AlphaFold2 assists in providing novel mechanistic insights into the interactions among the LUBAC subunits.

The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ligase complex in which the ubiquitin-like (UBL) domains of SHARPIN and HOIL-1L interact with HOIP to determine the structural stability of LUBAC. The interactions between subunits within LUBAC have been a topic of extensive research. However, the impact of the LTM motif on the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP remains unclear. Here, we discover that the absence of the LTM motif in the AlphaFold2-predicted LUBAC structure alters the HOIP-UBA structure. We employ GeoPPI to calculate the changes in binding free energy (ΔG) caused by single-point mutations between subunits, simulating their protein-protein interactions. The results reveal that the presence of the LTM motif decreases the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP, leading to a decrease in the structural stability of LUBAC. Furthermore, using the AlphaFold2-predicted results, we find that HOIP (629‒695) and HOIP-UBA bind to both sides of HOIL-1L-UBL, respectively. The experiments of Gromacs molecular dynamics simulations, SPR and ITC demonstrate that the elongated domain formed by HOIP (629‒695) and HOIP-UBA, hereafter referred to as the HOIP (466‒695) structure, interacts with HOIL-1L-UBL to form a structurally stable complex. These findings illustrate the collaborative interaction between HOIP-UBA and HOIP (629‒695) with HOIL-1L-UBL, which influences the structural stability of LUBAC.

High selectivity and fluorescence reversible Eu3+ sensor based on GSH-capped AgZnInS QDs.

Fluorescence sensors for trivalent europium ions (Eu3+) are seldom reported. We study the synthesis of water-soluble quaternary quantum dots (QDs) and investigate their fluorescence sensor application for detecting Eu3+ The as-synthesized glutathione (GSH)-capped AgZnInS (AZIS) QDs show great sensitivity and selectivity to Eu3+among 12 different metal cations. Detailed experimental results indicate that the fluorescence response of the AZIS QDs to increasing concentration of Eu3+ ([Eu3+]) include intensity quenching and peak wavelength blueshift. With the addition of OH-, the fluorescence response reverses. Electron transfer is considered to be the mechanism for the fluorescence quenching and peak wavelength blueshift of the GSH-capped AZIS QDs. Our work provides a new, to the best of our knowledge, method for the detection of Eu3+.

MiR-506-3p Promotes the Proliferation and Migration of Vascular Smooth Muscle Cells via Targeting KLF4.

BACKGROUND: The dysregulation of proliferation and migration of vascular smooth muscle cells (VSMCs) is one of the major causes of atherosclerosis (AS). Accumulating studies confirm that Kruppel-like factor 4 (KLF4) can regulate the proliferation and differentiation of VSMCs through multiple signaling pathways. However, the mechanism of KLF4 dysregulation remains unknown. METHODS: Apolipoprotein E-knockout (ApoE-/-) mice and human VSMCs were used to establish AS animal model and cell model, respectively. qRT-PCR was employed to determine the expressions of miR-506-3p and KLF4. Cell Counting Kit -8, Transwell, TUNEL assays, and flow cytometry were performed to measure the proliferation, migration, and apoptosis of VSMCs. The upstream miRNAs of KLF4 were predicted by microT, miRanda, miRmap, and TargetScan databases. The interaction between KLF4 and miR-506-3p was confirmed using qRT-PCR, Western blot, and luciferase reporter gene assay. RESULTS: KLF4 expression was significantly decreased in the VSMCs of ApoE-/- mice fed with high-fat diet and in human VSMCs treated with oxidized low-density lipoprotein in time-dependent and dose-dependent manners. The transfection of miR-506-3p mimics or KLF4 shRNA promoted the proliferation and migration of VSMCs but inhibited the apoptosis while miR-506-3p inhibitors and pcDNA3.1-KLF4 exerted opposite effects. Additionally, KLF4 was confirmed as a target gene of miR-506-3p and could be negatively regulated by miR-506-3p. CONCLUSION: MiR-506-3p can promote the proliferation and migration of VSMCs via targeting KLF4, which can probably contribute to the pathogenesis of AS.

Liver function recovery of COVID-19 patients after discharge, a follow-up study.

