A reference profile of N-glycosylation for human kidney and the identification of cell-cell interactions between parietal epithelial cells and capillary endothelial cells by single-cell glycosylation-sequencing.

Background N-glycosylation is one of the most common post-translational modifications in humans, and these alterations are associated with kidney diseases. Methods A novel technological approach, single-cell N-acetyllactosamine sequencing (scLacNAc-seq), was applied to simultaneously detect N-glycosylation expression and the transcriptome at single-cell resolution in three human kidney tissues from zero-time biopsy. Cell clusters, glycation abundance in each cell cluster, functional enrichment analysis, cell-cell crosstalk, and Pseudotime analysis were applied. Results Using scLacNAc-seq, 24,247 cells and 22 cell clusters were identified, and N-glycan abundance in each cell was obtained. Transcriptome analysis revealed a close connection between capillary endothelial cells (CapECs) and parietal epithelial cells (PECs). PECs and CapECs communicate with each other through several pairs of ligand receptors (e.g., TGFB1-EGFR, GRN-EGFR, TIMP1-FGFR2, VEGFB-FLT1, ANGPT2-TEK, and GRN-TNFRSF1A). Finally, a regulatory network of cell-cell crosstalk between PECs and CapECs was constructed, which is involved in cell development. Conclusions We here, for the first time, constructed the glycosylation profile of 22 cell clusters in the human kidney from time-zero biopsy. Moreover, cell-cell communication between PECs and CapECs through the ligand-receptor system may play a crucial regulatory role in cell proliferation.

Sedum aizoon L.: a review of its history, traditional uses, nutritional value, botany, phytochemistry, pharmacology, toxicology, and quality control.

In China, Russia, Mongolia, Japan, North Korea, and Mexico, Sedum aizoon L. (S. aizoon) is used as an edible plant. Up to now, over 234 metabolites, including phenolic acids, flavonoids, triterpenes, phytosterols, and alkaloids, among others, have been identified. In addition to its antioxidant, anti-inflammatory, anti-fatigue, antimicrobial, anti-cancer, and hemostatic activities, S. aizoon is used for the treatment of cardiovascular disease. This paper provides an overview of the history, botany, nutritional value, traditional use, phytochemistry, pharmacology, toxicology, and quality control of S. aizoon.

PI3Kδ inhibition alleviates the brain injury during cerebral ischemia reperfusion via suppressing pericyte contraction in a TNF-α dependent manner.

The pericytes (PCs) surrounding capillaries are vital regulators of capillary constriction. Persistent PC contraction results in the increased capillary constriction, therefore leading to the impaired cerebral blood flow (CBF) recovery after reperfusion and worsening the clinical outcomes in stroke patients. However, the potential determinants of PC functions during ischemia/reperfusion are poorly understood. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit Delta (PIK3CD/PI3Kδ) is a crucial factor involved with neuronflammation during ischemic stroke. PI3Kδ has shown the expression in PCs, while its effect on PC functions has not been explored yet. In this study, a rodent ischemia/reperfusion model was established in C57BL/6 mice via transient middle cerebral artery occlusion and reperfusion (MCAO/R). The PI3Kδ expression in ischemic penumbra was remarkably upregulated following MCAO/R induction. PI3Kδ inhibitor CAL-101 improved the CBF recovery, ischemic brain injury, and suppressed capillary constriction in MCAO/R mice. Besides, the production of tumor necrosis factor alpha (TNF-α), an inducer for tissue injury, and the expression of transient receptor potential vanilloid type 2 (TRPV2), a channel protein permitting calcium (Ca2+) uptake, were significantly reduced in ischemic penumbra after CAL-101 treatment. In vitro, oxygen-glucose deprivation and reoxygenation (OGD/R) enhanced the expression of PI3Kδ and TRPV2 in primary mouse PCs. CAL-101 suppressed the TNF-α-induced TRPV2 expression in OGD/R-treated PCs, thus inhibiting the Ca2+ uptake and PC contraction. Collectively, this study suggests that PI3Kδ is a critical regulator of PC function during ischemic stroke.

