Intestinal metabolite xylulose inhibits colorectal cancer by inducing apoptosis through the MAPK signalling pathway.

BACKGROUND: The intestinal metabolites are involved in the initiation, progression and metastasis of colorectal cancer (CRC). They are a potential source of agents for cancer therapy. Our previous study identified altered faecal metabolites between CRC patients and healthy volunteers. However, no specific metabolite was clearly illustrated for CRC therapy. RESULTS: We found that the level of xylulose was lower in the stools of CRC patients than in those of healthy volunteers. Xylulose inhibited cell growth without affecting the cell cycle by inducing apoptosis in CRC cells, which was evidenced by increased expression of the proapoptotic proteins C-PARP and C-Caspase3 and decreased expression of the antiapoptotic protein BCL-2 in CRC cells. Mechanistically, xylulose reduced the activity of the MAPK signalling pathway, represented by reduced phosphorylation of JNK, ERK, and P38. Furthermore, an ALI model was used to show the tumour killing ability of xylulose on human CRC spheres, as well as human colorectal adenoma (AD) spheres. CONCLUSION: Xylulose inhibits CRC growth by inducing apoptosis through attenuation of the MAPK signalling pathway. These results suggest that xylulose may serve as an effective agent for CRC therapy.

TRIM21-mediated ubiquitylation of TAT suppresses liver metastasis in gallbladder cancer.

Liver metastasis is common in patients with gallbladder cancer (GBC), imposing a significant challenge in clinical management and serving as a poor prognostic indicator. However, the mechanisms underlying liver metastasis remain largely unknown. Here, we report a crucial role of tyrosine aminotransferase (TAT) in liver metastasis of GBC. TAT is frequently up-regulated in GBC tissues. Increased TAT expression is associated with frequent liver metastasis and poor prognosis of GBC patients. Overexpression of TAT promotes GBC cell migration and invasion in vitro, as well as liver metastasis in vivo. TAT knockdown has the opposite effects. Intriguingly, TAT promotes liver metastasis of GBC by potentiating cardiolipin-dependent mitophagy. Mechanistically, TAT directly binds to cardiolipin and leads to cardiolipin externalization and subsequent mitophagy. Moreover, TRIM21 (Tripartite Motif Containing 21), an E3 ubiquitin ligase, interacts with TAT. The histine residues 336 and 338 at TRIM21 are essential for this binding. TRIM21 preferentially adds the lysine 63 (K63)-linked ubiquitin chains on TAT principally at K136. TRIM21-mediated TAT ubiquitination impairs its dimerization and mitochondrial location, subsequently inhibiting tumor invasion and migration of GBC cells. Therefore, our study identifies TAT as a novel driver of GBC liver metastasis, emphasizing its potential as a therapeutic target.

Social media trends in obstetrics and gynecology residency programs on Instagram and X (Twitter).

BACKGROUND: During the COVID pandemic, residency program's social media presence increased to aid in residency recruitment by attempting to increase engagement and readily available information for applicants across specialties. However, little information exists on what characteristics and content on obstetrics and gynecology (OBGYN) residency program accounts attract more followers or engagement. OBJECTIVES: To identify social media trends in OBGYN residencies and determine which aspects of programs influence the number of followers and interaction with content posted. METHODS: We performed a retrospective review of ACGME accredited OBGYN programs and determined their presence on Instagram and X in the fall of 2021. Content from the thirty programs with the most followers was analyzed independently by two authors. Multivariate analysis and a linear mixed model were used to characterize and evaluate content on Instagram and X. RESULTS: Most programs utilized Instagram (88.5%, N = 262/296) and were managed solely by residents (84.4%, N = 108/128). Number of followers on Instagram positively correlated with features such as program size, Instagram profile duration, and Doximity rankings (p < 0.0x01). Programs on X had more followers if their profile had a longer duration, followed more individuals, or were ranked higher on Doximity. The most posted Instagram content was biographical and social in nature. Instagram posts with the highest engagement were awards and/or the Match. CONCLUSIONS: Understanding what social media content attracts more followers and increases engagement is crucial as it likely impacts OBGYN resident recruitment. Professional groups should establish guidelines for social media use in recruitment for the protection of both residents and applicants.

