The repertoire of copy number alteration signatures in human cancer.

Copy number alterations (CNAs) are a predominant source of genetic alterations in human cancer and play an important role in cancer progression. However comprehensive understanding of the mutational processes and signatures of CNA is still lacking. Here we developed a mechanism-agnostic method to categorize CNA based on various fragment properties, which reflect the consequences of mutagenic processes and can be extracted from different types of data, including whole genome sequencing (WGS) and single nucleotide polymorphism (SNP) array. The 14 signatures of CNA have been extracted from 2778 pan-cancer analysis of whole genomes WGS samples, and further validated with 10 851 the cancer genome atlas SNP array dataset. Novel patterns of CNA have been revealed through this study. The activities of some CNA signatures consistently predict cancer patients' prognosis. This study provides a repertoire for understanding the signatures of CNA in cancer, with potential implications for cancer prognosis, evolution and etiology.

Directly Unveiling the Energy Transfer Dynamics between Alq3 Molecules and Si by Ultrafast Optical Pump-Probe Spectroscopy.

The energy transfer (ET) between organic molecules and semiconductors is a crucial mechanism for enhancing the performance of semiconductor-based optoelectronic devices, but it remains undiscovered. Here, ultrafast optical pump-probe spectroscopy was utilized to directly reveal the ET between organic Alq3 molecules and Si semiconductors. Ultrathin SiO2 dielectric layers with a thickness of 3.2-10.8 nm were inserted between Alq3 and Si to prevent charge transfer. By means of the ET from Alq3 to Si, the SiO2 thickness-dependent relaxation dynamics of photoexcited carriers in Si have been unambiguously observed on the transient reflectivity change (ΔR/R) spectra, especially for the relaxation process on a time scale of 200-350 ps. In addition, these findings also agree with the results of our calculation in a model of long-range dipole-dipole interactions, which provides critical information for developing future optoelectronic devices.

A critical role of outer membrane vesicles in antibiotic resistance in carbapenem-resistant Klebsiella pneumoniae.

BACKGROUND: This study aimed to illustrate the status of carbapenem-resistant Enterobacterales (CRE) infections in a Chinese tertiary hospital and to investigate the role of outer membrane vesicles (OMVs) in antibiotic resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP). METHODS: The data of CRE infections was collected from laboratory records, and the CRE isolates from two distinct periods (2015/07 to 2017/07 and 2020/04 to 2021/04) were enrolled to detect the carbapenemase genes by polymerase chain reaction (PCR). Multilocus sequence typing (MLST) was used to analyze the molecular characterization of CRKP. The conjugation assay was performed to verify the transmission of the antibiotic resistance plasmid. The OMVs of CRKP were isolated with a method combining an electrophoretic technique with a 300 kDa cut-off dialysis bag. The protein components in CRKP OMVs were analyzed by liquid chromatography tandem-mass spectrometry (LC-MS/MS), and the meropenem-hydrolyzing bioactivity of KPC in CRKP OMVs was determined with different treatments in vitro. RESULTS: A total of 178 CRE isolates, including 100 isolates from 2015/07 to 2017/07 and 78 isolates from 2020/04 to 2021/04, were collected for the detection of carbapenemase genes. We found that the carbapenemase gene blaKPC was the most prevalent, followed by blaNDM. By MLST, we found that sequence type (ST) 11 CRKP (96.1%) was the leading type during 2015/07 to 2017/07 and that the ST15 CRKP increased to 46.2% in the late period of 2020/04 to 2021/04. The diameters of Klebsiella pneumoniae OMVs ranged from 100 to 200 nm, and by proteomics analysis the most proteins from OMVs belonged to the "enzyme" group. The KPC enzyme was found in the OMVs from CRKP, and the OMVs could protect inside KPC from proteinase K digestion. Moreover, the KPC enzymes within OMVs, which could be released after Triton X-100 treatment, could hydrolyze meropenem. CONCLUSIONS: CRE has increasingly caused infections in hospitals, and blaKPC-positive CRKP infections have constituted a major proportion of infections in the past decade. The OMVs play a critical role in antibiotic resistance in CRKP.

Chinese expert consensus statement on the clinical application of AFP/AFP-L3%/DCP using GALAD and GALAD-like algorithm in HCC.