Convolutional neural network-based measurement of crown-implant ratio for implant-supported prostheses.

STATEMENT OF PROBLEM: Research has revealed that the crown-implant ratio (CIR) is a critical variable influencing the long-term stability of implant-supported prostheses in the oral cavity. Nevertheless, inefficient manual measurement and varied measurement methods have caused significant inconvenience in both clinical and scientific work. PURPOSE: This study aimed to develop an automated system for detecting the CIR of implant-supported prostheses from radiographs, with the objective of enhancing the efficiency of radiograph interpretation for dentists. MATERIAL AND METHODS: The method for measuring the CIR of implant-supported prostheses was based on convolutional neural networks (CNNs) and was designed to recognize implant-supported prostheses and identify key points around it. The experiment used the You Only Look Once version 4 (Yolov4) to locate the implant-supported prosthesis using a rectangular frame. Subsequently, two CNNs were used to identify key points. The first CNN determined the general position of the feature points, while the second CNN finetuned the output of the first network to precisely locate the key points. The network underwent testing on a self-built dataset, and the anatomic CIR and clinical CIR were obtained simultaneously through the vertical distance method. Key point accuracy was validated through Normalized Error (NE) values, and a set of data was selected to compare machine and manual measurement results. For statistical analysis, the paired t test was applied (α=.05). RESULTS: A dataset comprising 1106 images was constructed. The integration of multiple networks demonstrated satisfactory recognition of implant-supported prostheses and their surrounding key points. The average NE value for key points indicated a high level of accuracy. Statistical studies confirmed no significant difference in the crown-implant ratio between machine and manual measurement results (P>.05). CONCLUSIONS: Machine learning proved effective in identifying implant-supported prostheses and detecting their crown-implant ratios. If applied as a clinical tool for analyzing radiographs, this research can assist dentists in efficiently and accurately obtaining crown-implant ratio results.

AFB1 Triggers Lipid Metabolism Disorders through the PI3K/Akt Pathway and Mediates Apoptosis Leading to Hepatotoxicity.

As the most prevalent mycotoxin in agricultural products, aflatoxin B1 not only causes significant economic losses but also poses a substantial threat to human and animal health. AFB1 has been shown to increase the risk of hepatocellular carcinoma (HCC) but the underlying mechanism is not thoroughly researched. Here, we explored the toxicity mechanism of AFB1 on human hepatocytes following low-dose exposure based on transcriptomics and lipidomics. Apoptosis-related pathways were significantly upregulated after AFB1 exposure in all three hES-Hep, HepaRG, and HepG2 hepatogenic cell lines. By conducting a comparative analysis with the TCGA-LIHC database, four biomarkers (MTCH1, PPM1D, TP53I3, and UBC) shared by AFB1 and HCC were identified (hazard ratio > 1), which can be used to monitor the degree of AFB1-induced hepatotoxicity. Simultaneously, AFB1 induced abnormal metabolism of glycerolipids, sphingolipids, and glycerophospholipids in HepG2 cells (FDR < 0.05, impact > 0.1). Furthermore, combined analysis revealed strong regulatory effects between PIK3R1 and sphingolipids (correlation coefficient > 0.9), suggesting potential mediation by the phosphatidylinositol 3 kinase (PI3K) /protein kinase B (AKT) signaling pathway within mitochondria. This study revealed the dysregulation of lipid metabolism induced by AFB1 and found novel target genes associated with AFB-induced HCC development, providing reliable evidence for elucidating the hepatotoxicity of AFB as well as assessing food safety risks.

Modulation of SEMA4D-modified titanium surface on M2 macrophage polarization via activation of Rho/ROCK-mediated lactate release of endothelial cells: In vitro and in vivo.

