External lipid PI3P mediates entry of eukaryotic pathogen effectors into plant and animal host cells.

Pathogens of plants and animals produce effector proteins that are transferred into the cytoplasm of host cells to suppress host defenses. One type of plant pathogens, oomycetes, produces effector proteins with N-terminal RXLR and dEER motifs that enable entry into host cells. We show here that effectors of another pathogen type, fungi, contain functional variants of the RXLR motif, and that the oomycete and fungal RXLR motifs enable binding to the phospholipid, phosphatidylinositol-3-phosphate (PI3P). We find that PI3P is abundant on the outer surface of plant cell plasma membranes and, furthermore, on some animal cells. All effectors could also enter human cells, suggesting that PI3P-mediated effector entry may be very widespread in plant, animal and human pathogenesis. Entry into both plant and animal cells involves lipid raft-mediated endocytosis. Blocking PI3P binding inhibited effector entry, suggesting new therapeutic avenues.

Fine-tuning rice heading date through multiplex editing of the regulatory regions of key genes by CRISPR-Cas9.

Heading date (or flowering time) is a key agronomic trait that affects seasonal and regional adaption of rice cultivars. An unoptimized heading date can either not achieve a high yield or has a high risk of encountering abiotic stresses. There is a strong demand on the mild to moderate adjusting the heading date in breeding practice. Genome editing is a promising method which allows more precise and faster changing the heading date of rice. However, direct knock out of major genes involved in regulating heading date will not always achieve a new germplasm with expected heading date. It is still challenging to quantitatively adjust the heading date of elite cultivars with best adaption for broader region. In this study, we used a CRISPR-Cas9 based genome editing strategy called high-efficiency multiplex promoter-targeting (HMP) to generate novel alleles at cis-regulatory regions of three major heading date genes: Hd1, Ghd7 and DTH8. We achieved a series of germplasm with quantitative variations of heading date by editing promoter regions and adjusting the expression levels of these genes. We performed field trials to screen for the best adapted lines for different regions. We successfully expanded an elite cultivar Ningjing8 (NJ8) to a higher latitude region by selecting a line with a mild early heading phenotype that escaped from cold stress and achieved high yield potential. Our study demonstrates that HMP is a powerful tool for quantitatively regulating rice heading date and expanding elite cultivars to broader regions.

Phytophthora RxLR effector PcSnel4B promotes degradation of resistance protein AtRPS2.

Phytophthora capsici deploys effector proteins to manipulate host immunity and facilitate its colonization. However, the underlying mechanisms remain largely unclear. In this study, we demonstrated that a Sne-like (Snel) RxLR effector gene PcSnel4 is highly expressed at the early stages of P. capsici infection in Nicotiana benthamiana. Knocking out both alleles of PcSnel4 attenuated the virulence of P. capsici, while expression of PcSnel4 promoted its colonization in N. benthamiana. PcSnel4B could suppress the hypersensitive reaction (HR) induced by Avr3a-R3a and RESISTANCE TO PSEUDOMONAS SYRINGAE 2 (AtRPS2), but it did not suppress cell death elicited by Phytophthora infestin 1 (INF1) and Crinkler 4 (CRN4). COP9 signalosome 5 (CSN5) in N. benthamiana was identified as a host target of PcSnel4. Silencing NbCSN5 compromised the cell death induced by AtRPS2. PcSnel4B impaired the interaction and colocalization of Cullin1 (CUL1) and CSN5 in vivo. Expression of AtCUL1 promoted the degradation of AtRPS2 and disrupted HR, while AtCSN5a stabilized AtRPS2 and promoted HR, regardless of the expression of AtCUL1. PcSnel4 counteracted the effect of AtCSN5 and enhanced the degradation of AtRPS2, resulting in HR suppression. This study deciphered the underlying mechanism of PcSnel4-mediated suppression of HR induced by AtRPS2.

Efficacy of Deep Venous Catheterization in the Management of Pneumothorax: A Clinical Study Utilizing Conventional Closed Thoracic Drainage.

