Plasminogen activator urokinase interacts with the fusion protein and antagonizes the growth of Peste des petits ruminants virus.

Peste des petits ruminants is an acute and highly contagious disease caused by the Peste des petits ruminants virus (PPRV). Host proteins play a crucial role in viral replication. However, the effect of fusion (F) protein-interacting partners on PPRV infection is poorly understood. In this study, we found that the expression of goat plasminogen activator urokinase (PLAU) gradually decreased in a time- and dose-dependent manner in PPRV-infected goat alveolar macrophages (GAMs). Goat PLAU was subsequently identified using co-immunoprecipitation and confocal microscopy as an F protein binding partner. The overexpression of goat PLAU inhibited PPRV growth and replication, whereas silencing goat PLAU promoted viral growth and replication. Additionally, we confirmed that goat PLAU interacted with a virus-induced signaling adapter (VISA) to antagonize F-mediated VISA degradation, increasing the production of type I interferon. We also found that goat PLAU reduced the inhibition of PPRV replication in VISA-knockdown GAMs. Our results show that the host protein PLAU inhibits the growth and replication of PPRV by VISA-triggering RIG-I-like receptors and provides insight into the host protein that antagonizes PPRV immunosuppression.IMPORTANCEThe role of host proteins that interact with Peste des petits ruminants virus (PPRV) fusion (F) protein in PPRV replication is poorly understood. This study confirmed that goat plasminogen activator urokinase (PLAU) interacts with the PPRV F protein. We further discovered that goat PLAU inhibited PPRV replication by enhancing virus-induced signaling adapter (VISA) expression and reducing the ability of the F protein to degrade VISA. These findings offer insights into host resistance to viral invasion and suggest new strategies and directions for developing PPR vaccines.

SNX32 is a host restriction factor that degrades African swine fever virus CP204L via the RAB1B-dependent autophagy pathway.

African swine fever virus (ASFV) causes a highly contagious and deadly disease in domestic pigs and European wild boars, posing a severe threat to the global pig industry. ASFV CP204L, a highly immunogenic protein, is produced during the early stages of ASFV infection. However, the impact of CP204L protein-interacting partners on the outcome of ASFV infection is poorly understood. To accomplish this, coimmunoprecipitation and mass spectrometry analysis were conducted in ASFV-infected porcine alveolar macrophages (PAMs). We have demonstrated that sorting nexin 32 (SNX32) is a CP204L-binding protein and that CP204L interacted and colocalized with SNX32 in ASFV-infected PAMs. ASFV growth and replication were promoted by silencing SNX32 and suppressed by overexpressing SNX32. SNX32 degraded CP204L by recruiting the autophagy-related protein Ras-related protein Rab-1b (RAB1B). RAB1B overexpression inhibited ASFV replication, while knockdown of RAB1B had the opposite effect. Additionally, RAB1B, SNX32, and CP204L formed a complex upon ASFV infection. Taken together, this study demonstrates that SNX32 antagonizes ASFV growth and replication by recruiting the autophagy-related protein RAB1B. This finding extends our understanding of the interaction between ASFV CP204L and its host and provides new insights into exploring the relationship between ASFV infection and autophagy.IMPORTANCEAfrican swine fever (ASF) is a highly contagious and acute hemorrhagic viral disease with a high mortality near 100% in domestic pigs. ASF virus (ASFV), which is the only member of the family Asfarviridae, is a dsDNA virus of great complexity and size, encoding more than 150 proteins. Currently, there are no available vaccines against ASFV. ASFV CP204L represents the most abundantly expressed viral protein early in infection and plays an important role in regulating ASFV replication. However, the mechanism by which the interaction between ASFV CP204L and host proteins affects ASFV replication remains unclear. In this study, we demonstrated that the cellular protein SNX32 interacted with CP204L and degraded CP204L by upregulating the autophagy-related protein RAB1B. In summary, this study will help us understand the interaction mechanism between CP204L and its host upon infection and provide new insights for the development of vaccines and antiviral drugs.

Hydrogen sulfide alleviates chromium toxicity by promoting chromium sequestration and re-establishing redox homeostasis in Zea mays L.