SEMA4D-modified titanium surfaces can indirectly regulate macrophages through endothelial cells to achieve an anti-inflammatory effect, which is beneficial for healing soft tissues around the gingival abutment. However, the mechanism of surface-induced cellular phenotypic changes in SEMA4D-modified titanium has not yet been elucidated. SEMA4D activates the RhoA signaling pathway in endothelial cells, which coordinates metabolism and cytoskeletal remodeling. This study hypothesized that endothelial cells inoculated on SEMA4D-modified titanium surfaces can direct M2 polarization of macrophages via metabolites. An indirect co-culture model of endothelial cells and macrophages was constructed in vitro, and specific inhibitors were employed. Subsequently, endothelial cell adhesion and migration, metabolic changes, Rho/ROCK1 expression, and inflammatory expression of macrophages were assessed via immunofluorescence microscopy, specific kits, qRT-PCR, and Western blotting. Moreover, an in vivo rat bilateral maxillary implant model was constructed to evaluate the soft tissue healing effect. The in vitro experiments showed that the SEMA4D group had stronger endothelial cell adhesion and migration, increased Rho/ROCK1 expression, and enhanced release of lactate. Additionally, decreased macrophage inflammatory expression was observed. In contrast, the inhibitor group partially suppressed lactate metabolism and motility, whereas increased inflammatory expression. The in vivo analyses indicated that the SEMA4D group had faster and better angiogenic and anti-inflammatory effects, especially in the early stage. In conclusion, via the Rho/ROCK1 signaling pathway, the SEMA4D-modified titanium surface promotes endothelial cell adhesion and migration and lactic acid release, then the paracrine lactic acid promotes the polarization of macrophages to M2, thus obtaining the dual effects of angiogenesis and anti-inflammation.

Silencing geranylgeranyltransferase I inhibits the migration and invasion of salivary adenoid cystic carcinoma through RhoA/ROCK1/MLC signaling and suppresses proliferation through cell cycle regulation.

Geranylgeranyltransferase type I (GGTase-I) significantly affects Rho proteins, such that the malignant progression of several cancers may be induced. Nevertheless, the effect and underlying mechanism of GGTase-I in the malignant progression of salivary adenoid cystic carcinoma (SACC) remain unclear. This study primarily aimed to investigate the role and mechanism of GGTase-I in mediating the malignant progression of SACC. The level of GGTase-I gene in cells was stably knocked down by short hairpin RNA-EGFP-lentivirus. The effects of GGTase-I silencing on the migration, invasion, and spread of cells were examined, the messenger RNA levels of GGTase-I and RhoA genes of SACC cells after GGTase-I knockdown were determined, and the protein levels of RhoA and RhoA membrane of SACC cells were analyzed. Moreover, the potential underlying mechanism of silencing GGTase-I on the above-mentioned aspects in SACC cells was assessed by examining the protein expression of ROCK1, MLC, p-MLC, E-cadherin, Vimentin, MMP2, and MMP9. Furthermore, the underlying mechanism of SACC cells proliferation was investigated through the analysis of the expression of cyclinD1, MYC, E2F1, and p21CIP1/WAF1 . Besides, the change of RhoA level in SACC tissues compared with normal paracancer tissues was demonstrated through quantitative reverse-transcription polymerase chain reaction and western blot experiments. Next, the effect after GGTase-I silencing was assessed through the subcutaneous tumorigenicity assay. As indicated by the result of this study, the silencing of GGTase-I significantly reduced the malignant progression of tumors in vivo while decreasing the migration, invasion, and proliferation of SACC cells and RhoA membrane, Vimentin, ROCK1, p-MLC, MMP2, MMP9, MYC, E2F1, and CyclinD1 expression. However, the protein expression of E-cadherin and p21CIP1/WAF1 was notably upregulated. Subsequently, no significant transform of RhoA and MLC proteins was identified. Furthermore, RhoA expression in SACC tissues was significantly higher than that in paracancerous tissues. As revealed by the results of this study, GGTase-I shows a correlation with the proliferation of SACC through the regulation of cell cycle and may take on vital significance in the migration and invasion of SACC by regulating RhoA/ROCK1/MLC signaling pathway. GGTase-I is expected to serve as a novel exploration site of SACC.

