Omics Approaches Unveiling the Biology of Human Atherosclerotic Plaques.

Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by the buildup of plaques with the accumulation and transformation of lipids, immune cells, vascular smooth muscle cells, and necrotic cell debris. Plaques with collagen-poor thin fibrous caps infiltrated by macrophages and lymphocytes are considered unstable because they are at the greatest risk of rupture and clinical events. However, the current histologic definition of plaque types may not fully capture the complex molecular nature of atherosclerotic plaque biology and the underlying mechanisms contributing to plaque progression, rupture, and erosion. The advances in omics technologies have changed the understanding of atherosclerosis plaque biology, offering new possibilities to improve risk prediction and discover novel therapeutic targets. Genomic studies have shed light on the genetic predisposition to atherosclerosis, and integrative genomic analyses expedite the translation of genomic discoveries. Transcriptomic, proteomic, metabolomic, and lipidomic studies have refined the understanding of the molecular signature of atherosclerotic plaques, aiding in data-driven hypothesis generation for mechanistic studies and offering new prospects for biomarker discovery. Furthermore, advancements in single-cell technologies and emerging spatial analysis techniques have unveiled the heterogeneity and plasticity of plaque cells. This review discusses key omics-based discoveries that have advanced the understanding of human atherosclerotic plaque biology, focusing on insights derived from omics profiling of human atherosclerotic vascular specimens.

Stretchable, Programmable and Magnet-Insensitive Protonic Display Based on Integrated Ionic Circuit.

As a new approach to "More than Moore", integrated ionic circuits serve as a possible alternative to traditional electronic circuits, yet the integrated ionic circuit composed of functional ionic elements and ionic connections is still challenging. Herein, a stretchable and transparent ionic display module of the integrated ionic circuit has been successfully prepared and demonstrated by pixelating a proton-responsive hydrogel. It is programmed to excite the hydrogel color change by a Faraday process occurring at the electrode at the specific pixel points, which enables the display of digital information and even color information. Importantly, the display module exhibits stable performance under strong magnetic field conditions (1.7 T). The transparent and stretchable nature of such ionic modules also allows them to be utilized in a broad range of scenarios, which paves the way for integrated ionic circuits.

UV-A radiation increases biomass yield by enhancing energy flow and carbon assimilation in the edible cyanobacterium Nostoc sphaeroides.

Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides. Exposures to 5-15 W m-2 (15-46 µmol photons m-2 s-1) UV-A and 4.35 W m-2 (20 µmol photons m-2 s-1) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), QA re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides.IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides, which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO2 sequestration in the frame of a future CO2 neutral, circular, and sustainable bioeconomy.

Exosomal circ_0000735 contributes to non-small lung cancer malignant progression.

Circular RNA is an important regulator for non-small cell lung cancer (NSCLC). Circ_0000735 has been found to be significantly overexpressed in NSCLC tissues. Therefore, its role and mechanism in NSCLC progression need to be further explored. The expression levels of circ_0000735, miR-345-5p and A disintegrin and metalloprotease 19 (ADAM19) were determined using quantitative real-time PCR. EdU staining, wound healing and transwell assays were utilized to detect cell proliferation and metastasis. The protein levels of metastasis markers, exosome markers and ADAM19 were determined using western blot. Animal experiments were performed to confirm the role of circ_0000735 in NSCLC tumorigenesis. The exosomes from cells and serum were identified using transmission electron microscopy and nanoparticle tracking analysis. We found that circ_0000735 was upregulated in NSCLC, and its knockdown repressed NSCLC cell proliferation and metastasis. In terms of mechanism, circ_0000735 targeted miR-345-5p to regulate ADAM19. MiR-345-5p inhibitor reversed the suppressive effect of circ_0000735 knockdown on NSCLC progression, and ADAM19 overexpression abolished the inhibition effect of miR-345-5p on NSCLC progression. Also, animal experiments showed that silencing of circ_0000735 reduced NSCLC tumorigenesis. In addition, exosomes mediated the intercellular transmission of circ_0000735, and serum exosomal circ_0000735 might be an important indicator for the diagnosis of NSCLC. In conclusion, circ_0000735 facilitated NSCLC progression via miR-345-5p/ADAM19 pathway, and serum exosomal circ_0000735 might be a potential biomarker for NSCLC diagnosis.