Hydrogen sulfide (H2S) is a multifunctional gaseous signaling molecule involved in the regulation of Cr stress responses. In the present study, we combined transcriptomic and physiological analyses to elucidate the mechanism underlying the mitigation of Cr toxicity by H2S in maize (Zea mays L.). We showed that treatment with sodium hydrosulfide (NaHS, a donor of H2S) partially alleviated Cr-induced growth inhibition. However, Cr uptake was not affected. RNA sequencing suggested that H2S regulates the expression of many genes involved in pectin biosynthesis, glutathione metabolism, and redox homeostasis. Under Cr stress, NaHS treatment significantly increased pectin content and pectin methylesterase activity; thus, more Cr was retained in the cell wall. NaHS application also increased the content of glutathione and phytochelatin, which chelate Cr and transport it into vacuoles for sequestration. Furthermore, NaHS treatment mitigated Cr-induced oxidative stress by enhancing the capacity of enzymatic and non-enzymatic antioxidants. Overall, our results strongly support that H2S alleviates Cr toxicity in maize by promoting Cr sequestration and re-establishing redox homeostasis rather than by reducing Cr uptake from the environment.

Electrode Layout Optimization and Numerical Simulation of Cast Conductive Asphalt Concrete Steel Bridge Deck Pavement.

In order to obtain the optimal electrode layout and ice melting effect of cast conductive asphalt concrete steel bridge deck pavement, firstly, pouring conductive asphalt concrete was prepared; secondly, different electrode materials and layout methods were selected to test the heating rate of the specimen from start to 120 min, and the electrode materials and layout methods were optimized. Then, the finite element analysis software ANSYS was used to build the model for heating and ice melting simulation, and the indoor test was used to further verify the ice melting effect of the cast conductive asphalt coagulation with or without the insulation layer. Finally, the thermal-structural coupling analysis of cast conductive asphalt concrete steel bridge deck pavement was carried out using ANSYS finite element software. The results showed that the stainless steel electrode material had the best heating effect, and the electrode thickness in the range of 0.1~3 mm had no effect on the heating effect. The intermediate heating rate of the upper surface of the stainless steel sheet electrode cast conductive asphalt concrete in the left and right external electrodes was 8 ∘C/h, while the intermediate heating rate of the upper surface of the stainless steel mesh electrode cast conductive asphalt concrete was 12.9 ∘C/h. The layout of the left and right buried stainless steel metal mesh was able to effectively improve the snow melting efficiency; ANSYS finite element ice melting simulation was used to obtain the variation law of ice melting efficiency and a temperature field of cast conductive asphalt concrete. The indoor ice melting test showed that when melting the same thickness ice layer at 50 V voltage, it took 240 min with an insulation layer and 720 min without an insulation layer, which was three times that of the ice with an insulation layer, which further verifies the superiority of its ice melting effect. The most unfavorable load position of pavement under load and temperature field was determined. The maximum tensile stress and compressive stress of the pavement surface were transverse, and the maximum shear stress of the pavement bottom was transverse.

A QP509L/QP383R-Deleted African Swine Fever Virus Is Highly Attenuated in Swine but Does Not Confer Protection against Parental Virus Challenge.

