Succinate utilisation by Salmonella is inhibited by multiple regulatory systems.

Succinate is a potent immune signalling molecule that is present in the mammalian gut and within macrophages. Both of these infection niches are colonised by the pathogenic bacterium Salmonella enterica serovar Typhimurium during infection. Succinate is a C4-dicarboyxlate that can serve as a source of carbon for bacteria. When succinate is provided as the sole carbon source for in vitro cultivation, Salmonella and other enteric bacteria exhibit a slow growth rate and a long lag phase. This growth inhibition phenomenon was known to involve the sigma factor RpoS, but the genetic basis of the repression of bacterial succinate utilisation was poorly understood. Here, we use an experimental evolution approach to isolate fast-growing mutants during growth of S. Typhimurium on succinate containing minimal medium. Our approach reveals novel RpoS-independent systems that inhibit succinate utilisation. The CspC RNA binding protein restricts succinate utilisation, an inhibition that is antagonised by high levels of the small regulatory RNA (sRNA) OxyS. We discovered that the Fe-S cluster regulatory protein IscR inhibits succinate utilisation by repressing the C4-dicarboyxlate transporter DctA. Furthermore, the ribose operon repressor RbsR is required for the complete RpoS-driven repression of succinate utilisation, suggesting a novel mechanism of RpoS regulation. Our discoveries shed light on the redundant regulatory systems that tightly regulate the utilisation of succinate. We speculate that the control of central carbon metabolism by multiple regulatory systems in Salmonella governs the infection niche-specific utilisation of succinate.

Fermentation Practices Select for Thermostable Endolysins in Phages.

Endolysins are produced by (bacterio)phages and play a crucial role in degrading the bacterial cell wall and the subsequent release of new phage progeny. These lytic enzymes exhibit a remarkable diversity, often occurring in a multimodular form that combines different catalytic and cell wall-binding domains, even in phages infecting the same species. Yet, our current understanding lacks insight into how environmental factors and ecological niches may have influenced the evolution of these enzymes. In this study, we focused on phages infecting Streptococcus thermophilus, as this bacterial species has a well-defined and narrow ecological niche, namely, dairy fermentation. Among the endolysins found in phages targeting this species, we observed limited diversity, with a singular structural type dominating in most of identified S. thermophilus phages. Within this prevailing endolysin type, we discovered a novel and highly conserved calcium-binding motif. This motif proved to be crucial for the stability and activity of the enzyme at elevated temperatures. Ultimately, we demonstrated its positive selection within the host's environmental conditions, particularly under the temperature profiles encountered in the production of yogurt, mozzarella, and hard cheeses that rely on S. thermophilus.

Phage endolysins are adapted to specific hosts and are evolutionarily dynamic.

Endolysins are produced by (bacterio)phages to rapidly degrade the bacterial cell wall and release new viral particles. Despite sharing a common function, endolysins present in phages that infect a specific bacterial species can be highly diverse and vary in types, number, and organization of their catalytic and cell wall binding domains. While much is now known about the biochemistry of phage endolysins, far less is known about the implication of their diversity on phage-host adaptation and evolution. Using CRISPR-Cas9 genome editing, we could genetically exchange a subset of different endolysin genes into distinct lactococcal phage genomes. Regardless of the type and biochemical properties of these endolysins, fitness costs associated to their genetic exchange were marginal if both recipient and donor phages were infecting the same bacterial strain, but gradually increased when taking place between phage that infect different strains or bacterial species. From an evolutionary perspective, we observed that endolysins could be naturally exchanged by homologous recombination between phages coinfecting a same bacterial strain. Furthermore, phage endolysins could adapt to their new phage/host environment by acquiring adaptative mutations. These observations highlight the remarkable ability of phage lytic systems to recombine and adapt and, therefore, explain their large diversity and mosaicism. It also indicates that evolution should be considered to act on functional modules rather than on bacteriophages themselves. Furthermore, the extensive degree of evolvability observed for phage endolysins offers new perspectives for their engineering as antimicrobial agents.