Background: Currently, conventional closed thoracic drainage for pneumothorax involves a painful procedure with a higher risk and wider (1~1.5 cm) incision. Minimally invasive catheterized drainage techniques are urgently needed to address this challenge. Objective: This retrospective study aims to observe the effects of conventional closed thoracic drainage with deep venous catheterization drainage techniques on pneumothorax patients. Design: It was a retrospective study. Setting: This study was conducted at Huaian No.1 People's Hospital, Affiliated with Nanjing Medical University. Participants: A total of 105 pneumothorax patients who underwent conventional closed thoracic drainage (CCTD) or deep venous catheterization drainage technique (DVCDT) procedures at the hospital from 1st February 2020 to 30th October 2022 were selected. Interventions: Patients received either CCTD or DVCDT. Primary Outcome Measures: Included: (1) clinical variables; (2) catheterization procedure-related features; and (3) visual analogue scale (VAS) scores from pneumothorax patients. Results: Both conventional closed thoracic drainage and deep venous catheterization drainage techniques were successfully performed in all 105 (100%) patients, comprising 67 (63.8%) spontaneous pneumothorax, 20 (19%) iatrogenic pneumothorax, and 18 (17.1%) traumatic pneumothorax cases. Significant differences were observed between the enrolled spontaneous pneumothorax and traumatic pneumothorax patients in the two groups (CCTD and DVCDT) (P = .01 and P < .0001). Additionally, 55 (52.4%) patients underwent deep venous catheterization, while 50 (47.6%) patients underwent conventional closed thoracic drainage. The deep venous catheterization insertion procedure had a shorter mean timing (7.51±1.66 min) compared to the conventional closed thoracic drainage procedure (12.44±1.73 min) (P < .0001). Furthermore, VAS scores were significantly lower in pneumothorax patients undergoing deep venous catheterization (2.1±0.99) compared to conventional closed thoracic drainage (5.1±0.81) (P < .0001). Conclusion: Deep venous thoracic drainage technique appears to be safer and more beneficial than conventional closed thoracic drainage procedures for treating pneumothorax. This technique offers advantages such as minimal scarring, lower VAS scores, and shorter insertion time, thereby improving safety and surgical outcomes.

Characterization of Prochloraz Resistance in Fusarium fujikuroi from Heilongjiang Province in China.

Prochloraz is widely used to control rice bakanae disease caused by Fusarium fujikuroi. The current study was aimed at monitoring the development of F. fujikuroi resistance to prochloraz in the Heilongjiang Province and analyzing the fitness of F. fujikuroi strains with different resistance levels. The results indicated that most of the 89 F. fujikuroi strains collected from the Heilongjiang Province were resistant to prochloraz, with resistance frequency reaching 92.1%. To assess the field resistance risk of prochloraz, 21 F. fujikuroi strains with different resistance levels were selected to investigate their biological characteristics and assess their fitness. Mycelial growth, sporulation, and germination rates were significantly different among the tested strains. However, when grouped into two subpopulations, no significant difference was tested between prochloraz-resistant and prochloraz-sensitive strains. Pathogenicity assays revealed that the disease severity index of prochloraz-resistant strains was higher than that of prochloraz-sensitive strains. Cross-resistance assays showed no cross-resistance between prochloraz and five other fungicides, namely phenamacril, ipconazole, tebuconazole, carbendazim, and fluopyram. Ffcyp51A gene overexpression was observed in the prochloraz-resistant F. fujikuroi strains after exposure to prochloraz. Collectively, these results indicated that F. fujikuroi resistance against prochloraz was severe. Furthermore, prochloraz-resistant strains were highly fit and could potentially become a dominant population in rice fields, consequently resulting in yield loss.

A near infrared fluorescent probe based on ICT for monitoring mitophagy in living cells.

Mitophagy, the process in which cells degrade dysfunctional organelles and recycle their nutrient substances by lysosomes, plays a vital role in cell metabolism and physiology. Herein, we present a highly targeting and near-infrared (NIR) mitochondrion fluorescent probe, which can monitor the process of autophagy. The response mechanism of the probe is based on intramolecular charge transfer (ICT) for the detection of autophagy and real-time imaging of living cells. We designed a primary amine as a pH sensitizing group, and due to the ICT process, the probe exhibits green fluorescence, and when it is protonated the ICT process is broken, and the NIR fluorescence will be restored. Simultaneously, the green fluorescence of the probe disappears. This probe exhibits excellent selectivity, high sensitivity and clean responsiveness, which indicate that it can be applied for high-targeting and high-sensitive imaging of the process of autophagy in living systems.

The Histological, Effectoromic, and Transcriptomic Analyses of Solanum pinnatisectum Reveal an Upregulation of Multiple NBS-LRR Genes Suppressing Phytophthora infestans Infection.