The Association of Serum Complement C1q with Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Background: Coronary artery disease (CAD) is one of the leading causes of death in middle-aged and elderly people, and its incidence has been increasing in recent years. An in-depth understanding of the pathogenesis of CAD is important to ensure the health of CAD patients. Objective: To analyze the association of serum complement C1q with CAD," you could say something like "The objective of this meta-analysis is to investigate the relationship between serum complement C1q levels and the presence of CAD, aiming to provide insights for clinical diagnosis and treatment. Methods: Relevant studies on C1q and CAD were searched in PubMed, Web of Science and other literature databases. Two research team members independently cross-screened the literature according to the inclusion-exclusion criteria and assessed the literature quality. RevMan5.3 software was used for statistical analysis. Results: Three references were finally included, all of which had a Newcastle-Ottawa Scale (NOS) score ≥6, indicating high quality. A total of 2065 subjects were studied, including 1249 in the experimental group (CAD patients) and 816 in the control group (healthy population). Through the meta-analysis, it was found that the experimental group (CAD patients) had higher serum C1q than the control group (healthy controls) (P < .05). According to subgroup analysis, age, sex, sample size, diabetes mellitus (with/without), and serum complement C1q detection methods were not factors affecting the heterogeneity of the literature, and more data are needed for verification. Validation analysis with the fixed-effect model also showed higher C1q expression in the experimental group (P < .05). The graph of the funnel plot was basically symmetrical, suggesting low publication bias. Conclusions: Serum complement C1q is elevated in CAD patients, but its mechanism of action may have a dual effect, but further research is needed to understand its precise role and clinical implications.

Prioritized single vitrified blastocyst to be warmed between grades 3 or 4 blastocyst on day 5 transfer cycles.

PURPOSE: Selecting the optimal blastocyst to implant during cryopreservation and warming is critial for in vitro fertilization success. Therefore, the aim of this study was to explore which blastocyst should be prioritized to be thawed when facing a single vitrified blastocyst on day 5 transfer. METHODS: A retrospective study including 1,976 single vitrified-warmed blastocyst transfer cycles was conducted from January 2016 to December 2020. RESULTS: We found that grade 4 vitrified blastocyst had a higher clinical pregnancy (60.64% vs. 49.48%, P < 0.001) and live birth rates (50.12% vs 39.59%, P < 0.001) than the grade 3 vitrified blastocyst. However, no statistical difference was found between groups in miscarriage rate, birth weight, or gestational age. Besides, the grade 4 vitrified-thawed blastocyst had significant potential to develop into grade 6 blastocyst after further culturing for 16 h (73.68% vs. 48.60%, P < 0.001). The grade 6 transferred blastocyst was markedly higher in both clinical pregnancy rate (61.88% vs. 51.53%, P < 0.001) and live birth rate (50.91% vs. 40.46%, P < 0.001) compared to grade 5 transferred blastocyst. CONCLUSIONS: Grade 4 vitrified blastocyst is recommended when facing single vitrified blastocyst on day 5 transfer. More importantly, the "embryonic escape hypothesis" was firstly proposed to reveal the findings.

Joint-GWAS, Linkage Mapping, and Transcriptome Analysis to Reveal the Genetic Basis of Plant Architecture-Related Traits in Maize.

Plant architecture is one of the key factors affecting maize yield formation and can be divided into secondary traits, such as plant height (PH), ear height (EH), and leaf number (LN). It is a viable approach for exploiting genetic resources to improve plant density. In this study, one natural panel of 226 inbred lines and 150 family lines derived from the offspring of T32 crossed with Qi319 were genotyped by using the MaizeSNP50 chip and the genotyping by sequence (GBS) method and phenotyped under three different environments. Based on the results, a genome-wide association study (GWAS) and linkage mapping were analyzed by using the MLM and ICIM models, respectively. The results showed that 120 QTNs (quantitative trait nucleotides) and 32 QTL (quantitative trait loci) related to plant architecture were identified, including four QTL and 40 QTNs of PH, eight QTL and 41 QTNs of EH, and 20 QTL and 39 QTNs of LN. One dominant QTL, qLN7-2, was identified in the Zhangye environment. Six QTNs were commonly identified to be related to PH, EH, and LN in different environments. The candidate gene analysis revealed that Zm00001d021574 was involved in regulating plant architecture traits through the autophagy pathway, and Zm00001d044730 was predicted to interact with the male sterility-related gene ms26. These results provide abundant genetic resources for improving maize plant architecture traits by using approaches to biological breeding.

