SPINK4 modulates inhibition of glycolysis against colorectal cancer progression.

Dysregulation of glycolysis is frequently linked to aggressive tumor activity in colorectal cancer (CRC). Although serine peptidase inhibitor, Kazal type 4 (SPINK4) has been linked to CRC, its exact linkage to glycolytic processes and gene expression remains unclear. Differentially expressed genes (DEGs) were screened from two CRC-related datasets (GSE32323 and GSE141174), followed by expression and prognostic analysis of SPINK4. In vitro techniques such as flow cytometry, western blotting, transwell assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to assess SPINK4 expression in CRC cells. Its effects on apoptosis, glycolysis, and the cell cycle were also investigated. Finally, the impact of SPINK4 overexpression on tumor development was assessed using a xenograft model, while histological and immunohistochemical analyses characterized SPINK4 expression patterns in CRC tissues. SPINK4 expression was downregulated in CRC, correlating with poor patient prognosis. In vitro assays confirmed that overexpression of SPINK4 reduced CRC cell proliferation, invasion, and migration, while its knockdown promoted these processes and caused G1 arrest. SPINK4 also regulated apoptosis by altering caspase activation and Bcl-2 expression. Besides, SPINK4 overexpression altered glycolytic activity, reduced 2-Deoxy-D-glucose (2-DG) absorption, and controlled critical glycolytic enzymes, resulting in alterations in metabolic pathways, whereas SPINK4 knockdown reversed this effect. SPINK4 overexpression significantly reduced tumor volume in vivo, indicating its inhibitory role in carcinogenesis. Moreover, high expression of SPINK4, hexokinase 2 (HK2), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and pyruvate kinase M2 (PKM2) was observed in CRC tissues. As a key inhibitor of glycolytic metabolism in CRC, SPINK4 promises metabolic intervention in CRC therapy due to its impact on tumor growth and cell proliferation.

Development of visual detection of African swine fever virus using CRISPR/LwCas13a lateral flow strip based on structural protein gene D117L.

African swine fever virus (ASFV) is a large double stranded DNA arbovirus that is highly contagious and seriously endangers domestic and wild pigs. In the past decade, African swine fever (ASF) has spread in many countries in the Caucasus, Russian Federation, Eastern Europe and Asia, causing significant losses to the pig industry. At present, there is a lack of effective vaccine and treatment for ASF. Therefore, the rapid and accurate detection is crucial for ASF prevention and control. In this study, we have developed a portable lateral flow strip (LFS) detection mediated by recombinase polymerase amplification (RPA) and CRISPR/LwCas13a, which is performed at 37 ℃ and visualized by eyes without the need for complex instruments. This RPA-LwCas13a-LFS is based on the ASFV structural protein p17 gene (D117L), with a detection sensitivity up to 2 gene copies. This method is highly specific and has no cross reactivity to 7 other pig viruses. In the detection of two batches of 100 clinical samples, the p17 (D117L) RPA-LwCas13a-LFS had 100% coincidence with conventional quantitative PCR (qPCR). These findings demonstrate the potential of this simple, rapid, sensitive, and specific ASFV detection method for on-site ASFV detection.

Mammalian enabled protein enhances tamoxifen sensitivity of the hormone receptor-positive breast cancer patients by suppressing the AKT signaling pathway.

