Camellia sinensis polysaccharide attenuates inflammatory responses via the ROS-mediated pathway by endocytosis.

Polysaccharide CSTPs extracted from Camellia sinensis tea-leaves possessed unique against oxidative damage by scavenging ROS. Herein, acid tea polysaccharide CSTPs-2 with tightly packed molecular structure was isolated, purified and characterized in this research. Furthermore, the effects of CSTPs-2 on ROS-involved inflammatory responses and its underlying mechanisms were investigated. The results suggest that CSTPs-2 dramatically reduced the inflammatory cytokines overexpression and LPS-stimulated cell damage. CSTPs-2 could trigger the dephosphorylation of downstream AKT/MAPK/NF-κB signaling proteins and inhibit nuclear transfer of p-NF-κB to regulate the synthesis and release of inflammatory mediators in LPS-stimulated cells by ROS scavenging. Importantly, the impact of CSTPs-2 in downregulating pro-inflammatory cytokines and mitigating ROS overproduction is associated with clathrin- or caveolae-mediated endocytosis uptake mechanisms, rather than TLR-4 receptor-mediated endocytosis. This study presents a novel perspective for investigating the cellular uptake mechanism of polysaccharides in the context of anti-inflammatory mechanisms.

Excessive fatty acids activate PRMT5/MDM2/Drosha pathway to regulate miRNA biogenesis and lipid metabolism.

BACKGROUND: Excessive fatty acids in the liver lead to the accumulation of lipotoxic lipids and then cellular stress to further evoke the related disease, like non-alcoholic fatty liver disease (NAFLD). As reported, fatty acid stimulation can cause some specific miRNA dysregulation, which caused us to investigate the relationship between miRNA biogenesis and fatty acid overload. METHODS: Gene expression omnibus (GEO) dataset analysis, miRNA-seq, miRNA cleavage assay, RT-qPCR, western blotting, immunofluorescence and co-immunoprecipitation (co-IP) were used to reveal the change of miRNAs under pathological status and explore the relevant mechanism. High fat, high fructose, high cholesterol (HFHFrHC) diet-fed mice transfected with AAV2/8-shDrosha or AAV2/8-shPRMT5 were established to investigate the in vivo effects of Drosha or PRMT5 on NAFLD phenotype. RESULTS: We discovered that the cleavage of miRNAs was inhibited by analysing miRNA contents and detecting some representative pri-miRNAs in multiple mouse and cell models, which was further verified by the reduction of the Microprocessor activity in the presence of palmitic acid (PA). In vitro, PA could induce Drosha, the core RNase III in the Microprocessor complex, degrading through the proteasome-mediated pathway, while in vivo, knockdown of Drosha significantly promoted NAFLD to develop to a more serious stage. Mechanistically, our results demonstrated that PA can increase the methyltransferase activity of PRMT5 to degrade Drosha through MDM2, a ubiquitin E3 ligase for Drosha. The above results indicated that PRMT5 may be a critical regulator in lipid metabolism during NAFLD, which was confirmed by the knocking down of PRMT5 improved aberrant lipid metabolism in vitro and in vivo. CONCLUSIONS: We first demonstrated the relationship between miRNA dosage and NAFLD and proved that PA can activate the PRMT5-MDM2-Drosha signalling pathway to regulate miRNA biogenesis.

Femtosecond laser ablation in liquid synthesis of iron-oxidation nanoparticles with saturable absorption performance.

"Naked" ferroferric-oxide nanoparticles (FONPs) synthesized by a femtosecond laser ablation on a bulk stainless steel in liquid were applied to the Nd: YVO4 laser to achieve passive Q-switched pulse laser output. Without the pollution of ligand, the inherent light characteristic of "naked" FONPs was unaffected. The analysis of the morphological characteristics, dominant chemical elements, and phase composition of the FONPs showed that they were mainly composed of Fe3O4, which was spherical with an average diameter of 40 nm. The electron transition and orbital splitting of the iron element's octahedral center position under the laser-driven were considered the primary mechanisms of saturable absorption of Fe3O4 nanoparticles.

Network pharmacology study on the potential effect mechanism of Chuanzhi Tongluo Capsule in the treatment of cerebral infarction.

