LPCAT1 overexpression promotes the progression of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common malignant neoplasms. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a key role in the lipid remodelling and is correlated with various neoplasms. Nonetheless, the biological functions and molecular mechanisms of LPCAT1 underlying HCC remain obscure. METHODS: In the present study, we investigated the role of LPCAT1 in the progression of HCC. In-house RT-qPCR, tissue microarrays, and immunohistochemistry were performed to detect the expression levels and the clinical value of LPCAT1 in HCC. External datasets were downloaded to confirm the results. Proliferation, migration, invasiveness, cell cycle, and apoptosis assays were conducted to reveal the biological effects LPCAT1 has on SMMC-7721 and Huh7 cells. HCC differentially expressed genes and LPCAT1 co-expressed genes were identified to explore the molecular mechanisms underlying HCC progression. RESULTS: LPCAT1 showed upregulated expression in 3715 HCC specimens as opposed to 3105 non-tumour specimens. Additionally, LPCAT1 might be an independent prognostic factor for HCC. LPCAT1-knockout hampered cellular proliferation, migration, and metastasis in SMMC-7721 and Huh7 cells. More importantly, the cell cycle and chemical carcinogenesis were the two most enriched signalling pathways. CONCLUSIONS: The present study demonstrated that increased LPCAT1 correlated with poor prognosis in HCC patients and fuelled HCC progression by promoting cellular growth, migration, and metastasis.

Structural Diversity in Layered Hybrid Perovskites, A2PbBr4 or AA'PbBr4, Templated by Small Disc-Shaped Amines.

We present three new hybrid layered lead(II) bromide perovskites of generic composition A2PbBr4 or AA'PbBr4 that exhibit three distinct structure types. [TzH]2PbBr4 ([TzH+] = 1,2,4-triazolium) adopts a (001)-oriented layer structure and [AaH]2PbBr4, ([AaH+] = acetamidinium) adopts a (110)-oriented type, whereas [ImH][TzH]PbBr4, ([ImH+] = imidazolium) adopts a rare (110)-oriented structure with enhanced corrugation (i.e., 3 × 3 type). The crystal structures of each are discussed in terms of the differing nature of the templating molecular species. Photoluminescent spectra for each are reported and the behaviors discussed in relation to the different structure of each composition.

[Characteristic spectrum and decoction process of classical prescription Qingwei San].

In this experiment, by determination of the HPLC characteristic spectrum of the classical prescription Qingwei San decoction, the contents of isoferulic acid, palmatine and paeonol in Qingwei San decoction and the extraction rate were investigated. The factors such as the crushing degree of decoction pieces, the amount of decocting water, the decocting time, the filter material and the decocting container involved in Qingwei San decoction process were examined to make a detailed comparison of Qingwei San's decoction processes during the development.HPLC characteristic spectrum method of Qingwei San was established, and then the decoction process parameters of Qingwei San were optimized, with the similarity of characteristic spectrum, the concentration of the index components and the extraction rate as indexes. The decoction process of Qingwei San was determined as follows: Qingwei San decoction pieces were weighed according to the prescription amount and pulverized into the most coarse powder; the powder was put in a ceramic pot, added with 225 mL water, heated to boiling, cooked for 50 minutes with gentle heat(100 W), and filtered with a layer of 300 mesh nylon cloth.The similarity of Qingwei San's characteristics pectrum of different decoction methods was all above 0.9, and the concentration of isoferulic acid, palmatine and paeonol in Qingwei San under determined decoction process was 40.74, 26.73, 65.73 µg·mL~(-1), respectively, with an extraction rate of 33.80%.The characteristic spectrum determined in this experiment can better express the information and index components of Qingwei San, and if combined with the extraction rate information, it can provide the general information, index component content and extraction information. The decoction process after detailed investigation can better reflect the quality of Qingwei San decoction, with easier control and operation. It can provide a basis for the subsequent research and development of Qingwei San decoction standard, and can also provide experimental basis and reference for the decoction process research of other classical prescriptions.

Manipulation of the Structure and Optoelectronic Properties through Bromine Inclusion in a Layered Lead Bromide Perovskite.

