The critical mixed transport process in remediation agent radial injection into contaminated aquifer plumes.

Accurately depicting the subsurface mixing of radially injected remediation agents with contaminated plumes remains paramount yet challenging for understanding and simulating reactive transport. To address this, the present research employed the mixing dynamics of a potassium permanganate plume injected into a pre-existing contaminated plume. Through combining colour deconvolution and thresholding, we effectively isolated local mixing values within the Gaussian annular narrow mixing zone from the noise of mixed double-plume images. Key findings revealed increasing injection rate promotes plume mixing while adding xanthan gum to increase fluid viscosity moderates interface mixing, reducing mixing zone width by 25.3% and 37.4% for 100 mg/L and 400 mg/L xanthan gum, respectively. Grain size is pivotal, with a 30% increase in mixing areas observed in coarse-grained sands over medium-grained sands. Balancing sufficient mixing and preventing contaminated plume growth is essential for effective remediation. Injection rates below 5 mL/min may suppress contaminated plume expansion, albeit at the possible cost of protracted remediation durations. For the attainment of optimal remediation, it's imperative to harmonize robust mixing processes with the mitigation of contaminated plume expansion - a balance that adding xanthan gum during the initial injection phase seems poised to achieve (xanthan gum optimized the average mixing index (AMI)). These findings provide valuable insights into groundwater plume mixing, supporting effective remediation strategies.

Isolation, identification, molecular and pathogenicity characteristics of an infectious laryngotracheitis virus from Hubei province, China.

Multiple outbreaks of avian infectious laryngotracheitis (ILT) in chickens, both domestically and internationally, have been directly correlate to widespread vaccine use in affected countries and regions. Phylogenetic and recombination event analyses have demonstrated that avian infectious laryngotracheitis virus (ILTV) field strains are progressively evolving toward the chicken embryo-origin (CEO) vaccine strain. Even with standardized biosecurity measures and effective prevention and control strategies implemented on large-scale farms, continuous ILT outbreaks result in significant economic losses to the poultry industry worldwide. These outbreaks undoubtedly hinder efforts to control and eradicate ILTV in the future. In this study, an ILTV isolate was successfully obtained by laboratory PCR detection and virus isolation from chickens that exhibited dyspnea and depression on a broiler farm in Hubei Province, China. The isolated strain exhibited robust propagation on chorioallantoic membranes of embryonated eggs, but failed to establish effective infection in chicken hepatocellular carcinoma (LMH) cells. Phylogenetic analysis revealed a unique T441P point mutation in the gJ protein of the isolate. Animal experiments confirmed the virulence of this strain, as it induced mortality in 6-wk-old chickens. This study expands current understanding of the epidemiology, genetic variations, and pathogenicity of ILTV isolates circulating domestically, contributing to the elucidate of ILTV molecular basis of pathogenicity and development of vaccine.

PLK3 facilitates replication of swine influenza virus by phosphorylating viral NP protein.

Swine H1N1/2009 influenza is a highly infectious respiratory disease in pigs, which poses a great threat to pig production and human health. In this study, we investigated the global expression profiling of swine-encoded genes in response to swine H1N1/2009 influenza A virus (SIV-H1N1/2009) in newborn pig trachea (NPTr) cells. In total, 166 genes were found to be differentially expressed (DE) according to the gene microarray. After analyzing the DE genes which might affect the SIV-H1N1/2009 replication, we focused on polo-like kinase 3 (PLK3). PLK3 is a member of the PLK family, which is a highly conserved serine/threonine kinase in eukaryotes and well known for its role in the regulation of cell cycle and cell division. We validated that the expression of PLK3 was upregulated after SIV-H1N1/2009 infection. Additionally, PLK3 was found to interact with viral nucleoprotein (NP), significantly increased NP phosphorylation and oligomerization, and promoted viral ribonucleoprotein assembly and replication. Furthermore, we identified serine 482 (S482) as the phosphorylated residue on NP by PLK3. The phosphorylation of S482 regulated NP oligomerization, viral polymerase activity and growth. Our findings provide further insights for understanding the replication of influenza A virus.