Utilization of disease resistance components from wild potatoes is a promising and sustainable approach to control Phytophthora blight. Here, we combined avirulence (Avr) genes screen with RNA-seq analysis to discover the potential mechanism of resistance in Mexican wild potato species, Solanum pinnatisectum. Histological characterization displayed that hyphal expansion was significantly restricted in epidermal cells and mesophyll cell death was predominant, indicating that a typical defense response was initiated in S. pinnatisectum. Inoculation of S. pinnatisectum with diverse Phytophthora infestans isolates showed distinct resistance patterns, suggesting that S. pinnatisectum has complex genetic resistance to most of the prevalent races of P. infestans in northwestern China. Further analysis by Avr gene screens and comparative transcriptomic profiling revealed the presence and upregulation of multiple plant NBS-LRR genes corresponding to biotic stresses. Six NBS-LRR alleles of R1, R2, R3a, R3b, R4, and Rpi-smira2 were detected, and over 60% of the 112 detected NLR proteins were significantly induced in S. pinnatisectum. On the contrary, despite the expression of the Rpi-blb1, Rpi-vnt1, and Rpi-smira1 alleles, fewer NLR proteins were expressed in susceptible Solanum cardophyllum. Thus, the enriched NLR genes in S. pinnatisectum make it an ideal genetic resource for the discovery and deployment of resistance genes for potato breeding.

The inhibitory effects of ginsenoside Rd on the human glioma U251 cells and its underlying mechanisms.

OBJECTIVE: The current study was designed to investigate the inhibitory effects of ginsenoside Rd (Gs-Rd) on human glioma U251 cells in vitro and its possible underlying mechanisms. METHODS: The groups included blank control group, low concentration Gs-Rd treatment group (20 µM), mid concentration Gs-Rd treatment group (40 µM), and high concentration Gs-Rd treatment group (80 µM). The proliferative activity of human glioma U251 cells was detected by the MTT assay. Flow cytometry was performed to measure cell apoptosis of human glioma U251 cells. In addition, the ELISA assay was used to measure the telomerase activities in different groups on 24 hours, 48 hours, and 72 hours. Furthermore, real-time quantitative polymerase chain reaction (RT-PCR) and Western blot analysis were performed to measure the expression of Bcl-2, human telomerase catalytic subunit (hTERT), and caspase-3 in different groups on 48 hours at both messenger RNA (mRNA) and protein levels. RESULTS: The proliferation of U251 cells was inhibited by Gs-Rd with different concentrations in the dose- and time-dependent manners. In addition, Gs-Rd promoted U251 cell apoptosis rate in a dose-dependent manner. Gs-Rd with different concentrations (20 µM, 40 µM, and 80 µM) significantly enhanced the expression of teleomerase on 24 hours and 48 hours. In addition, Gs-Rd with different concentrations significantly increased caspase-3 and decreased Bcl-2 and hTERT expressions at both mRNA and protein levels. CONCLUSION: The Gs-Rd can remarkably inhibit the proliferation and promote cell apoptosis of human glioma U251 cells. The possible underlying mechanisms could be related to inhibiting telomerase activity, downregulating expression of Bcl-2 and hTERT, and upregulating expression of caspase-3 of human glioma U251 cells.

microRNA-383 regulates cell viability and apoptosis by mediating Wnt/ß-catenin signaling pathway in non-small cell lung cancer.

The aim of this study was to investigate the roles of microRNA-383 (miRNA-383) in progression of non-small cell lung cancer (NSCLC) and the potential mechanism. The expressions of miR-383 and Wnt1 protein were detected in lung cancer tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. After the transfection of miR-383 mimics, si-Wnt1 or miR-383+Wnt1, the viability and apoptosis of NSCLC cells were detected by cell counting kit-8 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, respectively. The interaction between miR-383 and Wnt1 was investigated by luciferase activity and Western blot analysis. Cells stably transfected with miR-383 mimics were inoculated into the right axillary of nude mice by subcutaneous injection. The tumor volume and weight were measured, and the expressions of miR-383, Wnt1, ß-catenin, and cyclin D1 were detected by qRT-PCR and Western blot analysis. The expression of miR-383 was significantly decreased, and the level of Wnt1 was significantly increased (P < 0.05) in lung cancer tissues and cells. Upregulation of miR-383 or inhibition of Wnt1 expression inhibited the cell viability and induce apoptosis in NSCLC cells. Moreover, Wnt1 was the target gene of miR-383, and its overexpression weakened the regulatory effect of miR-383 on cell viability and apoptosis in NSCLC cells. Besides, the addition of miR-383 decreased the tumor volume and size and inhibited the expressions of Wnt1, ß-catenin, and cyclin D1 at the protein level in nude mice. Collectively, miR-383 induced apoptosis and inhibited cell viability as well as tumorigenic capacity in nude mice via regulating the Wnt/ß-catenin signaling pathway.