[Preliminarily study of arthrocentesis combined with liquid phase concentrated growth factor injection in the treatment of unilateral temporomandibular joint osteoarthritis].

OBJECTIVE: To observe the clinical effect of arthrocentesis combined with liquid phase concentrated growth factor (CGF) injection in the treatment of unilateral temporomandibular joint osteoarthritis (TMJOA), in order to provide a new treatment option for TMJOA patients. METHODS: In this non-randomized controlled study, patients diagnosed with unilateral TMJOA who visited the center for temporomandibular joint disorder and orofacial pain of Peking University School and Hospital of Stomatology from June 2021 to January 2023 were selected as research objects. The patients were divided into experimental group and control group, which were selected by patients themselves. The experimental group received arthrocentesis combined with liquid phase CGF injection and the control group received arthrocentesis combined with HA injection. Both groups were treated 3 times, once every two weeks. The clinical effect was evaluated by the maximum mouth opening, pain value and the degree of mandibular function limitation 6 months after treatment. The change of condylar bone was evaluated by cone beam CT (CBCT) image fusion technology before and after treatment. RESULTS: A total of 20 patients were included in the experimental group, including 3 males and 17 females, with an average age of (34.40±8.41) years. A total of 15 patients were included in the control group, including 1 male and 14 females, with an average age of (32.20±12.00) years. There was no statistical difference in general information between the two groups (P > 0.05). There were no statistical differences in the mouth opening, pain value and the degree of jaw function limitation between the two groups before treatment (P > 0.05), and all of them improved 6 months after treatment compared with before treatment (P < 0.05). However, the mouth opening of experimental group was significantly higher than that of control group 6 months after treatment (P < 0.05), and the degree of jaw function limitation was significantly lower than that of control group (P < 0.05). CBCT 2D images showed that the condylar bone of both groups was smoother after treatment than before treatment, and image fusion results showed that 10 patients (50.0%) in the experimental group and 5 patients (33.3%) in the control group had reparative remodeling area of condylar bone, and there was no statistical difference between them (P > 0.05). Except for one CGF patient, the other patients in both groups had some absorption areas of condylar bone. CONCLUSION: The arthrocentesis combined with liquid phase CGF injection can improve the clinical symptoms and signs of unilateral TMJOA patients in short term, and is better than HA in increasing mouth opening and improving jaw function. CBCT fusion images of both patient groups show some cases of condylar bone reparative remodeling and its relevance to treatment plans still requires further study.

cis-Regulatory variation affecting gene expression contributes to the improvement of maize kernel size.

cis-Regulatory variations contribute to trait evolution and adaptation during crop domestication and improvement. As the most important harvested organ in maize (Zea mays L.), kernel size has undergone intensive selection for size. However, the associations between maize kernel size and cis-regulatory variations remain unclear. We chose two independent association populations to dissect the genetic architecture of maize kernel size together with transcriptomic and genotypic data. The resulting phenotypes reflected a strong influence of population structure on kernel size. Compared with genome-wide association studies (GWASs), which accounted for population structure and relatedness, GWAS based on a naïve or simple linear model revealed additional associated single-nucleotide polymorphisms significantly involved in the conserved pathways controlling seed size in plants. Regulation analyses through expression quantitative trait locus mapping revealed that cis-regulatory variations likely control kernel size by fine-tuning the expression of proximal genes, among which ZmKL1 (GRMZM2G098305) was transgenically validated. We also proved that the pyramiding of the favorable cis-regulatory variations has contributed to the improvement of maize kernel size. Collectively, our results demonstrate that cis-regulatory variations, together with their regulatory genes, provide excellent targets for future maize improvement.

Two Mesoporous Domains Are Better Than One for Catalytic Deconstruction of Polyolefins.