BACKGROUND: Chuanxiong Tongluo capsules have been widely used to treat recovered stroke and cerebral infarction, but their specific therapeutic mechanism is not well understood. METHODS: This study aims to investigate the mechanism of action for Chuanzhi Tongluo capsule on cerebral infarction based on a network pharmacology approach. The TCMSP platform collected the chemical composition of Chuanzhi Tongluo capsules. Its potential targets were predicted by Swiss target prediction and standardized using the Uniprot database for gene normalization. Meanwhile, the OMIM, Genecards, and TTD databases were used to obtain the targets related to cerebral infarction. The standard targets of Chuanzhi Tongluo capsule and cerebral infarction were uploaded to the STRING database to construct protein-protein interaction networks. Topological methods analyzed the key targets and components in the drug-component-disease-target network. Gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the shared targets were performed using the DAVID database. RESULTS: A total of 105 active ingredients and 427 targets were associated with Chuanzhi Tongluo capsule, and there were 3055 targets related to cerebral infarction disease and 240 common targets between the two keywords. The key targets included INS, ALB, IL-6, VEGFA, TNF, and TP53. The conduction pathways involved include the calcium signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway, and TNF signaling pathway. CONCLUSION: The active ingredients in Chuanzhi Tongluo capsule may participate in the therapeutic process of cerebral infarction by regulating the calcium, cAMP, cGMP-PKG, and TNF signaling pathway through critical targets such as INS, ALB, IL-6, VEGFA, TNF, and TP53.

Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin A.

Cyclosporine A (CsA) is an immunosuppressive drug that suppresses T cell responses and is broadly used in transplantation. Its immunosuppressive action is closely linked to its binding of cyclophilin A (CypA), which widely distributed in different cell types. CsA also regulates the functions of innate immune cells, but the mechanism remains elusive. Here, we investigate the role of CsA in regulating macrophages polarization in influenza A virus-infected mice and mouse bone marrow-derived macrophages. CsA downregulates pro-inflammatory cytokines expression and upregulates anti-inflammatory cytokines expression. Mechanically, CsA decreases the polarization of macrophages into pro-inflammatory M1 phenotype and increases the polarization of macrophages into anti-inflammatory M2 phenotype. Further studies show that CsA regulates macrophages polarization-associated IFN-γ/STAT1 and IL-4/STAT6 signaling pathways. Meanwhile, all these roles of CsA are eliminated when CypA is absent, suggesting that CsA regulates macrophages polarization and inflammatory responses depend on its binding to CypA. Collectively, these results reveal a crucial mechanism of CsA in attenuating IAV-induced inflammatory responses by a switch in macrophages polarization.

Curcumin Synergizes with Cisplatin to Inhibit Colon Cancer through Targeting the MicroRNA-137-Glutaminase Axis.

OBJECTIVE: Colorectal cancer (CRC) is one of the most lethal and prevalent malignancies world-wide. Currently, surgery, radiotherapy and chemotherapy are clinically applied as common approaches for CRC patients. Cisplatin is one of the most frequently used chemotherapy drugs for diverse cancers. Although chemotherapeutic strategies have improved the prognosis and survival of cancer patients, development of cisplatin resistance has led to cancer recurrence. Curcumin, isolated from turmeric, has been used as an effective anti-cancer agent. However, the molecular mechanisms for curcumin-mediated cisplatin sensitivity of CRC have not been elucidated. This study aimed to investigate the effects of curcumin treatment on cisplatin-resistant CRC cells. METHODS: Expression levels of miRNAs and mRNAs were determined by qRT-PCR. Protein expression levels were detected by Western blotting. Cell responses to curcumin treatments were evaluated by MTT assay, Clonogenic assay and Annexin V apoptosis assay. The glutamine metabolism of colon cancer cells was assessed by glutamine uptake and glutaminase (GLS) activity. The binding of miR-137 on 3' UTR of GLS was validated by Western blotting and luciferase assay. RESULTS: Results demonstrated that curcumin significantly synergized with cisplatin (combination index <1) to suppress proliferation of colon cancer cells compared with curcumin or cisplatin alone. Moreover, from the established cisplatin-resistant cell line (HT-29), glutamine metabolism was remarkedly elevated in cisplatin-resistant CRC cells that displayed a glutamine addictive phenotype. Furthermore, curcumin treatments attenuated glutamine metabolism in colon cancer cells. Under low glutamine supply, colon cancer cells showed less sensitivity to curcumin. Using a microRNA (miRNA) microArray assay, miR-137, a tumor suppressor in colon cancer, was significantly induced by curcumin treatments in CRC cells. Bioinformatics analysis and a luciferase assay illustrated miR-137 directly targeted the 3' UTR of GLS mRNA. Rescue experiments demonstrated that miR-137-induced cisplatin sensitization was through targeting of GLS. Finally, curcumin treatment overcame cisplatin resistance through miR-137-mediated glutamine inhibition. CONCLUSION: Collectively, these results indicate that curcumin could be clinically applied as an anti-chemoresistance approach against CRC by modulating miR-137-inhibited glutamine metabolism.

