maternal and neonatal morbidity and mortality. Defects in trophoblast invasion, differentiation of endovascular extravillous trophoblasts (enEVTs), and spiral artery remodeling are key factors in PE development. There are no markers clinically available to predict PE, leaving expedited delivery as the only effective therapy. Dysregulation of miRNA in clinical tissues and maternal circulation have opened a new avenue for biomarker discovery. In this study, we investigated the role of miR-218-5p in PE development. miR-218-5p was highly expressed in EVTs and significantly downregulated in PE placentas. Using first-trimester trophoblast cell lines and human placental explants, we found that miR-218-5p overexpression promoted, whereas anti-miR-218-5p suppressed, trophoblast invasion, EVT outgrowth, and enEVT differentiation. Furthermore, miR-218-5p accelerated spiral artery remodeling in a decidua-placenta co-culture. The effect of miR-218-5p was mediated by the suppression of transforming growth factor (TGF)-ß2 signaling. Silencing of TGFB2 mimicked, whereas treatment with TGF-ß2 partially reversed, the effects of miR-218-5p. Taken together, these findings demonstrate that miR-218-5p promotes trophoblast invasion and enEVT differentiation through a novel miR-218-5p-TGF-ß2 pathway. This study elucidates the role of an miRNA in enEVT differentiation and spiral artery remodeling and suggests that downregulation of miR-218-5p contributes to PE development.

A Conductive Self-Healing Double Network Hydrogel with Toughness and Force Sensitivity.

Mechanically tough and electrically conductive self-healing hydrogels may have broad applications in wearable electronics, health-monitoring systems, and smart robotics in the following years. Herein, a new design strategy is proposed to synthesize a dual physical cross-linked polyethylene glycol/poly(acrylic acid) (PEG/PAA) double network hydrogel, consisting of ferric ion cross-linked linear chain extensions of PEG (2,6-pyridinedicarbonyl moieties incorporated into the PEG backbone, PEG-H2 pdca) as the first physical network and a PAA-Fe3+ gel as the second physical network. Metal-ion coordination and the double network structure enable the double network hydrogel to withstand up to 0.4 MPa tensile stress and 1560 % elongation at breakage; the healing efficiency reaches 96.8 % in 12 h. In addition, due to dynamic ion transfer in the network, the resulting hydrogels exhibit controllable conductivity (0.0026-0.0061 S cm-1 ) and stretching sensitivity. These functional self-healing hydrogels have potential applications in electronic skin. It is envisioned that this strategy can also be employed to prepare other high-performance, multifunctional polymers.

Well-defined and biocompatible hydrogels with toughening and reversible photoresponsive properties.

In the present study, novel hydrogels with extremely high strength, reversible photoresponsive and excellent biocompatible properties were prepared. The functional hydrogels were synthesized from a well-defined poly (ethylene glycol) polymer with spiropyran groups at a given position (PEG-SP) via a Cu(i)-catalyst Azide-Alkyne Cycloaddition (CuAAC) reaction. The molecular structures of the sequential intermediates for PEG-SP hydrogel preparation were verified by (1)HNMR and FT-IR. The mechanical property, swelling ratio, compression strength, surface hydrophilicity, and biocompatibility of the resulting hydrogel were characterized. Since spiropyran is pivotal to the switch in hydrophilicity on the hydrogel surface, the swelling ratio of PEG-SP hydrogel under Vis irradiation has a major decrease (155%). Before and after UV light irradiation, the contact angle of the hydrogel has a change of 13.8°. The photoresponsive property of this hydrogel was thus demonstrated, and such a property was also shown to be reversible. The well-defined PEG-SP hydrogel can also sustain a compressive stress of 49.8 MPa without any macro- or micro-damage, indicating its outstanding mechanical performance. Furthermore, it possessed excellent biocompatibility as demonstrated by its performance in an in vivo porcine subcutaneous implantation environment. No inflammation was observed and it got along well with the adjacent tissue. The above features indicate that PEG-SP hydrogels are promising as an implantable matrix for potential applications in biomaterial.

Synthesis of fluorescent dye-doped silica nanoparticles for target-cell-specific delivery and intracellular microRNA imaging.