MOTAI: A Novel Method for the Study of O-GalNAcylation and Complex O-Glycosylation in Cancer.

The Tn antigen, an immature truncated O-glycosylation, is a promising biomarker for cancer detection and diagnosis. However, reliable methods for analyzing O-GalNAcylation and complex O-glycosylation are lacking. Here, we develop a novel method, MOTAI, for the sequential analysis of O-glycosylation using different O-glycoproteases. MOTAI conjugates glycopeptides on a solid support and releases different types of O-glycosylation through sequential enzymatic digestion by O-glycoproteases, including OpeRATOR and IMPa. Because OpeRATOR has less activity on O-GalNAcylation, MOTAI enriches O-GalNAcylation for subsequent analysis. We demonstrate the effectiveness of MOTAI by analyzing fetuin O-glycosylation and Jurkat cell lines. We then apply MOTAI to analyze colorectal cancer and benign colorectal polyps. We identify 32 Tn/sTn-glycoproteins and 43 T/sT-glycoproteins that are significantly increased in tumor tissues. Gene Ontology analysis reveals that most of these proteins are ECM proteins involved in the adhesion process of the intercellular matrix. Additionally, the protein disulfide isomerase CRELD2 has a significant difference in Tn expression, and the abnormally glycosylated T345 and S349 O-glycosylation sites in cancer group samples may promote the secretion of CRELD2 and ultimately tumorigenesis through ECM reshaping. In summary, MOTAI provides a powerful new tool for the in-depth analysis of O-GalNAcylation and complex O-glycosylation. It also reveals the upregulation of Tn/sTn-glycoproteins in colorectal cancer, which may provide new insights into cancer biology and biomarker discovery.

Immune Regulation Patterns in Response to Environmental Pollutant Chromate Exposure-Related Genetic Damage: A Cross-Sectional Study Applying Machine Learning Methods.

Exposure to hexavalent chromium damages genetic materials like DNA and chromosomes, further elevating cancer risk, yet research rarely focuses on related immunological mechanisms, which play an important role in the occurrence and development of cancer. We investigated the association between blood chromium (Cr) levels and genetic damage biomarkers as well as the immune regulatory mechanism involved, such as costimulatory molecules, in 120 workers exposed to chromates. Higher blood Cr levels were linearly correlated with higher genetic damage, reflected by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and blood micronucleus frequency (MNF). Exploratory factor analysis revealed that both positive and negative immune regulation patterns were positively associated with blood Cr. Specifically, higher levels of programmed cell death protein 1 (PD-1; mediated proportion: 4.12%), programmed cell death ligand 1 (PD-L1; 5.22%), lymphocyte activation gene 3 (LAG-3; 2.11%), and their constitutive positive immune regulation pattern (5.86%) indirectly positively influenced the relationship between blood Cr and urinary 8-OHdG. NOD-like receptor family pyrin domain containing 3 (NLRP3) positively affected the association between blood Cr levels and inflammatory immunity. This study, using machine learning, investigated immune regulation and its potential role in chromate-induced genetic damage, providing insights into complex relationships and emphasizing the need for further research.

Strain-induced excellent photocatalytic performance in Z-scheme BlueP/γ-SnS heterostructures for water splitting.

Constructing Z-scheme heterojunction photocatalysts with high solar-to-hydrogen (STH) efficiency is a practical alternative to produce clean and recyclable hydrogen energy on a large scale. This paper presents the design of stable Z-scheme blue phosphorene (BlueP)/γ-SnS heterostructures with excellent photocatalytic activities by applying strains. The first-principles calculations show that the BlueP/γ-SnS heterobilayer is a type-I heterojunction with an indirect bandgap of 1.41 eV and strong visible-light absorption up to 105 cm-1. Interestingly, biaxial strains (ε) can effectively regulate its bandgap width (semiconductor-metal) and induce the band alignment transition (type-I-type-II). Compressive and tensile strains can significantly enhance the interfacial interaction and visible-light absorption, respectively. More intriguingly, compressive strains can not only modulate the heterojunction types but also make the band edges meet the requirements for overall water splitting. In particular, the Z-scheme (type-I) BlueP/γ-SnS bilayer at -8% (-2%) strain exhibits a relatively high STH efficiency of 18% (17%), and the strained Z-scheme system (-8% ≤ ε ≤ -6%) also exhibits high and anisotropic carrier mobilities (158-2327 cm2 V-1 s-1). These strain-induced outstanding properties make BlueP/γ-SnS heterostructures promising candidates for constructing economically feasible photocatalysts and flexible nanodevices.