BACKGROUND: Primary hepatocellular carcinoma (HCC) is one of the most prevalent world-wide malignancies. Half of the newly developed HCC occurs in China. Optimizing the strategies for high-risk surveillance and early diagnosis are pivotal for improving 5-year survival. Constructing the scientific non-invasive detection technologies feasible for medical and healthcare institutions is among the key routes for elevating the efficacies of HCC identification and follow-up. RESULTS: Based on the Chinese and international guidelines, expert consensus statements, literatures and evidence-based clinical practice experiences, this consensus statement puts forward the clinical implications, application subjects, detection techniques and results interpretations of the triple-biomarker (AFP, AFP-L3%, DCP) based GALAD, GALAD like models for liver cancer. CONCLUSIONS: The compile of this consensus statement aims to address and push the reasonable application of the triple-biomarker (AFP, AFP-L3%, DCP) detections thus to maximize the clinical benefits and help improving the high risk surveillance, early diagnosis and prognosis of HCC.

Bitter melon derived extracellular vesicles enhance the therapeutic effects and reduce the drug resistance of 5-fluorouracil on oral squamous cell carcinoma.

BACKGROUND: Plant-derived extracellular vesicles (PDEVs) have been exploited for cancer treatment with several benefits. Bitter melon is cultivated as a vegetable and folk medicine with anticancer and anti-inflammatory activities. 5-Fluorouracil (5-FU) is widely used for cancer treatment. However, 5-FU-mediated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammation activation induced the resistance of oral squamous cell carcinoma (OSCC) cells to 5-FU. In this study, we explored the potential of bitter melon-derived extracellular vesicles (BMEVs) for enhancing the therapeutic efficacy and reduce the resistance of OSCC to 5-FU. RESULTS: Herein, we demonstrate that bitter melon derived extracellular vesicles (BMEVs), in addition to their antitumor activity against OSCC have intrinsic anti-inflammatory functions. BMEVs induced S phase cell cycle arrest and apoptosis. Apoptosis induction was dependent on reactive oxygen species (ROS) production and JUN protein upregulation, since pretreatment with N-acetyl cysteine or catechin hydrate could prevent apoptosis and JUN accumulation, respectively. Surprisingly, BMEVs significantly downregulated NLRP3 expression, although ROS plays a central role in NLRP3 activation. We further assessed the underlying molecular mechanism and proposed that the RNAs of BMEVs, at least in part, mediate anti-inflammatory bioactivity. In our previous studies, NLRP3 activation contributed to the resistance of OSCC cells to 5-FU. Our data clearly indicate that BMEVs could exert a remarkable synergistic therapeutic effect of 5-FU against OSCC both in vitro and in vivo. Most notably, NLRP3 downregulation reduced the resistance of OSCC to 5-FU. CONCLUSIONS: Together, our findings demonstrate a novel approach to enhance the therapeutic efficacy and reduce the drug resistance of cancer cells to chemotherapeutic agents, which provides proof-of-concept evidence for the future development of PDEVs-enhanced therapy.

Approaching autonomous driving with cautious optimism: analysis of road traffic injuries involving autonomous vehicles based on field test data.

OBJECTIVES: To examine the patterns and associated factors of road traffic injuries (RTIs) involving autonomous vehicles (AVs) and to discuss the public health implications and challenges of autonomous driving. METHODS: Data were extracted from the reports of traffic crashes involving AVs. All the reports were submitted to the California Department of Motor Vehicles by manufacturers with permission to operate AV test on public roads. Descriptive analysis and χ2 analysis or Fisher's exact test was conducted to describe the injury patterns and to examine the influencing factors of injury outcomes, respectively. Binary logistic regression using the Wald test was employed to calculate the OR, adjusted OR (AOR) and 95% CIs. A two-tailed probability (p<0.05) was adopted to indicate statistical significance. RESULTS: 133 reports documented 24 individuals injured in 19 crashes involving AVs, with the overestimated incidence rate of 18.05 per 100 crashes. 70.83% of the injured were AV occupants, replacing vulnerable road users as the leading victims. Head and neck were the most commonly injured locations. Driving in poor lighting was at greater risk of RTIs (AOR 6.37, 95% CI 1.47 to 27.54). Collisions with vulnerable road users or incidents happening during commute periods led to a greater number of victims (p<0.05). Autonomous mode cannot perform better than conventional mode in road traffic safety to date (p=0.468). CONCLUSIONS: Poor lighting improvement and the regulation of commute-period traffic and vulnerable road users should be strengthened for AV-related road safety. So far AVs have not demonstrated the potential to dramatically reduce RTIs. Cautious optimism about AVs is more advisable, and multifaceted efforts, including legislation, smarter roads, and knowledge dissemination campaigns, are fairly required to accelerate the development and acceptance.