Circular RNA circ-PRKCI functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR-3680-3p in esophageal squamous cell carcinoma.

Circular RNA (circRNA) is a new noncoding RNAs and plays an important role in many pathological processes. Recently, studies have shown that circular RNA_PRKCI (circ-PRKCI) regulates cell proliferation and cell migration of tumor cells. Esophageal carcinoma is a highly malignant digestive tract tumor, which is divided into esophageal adenocarcinoma and esophageal squamous cell carcinoma. In this study, we studied whether circ-PRKCI might influence cell proliferation and cell migration in esophageal squamous cell carcinoma. Quantitative reverse transcription PCR was performed to detect the relative expression of circ-PRKCI in five cases of esophageal squamous cell carcinoma and five cases of paired adjacent normal tissues. RNA immunoprecipitation assay and Luciferase assay confirm the direct interaction between miR-3680-3p and AKT3 or circ-PRKCI. Ethynyldeoxyuridine assays and cell counting Kit-8 were performed to evaluate the effect of miR-3680-3p or circ-PRKCI on cell proliferation, transwell assays were also performed to detect migration in vitro. We found circ-PRKCI is obviously upregulated in esophageal squamous cell carcinoma and upregulation of circ-PRKCI stimulated cell migration and proliferation of ESCC cells. In the mechanism, we confirm that circ-PRKCI, as a molecular sponge of miR-3680-3p, upregulates the expression of AKT. In conclusion, our current studies have been revealing that circ-PRKCI/miR-3680-3p/AKT3 regulatory network plays an important role in esophageal squamous cell carcinoma and that provide new insights into the pathogenesis of esophageal squamous cell carcinoma.

A highly sensitive naked-eye fluorescent probe for trace hydrazine based on 'C-CN' bond cleavage.

In this work, a colorimetric and ratiometric fluorescent probe, 2,3-bis(((E)-4-(diethylamino)-2-hydroxybenzylidene)amino)maleonitrile (DHM), was developed based on N2H4-induced bond cleavage. Two cyanide groups of DHM were applied to sense hydrazine (N2H4) for the first time, which was demonstrated using 1H NMR and HRMS spectra. The specific 'C-CN' bond cleavage induced by N2H4 showed an excellent fluorescence ratiometric behavior and a visible colorimetric change from purple to yellow. Meanwhile, it showed a low detection limit of 58.1 nM (1.65 ppb), which is far below the safety level (10 ppb) set by the U.S. EPA. Moreover, the probe was successfully employed for the quantitative detection toward N2H4 in real water samples.

Effect of GDF11 on proliferation and apoptosis of esophageal cancer cells.

This study was aimed at investigating the effect of growth differentiation factor 11 (GDF11) on the proliferation and apoptosis of esophageal cancer cells. Serum levels of GDF11 in esophageal cancer patients were determined with ELISA kits, and the correlation between serum GDF11 and pathological features of esophageal cancer were determined. The effect of recombinant GDF11 on the growth of esophageal cancer cells was measured by CCK6 method. In order to investigate the effect of recombinant GDF11 on the proliferation and apoptosis of esophageal cancer cells, the expression of apoptosis-promoting protein Bax and proliferative-associated protein Bcl-2 in esophageal cancer cells were determined using western blot. Moreover, GDF11 was used to treat esophageal cancer cells, and its effect on proliferation and apoptosis was determined with MTT assay and flow cytometry, respectively. The serum content of GDF11 was much less in esophageal cancer patients than in the control group. Esophageal GDF II in cancer patients was correlated with cancer differentiation: the higher the degree of differentiation, the higher the content of GDF11. GDF11 inhibits proliferation and apoptosis of esophageal cancer cells.

[Research on malignant arrhythmia detection algorithm using neural network optimized by genetic algorithm].

Detection and classification of malignant arrhythmia are key tasks of automated external defibrillators. In this paper, 21 metrics extracted from existing algorithms were studied by retrospective analysis. Based on these metrics, a back propagation neural network optimized by genetic algorithm was constructed. A total of 1,343 electrocardiogram samples were included in the analysis. The results of the experiments indicated that this network had a good performance in classification of sinus rhythm, ventricular fibrillation, ventricular tachycardia and asystole. The balanced accuracy on test dataset reached up to 99.06%. It illustrates that our proposed detection algorithm is obviously superior to existing algorithms. The application of the algorithm in the automated external defibrillators will further improve the reliability of rhythm analysis before defibrillation and ultimately improve the survival rate of cardiac arrest.