Objective: The aim of this study was to observe the liver function recovery of COVID-19 patients after discharge. Patients and Methods: A total of 253 discharged COVID-19 patients in Shenzhen city, China were selected. The clinical characteristics of these patients were assessed. A 2-month follow-up and laboratory hematology test were performed to examine the status of patients' liver function. Results: Patients combined with liver diseases, especially fatty liver, are more likely to progress to severe condition (P<0.05). Patients in severe condition and those with liver diseases have higher rates of liver injuries during hospitalization, characterized by a significant increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.01). The ALT, AST/ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), and A/G levels showed significant differences in comparison with the control group (P<0.05, and P<0.001); and the outlier ratio of A/G, ALT, GGT and ALP of patients remained abnormal higher within 14 days after discharge (P<0.001). Liver injuries of COVID-19 patients may be related to the epidemiological characteristics, clinical indexes, basic diseases, symptoms, drug treatment during hospitalization and the complications. Indicators of liver function were correlated with cardiac function, renal function, thyroid function, lipid metabolism, glucose metabolism, immune index, leukocyte, erythrocyte, hemoglobin and platelet related indexes. The outlier ratio of TP, ALB and GLB remained extremely low throughout the follow-up period; the outlier ratio of ALT, AST and GGT decreased below 10% from a high level at 40 days after discharged. However, the outlier ratio of A/G, AST/ALT and ALP remained high during the follow-up period. Conclusions: Abnormal liver function might indicate worse recovery of COVID-19 patients. Changes in liver function should be emphasized during long-term follow-up of COVID-19 patients after hospital discharge; the necessity of employing appropriate interventions for liver function repair should be emphasized.

Effects of wogonoside on the inflammatory response and oxidative stress in mice with nonalcoholic fatty liver disease.

CONTEXT: Wogonoside has many pharmacological activities, but whether it has a protective effect against non-alcoholic fatty liver disease (NAFLD) has not been reported. OBJECTIVE: This study investigates the protective effect of wogonoside against NAFLD in mice and its potential mechanism. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into control group, NAFLD group and low-, medium- and high-dose wogonoside groups (5, 10 and 20 mg/kg, respectively) (n= 12). Mice in the control group were fed with the standard diet, and those in NAFLD group and low-, medium- and high-dose wogonoside groups were fed with a high-fat diet. The different doses of wogonoside were administered by gavage once a day for 12 weeks. RESULTS: Compared with those in NAFLD group, the liver mass, liver index and the LDL, TG, TC, IL-2, IL-6, TNF-α, MDA and NF-κB p65 levels were decreased, and the SOD and GSH-Px activities, and HDL, IκBα, Nrf2 and HO-1 contents were increased in wogonoside groups. Compared with those in the NAFLD group, wogonoside (5, 10 and 20 mg/kg) reduced AST (132.21 ± 14.62, 115.70 ± 11.32 and 77.94 ± 8.86 vs. 202.35 ± 19.58 U/L) and ALT (104.37 ± 11.92, 97.53 ± 10.12 and 56.74 ± 6.33 vs. 154.66 ± 14.23 U/L) activities in the serum. DISCUSSION AND CONCLUSIONS: Wogonoside has a protective effect against NAFLD in mice, which may be related to its anti-inflammation and inhibition of oxidative stress, suggesting that wogonoside may be a potential therapeutic agent for the treatment of NAFLD.

Aptamer inhibitor selection of SpyCas9 through CE-SELEX.

CRISPR/Cas9 is a natural immune system of archaea and bacteria, which has been widely used in gene editing. In order to better control and improve the accuracy and safety of the system, inhibitors for SpyCas9 as "switches" have been selected for several years. The available inhibitors currently are all natural polypeptides inhibitors derived from phages, except one small molecule inhibitor. These natural inhibitors are challenging to obtain and are available in limited quantities, and the small molecule inhibitor is cytotoxic. Herein, we discover aptamers against the SpyCas9 protein, by coupling CE-SELEX within one-round pressure controllable selection strategy. One of the identified aptamers, Apt2, shows high affinity at the nanomolar level and leads for effective SpyCas9 enzymatic inhibition in vitro. It is predicted that Apt2 interacts with the HNH and RuvC domains of SpyCas9, competitively inhibiting the binding of substrate DNA to SpyCas9. The proposed aptamer inhibitor is the oligonucleotide inhibitor of SpyCas9, which has the potential in construction of the universal, simple and precise CRISPR-Cas9 system activity control strategy. Meanwhile, these aptamers could also be valuable tools for study of the functions of CRISPR/Cas9 and the related functional mechanisms.