Pregnancy induced hypertension and umbilical cord blood DNA methylation in newborns: an epigenome-wide DNA methylation study.

OBJECTIVIES: Pregnancy induced hypertension (PIH) syndrome is a disease that unique to pregnant women and is associated with elevated risk of offspring cardiovascular diseases (CVDs) and neurodevelopmental disorders in their kids. Previous research on cord blood utilizing the Human Methylation BeadChip or EPIC array revealed that PIH is associated with specific DNA methylation site. Here, we investigate the whole genome DNA methylation landscape of cord blood from newborns of PIH mother. METHODS: Whole-genome bisulfite sequencing (WGBS) was used to examine the changes in whole genome DNA methylation in the umbilical cord blood of three healthy (NC) and four PIH individuals. Using methylKit, we discovered Hypo- and hyper- differentially methylated probes (DMPs) or methylated regions (DMRs) in the PIH patients' cord blood DNA. Pathway enrichments were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays. DMPs or DMRs relevant to the immunological, neurological, and circulatory systems were also employed for enrichment assay, Metascape analysis and PPI network analysis. RESULTS: 520 hyper- and 224 hypo-DMPs, and 374 hyper- and 186 hypo-DMRs between NC and PIH group, respectively. Both DMPs and DMRs have enhanced pathways for cardiovascular, neurological system, and immune system development. Further investigation of DMPs or DMRs related to immunological, neurological, and circulatory system development revealed that TBK1 served as a hub gene for all three developmental pathways. CONCLUSION: PIH-associated DMPs or DMRs in umbilical cord blood DNA may play a role in immunological, neurological, and circulatory system development. Abnormal DNA methylation in the immune system may also contribute to the development of CVDs and neurodevelopment disorders.

Rapid and simultaneous detection of five mycotoxins and their analogs with a gold nanoparticle-based multiplex immuno-strip sensor.

Mycotoxins, as secondary metabolites produced by fungi, have been the focus of researchers in various countries and are considered to be one of the major risk factors in agricultural products. There is an urgent need for a rapid, simple and high-performance method to detect residues of harmful mycotoxins in agricultural foods. We have developed a gold nanoparticle-based multiplexed immunochromatographic strip biosensor that can simultaneously detect fifteen mycotoxins in cereal samples. With this optimized procedure, five representative mycotoxins, deoxynivalenol (DON), zearalenone (ZEN), T-2 toxin (T-2), tenuazonic acid (TEA) and alternariol (AOH) were detected in the range of 0.91-4.77, 0.04-0.56, 0.11-0.68, 0.12-1.02 and 0.09-0.75 ng/mL, respectively. The accuracy and stability of these measurements were demonstrated by analysis of spiked samples with recoveries of 91.8%-115.3% and coefficients of variation <8.7%. In addition, commercially available samples of real cereals were tested using the strips and showed good agreement with the results verified by LC-MS/MS. Therefore, Our assembled ICA strips can be used for the simultaneous detection of 5 mycotoxins and their analogs (15 mycotoxins in total) in grain samples, and the results were consistent between different types of cereal foods, this multiplexed immunochromatographic strip biosensor can be used as an effective tool for the primary screening of mycotoxin residues in agricultural products.

Sagittal en bloc resection of thoracolumbar tumours: a report of thirty one cases.