BACKGROUND: Mammalian enabled (MENA) protein is a member of the enabled/vasodilator stimulated phosphoprotein (Ena/VASP) protein family, which regulates cytoplasmic actin network assembly. It plays a significant role in breast cancer invasion, migration, and resistance against targeted therapy and chemotherapy. However, its role in the efficacy of endocrine therapy for the hormone receptor-positive (HR+) breast cancer patients is not known. This study investigated the role of MENA in the resistance against tamoxifen therapy in patients with HR+ breast cancer and the underlying mechanisms. METHODS: MENA expression levels in the clinical HR+ breast cancer samples (n = 119) were estimated using immunohistochemistry (IHC) to determine its association with the clinicopathological features, tamoxifen resistance, and survival outcomes. Western blotting (WB) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis was performed to estimate the MENA protein and mRNA levels in the tamoxifen-sensitive and -resistant HR+ breast cancer cell lines. Furthermore, CCK8, colony formation, and the transwell invasion and migration assays were used to analyze the effects of MENA knockdown on the biological behavior and tamoxifen sensitivity of the HR+ breast cancer cell lines. Xenograft tumor experiments were performed in the nude mice to determine the tumor growth rates and tamoxifen sensitivity of the control and MENA knockdown HR+ breast cancer cells in the presence and absence of tamoxifen treatment. Furthermore, we estimated the growth rates of organoids derived from the HR+ breast cancer patients (n = 10) with high and low MENA expression levels when treated with tamoxifen. RESULTS: HR+ breast cancer patients with low MENA expression demonstrated tamoxifen resistance and poorer prognosis compared to those with high MENA expression. Univariate and multivariate Cox regression analysis demonstrated that MENA expression was an independent predictor of tamoxifen resistance in patients with HR+ breast cancer. MENA knockdown HR+ breast cancer cells showed significantly reduced tamoxifen sensitivity in the in vitro experiments and the in vivo xenograft tumor mouse model compared with the corresponding controls. Furthermore, MENA knockdown increased the in vitro invasion and migration of the HR+ breast cancer cells. HR+ breast cancer organoids with low MENA expression demonstrated reduced tamoxifen sensitivity than those with higher MENA expression. Mechanistically, P-AKT levels were significantly upregulated in the MENA-knockdown HR + breast cancer cells treated with or without 4-OHT compared with the corresponding controls. CONCLUSIONS: This study demonstrated that downregulation of MENA promoted tamoxifen resistance in the HR+ breast cancer tissues and cells by enhancing the AKT signaling pathway. Therefore, MENA is a promising prediction biomarker for determining tamoxifen sensitivity in patients with HR+ breast cancer.

Pseudomonas aeruginosa isolation is an important predictor for recurrent hemoptysis after bronchial artery embolization in patients with idiopathic bronchiectasis: a multicenter cohort study.

BACKGROUND: Nearly half of bronchiectasis patients receiving bronchial artery embolization (BAE) still have recurrent hemoptysis, which may be life-threatening. Worse still, the underlying risk factors of recurrence remain unknown. METHODS: A retrospective cohort was conducted of patients with idiopathic bronchiectasis who received BAE from 2015 to 2019 at eight centers. Patients were followed up for at least 24 months post BAE. Based on the outcomes of recurrent hemoptysis and recurrent severe hemoptysis, a Cox regression model was used to identify risk factors for recurrence. RESULTS: A total of 588 individuals were included. The median follow-up period was 34.0 months (interquartile range: 24.3-53.3 months). The 1-month, 1-year, 2-year, and 5-year cumulative recurrent hemoptysis-free rates were 87.2%, 67.5%, 57.6%, and 49.4%, respectively. The following factors were relative to recurrent hemoptysis: 24-h sputum volume (hazard ratio [HR] = 1.99 [95% confidence interval [95% CI]: 1.25-3.15, p = 0.015]), isolation of Pseudomonas aeruginosa (HR = 1.50 [95% CI: 1.13-2.00, p = 0.003]), extensive bronchiectasis (HR = 2.00 [95% CI: 1.29-3.09, p = 0.002]), and aberrant bronchial arteries (AbBAs) (HR = 1.45 [95% CI: 1.09-1.93, p = 0.014]). The area under the receiver operating characteristic curve of the nomogram was 0.728 [95% CI: 0.688-0.769]. CONCLUSIONS: Isolation of Pseudomonas aeruginosa is an important independent predictor of recurrent hemoptysis. The clearance of Pseudomonas aeruginosa might effectively reduce the hemoptysis recurrence rate.

Chinese expert consensus on transradial access in percutaneous peripheral interventions.