Multiomics reveals new biomarkers and mechanistic insights into the combined toxicity effects of 2,2',4,4',5,5'-hexachlorobiphenyl and atrazine exposures in MCF-7 cells.

Humans are constantly exposed to complicated chemical mixtures from the environment and food rather than being exposed to a single pollutant. The underlying mechanisms of the complicated combined toxicity of endocrine disrupting chemicals (EDCs) are still mainly unexplored. In this study, two representative EDCs, 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) and atrazine (ATZ), were selected to explore their combined effects on MCF-7 cell proliferation at environmental exposure concentrations by an integrated analysis of metabolomics and transcriptomics. The results showed that 1 µM ATZ and PCB153 combined exposure significantly accelerated MCF-7 cell growth by 18.2%. More than 400 metabolites detected by UHPLC-QTOF/MS were used to observe metabolism differences induced by binary mixtures. Metabolomics analysis verified that ATZ and PCB153 exposure alone or in combination could have an additive effect on metabolism and induce significant disruption to glycolysis, purine metabolism and the TCA cycle, which provide energy demand and biosynthetic substrates for cell proliferation. Compared to PCB153 and ATZ exposure alone, a combined effect was observed in purine and pyrimidine metabolic pathways. Hexokinase 3 (HK3) and cytochrome P450 19 subfamily A1 (CYP19A1) were identified as differentially expressed genes based on transcriptomic analysis. By integrating metabolome and transcriptome analysis, the proliferation effects of ATZ and PCB153 were induced at low doses in MCF-7 cells through potential interference with the downstream transcription signaling of CYP19A1. Furthermore, molecular docking indicated that PCB153 and ATZ directly affected CYP19A1. Altogether, the regulation of pivotal metabolites and differentially expressed genes could provide helpful information to reveal the mechanism by which PCB153 and ATZ affect MCF-7 cell proliferation.

Molecular mechanisms involved in regulating protein activity and biological function of MST3.

Mammalian sterile 20-like (Ste20-like) protein kinase 3 (MST3) or serine/threonine-protein kinase 24 (STK24) is a serine/threonine protein kinase that belongs to the mammalian STE20-like protein kinase family. MST3 is a pleiotropic protein that plays a critical role in regulating a variety of events, including apoptosis, immune response, metabolism, hypertension, tumor progression, and development of the central nervous system. The MST3-mediated regulation is intricately related to protein activity, post-translational modification, and subcellular location. Here, we review the recent progress on the regulatory mechanisms against MST3 and its-mediated control of disease progression.

Oxymatrine inhibits TGF­ß1­mediated mitochondrial apoptotic signaling in alveolar epithelial cells via activation of PI3K/AKT signaling.

Although pulmonary fibrosis (PF) causes respiratory failure and death, effective therapies for PF have not been developed. Oxymatrine (OMT), an active ingredient in the Chinese herb Sophora flavescens, exerts antifibrotic effects; however, its effect on PF remains unclear. The present study aimed to determine whether OMT decreases transforming growth factor-ß1 (TGF-ß1)-induced PF in human lung cancer A549 cells by inhibiting apoptosis and targeting the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. To construct a PF cell model, A549 cells were stimulated with TGF-ß1. The experimental groups were as follows: control (untreated cells grown in complete medium), TGF-ß1 (cells treated with 5 ng/ml TGF-ß1), OMT (cells treated with 5 ng/ml TGF-ß1 and 0.25, 0.50, or 1.00 mg/ml OMT), and OMT + LY294002 (cells treated with 5 ng/ml TGF-ß1, 1.0 mg/ml OMT. and 25 µmol/l LY294002). The effects of OMT on cell morphology (via electron microscopy), apoptosis (via Annexin V-PI staining), mitochondrial apoptosis signaling [using JC-1 method to analyze mitochondrial membrane potential (MMP)], and Bcl-2, as well as Bax expression (via western blotting and reverse transcription-quantitative polymerase chain reaction), were analyzed. OMT significantly protected cells against TGF-ß1-induced PF by inhibiting apoptosis. The specific manifestations were cell injury, as evidenced by morphological changes and decreased MMP. Following OMT treatment, the expression of the pro-apoptotic protein Bax increased, whereas that of the anti-apoptotic protein Bcl-2 decreased. The PI3K/AKT-specific inhibitor LY294002 significantly inhibited the ameliorative effects of OMT on TGF-ß1-induced apoptosis. Collectively, OMT attenuated TGF-ß1-mediated mitochondrial apoptosis of alveolar epithelial cells by activating the PI3K/AKT signaling pathway. Therefore, OMT may be a promising drug for PF treatment.