PURPOSE: To develop a novel classification of sagittal en bloc resection (SEBR) based on anatomical locations for thoracolumbar spine tumors and assess the clinical outcomes of this surgical procedure. METHODS: 31 patients with thoracolumbar tumours treated with SEBR were enrolled in this study. The individualized surgical strategy was adopted based on our surgical classification. Demographics, perioperative outcomes, complications and postoperative outcomes were assessed. RESULTS: Based on our surgical classifications, patients were divided into four types. All bony resection margins were negative, wide resection was achieved in 25 patients, marginal resection in four, and intralesional resection in two. 18 patients underwent anterior reconstruction. Complications were encountered in five patients, and instrumentation failure occurred in one patient. The median follow-up was 24 (range, 6-72) months and recurrence was found in only one patient. CONCLUSION: SEBR is a safe and effective surgical procedure for patients with thoracolumbar spinal tumours in specific anatomical locations. The proposed surgical classification covers all SEBR types and is easy to apply, it may assist surgical decision-making in patients with spinal tumours.

Relationships between blood chromium exposure and liver injury: Exploring the mediating role of systemic inflammation in a chromate-exposed population.

Hexavalent chromium and its compounds are prevalent pollutants, especially in the work environment, pose a significant risk for multisystem toxicity and cancers. While it is known that chromium accumulation in the liver can cause damage, the dose-response relationship between blood chromium (Cr) and liver injury, as well as the possible potential toxic mechanisms involved, remains poorly understood. To address this, we conducted a follow-up study of 590 visits from 305 participants to investigate the associations of blood Cr with biomarkers for liver injury, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL), and to evaluate the mediating effects of systemic inflammation. Platelet (PLT) and the platelet-to-lymphocyte ratio (PLR) were utilized as biomarkers of systemic inflammation. In the linear mixed-effects analyses, each 1-unit increase in blood Cr level was associated with estimated effect percentage increases of 0.82% (0.11%, 1.53%) in TBIL, 1.67% (0.06%, 3.28%) in DBIL, 0.73% (0.04%, 1.43%) in ALT and 2.08% (0.29%, 3.87%) in AST, respectively. Furthermore, PLT mediated 10.04%, 11.35%, and 10.77% increases in TBIL, DBIL, and ALT levels induced by chromate, respectively. In addition, PLR mediated 8.26% and 15.58% of the association between blood Cr and TBIL or ALT. These findings shed light on the mechanisms underlying blood Cr-induced liver injury, which is partly due to worsening systemic inflammation.

Proprotein convertase furina is required for heart development in zebrafish.

Cardiac looping and trabeculation are key processes during cardiac chamber maturation. However, the underlying mechanisms remain incompletely understood. Here, we report the isolation, cloning and characterization of the proprotein convertase furina from the cardiovascular mutant loft in zebrafish. loft is an ethylnitrosourea-induced mutant and has evident defects in the cardiac outflow tract, heart looping and trabeculation, the craniofacial region and pharyngeal arch arteries. Positional cloning revealed that furina mRNA was barely detectable in loft mutants, and loft failed to complement the TALEN-induced furina mutant pku338, confirming that furina is responsible for the loft mutant phenotypes. Mechanistic studies demonstrated that Notch reporter Tg(tp1:mCherry) signals were largely eliminated in mutant hearts, and overexpression of the Notch intracellular domain partially rescued the mutant phenotypes, probably due to the lack of Furina-mediated cleavage processing of Notch1b proteins, the only Notch receptor expressed in the heart. Together, our data suggest a potential post-translational modification of Notch1b proteins via the proprotein convertase Furina in the heart, and unveil the function of the Furina-Notch1b axis in cardiac looping and trabeculation in zebrafish, and possibly in other organisms.

Enhanced Goos-Hänchen shift in a defective Pell quasiperiodic photonic crystal with monolayer MoS2.