One of the great advantages of organic-inorganic metal halides is that their structures and properties are highly tuneable and this is important when optimizing materials for photovoltaics or other optoelectronic devices. One of the most common and effective ways of tuning the electronic structure is through anion substitution. Here, we report the inclusion of bromine into the layered perovskite [H3N(CH2)6NH3]PbBr4 to form [H3N(CH2)6NH3]PbBr4·Br2, which contains molecular bromine (Br2) intercalated between the layers of corner-sharing PbBr6 octahedra. Bromine intercalation in [H3N(CH2)6NH3]PbBr4·Br2 results in a decrease in the band gap of 0.85 eV and induces a structural transition from a Ruddlesden-Popper-like to Dion-Jacobson-like phase, while also changing the conformation of the amine. Electronic structure calculations show that Br2 intercalation is accompanied by the formation of a new band in the electronic structure and a significant decrease in the effective masses of around two orders of magnitude. This is backed up by our resistivity measurements that show that [H3N(CH2)6NH3]PbBr4·Br2 has a resistivity value of one order of magnitude lower than [H3N(CH2)6NH3]PbBr4, suggesting that bromine inclusion significantly increases the mobility and/or carrier concentration in the material. This work highlights the possibility of using molecular inclusion as an alternative tool to tune the electronic properties of layered organic-inorganic perovskites, while also being the first example of molecular bromine inclusion in a layered lead halide perovskite. By using a combination of crystallography and computation, we show that the key to this manipulation of the electronic structure is the formation of halogen bonds between the Br2 and Br in the [PbBr4]∞ layers, which is likely to have important effects in a range of organic-inorganic metal halides.

Type A aortic dissection following heart transplantation: A case report.

BACKGROUND: Cardiac transplantation is considered the standard treatment for refractory end-stage heart failure. Worldwide, 5074 heart transplantations were performed in 2015. About 100 heart transplants are performed at the authors' center each year. The usual complications of heart transplantation include graft rejection, infection, and graft dysfunction. Aortic dissection after heart transplantation is very rare and is a serious complication that requires a hybrid procedure. CASE SUMMARY: A 58-year-old female patient was admitted to Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in July 2020 because of unprovoked low back pain without precipitating causes. Magnetic resonance imaging and computed tomography angiography showed type A aortic dissection with an aberrant right subclavian artery. After admission, urapidil was used to control blood pressure. Ten days later, the patient underwent ascending aortic and aortic arch replacement, subclavian artery reconstruction, and endovascular repair of abdominal and thoracic aortic aneurysms. A cardiopulmonary bypass was established through the right femoral artery and femoral vein. The aberrant right subclavian artery, innominate artery, left common carotid artery, and left subclavian artery were blocked, and the left and right common carotid arteries were cannulated for bilateral cerebral perfusion. CONCLUSION: The right axillary artery could not be selected for cardiopulmonary bypass intubation because of aberrant right subclavian artery.

BCAT1: A risk factor in multiple cancers based on a pan-cancer analysis.

BACKGROUND: Although branched chain amino acid transaminase 1 (BCAT1) has been identified to play an essential role in multiple tumors, no studies on its role in pan-cancer have been consulted before. METHODS: The study comprehensively analyzes the expression, potential mechanisms, and clinical significance of BCAT1 in pan-cancer through utilizing 16,847 samples, providing novel clues for the treatment of cancers. A Kruskal-Wallis test and the Wilcoxon rank-sum and signed-rank tests were applied to investigate diverse BCAT1 expression between various groups (e.g., cancer tissues versus normal tissues). Spearman's rank correlation coefficient was used in all correlation analyses in the study. Cox analyses and Kaplan-Meier curves were utilized to identify the prognosis significance of BCAT1 expression in cancers. The significance of BCAT1 expression in differentiating cancer and non-cancer tissues was explored via the area under the receiver operating characteristic curves (AUC). RESULTS: The differential expression of BCAT1 was detected in various cancers (p < 0.05), which is relevant to some DNA methyltransferases expression. BCAT1 expression was associated with mismatch repair gene expression, immune checkpoint inhibitors expression, microsatellite instability, and tumor mutational burden in some cancers, indicating its potential in immunotherapy. BCAT1 expression showed prognosis significance and played a risk role in multiple cancers (hazard ratio > 0, p < 0.05). BCAT1 expression also demonstrated conspicuous ability to distinguish some cancers tissues from their normal tissues (AUC > 0.7), indicating its potential to detect cancers. Further analyses on head and neck squamous cell carcinoma certified upregulated BCAT1 expression at both mRNA and protein levels in this disease based on in-house tissue microarrays and multicenter datasets. CONCLUSIONS: For the first time, the research comprehensively demonstrates the overexpression of BCAT1 in pan-cancer, which improves the understanding of the pathogenesis of BCAT1 in pan-cancer. Upregulated BCAT1 expression represented a poor prognosis for cancers patients, and it serves as a potential marker for cancer immunotherapy.