African swine fever (ASF), a devastating infectious disease in swine, severely threatens the global pig farming industry. Disease control has been hampered by the unavailability of vaccines. Here, we report that deletion of the QP509L and QP383R genes (ASFV-ΔQP509L/QP383R) from the highly virulent ASF virus (ASFV) CN/GS/2018 strain results in complete viral attenuation in swine. Animals inoculated with ASFV-ΔQP509L/QP383R at a 104 50% hemadsorbing dose (HAD50) remained clinically normal during the 17-day observational period. All ASFV-ΔQP509L/QP383R-infected animals had low viremia titers and developed a low-level p30-specific antibody response. However, ASFV-ΔQP509L/QP383R did not induce protection against challenge with the virulent parental ASFV CN/GS/2018 isolate. RNA-sequencing analysis revealed that innate immune-related genes (Ifnb, Traf2, Cxcl10, Isg15, Rantes, and Mx1) were significantly lower in ASFV-ΔQP509L/QP383R-infected than in ASFV-infected porcine alveolar macrophages. In addition, ASFV-ΔQP509L/QP383R-infected pigs had low levels of interferon-ß (IFN-ß) based on enzyme-linked immunosorbent assay (ELISA). These data suggest that deletion of ASFV QP509L/383R reduces virulence but does not induce protection against lethal ASFV challenge. IMPORTANCE African swine fever (ASF) is endemic to several parts of the word, with outbreaks of the disease devastating the swine farming industry; currently, no commercially available vaccine exists. Here, we report that deletion of the previously uncharacterized QP509L and QP383R viral genes completely attenuates virulence in the ASF virus (ASFV) CN/GS/2018 isolate. However, ASFV-ΔQP509L/QP383R-infected animals were not protected from developing an ASF infection after challenge with the virulent parental virus. ASFV-ΔQP509L/QP383R induced lower levels of innate immune-related genes and IFN-ß than the parental virus. Our results increase our knowledge of developing an effective and live ASF attenuated vaccine.

Research Progress on the Structure and Function of G3BP.

Ras-GTPase-activating protein (SH3 domain)-binding protein (G3BP) is an RNA binding protein. G3BP is a key component of stress granules (SGs) and can interact with many host proteins to regulate the expression of SGs. As an antiviral factor, G3BP can interact with viral proteins to regulate the assembly of SGs and thus exert antiviral effects. However, many viruses can also use G3BP as a proximal factor and recruit translation initiation factors to promote viral proliferation. G3BP regulates mRNA translation and attenuation to regulate gene expression; therefore, it is closely related to diseases, such as cancer, embryonic death, arteriosclerosis, and neurodevelopmental disorders. This review discusses the important discoveries and developments related G3BP in the biological field over the past 20 years, which includes the formation of SGs, interaction with viruses, stability of RNA, and disease progression.

First case report of papillary thyroid carcinoma arising within a functional teratoma in Graves' disease patient.

AIM: Mature cystic teratoma is the most common kind of ovarian germ tumor. However, malignant transformation is uncommon, differentiated thyroid carcinoma is even rare. Hyperthyroidism due to coexistence of Graves' disease (GD) and struma ovarii has been reported. Functional teratoma with papillary thyroid carcinoma (PTC) in GD case has never been reported in literature. MATERIAL AND METHOD: A 48-year-old woman with GD for 4 years, who visited our hospital with complaints of severe abdominal pain for 1 day. Computed tomography of the abdominal revealed a large fat-containing lesion with dense calcification, measured 8.6 × 7.2 cm in size. Laparotomy right total oophorectomy was performed, and a huge gangrenous right ovary was noted during exploration. The final pathological diagnosis was teratoma with PTC change at right ovary. We performed thyroglobulin, TTF-1 and CK19 staining in the teratoma, the results were positive, suggesting the thyroid-hormone secretion in the PTC tissue. RESULT: After resection of the ovarian lesion, euthyroidism was achieved. Adjuvant thyroidectomy is not performed for no evidence of thyroid lesion or distant metastases. No GD recurrence in the 2 years after operation. The patient also does not manifest any gynecological disease symptoms, whereas the other ovary, in the follow-up ultrasound examinations, shows normal size and echo structure. CONCLUSION: PTC can arise within ovarian teratoma and may have thyroid hormone production. Surgeries of unilateral oophorectomy or cystectomy are a reasonable treatment, and follow-up of thyroid image and data is necessary.

Picornavirus 3C - a protease ensuring virus replication and subverting host responses.

The protease 3C is encoded by all known picornaviruses, and the structural features related to its protease and RNA-binding activities are conserved; these contribute to the cleavage of viral polyproteins and the assembly of the viral RNA replication complex during virus replication. Furthermore, 3C performs functions in the host cell through its interaction with host proteins. For instance, 3C has been shown to selectively 'hijack' host factors involved in gene expression, promoting picornavirus replication, and to inactivate key factors in innate immunity signaling pathways, inhibiting the production of interferon and inflammatory cytokines. Importantly, 3C maintains virus infection by subtly subverting host cell death and modifying critical molecules in host organelles. This Review focuses on the molecular mechanisms through which 3C mediates physiological processes involved in virus-host interaction, thus highlighting the picornavirus-mediated pathogenesis caused by 3C.