Monolayer M o S 2 has attracted wide attention because of its finite bandgap, and it has become a potential candidate for the investigation of the Goos-Hänchen (GH) shift. However, the magnitude of the GH shift in free-standing monolayer M o S 2 is small, which greatly hinders its possible applications in the photoelectric sensors and detectors. We have theoretically designed a defective quasiperiodic photonic crystal and investigated its GH shift, where monolayer M o S 2 is sandwiched between two quasiperiodic photonic crystals arranged by the Pell sequence. By optimizing the thicknesses of all the components and the period number of the Pell quasiperiodic photonic crystal, we find that the GH shift of the designed structure is significantly enhanced at the specific working wavelength. In addition, we discuss the influence of the thicknesses of the dielectric components on the GH shift. Our work confirms that the quasiperiodic photonic crystal structure has the ability to enhance the GH shift of monolayer transition metal dichalcogenides, which provides a new platform for the GH investigations and greatly promotes the applications of this defective structure in optoelectric devices.

High-power tapered two-section distributed feedback laser based on a chirped sampled grating.

We propose and theoretically study a two-section high-power distributed feedback (DFB) laser with three equivalent phase shifts (3EPSs). A tapered waveguide with a chirped sampled grating is introduced to amplify the output power and keep a stable single-mode operation. The simulation exhibits the maximum output power and side mode suppression ratio of a 1200 µm length two-section DFB laser as high as 306.5 mW and 40 dB, respectively. Compared with traditional DFB lasers, the proposed laser has a higher output power, which may benefit wavelength division multiplexing transmission systems, gas sensors, and large-scale silicon photonics.

Highly sensitive temperature and refractive index sensor based on no-core fiber cascaded with a balloon-shaped bent single-mode fiber.

A highly sensitive temperature and refractive index (RI) sensor based on no-core fiber (NCF) cascaded with a balloon-shaped bent single-mode fiber (BSBSF) is proposed and demonstrated. The NCF can excite higher-order modes which will be concentrated and transmitted into the BSBSF due to the characteristic of self-imaging effect. The BSBSF has an excellent temperature performance due to the high thermo-optical coefficient and thermal expansion coefficient of the polymer coating. The NCF and BSBSF are both conducive to the excitation of higher-order modes, which induces the sensitivity of the sensor with an efficiency improvement. The experimental results show that the maximum temperature sensitivity is -3.19n m/ ∘ C in the range of 22°C-83°C, which is the highest temperature sensitivity in the cascaded BSBSF structure to our best knowledge. In addition, the maximum RI sensitivity is 232.16 nm/RIU when the RI changes from 1.3234 to 1.3512. Compared with other cascaded BSBSF structures, this sensor has a higher temperature sensitivity and can be applicated in the prospects of food, biology, and environmental monitoring.

The efficacy and safety of short-course neoadjuvant denosumab for en bloc spondylectomy in spinal giant cell tumor of bone: a preliminary report.

PURPOSE: This study aimed to investigate whether short course of neoadjuvant denosumab treatment for spinal GCTB could (1) Induce radiological and histological response? (2) Facilitate en bloc resection? (3) Achieve satisfactory oncological and functional outcomes? METHODS: The clinical information of ten consecutive patients between 2018 and 2022 with spinal GCTB treated with short course of neoadjuvant denosumab (≤ 5 doses) and en bloc spondylectomy was retrospectively reviewed. The radiological and histological response, operative data, oncological and functional outcomes were analyzed. RESULTS: The mean doses of neoadjuvant denosumab were 4.2 (range 3-5 doses). After neoadjuvant denosumab, there were 9 cases showing new ossification and 5 cases with reappearance of cortical integrity. The values of Hounsfield units (HU) of the soft tissue component were increased by > 50% in 7 cases. The signal intensity (SI) ratios of tumor/muscle in T2WI of plain MRI were decreased by > 10% in 60% of the cases. Shrinkage of soft tissue mass by > 10% was observed in 4 cases. The mean duration of operation was 575 ± 174 min, and the mean estimated blood loss (EBL) was 2790 ± 1934 ml. No obvious adhesion to dura mater or major vessels was encounter intraoperatively. There is no tumor collapse or breakage during surgery. Multinucleated giant cells were decreased in 6 cases (60%) with the remaining 4 cases showing absence of multinucleated giant cells. Mononuclear stromal cells existed in most of the cases (8 cases, 80%). New bone formation was noticed in 8 cases (80%). No patient had a worsening of neurologic function after surgery. No tumor recurrence was noticed within the mean follow-up of 24 ± 20 months. CONCLUSION: Short-term neoadjuvant denosumab could yield radiological and histological responses and might facilitate en bloc spondylectomy by hardening the tumor and causing less adhesion to segmental vessels, major vessels and nerve roots, which was beneficial to achieve the optimal oncological and functional outcomes.