Laryngeal Squamous Cell Carcinoma: Clinical Significance and Potential Mechanism of Cell Division Cycle 45.

Background: Cell division cycle 45 (CDC45) plays an important role in the occurrence and development of numerous carcinomas, but its effect in laryngeal squamous cell carcinoma (LSCC) remains unclear. Materials and Methods: The messenger RNA and protein expression levels of CDC45 in LSCC were evaluated with a t test and the standard mean difference (SMD). The ability of CDC45 expression to distinguish the LSCC was assessed through receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA), protein-protein interaction, public databases, and online tools were used to explore the potential molecular mechanism of CDC45 in LSCC. Results: A high expression of CDC45 was identified in LSCC (SMD = 2.61, 95% confidence interval [1.62-3.61]). Through ROC curves, the expression of CDC45 makes it feasible to distinguish the LSCC group from the non-LSCC counterpart. CDC45 was relevant to the progression-free interval of LSCC patients (log-rank p = 0.03). GSEAs show that CDC45 is related to the cell cycle. CDC45, CDC6, KIF2C, and AURKB were identified as hub genes of LSCC. E2F1 may be the regulatory transcription factor of CDC45. Conclusions: High expression of CDC45 likely demonstrates carcinogenic effects in LSCC, and CDC45 is a potential target in screening and treatment of LSCC.

Downregulation of miR-125b-5p and Its Prospective Molecular Mechanism in Lung Squamous Cell Carcinoma.

Background: To explore the clinical significance of miR-125b-5p and its potential mechanisms in lung squamous cell carcinoma (LUSC). Materials and Methods: An integrated analysis of data from in-house quantitative real-time polymerase chain reaction (qRT-PCR), microRNA-sequencing, and microarray assays to appraise the expression level of miR-125b-5p in LUSC tissues compared to adjacent noncancerous controls. The authors identified the candidate targets of miR-125b-5p and conducted functional analysis using computational biology strategies from gene ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, disease ontology (DO), and protein-protein interaction (PPI) network analyses to investigate the prospective mechanisms. Results: According to qRT-PCR results, the expression level of miR-125b-5p was markedly decreased in LUSC tissues compared to noncancerous control tissues. Receiver operating characteristic and summary receiver operating characteristic analyses showed that miR-125b-5p had good specificity and sensitivity for distinguishing LUSC tissue from noncancerous lung tissue. The standard mean difference revealed that men and women with lower expression levels of miR-125b-5p may have a higher risk for LUSC. KEGG analysis and DO analysis intimated that target genes were evidently enriched in pyrimidine metabolism and pancreatic carcinoma. The PPI network of the top assembled KEGG pathway indicated that RRM2, UMPS, UCK2, and CTPS1 were regarded as crucial target genes for miR-125b-5p, and RRM2 was eventually deemed a key target. Conclusions: The authors' findings implicate a low expression level of miR-125b-5p in LUSC. A tumor-suppressive role of miR-125b-5p is proposed, based on its effects on LUSC tumor growth, clinical stage progression, and lymph node metastasis.

Prognostic signature of esophageal adenocarcinoma based on pyroptosis-related genes.