Clinical Observation of Low-Temperature Plasma Ablation Combined with Drug Therapy in the Treatment of Fungal Keratitis.

Objective: To observe the efficacy and prognosis of low-temperature plasma ablation + drug therapy in the treatment of fungal corneal ulcers. Methods: The present paper presents a retrospective clinical study with a subject base of 34 eyes. Patients with a fungal corneal ulcer who visited the Affiliated Eye Hospital of Nanchang University between August 2019 and December 2021 were selected as the study participants. They were found to have highly reflective fungal hyphae in the corneal stroma layer via confocal microscope examination, which were revealed to be positive on etiology examination, with the ulcer and infiltration depths ≤1/2 of the corneal thickness. The efficacy and prognosis were observed after treatment with low-temperature plasma ablation + drug therapy. Results: A total of 34 cases (34 eyes) had clinical manifestations of corneal infiltration and corneal ulcer formation, with a corneal lesion diameter of 1.31-8.64 mm (average = 4.79 ± 2.03 mm). The average healing time of corneal ulcers was 6.2 ± 1.7 days. Among a total of 34 cases (34 eyes) in patients with fungal keratitis, the infection was controlled and the ulcers gradually healed after treatment with low-temperature plasma system + drug therapy in a total of 30 cases (30 eyes, 88%). A total of three cases (3 eyes, 9%) exhibited no clear improvement after the treatment, and the patients underwent conjunctival flap covering surgery. One case (one eye, 3%) exhibited no clear improvement after further treatment, with the patient experiencing corneal perforation and ultimately undergoing penetrating keratoplasty. Conclusion: Low-temperature plasma ablation + drug therapy can effectively control the progression of fungal keratitis infection, as well as significantly shorten the ulcer healing time, and is, therefore, an effective method.

Transcriptional investigation of the toxic mechanisms of perfluorooctane sulfonate in rats based on an RNA-Seq approach.

Perfluorooctane sulfonate (PFOS) was widely used in industrial applications before it was listed as a persistent organic pollutant by the Conference of the Parties in the Stockholm Convention in 2009. Although the potential toxicity of PFOS has been studied, its toxic mechanisms remain largely undefined. Here, we investigated novel hub genes and pathways affected by PFOS to gain new conceptions of the toxic mechanisms of PFOS. Reduced body weight gain and abnormal ultra-structures in the liver and kidney tissues were spotted in PFOS-exposed rats, indicating successful establishment of the PFOS-exposed rat model. The transcriptomic alterations of blood samples upon PFOS exposure were analysed using RNA-Seq. GO analysis indicates that the differentially expressed gene-enriched GO terms are related to metabolism, cellular processes, and biological regulation. Kyoto encyclopaedia of gene and genomes (KEGG) and gene set enrichment analysis (GSEA) were conducted to identify six key pathways: spliceosome, B cell receptor signalling pathway, acute myeloid leukaemia, protein processing in the endoplasmic reticulum, NF-kappa B signalling pathway, and Fc gamma R-mediated phagocytosis. The top 10 hub genes were screened from a protein-protein interaction network and verified via quantitative real-time polymerase chain reaction. The overall pathway network and hub genes may provide new insights into the toxic mechanisms of PFOS exposure states.