Inhaled polystyrene microplastics impaired lung function through pulmonary flora/TLR4-mediated iron homeostasis imbalance.

Microplastics (MPs) have been found in the air, human nasal cavity, and lung, suggesting that the respiratory tract is one of the important exposure routes for MPs. The lung is a direct target organ for injury from inhaled MPs, but data on lung injury from longer-term exposure to environmental doses of MPs are limited, and the mechanisms remain unclear. Here, C57BL/6 J mice were treated with 5 µm polystyrene (PS)-MPs by intratracheal instillation (0.6, 3, and 15 mg/kg) for 60 days to establish MPs exposure model. We found that PS-MPs lead to increased collagen fibers and decreased lung barrier permeability and lung function in lung tissue. Mechanistically, the abundance of gram-negative bacteria in the pulmonary flora increased after inhalation of PS-MPs, causing lipopolysaccharide (LPS) release. The expression of Toll-like receptor 4 (TLR4), the key receptor of LPS, was increased, and ferroptosis occurred in lung tissue cells. Further in vitro intervention experiments were performed, pulmonary flora/TLR4-induced imbalance of lung iron homeostasis is an important mechanism of PS-MPs-induced lung injury. Our study provides new evidence for lung injury caused by environmental doses of MPs and strategies to prevent it through longer-term dynamic observation.

Cuproptosis is involved in decabromodiphenyl ether-induced ovarian dysfunction and the protective effect of melatonin.

Decabromodiphenyl ether (BDE-209) has been universally detected in environmental media and animals, but its damage to ovarian function and mechanism is still unclear, and melatonin has been shown to improve mammalian ovarian function. This study aimed to investigate the toxic effects of BDE-209 on the ovary and tried to improve ovarian function with melatonin. Herein, BDE-209 was administered orally to female SD rats for 60 days. Enzyme-linked immunosorbent assay, HE staining, transcriptome analysis, qPCR and immunohistochemical staining were used to explore and verify the potential mechanism. We found that BDE-209 exposure had effects on the ovary, as shown by abnormal changes in the estrous cycle, hormone levels and ovarian reserve function in rats, while increasing the proportion of collagen fibres in ovarian tissue. In terms of mechanism, cuproptosis, a form of cell death, was identified to play a crucial role in BDE-209-induced ovarian dysfunction, with the phenotype manifested as copper salt accumulation in ovary, downregulation of glutathione pathway metabolism and copper transfer molecule (ATP7A/B), and upregulation of FDX1, lipoic acid pathway (LIAS, LIPT1), pyruvate dehydrogenase complex components (DLAT, PDHB, PDHA1), and copper transfer molecule (SLC31A1). Furthermore, possible interventions were explored. Notably, a supplement with melatonin has a repair effect on the damage to ovarian function by reversing the gene expression of cuproptosis-involved molecules. Overall, this study revealed that cuproptosis is involved in BDE-209-induced ovarian damage and the beneficial effect of melatonin on ovarian copper damage, providing evidence for the prevention and control of female reproductive damage induced by BDE-209.

Effects of Hibernation on Colonic Epithelial Tissue and Gut Microbiota in Wild Chipmunks (Tamias sibiricus).