Prohibitin1 facilitates viral replication by impairing the RIG-I-like receptor signaling pathway.

IMPORTANCE: Type I interferon (IFN-I), produced by the innate immune system, plays an essential role in host antiviral responses. Proper regulation of IFN-I production is required for the host to balance immune responses and prevent superfluous inflammation. IFN regulatory factor 3 (IRF3) and subsequent sensors are activated by RNA virus infection to induce IFN-I production. Therefore, proper regulation of IRF3 serves as an important way to control innate immunity and viral replication. Here, we first identified Prohibitin1 (PHB1) as a negative regulator of host IFN-I innate immune responses. Mechanistically, PHB1 inhibited the nucleus import of IRF3 by impairing its binding with importin subunit alpha-1 and importin subunit alpha-5. Our study demonstrates the mechanism by which PHB1 facilitates the replication of multiple RNA viruses and provides insights into the negative regulation of host immune responses.

Characteristic analysis of adverse reactions of five anti-TNFɑ agents: a descriptive analysis from WHO-VigiAccess.

Introduction: Tumor necrosis factor (TNF) inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab pegol) have revolutionized the treatment of severe immune-mediated inflammatory diseases, including rheumatoid arthritis, Crohn's disease, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis. This study assessed adverse drug reactions (ADRs) after the use of TNFα inhibitors in VigiAccess of the World Health Organization (WHO) and compared the adverse reaction characteristics of five inhibitors to select the drug with the least risk for individualized patient use. Methods: The study was a retrospective descriptive analysis method in design. We sorted out five marketed anti-TNFα drugs, and their ADR reports were obtained from WHO-VigiAccess. Data collection included data on the age groups, sex, and regions of patients worldwide covered by ADR reports, as well as data on disease systems and symptoms caused by ADRs recorded in annual ADR reports and reports received by the WHO. By calculating the proportion of adverse reactions reported for each drug, we compared the similarities and differences in adverse reactions for the five drugs. Results: Overall, 1,403,273 adverse events (AEs) related to the five anti-TNFα agents had been reported in VigiAccess at the time of the search. The results show that the 10 most commonly reported AE manifestations were rash, arthralgia, rheumatoid arthritis, headache, pneumonia, psoriasis, nausea, diarrhea, pruritus, and dyspnea. The top five commonly reported AE types of anti-TNFα drugs were as follows: infections and infestations (184,909, 23.0%), musculoskeletal and connective tissue disorders (704,657, 28.6%), gastrointestinal disorders (122,373, 15.3%), skin and subcutaneous tissue disorders (108,259, 13.5%), and nervous system disorders (88,498, 11.0%). The preferred terms of myelosuppression and acromegaly were obvious in golimumab. Infliximab showed a significantly higher ADR report ratio in the infusion-related reaction compared to the other four inhibitors. The rate of ADR reports for lower respiratory tract infection and other infections was the highest for golimumab. Conclusion: No causal associations could be established between the TNFα inhibitors and the ADRs. Current comparative observational studies of these inhibitors revealed common and specific adverse reactions in the ADR reports of the WHO received for these drugs. Clinicians should improve the rational use of these high-priced drugs according to the characteristics of ADRs.

Efficacy Evaluation of 64-Slice Spiral Computed Tomography Images in Laparoscopic-Assisted Distal Gastrectomy for Gastric Cancer under the Reconstruction Algorithm.