Comparative Metabolomic Analysis of the Nutritional Aspects from Ten Cultivars of the Strawberry Fruit.

Strawberry (Fragaria × ananassa) is among the most widely cultivated fruits with good taste and rich nutrients. Many strawberry species, including white strawberries, are planted all over the world. The metabolic profiles of strawberry and distinctions among different cultivars are not fully understood. In this study, non-targeted metabolomics based on UHPLC-Q-Exactive Orbitrap MS was used to analysis the metabolites in 10 strawberry species. A total of 142 compounds were identified and were divided into six categories. Tochiotome may differ most from the white strawberry (Baiyu) by screening 72 differential metabolites. Histidine, apigenin, cyanidin 3-glucoside and peonidin 3-glucoside had potential as biomarkers for distinguishing Baiyu and another 11 strawberry groups. Amino acid metabolisms, anthocyanin biosynthesis and flavonoid biosynthesis pathways were mainly involved in the determination of the nutrition distinctions. This research contributes to the determination of the nutrition and health benefits of different strawberry species.

Predicting symptomatic intracranial hemorrhage in anterior circulation stroke patients with contrast enhancement after thrombectomy: the CAGA score.

BACKGROUND: The aim of the study was to establish a reliable scoring tool to identify the probability of symptomatic intracranial hemorrhage (sICH) in anterior circulation stroke patients with contrast enhancement (CE) on brain non-contrast CT (NCCT) after endovascular thrombectomy (EVT). METHODS: We retrospectively reviewed consecutive patients with acute ischemic stroke (AIS) who had CE on NCCT immediately after EVT for anterior circulation large vessel occlusion (LVO). We used the Alberta stroke program early CT score (ASPECTS) scoring system to estimate the extent and location of CE. Multivariable logistic regression was performed to derive an sICH predictive score. The discrimination and calibration of this score were assessed using the area under the receiver operator characteristic curve, calibration curve, and decision curve analysis. RESULTS: In this study, 194 of 322 (60.25%) anterior circulation AIS-LVO patients had CE on NCCT. After excluding 85 patients, 109 patients were enrolled in the final analysis. In multivariate regression analysis, age ≥70 years (adjusted OR (aOR) 9.23, 95% CI 2.43 to 34.97, P＜0.05), atrial fibrillation (AF) (aOR 4.17, 95% CI 1.33 to 13.12, P＜0.05), serum glucose ≥11.1 mmol/L (aOR 9.39, 95% CI 2.74 to 32.14, P＜0.05), CE-ASPECTS ＜5 (aOR 3.95, 95% CI 1.30 to 12.04 P＜0.05), and CE at the internal capsule (aOR 3.45, 95% CI 1.03 to 11.59, P＜0.05) and M1 region (aOR 3.65, 95% CI 1.13 to 11.80, P＜0.05) were associated with sICH. These variables were incorporated as the CE-age-glucose-AF (CAGA) score. The CAGA score demonstrated good discrimination and calibration in this cohort, as well as the fivefold cross validation. CONCLUSION: The CAGA score reliably predicted sICH in patients with CE on NCCT after EVT treatment.

[Retracted] MicroRNA­488 inhibits proliferation, invasion and EMT in osteosarcoma cell lines by targeting aquaporin 3.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that several of the panels showing cell invasion assay data in Fig. 3A were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 53: 1493­1504, 2018; DOI: 10.3892/ijo.2018.4483].

Huntingtin-associated protein 1 is a potential tumor suppressor for gastric cancer.