Design and analysis of a lower limb assistive exoskeleton robot.

BACKGROUND: In recent years, exoskeleton robot technology has developed rapidly. Exoskeleton robots that can be worn on a human body and provide additional strength, speed or other abilities. Exoskeleton robots have a wide range of applications, such as medical rehabilitation, logistics and disaster relief and other fields. OBJECTIVE: The study goal is to propose a lower limb assistive exoskeleton robot to provide extra power for wearers. METHODS: The mechanical structure of the exoskeleton robot was designed by using bionics principle to imitate human body shape, so as to satisfy the coordination of man-machine movement and the comfort of wearing. Then a gait prediction method based on neural network was designed. In addition, a control strategy according to iterative learning control was designed. RESULTS: The experiment results showed that the proposed exoskeleton robot can produce effective assistance and reduce the wearer's muscle force output. CONCLUSION: A lower limb assistive exoskeleton robot was introduced in this paper. The kinematics model and dynamic model of the exoskeleton robot were established. Tracking effects of joint angle displacement and velocity were analyzed to verify feasibility of the control strategy. The learning error of joint angle can be improved with increase of the number of iterations. The error of trajectory tracking is acceptable.

Sequential activation of strigolactone and salicylate biosynthesis promotes leaf senescence.

Leaf senescence is a complex process strictly regulated by various external and endogenous factors. However, the key signaling pathway mediating leaf senescence remains unknown. Here, we show that Arabidopsis SPX1/2 negatively regulate leaf senescence genetically downstream of the strigolactone (SL) pathway. We demonstrate that the SL receptor AtD14 and MAX2 mediate the age-dependent degradation of SPX1/2. Intriguingly, we uncover an age-dependent accumulation of SLs in leaves via transcriptional activation of SL biosynthetic genes by the transcription factors (TFs) SPL9/15. Furthermore, we reveal that SPX1/2 interact with the WRKY75 subclade TFs to inhibit their DNA-binding ability and thus repress transcriptional activation of salicylic acid (SA) biosynthetic gene SA Induction-Deficient 2, gating the age-dependent SA accumulation in leaves at the leaf senescence onset stage. Collectively, our new findings reveal a signaling pathway mediating sequential activation of SL and salicylate biosynthesis for the onset of leaf senescence in Arabidopsis.

Q negatively regulates wheat salt tolerance through directly repressing the expression of TaSOS1 and reactive oxygen species scavenging genes.

The Q transcription factor plays important roles in improving multiple wheat domestication traits such as spike architecture, threshability and rachis fragility. However, whether and how it regulates abiotic stress adaptation remain unclear. We found that the transcriptional expression of Q can be induced by NaCl and abscisic acid treatments. Using the q mutants generated by CRISPR/Cas9 and Q overexpression transgenic lines, we showed that the domesticated Q gene causes a penalty in wheat salt tolerance. Then, we demonstrated that Q directly represses the transcription of TaSOS1-3B and reactive oxygen species (ROS) scavenging genes to regulate Na+ and ROS homeostasis in wheat. Furthermore, we showed that wheat salt tolerance protein TaWD40 interacts with Q to competitively interfere with the interaction between Q and the transcriptional co-repressor TaTPL. Taken together, our findings reveal that Q directly represses the expression of TaSOS1 and some ROS scavenging genes, thus causing a harmful effect on wheat salt tolerance.

Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy.