MicroRNA (miRNA) is found to be up-regulated in many kinds of cancer and therefore is classified as an oncomiR. Herein, we design a multifunctional fluorescent nanoprobe (FSiNP-AS/MB) with the AS1411 aptamer and a molecular beacon (MB) co-immobilized on the surface of the fluorescent dye-doped silica nanoparticles (FSiNPs) for target-cell-specific delivery and intracellular miRNA imaging. The FSiNPs were prepared by a facile reverse microemulsion method from tetraethoxysilane and silane derivatized coumarin that was previously synthesized by click chemistry. The as-prepared FSiNPs possess uniform size distribution, good optical stability and biocompatibility. In addition, there is a remarkable affinity interaction between the AS1411 aptamer and the nucleolin protein on the cancer cell surface. Thus, a target-cell-specific delivery system by the FSiNP-AS/MB is proposed for effectively transferring a MB into the cancer cells to recognize the target miRNA. Using miRNA-21 in MCF-7 cells (a human breast cancer cell line) as a model, the proposed multifunctional nanosystems not only allow target-cell-specific delivery with the binding affinity of AS1411, but also can track simultaneously the transfected cells and detect intracellular miRNA in situ. The proposed multifunctional nanosystems are a promising platform for a highly sensitive luminescent nonviral vector in biomedical and clinical research.

Direct detection of microRNA based on plasmon hybridization of nanoparticle dimers.

MicroRNAs (miRNA) are important for regulating a range of biochemical pathways. Abnormal levels of miRNA in cells or secreted into biological fluids have been identified in diseases. MiRNA can therefore be potential biomarkers for early disease diagnosis; however their detection and quantification are challenging. Herein we apply the sensing platform of discrete actuatable dimers for the detection of human miR-210 (hsa-miR-210-3p). The detection signal is a spectral blue shift in the hybridized plasmon mode as monitored by single-nanostructure spectroscopy. We investigate the specificity and detection limit of the platform and quantify miR-210 levels in RNA extracts of cells cultured under different oxygen tensions. In addition we demonstrate the feasibility of detection in complex media by examining miR-210 secreted in cell media. This sensing platform may be developed as a bioanalytical tool for validating miRNA profiles of biological fluids.

MicroRNA-378a-5p promotes trophoblast cell survival, migration and invasion by targeting Nodal.

Nodal is a member of the transforming growth factor-ß superfamily that plays crucial roles during embryogenesis. Recently, we have reported that Nodal inhibits trophoblast cell proliferation, migration and invasion, but induces apoptosis in the human placenta. In this study, we examined the regulation of Nodal by microRNAs. In silico analysis of Nodal 3'UTR revealed a potential binding site for miR-378a-5p. In luciferase reporter assays, we found that miR-378a-5p suppressed the luciferase activity of a reporter plasmid containing Nodal 3'UTR but this suppressive effect was completely abolished when the predicted target site was mutated. Western blot analysis showed that miR-378a-5p decreased whereas anti-miR-378a-5p increased Nodal protein levels. These results indicate that miR-378a-5p targets Nodal 3'UTR to repress its expression. Stable transfection of the miR-378a-5p precursor, mir-378a, into HTR8/SVneo cells enhanced cell survival, proliferation, migration and invasion. Transient transfection of mature miR-378a-5p mimic, and to a lesser extent, siRNA targeting Nodal, produced similar effects. However, anti-miR-378a-5p inhibited cell migration and invasion. In addition, overexpression of Nodal reversed the invasion-promoting effect of miR-378a-5p. Furthermore, miR-378a-5p enhanced, whereas anti-miR-378a-5p suppressed, the outgrowth and spreading of extravillous trophoblast cells in first trimester placental explants. Finally, miR-378a-5p was detected in human placenta throughout different stages of gestation and in preterm pregnancies, placental miR-378a-5p levels were lower in preeclamptic patients than in healthy controls. Taken together, these findings strongly suggest that miR-378a-5p plays an important role in human placental development by regulating trophoblast cell growth, survival, migration and invasion, and that miR-378a-5p exerts these effects, at least in part, through the suppression of Nodal expression.

Discriminating Interpatient Variabilities of RAS Gene Variants for Precision Detection of Thyroid Cancer.