Cisplatin loaded multiwalled carbon nanotubes reverse drug resistance in NSCLC by inhibiting EMT.

BACKGROUND: Lung cancer is one of the important health threats worldwide, of which 5-year survival rate is less than 15%. Non-small-cell lung cancer (NSCLC) accounts for about 80% of all lung cancer with high metastasis and mortality. METHODS: Cisplatin loaded multiwalled carbon nanotubes (Pt-MWNTS) were synthesized and used to evaluate the anticancer effect in our study. The NSCLC cell lines A549 (cisplatin sensitive) and A549/DDP (cisplatin resistant) were used in our in vitro assays. MTT was used to determine Cancer cells viability and invasion were measured by MTT assay and Transwell assay, respectively. Apoptosis and epithelial-mesenchymal transition related marker proteins were measured by western blot. The in vivo anti-cancer effect of Pt-MWNTs were performed in male BALB/c nude mice (4-week old). RESULTS: Pt-MWNTS were synthesized and characterized by X-ray diffraction, Raman, FT-IR spectroscopy and scan electron microscopy. No significant cytotoxicity of MWNTS was detected in both A549/DDP and A549 cell lines. However, Pt-MWNTS showed a stronger inhibition effect on cell growth than free cisplatin, especially on A549/DDP. We found Pt-MWNTS showed higher intracellular accumulation of cisplatin in A549/DDP cells than free cisplatin and resulted in enhanced the percent of apoptotic cells. Western blot showed that application of Pt-MWNTS can significantly upregulate the expression level of Bax, Bim, Bid, Caspase-3 and Caspase-9 while downregulate the expression level of Bcl-2, compared with free cisplatin. Moreover, the expression level of mesenchymal markers like Vimentin and N-cadherin was more efficiently reduced by Pt-MWNTS treatment in A549/DDP cells than free cisplatin. In vivo study in nude mice proved that Pt-MWNTS more effectively inhibited tumorigenesis compared with cisplatin, although both of them had no significant effect on body weight. CONCLUSION: Pt-MWNT reverses the drug resistance in the A549/DDP cell line, underlying its possibility of treating NSCLC with cisplatin resistance.

Analysis of the population structure and genetic diversity of the red swamp crayfish (Procambarus clarkii) in China using SSR markers

BACKGROUND: Procambarus clarkii produces high-quality, delicious meat that is high in protein, low in fat, and rich in calcium and phosphorus. It has become an important aquatic resource in China. Our objectives are (i) to analyze the level of genetic diversity of P. clarkii populations; (ii) to explore the genetic differentiation (Gst); and (iii) to propose appropriate strategies for the conservation. RESULTS: In this study, Shannon's index (I) and Nei's gene diversity index (H) for P. clarkii were high (I = 0.3462 and H = 0.2325 on average and I = 0.6264, H = 0.4377 at the species level) based on the SSR markers. The expected heterozygosity value of 17 microsatellite loci in 25 crayfish populations was 0.9317, the observed heterozygosity value was 0.9121, and the observed number of alleles per locus was 2.000; and the effective number of alleles per locus was 1.8075. Among the P. clarkii populations, the inbreeding coefficient within populations (Fis) was 0.2315, overall inbreeding coefficient (Fit) was 0.4438, genetic differentiation coefficient among populations (Fst) was 0.3145 and gene differentiation (Gst) was 0.4785 based on SSR analyses. The cluster analysis results obtained by unweighted pair-group method with arithmetic mean (UPGMA) analysis, principal coordinate analysis (PCoA) and STRUCTURE analysis were similar. A mantel test showed that the isolation-by-distance pattern was not significant. CONCLUSIONS: The high Gst among P. clarkii populations is attributed to genetic drift and geographic isolation. The results indicated that more P. clarkii populations should be collected when formulating conservation and aquaculture strategies.

Effects of hesperidin on the growth performance, antioxidant capacity, immune responses and disease resistance of red swamp crayfish (Procambarus clarkii).