Catalytic hydrogenolysis of polyolefins into valuable liquid, oil, or wax-like hydrocarbon chains for second-life applications is typically accompanied by the hydrogen-wasting co-formation of low value volatiles, notably methane, that increase greenhouse gas emissions. Catalytic sites confined at the bottom of mesoporous wells, under conditions in which the pore exerts the greatest influence over the mechanism, are capable of producing less gases than unconfined sites. A new architecture was designed to emphasize this pore effect, with the active platinum nanoparticles embedded between linear, hexagonal mesoporous silica and gyroidal cubic MCM-48 silica (mSiO2/Pt/MCM-48). This catalyst deconstructs polyolefins selectively into ∼C20-C40 paraffins and cleaves C-C bonds at a rate (TOF = 4.2 ± 0.3 s-1) exceeding that of materials lacking these combined features while generating negligible volatile side products including methane. The time-independent product distribution is consistent with a processive mechanism for polymer deconstruction. In contrast to time- and polymer length-dependent products obtained from non-porous catalysts, mSiO2/Pt/MCM-48 yields a C28-centered Gaussian distribution of waxy hydrocarbons from polyolefins of varying molecular weight, composition, and physical properties, including low-density polyethylene, isotactic polypropylene, ultrahigh-molecular-weight polyethylene, and mixtures of multiple, post-industrial polyolefins. Coarse-grained simulation reveals that the porous-core architecture enables the paraffins to diffuse away from the active platinum site, preventing secondary reactions that produce gases.

Facile and Unplugged Surface Plasmon Resonance Biosensor with NIR-Emitting Perovskite Nanocomposites for Fast Detection of SARS-CoV-2.

The emergence of the coronavirus disease 2019 (COVID-19) pandemic prompted researchers to develop portable biosensing platforms, anticipating to detect the analyte in a label-free, direct, and simple manner, for deploying on site to prevent the spread of the infectious disease. Herein, we developed a facile wavelength-based SPR sensor built with the aid of a 3D printing technology and synthesized air-stable NIR-emitting perovskite nanocomposites as the light source. The simple synthesis processes for the perovskite quantum dots enabled low-cost and large-area production and good emission stability. The integration of the two technologies enabled the proposed SPR sensor to exhibit the characteristics of lightweight, compactness, and being without a plug, just fitting the requirements of on-site detection. Experimentally, the detection limit of the proposed NIR SPR biosensor for refractive index change reached the 10-6 RIU level, comparable with that of state-of-the-art portable SPR sensors. In addition, the bio-applicability of the platform was validated by incorporating a homemade high-affinity polyclonal antibody toward the SARS-CoV-2 spike protein. The results demonstrated that the proposed system was capable of discriminating between clinical swab samples collected from COVID-19 patients and healthy subjects because the used polyclonal antibody exhibited high specificity against SARS-CoV-2. Most importantly, the whole measurement process not only took less than 15 min but also needed no complex procedures or multiple reagents. We believe that the findings disclosed in this work can open an avenue in the field of on-site detection for highly pathogenic viruses.

The TGF-ß/Smad2/3 signaling pathway is involved in Musashi2-induced invasion and metastasis of colorectal cancer.

To identify Musashi2 as an effective biomarker regulated by the TGF-ß/Smad2/3 signaling pathway for the precise diagnosis and treatment of colorectal cancer (CRC) through bioinformatic tools and experimental verification. The Cancer Genome Atlas, Timer, and Kaplan-Meier analyses were performed to clarify the expression of Musashi2 and its influence on the prognosis of CRC. Transforming growth factor beta 1 (TGF-ß1) was used to activate the TGF-ß/Smad2/3 signaling pathway to identify whether it could regulate the expression and function of Musashi2. Western blot analysis and quantitative PCR analyses were conducted to verify the expression of Musashi2. Cell counting kit-8 (CCK8), EdU, wound healing, and Transwell assays were conducted to reveal the role of Musashi2 in the proliferation, migration, and invasion of CRC. Musashi2 was upregulated in CRC and promoted proliferation and metastasis. TGF-ß1 increased the expression of Musashi2, while the antagonist inducer of type II TGF-ß receptor degradation-1 (ITD-1) decreased the expression. CCK8 and EdU assays demonstrated that inhibition of Musashi2 or use of ITD-1 lowered proliferation ability. The Transwell and wound healing assays showed that the migration and invasion abilities of CRC cells could be regulated by Musashi2. The above functions could be enhanced by TGF-ß1 by activating the TGF-ß/Smad2/3 signaling pathway and reversed by ITD-1. A positive correlation was found between Musashi2 and the TGF-ß/Smad2/3 signaling pathway. TGF-ß1 activates the TGF-ß/Smad2/3 pathway to stimulate the expression of Musashi2, which promotes the progression of CRC. Musashi2 might become a target gene for the development of new antitumor drugs.