Cyclophilin A is a key positive and negative feedback regulator within interleukin-6 trans-signaling pathway.

Cyclophilin A (CypA), a member of the cyclophilin family, plays a vital role in microorganismal infections, inflammatory diseases, and cancers. Interleukin-6 (IL-6) is a pleiotropic cytokine, exerting variety of effects on inflammation, immune response, hematopoiesis, and tumor proliferation. Binding of IL-6 to soluble IL-6 receptor (sIL-6R) induces pro-inflammatory trans-signaling, which has been described to be stronger than anti-inflammatory classic signaling triggered by the binding of IL-6 to membrane-bound IL-6 receptor. Here we found that upon the treatment of IL-6 and sIL-6R, CypA inhibited the ubiquitination-mediated degradation of IL-6 membrane receptor gp130 and enhanced its dimerization, thereby positively regulated the IL-6 trans-signaling and increased the expression of downstream iNOS, IL-6, and CypA. Furthermore, CypA expression could be negatively regulated by suppressor of cytokine signaling 1 (SOCS1). The SH2 and Box domains of SOCS1 interacted with CypA and promoted its K48-linked ubiquitination-mediated degradation, which inhibited the IL-6 trans-signaling pathway. Collectively, our findings reveal an important role of CypA in the positive and negative feedback regulation of the IL-6 trans-signaling pathway.

Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection.

Polarization of macrophages to different functional states is important for mounting responses against pathogen infections. Macrophages are the major target cells of porcine circovirus type 2 (PCV2), which is the primary causative agent of porcine circovirus-associated disease (PCVAD) leading to immense economic losses in the global swine industry. Clinically, PCV2 is often found to increase risk of other pathogenic infections yet the underlying mechanisms remain to be elusive. Here we found that PCV2 infection skewed macrophages toward a M1 status through reprogramming expression of a subset of M1-associated genes and M2-associated genes. Mechanistically, induction of M1-associated genes by PCV2 infection is dependent on activation of nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways whereas suppression of M2-associated genes by PCV2 is via inhibiting expression of jumonji domain containing-3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase that regulates M2 activation of macrophages. Finally, we identified that PCV2 capsid protein (Cap) directly inhibits JMJD3 transcription to restrain expression of interferon regulatory factor (IRF4) that controls M2 macrophage polarization. Consequently, sustained infection of PCV2 facilitates bacterial infection in vitro. In summary, these findings showed that PCV2 infection functionally modulated M1 macrophage polarization via targeting canonical signals and epigenetic histone modification, which contributes to bacterial coinfection and virial pathogenesis.

lncRNA NEAT1 promotes the Taxol resistance of breast cancer via sponging the miR-23a-3p-FOXA1 axis.

Breast cancer is the most prevalent malignancy among women worldwide. Paclitaxel (Taxol) is a widely applied chemotherapeutic agent against breast cancer. Although Taxol therapy has achieved improvements recently, development of chemoresistance of breast cancer patients is a major obstacle, leading to therapeutic failure. Long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis and progresses of breast cancer. However, the biological roles and molecular targets of lncRNA NEAT1 in Taxol-resistant breast cancer remain unclear. Here, we report that NEAT1 is significantly upregulated in breast tumors and cell lines. In addition, silencing NEAT1 effectively sensitizes breast cancer cells to Taxol. Bioinformatical analysis and luciferase assay demonstrated that miR-23a-3p could be sponged and downregulated by NEAT1. We demonstrated that miR-23a-3p was downregulated and functioned as a tumor suppressor in breast cancer. Furthermore, in the established Taxol-resistant MDA-MB-231 breast cancer cell line, we detected significantly increased NEAT1 expression and downregulated miR-23a-3p expression. Importantly, FOXA1 was identified and validated as a direct target of miR-23a-3p in breast cancer cells. Rescue experiments demonstrated that the restoration of miR-23a-3p in NEAT1-overexpressing Taxol-resistant breast cancer cells successfully overcame the NEAT1-promoted Taxol resistance. Taken together, our results revealed the clinical roles and molecular mechanisms for the NEAT1-mediated chemoresistance, providing new insights into the development of non-coding RNA-based therapeutic strategies for enhancing the anti-cancer effects of traditional chemotherapeutic drugs.