The combination of immune checkpoint inhibitors and immunogenic cell death (ICD) inducers has become a promising strategy for the treatment of various cancers. However, its efficacy remains unmet because of the dense stroma and defective vasculatures in the tumor microenvironment (TME) that restricts the intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Herein, cancer-associated fibroblasts (CAFs)-targeted nanoemulsions are tailored to combine the ICD induction and the TME reprogramming to sensitize checkpoint blockade immunotherapy. Melittin, as an ICD inducer and an antifibrotic agent, is efficiently encapsulated into the nanoemulsion accompanied by a nitric oxide donor to improve its bioavailability and tumor targeting. The nanoemulsions exhibited dual functionality by directly inducing direct cancer cell death and enhancing the tumoral immunogenicity, while also synergistically reprogramming the TME through reversing the activated CAFs, decreasing collagen deposition and restoring tumor vessels. Consequently, these nanemulsions successfully facilitated the CTLs infiltration and suppressing the recruitment of immunosuppressive cells. A combination of AE-MGNPs and anti-CTLA-4 antibody greatly elicited a striking level of antitumor T-cell response to suppress tumor growth in CAFs-rich colorectal tumor models. Our work emphasized the integration of the ICD induction with simultaneous modulation of the TME to enhance the sensitivity of patients to checkpoint blockade immunotherapy.

Predicting the effect of chemicals on fruit using graph neural networks.

The neural network method is a type of machine learning that has made significant advances over the past few years in a variety of fields, particularly text, speech, images, videos, etc. In areas where data is unstructured, traditional machine learning has not been able to surpass the 'glass ceiling'; therefore, researchers have turned to neural networks as auxiliary tools to achieve significant breakthroughs or develop new research methods. An array of computational chemistry challenges can be addressed using neural networks, including virtual screening, quantitative structure-activity relationships, protein structure prediction, materials design, quantum chemistry, and property prediction, among others. This paper proposes a strategy for predicting the chemical properties of fruits by using graph neural networks, and it aims to provide some guidance to researchers and streamline the identification process.

Enhanced direct gaseous CO2 fixation into higher bio-succinic acid production and selectivity.

Utilizing CO2 for bio-succinic acid production is an attractive approach to achieve carbon capture and recycling (CCR) with simultaneous production of a useful platform chemical. Actinobacillus succinogenes and Basfia succiniciproducens were selected and investigated as microbial catalysts. Firstly, the type and concentration of inorganic carbon concentration and glucose concentration were evaluated. 6 g C/L MgCO3 and 24 g C/L glucose were found to be the optimal basic operational conditions, with succinic acid production and carbon yield of over 30 g/L and over 40%, respectively. Then, for maximum gaseous CO2 fixation, carbonate was replaced with CO2 at different ratios. The "less carbonate more CO2" condition of the inorganic carbon source was set as carbonate: CO2 = 1:9 (based on the mass of carbon). This condition presented the highest availability of CO2 by well-balanced chemical reaction equilibrium and phase equilibrium, showing the best performance with regarding CO2 fixation (about 15 mg C/(L·hr)), with suppressed lactic acid accumulation. According to key enzymes analysis, the ratio of phosphoenolpyruvate carboxykinase to lactic dehydrogenase was enhanced at high ratios of gaseous CO2, which could promote glucose conversion through the succinic acid path. To further increase gaseous CO2 fixation and succinic acid production and selectivity, stepwise CO2 addition was evaluated. 50%-65% increase in inorganic carbon utilization was obtained coupled with 20%-30% increase in succinic acid selectivity. This was due to the promotion of the succinic acid branch of the glucose metabolism, while suppressing the pyruvate branch, along with the inhibition on the conversion from glucose to lactic acid.

Sphingomonas bacteria could serve as an early bioindicator for the development of chlorantraniliprole resistance in Spodoptera frugiperda.