An efficient method to isolate lemon derived extracellular vesicles for gastric cancer therapy.

BACKGROUND: Plant-derived extracellular vesicles (PDEVs) have great potential for clinical applications. Ultracentrifugation, considered the gold standard method for the preparation of PDEVs, is efficacious but time-consuming and highly instrument-dependent. Thus, a rapid and handy method is needed to facilitate the basic researches and clinical applications of PDEVs. RESULTS: In this study, we combined electrophoretic technique with 300 kDa cut-off dialysis bag (named ELD) for the isolation of PDEVs, which was time-saving and needed no special equipment. Using ELD, lemon derived extracellular vesicles (LDEVs) could be isolated from lemon juice. Nanoparticle tracking analysis and transmission electron microscopy confirmed that the method separated intact vesicles with a similar size and number to the standard method-ultracentrifugation. LDEVs caused the gastric cancer cell cycle S-phase arrest and induced cell apoptosis. The anticancer activities of LDEVs on gastric cancer cells were mediated by the generation of reactive oxygen species. In addition, LDEVs were safe and could be remained in gastrointestinal organs. CONCLUSIONS: ELD was an efficient method for the isolation of LDEVs, and could be carried out in any routine biological laboratory as no special equipment needed. LDEVs exerted anticancer activities on gastric cancer, indicating the great potentials for clinical application as edible chemotherapeutics delivery vehicle.

Transcriptome analysis of leg muscles in fast and slow growth Bian chickens.

Chicken is popular among consumers in the market, but the mechanism for regulating its growth is still unclear. In this experiment, two groups of Bian chickens of different body weights at 16 weeks of age were studied. The leg muscles were taken for transcriptome sequencing after slaughter. In the differential gene screening, all the genes obtained by sequencing the fast and slow growth groups were screened by Fold Change ≥2 and False Discovery Rate (FDR) <0.05, and 108 differentially expressed genes were obtained. The slow growth group has 17 up-regulated genes and 91 down-regulated genes compared with the fast growing group. Significance analysis of differentially expressed genes in gene ontology (GO) enrichment indicates that there are 65, 16 and 6 significantly enriched entries in the three main categories of biological processes, cellular components and molecular functions (P-value <0.05), respectively. Pathway enrichment analysis yielded three significantly enriched signal pathways: Adrenergic signaling in cardiomyocytes, Cardiac muscle contraction and Tight junction. The experiment would contribute to reveal the molecular mechanism of chicken growth and provide a theoretical basis for improving the performance of Bian chicken.

Dynamic expression and functional analysis of circRNA in granulosa cells during follicular development in chicken.

BACKGROUND: Circular RNA (circRNA) is a type of noncoding RNA involved in a variety of biological processes, especially in post-transcriptional regulation. The granulosa cells of follicles play a determining role in ovarian development. However, the function of circRNA in chicken follicles is unclear. To better understand the molecular mechanism underlying follicular development and granulosa cell function, we performed a strategy of second-generation sequencing and linear RNA depletion for granulosa cells from small yellow follicles (SYF, 5-8 mm), the smallest hierarchal follicles (F6, 9-12 mm), and the largest hierarchal follicles (F1, ~ 40 mm). RESULTS: We predicted a total of 11,642 circRNAs that distributed on almost all chromosomes. The majority of the splice lengths of circRNAs were 200-500 nt and mainly produced from intron and CDS regions. During follicle growth, differentially expressed (DE) circRNAs showed dynamic changes which were tissue- and stage-specific. The host genes of DE circRNAs were functionally enriched in GTPase activity and several pathways involved in reproduction. Moreover, bioinformatic prediction analysis for circRalGPS2 demonstrated that circRNAs from the same genes may share common miRNA to act as a sponge. The predicted target genes were enriched in various biological processes including cognition, cell communication, and regulation of signaling, and several pathways related to reproduction such as tight junction, oocyte meiosis, progesterone-mediated oocyte maturation, and GnRH signaling. CONCLUSIONS: This study provides a starting point for further experimental investigations into chicken circRNAs and casts a light on the understanding of follicle development.

