LINC01480 as a Prognostic Biomarker Associated With Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: The present study aimed to identify key long noncoding RNAs (lncRNAs) involved in survival and metastasis of clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: A systemic screening for genes with differential expression in ccRCC was performed using publicly available databases. Cox regression analysis was used to identify lncRNAs associated with survival. A competing endogenous RNAs (ceRNA) regulation network of metastasis-related lncRNAs was constructed and hub lncRNAs were identified. Functional and pathway enrichment analyses were performed to investigate the role of lncRNA in ccRCC. Cell Counting Kit-8 and Transwell assays were used to determine the levels of cell proliferation, migration, and invasion. RESULTS: A total of 732 lncRNAs were found to be differentially expressed between ccRCC tumors and healthy samples. Among them, 139 lncRNAs were differentially expressed between metastasis and non-metastasis ccRCC samples and 75 lncRNAs were associated with overall survival and curated metastasis-related genes. Notably, LINC01480 was identified as the hub lncRNA involved in regulation of ccRCC metastasis. Clinically, LINC01480 may act as an independent factor for poor overall survival of ccRCC patients (log-rank p<0.05). Reverse transcription-quantitative PCR analysis validated that LINC01480 was significantly up-regulated in ccRCC compared to paired normal samples (n=20). Moreover, LINC01480 silencing inhibited the proliferation, migration, and invasion of ccRCC cells in vitro. Gene set enrichment analysis showed that high LINC01480 expression may promote ccRCC metastasis through enhancing immunodeficiency and amino acid metabolism. CONCLUSION: LINC01480 may act as a novel biomarker for overall prognosis in ccRCC and exhibit potential as a therapeutic target for the treatment of metastatic ccRCC.

Characterization difference of typical KL1, KL2 and ST11-KL64 hypervirulent and carbapenem-resistant Klebsiella pneumoniae.

Almost all the formation of hypervirulent and carbapenem-resistant Klebsiella pneumoniae follow two major patterns: KL1/KL2 hvKP strains acquire carbapenem-resistance plasmids (CR-hvKP), and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains obtain virulence plasmids (hv-CRKP). These two patterns may pose different phenotypes. In this study, three typical resistance and hypervirulent K. pneumoniae (KL1, KL2, and ST11-KL64), isolating from poor prognosis patients, were selected. Compared with ST11-KL64 hv-CRKP, KL1/KL2 hypervirulent lineages harbor significantly fewer resistance determinants and exhibited lower-level resistance to antibiotics. Notably, though the blaKPC gene could be detected in all these isolates, KL1/KL2 hvKP strain did not exhibit corresponding high-level carbapenem resistance. Unlike the resistance features, we did not observe significant virulence differences between the three strains. The ST11-KL64 hv-CRKP (1403) in this study, showed similar mucoviscosity, siderophores production, and biofilm production compared with KL1 and KL2 hvKP. Moreover, the hypervirulent of ST11-KL64 hvKP also verified with the human lung epithelial cells infection and G. mellonella infection models. Moreover, we found the pLVPK-like virulence plasmid and IncF blaKPC-2 plasmid was crucial for the formation of hypervirulent and carbapenem-resistant K. pneumoniae. The conservation of origin of transfer site (oriT) in these virulence and blaKPC-2 plasmids, indicated the virulence plasmids could transfer to CRKP with the help of blaKPC-2 plasmids. The co-existence of virulence plasmid and blaKPC-2 plasmid facilitate the formation of ST11-KL64 hv-CPKP, which then become nosocomial epidemic under the antibiotic stress. The ST11-KL64 hv-CPKP may poses a substantial threat to healthcare networks, urgent measures were needed to prevent further dissemination in nosocomial settings.

Two independent allohexaploidizations and genomic fractionation in Solanales.