[A New Algorithmic Method to Detect Ventricular Fibrillation Using Electrocardiogram Signals During Cardiopulmonary Resuscitation by Artificial Pressing].

On account of the mechanical disturbance of external chest pressing to electrocardiogram(ECG)signal,the ECG rhythm cannot be identified reliably during the cardio-pulmonary resuscitation period.Whereas the possibility of successful resuscitation will be lowered due to interrupted external chest pressing,a new filtering algorithm,enhanced leastmean-square(eLMS)algorithm,was proposed and developed in our laboratory.The algorithm can filter the disturbance of external chest pressing without the support of hardware reference signal and correctly identify ventricular fibrillation(VF)rhythm and normal sinus rhythm in case of uninterrupted external chest pressing.Without other reference signals,this algorithm realizes filtering only through the interrupted electrocardiograma(cECG)signal.It was verified with ECG signal and disturbance signal under different signal to noise ratios and contrasted with other mature algorithms.The verification results showed that the identification effect of eLMS was superior to those of others under different signal to noise ratios.Furthermore,ECG rhythm can be correctly identified only through cECG signal.This algorithm not only reduces the research and development(R&D)costs of automated external defibrillator but also raises the identification accuracy of ECG rhythm and the possibility of successful resuscitation.

[Adaptive Cardiopulmonary Resuscitation Artifacts Elimination Algorithm Based on Empirical Mode Decomposition and Independent Component Analysis].

Artifacts produced by chest compression during cardiopulmonary resuscitation(CPR)seriously affect the reliability of shockable rhythm detection algorithms.In this paper,we proposed an adaptive CPR artifacts elimination algorithm without needing any reference channels.The clean electrocardiogram(ECG)signals can be extracted from the corrupted ECG signals by incorporating empirical mode decomposition(EMD)and independent component analysis(ICA).For evaluating the performance of the proposed algorithm,a back propagation neural network was constructed to implement the shockable rhythm detection.A total of 1 484 corrupted ECG samples collected from pigs were included in the analysis.The results of the experiments indicated that this method would greatly reduce the effects of the CPR artifacts and thereby increase the accuracy of the shockable rhythm detection algorithm.

An ESIPT-based fluorescent probe for highly selective and ratiometric detection of mercury(II) in solution and in cells.

A novel ratiometric fluorescent Hg(2+) detecting system was rationally developed based on the typical excited state intramolecular proton transfer (ESIPT) characteristic of the latent fluorophore, 2-(1-(p-tolyl)-1H-phenanthro[9,10-d]imidazol-2-yl)phenol (Pol) and the Hg(2+)-mediated cleavage of the vinyl group. The probe responds selectively to Hg(2+) over various other metal ions with a larger bathochromic shift (∼100 nm). The sensing mechanism was investigated in detail by fluorescence spectroscopy, NMR spectra and mass spectrometry. Taking advantage of the enhancement effect of dichloromethane on the ESIPT efficiency, a facile dichloromethane extraction was introduced in the process of detection of Hg(2+), which affords a high sensitivity for the probe with a detection limit of 7.8 × 10(-9) M for Hg(2+). By using the new strategy, the novel probe can be used for the detection of Hg(2+) in practical water samples with good recovery. Moreover, the probe was successfully applied to the fluorescence image of Hg(2+) in living cells. These results indicated that the probe and the proposed method have promising applications for Hg(2+) sensing in biological and environmental sciences.

Transcriptional programming and functional interactions within the Phytophthora sojae RXLR effector repertoire.

The genome of the soybean pathogen Phytophthora sojae contains nearly 400 genes encoding candidate effector proteins carrying the host cell entry motif RXLR-dEER. Here, we report a broad survey of the transcription, variation, and functions of a large sample of the P. sojae candidate effectors. Forty-five (12%) effector genes showed high levels of polymorphism among P. sojae isolates and significant evidence for positive selection. Of 169 effectors tested, most could suppress programmed cell death triggered by BAX, effectors, and/or the PAMP INF1, while several triggered cell death themselves. Among the most strongly expressed effectors, one immediate-early class was highly expressed even prior to infection and was further induced 2- to 10-fold following infection. A second early class, including several that triggered cell death, was weakly expressed prior to infection but induced 20- to 120-fold during the first 12 h of infection. The most strongly expressed immediate-early effectors could suppress the cell death triggered by several early effectors, and most early effectors could suppress INF1-triggered cell death, suggesting the two classes of effectors may target different functional branches of the defense response. In support of this hypothesis, misexpression of key immediate-early and early effectors severely reduced the virulence of P. sojae transformants.