BACKGROUND: Gastric cancer is heterogeneous cancer and the causes of this disease are complex. New diagnostic and therapeutic targets are urgently needed to explore. Huntingtin-associated protein 1 (HAP1) is directly related to Huntington's disease (HD). However, patients with Huntington's disease have a lower incidence of cancer. Therefore, we are committed to studying the correlation between HAP1 and gastric carcinogenesis and development. METHODS AND RESULTS: Immunohistochemical staining, western blot analysis, and RT-qPCR were conducted to explore the localization and expression of HAP1 in gastric cancer. To study the biological significance of HAP1, we overexpressed HAP1 in both MKN28 and AGS cell lines by lentivirus infection. To explore the role of HAP1 in cell proliferation, the cells counting assay, EdU incorporation assay, and colony formation assay were carried out. We performed the wound healing assay and transwell assay to study the cell migration and invasion. To further investigate whether HAP1 could regulate gastric cancer cell death during glucose deprivation, Annexin V-FITC/PI staining was performed. In our study, we elucidated that HAP1 was downregulated in gastric cancer. What's more, overexpressing HAP1 inhibited cell proliferation, cell migration and invasion, and triggered apoptosis during glucose deprivation. More importantly, the antitumor properties and mechanisms of HAP1 have been elucidated further in gastric cancer. CONCLUSIONS: Taken together, the available evidence implies that HAP1 may serve as a potential tumor suppressor, making it a significant target in preventing and treating gastric cancer. This research provides a theoretical basis for the early diagnosis, clinical targeted therapy, and prognosis evaluation of gastric cancer.

Long noncoding RNA HULC regulates the NF-κB pathway and represents a promising prognostic biomarker in liver cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in a diverse array of biological processes. While lncRNAs are commonly upregulated in hepatocellular carcinoma (HCC), the specific regulatory roles they play in this oncogenic context require further study and clarification. Although HULC (lncRNA highly upregulated in liver cancer) is involved in disease pathogenesis, its precise role in this context remains unclear. METHODS: Here, we have explored the mechanistic relevance of HULC expression by assessing its expression in patient samples. The importance of this lncRNA in the onset and progression of HCC was investigated through in vitro approaches including Western blotting, quantitative PCR, Transwell assays, electron microscopy, wound healing assays, and real-time cell analysis (RTCA). Additionally, the in vivo functions of this lncRNA were assessed using an orthotopic HCC xenograft in nude mouse model system. RESULTS: HULC was identified as a lncRNA that is highly upregulated in human liver tumors. In vitro, HULC was able to promote HCC malignancy, although its excess overexpression also led robust autophagic induction, promoting the increased expression of autophagy-associated genes including LC3 and Beclin-1. At a mechanistic level, HULC was able to promote the phosphorylation of p65 and IkBkB thus enhancing autophagy by increasing LC3II levels in a manner dependent upon the NF-κB pathway. HULC downregulation was also linked to impaired orthotopic HCC tumor growth in vivo. The link between HULC and autophagy may play a role in disease progression. CONCLUSIONS: These results suggest that HULC is an oncogenic lncRNA, and may thus offer value as a prognostic biomarker and promoter of HCC development, in addition to being a potential therapeutic target in this cancer type.

A national-scale distribution of organochlorine pesticides (OCPs) in cropland soils and major types of food crops in China: Co-occurrence and associated risks.