We evaluated the effects of hesperidin on the nonspecific immunity, antioxidant capacity and growth performance of red swamp crayfish (Procambarus clarkii). A total of 900 healthy crayfish were randomly divided into six groups: the control group (fed the basal diet) and the HES25, HES50, HES75, HES100 and HES150 groups, which were fed the basal diet supplemented with 25, 50, 75, 100 and 150 mg kg-1 hesperidin, respectively. The feeding experiment lasted 8 weeks. The results indicated that compared with the control group, the crayfish groups supplemented with 50-150 mg kg-1 hesperidin had a decreased feed conversion ratio (FCR) and increased final body weight (FBW), specific growth rate (SGR) and weight gain (WG) (P < 0.05). The protein carbonyl content (PCC), reactive oxygen species (ROS) level and malondialdehyde (MDA) level in the hepatopancreas and hemocytes were significantly lower, while the total antioxidant capacity (T-AOC), glutathione peroxidase (GPx) activity, and superoxide dismutase (SOD) activity were significantly higher in the crayfish groups supplemented with 50-150 mg kg-1 hesperidin than in the control group. Supplementation with 50-150 mg kg-1 hesperidin significantly increased the activities of acid phosphatase (ACP), alkaline phosphatase (AKP), lysozyme (LZM), and phenoloxidase (PO) compared with the control group (P < 0.05); upregulated the mRNA expression of cyclophilin A (CypA), extracellular copper-zinc superoxide dismutase (ecCuZnSOD), GPxs, crustin, astacidin, Toll3 and heat shock protein 70 (HSP70) (P < 0.05); and decreased crayfish mortality following white spot syndrome virus (WSSV) infection. These findings indicate that dietary hesperidin supplementation at an optimum dose of 50-150 mg kg-1 may effectively improve nonspecific immunity, antioxidant capacity and growth performance in crayfish.

Iron Overload Associated Endocrine Dysfunction Leading to Lower Bone Mineral Density in Thalassemia Major.

CONTEXT: Patients with thalassemia major (TM) have a lower bone mineral density (BMD) and higher risk of fracture than the general population. The possible mechanisms include anemia, iron overload, malnutrition, and hormonal deficiency, but these have not been thoroughly investigated. OBJECTIVE: To identify major mineral and hormonal factors related to BMD in adult TM patients to provide human evidence for the proposed mechanisms. DESIGN: Retrospective study. SETTING: Referral center. PATIENTS: Twenty-nine patients with ß-TM, aged 23 to 44 years who were followed-up during 2017 to 2018 were enrolled. OUTCOME MEASUREMENTS: Endocrine profiles, including thyroid, parathyroid, and pituitary function, glucose, vitamin D, calcium, phosphate, and fibroblast growth factor 23 (FGF23) were obtained. The relationships among the above parameters, body height, fractures, and BMD were analyzed. RESULTS: Abnormal BMD was observed in 42.9% of women and 23.1% of men. The mean final heights of women and men were 3.7 cm and 7.3 cm lower than the mean expected values, respectively. Fracture history was recorded in 26.7% of women and 35.7% of men. BMD was negatively correlated with parathyroid hormone, FGF23, thyrotropin, and glycated hemoglobin (HbA1c) levels, and positively correlated with testosterone, IGF-1, and corticotropin levels (all P < .05). Moreover, hypothyroidism was associated with lower BMD in both the lumbar spine (P = .024) and the femoral neck (P = .004). Patients with hypothyroidism had a higher percentage of abnormal BMD (P = .016). CONCLUSION: Hypothyroidism, higher HbA1c, and lower adrenocorticotropin were predictors of abnormal BMD in patients with ß-TM. Whether the correction of these factors improves BMD warrants further research.

Foot-and-Mouth Disease Virus 3A Protein Causes Upregulation of Autophagy-Related Protein LRRC25 To Inhibit the G3BP1-Mediated RIG-Like Helicase-Signaling Pathway.

