Experimental evidence of effective disinfectant to control the transmission of Micropterus salmoides rhabdovirus.

Micropterus salmoides rhabdovirus (MSRV) is a significant pathogen that causes high morbidity and mortality in largemouth bass, leading to enormous economic losses for largemouth bass aquaculture in China. The aim of this study was to investigate the efficacy of four disinfectants (potassium permanganate, glutaraldehyde, trichloroisocyanuric acid and povidone iodine) on MSRV, to control the infection and transmission of MSRV in largemouth bass aquaculture. The disinfectants were tested at different concentrations (5, 25, 50, 100 and 500 mg/L) prepared with distilled water for 30 min contact time, and the viral nucleic acid was quantified using qPCR and the infectivity was tested by challenge experiment. Potassium permanganate at 5-500 mg/L, glutaraldehyde at 500 mg/L, trichloroisocyanuric acid at 50-500 mg/L and povidone iodine at 500 mg/L concentration could effectively decrease the virus nucleic acid, and the survival rate of largemouth bass juveniles after challenge experiment increased significantly from 3.7% ± 6.41% to 33.33 ± 11.11% - 100%. Moreover, the minimum effective time of 5 mg/L potassium permanganate was further studied at 2, 5, 10 and 20 min contact time. The viral nucleic acid decreased significantly at 5-20 min exposure time, and the survival rate increased significantly from 7.41% ± 6.41% to 77.78 ± 11.11% - 100%. The median lethal concentration (LC50 ) values of potassium permanganate were 10.64, 6.92 and 3.7 mg/L at 24, 48 and 96 h, respectively. Potassium permanganate could be used for the control of MSRV in the cultivation process; the recommended concentration is 5 mg/L and application time should be less than 24 h. The results could be applied to provide a method to control the infection and transmission of MSRV in water, and improve the health status of largemouth bass.

A Novel Prophylaxis Strategy Using Liposomal Vaccine Adjuvant CAF09b Protects against Influenza Virus Disease.

The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future respiratory virus pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF®09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b liposomes as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b liposomes to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I-related gene expression. When CAF09b liposomes were administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although the virus was still detectable in the lungs. However, when CAF09b liposomes were administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective.

Live-Attenuated Influenza Vaccine Induces Tonsillar Follicular T Helper Cell Responses That Correlate With Antibody Induction.

BACKGROUND: Influenza remains a major threat to public health. Live-attenuated influenza vaccines (LAIV) have been shown to be effective, particularly in children. Follicular T helper (TFH) cells provide B-cell help and are crucial for generating long-term humoral immunity. However the role of TFH cells in LAIV-induced immune responses is unknown. METHODS: We collected tonsils, plasma, and saliva samples from children and adults receiving LAIV prior to tonsillectomy. We measured influenza-specific TFH-cell responses after LAIV by flow cytometry and immunohistochemistry. Systemic and local antibody responses were analysed by hemagglutination inhibition assay and enzyme-linked immunosorbent assay. RESULTS: We report that LAIV induced early (3-7 days post-vaccination) activation of tonsillar follicles and influenza-specific TFH-cell (CXCR5+CD57+CD4+ T cell) responses in children, and to a lesser extent in adults. Serological analyses showed that LAIV elicited rapid (day 14) and long-term (up to 1 year post-vaccination) antibody responses (hemagglutination inhibition, influenza-specific IgG) in children, but not adults. There was an inverse correlation between pre-existing influenza-specific salivary IgA concentrations and tonsillar TFH-cell responses, and a positive correlation between tonsillar TFH-cell and systemic IgG induction after LAIV. CONCLUSIONS: Our data, taken together, demonstrate an important role of tonsillar TFH cells in LAIV-induced immunity in humans.

Precise engineering of neutrophil membrane coated with polymeric nanoparticles concurrently absorbing of proinflammatory cytokines and endotoxins for management of sepsis.