This study was aimed to analyze the application value of the filtered back-projection (FBP) reconstruction algorithm of computed tomography (CT) images in laparoscopic-assisted distal gastrectomy. In this study, 56 patients with gastric cancer were selected as research subjects and randomly divided into the control group (CT-guided laparoscopic radical gastrectomy) and the observation group (CT-guided laparoscopic radical gastrectomy with the FBP reconstruction algorithm), with 28 patients in each group. Fourier transform and iterative reconstruction were introduced for comparison, and finally, the postoperative curative effect and adverse events were compared between the two groups. The results showed that the CT image quality score processed by the FBP reconstruction algorithm (4.31 ± 0.31) was significantly higher than that of the iterative reconstruction method (3.5 ± 0.29) and the Fourier transform method (3.97 ± 0.38) (P < 0.05). The incidences of postoperative wound infection and gastric motility disorder (5.88% and 8.16%, respectively) in the observation group were significantly lower than those in the control group (8.21% and 10.82%, respectively) (P < 0.05). The levels of serum interleukin-6 (IL-6) (280.35 ± 15.08 ng/L) and tumor necrosis factor-α (TNF-α) (144.32 ± 10.32 ng/L) in the observation group after the treatment were significantly lower than those in the control group, which were 399.71 ± 14.19 ng/L and 165.33 ± 10.08 ng/L, respectively (P < 0.05). In conclusion, the FBP reconstruction algorithm was better than other algorithms in the processing of gastric cancer CT images. The FBP reconstruction algorithm showed a good reconstruction effect on CT images of gastric cancer; CT images based on this algorithm helped to formulate targeted surgical treatment plans for gastric cancer, showing a high clinical application value.

Morphology-Dependent Electrocatalytic Performance of a Two-Dimensional Nickel-Iron MOF for Oxygen Evolution Reaction.

Developing highly efficient, low-cost, and durable oxygen evolution reaction (OER) electrocatalysts is extraordinarily desirable for achieving clean and sustainable hydrogen energy. Metal-organic frameworks (MOFs) are emerging as attractive candidates for OER electrocatalysts. Herein, a two-dimensional Fe-Ni MOF of Fe(py)2Ni(CN)4 (py = pyridine) is synthesized controllably to generate various nanostructures, including nanoboxes, nanocubes, nanoplates, and nanosheets. Since different morphologies expose different active crystal planes and generate disparate intrinsic active sites, these nanostructures exhibit obviously different electrocatalytic activities. Particularly, the nanoboxes with a hollow structure display superior electrocatalytic activity and stability for OER due to greater active surface area and higher intrinsic activity of the exposed crystal planes, delivering a low overpotential of 285 mV at 10 mA cm-2 and a small Tafel value of 50.9 mV dec-1 in a 1.0 M KOH solution. The morphology-dependent electrocatalytic properties demonstrated in this work provide an efficient strategy to optimize MOF precatalysts for electrochemical energy storage and conversion.

Effect of Controlled Microtopography on Osteogenic Differentiation of Mesenchymal Stem Cells.

Various kinds of controlled microtopographies can promote osteogenic differentiation of mesenchymal stem cells (MSCs), such as microgrooves, micropillars, and micropits. However, the optimal shape, size, and mechanism remain unclear. In this review, we summarize the relationship between the parameters of different microtopographies and the behavior of MSCs. Then, we try to reveal the potential mechanism between them. The results showed that the microgrooves with a width of 4-60 µm and ridge width <10 µm, micropillars with parameters less than 10 µm, and square micropits had the full potential to promote osteogenic differentiation of MSCs, while the micromorphology of the same size could induce larger focal adhesions (FAs), well-organized cytoskeleton, and superior cell areas. Therefore, such events are possibly mediated by microtopography-induced mechanotransduction pathways.

Optimisation of the Conversion and Extraction of Arctigenin From Fructus arctii Into Arctiin Using Fungi.

Fructus arctii is commonly used in Chinese medicine, and arctiin and arctigenin are its main active ingredients. Arctiin has low bioavailability in the human body and needs to be converted into arctigenin by intestinal microbes before it can be absorbed into the blood. Arctigenin has antiviral, anti-inflammatory, and anti-tumour effects and its development has important value. In this study, we used external microbial fermentation with Aspergillus awamori and Trichoderma reesei to process and convert arctiin from F. arctii powder into arctigenin, hence increasing its bioavailability. We developed a fermentation process by optimising the carbon and nitrogen source/ratio, fermentation time, pH, liquid volume, inoculation volume, and substrate solid-liquid ratio. This allowed for an arctiin conversion rate of 99.84%, and the dissolution rate of the final product was 95.74%, with a loss rate as low as 4.26%. After the fermentation of F. arctii powder, the average yield of arctigenin is 19.51 mg/g. Crude fermented F. arctii extract was purified by silica gel column chromatography, and we observed an arctigenin purity of 99.33%. Our technique effectively converts arctiin and extracts arctigenin from F. arctii and provides a solid basis for further development and industrialisation.