Noncoplanar Versus Coplanar Intensity-Modulated Radiation Therapy (IMRT) for Protection of the Lip and Buccal Mucosa.

OBJECTIVE: In this study, by comparing coplanar and noncoplanar intensity-modulated radiation therapy (IMRT) treatment planning in treating tongue cancer, the significance of noncoplanar fields in the protection of the lip and buccal mucosa was determined, and a reasonable solution was selected. METHODS: Forty-eight tongue cancer patients treated from June 2019 to February 2021 were selected and randomly divided into a coplanar field group and a noncoplanar field group. The mucosal dose limit changed from 15 Gy to 45 Gy for comparison of the two treatment plans. The evaluation indicators (conformal index (CI); homogeneity index (HI); D5, D50, and D98 of the target volume; and the dose of normal tissues) were calculated under different mucosal dose limits. The clinical observation of the lip and buccal mucosa of 48 cases was monitored and graded carefully according to NCI-CTCAE V4.0. Statistical analyses were performed. RESULTS: The differences in CI, HI, D98, D50 and D5 between the two groups in the target volume tended to decrease when the mucosal dose limit was less than 30 Gy, with a significant difference (P < 0.05). When the limit exceeded 30 Gy, significant differences in other indicators except CI (P < 0.05) were still noted. In normal tissue, differences in doses between the two groups existed when the mucosal limit was less than 20 Gy, with a significant difference (P < 0.05). When the limit exceeded 20 Gy, no significant difference was noted. Patients in the noncoplanar group showed significantly better results than those in the other group in terms of the radiation-related toxicity of the lip and cheek membrane(P < 0.001). CONCLUSIONS: Compared with coplanar field radiotherapy, noncoplanar field radiotherapy can effectively reduce the exposure dose to the lip and buccal mucosa. The application of noncoplanar treatment plans exhibits good clinical significance and deserves to be promoted.

Fluorescent Nanogel Sensors for X-ray Dosimetry.

X-ray dosimeters are of significance for detecting the levels of ionizing radiation exposure in cells and phantoms; thus, they can further optimize X-ray radiotherapy in the clinic. In this paper, we designed a polyacrylamide-based nanogel sensor that is capable of measuring X-ray doses. The dosimeters were prepared by anchoring an X-ray-responsive probe (aminophenyl fluorescein, APF) to poly(acrylamide-co-N-(3-aminopropyl) methyl acrylamide) nanogels. The premise behind the dose measurement is the transition of APF to fluorescence in the presence of hydroxyl radicals that are caused by the radiolysis of water molecules under X-rays. Therefore, the dose of X-rays can be readily detected by measuring the fluorescence intensity of the resultant nanogel immediately after irradiation using fluorescence spectroscopy principles. Using an RS2000 X-ray biological irradiator, our dosimeters showed good linearity responsivity at X-ray doses ranging from 0 to 15 Gy, with a limit of detection (LOD) of 0.5 Gy. Additionally, the signals showed temperature stability (25-65 °C), durability (5 weeks), and dose-rate (1.177 and 6 Gy/min) and energy independence (160 kVp and 6 MV). As a proof-of-concept, we used our sensors to fluorescently detect X-ray doses in A549 tumor cells and 3D-printed eye phantoms. The results showed that our dosimeters were able to accurately predict doses similar to those used by treatment plan systems.

Forkhead box O1-mediated ubiquitination suppresses RIG-I-mediated antiviral immune responses.