Sepsis, ensuing from unrestrained inflammatory replies to bacterial infections, endures with high injury and mortality worldwide. Presently, active sepsis management is missing in the hospitals during the surgery, and maintenance remnants mainly helpful. Now, we have constructed the macrophage bio-mimic nanoparticles for the treatment of sepsis and its management. Biomimetic macrophage nanoparticles containing a recyclable polymeric nanoparticle covered with cellular membrane resulting from macrophages (represented PEG-Mac@NPs) have an antigenic external similar to the cells. The PEG-Mac@NPs, Isorhamnetin (Iso) on the free LPS encouraged endotoxin in BALB/c mice through evaluating the nitric acid, TNF-α, and IL-6. Further, the COX-2 and iNOS expression ratio was examined to recognize the connection of several trails to find the exact mode of action PEG-Mac@NPs and Iso. The outcome reveals that the PEG-Mac@NPs inhibited and LPS triggered the NO production though the macrophages peritoneal. Furthermore, the anti-inflammatory possessions were additionally categorized through the reduction of COX-2 and iNOS protein expressions. Engaging PEG-Mac@NPs as a biomimetic decontamination approach displays potential for refining sepsis patient consequences, possibly in the use of sepsis management.

Finite elements analysis of the temporomandibular joint disc in patients with intra-articular disorders.

BACKGROUND: Intra-articular disorders (ID) or anterior and/or medial displacement of the temporomandibular joint disorder (TMJ) disc are the most common form of TMJ dysfunction (TMD). TMD causes changes in the friction coefficient during TMJ movement. Herein, we provided a three-dimensional (3D) finite-elements model (FEM) including the maxilla, disc, and mandible and evaluated the stress distribution with different friction coefficient. METHODS: Fourteen volunteers without TMD and 20 patients with MRI-diagnosed TMD were selected. CT and MRI data were collected to build the 3D FEA model of the mandible and TMJ disc. Stress distribution with different friction coefficient was measured. RESULT: In the normal model, stress distribution on the TMJ disc was 2.07 ± 0.17, 1.49 ± 0.14, and 1.41 ± 0.14 MPa with 0.001, 0.3, and 0.4 friction coefficient, respectively. In the TMD model, stress distribution was 3.87 ± 0.15, 7.23 ± 0.22, and 7.77 ± 0.19 MPa respectively. CONCLUSION: When the friction coefficient of the side with anterior displacement increased, stress on the disc, condyle and mandible of the opposite side increased. Simultaneously, stress values of the disc, condyle and mandible were higher than those of the normal lateral joint.

Relationship between occupational noise exposure and hypertension: A cross-sectional study in steel factories.

BACKGROUND: Hazardous exposure to occupational noise may be associated with an increased risk of cardiovascular disease and hypertension. This study was performed to assess the relationship between noise exposure and hypertension prevalence in steelworkers. METHODS: A cross-sectional survey using self-reported noise exposure and audiometrically measured hearing loss was performed. One thousand eight hundred and seventy-four workers were interviewed. Multiple logistic regression was used to calculate odds ratios for hypertension by noise exposure. Linear regression analysis was used to test associations between noise exposure and systolic blood pressure (SBP) and diastolic blood pressure (DBP). RESULTS: Occupational noise-exposed subjects had significantly higher blood pressure levels than nonexposed subjects (SBP: 123.18 ± (standard deviation) 12.44 vs 119.80 ± 12.50 mm Hg; DBP: 77.86 ± 9.34 vs 75.49 ± 8.73 mmHg). The prevalence of hypertension was approximately 5% in the control group without noise exposure or hearing impairment and increased from 6% to 21% across the range of increasing degree of hearing loss and, separately, of cumulative exposure time. Noise exposure (any) was associated with an increase in the prevalence of hypertension (odds ratio, 2.03, 95% confidence interval [CI]: 1.15-3.58). Noise-induced hearing loss and cumulative noise exposure time were positively correlated with BP (hearing loss: SBP: ß = .09, 95% CI: 0.04-0.15 mm Hg, DBP: ß = .11, 95% CI: 0.06-0.17 mm Hg; cumulative exposure time: SBP: ß = .10, 95% CI: 0.04-0.15 mm Hg, DBP: ß = .09, 95% CI: 0.04-0.15 mm Hg). CONCLUSIONS: Noise exposure measured in two different ways was strongly associated with the prevalence of hypertension in steelworkers. Reducing noise in the steel factory could be a way of decreasing the risk of hypertension in this population.

Highly sensitive, label-free and real-time detection of alpha-fetoprotein using a silicon nanowire biosensor.