The fall armyworm (Spodoptera frugiperda) was found to have invaded China in December 2018, and in just one year, crops in 26 provinces were heavily affected. Currently, the most effective method for emergency control of fulminant pests is to use of chemical pesticides. Recently, most fall armyworm populations in China were begining to exhibite low level resistance to chlorantraniliprole. At present, it is not possible to sensitively reflect the low level resistance of S. frugiperda by detecting target mutation and detoxification enzyme activity. In this study we found that 12 successive generations of screening with chlorantraniliprole caused S. frugiperda to develop low level resistance to this insecticide, and this phenotype was not attribute to genetic mutations in S. frugiperda, but rather to a marked increase in the relative amount of the symbiotic bacteria Sphingomonas. Using FISH and qPCR assays, we determined the amount of Sphingomonas in the gut of S. frugiperda and found Sphingomonas accumulation to be highest in the 3rd-instar larvae. Additionally, Sphingomonas was observed to provide a protective effect to against chlorantraniliprole stress to S. frugiperda. With the increase of the resistance to chlorantraniliprole, the abundance of bacteria also increased, we propose Sphingomonas monitoring could be adapted into an early warning index for the development of chlorantraniliprole resistance in S. frugiperda populations, such that timely measures can be taken to delay or prevent the widespread propagation of resistance to this highly useful agricultural chemical in S. frugiperda field populations.

The Norepinephrine-QseC Axis Aggravates F. nucleatum-associated Colitis Through Interkingdom Signaling.

AIMS: Inflammatory bowel disease (IBD) is associated with F. nucleatum, and chronic stress can increase the risk of aggravation. However, whether norepinephrine (NE) can enhance the pathogenicity of F. nucleatum to aggravate dextran sulfate sodium salt (DSS)-induced colitis is unclear. METHODS: Transcriptome sequencing was used to identify differentially expressed genes in bacteria treated with NE. Affinity testing and molecular docking were applied to calculate and predict the binding of NE and Quorum sensing  regulators C (QseC). The pathogenicity of Fusobacterium nucleatum treated with NE and QseC inhibitors was examined in vitro and further verified using the IBD mouse model induced by DSS. RESULTS: Norepinephrine could bind to QseC directly to upregulate the quorum sensing pathway of F. nucleatum and enhance its virulence gene expression (FadA, FomA, Fap2) and invasiveness in vitro. Meanwhile, it promoted the invasion of F. nucleatum into the intestine and increased the expression of host inflammatory cytokines (IL-6, IL-1ß) to aggravate colonic inflammation in IBD mice. The QseC inhibitor LED209 inhibited the effect of NE on F. nucleatum and partially restored short-chain fatty acid (SCFA)-producing bacteria (Prevotellaceae, Lactobacillaceae) to attenuate colonic inflammation in IBD mice. CONCLUSIONS: Generally, the NE-QseC axis enhanced the pathogenicity of F. nucleatum through interkingdom signaling to aggravate colonic inflammation in IBD mice. We see that QseC may be a potential target for microbiota management of IBD under chronic pressure.

Norepinephrine could bind to QseC directly to enhance the pathogenicity of F. nucleatum to aggravate colonic inflammation. The QseC inhibitor inhibited the effect of NE on F. nucleatum and partially restored short-chain fatty acid­producing bacteria to attenuate colonic inflammation.

Discovery of sesquiterpenoids from an actinomycete Crossiella cryophila through genome mining and heterologous expression.

Genome mining of the Actinomycete Crossiella cryophila facilitated the discovery of a minimal terpenoid biosynthetic gene cluster of cry consisting of a class I terpene cyclase CryA and a CYP450 monooxygenase CryB. Heterologous expression of cry allowed the isolation and characterization of two new sesquiterpenoids, ent-viridiflorol (1) and cryophilain (2). Notably, cryophilain (2) possesses a 5/7/3-fused tricyclic skeleton bearing a distinctive bridgehead hydroxy group. The combined in vivo and in vitro experiments revealed that CryA, the first ent-viridiflorol terpene cyclase, catalyzes farnesyl diphosphate to form the 5/7/3 sesquiterpene core scaffold and P450 CryB serves as a tailoring enzyme responsible for installing a hydroxy group at the bridgehead carbon.

Identification of COQ2 as a regulator of proliferation and lipid peroxidation through genome-scale CRISPR-Cas9 screening in myeloma cells.