Solanales, an order of flowering plants, contains the most economically important vegetables among all plant orders. To date, many Solanales genomes have been sequenced. However, the evolutionary processes of polyploidization events in Solanales and the impact of polyploidy on species diversity remain poorly understood. We compared two representative Solanales genomes (Solanum lycopersicum L. and Ipomoea triloba L.) and the Vitis vinifera L. genome and confirmed two independent polyploidization events. Solanaceae common hexaploidization (SCH) and Convolvulaceae common hexaploidization (CCH) occurred ∼43-49 and ∼40-46 million years ago (Mya), respectively. Moreover, we identified homologous genes related to polyploidization and speciation and constructed multiple genomic alignments with V. vinifera genome, providing a genomic homology framework for future Solanales research. Notably, the three polyploidization-produced subgenomes in both S. lycopersicum and I. triloba showed significant genomic fractionation bias, suggesting the allohexaploid nature of the SCH and CCH events. However, we found that the higher genomic fractionation bias of polyploidization-produced subgenomes in Solanaceae was likely responsible for their more abundant species diversity than that in Convolvulaceae. Furthermore, through genomic fractionation and chromosomal structural variation comparisons, we revealed the allohexaploid natures of SCH and CCH, both of which were formed by two-step duplications. In addition, we found that the second step of two paleohexaploidization events promoted the expansion and diversity of ß-amylase (BMY) genes in Solanales. These current efforts provide a solid foundation for future genomic and functional exploration of Solanales.

A common whole-genome paleotetraploidization in Cucurbitales.

Cucurbitales are an important order of flowering plants known for encompassing edible plants of economic and medicinal value and numerous ornamental plants of horticultural value. By reanalyzing the genomes of two representative families (Cucurbitaceae and Begoniaceae) in Cucurbitales, we found that the previously identified Cucurbitaceae common paleotetraploidization that occurred shortly after the core-eudicot-common hexaploidization event is shared by Cucurbitales, including Begoniaceae. We built a multigenome alignment framework for Cucurbitales by identifying orthologs and paralogs and systematically redating key evolutionary events in Cucurbitales. Notably, characterizing the gene retention levels and genomic fractionation patterns between subgenomes generated from different polyploidizations in Cucurbitales suggested the autopolyploid nature of the Begoniaceae common tetraploidization and the allopolyploid nature of the Cucurbitales common tetraploidization and the Cucurbita-specific tetraploidization. Moreover, we constructed the ancestral Cucurbitales karyotype comprising 17 proto-chromosomes, confirming that the most recent common ancestor of Cucurbitaceae contained 15 proto-chromosomes and rejecting the previous hypothesis for an ancestral Cucurbitaceae karyotype with 12 proto-chromosomes. In addition, we found that the polyploidization and tandem duplication events promoted the expansion of gene families involved in the cucurbitacin biosynthesis pathway; however, gene loss and chromosomal rearrangements likely limited the expansion of these gene families.

Osteotomized debridement versus curetted debridement in posterior approach in treating thoracolumbar tuberculosis: a comparative study.

PURPOSE: This study aimed to compare osteotomized debridement (OD) with traditional curetted debridement (CD) in treating thoracolumbar tuberculosis (TB). METHODS: A total of 188 patients were diagnosed with active thoracolumbar TB and underwent one-stage posterior surgery at our institution. Of the 188 patients, 85 patients were treated with OD, and 103 patients were treated with traditional CD. The patient information, laboratory results, imaging findings, and clinical effectiveness were, respectively, compared between the two groups. RESULTS: Group OD consumed less operation time and blood loss than group CD (P < 0.05 for both values). No significant difference in hospitalization time was found between the two groups (P > 0.05). The values of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in both groups returned to the normal range within one month postoperatively. All patients had significant improvement in visual analog scale (VAS) and oswestry disability index (ODI) postoperatively. The mean fusion time in group OD was shorter than that in group CD (P < 0.05). There was no statistically significant difference in preoperative kyphotic angle between the two groups (P > 0.05), but group OD showed less correction loss than group CD at the final follow-up (P < 0.05). The rate of recurrence and surgery-related complications in group OD was lower than group CD. CONCLUSIONS: Posterior OD, reconstruction with titanium mesh cages (TMCs), and instrumentation is feasible and effective in treating thoracolumbar TB. Compared with the traditional CD, OD can achieve radical lesion removal, more effective kyphosis correction, lower recurrence rate, and fewer complications.