The gut microbiota plays a crucial role in the host's metabolic processes. Many studies have shown significant changes in the gut microbiota of mammals during hibernation to adapt to the changes in the external environment, but there is limited research on the colonic epithelial tissue and gut microbiota of the wild chipmunks during hibernation. This study analyzed the diversity, composition, and function of the gut microbiota of the wild chipmunk during hibernation using 16S rRNA gene high-throughput sequencing technology, and further conducted histological analysis of the colon. Histological analysis of the colon showed an increase in goblet cells in the hibernation group, which was an adaptive change to long-term fasting during hibernation. The dominant gut microbial phyla were Bacteroidetes, Firmicutes, and Proteobacteria, and the relative abundance of them changed significantly. The analysis of gut microbiota structural differences indicated that the relative abundance of Helicobacter typhlonius and Mucispirillum schaedleri increased significantly, while unclassified Prevotella-9, unclassified Prevotellaceae-UCG-001, unclassified Prevotellaceae-UCG-003 and other species of Prevotella decreased significantly at the species level. Alpha diversity analysis showed that hibernation increased the diversity and richness of the gut microbiota. Beta diversity analysis revealed significant differences in gut microbiota diversity between the hibernation group and the control group. PICRUSt2 functional prediction analysis of the gut microbiota showed that 15 pathways, such as lipid metabolism, xenobiotics biodegradation and metabolism, amino acid metabolism, environmental adaptation, and neurodegenerative diseases, were significantly enriched in the hibernation group, while 12 pathways, including carbohydrate metabolism, replication and repair, translation, and transcription, were significantly enriched in the control group. It can be seen that during hibernation, the gut microbiota of the wild chipmunk changes towards taxa that are beneficial for reducing carbohydrate consumption, increasing fat consumption, and adapting more strongly to environmental changes in order to better provide energy for the body and ensure normal life activities during hibernation.

[Neonatal intrahepatic cholestasis caused by citrin deficiency: a histopathologic study of 10 cases].

OBJECTIVE: To investigate the diagnostic value of histopathological changes in the liver of patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). METHODS: Liver specimens from 10 cases of NICCD were evaluated by hematoxylin-eosin stain, histochemistry and immunohistochemistry (EnVision method). SLC25A13 mutation analysis was performed to correlate with histopathology. RESULTS: Most specimens showed varying degrees of fat deposition in hepatocytes, necrotic inflammation, cholestasis and fibrosis (so-called tetralogy). The combination of the above four histological changes was highly characteristic for NICCD. With the progression of the disease, hepatic fibrosis deteriorated and ultimately led to cirrhosis. CONCLUSIONS: NICCD should be suspected in the presence of cholestasis during infancy. A liver biopsy must be performed to rule out other liver diseases. The tetralogy of the hepatic histopathological changes has a highly diagnostic value for NICCD, which is also practical for accurately assessing the degree of inflammation and fibrosis, and similarly the progression of hepatic cirrhosis.

[Pathological observation of lung injury in experimental animals induced by non-ferrous metal (tin) dusts].

OBJECTIVE: To explore the characters of lung injury induced by tin dusts and to provide the diagnosis evidence of tin pneumoconiosis. METHODS: Forty SD rats were randomly divided into four groups: the group exposed to tin dusts from smelting workshop, the group exposed to tin dusts from tin refining workshop, the positive control group exposed to standard quartz dusts and the negative control group exposed to saline. The pathological changes of rat lungs were observed dynamically. RESULTS: In rats exposed to tin dusts, on the 30th day after exposure to tin dusts, the scattered hoar tip size of the spots in surface and section of the lungs were observed, the scattered focal granulomatous inflammation around the small bronchi and dust particles in lung tissue were observed under microscope; on the 90th day after exposure to tin dusts, the granulomatous inflammation increase, the fibroblasts proliferation, collagen fibers formation and positive VG staining were found. There were significant differences, as compared with positive or negative controls (P < 0.05). These pathological changes were basically the characters of specific pathological changes in early tin pneumoconiosis. CONCLUSION: Non-ferrous metal tin dusts can induce the specific lung injury (granuloma formation) in lung tissue of rats exposed to tin dusts, which fulfilled the diagnostic criteria of specific pathological changes in early tin pneumoconiosis.

LncRNA OIP5-AS1 promotes the proliferation and migration of vascular smooth muscle cells via regulating miR-141-3p/HMGB1 pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to play critical roles in the pathogenesis of cardiovascular diseases. However, whether lncRNA opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) regulates the pathogenesis of atherosclerosis (AS) is still unknown. METHODS: Human vascular smooth muscle cells (VSMCs) were treated with oxidized low-density lipoprotein (ox-LDL). OIP5-AS1, miR-141-3p and HMGB1 mRNA expressions were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and apoptosis of VSMCs were measured using MTT method, Transwell assay and TUNEL assay, respectively. Dual-luciferase reporter gene assay, qRT-PCR, and Western blot were conducted to investigate the interactions among OIP5-AS1, miR-141-3p and high mobility group box 1 (HMGB1). RESULTS: OIP5-AS1 expression was markedly increased in serum samples of AS patients and VSMCs treated with ox-LDL. OIP5-AS1 over-expression remarkably promoted proliferation, migration and inhibited apoptosis of VSMCs while miR-141-3p exerted the opposite effects. Furthermore, the binding sites between OIP5-AS1 and miR-141-3p were identified. OIP5-AS1 indirectly increased HMGB1 expression in VSMCs by targeting miR-141-3p. CONCLUSIONS: OIP5-AS1 promotes the proliferation, migration and suppresses apoptosis of VSMCs through regulating miR-141-3p/HMGB1 axis.