Extracting copper and cobalt from non-ferrous residues by iron- and sulfur-oxidizing bacteria.

How to recycle metals from the waste resources becomes a hotspot all around the world. Non-ferrous residues, which was produced by non-ferrous melting industry, and various of Cu and Co compounds exist in the residues in the form of CuxOy, CuxSy, CoxSy. In order to efficiently extract valuable metals from the non-ferrous residues, this study investigated the bioleaching behavior of Cu and Co from non-ferrous residues, using iron-oxidizing bacteria (IOB, Leptospirillum ferriphilum CS13) and sulfur-oxidizing bacteria (SOB, Acidithiobacillus caldus S2) by controlling the microbial composition, initial pH, and initial ferrous ion concentration. The results showed that IOB had a better performance on extracting Cu and Co than that of SOB, especially for Cu. Furthermore, 77.7 and 79.8% of Cu and Co were extracted under the optimal ratio of the initial number of IOB and SOB (1:1) after bioleaching, which was more than that when bioleaching by any one of these two kinds of bacteria. However, the changes of initial pH and ferrous ion concentration could not significantly enhance bioleaching performance. The results indicated that bioleaching had a good performance on recovering of metals from non-ferrous residues and excellent application prospect for the cleaner resource recycling.

Eukaryotic Translation Elongation Factor 1 Delta Inhibits the Nuclear Import of the Nucleoprotein and PA-PB1 Heterodimer of Influenza A Virus.

The viral ribonucleoprotein (vRNP) of the influenza A virus (IAV) is responsible for the viral RNA transcription and replication in the nucleus, and its functions rely on host factors. Previous studies have indicated that eukaryotic translation elongation factor 1 delta (eEF1D) may associate with RNP subunits, but its roles in IAV replication are unclear. Herein, we showed that eEF1D was an inhibitor of IAV replication because knockout of eEF1D resulted in a significant increase in virus yield. eEF1D interacted with RNP subunits polymerase acidic protein (PA), polymerase basic 1 (PB1), polymerase basic 2 (PB2), and also with nucleoprotein (NP) in an RNA-dependent manner. Further studies revealed that eEF1D impeded the nuclear import of NP and PA-PB1 heterodimer of IAV, thereby suppressing the vRNP assembly, viral polymerase activity, and viral RNA synthesis. Together, our studies demonstrate eEF1D negatively regulating the IAV replication by inhibition of the nuclear import of RNP subunits, which not only uncovers a novel role of eEF1D in IAV replication but also provides new insights into the mechanisms of nuclear import of vRNP proteins.IMPORTANCE Influenza A virus is the major cause of influenza, a respiratory disease in humans and animals. Different from most other RNA viruses, the transcription and replication of IAV occur in the cell nucleus. Therefore, the vRNPs must be imported into the nucleus for viral transcription and replication, which requires participation of host proteins. However, the mechanisms of the IAV-host interactions involved in nuclear import remain poorly understood. Here, we identified eEF1D as a novel inhibitor for the influenza virus life cycle. Importantly, eEF1D impaired the interaction between NP and importin α5 and the interaction between PB1 and RanBP5, which impeded the nuclear import of vRNP. Our studies not only reveal the molecular mechanisms of the nuclear import of IAV vRNP but also provide potential anti-influenza targets for antiviral development.

Swine ANP32A Supports Avian Influenza Virus Polymerase.