Case Report of Angular Post-Tuberculotic Kyphosis Corrected Through Pedicle Subtraction Osteotomy Above C7.

BACKGROUND AND IMPORTANCE: Angular cervical kyphosis and its association with syringomyelia were rarely described. Correcting this kind of deformity from the front is extremely difficult or even impossible. Meanwhile, no study has made a report about correcting angular cervical kyphosis through pedicle subtraction osteotomy (PSO) above C7 because of the special anatomy of the vertebral artery. This is the first case of cervical deformity correction through PSO above C7. CLINICAL PRESENTATION: We present the case of a 52-yr-old man who previously underwent debridement, decompression, and skull traction for cervical tuberculosis at age 6 yr. The sequelae of right-hand weakness occurred after surgery, and cervical kyphosis formed gradually. The patient recently started to complain of a severe neck pain. X-rays showed a cervical sagittal malalignment due to the angular kyphosis. Computed tomography scans revealed a fused angular kyphosis at C6-7, and MRI showed a long syringomyelia distal to the kyphosis. The definite diagnosis of the patient was post-tuberculotic cervical angular kyphosis, and because of the extremely narrow surgery corridor from the front, we decided to perform the surgery in a posterior approach. Hence, the patient was treated with the PSO with a long-segment pedicle screw fixation from C3 to T5 and received satisfactory angular kyphosis correction. CONCLUSION: PSO above C7 to correct angular cervical kyphosis is feasible and reasonable when there is no other better solution, and it can achieve a satisfactory kyphotic deformity correction.

LncRNA FOXP4-AS1 Promotes Progression of Ewing Sarcoma and Is Associated With Immune Infiltrates.

Ewing sarcoma (ES) is a highly malignant primary bone tumor with poor prognosis. Studies have shown that abnormal expression of lncRNA influences the prognosis of tumor patients. Herein, we established that FOXP4-AS1 was up-regulated in ES and this correlated with poor prognosis. Further analysis illustrated that FOXP4-AS1 down-regulation repression growth, migration, along with invasion of ES. On the contrary, up-regulation of FOXP4-AS1 promoted the growth, migration, as well as invasion of ES. To explore the mechanism of FOXP4-AS1, Spearman correlation analysis was carried out to determine genes that were remarkably linked to FOXP4-AS1 expression. The potential functions and pathways involving FOXP4-AS1 were identified by GO analysis, Hallmark gene set enrichment analysis, GSEA, and GSVA. The subcellular fractionation results illustrated that FOXP4-AS1 was primarily located in the cytoplasm of ES cells. Then a ceRNA network of FOXP4-AS1 was constructed. Analysis of the ceRNA network and GSEA yielded two candidate mRNAs for FOXP4-AS1. Results of the combined survival analysis led us to speculate that FOXP4-AS1 may affect the expression of TMPO by sponging miR-298, thereby regulating the malignant phenotype of ES. Finally, we found that FOXP4-AS1 may modulates the tumor immune microenvironment in an extracellular vesicle-mediated manner. In summary, FOXP4-AS1 correlates with poor prognosis of ES. It promotes the growth, migration, as well as invasion of ES cells and may modulate the tumor immune microenvironment.

Conversion between 100-million-year-old duplicated genes contributes to rice subspecies divergence.