Integrated analysis of the genomic and transcriptional profile of gliomas with isocitrate dehydrogenase-1 and tumor protein 53 mutations.

Background: The gene mutation of isocitrate dehydrogenase-1 (IDH1) is commonly found in LGG and some GBM patients and usually carries tumor protein 53 (TP53) mutations. However, the underlying mechanisms on both mutations of glioma patients in IDH1 and TP53 are still unclear. Aim: To find the potential target markers in GBM and LGG patients with IDH1 and TP53 mutation.Method: A total of 1122 glioma patients from The Cancer Genome Atlas were enrolled and divided as wild-type (without IDH1 and TP53 mutations) or both mutant (both IDH1 and TP53 mutations). The data of clinicopathological characteristics, mRNA, mutations, and copy number alteration were analyzed. Results: IDH1 and TP53 mutations, not gene expression, affect the survival probability of GBM and LGG patients, which might be related to neuron function, immune function, tumor invasion, and metastasis. The effects of the selected gene (EMILIN3, SAA1, VSTM2A, HAMP, IFT80, and CHIC2) on glioma patients could be regulated by IDH1 and TP53 mutations and had a higher survival possibility in these patients. Conclusions: The selected genes in GBM and LGG patients with IDH1 and TP53 mutations could be a potential prognosis marker in the future.

A prospective study of dual-energy computed tomography for differentiating metastatic and non-metastatic lymph nodes of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignancy worldwide, and lymph node metastasis is considered to be a risk factor for local recurrence and a poor prognosis in colorectal cancer. However, there remains a lack of reliable and non-invasive biomarkers to identify the lymph node status of CRC patients preoperatively. The purpose of this study was to explore the ability of dual-energy computed tomography (DECT) to differentiate metastatic from non-metastatic lymph nodes in colorectal cancer. METHODS: Seventy-one patients with primary colorectal cancer underwent contrast-enhanced dual-energy computed tomography imaging preoperatively. The colorectal specimen was scanned postoperatively, and lymph nodes were matched to the pathology report. The following dual-energy computed tomography quantitative parameters were analyzed: dual-energy curve slope value (λHU), standardized iodine concentration (n△HU), iodine water ratio (nIWR), electron density value (nρeff), and effective atom-number (nZ), based on metastatic and non-metastatic lymph node differentiation. Also, sensitivity and specificity analyses were performed using receiver operating characteristic curves. RESULTS: In all patients, one hundred and fifty lymph nodes, including 66 non-metastatic and 84 metastatic lymph nodes, were matched using the radiological-pathological correlation. Metastatic nodes had significantly greater λHU, n△HU, and nIWR values than non-metastatic nodes in both the arterial and venous phases (P<0.01). The area under curve (AUC), sensitivity, and specificity were 0.80, 80%, and 66% for λHU; 0.86, 70%, and 95% for n△HU; and 0.88, 71%, and 95% for nIWR in the arterial phase. There was no significant difference in electron density and effective Z values between metastatic and non-metastatic lymph nodes. CONCLUSIONS: DECT quantitative parameters may help differentiate between metastatic and normal lymph nodes in patients with CRC.

Inhibition of human cytomegalovirus infection by IE86-specific short hairpin RNA-mediated RNA interference.

To develop a gene therapeutic method for human cytomegalovirus (HCMV), the IE86 specific short hairpin (sh) RNA expressing vector was constructed and subsequently transfected into MRC-5 cells. After infection of these cells with HCMV AD169, expression of IE86 was reduced strikingly as compared to the control. In addition, the inhibitory effect corresponded to a decrease in viral DNA replication and the virus-induced cytopathic effect. Measurement of the virus yield demonstrated that infection of cells expressing IE86-specific shRNA resulted in suppression of the formation of infectious viral progeny. These observations indicate that IE86 can be used as an effective target against HCMV infection using RNA interference (RNAi) technology, which provides new possibilities for anti-HCMV studies.