MicroRNA-22 suppresses cell proliferation, migration and invasion in oral squamous cell carcinoma by targeting NLRP3.

MicroRNAs (miRNAs) have been implicated as important regulators of carcinogenesis and tumor development. Recently, microRNA-22 (miR-22) has been reported to be a cancer-related miRNA in several types of tumors. In this study, we aimed to investigate the role of miR-22 in oral squamous cell carcinoma (OSCC). We found that miR-22 expression was significantly decreased in OSCC tissues compared with that in the adjacent noncancerous tissues. Furthermore, lentivirus-mediated miR-22 overexpression markedly reduced OSCC cell viability, migration and invasion, whereas miR-22 inhibitor promoted these parameters. Mechanistically, NLR family pyrin domain containing three (NLRP3) was identified as a direct target of miR-22. miR-22 expression was inversely correlated with NLRP3 expression both in OSCC tissues and cell lines. Moreover, overexpression of miR-22 in OSCC cells could reverse the tumor-promoting effect of the activated NLRP3 inflammasome and vice versus. Therefore, our results indicate that miR-22 may play a suppressive role in OSCC by targeting NLRP3, which offer new insights into the molecular mechanisms of the growth and metastasis of OSCC.

NLRP3 promotes tumor growth and metastasis in human oral squamous cell carcinoma.

BACKGROUND: Inflammasomes are reported to be abnormally expressed and activated in several malignancies and play important roles in tumor development. The present study was designed to investigate the expression and function of the NLR family pyrin domain containing protein 3 (NLRP3) inflammasome in oral squamous cell carcinoma (OSCC). METHODS: NLRP3 expression in OSCC cell lines and the normal human immortalized oral epithelial cells (HIOEC) was determined by real-time PCR and western blot. Immunohistochemistry was used to examine the expression of NLRP3 and IL-1ß in the paraffin-embedded OSCC tissues. The proliferation of OSCC cells was detected by the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and cell colony formation ability of the OSCC cells was also evaluated. Tumor cell migration or invasion was measured by the transwell assay and related protein markers were determined by western blot. A mouse xenograft model was established to investigate the OSCC tumor growth in vivo. RESULTS: Significant higher expression of NLRP3 was observed in the OSCC cells. Obvious expression of NLRP3 and IL-1ß was found in the paraffin-embedded OSCC tissues, and the NLRP3 expression levels were correlated with the tumor size, lymphonode metastatic status and IL-1ß expression. Downregulating NLRP3 expression markedly reduced the cleavage of caspase-1 and production of IL-1ß in OSCC cells. NLRP3 knockdown also inhibited the proliferation, migration and invasion of OSCC cells. Further investigation indicated that expressions of E-cadherin and vimentin in OSCC cells were increased, while N-cadherin expression was decreased after NLRP3 knockdown. Downregulating NLRP3 expression in OSCC cells significantly reduced the tumor growth in vivo. CONCLUSIONS: Our data suggested that the increased expression of NLRP3 in OSCC was associated with tumor growth and metastasis. NLRP3 may be considered as a potential target for OSCC therapy.

Distribution and expression of brain-derived neurotrophic factor, nerve growth factor, and neurotrophic factor-3 in refractory epilepsy-associated focal cortical dysplasia.

OBJECTIVE: To investigate the expression and distribution of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophic factor-3 (NT-3) in refractory epilepsy-associated type I focal cortical dysplasia (FCD I) and FCD IIA patients, and to explore their effects on pathogenesis of FCD I and FCD IIA. MATERIALS AND METHODS: 19 subjects who received surgery at the Department of Neurosurgery, First Affiliated Hospital, Fujian Medical University, China between June 2010 and May 2012, were enrolled in this study. They were pathologically diagnosed as FCD IIA (n = 7) and FCD I (n = 12) after surgery and were considered as two experimental groups. Temporal lobe samples of 10 subjects who had suffered craniocerebral injury but did not have nervous system disease were collected as a control group. Immunohistochemical methods and Western blot assays were used to detect the expression and distribution of BDNF, NGF, and NT-3 in temporal lobes, and differences in their expression and distribution were compared between experimental and control groups. RESULTS: BDNF expression was slightly higher in the FCD IIA group compared to that in the FCD I group and was significantly greater when compared with the control group. Compared with the control group, NGF and NT-3 expression was higher in the FCD groups. However, no significant difference was observed between the FCD IIA and FCD I group. CONCLUSION: Abnormal distribution and expression of BDNF, NGF, and NT-3 may play an important role in the mechanism of FCD I and FCD IIA-induced epilepsy.
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Decreased expression of glutathione S-transferase pi correlates with poorly differentiated grade in patients with oral squamous cell carcinoma.