Multiple myeloma (MM) is the second most common malignant haematological disease with a poor prognosis. The limit therapeutic progress has been made in MM patients with cancer relapse, necessitating deeper research into the molecular mechanisms underlying its occurrence and development. A genome-wide CRISPR-Cas9 loss-of-function screening was utilized to identify potential therapeutic targets in our research. We revealed that COQ2 plays a crucial role in regulating MM cell proliferation and lipid peroxidation (LPO). Knockout of COQ2 inhibited cell proliferation, induced cell cycle arrest and reduced tumour growth in vivo. Mechanistically, COQ2 promoted the activation of the MEK/ERK cascade, which in turn stabilized and activated MYC protein. Moreover, we found that COQ2-deficient MM cells increased sensitivity to the LPO activator, RSL3. Using an inhibitor targeting COQ2 by 4-CBA enhanced the sensitivity to RSL3 in primary CD138+ myeloma cells and in a xenograft mouse model. Nevertheless, co-treatment of 4-CBA and RSL3 induced cell death in bortezomib-resistant MM cells. Together, our findings suggest that COQ2 promotes cell proliferation and tumour growth through the activation of the MEK/ERK/MYC axis and targeting COQ2 could enhance the sensitivity to ferroptosis in MM cells, which may be a promising therapeutic strategy for the treatment of MM patients.

TDCPP and TiO2 NPs aggregates synergistically induce SH-SY5Y cell neurotoxicity by excessive mitochondrial fission and mitophagy inhibition.

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a halogen-containing phosphorus flame retardant, is widely used and has been shown to possess health risks to humans. The sustained release of artificial nanomaterials into the environment increases the toxicological risks of their coexisting pollutants. Nanomaterials may seriously change the environmental behavior and fate of pollutants. In this study, we investigated this combined toxicity and the potential mechanisms of toxicity of TDCPP and titanium dioxide nanoparticles (TiO2 NPs) aggregates on human neuroblastoma SH-SY5Y cells. TDCPP and TiO2 NPs aggregates were exposed in various concentration combinations, revealing that TDCPP (25 µg/mL) reduced cell viability, while synergistic exposure to TiO2 NPs aggregates exacerbated cytotoxicity. This combined exposure also disrupted mitochondrial function, leading to dysregulation in the expression of mitochondrial fission proteins (DRP1 and FIS1) and fusion proteins (OPA1 and MFN1). Consequently, excessive mitochondrial fission occurred, facilitating the translocation of cytochrome C from mitochondria to activate apoptotic signaling pathways. Furthermore, exposure of the combination of TDCPP and TiO2 NPs aggregates activated upstream mitochondrial autophagy but disrupted downstream Parkin recruitment to damaged mitochondria, preventing autophagosome-lysosome fusion and thereby disrupting mitochondrial autophagy. Altogether, our findings suggest that TDCPP and TiO2 NPs aggregates may stimulate apoptosis in neuronal SH-SY5Y cells by inducing mitochondrial hyperfission and inhibiting mitochondrial autophagy.

Bibliometric and visualized analysis of reporting and data systems from 2000 to 2022: research situation, global trends, and hotspots.

Background: The reporting and data system (RADS) has been researched across the world since it was first developed. This study used bibliometrics to analyze the research trends and current status of this field over the past almost 23 years and explored possible future research hotspots. Methods: We searched the Web of Science (WOS) literature on RADSs from January 1, 2000, to November 1, 2022, and evaluated the findings visually with VOSviewer (1.6.18), CiteSpace (6.1.3), and the "bibliometrix" package in R version 4.2.1. Results: We included 6,239 publications from 88 countries and regions. The number of published has shown an overall growth trend, especially since 2016. The United States was the country with the highest number of publications and citations. The top 10 most productive institutions in RADS research were mainly from South Korea and the United States. Kim EK was the most published author, and Turkbey B had the most cited publication. European Radiology had the most publications on the subject, while Radiology was the most influential journal. Magnetic resonance imaging, carcinoma, ultrasound, RADS, mammography, breast neoplasms, and diagnosis were the most common keywords. Artificial intelligence (AI) appears to be an emerging hotspot in the research of RADS. Conclusions: This study provides an overview of the development status of research into RADSs over the past 23 years. Research into RADSs has included various systems of the body, with the most studied being the breast, prostate, liver, and thyroid. In terms of auxiliary diagnosis, there is an increasing amount of research into the application of AI in RADSs, which along with the interpretability of AI, will be a hotspot of research in the following years.