Surgical outcomes and risk factors for surgical complications after en bloc resection following reconstruction with 3D-printed artificial vertebral body for thoracolumbar tumors.

BACKGROUND: The outcomes of patients with tumors of the thoracolumbar spine treated with en bloc resection (EBR) using three-dimensional (3D)-printed endoprostheses are underreported. METHODS: We retrospectively evaluated patients with thoracolumbar tumors who underwent surgery at our institution. Logistic regression analysis was performed to identify the potential risk factors for surgical complications. Nomograms to predict complications were constructed and validated. RESULTS: A total of 53 patients with spinal tumors underwent EBR at our hospital; of these, 2 were lost to follow-up, 45 underwent total en bloc spondylectomy, and 6 were treated with sagittal en bloc spondylectomy. The anterior reconstruction materials included a customized 3D-printed artificial vertebral body (AVB) in 10 cases and an off-the-shelf 3D-printed AVB in 41 cases, and prosthesis mismatch occurred in 2 patients reconstructed with the off-the-shelf 3D-printed AVB. The median follow-up period was 21 months (range, 7-57 months). Three patients experienced local recurrence, and 5 patients died at the final follow-up. A total of 50 perioperative complications were encountered in 29 patients, including 25 major and 25 minor complications. Instrumentation failure occurred in 1 patient, and no prosthesis subsidence was observed. Using a combined surgical approach was a dependent predictor of overall complications, while Karnofsky performance status score, lumbar spine lesion, and intraoperative blood loss ≥ 2000 mL were predictors of major complications. Nomograms for the overall and major complications were constructed using these factors, with C-indices of 0.850 and 0.891, respectively. CONCLUSIONS: EBR is essential for the management of thoracolumbar tumors; however, EBR has a steep learning curve and a high complication rate. A 3D-printed AVB is an effective and feasible reconstruction option for patients treated with EBR.

Evasion of MAIT cell recognition by the African Salmonella Typhimurium ST313 pathovar that causes invasive disease.

Mucosal-associated invariant T (MAIT) cells are innate T lymphocytes activated by bacteria that produce vitamin B2 metabolites. Mouse models of infection have demonstrated a role for MAIT cells in antimicrobial defense. However, proposed protective roles of MAIT cells in human infections remain unproven and clinical conditions associated with selective absence of MAIT cells have not been identified. We report that typhoidal and nontyphoidal Salmonella enterica strains activate MAIT cells. However, S. Typhimurium sequence type 313 (ST313) lineage 2 strains, which are responsible for the burden of multidrug-resistant nontyphoidal invasive disease in Africa, escape MAIT cell recognition through overexpression of ribB This bacterial gene encodes the 4-dihydroxy-2-butanone-4-phosphate synthase enzyme of the riboflavin biosynthetic pathway. The MAIT cell-specific phenotype did not extend to other innate lymphocytes. We propose that ribB overexpression is an evolved trait that facilitates evasion from immune recognition by MAIT cells and contributes to the invasive pathogenesis of S. Typhimurium ST313 lineage 2.

A Mixed-Reality-Based Unknown Space Navigation Method of a Flexible Manipulator.