BACKGROUND: Glutathione S transferase pi (GSTP1) is a member of phase II detoxification enzymes as a major regulator of cell signaling in response to stress, hypoxia, growth factors, and other stimuli. The clinical role of GSTP1 in cancer is still unclear. The aim of this study was to investigate the serum GSTP1 level in patients with oral squamous cell carcinoma (OSCC) and the GSTP1 expression in tissue samples from patients with OSCC and OSCC lines. METHODS: One hundred and sixty-six patients with OSCC and 120 normal persons were used to screen potential serum peptide biomarkers using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Serum GSTP1 concentration was detected in 18 patients with OSCC and 18 normal persons using ELISA. Immunohistochemistry was used to detect GSTP1 expression in tissue samples from twenty-eight OSCC patients. Western blot and real-time PCR were used to detect GSTP1 expression in nine OSCC lines. RESULTS: Decreased GSTP1 concentration was found in the patients with OSCC compared with the normal persons by MALDI-TOF-MS, which was then confirmed by ELISA (P = 0.019). Decreased GSTP1 mRNA level and protein expression were also found in the OSCC lines. Decreased GSTP1 expression was found correlating with pathological differentiation grade in the tissue samples from OSCC patients, a lower GSTP1 expression indicating a poorer pathological differentiation grade (P = 0.041). CONCLUSIONS: These results suggest that decreased GSTP1 expression in patients with OSCC and a lower GSTP1 expression indicating a poorer pathological differentiation grade in OSCC tissue samples.

Low paraoxonase 1 arylesterase activity and high von Willebrand factor levels are associated with severe coronary atherosclerosis in patients with non-diabetic stable coronary artery disease.

BACKGROUND: Paraoxonase 1 (PON1) activity and von Willebrand factor (VWF) release are associated with lesion initiation in atherosclerosis. Diabetes can complicate coronary artery disease (CAD) due to the production of advanced glycation end products. This study evaluated PON1 activity and VWF levels in non-post-acute coronary syndrome, stable CAD (SCAD) patients without diabetes. MATERIAL/METHODS: Non-diabetic SCAD patients and patients experiencing acute stress periods were selected (n=130). Forty-seven cases with normal coronary angiography and 50 healthy individuals served as controls. The non-diabetic SCAD group was then stratified into single-vessel lesions, multiple-vessel lesions, and mild or severe luminal stenosis according to the number and the degree of luminal stenoses. Serum PON1 paraoxonase and arylesterase activities, and plasma VWF levels were measured, as well as serum total cholesterol, total triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A1. PON1 arylesterase activity was detected with an ordinary chemistry system using a novel phenylacetate derivative. RESULTS: Both PON1 paraoxonase and arylesterase were lower in the non-diabetic SCAD group, but VWF levels were higher (versus controls, all P<0.001). PON1 paraoxonase activity (OR=0.991), PON1 arylesterase activity (OR=0.981), and VWF (OR 2.854) influenced SCAD in multiple logistic regression. Decreased PON1 arylesterase activity and increased VWF levels were associated with severe atherosclerosis in non-diabetic SCAD patients. We also observed a slight negative correlation between VWF and PON1 paraoxonase/arylesterase. CONCLUSIONS: PON1 and VWF are detectable markers that may predict the severity of stenoses, ideally facilitating a non-diabetic SCAD diagnosis before the sudden onset of life-threatening symptoms.

Expansion and Polarization of Human γδT17 Cells in vitro from Peripheral Blood Mononuclear Cells.