Ultraviolet sensing based on an in-fiber ZnO microwire constructed Mach-Zehnder interferometer.

We propose a Mach-Zehnder interferometer based on an in-fiber ZnO microwire structure for ultraviolet sensing. The device undergoes femtosecond laser micromachining and chemical etching on a single-mode optical fiber initially, creating a microgroove that extends to half of the core's depth, into which a single ZnO microwire is transferred. The ZnO microwire and the remaining core are used as the sensing arm and the reference arm, respectively, forming a Mach-Zehnder interferometer. To enhance the stability and the sensitivity, ZnO nanoparticles are filled into the microgroove after the ZnO microwire is transferred. The fabricated device exhibits a sensitivity of 0.86 nm/(W·cm-2) for ultraviolet sensing, along with a response time of 115 ns (rise time) and 133 µs (decay time), respectively. The proposed sensor exhibits good ultraviolet sensitivity, offering a novel approach for ultraviolet sensing technology.

Sustainable Biochar Nanosheets Derived from Sweet Sorghum Residues via Superbase Pretreatment.

Two-dimensional (2D) sheet-like biochar as promising alternatives to graphene nanosheets has gained significant attention in materials science while being highly restricted by its complicated synthetic steps. In this study, the dimethyl sulfoxide/potassium hydroxide (DMSO/KOH) superbase system was first used to pretreat sweet sorghum residues (SS) and then carbonized to prepare sheet-like biochar. Ascribing to the strong nucleophilicity of DMSO/KOH, a synergistic effect was achieved by partially removing non-cellulosic components in SS and swelling the amorphous region of cellulose, leaving more layered cellulose behind (∼46.5 wt %), which was favorable for the formation of 2D biochar nanosheets with high graphitization degrees (∼93.1%). This strategy was also suitable for other biomass fibers (e.g., straw, wood powders, and nuclear shells) to obtain sheet-like biochar. The resulting sheet-like biochar could be compounded with cellulose nanofibers to achieve the structural design of composites and solve the molding problem of biochar, which was beneficial for dyeing wastewater treatment. Thus, this work provides insight into a simple strategy for developing 2D ultrathin sheet-like biochar from sustainable biomass wastes.

ILRUN Promotes Atherosclerosis Through Lipid-Dependent and Lipid-Independent Factors.

BACKGROUND: Common genetic variation in close proximity to the ILRUN gene are significantly associated with coronary artery disease as well as with plasma lipid traits. We recently demonstrated that hepatic inflammation and lipid regulator with ubiquitin-associated domain-like and NBR1-like domains (ILRUN) regulates lipoprotein metabolism in vivo in mice. However, whether ILRUN, which is expressed in vascular cells, directly impacts atherogenesis remains unclear. We sought to determine the role of ILRUN in atherosclerosis development in mice. METHODS: For our study, we generated global Ilrun-deficient (IlrunKO) male and female mice on 2 hyperlipidemic backgrounds: low density lipoprotein receptor knockout (LdlrKO) and apolipoprotein E knockout (ApoeKO; double knockout [DKO]). RESULTS: Compared with littermate control mice (single LdlrKO or ApoeKO), deletion of Ilrun in DKO mice resulted in significantly attenuated both early and advanced atherosclerotic lesion development, as well as reduced necrotic area. DKO mice also had significantly decreased plasma cholesterol levels, primarily attributable to non-HDL (high-density lipoprotein) cholesterol. Hepatic-specific reconstitution of ILRUN in DKO mice on the ApoeKO background normalized plasma lipids, but atherosclerotic lesion area and necrotic area remained reduced in DKO mice. Further analysis showed that loss of Ilrun increased efferocytosis receptor MerTK expression in macrophages, enhanced in vitro efferocytosis, and significantly improved in situ efferocytosis in advanced lesions. CONCLUSIONS: Our results support ILRUN as an important novel regulator of atherogenesis that promotes lesion progression and necrosis. It influences atherosclerosis through both plasma lipid-dependent and lipid-independent mechanisms. These findings support ILRUN as the likely causal gene responsible for genetic association of variants with coronary artery disease at this locus and suggest that suppression of ILRUN activity might be expected to reduce atherosclerosis.