Alpha-fetoprotein (AFP) is a tumor-associated fetal protein that can be expressed in large amounts in adult tumor cells, serving as a useful clinical tumor-marker. Silicon nanowire (SiNW) biosensors have emerged as a powerful tool in detecting protein biomarkers, due to their ultrahigh sensitivity, real-time response and label-free detection. We fabricated a SiNW-based field-effect transistor (FET) according to "top-down" methodology. First, anti-AFP antibodies were immobilized onto the surface of the SiNW-FET. A polydimethylsiloxane (PDMS) microchannel was then integrated to the modified SiNW-FET. Various concentrations of AFP were then pumped through the sensing area. We observed a current change that corresponded to binding of AFP onto the surface of our anti-AFP functionalized SiNW-FET biosensor. Concentrations of AFP as low as 0.1 ng/mL were detected. The results implicate our SiNW biosensor as an effective AFP biomarker detector with promising potential in clinical applications.

Transparent and luminescent ionogels composed of Eu(3+)-coordinated ionic liquids and poly(methyl methacrylate).

We report here on transparent and luminescent ionogels that consist of ionic ternary europium (III) complexes and the inexpensive non-toxic compound, poly(methyl methacrylate) (PMMA) and that were formed by dissolving these complexes in methacrylate (MMA) monomers followed by in situ polymerization. The resulting ionogels show a bright red emission under near-UV light irradiation. Luminescence data confirm the energy transfer from terpyridine-functionalized ionic liquid to Eu(3+) ions.

Effects of synthesizing parameters on surface roughness and contact angles of ZnO nanowire films.

Effects of the synthesizing parameters on the surface roughness and the contact angles of ZnO nanowire films were studied in this paper. ZnO nanowire films were synthesized with the hydrothermal method on glass substrates, and the synthesizing parameters include the concentrations of the growth solution and the seed layer solution, the growth time span as well as the temperature. Atomic force microscopy and scanning electron microscopy were employed respectively to characterize the surface and the profile roughness of ZnO nanowire films. The measurement results by atomic force microscopy were in agreement with that by scanning electron microscopy, hence the former was used for the investigation of aforementioned effects. Relationships between the synthesizing parameters, the surface roughness and the contact angles of ZnO nanowire films were established, revealing that the synthesizing parameters affected significantly not only the surface roughness but also the contact angles of ZnO nanowire films. The results can be used for batch fabrication of ZnO nanowire-based structures and these structures-based sensors in a wide variety of applications.

Wearable electrochemical glucose sensor of high flexibility and sensitivity using novel mushroom-like gold nanowires decorated bendable stainless steel wire sieve.

Long-term high blood glucose levels brings extremely detrimental effect on diabetic patients, such as blindness, renal failure, and cardiovascular diseases. Therefore, there is an urgent need to develop highly flexible and sensitive sensors for precisely non-invasive and continuous monitoring glucose levels. Herein, we present a highly flexible and sensitive wearable sensor for non-enzymatic electrochemical glucose analysis with vertically aligned mushroom-like gold nanowires (v-AuNWs) chemically grown on stainless steel wire sieve (SSWS) as integrated electrode. Owing to the unique nanostructures and excellent catalysis of the v-AuNWs, the as-fabricated glucose sensors exhibit superior flexibility and excellent electro-catalytic capability. In detail, these sensors display rapid response towards glucose within 5 s, and the sensor constructed with v-AuNWs for growth time of 15 min shows the highest sensitivity of 180.1 µA mM-1 cm-2 within a wide linear range of 6.5 × 10-4 mM-12.0 mM and the lowest detection limit of 0.65 µM (S/N = 3). It is noteworthy that due to the good ductility of the v-AuNWs and their strong contact with the SSWS substrate, these glucose sensors exhibit no obvious response variation after repeated bending for 100 times at bending angle of 180°. Additionally, the glucose sensors display superior anti-interfering capability as well as desirable repeatability. More importantly, these glucose sensors can be attached on human skin to determine sweat glucose reliably and analyze glucose concentration in human serum in vitro.

Preparation of myocardial patches from DiI-labeled rat bone marrow mesenchymal stem cells and neonatal rat cardiomyocytes contact co-cultured on polycaprolactone film.