RNA virus infection activates the RIG-I-like Receptor (RLR) signaling pathway to produce type I interferons (IFNs), the key components of the antiviral immune response. Forkhead box O1 (FoxO1) is a host transcription factor that participates in multiple biological processes. In this study, FoxO1 was identified as a critical negative regulator of RIG-I-triggered signaling. FoxO1 promoted Sendai virus (SeV) replication and downregulated type I IFN production. Upon SeV infection, FoxO1 suppressed K63-linked ubiquitination of TRAF3 and the interaction between TRAF3 and TBK1, after which the production of type I IFNs via the interferon regulatory transcription factor 3 (IRF3) pathways was reduced. In addition, FoxO1 destabilized IRF3 by facilitating E3 ligase TRIM22- or TRIM21-mediated K48-linked ubiquitination of IRF3. Moreover, the inhibitory effect of FoxO1 was found to depend on its DNA binding domain (DBD). Thus, our findings highlight novel important roles of FoxO1 in controlling RLR-mediated antiviral innate immunity.

[Establishment of RIG-I knockout 293T cell line and its effect on the replication of influenza B virus].

The CRISPR/Cas9 gene editing technology directs Cas9 protein to recognize, bind and cleave the target site specifically by using artificial single-guide RNA (sgRNA), through non-homologous end joining or homologous end-recombinant repair mechanisms of cells, which can be engineered to knockout or knock-in of genomes. RIG-I is a pattern recognition receptor that recognizes the 5'-triphosphate-containing RNA in the cytoplasm and activates IRF3/7 and NF-κB by interacting with the downstream signaling molecule MAVS, thus initiating the expression of type I interferons and inflammatory factors. Previous studies found that influenza B virus (IBV) can up-regulate the expression of RIG-I. In the present study, to explore whether RIG-I is the major receptor for IBV to active the antiviral innate immune response and its effect on IBV replication, RIG-I gene in 293T cells was knocked out by CRISPR-Cas9 system, and a stable RIG-I knockout 293T (RIG-I(-/-) 293T) cell line was screened by puromycin pressure. The results of Western blotting showed that RIG-I was not expressed in this cell line after IBV or Sendai virus (SeV) infection, indicating that the RIG-I(-/-) 293T cell line was successfully constructed. The transcription levels of interferons, inflammatory factors and interferon-stimulated genes in RIG-I(-/-) 293T cells which were infected by IBV decreased significantly compared with those in wild-type 293T cells. Moreover, the phosphorylation of p65 and IRF3 were not detected in IBV or SeV infected RIG-I(-/-) 293T cells. It is indicated that the expression of cytokines mainly depends on the RIG-I-mediated signaling pathway at the early stage of IBV infection. Furthermore, the multi-step growth curves of IBV in the wild type and RIG-I(-/-) 293T cells showed that RIG-I inhibited the replication of IBV. Collectively, the RIG-I knockout 293T cell line was successfully constructed. We found that RIG-I is the main receptor for IBV to active the antiviral innate immune response and is critical for inhibiting IBV replication, which lays the foundation for further study of IBV infection mechanism.

IMP-ICDX: an injury mortality prediction based on ICD-10-CM codes.

Background: The International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) Injury Severity Score (ICISS) is a risk adjustment model when injuries are recorded using ICD-9-CM coding. The trauma mortality prediction model (TMPM-ICD9) provides better calibration and discrimination compared with ICISS and injury severity score (ISS). Though TMPM-ICD9 is statistically rigorous, it is not precise enough mathematically and has the tendency to overestimate injury severity. The purpose of this study is to develop a new ICD-10-CM injury model which estimates injury severities for every injury in the ICD-10-CM lexicon by a combination of rigorous statistical probit models and mathematical properties and improves the prediction accuracy. Methods: We developed an injury mortality prediction (IMP-ICDX) using data of 794,098 patients admitted to 738 hospitals in the National Trauma Data Bank from 2015 to 2016. Empiric measures of severity for each of the trauma ICD-10-CM codes were estimated using a weighted median death probability (WMDP) measurement and then used as the basis for IMP-ICDX. ISS (version 2005) and the single worst injury (SWI) model were re-estimated. The performance of each of these models was compared by using the area under the receiver operating characteristic (AUC), the Hosmer-Lemeshow (HL) statistic, and the Akaike information criterion statistic. Results: IMP-ICDX exhibits significantly better discrimination (AUCIMP-ICDX, 0.893, and 95% confidence interval (CI), 0.887 to 0.898; AUCISS, 0.853, and 95% CI, 0.846 to 0.860; and AUCSWI, 0.886, and 95% CI, 0.881 to 0.892) and calibration (HLIMP-ICDX, 68, and 95% CI, 36 to 98; HLISS, 252, and 95% CI, 191 to 310; and HLSWI, 92, and 95% CI, 53 to 128) compared with ISS and SWI. All models were improved after the extension of age, gender, and injury mechanism, but the augmented IMP-ICDX still dominated ISS and SWI by every performance. Conclusions: The IMP-ICDX has a better discrimination and calibration compared to ISS. Therefore, we believe that IMP-ICDX could be a new viable trauma research assessment method.