BACKGROUND: The role of pyroptosis-related genes (PRGs) in esophageal adenocarcinoma (EAC) remains unknown. METHODS: In this study, the first PRGs prognostic signature (PPS) of EAC was constructed based on the results of multivariate stepwise Cox regression analysis. Based on 1,047 samples of EAC and normal esophagus (NE), differentially expressed PRGs were selected for the establishment of the PPS. The discrimination effect of this PPS was detected by receiver operating characteristic curves, and the prognosis value of this PPS was determined through Cox regression analysis and Kaplan-Meier curves. Net benefits of the EAC patients from the nomogram (constructed based on the PPS and some clinical parameters) were assessed via decision curve analysis. The potential molecular mechanism of the PPS in EAC was explored via gene set enrichment analysis. The ability of PPS to distinguish EAC and NE was evaluated based on the results of summary receiver operating characteristic curves. RESULTS: The significant prognostic value of PPS can be observed at all of the training cohort, test cohort, and validation cohort, such as its independent risk role in the prognosis of the EAC patients (hazard ratio > 0; 95% CI not including 0). The positive net benefits of the nomogram for the EAC patients can be detected via decision curve analysis, and the potential molecular mechanism of the PPS in EAC is likely related to cell pyroptosis. Last, some of the PRGs (particularly CASP5) included in this PPS specifically support its feasibility for identifying EAC (area under the curves > 0.7). CONCLUSIONS: The construction of this PPS in EAC enhances the present understanding of the relationship between PRGs and EAC, thus representing a novel approach to the clinical identification and management of EAC based on PRGs.

Upregulation of microRNA miR-141-3p and its prospective targets in endometrial carcinoma: a comprehensive study.

The clinicopathological value of microRNA-141-3p (miR-141-3p) and its prospective target genes in endometrial carcinoma (EC) remains unclear. The present study determined the expression level of miR-141-3p in EC via quantitative real-time PCR (RT-qPCR). RT-qPCR showed a markedly higher expression level of miR-141-3p in EC tissues than in non-EC endometrium tissues (P < 0.0001). The microarray and miRNA-seq data revealed upregulation of miR-141-3p. Integrated analysis based on 675 cases of EC and 63 controls gave a standardized mean difference of 1.737, confirmed the upregulation of miR-141-3p. The Kaplan-Meier survival curve showed that a higher expression of miR-141-3p positively corelated with a poorer prognosis. Combining the predicted targets and downregulated genes in EC, we obtained 271 target genes for miR-141-3p in EC. Two potential targets, PPP1R12A and PPP1R12B, were downregulated at both the mRNA and protein levels. This study indicates that the overexpression of miR-141-3p may play an important part in the carcinogenesis of EC. The overexpression of miR-141-3p may be a risk factor for the prognosis of patients with EC.

Structural variations in (001)-oriented layered lead halide perovskites, templated by 1,2,4-triazolium.

A new hybrid lead(ii) halide perovskite, (TzH)2PbCl4, ([TzH+] = 1,2,4-triazolium), adopts a (001)-oriented layered perovskite structure, which can be considered as derived from the n = 1 Ruddlesden-Popper (RP) type. Variable temperature single crystal X-ray diffraction reveals a structural phase transition in the region 125 K < T < 173 K between a high temperature, high symmetry polymorph, space group Cmcm, and a low temperature, low symmetry chiral polymorph, space group P212121, which has a tripled unit cell volume. UV-Vis spectra suggest a band gap of 3.30 eV for (TzH)2PbCl4. A second polymorph of the bromide analogue, (TzH)2PbBr4-II, is also reported, and structural relationships between all three variants are discussed.

Integrated expression analysis revealed RUNX2 upregulation in lung squamous cell carcinoma tissues.