Long non­coding RNA Unigene56159 promotes glioblastoma multiforme cell proliferation and invasion through negatively regulating microRNA­194­5p.

Long non­coding RNAs (lncRNA) serve a vital role in tumor progression. The present study identified a fundamental role for a novel lincRNA, Unigene56159, in the progression of glioblastoma (GBM). Unigene56159 gene expression was found to be significantly upregulated in tissue samples from patients with GBM as well as in GBM cell lines by reverse transcription­quantitative PCR, while microRNA (miR)­194­5p expression levels were decreased. This higher expression level of Unigene56159 was positively correlated with poor overall survival in patients with GBM. However, the mechanism by which this occurs remains to be elucidated. lncRNAs may act as endogenous miRNA sponges for binding to miRNAs or participating in the competitive endogenous RNAs (ceRNA) regulatory network. Small interfering RNA (siRNA) was used to silence the expression of Unigene56159 and inhibit the proliferation and invasion of GBM cell lines by MTT and Transwell assay. Unigene56159 was found to directly interact with miR­194­5p, and rescue assay was performed to further confirm that Unigene56159 contributed to glioma progression by regulating miR­194­5p. Thus, Unigene56159 may function as a competing endogenous RNA by sequestering miR­194­5p in GBM cells. These findings suggested that Unigene56159 may serve an oncogenic role in GBM and may promote disease progression through interacting with miR­194­5p. This could be a potential therapeutic target for the treatment of GBM.

Dispositional Mindfulness and Past-Negative Time Perspective: The Differential Mediation Effects of Resilience and Inner Peace in Meditators and Non-Meditators.

PURPOSE: Past-negative time perspective (PNTP) can affect our everyday lives and is associated with negative emotions, unhealthy behaviors, rumination, anxiety, depression, and post-traumatic stress disorder (PTSD). Dispositional mindfulness may be able to reduce the negative effects of PNTP; however, few studies have investigated their relationship. Thus, the purpose of this study was to explore the effect dispositional mindfulness has on PNTP, as well as the mediating role of resilience and inner peace in this regard. METHODS: This study investigated the cross-sectional relationship between self-reported mindfulness, resilience, inner peace, and PNTP. In order to further explore the relationship between mindfulness and PNTP, this study specially selected and analyzed the samples of 185 meditators and 181 non-meditators. RESULTS: Correlation analysis revealed that mindfulness is significantly positively correlated with resilience and inner peace. Conversely, PNTP is significantly negatively correlated with mindfulness, resilience, and inner peace. Structural equation model analysis revealed that resilience and inner peace partially mediated the relationship between mindfulness and PNTP. Furthermore, a multi-group analysis showed that the mediating effects are different between meditators and non-meditators. For meditators, the effect of mindfulness on PNTP was fully mediated by resilience and inner peace. For non-meditators, the effect of mindfulness on PNTP was only partially mediated by resilience and inner peace. CONCLUSION: Based on the significant differences between the mediational models of meditators and non-meditators, we believe that dispositional mindfulness can negatively predict PNTP, and practicing meditation consistently improves dispositional mindfulness, resilience and inner peace and effectively reduces PNTP. Our findings indicate that a combination of mindfulness and PNTP could be used to design new psychological interventions to reduce the symptoms of mental health concerns such as negative bias, rumination, depression, anxiety, and PTSD.

Insights into N, P, S multi-doped Mo2C/C composites as highly efficient hydrogen evolution reaction catalysts.