Effects of UV-B radiation on the survival, egg hatchability and transcript expression of antioxidant enzymes in a high-temperature adapted strain of Neoseiulus barkeri.

Biological control of spider mites in hot and dry weather is a serious technical issue. A high-temperature adapted strain (HTAS) of the predatory mite Neoseiulus barkeri Hughes was selected from its conventional strain (CS), via long-term heat acclimation and frequent heat hardenings in our previous studies. However, the environment of high temperature is usually associated with enhanced ultraviolet (UV) radiation. In the present study, the physiological effects of UV-B radiation on survival rate and egg damage of N. barkeri were investigated, as well as the activities and expression profiles of antioxidant enzymes to UV-B radiation stress. UV-B radiation had deleterious effects on egg hatchability and survival of N. barkeri. Adults of the HTAS strain were less UV-B resistant than those of the CS strain; they also had lower levels of enzymatic activity of superoxide dismutase (SOD) and catalase against oxidative damage and weaker upregulation of SOD genes. The mRNA expression of three SOD genes of CS adult females immediately increased whereas that of HTAS showed almost no difference under UV-B stress for 1 h. The results showed the HTAS of N. barkeri had lower fitness under UV-B stress compared with the CS of N. barkeri. These results suggested that long-term heat acclimation may exert a profound impact on the developmental physiology of N. barkeri.

DTI study on rehabilitation of the congenital deafness auditory pathway and speech center by cochlear implantation.

PURPOSE: To explore the correlation between hearing and speech recovery levels after cochlear implantation and examined the preoperative microstructure of auditory pathways and speech centre using DTI. METHODS: (1) Fifty-two SNHL children between 0 and 6 years and 19 age and gender matched normal hearing subjects had received 3.0 T-MRI examination of the brain.FA, axial diffusion coefficient (λ‖), radial diffusion coefficient (λ⊥), and MD values in the lateral lemniscus, inferior colliculus, medial geniculate bodies, auditory radiations, Brodmann areas 41, 42, 22, 44, 45, and 39 were all measured bilaterally. (2) CAP and SIR scores were assessed in fourty-six cochlear implantation children at 6 months post-implant. Correlations among deaf children ages, FA value of bilateral inferior colliculus FA values, BA22, BA44, and postoperative CAP, and SIR scores were analyzed using multiple linear regression. RESULTS: The preoperative standard partial regression age coefficient of deaf children (|bi'| = 0.404) was slightly greater than that of the inferior colliculus (|bi'| = 0.377) FA value. CONCLUSION: Preoperative children ages and inferior colliculus FA values were important factors influencing postoperative CAP score. Inferior colliculus FA value is a vital influencing factor in rehabilitation after cochlear implantation.

Effects of Puerarin on Clinical Parameters, Vascular Endothelial Function, and Inflammatory Factors in Patients with Coronary Artery Disease.

BACKGROUND The aim of this study was to investigate the effects of puerarin on vascular endothelial function and inflammatory factors in coronary artery disease (CAD) patients with stable angina pectoris (SAP). MATERIAL AND METHODS To evaluate the effects of angina pectoris, the differences of scores of the Seattle angina questionnaire (SAQ), vascular endothelial function [endothelial progenitor cells (EPCs), nitric oxide (NO) and endothelin 1 (ET-1)], and inflammatory factors [tumor necrosis factor a (TNF-α), hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6)] in 2 groups were assessed before and after treatment. RESULTS Regarding the curative effect of angina pectoris, the total effective rate of the treatment group was significantly superior to that of the control group (89% vs. 65%, P<0.05). The duration of angina pectoris, the number of abnormal leads, the improvement of the ST segment depression of electrocardiogram, and the scores of SAQ life quality indexes in the treatment group were better than those of the control group (P<0.05). In the 2 groups, EPCs and NO were both elevated, while ET-1 was decreased, and the improvements of the treatment group were superior to those of the control group (P<0.05). After treatment, the average levels of serum TNF-α, hs-CRP and IL-6 in the 2 groups were all decreased, which the treatment group showed a much sharper decrease than in the control group (P<0.05). CONCLUSIONS Puerarin effectively improves clinical symptoms and vascular endothelial function and reduces the levels of inflammatory factors in patients with CAD.