This study aimed to investigate the clinicopathological significance and prospective molecular mechanism of RUNX family transcription factor 2 (RUNX2) in lung squamous cell carcinoma (LUSC). The authors used immunohistochemistry (IHC), RNA-seq, and microarray data from multi-platforms to conduct a comprehensive analysis of the clinicopathological significance and molecular mechanism of RUNX2 in the occurrence and development of LUSC. RUNX2 expression was significantly higher in 16 LUSC tissues than in paired non-cancerous tissues detected by IHC (P < 0.05). RNA-seq data from the combination of TCGA and genotype-tissue expression (GTEx) revealed significantly higher expression of RUNX2 in 502 LUSC samples than in 476 non-cancer samples. The expression of RUNX2 protein was also significantly higher in pathologic T3-T4 than in T1-T2 samples (P = 0.031). The pooled standardised mean difference (SMD) for RUNX2 was 0.87 (95% CI, 0.58-1.16), including 29 microarrays from GEO and one from ArrayExpress. The co-expression network of RUNX2 revealed complicated connections between RUNX2 and 45 co-expressed genes, which were significantly clustered in pathways including ECM-receptor interaction, focal adhesion, protein digestion and absorption, human papillomavirus infection and PI3K-Akt signalling pathway. Overexpression of RUNX2 plays an essential role in the clinical progression of LUSC.

The Clinical Significance and Potential Molecular Mechanism of PTTG1 in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide. Transcription factor PTTG1 was seen highly expressed in a variety of tumors and was related to the degree of tumor differentiation, invasion, and metastasis. However, the clinical significance of PTTG1 had yet to be verified, and the mechanism of abnormal PTTG1 expression in ESCC was not clear. In this study, the comprehensive analysis and evaluation of PTTG1 expression in ESCC were completed by synthesizing in-house immunohistochemistry (IHC), clinical sample tissue RNA-seq (in-house RNA-seq), public high-throughput data, and literature data. We also explored the possible signaling pathways and target genes of PTTG1 in ESCC by combining the target genes of PTTG1 (displayed by ChIP-seq), differentially expressed genes (DEGs) of ESCC, and PTTG1-related genes, revealing the potential molecular mechanism of PTTG1 in ESCC. In the present study, PTTG1 protein and mRNA expression levels in ESCC tissues were all significantly higher than in non-cancerous tissues. The pool standard mean difference (SMD) of the overall PTTG1 expression was 1.17 (95% CI: 0.72-1.62, P < 0.01), and the area under curve (AUC) of the summary receiver operating characteristic (SROC) was 0.86 (95% CI: 0.83-0.89). By combining the target genes displayed by ChIP-seq of PTTG1, DEGs of ESCC, and PTTG1-related genes, it was observed that PTTG1 may interact with these genes through chemokines and cytokine signaling pathways. By constructing a protein-protein interaction (PPI) network and combining ChIP-seq data, we obtained four PTTG1 potential target genes, SPTAN1, SLC25A17, IKBKB, and ERH. The gene expression of PTTG1 had a strong positive correlation with SLC25A17 and ERH, which suggested that PTTG1 might positively regulate the expression of these two genes. In summary, the high expression of PTTG1 may play an important role in the formation of ESCC. These roles may be completed by PTTG1 regulating the downstream target genes SLC25A17 and ERH.

Clinical significance of transcription factor RUNX2 in lung adenocarcinoma and its latent transcriptional regulating mechanism.

RUNX family transcription factor 2 (RUNX2) overexpression has been found in various human malignancies. However, the expression levels of RUNX2 mRNA and protein in lung adenocarcinoma (LUAD) were not investigated. This study aims to thoroughly analysis the expression level and potential mechanisms of RUNX2 mRNA in LUAD. We applied in-house immunohistochemistry, high-throughput RNA-sequencing, and gene microarrays to comprehensively investigate the expression level of RUNX2 in LUAD. A pool standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were calculated to assess the integrated expression value of RUNX2 in LUAD. The hazard ratios (HRs) were integrated to evaluate the overall prognostic effect of RUNX2 on the LUAD patients. The differentially expressed genes (DEGs) of LUAD, the potential target genes of RUNX2, and its co-expressed genes were overlapped to obtain a set of specific genes for GO and KEGG enrichment analyses. RUNX2 overexpression in LUAD was validated using a large number of cases (2 418 LUAD and 1 574 non-tumor lung samples). The pooled SMD was 0.85 (95 % CI: 0.64-1.05) and the area under the curve (AUC) of the SROC was 0.86 (95 %CI: 0.83-0.89). The integrated HR was 1.20 [1.04-1.38], indicating that increased expression of RUNX2 was an independent risk factor for the poor survival of the LUAD patients. RUNX2 and its transcriptionally regulates potential target genes may promote cell proliferation and drug resistance of LUAD by modulating the cell cycle and MAPK signaling pathways. RUNX2 can provide new research directions for targeted drug therapy and drug resistance for LUAD treatment.