Importance: Interpatient variabilities in genomic variants may reflect differences in tumor statuses among individuals. Objectives: To delineate interpatient variabilities in RAS variants in thyroid tumors based on the fifth World Health Organization classification of thyroid neoplasms and assess their diagnostic significance in cancer detection among patients with thyroid nodules. Design, Setting, and Participants: This prospective diagnostic study analyzed surgically resected thyroid tumors obtained from February 2016 to April 2022 and residual thyroid fine-needle aspiration (FNA) biopsies obtained from January 2020 to March 2021, at Mount Sinai Hospital, Toronto, Ontario, Canada. Data were analyzed from June 20, 2022, to October 15, 2023. Exposures: Quantitative detection of interpatient disparities of RAS variants (ie, NRAS, HRAS, and KRAS) was performed along with assessment of BRAF V600E and TERT promoter variants (C228T and C250T) by detecting their variant allele fractions (VAFs) using digital polymerase chain reaction assays. Main Outcomes and Measures: Interpatient differences in RAS, BRAF V600E, and TERT promoter variants were analyzed and compared with surgical histopathologic diagnoses. Malignancy rates, sensitivity, specificity, positive predictive values, and negative predictive values were calculated. Results: A total of 438 surgically resected thyroid tumor tissues and 249 thyroid nodule FNA biopsies were obtained from 620 patients (470 [75.8%] female; mean [SD] age, 50.7 [15.9] years). Median (IQR) follow-up for patients who underwent FNA biopsy analysis and subsequent resection was 88 (50-156) days. Of 438 tumors, 89 (20.3%) were identified with the presence of RAS variants, including 51 (11.6%) with NRAS, 29 (6.6%) with HRAS, and 9 (2.1%) with KRAS. The interpatient differences in these variants were discriminated at VAF levels ranging from 0.15% to 51.53%. The mean (SD) VAF of RAS variants exhibited no significant differences among benign nodules (39.2% [11.2%]), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) (25.4% [14.3%]), and malignant neoplasms (33.4% [13.8%]) (P = .28), although their distribution was found in 41.7% of NIFTPs and 50.7% of invasive encapsulated follicular variant papillary thyroid carcinomas (P < .001). RAS variants alone, regardless of a low or high VAF, were significantly associated with neoplasms at low risk of tumor recurrence (60.7% of RAS variants vs 26.9% of samples negative for RAS variants; P < .001). Compared with the sensitivity of 54.2% (95% CI, 48.8%-59.4%) and specificity of 100% (95% CI, 94.8%-100%) for BRAF V600E and TERT promoter variant assays, the inclusion of RAS variants into BRAF and TERT promoter variant assays improved sensitivity to 70.5% (95% CI, 65.4%-75.2%), albeit with a reduction in specificity to 88.8% (95% CI, 79.8%-94.1%) in distinguishing malignant neoplasms from benign and NIFTP tumors. Furthermore, interpatient differences in 5 gene variants (NRAS, HRAS, KRAS, BRAF, and TERT) were discriminated in 54 of 126 indeterminate FNAs (42.9%) and 18 of 76 nondiagnostic FNAs (23.7%), and all tumors with follow-up surgical pathology confirmed malignancy. Conclusions and Relevance: This diagnostic study delineated interpatient differences in RAS variants present in thyroid tumors with a variety of histopathological diagnoses. Discrimination of interpatient variabilities in RAS in combination with BRAF V600E and TERT promoter variants could facilitate cytology examinations in preoperative precision malignancy diagnosis among patients with thyroid nodules.

Characterization of Water Vapor Sorption Performance and Heat Storage of MIL-101 (Cr) Complex MgCl2, LiCl/LaCl3 System for Adsorptive Thermal Conversion.