Foot-and-mouth disease virus (FMDV) is one of the most notorious pathogens in the global livestock industry. To establish an infection, FMDV needs to counteract host antiviral responses. Several studies have shown how FMDV suppresses the type I interferon (IFN) response; however, whether FMDV modulates the integrated autophagy and innate immunity remains largely unknown. Here, the porcine Ras-GAP SH3-binding protein 1 (G3BP1) was shown to promote the retinoic acid-inducible gene I (RIG-I)-like helicase (RLH) signaling by upregulating the expression of RIG-I and melanoma differentiation-associated gene 5 (MDA5). FMDV nonstructural protein 3A interacted with G3BP1 to inhibit G3BP1 expression and G3BP1-mediated RLH signaling by upregulating the expression of autophagy-related protein LRRC25. In addition, 3A proteins of other picornaviruses, including Seneca Valley virus (SVV) 3A, enterovirus 71 (EV71) 3A, and encephalomyocarditis virus (EMCV) 3A, also showed similar actions. Taking the data together, we elucidated, for the first time, a novel mechanism by which FMDV has evolved to inhibit IFN signaling and counteract host innate antiviral responses by autophagy.IMPORTANCE We show that foot-and-mouth disease virus (FMDV) 3A inhibits retinoic acid-inducible gene I (RIG-I)-like helicase signaling by degrading G3BP1 protein. Furthermore, FMDV 3A reduces G3BP1 by upregulating the expression of autophagy-related protein LRRC25. Additionally, other picornavirus 3A proteins, such as Seneca Valley virus (SVV) 3A, enterovirus 71 (EV71) 3A, and encephalomyocarditis virus (EMCV) 3A, also degrade G3BP1 by upregulating LRRC25 expression. This study will help us improve the design of current vaccines and aid the development of novel control strategies to combat FMD.

G3BP1 inhibits RNA virus replication by positively regulating RIG-I-mediated cellular antiviral response.

Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor and is involved in the innate immune response against RNA viruses infection. Here, we demonstrate that the Ras-GTPase-activating protein SH3-domain-binding protein 1 (G3BP1) serves as a positive regulator of the RIG-I-mediated signaling pathway. G3BP1-deficient cells inhibited RNA virus-triggered induction of downstream antiviral genes. Furthermore, we found that G3BP1 inhibited the replication of Sendai virus and vesicular stomatitis virus, indicating a positive regulation of G3BP1 to cellular antiviral responses. Mechanistically, G3BP1 formed a complex with RNF125 and RIG-I, leading to decreased RNF125 via its auto-ubiquitination; thus, promoting expression of RIG-I. Overall, the results suggest a novel mechanism for G3BP1 in the positive regulation of antiviral signaling mediated by RIG-I.

Antioxidant system of soiny mullet (Liza haematocheila) is responsive to dietary poly-ß-hydroxybutyrate (PHB) supplementation based on immune-related enzyme activity and de novo transcriptome analysis.

As a dietary supplement, poly-ß-hydroxybutyrate (PHB) has been reported to positively influence growth, boost the immune system and enhance disease resistance in fish and shellfish. However, the protective mechanism is little known. Thus, the present study was conducted to evaluate the effect of PHB supplementation on immune-related enzyme activity and transcriptome-based gene expression in soiny mullet (Liza haematocheila). Results showed that dietary PHB supplementation could increase antioxidant enzyme activity, including total antioxidant capacity, catalase and superoxide dismutase. A total of 7,082,094,175 and 7,650,341,357 raw reads with mean length of 757 bp were obtained from control and PHB (dietary PHB supplementation at 2%) groups, respectively. There were 46,106 differentially expressed genes (DEGs) between control and PHB groups, including 21,828 upregulated and 24,278 downregulated DEGs. All the DEGs were classified into three gene ontology categories, and 312 DEGs related with immune system process and 760 with the response to a stimulus. Additionally, all DEGs were allocated to 261 Kyoto Encyclopedia of Gene and Genome pathways, and major immune-related pathways were detected, including MAPK/PI3K-Akt/TNF/NF-κB/TCR/TLR signaling pathways. Moreover, the regulation of several observed immune-related genes was confirmed by qRT-PCR. Altogether, this study suggests that antioxidant system is more effective for dietary PHB supplementation and lays the foundation for further study on the precise immunostimulatory mechanism of PHB. Hopefully, it provides insights into exploring biomarker for assessment of immunostimulants in fish culture.