γδ T cells play a critical role in homeostasis and diseases such as infectious diseases and tumors in both mice and humans. They can be categorized into two main functional subsets: IFN-γ-producing γδT1 cells and IL-17-producing γδT17 cells. While CD27 expression segregates these two subsets in mice, little is known about human γδT17 cell differentiation and expansion. Previous studies have identified γδT17 cells in human skin and mucosal tissues, including the oral cavity and colon. However, human γδ T cells from peripheral blood mononuclear cells (PBMCs) primarily produce IFN-γ. In this protocol, we describe a method for in vitro expansion and polarization of human γδT17 cells from PBMCs. Key Features • Expansion of γδ T cells from peripheral blood mononuclear cells. • Human IL-17A-producing γδ T-cell differentiation and expansion using IL-7 and anti-γδTCR. • Analysis of IL-17A production post γδ T-cell expansion. This protocol is used in: Science Advances (2022), DOI: 10.1126/sciadv.abm9120.

Enhanced Treatment Options for Dural Arteriovenous Fistulas at the Craniocervical Junction: Endovascular Embolization Versus Microsurgery? A Single-Center 23-Year Experience.

OBJECTIVE: The occurrence of dural arteriovenous fistulas (DAVFs) at the craniocervical junction (CCJ) is an uncommon vascular malformation. The diagnosis and treatment of CCJ DAVFs present a formidable challenge. This study aims to investigate the effect of endovascular embolization and microsurgery on improving patient prognosis. METHODS: This retrospective study included patients diagnosed with CCJ DAVFs who received treatment at the First Affiliated Hospital of Fujian Medical University between January 2000 and January 2023. The clinical records, imaging data, and treatment methods were obtained from the hospital's medical record system. The patients were classified into microsurgery and embolization groups based on the surgical technique employed for treatment. The primary outcome measures were surgical-associated neurological dysfunction (SAND) and long-term neurological outcomes. The Cox proportional hazard regression was utilized to determine hazard ratios and 95% confidence intervals (CI) to assess the relationship between treatment methods and prognosis. Kaplan-Meier survival analysis was employed to evaluate the incidence of SAND in both cohorts. RESULTS: This study recruited 46 patients with an average age of 53.72 ± 13.83 years. In the microsurgery group, there were 12 cases (26.1%) observed. While in the embolization group, there were 34 cases (73.9%). Of these patients, 16 (34.8%) experienced SAND after treatment. In the microsurgery group, there were 8 cases (75.0%), while in the embolization group, only 8 cases (23.5%) were reported. Specifically, the embolization group exhibited a significantly lower risk of SAND [adjusted hazard ratio = 0.259, 95% CI = 0.096-0.700; P = 0.008)] compared to the microsurgery group. Additionally, the combined Borden grade 2-3 was found to be significantly associated with SAND (adjusted hazard ratio = 3.150, 95% CI = 1.132-8.766; P = 0.028). The results of the Kaplan-Meier survival analysis indicated a statistically significant difference in the occurrence of favorable functional outcomes between the 2 groups (log-rank P = 0.0081). CONCLUSIONS: CCJ DAVFs are uncommon disorders characterized by a diverse range of clinical manifestations. The functional prognosis of endovascular treatment may be superior to microsurgery.

Rapid automated extracellular vesicle isolation and miRNA preparation on a cost-effective digital microfluidic platform.

As a prerequisite for extracellular vesicle (EV) -based studies and diagnosis, effective isolation, enrichment and retrieval of EV biomarkers are crucial to subsequent analyses, such as miRNA-based liquid biopsy for non-small-cell lung cancer (NSCLC). However, most conventional approaches for EV isolation suffer from lengthy procedure, high cost, and intense labor. Herein, we introduce the digital microfluidic (DMF) technology to EV pretreatment protocols and demonstrate a rapid and fully automated sample preparation platform for clinical tumor liquid biopsy. Combining a reusable DMF chip technique with a low-cost EV isolation and miRNA preparation protocol, the platform completes automated sample processing in 20-30 min, supporting immediate RT-qPCR analyses on EV-derived miRNAs (EV-miRNAs). The utility and reliability of the platform was validated via clinical sample processing for EV-miRNA detection. With 23 tumor and 20 non-tumor clinical plasma samples, we concluded that EV-miR-486-5p and miR-21-5p are effective biomarkers for NSCLC with a small sample volumn (20-40 µL). The result was consistent to that of a commercial exosome miRNA extraction kit. These results demonstrate the effectiveness of DMF in EV pretreatment for miRNA detection, providing a facile solution to EV isolation for liquid biopsy.