BACKGROUND: Duplicated gene pairs produced by ancient polyploidy maintain high sequence similarity over a long period of time and may result from illegitimate recombination between homeologous chromosomes. The genomes of Asian cultivated rice Oryza sativa ssp. indica (XI) and Oryza sativa ssp. japonica (GJ) have recently been updated, providing new opportunities for investigating ongoing gene conversion events and their impact on genome evolution. RESULTS: Using comparative genomics and phylogenetic analyses, we evaluated gene conversion rates between duplicated genes produced by polyploidization 100 million years ago (mya) in GJ and XI. At least 5.19-5.77% of genes duplicated across the three rice genomes were affected by whole-gene conversion after the divergence of GJ and XI at ~ 0.4 mya, with more (7.77-9.53%) showing conversion of only portions of genes. Independently converted duplicates surviving in the genomes of different subspecies often use the same donor genes. The ongoing gene conversion frequency was higher near chromosome termini, with a single pair of homoeologous chromosomes, 11 and 12, in each rice genome being most affected. Notably, ongoing gene conversion has maintained similarity between very ancient duplicates, provided opportunities for further gene conversion, and accelerated rice divergence. Chromosome rearrangements after polyploidization are associated with ongoing gene conversion events, and they directly restrict recombination and inhibit duplicated gene conversion between homeologous regions. Furthermore, we found that the converted genes tended to have more similar expression patterns than nonconverted duplicates. Gene conversion affects biological functions associated with multiple genes, such as catalytic activity, implying opportunities for interaction among members of large gene families, such as NBS-LRR disease-resistance genes, contributing to the occurrence of the gene conversion. CONCLUSION: Duplicated genes in rice subspecies generated by grass polyploidization ~ 100 mya remain affected by gene conversion at high frequency, with important implications for the divergence of rice subspecies.

Identification of Key Reversible Intermediates in Self-Reconstructed Nickel-Based Hybrid Electrocatalysts for Oxygen Evolution.

The oxygen evolution reaction (OER) has been explored extensively for reliable hydrogen supply to boost the energy conversion efficiency. The superior OER performance of newly developed non-noble metal electrocatalysts has concealed the identification of the real active species of the catalysts. Now, the critical active phase in nickel-based materials (represented by NiNPS) was directly identified by observing the dynamic surface reconstruction during the harsh OER process via combining in situ Raman tracking and ex situ microscopy and spectroscopy analyses. The irreversible phase transformation from NiNPS to α-Ni(OH)2 and reversible phase transition between α-Ni(OH)2 and γ-NiOOH prior to OER demonstrate γ-NiOOH as the key active species for OER. The hybrid catalyst exhibits 48-fold enhanced catalytic current at 300 mV and remarkably reduced Tafel slope to 46 mV dec-1 , indicating the greatly accelerated catalytic kinetics after surface evolution.

Accuracy and Safety of Lateral Vertebral Notch-Referred Technique Used in Subaxial Cervical Pedicle Screw Placement.

BACKGROUND: Biomechanical studies revealed that pedicle screw instrumentation has a superior stabilizing effect compared with other internal fixations in reconstructing the subaxial cervical spine. However, severe neurovascular risks preclude surgeons from routinely conducting pedicle screw manipulation in cervical spine. OBJECTIVE: To evaluate the accuracy and safety of the lateral vertebral notch (LVN)-referred technique used in subaxial cervical pedicle screw (CPS) placement. METHODS: One hundred thirty-five consecutive retrospective patients with cervical disorders underwent the LVN-referred technique for CPS placements in 3 spine centers. Postoperative pedicle perforations were confirmed by CT scans to assess the technical accuracy. Neurovascular complications derived from CPS misplacements were recorded to evaluate the technical safety. RESULTS: A total of 718 CPSs were inserted into subaxial cervical spine. Postoperative CT scans revealed that the accuracy of CPS placement was superior. Neither vertebral artery injury nor spinal cord injury occurred. One radiculopathy was from a unilateral C6 nerve root compression. A screw-related neurovascular injury rate of 0.7% occurred in this cohort. Additionally, there was no significant difference in the accuracy of CPS placement among 3 surgeons (H = 1.460, P = .482). The relative standard deviation values revealed that technical reproducibility was acceptable. Furthermore, there was no significant difference between the patients' pedicle transverse angles and inserted CPS transverse angles from C3 to C7 (all P > .05). CONCLUSION: The LVN is a reliable and consistent anatomic landmark for CPS placement. The accuracy and safety of subaxial CPS placement by using LVN-referred technique are highly acceptable, which may endow this technique to be practicably performed in selected patients.