[Ca(2+)-dependent potassium channels play important roles in regulatory volume decrease in human nasopharyngeal carcinoma cells].

It has been shown that cell volume regulation mechanisms play important roles in various cell functions. We demonstrated previously that volume-activated chloride channels were involved in cell volume regulation. The present study aimed to clarify the roles of various types of potassium channels in regulatory volume decrease (RVD) induced by hypotonic challenges in human nasopharyngeal carcinoma cells (CNE-2Z cells). The whole-cell patch clamp technique was used to record hypotonic challenge-induced potassium currents. During current recordings, cells were held at 0 mV and stepped to +/-46 and +/-92 mV, repeatedly. The cell volume was computed from cell diameters. The changes of cell volume were monitored and analyzed by the time-lapse imaging technique. The results showed that the exposure to 160 mOsm/L hypotonic solution caused the cells to swell by (144.5+/-4.2)%, activated a potassium current (59.2 pA/pF+/-13.3 pA/pF at 92 mV), and induced RVD. Cell volume was recovered from hypotonic challenge-induced swelling by (48.9+/-4.6)% after 20 min. The potassium current (at 92 mV) and RVD were inhibited by the calcium-dependent potassium channel blocker, clotrimazole (100 mumol/L), by (98.5+/-2.8)% and (89.3+/-4.9)%, respectively. Depletion of extracellular calcium prevented the activation of the hypotonic challenge-induced potassium current and inhibited the process of RVD. The voltage-gated potassium channel blocker, 4-AP (5 mmol/L), partially inhibited the hypotonic challenge-activated potassium currents by (66.6+/-5.3)% (at 92 mV). These results suggest that the Ca(2+)-dependent potassium channel is the main component of volume-activated potassium channels and plays an important role in volume regulation of CNE-2Z cells. The voltage-gated potassium channels may also contribute in part to the formation of the volume-activated potassium current.

Differentiation of human bone marrow mesenchymal stem cells into neuron-like cells in vitro.

STUDY DESIGN: Responses of human mesenchymal stem cells from bone marrow (hBMSCs) were analyzed under chemical conditions, and then characterization of ion channels was evaluated by whole-cell patch clamp. OBJECTIVE: To explore the possibility of differentiation of human bone marrow-derived mesenchymal stem cells into neuron-like cells in vitro under different conditions. SUMMARY OF BACKGROUND DATA: The generation of mesenchymal stem cells into neuron-like cells has been studied. However, few of these studies characterized functional properties of the differentiated hBMSCs. METHODS: hBMSCs (Passage 2) were expanded and cultured in vitro. After Passage 5 was subcultured, the cells were induced by cytokines and antioxidants. Morphologic observation, immunocytochemistry, Western blot analysis, and patch-clamp techniques were performed to evaluate properties of treated and control groups. RESULTS: The differentiated neuronal cells from hBMSCs not only expressed neuron phenotype and membrane channel protein including Nav1.6, Kv1.2, Kv1.3, and Cav1.2 but also exhibited functional ion currents. Both hBMSCs and differentiated cells expressed Nav1.6, Kv1.2, Kv1.3, and Cav1.2 and voltage-activated potassium currents, including delayed rectifier, noise-like and transient outward currents. However, expression of channel proteins, such as sodium channel Nav1.6 and potassium channels Kv1.2 and Kv1.3, were upregulated. Consistently, their potassium currents were also enhanced in the differentiated cells. CONCLUSION: hBMSCs possess of great potential to differentiate into functional neurons, indicating that hBMSCs may be an ideal cell source in managing a variety of clinical diseases such as spinal cord injury.