DDX56 inhibits type I interferon by disrupting assembly of IRF3-IPO5 to inhibit IRF3 nucleus import.

Transcription factor IRF3-mediated type I interferon induction plays a role in antiviral innate immunity. However, mechanisms for the control and regulation of IRF3 nuclear import remain largely unknown. We have identified DEAD box polypeptide 56 (DDX56) as a negative regulator of virus-triggered IFN-ß induction. Overexpression of DDX56 suppressed nuclear translocation of IRF3 via disrupting the IRF3-IOP5 interaction, whereas knockdown or knockout of DDX56 had the opposite effect. In addition, the interaction between DDX56 and IRF3 increased during viral infection. We further found that the D166 site of DDX56 was essential for inhibiting IRF3 import into the nucleus. Our findings suggest that DDX56 regulates antiviral innate immunity by inhibiting the nuclear translocation of IRF3, revealing a novel mechanism of the DDX56-mediated innate antiviral response.This article has an associated First Person interview with the first author of the paper.

UNBS5162 as a novel naphthalimide holds efficacy in human gastric carcinoma cell behaviors mediated by AKT/ERK signaling pathway.

Purpose: Studies have determined that UNBS5162, recognized as a new naphthalimide, holds inhibitory effects in prostate and breast tumors; however, its functional implication on gastric carcinoma is currently undetermined. Based on this, this study designed to assess the functional role of it on human gastric carcinoma and underlying mechanism of action. Methods: Cell counting kit-8 (CCK-8) assay, transwell assay, and flow cytometry were used to assess capabilities of SGC-7901 cell proliferation, invasion/migration, and apoptosis, respectively. Moreover, western blot was performed to determine the relative expression of protein related to autophagy and protein kinase B (AKT)/extracellular regulated protein kinases (ERK) signaling pathway. Results: We found SGC-7901 cells proliferation, invasion, and migration were significantly inhibited after treatment of UNBS5162. Moreover, the expression levels of anti-apoptotic protein Bcl-2 decreased while the expression of pro-apoptotic protein active caspase 3 and Bax increased concurrently after UNBS5162 stimulation. Further, upregulated LC3 II/I and Beclin-1 and downregulated P62 were induced by UNBS5162 addition. Mechanically, the ratios of phosphorylated-(p-)AKT/AKT, p-mammalian target of rapamycin (mTOR)/mTOR, and p-ERK/ERK were hampered by UNBS5162 application. Conclusion: UNBS5162 could restrain gastric carcinoma cell proliferation, invasion, and migration, which maybe induced by enhancement of apoptosis, autophagy manipulated through AKT/ERK signaling pathway.

Effect of Simvastatin on the Intestinal Rho/ROCK Signaling Pathway in Rats With Sepsis.

BACKGROUND: Simvastatin may alleviate the intestinal barrier dysfunction induced by sepsis. This study aimed to investigate the role of the Ras homolog (Rho)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway in the intestinal barrier of simvastatin-treated rats with sepsis. MATERIALS AND METHODS: Male Wistar rats were pretreated with simvastatin (0.2 µg/g of body weight) for 1 week before cecal ligation and puncture. Twenty-four hours after cecal ligation and puncture, the condition of bacterial translocation was evaluated. Plasma levels of intestinal fatty acid binding protein, D-lactic acid and inflammatory factors, and oxidative stress in the intestine were determined. The intestinal injury scores, as well as the protein levels of Rho, ROCK1, and tight junction proteins ZO-1 and occludin were analyzed. RESULTS: Treatment with simvastatin alleviated the sepsis-induced increases in the plasma concentration of intestinal fatty acid binding protein and D-lactic acid, as well as the number of colony-forming units in the bacterial culture of the blood, liver, spleen, and kidney. In addition, simvastatin effectively reduced the intestinal levels of tumor necrosis factor α, interleukin-6, high-mobility group box 1, and malondialdehyde and increased the activity of superoxide dismutase in rats with sepsis. Staining with hematoxylin and eosin showed that severe intestinal injury occurred in the sepsis group, which was reduced by the treatment of simvastatin. Furthermore, the expression of Rho and ROCK1 was significantly downregulated and the protein expression levels of ZO-1 and occludin were significantly increased in simvastatin-treated rats (P < 0.05). CONCLUSIONS: Simvastatin can ameliorate the intestinal barrier dysfunction caused by sepsis by inhibiting the Rho/ROCK signaling pathway and reducing the levels of inflammatory factors and oxidative stress in the intestine, which also increase the expression of tight junction proteins.