Avian influenza viruses occasionally infect and adapt to mammals, including humans. Swine are often described as "mixing vessels," being susceptible to both avian- and human-origin viruses, which allows the emergence of novel reassortants, such as the precursor to the 2009 H1N1 pandemic. ANP32 proteins are host factors that act as influenza virus polymerase cofactors. In this study, we describe how swine ANP32A, uniquely among the mammalian ANP32 proteins tested, supports the activity of avian-origin influenza virus polymerases and avian influenza virus replication. We further show that after the swine-origin influenza virus emerged in humans and caused the 2009 pandemic, it evolved polymerase gene mutations that enabled it to more efficiently use human ANP32 proteins. We map the enhanced proviral activity of swine ANP32A to a pair of amino acids, 106 and 156, in the leucine-rich repeat and central domains and show these mutations enhance binding to influenza virus trimeric polymerase. These findings help elucidate the molecular basis for the mixing vessel trait of swine and further our understanding of the evolution and ecology of viruses in this host.IMPORTANCE Avian influenza viruses can jump from wild birds and poultry into mammalian species such as humans or swine, but they only continue to transmit if they accumulate mammalian adapting mutations. Pigs appear uniquely susceptible to both avian and human strains of influenza and are often described as virus "mixing vessels." In this study, we describe how a host factor responsible for regulating virus replication, ANP32A, is different between swine and humans. Swine ANP32A allows a greater range of influenza viruses, specifically those from birds, to replicate. It does this by binding the virus polymerase more tightly than the human version of the protein. This work helps to explain the unique properties of swine as mixing vessels.

A centrifugal microfluidic emulsifier integrated with oil storage structures for robust digital LAMP.

Centrifugal droplet-based microfluidic devices have been applied to biomedical analysis and diagnostics recently. However, in centrifugal droplet-based microfluidic devices, droplets are tightly packed (i.e., the oil film between neighbouring droplets is thin). Therefore, droplet coalescence usually occurs especially during thermal incubation process. To preserve individual droplets in the devices, we report a new design for monodisperse droplet generation and storage that exploits a centrifugal configuration for droplet emulsification and oil-storage structures (OSSs) for regulation of the thickness of oil film between neighbouring droplets. The centrifugal emulsifier was well designed to ensure uniform droplet generation. Meanwhile, the OSSs could store oil during centrifugal emulsification while release oil before thermal incubation, which "loosen" tightly packed droplets to prevent droplets from coalescing. In this paper, the working process of OSS was analysed, and its shape and size were optimized. Then, the optimized OSSs were integrated into a centrifugal emulsifier for droplet digital loop mediated isothermal amplification (ddLAMP) by which detection of JAK2 V617F mutation within myeloproliferative neoplasms with a dynamic range of 101 to 104 copies per µL was achieved. We anticipate that the simplicity and robustness of our system make it attractive as an inexpensive and easy-to-operate device for DNA amplification, particularly applicable in point-of-care settings.

Activation of reactive oxygen species-mediated mitogen-activated protein kinases pathway regulates both extrinsic and intrinsic apoptosis induced by arctigenin in Hep G2.

OBJECTIVES: Arctigenin (ARG) has been proved to inhibit the viability of hepatocellular carcinoma (HCC) via inducing apoptosis. However, the precise mechanism remains unknown. The present study was aimed to further investigate the mechanism of ARG against HCC in vitro and in vivo. METHODS: Arctigenin was applied in vitro and in vivo. Western blotting, immunohistochemistry, etc., were used to investigate the mechanisms. KEY FINDINGS: The time-dependent enhancement of Bax/Bcl-2 ratio, cytochrome c release, Fas and FasL levels, caspase cascade activation and the loss in the mitochondrial out membrane potential indicated that both intrinsic and extrinsic apoptotic pathways were triggered by ARG. Moreover, Jun NH2-terminal kinase (JNK) and p38 phosphorylated time-dependently. And inhibition of the phosphorylation of either p38 or JNK led to a significant reduction in HepG2 apoptosis, owing to the crucial roles of p38 and JNK played in regulating the apoptosis pathways. In addition, ARG increased the generation of reactive oxygen species (ROS) in HepG2 cells, while the antioxidant N-acetyl cysteine almost reversed ARG-induced JNK and p38 activation, and dramatically decreased cell apoptosis. In vivo, ARG increased the cell apoptosis in tumour tissues, and p-p38, p-JNK and Bax were significantly upregulated. CONCLUSIONS: Our findings demonstrated that ARG induced apoptosis in HCC via ROS-mediated mitogen-activated protein kinases apoptosis pathway.