Transradial access (TRA) is a safe and comfortable approach and the preferred access for percutaneous coronary intervention. However, TRA is not widely used for peripheral interventions. Currently, there is a lack of data on patient selection, appropriate medical devices, complication prevention, and TRA adoption. Therefore, the Chinese Society of Interventional Oncology of the China Anti-Cancer Association organized nationwide experts to establish a Working Group of China Expert Consensus on TRA in percutaneous peripheral interventions in 2022, and jointly formulated this consensus to better promote the application of TRA in peripheral interventions to guide clinicians on patient selection, technical recommendations, and physician training. This consensus mainly focuses on the current situation, advantages and limitations of TRA in peripheral interventions, anatomical characteristics of the radial artery, patient selection, technical aspects, prevention and management of complications, radiation dose, and learning curve. A consensus was reached through a literature evaluation and by referring to the opinions of the expert group.

The Porcine Cyclic GMP-AMP Synthase-STING Pathway Exerts an Unusual Antiviral Function Independent of Interferon and Autophagy.

The innate immune DNA-sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (IFN) gene (STING) pathway exerts strong antiviral activity through downstream IFN production; however, it has been recently recognized that an IFN-independent activity of STING also plays an important role in antiviral functions. Nevertheless, the IFN-independent antiviral activity of STING is not fully understood. Here, we showed that porcine STING (pSTING) played a critical role against herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) infections, and IFN-defective mutants, including pSTING pLxIS sub, S365A, and △CTT, all exhibited similar antiviral functions, compared to wild-type (WT) pSTING. Furthermore, all of these IFN-defective pSTING mutants possessed comparable autophagy activity, relative to WT pSTING, as expected. From pSTING WT, S365A, and △CTT, the residues responsible for autophagy, including L333A/R334A, Y167A/L170A, and Y245A/L248A, were mutated. Surprisingly, all of these autophagy-defective pSTING mutants still resisted the two viral infections, demonstrating that the pSTING antiviral function is independent of IFN as well as autophagy. On the other hand, all of the autophagy-defective pSTING mutants triggered cell apoptosis, which was associated with and participated in the antiviral functions. Additionally, pSTING lost its antiviral activity in TANK-binding kinase 1 (TBK1)-/- and IFN regulatory factor 3 (IRF3)-/- porcine macrophages, indicating the involvement of TBK1 and IRF3 in other STING activities such as apoptosis. Collectively, our results revealed that STING exerts both IFN- and autophagy-independent antiviral activity, and they also suggested that STING-triggered cell apoptosis resists viral infections. IMPORTANCE The IFN-independent antiviral function of the cGAS-STING pathway has attracted great attention in recent years; however, the nature of this IFN-independent antiviral function is unknown, although STING-induced autophagy has been shown to mediate the STING antiviral activity. First, we analyzed the antiviral activity through the porcine cGAS-pSTING pathway and established that pSTING signaling exerts an IFN-independent antiviral function. Second, we found that pSTING-induced IFN-independent autophagy and the antiviral activity of pSTING are independent of both IFN and autophagy. Finally, pSTING signaling activates cell apoptosis independently of IFN and autophagy, and the apoptosis is associated with antiviral activity. Our results suggest that pSTING-activated apoptosis at least partially mediates the antiviral activity or multiple pSTING-activated signals, including IFN production, nuclear factor κ light chain enhancer of activated B cells (NF-κB) expression, autophagy, and apoptosis, exert a redundant antiviral role. Thus, the work reveals a new layer of complexity in STING antiviral activity.

Safety and efficacy of human umbilical cord mesenchymal stem cells for the treatment of sepsis induced by pneumonia: study protocol for a single-centre, randomised single-blind parallel group trial.