LIM domain-containing protein Ajuba inhibits chemotherapy-induced apoptosis by negatively regulating p53 stability in colorectal cancer cells.

LIM protein-domain containing protein Ajuba (encoded by AJUBA) functions as a scaffold protein to regulate protein-protein interactions, signalling transduction and genes transcription. AJUBA expression is higher in colorectal cancer (CRC) tissues than normal tissues, but its specific molecular function in CRC progression is still not very clear. Here, we found that, in CRC cancer cell lines, overexpression of AJUBA decreased p53 levels, whereas knock-down of AJUBA significantly increased p53 levels. Although the presence of Ajuba did not influence p53 transcription, it formed a complex with p53 and MDM2 to promote the degradation of p53. AJUBA overexpression reduced the sensitivity of cancer cells to chemotherapeutic drugs and vice versa. In addition, chemotherapeutic drugs significantly induced AJUBA expression, which was largely dependent on the presence of p53. Therefore, Ajuba formed a negative feedback loop to regulate p53 expression and activity. In conclusion, as a novel p53-negative regulator, Ajuba inhibits the apoptosis of CRC cells induced by chemotherapeutic drugs and it may be a new therapeutic target for CRC treatment.

Lower Serum Iron Level Predicts Postoperative Global Cerebral Edema Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Iron plays an important role in neuronal injury and edema formation after intracranial hemorrhage. However, the role of serum iron in aneurysmal subarachnoid hemorrhage (aSAH) is yet to be well-established. This study aims to identify whether serum iron could predict postoperative global cerebral edema (GCE) and poor outcome in aSAH. METHODS: 847 patients' aSAH clinical data were retrospectively collected at the First Affiliated Hospital of Fujian Medical University. Data on demographics, clinical characteristics, and laboratory values were collected and analyzed through univariate and multivariate analyses. Propensity score matching (PSM) analysis was performed to balance the baseline differences between the groups. RESULTS: The incidence of high-grade global cerebral edema (H-GCE) following aSAH was 12.99% (110/847). Serum iron levels [odds ratio (OR) = 1.143; 95% confidence interval (CI), (1.097-1.191); p < 0.001] were associated with the occurrence of H-GCE following aSAH in the univariate analysis. This association remained statistically significant even after adjusting for other variables in the multivariate model, with serum iron having an OR of 1.091 (95% CI, 1.043-1.141; p < 0.001) for GCE. After 1:1 PSM, serum iron levels ≤ 10.7 µmol/L remained a significant independent predictor of GCE (p = 0.002). The receiver operating characteristic (ROC) curve analysis determined that a serum iron cut-off value of ≤ 10.7 µmol/L was optimal for predicting H-GCE [Areas under the ROC curves (AUC) = 0.701, 95% CI, (0.669-0.732), p < 0.001; sensitivity, 67.27%; specificity, 63.77%] in patients with aSAH. Additionally, a trend was observed in which higher Hunt-Hess grades (HH grade) were associated with lower serum iron levels, and higher modified Fisher grades (mFisher grade) were associated with lower serum iron levels. In addition, the serum iron level was also associated with a 3-month functional neurological outcome (p < 0.001). CONCLUSIONS: The results of this study indicate that a decreased serum iron level serves as a clinically significant biomarker for the prediction of postoperative GCE and a poor outcome at 3-months in patients with aSAH.

Deep learning based atomic defect detection framework for two-dimensional materials.

Defects to popular two-dimensional (2D) transition metal dichalcogenides (TMDs) seriously lower the efficiency of field-effect transistor (FET) and depress the development of 2D materials. These atomic defects are mainly identified and researched by scanning tunneling microscope (STM) because it can provide precise measurement without harming the samples. The long analysis time of STM for locating defects in images has been solved by combining feature detection with convolutional neural networks (CNN). However, the low signal-noise ratio, insufficient data, and a large amount of TMDs members make the automatic defect detection system hard to be applied. In this study, we propose a deep learning-based atomic defect detection framework (DL-ADD) to efficiently detect atomic defects in molybdenum disulfide (MoS2) and generalize the model for defect detection in other TMD materials. We design DL-ADD with data augmentation, color preprocessing, noise filtering, and a detection model to improve detection quality. The DL-ADD provides precise detection in MoS2 (F2-scores is 0.86 on average) and good generality to WS2 (F2-scores is 0.89 on average).