Arctigenin Attenuates Tumor Metastasis Through Inhibiting Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma via Suppressing GSK3ß-Dependent Wnt/ß-Catenin Signaling Pathway In Vivo and In Vitro.

Arctigenin (ARG) has been reported to be a bioactive lignan from Arctium lappa exerting various activities including anti-cancer and immune-regulation. The present study aimed to investigate the anti-metastasis activity and mechanism of ARG against hepatocellular carcinoma in vitro and in vivo. The results showed that ARG exhibited a significant cytotoxicity on Hep G2 and SMMC 7721 cells (but not on normal liver cells LO2). In addition, the migration and invasion of Hep G2 and SMMC 7721 cells were also remarkably repressed. Furthermore, ARG attenuated Wnt/ß-catenin signaling activation, resulting in the down-regulation of ß-catenin target genes including c-Myc, cyclin D1, MMP-9, and ZO-1. Noticeably, ARG attenuated the activation of Wnt/ß-catenin through a GSK3ß-dependent pathway. Besides, we also found that ARG potentially inhibited epithelial-mesenchymal transition by up-regulating the epithelial and down-regulating the mesenchymal marker proteins. In vivo, intraperitoneal injection of ARG not only significantly inhibited the growth of subcutaneous transplanted tumor but also dramatically alleviated the tumor metastasis in liver. Our data demonstrated that ARG exerted anti-epithelial-mesenchymal transition and anti-metastasis activities against hepatocellular carcinoma, which might make it a candidate as a preventive agent for cancer metastasis.

A 3-mRNA-based prognostic signature of survival in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common type of head and neck squamous cell carcinoma with an unsatisfactory prognosis. The aim of this study was to identify potential prognostic mRNA biomarkers of OSCC based on analysis of The Cancer Genome Atlas (TCGA). METHODS: Expression profiles and clinical data of OSCC patients were collected from TCGA database. Univariate Cox analysis and the least absolute shrinkage and selection operator Cox (LASSO Cox) regression were used to primarily screen prognostic biomarkers. Then multivariate Cox analysis was performed to build a prognostic model based on the selected prognostic mRNAs. Nomograms were generated to predict the individual's overall survival at 3 and 5 years. The model performance was assessed by the time-dependent receiver operating characteristic (ROC) curve and calibration plot in both training cohort and validation cohort (GSE41613 from NCBI GEO databases). In addition, machine learning was used to assess the importance of risk factors of OSCC. Finally, in order to explore the potential mechanisms of OSCC, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was completed. RESULTS: Three mRNAs (CLEC3B, C6 and CLCN1) were finally identified as a prognostic biomarker pattern. The risk score was imputed as: (-0.38602 × expression level of CLEC3B) + (-0.20632 × expression level of CLCN1) + (0.31541 × expression level of C6). In the TCGA training cohort, the area under the curve (AUC) was 0.705 and 0.711 for 3- and 5-year survival, respectively. In the validation cohort, AUC was 0.718 and 0.717 for 3- and 5-year survival. A satisfactory agreement between predictive values and observation values was demonstrated by the calibration curve in the probabilities of 3- and 5- year survival in both cohorts. Furthermore, machine learning identified the 3-mRNA signature as the most important risk factor to survival of OSCC. Neuroactive ligand-receptor interaction was most enriched mostly in KEGG pathway analysis. CONCLUSION: A 3-mRNA signature (CLEC3B, C6 and CLCN1) successfully predicted the survival of OSCC patients in both training and test cohort. In addition, this signature was an independent and the most important risk factor of OSCC.