Mechanism of METTL14 and m6A modification of lncRNA MALAT1 in the proliferation of oral squamous cell carcinoma cells.

OBJECTIVES: Methyltransferase-like 14 (METTL14) plays an epigenetic role in various cancer through N6-methyladenosine (m6A) modification. This study sought to analyze the mechanism of METTL14 in oral squamous cell carcinoma (OSCC) cell proliferation. METHODS: Expression levels of METTL14, lncRNA metastasis associated with lung adenocarcinoma transcript 1 (lncRNA MALAT1), microRNA (miR)-224-5p, and histone lysine demethylase 2A (KDM2A) in OSCC tissues (N = 40), and cell lines (FaDu, SCC-25, CAL-27, and SCC-15) were detected. Cell viability and colony formation capacity were assessed. m6A level, stability, and subcellular localization of lncRNA MALAT1 were determined. Nude mouse xenograft tumor assay was performed to confirm the role of METTL14 in vivo. RESULTS: METTL14 and lncRNA MALAT1 were upregulated, and miR-224-5p was downregulated in OSCC tissues and cells. Silencing METTL14 repressed OSCC cell viability and colony formation. Overexpression of MALAT1 and KDM2A or miR-224-5p downregulation reversed the inhibition of silencing METTL14 on OSCC cell proliferation. METTL14 induced m6A modification of MALAT1 to upregulate MALAT1. MALAT1 is comparatively bound to miR-224-5p to promote KDM2A transcription. In vivo, METTL14 promoted tumor growth via regulating MALAT1/miR-224-5p/ KDM2A. CONCLUSIONS: Overall, our findings verified the therapeutic role of silencing METTL14 in OSCC treatment through the MALAT1/miR-224-5p/KDM2A axis.

Clinical outcomes of subtypes of mosaic single aneuploid embryos after preimplantation genetic testing for aneuploidy.

OBJECTIVE: Mosaic embryos are often characterized by different numbers (single or double or ≥ 3 aneuploidies) or types of chromosomal abnormalities (monosomy or trisomy and involving whole chromosome or chromosome segments). However, due to limitations in the number of samples, the relationship between these abnormalities and clinical outcomes is often not evaluated. METHODS: This study analyzed chromosomal abnormalities and clinical outcomes in 591 aneuploid mosaic and 3071 euploid embryos from multiple retrospective cohorts as well as from the current authors' unpublished retrospective cohort. RESULTS: Through meta-analysis, it was found that single aneuploid mosaicism reduced implantation and clinical pregnancy rates. In addition, no significant differences were noted between mosaic trisomies and mosaic monosomies in terms of their effects on implantation and clinical pregnancy rates. All subtypes of single aneuploid mosaicism were found to reduce implantation and clinical pregnancy rates for women of over 35 years old. Furthermore, it was observed that all subtypes of single aneuploid in higher-level mosaicism reduced implantation and clinical pregnancy rates. Regarding the lower-level group, only segmental mosaicism with segmental chromosome gain reduced both of the above rates. Unexpectedly, the type of chromosome abnormality was more likely to influence miscarriage rates compared with the level of mosaicism. Indeed, monosomy aneuploid mosaic embryos increased miscarriage rates in both lower- and higher-levels mosaic ratio groups, but not other subtypes. CONCLUSIONS: Although the mechanism for the above phenomenon remains unknown, it is recommended that attention should still be paid to the increased miscarriage rates caused by monosomy in aneuploid mosaic embryos.

Molecular characterization of extracellular vesicles derived from follicular fluid of women with and without PCOS: integrating analysis of differential miRNAs and proteins reveals vital molecules involving in PCOS.