INTRODUCTION: Sepsis is a life-threatening organ disorder caused by a dysregulated inflammatory response to infection with no effective treatment options exist thus far. Therefore, novel therapeutic methods are urgently advocated for decreasing the high mortality rate. Recently, preclinical studies supported the efficacy of mesenchymal stem cells (MSCs) in the treatment of sepsis. In this study, we aim to test the safety, tolerability and efficacy of human umbilical cord MSCs (HUC-MSCs) for the treatment of pneumonia induced sepsis. METHODS AND ANALYSIS: This study is a single-centre, randomised single-blind parallel group, placebo-controlled trial. Forty eligible participants with pneumonia-induced sepsis will be randomly assigned to the observational cohort and the interventional cohort in a 1:1 ratio. In addition to the standard treatments recommended by the Sepsis 3.0 guidelines, HUC-MSCs will be administered intravenously as adjunctive therapy on day 0 at a dose of 1×106 cells/kg with a total volume of 100 mL diluted with normal saline through 120 mL/hour intravenous central line infusion in the interventional cohort. Placebo (normal saline) will also be administered through 120 mL/hour intravenous central line infusion at the same quantity (total volume of 100 mL) in the observational cohort. The study is approved by Research Ethics Board of East Hospital/Tongji University, which has been registered on Chinese clinical trial registry (chictr.org.cn) and initiated from October 2021. All the participants will be followed at regular intervals for 1 year. Funding is from the 'National Natural Science Foundation, China and top-level clinical discipline project of Shanghai Pudong'. This study is the first trial to assess the safety and efficacy of HUC-MSCs for the treatment of sepsis induced by pneumonia. The results will advance our understanding of the mode of action of HUC-MSCs and will also be critical for the design of future investigation in larger randomised controlled trials in multicentre. These data will offer insight into defining endpoints, key biomarkers and sample size determination. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Board of East Hospital, Tongji University (Shanghai, China), which has accepted responsibility for supervising all aspects of the study (DFSC-2021(CR-04). The results of this study will be presented at both national and international conferences and be considered for publication in a peer-reviewed scientific journal. All the results presented in this study will be of group data, therefore, individual participants will not be identifiable. TRIAL REGISTRATION NUMBER: ChiCTR2100050544, the trial is now at the stage of pre-results.

Identification of Nanog as a novel inhibitor of Rad51.

To develop inhibitors targeting DNA damage repair pathways is important to improve the effectiveness of chemo- and radiotherapy for cancer patients. Rad51 mediates homologous recombination (HR) repair of DNA damages. It is widely overexpressed in human cancers and overwhelms chemo- and radiotherapy-generated DNA damages through enhancing HR repair signaling, preventing damage-caused cancer cell death. Therefore, to identify inhibitors of Rad51 is important to achieve effective treatment of cancers. Transcription factor Nanog is a core regulator of embryonic stem (ES) cells for its indispensable role in stemness maintenance. In this study, we identified Nanog as a novel inhibitor of Rad51. It interacts with Rad51 and inhibits Rad51-mediated HR repair of DNA damage through its C/CD2 domain. Moreover, Rad51 inhibition can be achieved by nanoscale material- or cell-penetrating peptide (CPP)-mediated direct delivery of Nanog-C/CD2 peptides into somatic cancer cells. Furthermore, we revealed that Nanog suppresses the binding of Rad51 to single-stranded DNAs to stall the HR repair signaling. This study provides explanation for the high γH2AX level in unperturbed ES cells and early embryos, and suggests Nanog-C/CD2 as a promising drug candidate applied to Rad51-related basic research and therapeutic application studies.

Clinical outcomes of vinorelbine loading CalliSpheres beads in the treatment of previously treated advanced lung cancer with progressive refractory obstructive atelectasis.