The accuracy of the lateral vertebral notch-referred pedicle screw insertion technique in subaxial cervical spine: a human cadaver study.

STUDY DESIGN: This is a cadaver specimen study to confirm new pedicle screw (PS) entry point and trajectory for subaxial cervical PS insertion. OBJECTIVE: To assess the accuracy of the lateral vertebral notch-referred PS insertion technique in subaxial cervical spine in cadaver cervical spine. BACKGROUNDS: Reported morphometric landmarks used to guide the surgeon in PS insertion show significant variability. In the previous study, we proposed a new technique (as called "notch-referred" technique) primarily based on coronal multiplane reconstruction images (CMRI) and cortical integrity after PS insertion in cadavers. However, the PS position in cadaveric cervical segment was not confirmed radiologically. Therefore, the difference between the pedicle trajectory and the PS trajectory using the notch-referred technique needs to be illuminated. METHODS: Twelve cadaveric cervical spines were conducted with PS insertion using the lateral vertebral notch-referred technique. The guideline for entry point and trajectory for each vertebra was established based on the morphometric data from our previous study. After 3.5-mm diameter screw insertion, each vertebra was dissected and inspected for pedicle trajectory by CT scan. The pedicle trajectory and PS trajectory were measured and compared in axial plane. The perforation rate was assessed radiologically and was graded from ideal to unacceptable: Grade 0 = screw in pedicle; Grade I = perforation of pedicle wall less than one-fourth of the screw diameter; Grade II = perforation more than one-fourth of the screw diameter but less than one-second; Grade III = perforation more than one-second outside of the screw diameter. In addition, pedicle width between the acceptable and unacceptable screws was compared. RESULTS: A total of 120 pedicle screws were inserted. The perforation rate of pedicle screws was 78.3% in grade 0 (excellent PS position), 10.0% in grade I (good PS position), 8.3% in grade II (fair PS position), and 3.3% in grade III (poor PS position). The overall accepted accuracy of pedicle screws was 96.7% (Grade 0 + Grade I + Grade II), and only 3.3% had critical breach. There was no statistical difference between the pedicle trajectory and PS trajectory (p > 0.05). Compared to the pedicle width (4.4 ± 0.7 mm) in acceptably inserted screw, the unacceptably screw is 3.2 ± 0.3 mm which was statistically different (p < 0.05). CONCLUSION: The accuracy of the notch-referred PS insertion in cadaveric subaxial cervical spine is satisfactory.

PCSK9 siRNA suppresses the inflammatory response induced by oxLDL through inhibition of NF-κB activation in THP-1-derived macrophages.

Proprotein convertase subtilisin/kexin 9 (PCSK9), a member of the protein-converting enzyme family, is highly expressed in adult hepatocytes and small intestinal enterocytes. To our knowledge, in this study, we demonstrate for the first time that PCSK9 is upregulated in a dose-dependent manner via oxidized low-density lipoprotein (oxLDL) stimulation in THP-1-derived macrophages. PCSK9 small interfering RNA (siRNA) suppresses the oxLDL-induced inflammatory cytokine expression in THP-1-derived macrophages. The exposure of macrophages to oxLDL markedly increased the expression of NF-κB protein in the nucleus. However, this effect was significantly attenuated by PCSK9 siRNA. These findings indicate that PCSK9 expression is induced by oxLDL, and that PCSK9 siRNA protects against inflammation via the inhibition of NF-κB activation in oxLDL-stimulated THP-1-derived macrophages. Our results suggest that PCSK9 may be used as a therapeutic target for the treatment of atherosclerosis since PCSK9 siRNA suppresses oxLDL-induced IκB-α degradation and NF-κB nuclear translocation into THP-1-derived macrophages.