PURPOSE: To elucidate the characterization of extracellular vesicles (EVs) in the follicular fluid-derived extracellular vesicles (FF-EVs) and discover critical molecules and signaling pathways associating with the etiology and pathobiology of PCOS, the differentially expressed miRNAs (DEmiRNAs) and differentially expressed proteins profiles (DEPs) were initially explored and combinedly analyzed. METHODS: First, the miRNA and protein expression profiles of FF-EVs in PCOS patients and control patients were compared by RNA-sequencing and tandem mass tagging (TMT) proteomic methods. Subsequently, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to analyze the biological function of target genes of DEmiRNAs and DEPs. Finally, to discover the functional miRNA-target gene-protein interaction pairs involved in PCOS, DEmiRs target gene datasets and DEPs datasets were used integratedly. RESULTS: A total of 6 DEmiRNAs and 32 DEPs were identified in FF-EVs in patients with PCOS. Bioinformatics analysis revealed that DEmiRNAs target genes are mainly involved in thiamine metabolism, insulin secretion, GnRH, and Apelin signaling pathway, which are closely related to the occurrence of PCOS. DEPs also closely related to hormone metabolism processes such as steroid hormone biosynthesis. In the analysis integrating DEmiRNAs target genes and DEPs, two molecules, GRAMD1B and STPLC2, attracted our attention that are closely associated with cholesterol transport and ceramide biosynthesis, respectively. CONCLUSION: Dysregulated miRNAs and proteins in FF-EVs, mainly involving in hormone metabolism, insulin secretion, neurotransmitters regulation, adipokine expression, and secretion, may be closely related to PCOS. The effects of GRAMD1B and STPLC2 on PCOS deserve further study.

Quantitative biochemical phenotypic heterogeneity of senescent macrophage at a single cell level by Synchrotron Radiation Fourier Transform Infrared Microspectroscopy.

Macrophage senescence plays an important role in pathophysiological process of age-related diseases such as atherosclerosis, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and lung cancer. After macrophage senescence, the biochemical phenotypes related to biological functions showed great heterogeneity. However, the biochemical phenotype and phenotypic heterogeneity of senescent macrophage has not been fully understood. Exploring the phenotype of biochemical substances in senescent macrophage will be helpful for understanding the function of senescent macrophage and finding out the potential mechanism between immune macrophage senescence and age-related diseases. In this study, we employed SR-FTIR microspectroscopy to detect the biochemical phenotype and phenotypic heterogeneity of single macrophage. The whole infrared spectra of senescent macrophages shifted, indicating biochemical substance changes within senescent macrophages. PCA and intercellular Euclidean distance statistical analysis based on specific spectra regions revealed dynamic changes of lipids and proteins during macrophage senescence. This proved that SR-FTIR microspectroscopy is an effective tool to detect the single cell biochemical phenotype transformation and phenotypic heterogeneity during macrophage senescence. It is of great significance to provide an evaluation method or clue for the study of cellular functions related to intracellular biochemical substances.

Integrated IBD Analysis, GWAS Analysis and Transcriptome Analysis to Identify the Candidate Genes for White Spot Disease in Maize.

Foundation parents (FPs) play an irreplaceable role in maize breeding practices. Maize white spot (MWS) is an important disease in Southwest China that always seriously reduces production. However, knowledge about the genetic mechanism of MWS resistance is limited. In this paper, a panel of 143 elite lines were collected and genotyped by using the MaizeSNP50 chip with approximately 60,000 single nucleotide polymorphisms (SNPs) and evaluated for resistance to MWS among 3 environments, and a genome-wide association study (GWAS) and transcriptome analysis were integrated to reveal the function of the identity-by-descent (IBD) segments for MWS. The results showed that (1) 225 IBD segments were identified only in the FP QB512, 192 were found only in the FP QR273 and 197 were found only in the FP HCL645. (2) The GWAS results showed that 15 common quantitative trait nucleotides (QTNs) were associated with MWS. Interestingly, SYN10137 and PZA00131.14 were in the IBD segments of QB512, and the SYN10137-PZA00131.14 region existed in more than 58% of QR273's descendants. (3) By integrating the GWAS and transcriptome analysis, Zm00001d031875 was found to located in the region of SYN10137-PZA00131.14. These results provide some new insights for the detection of MWS's genetic variation mechanisms.