Background: Drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) has been used in the treatment of locally advanced lung cancer and has the potential to improve outcomes and reduce recurrence. However, DEB-BACE shows a poor therapeutic effect in advanced lung cancer after failure of multiple therapies. This study assessed the effect of DEB-BACE in the treatment of progressive lung cancer with refractory obstructive atelectasis. Methods: Progressive advanced lung cancer patients with refractory obstructive atelectasis were voluntarily enrolled in this study after failure of multiple conventional therapies. Baseline information, DEB-BACE treatment process, and changes in clinical symptoms were recorded. The primary endpoints were the objective response rate (ORR) and improvement rate of dyspnea. The secondary endpoints were time-to-progression (TTP), overall survival (OS), and rate of pulmonary re-expansion. Treatment-related adverse events and serious adverse events were analyzed to assess the safety of DEB-BACE. The Cox regression model was performed to analyze the possible factors impacting prognosis of DEB-BACE. Results: DEB-BACE was successfully performed with CalliSpheres beads loaded with vinorelbine in the 20 enrolled patients. ORR and disease control rate were 80% and 85%, respectively, at the first follow-up (43.4 ± 15.26 days). The improvement rate of dyspnea was 85% and 80% at 1 week and 1 month (p < 0.0001, p < 0.0001), respectively. TTP was 41.25 ± 14.43 days and 89.55 ± 61.7 days before and after DEB-BACE, respectively; DEB-BACE delayed the progression of advanced lung cancer (p < 0.0001). OS was 238.03 ± 33.74 days (95% confidence interval: 171.9-304.16). The rate of pulmonary re-expansion was 80% at the first follow-up. The reasons for poor prognosis were tumor necrosis, longer disease duration, and pulmonary atelectasis duration (p = 0.012, p = 0.038, p = 0.029). Massive hemoptysis was observed in two cases, and one patient died of asphyxia caused by hemoptysis. Moderate hemoptysis occurred in one case. All three adverse events were considered as the result of the tumor cavity after DEB-BACE. Conclusion: DEB-BACE loaded with vinorelbine is a feasible option for progressive advanced lung cancer with obstructive atelectasis after failure of other treatments.

Effect of Pramipexole on Inflammatory Response in Central Nervous System of Parkinson's Disease Rat Model.

BACKGROUND: Pramipexole is the dopamine receptor agonist commonly used for treatment of PD, the effect of which on immunity played an important role in pathological process is also deserved to be further studied. AIM OF STUDY: We observed the effect of pramipexole on behavior and central nervous system (CNS) inflammatory cytokines of Parkinson's Disease (PD) model rats. METHODS: We injected 3.0 µL lipopolysaccharide into the right substantia nigra compact (SNc) and ventral tegmental area (VTA) of sprague-dawley (SD) rats to establish PD models which were divided as treated group feeded with pramipexole for 14 d and untreated group feeded with saline. And SD rats were selected as control group feeded with saline. We conducted rotation test on PD model rats before and after treatment. We also performed euthanasia on all rats to obtain the striatum area and nearby tissues after treatment, measuring mRNA expression and concentration of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by reverse transcription polymerase chain reaction test and elisa method, respectively. RESULTS: It was observed that the degree of behavior improvement in treated group was greater than that in untreated group. In addition, mRNA expression and concentrations of IL-6 and TNF-α in treated group were lower than those in untreated group and higher than those in control group. CONCLUSIONS: Pramipexole improved behavior of PD model rat, and down regulated the mRNA expression and concentrations of IL-6 and TNF-α in their CNS.

The Innate Immune DNA Sensing cGAS-STING Signaling Pathway Mediates Anti-PRRSV Function.

Porcine reproductive and respiratory syndrome virus (PRRSV) modulates host innate immunity which plays a key role against PRRSV infection. As a RNA virus, PRRSV is mainly sensed by innate immune RNA receptors, whereas the role of innate immune DNA sensors in the PRRSV infection has not been elucidated. Here, we investigated the roles of DNA sensing cGAS-STING pathway in both PRRSV infected Marc-145 cells and porcine macrophages. The results show that in Marc-145 cells, the stable expression of STING with or without stimulations exhibited anti-PRRSV activity, and STING knockout heightened PRRSV infection. In CD163-3D4/21 porcine macrophages, either expression of STING or stimulation of cGAS-STING signaling obviously suppressed PRRSV infection, whereas in STING knockdown macrophages, the PRRSV infection was upregulated. Our results clearly demonstrate that the host cGAS-STING signal exerts an important antiviral role in PRRSV infection.

NF­κB is negatively associated with Nurr1 to reduce the inflammatory response in Parkinson's disease.