Effect of non-surgical periodontal therapy on glycemic control of type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Glycemic control is vital in the care of type 2 diabetes mellitus (T2DM) and is significantly associated with the incidence of clinical complications. This Bayesian network analysis was conducted with an aim of evaluating the efficacy of scaling and root planning (SRP) and SRP + adjuvant treatments in improving glycemic control in chronic periodontitis (CP) and T2DM patients, and to guide clinical practice. METHODS: We searched the Pubmed, Embase, Cochrane Library and Web of Science databases up to 4 May 2018 for randomized controlled trials (RCTs). This was at least three months of the duration of study that involved patients with periodontitis and T2DM without other systemic diseases given SRP. Patients in the control group did not receive treatment or SRP combination with adjuvant therapy. Outcomes were given as HbA1c% and levels fasting plasma glucose (FPG). Random-effects meta-analysis and Bayesian network meta-analysis were conducted to pool RCT data. Cochrane's risk of bias tool was used to assess the risk of bias. RESULTS: Fourteen RCTs were included. Most were unclear or with high risk of bias. Compared to patients who did not receive treatment, patients who received periodontal treatments showed improved HbA1c% level, including SRP (the mean difference (MD) -0.399 95% CrI 0.088 to 0.79), SRP + antibiotic (MD 0.62, 95% CrI 0.18 to 1.11), SRP + photodynamic therapy (aPDT) + doxycycline (Doxy) (MD 1.082 95% CrI 0.13 to 2.077) and SRP + laser (MD 0.66 95% CrI 0.1037, 1.33). Among the different treatments, SRP + aPDT + Doxy ranked best. Regarding fasting plasma glucose (FPG), SRP did not show advantage over no treatment (MD 4.91 95% CI - 1.95 to 11.78) and SRP with adjuvant treatments were not better than SRP alone (MD -0.28 95% CI -8.66, 8.11). CONCLUSION: The results of this meta-analysis seem to support that periodontal treatment with aPDT + Doxy possesses the best efficacy in lowering HbA1c% of non-smoking CP without severe T2DM complications. However, longer-term well-executed, multi-center trails are required to corroborate the results.

Efficacy of locally-delivered statins adjunct to non-surgical periodontal therapy for chronic periodontitis: a Bayesian network analysis.

BACKGROUND: Studies indicate locally-delivered statins offer additional benefits to scaling and root planning (SRP), however, it is still hard to say which type of statins is better. This network meta-analysis aimed to assess the effect of locally-delivered statins and rank the most efficacious statin for treating chronic periodontitis (CP) in combination with SRP. METHODS: We screened four literature databases (Pubmed, Embase, Cochrane Library, and Web of Science) for randomized controlled clinical trials (RCTs) published up to June 2018 that compared different statins in the treatment of chronic periodontitis. The outcomes analyzed were changes in intrabony defect depth (IBD), pocket depth (PD), and clinical attachment level (CAL). We carried out Bayesian network meta-analysis of CP without systemic diseases. Traditional and Bayesian network meta-analyses were conducted using random-effects models. RESULTS: Greater filling of IBD, reduction in PD, and gain in CAL were observed for SRP treated in combination with statins when compared to SRP alone for treating CP without systemic diseases. Specifically, SRP+ Atorvastatin (ATV) (mean difference [MD]: 1.5 mm, 1.4 mm, 1.8 mm, respectively), SRP + Rosuvastatin (RSV) (MD: 1.8 mm, 2.0 mm, 2.1 mm, respectively), and SRP + Simvastatin (SMV) (MD: 1.1 mm, 2.2 mm, 2.1 mm, respectively) were identified. However, no difference was found among the statins tested. In CP patients with type 2 diabetic (T2DM) or in smokers, additional benefits were observed from locally delivered statins. CONCLUSION: Local statin use adjunctive to SRP confers additional benefits in treating CP by SRP, even in T2DM and smokers. RSV may be the best one to fill in IBD. However, considering the limitations of this study, clinicians must use cautious when applying the results and further studies are required to explore the efficacy of statins in CP with or without the risk factors (T2DM comorbidity or smoking history).