Organochlorine pesticides (OCPs) are persistent organic pollutants (POPs) that resist degradation in the environment. OCPs remain detectable in cropland systems in China. However, spatial distribution of OCPs across China and associated ecological and health risks, as well as the relationship between levels of OCPs in cropland soils and crops, remain to be elucidated. To fill these gaps, we conducted a national-scale characterization of 19 individual OCPs in cropland soils and food crops including cereals and legumes in China, which were on-spot sampled simultaneously. Sparse canonical correlation analysis was employed to investigate the co-occurrence of OCPs in cropland soils and corresponding food crops. The ecological soil screening levels and risk quotient method were adopted for ecological and health risk assessment, respectively. Dichlorodiphenyltrichloroethanes (DDTs) were dominant in cropland systems, with its levels ranging up to 337 and 22.8 µg/kg in cropland soils and food crops, respectively. The mean ∑OCP levels in cropland soils varied from below the limit of detection to 337 µg/kg. Peanuts were the most contaminated crop, in which endosulfans and hexachlorobenzene (HCB) were co-occurrent with those in cropland soils (correlation coefficient R = 0.999 and 0.947, respectively). Besides, lindane and ß-endosulfan in rice were co-occurrent with those in cropland soils (R = 0.810 and 0.868, respectively). The componential ratio analysis indicated fresh inputs of technical DDT, lindane, chlordane, endosulfan, HCB and aldrin. Among these pesticides, ecological impacts of DDTs, lindane, aldrin and ß-endosulfan could be expected. Human health risk assessment suggested that daily consumption of the OCP-contaminated food crops raises a health concern especially for male teens. It is concluded that OCPs remain present in cropland systems in China at levels that raise a concern for both environment and human health.

Changes in blood gas values and electrolytes in the occluded artery predict outcomes after endovascular treatment in ischemic stroke.

BACKGROUND AND PURPOSE: Endovascular treatment (EVT) is the best treatment for acute ischemic stroke with large vessel occlusion (LVO) and makes it possible to analyze the blood contents from the occluded vascular compartments. In this study, we attempted to evaluate regional changes in blood gas values and electrolytes in the occluded vessels, aiming to determine whether these changes can predict outcomes in LVO patients receiving EVT. MATERIALS AND METHODS: We prospectively observed 45 consecutive ischemic stroke patients with LVO of the anterior circulation who underwent EVT. We collected the arterial blood proximal to the occlusion site before and after EVT, and the blood within the core of the occluded vascular compartment (distal to the thrombus) and evaluated the labs for blood gas values and electrolytes. Femoral samples were obtained under physiological flow conditions to represent systemic arterial blood. RESULTS: Compared with the femoral arterial blood samples, significant decreases in K+, Ca2+, HCO3-, BE, HCT, tHbc, and TCO2 levels were observed in the proximal luminal blood before EVT. Decreases in K+ and Ca2+ levels were also observed in the proximal luminal blood after EVT. Proximal/femoral ratio of pH and Na+ was associated with short-term clinical outcomes at 72 hours after EVT. A higher proximal/femoral Na+ ratio was associated with successful recanalization. Further analysis after propensity score matching showed significant changes in blood gas and electrolyte among different arterial locations in ICA and MCA LVO participants. Linear regression analyses indicated that the proximal/femoral ratio of pH, Na+, pCO2, HCO3, and TCO2 before EVT were associated with decrease in NIHSS score at 72 hours in ICA-LVO group. CONCLUSIONS: Obvious changes in several parameters of arterial blood gas and electrolyte from the ischemic vasculature occur during hyperacute stroke. Proximal/femoral pH and Na+ ratio before EVT may be associated with short-term clinical outcome, which deserve to be further investigated.

Wide-Scope Multi-residue analysis of pesticides in beef by gas chromatography coupled with quadrupole Orbitrap mass spectrometry.

Increasing pesticide contamination in foods of animal origin has made the wide-scope multi-residue analysis of pesticides an international concern. By using 191 pesticides, this study investigates a sensitive and reliable method for multi-residue analysis of pesticides in beef to determine the extent of the application of this method. The QuEChERS method was employed to extract and purify the pesticides as C18 was utilized as the absorbents. Then, the purified pesticides were analysed using gas chromatography - quadrupole orbitrap mass spectrometry (GC-Q-Orbitrap-MS). The validation test results revealed that this method was satisfactorily sensitive since its screening detection limit (SDL) ranged from 0.2 to 100 µg∙kg-1. The recovery tests implemented at three spiking levels, namely 100, 200, and 500 µg∙kg-1, generated the results of 71.95 %-113.97 %, while the intra- and inter-day precisions were 0.27 %-17.94 %, indicating that this method had excellent accuracy and precision.