Adsorption heat conversion systems can provide heating and cooling across time and space in a more environmentally friendly way. Porous materials are potential candidates for water-based adsorption thermal conversion, in which a metal-organic framework (MOF) has a larger specific surface area and porosity than other porous matrices. However, many MOFs with high saturated adsorption capacity have great deficiencies in performance at low water vapor partial pressure, which hinder their application in adsorption thermal conversion. To improve the water vapor adsorption performance of MIL-101 (Cr), different contents of magnesium chloride, lithium chloride, and lanthanum chloride are mixed into MIL-101 (Cr) by an impregnation method. The properties and structures of the materials are characterized by XRD, SEM, nitrogen adsorption tests, water vapor adsorption tests, TG, FTIR, and so on. The results show that the saturated water vapor adsorption capacity of the sample impregnated with salt increases by 1.5-2.3 times, up to 2.24 g/g, compared with that of the unimpregnated sample. When the partial pressure of water vapor is 0.3, the adsorption capacity increases by 5.3-7.5 times and reaches 0.68 g/g at most. The maximum heat storage density of impregnated samples can be increased by 866 J/g. Impregnated MgCl2 can greatly improve the adsorption and thermal conversion performance of MOF, and impregnated MgCl2 and the proper amount of LiCl can further improve the performance of the material system. Our experiments show that the composite impregnation of magnesium chloride and the proper amount of lithium chloride can improve the application performance of the MOF materials in the adsorption thermal conversion process.

Multifunctional, Degradable Wearable Sensors Prepared with an Initiator and Crosslinker-Free Method.

The present zwitterionic hydrogel-based wearable sensor exhibits various limitations, such as limited degradation capacity, unavoidable toxicity resulting from initiators, and poor mechanical properties that cannot satisfy practical demands. Herein, we present an initiator and crosslinker-free approach to prepare polyethylene glycol (PEG)@poly[2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl) (PSBMA) interpenetrating polymer network (IPN) hydrogels that are self-polymerized via sunlight-induced and non-covalent crosslinking through electrostatic interaction and hydrogen bonding among polymer chains. The PEG@PSBMA IPN hydrogel possesses tissue-like softness, superior stretchability (∼2344.6% elongation), enhanced fracture strength (∼39.5 kPa), excellent biocompatibility, antibacterial property, reliable adhesion, and ionic conductivity. Furthermore, the sensor based on the IPN hydrogel demonstrates good sensitivity and cyclic stability, enabling effective real-time monitoring of human body activities. Moreover, it is worth noting that the excellent degradability in the saline solution within 8 h makes the prepared hydrogel-based wearable sensor free from the electronic device contamination. We believe that the proposed strategy for preparing physical zwitterionic hydrogels will pave the way for fabricating eco-friendly wearable devices.

Comparison of the therapeutic effects of medication therapy, specific immunotherapy and anti-IgE (Omalizumab) in patients with hay fever.

Background: Hay fever, characterized by seasonal allergic reactions, poses a significant health challenge. Existing therapies encompass standard drug regimens, biological agents, and specific immunotherapy. This study aims to assess and compare the effectiveness of anti-IgE (omalizumab), medication therapy, and subcutaneous immunotherapy (SCIT) for hay fever. Methods: Conducted as a retrospective cohort study, this research involved 98 outpatient hay fever patients who underwent routine medication, omalizumab treatment, or SCIT before the onset of the spring pollen season. A follow-up was performed one month after the start of the pollen season. The comprehensive symptoms and drug scores were used to evaluate patients with different intervention methods, facilitating a comparative analysis of therapeutic outcomes. Results: Compared with before treatment, the symptoms of patients treated with the three methods were all significantly relieved, and the medication score were significantly reduced. Patients treated with omalizumab demonstrated higher symptoms and medication scores than SCIT group before treatment, but similar scores after treatment, which were both lower than medicine treatment group. After treatment with omalizumab or SCIT, patients in both groups had significantly lower medication scores than the medication group and were close to no longer using medication for symptom relief. The mountain juniper-sIgE was significantly higher after treatment than before treatment in both medicine treatment group and omalizumab treatment group. Conclusion: Omalizumab and SCIT offer superior effects than medication therapy in hay fever patients.

MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance.