A hyper-redundant flexible manipulator is characterized by high degree(s) of freedom (DoF), flexibility, and environmental adaptability. It has been used for missions in complex and unknown spaces, such as debris rescue and pipeline inspection, where the manipulator is not intelligent enough to face complex situations. Therefore, human intervention is required to assist in decision-making and control. In this paper, we designed an interactive navigation method based on mixed reality (MR) of a hyper-redundant flexible manipulator in an unknown space. A novel teleoperation system frame is put forward. An MR-based interface was developed to provide a virtual model of the remote workspace and virtual interactive interface, allowing the operator to observe the real-time situation from a third perspective and issue commands to the manipulator. As for environmental modeling, a simultaneous localization and mapping (SLAM) algorithm based on an RGB-D camera is applied. Additionally, a path-finding and obstacle avoidance method based on artificial potential field (APF) is introduced to ensure that the manipulator can move automatically under the artificial command in the remote space without collision. The results of the simulations and experiments validate that the system exhibits good real-time performance, accuracy, security, and user-friendliness.

HDAC5 inactivates CYR61-regulated CD31/mTOR axis to prevent the occurrence of preeclampsia.

Our study was to pinpoint the significance of histone deacetylase 5 (HDAC5) affecting the pathogenesis of preeclampsia (PE) via CD31/mammalian target of rapamycin (mTOR) axis by regulating cysteine-rich angiogenic inducer 61 (CYR61). Expression of HDAC5, CYR61, and CD31/mTOR in placental tissues of patients with PE and trophoblast cells HTR-8/SVneo cells was determined first followed by their interaction analysis. Following different transfection, the significance of HDAC5 in cell functions was assayed in relation to CYR61 and CD31/mTOR. An in vivo PE mouse model was constructed for further validation. The clinical tissue and in vitro cell experimentations discovered that HDAC5 was downregulated in placental tissues of PE patients and trophoblast cells, while CYR61, CD31, mTOR, and p-mTOR displayed upregulation. After overexpression of HDAC5, trophoblast cell functions were enhanced. HDAC5 reduced the acetylation enrichment of H3K27 to inhibit the expression of CYR61. Furthermore, CYR61 promoted the activation of CD31/mTOR axis, thereby inhibiting HTR-8/SVneo cell functions. The in vivo rat model confirmed the above alterations. Taken together, HDAC5 contributes to downregulation of CYR61 through histone deacetylation, inactivating CD31/mTOR axis, which prevents the occurrence and development of PE.

Long non-coding RNA CYTOR modulates cancer progression through miR-136-5p/MAT2B axis in renal cell carcinoma.

BACKGROUND: To explore the role of long noncoding RNAs (lncRNAs) cytoskeleton regulator RNA (CYTOR) in renal cell carcinoma (RCC). METHODS: The levels of CYTOR in RCC tissues and cell lines were detected by RT-qPCR. 786-O and Caki-1 cells were transfected with CYTOR-shRNA or pcDNA-CYTOR respectively, or co-transfected with CYTOR-shRNA and miR-136-5p inhibitor, or co-transfected with miR-136-5p mimic and pcDNA-MAT2B. MTT assay, Transwell assay and flow cytometry were used to evaluate cell proliferation, invasion and apoptosis. The relationship between lncRNA CYTOR and miRNA-136-5p was detected by dual luciferase reporter gene and RNA pull down assays, and the targeted relationship between miRNA-136-5p and MAT2B was verified by dual luciferase reporter gene assay. The interaction between MAT2B and BAG3 protein was verified by co-IP experiment. The role of lncRNA CYTOR in vivo was also examined. RESULTS: LncRNA CYTOR was up-regulated in RCC tissues and cell lines, and miR-136-5p was down-regulated in renal carcinoma cell lines and tissues. Downregulation of CYTOR inhibited cell proliferation and invasion and promoted apoptosis. miR-136-5p was sponged by lncRNA CYTOR, which negatively regulated the development of RCC. MAT2B was a target gene of miR-136-5p. MAT2B protein interacted directly with BAG3 protein to affect the proliferation, invasion and apoptosis of RCC cells. In vivo experiments showed that the expression level of miR-136-5p was increased, and MAT2B expression was decreased after CYTOR knockdown, thereby inhibiting the development of RCC. CONCLUSIONS: LncRNA CYTOR promoted the progression of RCC by targeting miR-136-5p to regulate the target gene MAT2B, which interacted with BAG3 protein.