Polystyrene-based Hollow Microsphere Synthesized by γ-ray Irradiation-assisted Polymerization and Self-Assembly and Its Application in Detection of Ionizing Radiation.

To simply and multitudinously synthesize hollow microspheres in a pure system is important for relevant research and application. Here, a simple and novel one-pot synthetic strategy to prepare polystyrene (PS) hollow microspheres via irradiation-assisted free-radical polymerizing and self-assembly (IFPS) approach under γ-ray irradiation with no additives introduced into the system is presented. And PS/2,5-Diphenyloxazole (PPO) fluorescent microspheres have been prepared successfully by IFPS reaction, which can be used as scintillators for the detection of ionizing radiation. A linear relationship between emitted luminescence and dose-activity in water is obtained, which suggests that composite microspheres could be used as liquid scintillation in specific environment.

Threonine 80 phosphorylation of non-structural protein 1 regulates the replication of influenza A virus by reducing the binding affinity with RIG-I.

Influenza A virus evades host antiviral defense through hijacking innate immunity by its non-structural protein 1 (NS1). By using mass spectrometry, threonine 80 (T80) was identified as a novel phosphorylated residue in the NS1 of the influenza virus A/WSN/1933(H1N1). By generating recombinant influenza viruses encoding NS1 T80 mutants, the roles of this phosphorylation site were characterized during viral replication. The T80E (phosphomimetic) mutant attenuated virus replication, whereas the T80A (non-phosphorylatable) mutant did not. Similar phenotypes were observed for these mutants in a mouse model experiment. In further study, the T80E mutant decreased the binding capacity between NS1 and viral nucleoprotein (NP), leading to impaired viral ribonucleoprotein (vRNP)-mediated viral transcription. The T80E mutant was also unable to inhibit interferon (IFN) production by reducing the binding affinity between NS1 and retinoic acid-induced gene 1 protein (RIG-I), causing attenuation of virus replication. Taken together, the present study reveals that T80 phosphorylation of NS1 reduced influenza virus replication through controlling RIG-I-mediated IFN production and vRNP activity.

Preoperative assessment of labial bone perforation for virtual immediate implant surgery in the maxillary esthetic zone: A computer simulation study.

BACKGROUND: In this computer simulation study, the authors investigated the frequency distribution of labial bone perforation (LBP) between various sagittal root position (SRP) classes with respect to the anterior maxillary osseous housing and evaluated the associated factors correlated with a higher risk of LBP when performing a virtual immediate implant surgery in the esthetic zone. METHODS: The authors analyzed cone-beam computed tomography (CBCT) images from 285 qualified study participants (1,449 teeth) to determine the probability of LBP when associated with selected variables, such as tooth type, SRP class, and morphologic parameters. The authors examined associated factors and analyzed the adjusted odds ratios by means of multiple logistic regression analysis. RESULTS: The overall probability of LBP was 81.7%, which presented statistically significant differences between each specific tooth type and SRP class (all P<.001). After adjusting for other factors, the authors found that the maxillary central incisor was 2.37 times more likely to have LBP than the canine. SRP class I was 4.9 times more likely to be associated with LBP when compared with SRP class IV. CONCLUSIONS: When a clinician performs an immediate implant in the anterior esthetic zone, he or she should be aware that the specific tooth type, SRP class, and morphologic features of fossa concavities are associated with a risk of experiencing LBP. PRACTICAL IMPLICATIONS: Presurgical cross-sectional images can be analyzed to identify anatomic features relative to LBP in the maxillary esthetic region, and this can avoid unpleasant complications, specifically when performing immediate implant procedures.