To provide better treatment of myocardial infarction, DiI-labeled bone marrow mesenchymal stem cells (BMSCs) were contact co-cultured with cardiomyocytes (CMs) on polycaprolactone (PCL) film to prepare myocardial patches. BMSCs from Sprague Dawley rats were isolated, cultured, and characterized for expression of surface markers by flow cytometry. CMs were isolated from suckling rats. After BMSCs were cultured for three generations, they were labeled with DiI dye. DiI-labeled BMSCs were co-cultured with CMs on PCL film in the experimental group, while CMs were replaced with the same amount of unlabeled BMSCs in the control group. After 24 h, cell growth was observed by light microscopy and cells were fixed for scanning electron microscopy (SEM). After 7 d of co-culture, cells were stained for immunofluorescence detection of myocardial markers cardiac troponin T (cTnT) andα-actin. Differentiation of BMSCs on PCL was observed by fluorescence microscopy. The efficiency of BMSC differentiation into CMs was analyzed by flow cytometry on the first and seventh days of co-culture. CMs were stained with calcein alone and contact co-cultured with DiI-labeled BMSCs on PCL film to observe intercellular dye transfer. Finally, cells were stained for immunofluorescence detection of connexin 43 (Cx43) expression and to observe the relationship between gap junctions and contact co-culture. BMSCs were identified by flow cytometry as strongly positive for CD90 and CD44H, and negative for CD11b/c and CD45. After co-culture for 24 h, cells were observed to have attached to PCL by light microscopy. Upon appropriate excitation, DiI-labeled BMSCs exhibited red fluorescence, while unlabeled CMs did not. SEM revealed a large number of cells on the PCL membrane and their cell state appeared normal. On the seventh day, some DiI-labeled BMSCs expressed cTnT andα-actin. Flow cytometry showed that the rate of stem cell differentiation in the experimental group was significantly higher than the control group on the seventh day (20.12% > 3.49%,P< 0.05). From the second day of co-culture, immunofluorescence staining for Cx43 revealed green fluorescent puncta in some BMSCs; from the third day of co-culture, a portion of BMSCs exhibited green fluorescence in dye transfer tests. Contact co-culture of DiI-labeled BMSCs and CMs on PCL film generated primary myocardial patches. The mechanism by which contact co-culture promoted differentiation of the myocardial patch may be related to gap junctions and gap junction-mediated intercellular signaling pathways.