Enantio- and Regioselective Cascade Hydroboration of Methylenecyclopropanes for Facile Access to Chiral 1,3- and 1,4-Bis(boronates).

Chiral 1, n-bis(boronate) plays a crucial role in organic synthesis and medicinal chemistry. However, their catalytic and asymmetric synthesis has long posed a challenge in terms of operability and accessibility from readily available substrates. The recent discovery of the C═C bond formation through ß-C elimination of methylenecyclopropanes (MCP) has provided an exciting opportunity to enhance molecular complexity. In this study, the catalyzed asymmetric cascade hydroboration of MCP is developed. By employing different ligands, various homoallylic boronate intermediate are obtained through the hydroboration ring opening process. Subsequently, the cascade hydroboration with HBpin or B2 pin2 resulted in the synthesis of enantioenriched chiral 1,3- and 1,4-bis(boronates) in high yields, accompanied by excellent chemo- and enantioselectivities. The selective transformation of these two distinct C─B bonds also demonstrated their application potential in organic synthesis.

A Crossover Trial Evaluating Coconut Oil as an Alternative to Commercial Ultrasound Gel in Obstetrical Ultrasounds.

OBJECTIVE: Our objective was to evaluate the quality of obstetrical ultrasound images obtained with coconut oil compared with commercial ultrasound gel and to assess patient acceptability. STUDY DESIGN: This was a randomized two-period crossover study in which 40 pregnant patients had standard biometry images obtained with both coconut oil and commercial ultrasound gel during their growth or anatomy ultrasound. All images were then rated by two blinded maternal-fetal medicine physicians on quality, resolution, and detail using a 0 to 100 scale. Contrasts obtained from linear mixed models were used to estimate the differences in image parameters between the agents. Participant experience was evaluated with an acceptability survey which included five items measured on a five-point Likert scale. RESULTS: Image quality, as rated by physicians, was found to be equivalent between commercial ultrasound gel and coconut oil. Additionally, there was not a statistically significant difference in image resolution or detail between the two coupling agents. The overall patient experience was significantly lower for commercial ultrasound gel when compared with coconut oil (mean difference = - 5.48, 95% confidence interval = [-6.89, -4.06]). CONCLUSION: Ultrasound images collected with coconut oil as the coupling agent are equivalent in quality to those collected using commercial ultrasound gel. Patients also preferred the use of coconut oil during their ultrasound, making its use a possible way to improve the patient ultrasound experience. Coconut oil has the potential as an alternative coupling agent that could significantly increase access to ultrasound use in resource-limited settings. KEY POINTS: · Coconut oil produces quality images during obstetrical ultrasounds.. · Patients prefer the use of coconut oil to standard ultrasound gel during obstetrical ultrasounds.. · Coconut oil is a coupling agent that could increase ultrasound use in resource-limited settings..

Trends and Hotspots in Global Radiomics Research: A Bibliometric Analysis.