Parkinson's disease (PD) is one of the most disabling diseases of the central nervous system, seriously affecting health and quality of life for the elderly. The present study aimed to explore the effects of nuclear receptor subfamily 4 group A member 2 (Nurr1) and nuclear factor­κB (NF­κB) on the progression of Parkinson's disease (PD). Pheochromocytoma (PC12) cells were pretreated with the NF­κB inhibitor quinazoline (QNZ) or transfected with small interfering (si)RNA­NF­κB, followed by the addition of lipopolysaccharide (LPS). After culturing for 24 h, Cell Counting Kit­8 (CCK­8) was utilized to measure cell viability. Next, the expression levels of interleukin (IL)­1ß, IL­6 and tumor necrosis factor (TNF)­α were determined using the relevant Enzyme­linked immunosorbent assay kits. Expression levels of p65, tyrosine hydroxylase (TH), α­Synuclein (A­SYN) and Nurr1 were examined by immunofluorescence and western blotting. CCK­8 results showed that the cell viability was significantly reduced in the LPS group than in the control group (P<0.05), whereas QNZ and si­NF­κB demonstrated significantly enhanced viability induced by LPS (P<0.05). After LPS induction, the levels of IL­1ß, IL­6 and TNF­α were significantly elevated when compared with those in the control group (P<0.05), whereas QNZ and NF­κB interference partially restored their levels. Additionally, after LPS induction, the expression of p65 and A­SYN was higher, while the expression of TH and Nurr1 was lower. However, QNZ and NF­κB treatment significantly reversed the expression levels induced by LPS (P<0.05). Finally, it was observed that NF­κB may be negatively associated with Nurr1. In conclusion, inhibition of NF­κB may reduce the production of inflammatory factors by upregulating Nurr1 and TH and downregulating A­SYN, thus relieving the inflammatory response in PD.

Different clinical features between patients with ROS1-positive and ALK-positive advanced non-small cell lung cancer.

OBJECTIVE: To compare the baseline clinical characteristics between patients with ROS1-positive and ALK-positive advanced non-small cell lung cancer (NSCLC), and the correlations of these subtypes with the distribution of metastases. METHODS: We compared the clinical characteristics and imaging features of patients with ROS1-positive and ALK-positive NSCLC using statistical methods. RESULTS: Data for 232 patients were analyzed. Compared with ALK-positive NSCLC, ROS1-positive NSCLC was more likely to occur in women (71% vs 53%), and primary lesions ≤3 cm were more common in patients with ROS1-positive compared with ALK-positive NSCLC (58% vs 37%). There was no significant difference in the distribution of metastases between the two groups. Subgroup analysis within the ROS1-positive group showed that, compared with primary lesions >3 cm, primary lesions ≤3 cm were more likely to present as peripheral tumors (72% vs 43%) and more likely to exhibit non-solid density (44% vs 4%). CONCLUSIONS: Although ROS1-positive and ALK-positive NSCLCs show similar clinical features, the differences may help clinicians to identify patients requiring further genotyping at initial diagnosis.

pH-responsive hollow Fe-gallic acid coordination polymer for multimodal synergistic-therapy and MRI of cancer.

Tumor-microenvironment (TME) responsive nanostructures are attractive for drug delivery in clinical cancer treatment. The coordination polymer Fe-gallic acid (Fe-GA) is one of the promising drug carriers due to its pH-response, good biocompatibility, and minimal side effects. However, the hollow nanostructures of Fe-GA have not been reported until now, which seriously limits the quantity of drug delivery. Herein, hollow Fe-GA nanospheres were prepared for the first time with bovine serum albumin (BSA) combination (denoted as Fe-GA/BSA) under mild reaction conditions. Then, the antitumor drug doxorubicin (DOX) was loaded in the hollow Fe-GA/BSA to obtain Fe-GA/BSA@DOX. A series of experiments in vitro and in vivo indicated that the Fe-GA/BSA@DOX could efficiently respond to TME and release DOX and Fe(iii) ions. Furthermore, the Fe(iii) could consume overexpressed glutathione (GSH) in cancer cells and generate Fe(ii) to trigger the Fenton reaction, producing ·OH for chemodynamic treatment (CDT) of cancer. In addition, the Fe-GA/BSA@DOX could effectively convert near-infrared (NIR) light into heat by acting as a photothermal therapy (PTT) agent. Besides that, magnetic resonance imaging (MRI) data also showed that the Fe-GA/BSA had beneficial T1 and T2 imaging effects, demonstrating that the hollow Fe-GA/BSA has potential for multimodal synergistic cancer MRI diagnosis and therapies of drugs, CDT, and PTT.