An ESIPT + AIE based dual-response fluorescent probe for continuous detection of PhSH and HClO and visualization of PhSH-induced oxidative stress in living cells.

As a valuable industrial chemical, thiophenol (PhSH) is poisonous, which can be easily absorbed by the human body, leading to many serious health issues. In addition, PhSH-triggered oxidative stress is considered to be related with the pathogenesis and toxicity of PhSH. Therefore, efficient methods for monitoring PhSH and ROS production induced by PhSH in living systems are very meaningful and desired. Herein, we reasonably developed a facile dual-response fluorescent probe (HDB-DNP) by incorporating the dinitrophenyl (DNP) group into a novel methylthio-substituted salicylaldehyde azine (HDB) with AIE and ESIPT features. The probe itself was non-fluorescent owing to the strong quenching effect of DNP group. In the presence of PhSH, HDB-DNP gave an intense red fluorescence (610 nm), which can rapidly switch to green fluorescence (510 nm) upon further addition of HClO, allowing the successive detection of PhSH and HClO in two well-separated channels. HDB-DNP proved to be a very promising dual-functional probe for rapid (PhSH: < 17 min; HClO: 10 s) and selective detection of PhSH and HClO in physiological conditions with low detection limit (PhSH: 13.8 nM; HClO: 88.6 nM). Inspired by its excellent recognition properties and low cytotoxicity, HDB-DNP was successfully applied for monitoring PhSH and PhSH-induced HClO generation in living cells with satisfactory results, which may help to better understand the pathogenesis of PhSH-related diseases.

Microbe-independent entry of oomycete RxLR effectors and fungal RxLR-like effectors into plant and animal cells is specific and reproducible.

A wide diversity of pathogens and mutualists of plant and animal hosts, including oomycetes and fungi, produce effector proteins that enter the cytoplasm of host cells. A major question has been whether or not entry by these effectors can occur independently of the microbe or requires machinery provided by the microbe. Numerous publications have documented that oomycete RxLR effectors and fungal RxLR-like effectors can enter plant and animal cells independent of the microbe. A recent reexamination of whether the RxLR domain of oomycete RxLR effectors is sufficient for microbe-independent entry into host cells concluded that the RxLR domains of Phytophthora infestans Avr3a and of P. sojae Avr1b alone are NOT sufficient to enable microbe-independent entry of proteins into host and nonhost plant and animal cells. Here, we present new, more detailed data that unambiguously demonstrate that the RxLR domain of Avr1b does show efficient and specific entry into soybean root cells and also into wheat leaf cells, at levels well above background nonspecific entry. We also summarize host cell entry experiments with a wide diversity of oomycete and fungal effectors with RxLR or RxLR-like motifs that have been independently carried out by the seven different labs that coauthored this letter. Finally we discuss possible technical reasons why specific cell entry may have been not detected by Wawra et al. (2013).

Progranulin modulates the progression of non-small cell lung cancer through lncRNA H19.

OBJECTIVE: This study aimed to explore the specific mechanism of action of Progranulin (PGRN) in non-small cell lung cancer (NSCLC) and its interaction with lncRNA H19. METHODS: Normal and cancerous lung tissues were collected from patients with NSCLC and healthy volunteers. We assessed the expression of PGRN in both groups using immunohistochemistry, quantitative-reverse transcription-polymerase chain reaction (qRT-PCR), and western blotting (WB). RESULTS: Compared to the controls, PGRN expression was noticeably higher in tumor tissues. The high expression of PGRN in patients with NSCLC was inversely correlated to the prognosis and strongly associated with the biological features and clinicopathologic data. High PGRN expression significantly improved the ability of NSCLC cells to proliferate and migrate and was positively correlated with tumor formation, based on in vitro and in vivo cellular tests. Expression of lncRNA H19 was also found to be elevated in NSCLC tissue and cells. The expression of H19 was correlated with tumor growth in vivo and in vitro, and H19 regulated PGRN by mediating the expression of miR-29b-3p. CONCLUSIONS: H19 and PGRN can serve as biomarkers and therapeutic targets in NSCLC.