Effects of various feeding patterns of Bacillus coagulans on growth performance, antioxidant response and Nrf2-Keap1 signaling pathway in juvenile gibel carp (Carassius auratus gibelio).

The present study was conducted to evaluate the effects of various Bacillus coagulans feeding patterns on growth, antioxidant parameter and Nrf2 pathway in juvenile gibel carp. The similar size of gibel carp (initial weight: 14.33 ± 0.15 g) were subjected to three levels of B. coagulans supplementation (0, 500, and 1000 mg/kg) and two feeding modes (supplementing B. coagulans continuously or for two days of B. coagulans after 5 days of a basal diet) according to a 3 × 2 factorial design. The fish that were continuously fed 500 mg/kg B. coagulans (P2) and those fed the first basal diet for 5 days followed by 500 mg/kg or 1000 mg/kg B.coagulans for 2 days (P4 or P5) showed higher weight gain rate and specific growth rate than the other groups. Blood respiratory burst (RB), myeloperoxidase (MPO), and anti-superoxide anion free radical (AFASER) activities in the P4 group were higher than those of the control. White blood cell count (WBC), RB activity, MPO activity, and glutathione (GSH) content in the P5 group were also higher than those of the control. A similar higher trend was observed in the gene expressions of NADPH oxidase 2 (NOX2), NFE2-related factor (Nrf2), Kelch-like-ECH-associated protein(Keap1) in the P4 and NOX2, NRF2, CNC homolog 1 (Bach1), peroxiredoxin 2 (Prx2) in the P5 group compared with the control. Additionally, we observed a significantly lower level of plasma aspartate aminotransferase (AST), lower activity of alanine aminotransferase (ALT), a higher level of MPO, higher GPX activity, and increased NRF2 and Prx2 expression were all observed in the P2 treatment group compared with the control. Furthermore, the malondialdehyde (MDA) content in the P2, P3, and P4 groups was lower than that of the control. These results indicate that a diet supplemented with appropriate levels of B.coagulans could improve the growth, immune response, and antioxidant capability of gibel carp. We concluded that the pattern of two days of 500 or 1000 mg/kg B. coagulans after 5 days of a basal diet was recommended for gibel carp.

A faster and simpler way of operation for Meckel's diverticulum: basal ligation combined with intraoperative frozen section.

BACKGROUND: The key step in Meckel's diverticulectomy (MD) is to achieve complete resection of MD along with the ectopic epithelium. Currently main treatment methods for Meckel's diverticulum are either intestinal resection and anastomosis or wedge resection. Here we introduced a new method to treat MD. The goal of this study was to investigate the clinical effects and advantages of a new operation method for Meckel's diverticulum: basal ligation combined with intraoperative frozen section. METHODS: 262 cases of Meckel's diverticulum were resected with simple basal ligation operation. Intraoperative frozen pathological section was performed to determine surgery strategies. Based on the existence of basal residual ectopic mucosa, surgery was either terminated or further wedge intestinal resection or bowel resection was performed. RESULTS: All 262 surgeries were successfully completed. Additional wedge resection or bowel resection was performed in only 23 of them due to the presence of ectopic basal residual gastric mucosa. No ectopic mucosa was found for the other cases, and the operation ended after basal ligation. All patients had no complications such as intestinal fistula, bleeding for 6 months-7.6 years after surgery. CONCLUSIONS: Intraoperative frozen pathological examination can well determine whether ectopic Meckel's diverticulum mucosa locates at the basal part. Basal ligation is a safe and effective operation method, and it can significantly shorten the operation time and postoperative fasting time.