A complement factor I (CFI) gene mediates innate immune responses in yellow catfish Pelteobagrus fulvidraco.

This study isolated CFI gene from Pelteobagrus fulvidraco and named it PfCFI. The cDNA of PfCFI is 2374 bp long, including a 52 bp 5' untranslated sequence, a 222 bp 3' untranslated sequence, and an open reading frame (ORF) of 2100 bp encoding polypeptide consisting of 699 amino acids. Phylogenetic analysis revealed that the PfCFI was closely related to CFI of Ictalurus punctatus. Real-time quantitative reverse transcription-PCR (qRT-PCR) analysis indicate that there is the PfCFI gene which expressed in all the rest of tested tissues in varied levels, and mainly distributed in liver and least in heart. The reseachers induce the expressions level of PfCFI gene in liver, spleen, head kidney and blood at different points in time after challenged with lipopolysaccharide (LPS), and polyriboinosinic polyribocytidylic acid (poly I:C), respectively. Together these results suggested that CFI gene plays an important role in resistance to pathogens in yellow catfish immunity.

ATP13A2 Gene Variants in Patients with Parkinson's Disease in Xinjiang.

OBJECTIVE: To analyze the ATP13A2 gene variants in the Han and Uyghur populations residing in Xinjiang and to determine their correlation with the risk of Parkinson's disease (PD). METHODS: Four ATP13A2 SNVs-rs56367069 (Arg294Gln), rs151117874 (Thr12Met), rs147277743 (Ala746Thr), and rs2076603-were analyzed in 218 patients (75 Uyghurs and 143 Hans) with sporadic PD and 234 healthy controls (90 Uyghurs and 144 Hans) by Sanger DNA sequencing. RESULTS: Only one Han patient harbored the AG genotype of the rs147277743 SNV, indicating a frequency of 0.46% in the Han population. In addition, this SNV was not associated with PD risk. The rs2076603 SNV was correlated with PD development, and the A allele in particular was significantly different across ethnicity and age. The rs56367069 and rs151117874 SNVs were not detected in the entire cohort. CONCLUSION: ATP13A2 rs2076603 SNV is associated with PD susceptibility, and the A allele is a PD protective factor in the Han population.

African Swine Fever Virus Structural Protein p17 Inhibits Cell Proliferation through ER Stress-ROS Mediated Cell Cycle Arrest.

African swine fever virus (ASFV) is a highly pathogenic large DNA virus that causes African swine fever (ASF) in domestic pigs and wild boars. The p17 protein, encoded by the D117L gene, is a major transmembrane protein of the capsid and the inner lipid envelope. The aim of this study was to investigate the effects of p17 on cell proliferation and the underlying mechanisms of action. The effects of p17 on cell proliferation, cell cycle, apoptosis, oxidative stress, and endoplasmic reticulum (ER) stress have been examined in 293T, PK15, and PAM cells, respectively. The results showed that p17 reduced cell proliferation by causing cell cycle arrest at G2/M phase. Further, p17-induced oxidative stress and increased the level of intracellular reactive oxygen species (ROS). Decreasing the level of ROS partially reversed the cell cycle arrest and prevented the decrease of cell proliferation induced by p17 protein. In addition, p17-induced ER stress, and alleviating ER stress decreased the production of ROS and prevented the decrease of cell proliferation induced by p17. Taken together, this study suggests that p17 can inhibit cell proliferation through ER stress and ROS-mediated cell cycle arrest, which might implicate the involvement of p17 in ASF pathogenesis.