Heteroatom doping has been proved to be an effective strategy to optimize the activity of hydrogen evolution reaction (HER) catalysts. Herein, we report N, P, S multi-doped Mo2C/C composites exhibiting highly efficient HER performance in acidic solution, which are facilely fabricated via annealing of N, P, S-containing MoO x -polyaniline (MoO x -PANI) hybrid precursors. The optimized N, P, S multi-doped Mo2C/C catalyst with a moderate P dopant level (NPS-Mo2C/C-0.5) exhibits excellent performance with an overpotential of 53 mV to achieve a current density of 20 mA cm-2, a Tafel slope of 72 mV dec-1 and good stability in acidic electrolytes. Based on the study of XPS, EPR and 31P MAS NMR, the excellent electrocatalytic performance could be attributed to the effective electronic configuration modulation of both Mo2C nanorods and the carbon matrix, derived from stronger synergistic N, P, S multi-doping coupling effects. This work provides a promising methodology for the design and fabrication of multi-doped transition metal based electrocatalysts via electronic structure engineering.

Long non-coding RNA EWSAT1 contributes to the proliferation and invasion of glioma by sponging miR-152-3p.

Long non-coding RNAs (lncRNA) are a type of ncRNA with a length ranging from 200-1,000 nucleotides. Previous studies have confirmed that the lncRNA Ewing sarcoma associated transcript 1 (EWSAT1) exerts regulatory roles in cancer development and progression. However, its clinical significance in glioma remains unknown. In the present study, RNA-sequencing data from the Gene Expression Omnibus database and The Cancer Genome Atlas was explored to investigate the association between EWSAT1 expression and prognosis in patients with glioma. Increased EWSAT1 was associated with the presence of necrosis on magnetic resonance imaging scans in patients with glioma. Furthermore, knockdown of EWSAT1 was indicated to suppress the proliferative and invasive abilities of glioblastoma cell lines using Cell Counting Kit-8 and Transwell assays. Additionally, microRNA (miR)-152-3p was identified as a potential target of EWSAT1. The present study demonstrated that EWSAT1 interacted directly with miR-152-3p, and rescue experiments confirmed that EWSAT1 participated in glioma development by suppressing miR-152-3p. These results indicated that EWSAT1 is involved in the occurrence and progression of glioma, and may serve as a novel target and potential prognostic biomarker of glioma treatment.

Sinoporphyrin sodium is a promising sensitizer for photodynamic and sonodynamic therapy in glioma.

The aim of the present study was to explore the antitumor effects of sinoporphyrin sodium (DVDMS)­mediated photodynamic therapy (PDT) and sonodynamic therapy (SDT) in glioma, and to reveal the underlying mechanisms. The uptake of DVDMS by U­118 MG cells was detected by flow cytometry (FCM). A 630­nm semiconductor laser and 1­MHz ultrasound were used to perform PDT and SDT, respectively. Cell proliferation and apoptosis were evaluated using the Cell Counting Kit­8 assay, FCM and Hoechst 33258 staining, respectively. Western blot analysis was used to detect protein expression and phosphorylation levels. BALB/c nude mice were used to establish a xenograft model of U­118 MG cells. DVDMS was injected intravenously and PDT and SDT were performed 24 h later. An in vivo imaging system was used to evaluate the fluorescence of DVDMS, to measure tumor sizes, and to evaluate the therapeutic effects. The uptake of DVDMS by U­118 MG cells was optimal after 4 h. PDT and SDT following DVDMS injection significantly inhibited the proliferation and increased apoptosis of glioma cells in vitro (P<0.05, P<0.01) respectively. In vivo, the fluorescence intensity of DVDMS was lower in the PDT and SDT groups compared with the DVDMS group, while tumor cell proliferation and weight were lower in the PDT and SDT groups than in the control group (P<0.05, P<0.01). However, there was no significant difference when laser, ultrasound or DVDMS were applied individually, compared with the control group. Hematoxylin and eosin staining suggested that both PDT and SDT induced significant apoptosis and vascular obstruction in cancer tissues. DVDMS­mediated PDT and SDT inhibited the expression levels of proliferating cell nuclear antigen (PCNA) and Bcl­xL, increased cleaved ­caspase 3 levels, and decreased the protein phosphorylation of the PI3K/AKT/mTOR signaling pathway. Changes in the expression of PCNA, and Bcl­xL and in the levels of cleaved­caspase 3 were partly reversed by N­acetyl­L­cysteine, a reactive oxygen species (ROS) scavenger. Similar results were obtained with FCM. DVDMS­mediated PDT and SDT inhibited glioma cell proliferation and induced cell apoptosis in vitro and in vivo, potentially by increasing the generation of ROS and affecting protein expression and phosphorylation levels.