Objectives: The purpose of this research is to summarize the structure of radiomics-based knowledge and to explore potential trends and priorities by using bibliometric analysis. Methods: Select radiomics-related publications from 2012 to October 2022 from the Science Core Collection Web site. Use VOSviewer (version 1.6.18), CiteSpace (version 6.1.3), Tableau (version 2022), Microsoft Excel and Rstudio's free online platforms (http://bibliometric.com) for co-writing, co-citing, and co-occurrence analysis of countries, institutions, authors, references, and keywords in the field. The visual analysis is also carried out on it. Results: The study included 6428 articles. Since 2012, there has been an increase in research papers based on radiomics. Judging by publications, China has made the largest contribution in this area. We identify the most productive institutions and authors as Fudan University and Tianjie. The top three magazines with the most publications are《FRONTIERS IN ONCOLOGY》, 《EUROPEAN RADIOLOGY》, and 《CANCERS》. According to the results of reference and keyword analysis, "deep learning, nomogram, ultrasound, f-18-fdg, machine learning, covid-19, radiogenomics" has been determined as the main research direction in the future. Conclusion: Radiomics is in a phase of vigorous development with broad prospects. Cross-border cooperation between countries and institutions should be strengthened in the future. It can be predicted that the development of deep learning-based models and multimodal fusion models will be the focus of future research. Advances in knowledge: This study explores the current state of research and hot spots in the field of radiomics from multiple perspectives, comprehensively, and objectively reflecting the evolving trends in imaging-related research and providing a reference for future research.

RhoGDIß inhibition via miR-200c/AUF1/SOX2/miR-137 axis contributed to lncRNA MEG3 downregulation-mediated malignant transformation of human bronchial epithelial cells.

Nickel pollution is a recognized factor contributing to lung cancer. Understanding the molecular mechanisms of its carcinogenic effects is crucial for lung cancer prevention and treatment. Our previous research identified the downregulation of a long noncoding RNA, maternally expressed gene 3 (MEG3), as a key factor in transforming human bronchial epithelial cells (HBECs) into malignant cells following nickel exposure. In our study, we found that deletion of MEG3 also reduced the expression of RhoGDIß. Notably, artificially increasing RhoGDIß levels counteracted the malignant transformation caused by MEG3 deletion in HBECs. This indicates that the reduction in RhoGDIß contributes to the transformation of HBECs due to MEG3 deletion. Further exploration revealed that MEG3 downregulation led to enhanced c-Jun activity, which in turn promoted miR-200c transcription. High levels of miR-200c subsequently increased the translation of AUF1 protein, stabilizing SOX2 messenger RNA (mRNA). This stabilization affected the regulation of miR-137, SP-1 protein translation, and the suppression of RhoGDIß mRNA transcription and protein expression, leading to cell transformation. Our study underscores the co-regulation of RhoGDIß expression by long noncoding RNA MEG3, multiple microRNAs (miR-200c and miR-137), and RNA-regulated transcription factors (c-Jun, SOX2, and SP1). This intricate network of molecular events sheds light on the nature of lung tumorigenesis. These novel findings pave the way for developing targeted strategies for the prevention and treatment of human lung cancer based on the MEG3/RhoGDIß pathway.

MALAT1 expression in granulosa cells in PCOS patients with different phenotypes.

Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine metabolic disorders. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) reportedly can regulate the reproductive system. Despite studies, the alteration of MALAT1 expression in granulosa cells (GCs) from PCOS patients was inconsistent. To evaluate MALAT1 expression in GCs in different PCOS subgroups and its association with PCOS phenotypes, we collected GCs from 110 PCOS cases and 71 controls, and examined MALAT1 expression by quantitative PCR. The results showed MALAT1 expression was upregulated in PCOS cases, especially in insulin resistant (IR) PCOS subgroup, obese PCOS subgroup and non-hyperandrogenic (NHA) PCOS subgroup. MALAT1 expression was positively correlated with BMI and several metabolic parameters in controls. Interestingly, MALAT1 expression was notably associated with some critical endocrine indexes for PCOS, including E2, FSH, LH and LH/FSH ratio. In different PCOS subgroups, we found significant positive correlations with LH/FSH ratio in IR-PCOS and PCOS with normal weight, and with serum T and LH level in NHA-PCOS subgroup. Integrated analysis with lncRNA target databases and PCOS-related databases revealed MALAT1 could participate in PCOS by influencing immune response and lipids metabolism in GCs. In conclusion, MALAT1 was differently expressed in GCs in PCOS, especially in IR, obese and NHA PCOS subgroups. MALAT1 was likely involved in metabolism and immune response in GCs in PCOS. However, more studies are necessary to establish this concept.