MicroRNAs (miRNAs) are small noncoding RNAs that have important roles in gene regulation. We have previously reported that activin receptor-like kinase 7 (ALK7) and its ligand, Nodal, induce apoptosis in human epithelial ovarian cancer cells. In this study, we examined the regulation of ALK7 by miRNAs and demonstrate that miR-376c targets ALK7. Ectopic expression of miR-376c significantly increased cell proliferation and survival, enhanced spheroid formation and blocked Nodal-induced apoptosis. Interestingly, overexpression of miR-376c blocked cisplatin-induced cell death, whereas anti-miR-376c enhanced the effect of cisplatin. These effects of miR-376c were partially compensated by the overexpression of ALK7. Moreover, in serous carcinoma samples taken from ovarian cancer patients who responded well to chemotherapy, strong ALK7 staining and low miR-376c expression was detected. By contrast, ALK7 expression was weak and miR-376c levels were high in samples from patients who responded poorly to chemotherapy. Finally, treatment with cisplatin led to an increase in expression of mRNA encoding Nodal and ALK7 but a decrease in miR-376c levels. Taken together, these results demonstrate that the Nodal-ALK7 pathway is involved in cisplatin-induced cell death in ovarian cancer cells and that miR-376c enhances proliferation, survival and chemoresistance by targeting, at least in part, ALK7.

Expression and regulation of miR-17a and miR-430b in zebrafish ovarian follicles.

MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression and control many developmental and physiological processes. Oocyte maturation in fish is mainly regulated by luteinizing hormone (LH) and maturation-inducing hormone (MIH). In addition, growth factors, including members of the transforming growth factor ß (TGF-ß) superfamily, have also been shown to play important roles in regulating oocyte maturation. In this study, we determined the expression and regulation of two miRNAs, miR-17a and miR-430b, which potentially target signalling molecules in the TGF-ß pathway, in zebrafish ovarian follicles. Using real-time PCR, we observed that miR-17a and miR-430b levels in follicular cells were significantly lower in late vitellogenic and full grown follicles than in early vitellogenic follicles. Treatment with a LH analog, human chorionic gonadotropin, significantly down-regulated miR-17a and miR-430b expression in follicular cells but had no effect on their expression in oocytes. Forskolin also inhibited follicular cell miR-430b expression; however, no significant changes in miR-17a levels were observed after Forskolin treatment. Finally, MIH did not affect the expression of these miRNAs either in follicular cells or oocytes at the time points tested. These findings suggest that miR-17a and miR-430b may be involved in the regulation of follicle development and oocyte maturation in zebrafish.

MicroRNAs in Human Placental Development and Pregnancy Complications.

MicroRNAs (miRNAs) are small non-coding RNAs, which function as critical posttranscriptional regulators of gene expression by promoting mRNA degradation and translational inhibition. Placenta expresses many ubiquitous as well as specific miRNAs. These miRNAs regulate trophoblast cell differentiation, proliferation, apoptosis, invasion/migration, and angiogenesis, suggesting that miRNAs play important roles during placental development. Aberrant miRNAs expression has been linked to pregnancy complications, such as preeclampsia. Recent research of placental miRNAs focuses on identifying placental miRNA species, examining differential expression of miRNAs between placentas from normal and compromised pregnancies, and uncovering the function of miRNAs in the placenta. More studies are required to further understand the functional significance of miRNAs in placental development and to explore the possibility of using miRNAs as biomarkers and therapeutic targets for pregnancy-related disorders. In this paper, we reviewed the current knowledge about the expression and function of miRNAs in placental development, and propose future directions for miRNA studies.

Improvement of water adsorption performance of UiO-66 by post-synthetic modification.

Post-synthetic modification can be used for structural replacement or functional modification of materials after they have been formed or assembled. It can effectively combine various modification methods for metal-organic frameworks (MOFs) such as defect control, replacement of metal sites, or functionalization of ligands. In this work, organic ligands that incorporate N-functionalities or amino groups were introduced into defective UiO-66 through post-synthetic ligand exchange (PSE) to improve its water adsorption performance. Parameters such as water adsorption capacity, half adsorption value (α), and Henry constant KH were used to characterize the water adsorption performance. After PSE, new ligands in different molar ratios entered the skeleton of UiO-66. The N sites or amino groups on the ligands provided new sites for the adsorption of water molecules. The water adsorption capacity and hydrophilicity of all samples were significantly superior to those of LD-UiO-66, which had almost no defects. H-UiO-66-PyDC samples exhibited the highest ligand replacement ratio and a significant enhancement of water adsorption performance. Compared to the unchanged H-UiO-66, the water uptake of H-UiO-66-PyDC increased from 0.08 g g-1 to 0.23 g g-1 at P/P0 = 0.30 and α decreased from 0.36 to 0.28. After 20 water adsorption/desorption tests, the water uptake of all samples did not decrease, showing excellent cycling stability. These results suggest that the combination of defect modulation and PSE is a potential tool to make UiO-66 more appropriate for applications based on reversible adsorption.