EGFR point mutation detection of single circulating tumor cells for lung cancer using a micro-well array.

In view of their critical function in metastasis, characterization of single circulating tumor cells (CTCs) can provide important clinical information to monitor tumor progression and guide personal therapy. Single-cell genetic analysis methods based on microfluidics have some inherent shortcomings such as complicated operation, low throughput, and expensive equipment requirements. To overcome these barriers, we developed a simple and open micro-well array containing 26,208 units for either nuclear acids or single-cell genetic analysis. Through modification of the polydimethylsiloxane surface and optimization of chip packaging, we addressed protein adsorption and solution evaporation for PCR amplification on a chip. In the detection of epidermal growth factor receptor (EGFR) exon gene 21, this micro-well array demonstrated good linear correlation at a DNA concentration from 1 × 101 to 1 × 105 copies/µL (R2 = 0.9877). We then successfully integrated cell capture, lysis, PCR amplification, and signal read-out on the micro-well array, enabling the rapid and simple genetic analysis of single cells. This device was used to detect duplex EGFR mutation genes of lung cancer cell lines (H1975 and A549 cells) and normal leukocytes, demonstrating the ability to perform high-throughput, massively parallel duplex gene analysis at the single-cell level. Different types of point mutations (EGFR-L858R mutation or EGFR-T790M mutation) were detected in single H1975 cells, further validating the significance of single-cell level gene detection. In addition, this method showed a good performance in the heterogeneity detection of individual CTCs from lung cancer patients, required for micro-invasive cancer monitoring and treatment selection.

Influenza M2 protein regulates MAVS-mediated signaling pathway through interacting with MAVS and increasing ROS production.

Influenza A virus can evade host innate immune response that is involved in several viral proteins with complicated mechanisms. To date, how influenza A M2 protein modulates the host innate immunity remains unclear. Herein, we showed that M2 protein colocalized and interacted with MAVS (mitochondrial antiviral signaling protein) on mitochondria, and positively regulated MAVS-mediated innate immunity. Further studies revealed that M2 induced reactive oxygen species (ROS) production that was required for activation of macroautophagy/autophagy and enhancement of MAVS signaling pathway. Importantly, the proton channel activity of M2 protein was demonstrated to be essential for ROS production and antagonizing the autophagy pathway to control MAVS aggregation, thereby enhancing MAVS signal activity. In conclusion, our studies provided novel insights into mechanisms of M2 protein in modulating host antiviral immunity and uncovered a new mechanism into biology and pathogenicity of influenza A virus. Abbreviations: AKT/PKB: AKT serine/threonine kinase; Apo: apocynin; ATG5: autophagy related 5; BAPTA-AM: 1,2-Bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetrakis; BECN1: beclin 1; CARD: caspase recruitment domain; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CQ: chloroquine; DCF: dichlorodihyd-rofluorescein; DPI: diphenyleneiodonium; DDX58: DExD/H-box helicase 58; eGFP: enhanced green fluorescent protein; EGTA: ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid; ER: endoplasmic reticulum; hpi: hours post infection; IAV: influenza A virus; IFN: interferon; IP: immunoprecipitation; IRF3: interferon regulatory factor 3; ISRE: IFN-stimulated response elements; LIR: LC3-interacting region; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAVS: mitochondrial antiviral signaling protein; MMP: mitochondrial membrane potential; MOI, multiplicity of infection; mRFP: monomeric red fluorescent protein; MTOR: mechanistic target of rapamycin kinase; NC: negative control; NFKB/NF-κB: nuclear factor kappa B; PI3K: class I phosphoinositide 3-kinase; RLR: RIG-I-like-receptor; ROS: reactive oxygen species; SEV: sendai virus; TM: transmembrane; TMRM: tetramethylrhodamine methylester; VSV: vesicular stomatitis virus.