Facilitation of Definitive Cancer Diagnosis With Quantitative Molecular Assays of BRAF V600E and TERT Promoter Variants in Patients With Thyroid Nodules.

Importance: Molecular testing of the presence of pathogenic genomic variants in a tumor without quantifying the variant allele fraction (VAF) does not differentiate the variation extent among tumors, often resulting in an inconclusive diagnosis because of interpatient variability. Objective: To examine the association between the quantification of VAFs of BRAF V600E and TERT promoter variants and a definitive cancer diagnosis of thyroid tumors. Design, Setting, and Participants: This diagnostic study analyzed a cohort of 378 surgically resected thyroid tumors with a maximum dimension of 1 cm or larger between March 15, 2016, and March 16, 2020, and a separate cohort of 217 residual thyroid fine-needle aspiration (FNA) biopsy specimens obtained from January 22, 2020, to March 2, 2021, at Mount Sinai Hospital, Toronto, Ontario, Canada. Data analysis was conducted between February 1, 2021, and February 1, 2023. Exposures: Quantitative VAF assays of BRAF V600E and TERT promoter variants (C228T and C250T) were performed by digital polymerase chain reaction molecular assays. Main Outcomes and Measures: The VAFs of BRAF V600E and TERT promoter variants were correlated with tumor histologic diagnoses and histopathologic features to delineate the association of VAF assays with tumor malignancy. The receiver operating characteristic curve analysis, sensitivity, specificity, positive predictive value, negative predictive value, and logistic regression analysis based on follow-up histopathologic types were used to determine the diagnostic utility of the quantitative molecular assays. Results: A total of 595 specimens, including 378 surgically resected thyroid tumors and 217 thyroid nodule FNA biopsy specimens, were collected from 580 patients (436 [75.2%] female with a mean [SD] age of 50 [16] years and 144 [24.8%] male with a mean [SD] age of 55 [14] years). Sensitive VAF assays of 378 thyroid tumors revealed the presence of the BRAF V600E variant in 162 tumors (42.9%), with 26 (16.0%) at a low VAF of 1% or less and 136 (84.0%) at a high VAF of greater than 1%, and the presence of TERT promoter variants in 49 tumors (13.0%), including 45 C228T variants (91.8%), 15 (33.3%) of which were quantified as having a low VAF (≤1%) and 30 (66.7%) as having a high VAF (>1%), and 4 C250T variants (8.2%) with VAFs between 40.0% and 47.0%. All tumors detected with BRAF V600E and/or TERT promoter variants, whether at low or high VAFs, received a definitive cancer diagnosis. Further analysis delineated a significant association between high VAFs of either variant individually or different VAF levels for both variants in coexistence and aggressive histopathologic features of tumors. Excluding low VAFs assisted in identifying patients at an intermediate-to-high risk of recurrence (odds ratio, 5.3; 95% CI, 1.9-14.6; P = .001). The VAF assays on the residual FNA biopsy specimens showed a high agreement to those on surgical tissues (κ = 0.793, P < .001) and stratified malignancy in 40 of 183 indeterminate FNA cases (21.9%), with a sensitivity of 93.8% (95% CI, 67.7%-99.7%), specificity of 90.0% (95% CI, 75.4%-96.7%), positive predictive value of 78.9% (95% CI, 53.9%-93.0%), and negative predictive value of 97.3% (95% CI, 84.2%-99.9%). Conclusions and Relevance: This diagnostic study suggests that sensitive quantitative VAF assays of BRAF V600E and TERT promoter variants can elucidate the interpatient variability in tumors and facilitate a definitive cancer diagnosis of thyroid nodules by differentiating the variation extent of genomic variants, even at low VAFs.