Efficacy of Traditional Chinese Medicine, Maxingshigan-Weijing in the management of COVID-19 patients with severe acute respiratory syndrome: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We aimed to test our expectation that additional administration of Traditional Chinese medicine (TCM), maxingshigan-weijing decoction, is more effective in the management of COVID-19 patients compared to those treated with routine supportive care alone. TRIAL DESIGN: This is a multicenter, open-label 2-arm (1:1 ratio) randomized controlled trial. PARTICIPANTS: Patients will be recruited from 3 hospitals in Wenzhou China: the First Affiliated Hospital of Wenzhou Medical University, the Second Affiliated Hospital of Wenzhou Medical University and Wenzhou Center Hospital. The inclusion and exclusion criteria are as follows: Inclusion criteria 1. Participants are 18-85 years of age, either male or female. 2. Diagnosed as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3. Symptomatic. Mild (mild clinical symptoms without signs of pneumonia in chest X-ray) and Moderate (fever or respiratory symptom with signs of pneumonia in chest X-ray) . 1. Signed the informed consent before treatment. 2. Agreed not to enroll in any other clinical trials. 3. Inpatients Exclusion criteria 1. < 18 or > 85 years old. 2. Pregnancy and lactation. 3. Serious heart, liver, kidney and hematopoietic system diseases, abnormal liver or kidney function. 4. Suffering from other known virus pneumonia. 5. Allergic to Chinese herbal medicine or suffering from allergies. 6. Critical patients (respiratory failure treated by mechanical ventilation or shock or multiple organ failure). INTERVENTION AND COMPARATOR: Patients in the control group will receive routine supportive clinically care including the therapies of anti-viral, anti-bacterial and ameliorating the related symptoms, while patients in TCM group will be asked to take maxingshigan-weijing decoction (composed of 14 Chinese herbal medicines), orally 200 mL 2 times daily, for 14 consecutive days in addition to routine supportive care as mentioned above. Maxingshigan-weijing decoction consists of 10 g of Herba Ephedra (Mahuang), 10 g of Amygdalus Communis Vas (Xingren), 45 g of Gypsum Fibrosum (Shigao), 30 g of Rhizoma phragmitis (Lugen), 20 g of Peach kernel (Taoren), 20 g of Winter Melon kernel (Dongguaren), 30 g of Trichosanthes Kirilowii Maxim (Gualou), 12 g of Pericarpium Citri Reticulatae (Chenpi), 12 g of Rhizoma Pinelliae (Jiangbanxia), 12 g of caulis bambusae in taeniis (Zhuru), 30 g of semen lepidii (Tingliz), 15 g of semen lepidii (Shichangpu), 10 g of curcuma zedoary (ezhu) and 5 g of Radix Glycyrrhizae (Gancao). MAIN OUTCOMES: The primary outcome will be the number of days until the clinical symptom of fever improves in the first 14 days of treatment following randomisation. Fever will be defined as an improvement when the temperature is less than 37°C. Secondary outcomes will be TCM Syndrome Scores, the time it takes until individuals have negative test results for SARS-CoV-2 nucleic acid, the proportion of cases with chest X-ray improvements and the rate of symptom (fever, cough, malaise, shortness of breath) recovery. TCM Syndrome Scoring System is a checklist covering 4 main, 7 secondary and 13 accompanying items. The 4 main items consisting of fever, cough, malaise and shortness of breath, use a four-point scale (0, 2, 4 and 6) depending on the severity; the 7 secondary items including dysphoria, diarrhea, pharyngalgia, expectoration, muscular soreness, nasal obstruction and rhinorrhoea use 0-3-point scale; the 13 accompanying items contain chest pain, headache, aversion to cold, dizziness, nausea and vomiting, anorexia, abdominal distension, dry mouth, anxiety, spontaneous sweating, insomnia, wheezing and blood tinged sputum, and each item is rated on 0-1 scale ( 0 stands for asymptomatic, 1 stands for symptomatic ). The total scores sum up to a range from 0 to 58, with higher scores indicating more severe levels of disease. RANDOMIZATION: Minimization method will be used, balancing the two arms for pneumonia severity. Patients are randomized (1:1 ratio) to each group. Clinical researchers will get a random sequence number which is automatically generated by a random number generator (IBM Corp., Armonk, NY, USA), and sequentially number them in an opaque envelope. Researchers will open random allocation envelopes and assign participants accordingly. Eligible patients will be randomly divided into a routine supportive care group and a routine supportive care plus oral administration of traditional Chinese medicine group, with 70 patients in each group. BLINDING (MASKING): This is an open-label study. The statistical analysis will be carried out by the Professor of Statistics at Wenzhou Medical University, who is blinded to patient allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The previous study reported the efficacy of TCM for COVID-19 and H1N1 influenza patients, the median survival time in the TCM group is estimated as 3 days; this time will be 1.5 times longer in the control group. Accordingly, Kaplan-Meier method and log-rank test will be used. And assuming a statistical power of 70% (one-sided type-1 error of α = 5%, ß = 30%) and a rate of withdrawal and loss to follow-up of 10%, we plan to include 140 participants in both groups ( TCM group = 70, control group = 70). TRIAL STATUS: The trial protocol is Version 2.0, October 14, 2020. Recruitment began March, 2020, and is anticipated to be completed by December 31, 2020. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030759 . Registered on 13 March 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Acetone adsorption capacity of sulfur-doped microporous activated carbons prepared from polythiophene.

Sulfur-doped activated carbons (SACs) with high sulfur content and large specific surface area were synthesized from polythiophene for acetone removal. The sulfur content of carbons (3.10-8.43 at.%) could be tunable by adjusting the activation temperature. The BET surface area and pore volume of the obtained samples were 916-2020 m2 g-1 and 0.678-1.100 cm3 g-1, with a significant proportion of microporosity (up to 84% and 72% for BET surface area and pore volume, respectively). The resulting SACs show a superior acetone adsorption capacity (i.e., 716.4 mg g-1 at 15 °C and 705 mg g-1 at 25 °C for SAC700). In terms of the adsorption behavior of acetone on the activated carbons, compared to the Langmuir model, the Langmuir-Freundlich model showed better agreement with the adsorption amount. The results reveal that the surface area and micropore volume are the key factors for acetone adsorption, while the sulfur-doped functional groups, especially oxidized sulfur functional groups, can enhance the acetone adsorption capacity at a certain low pressure. Temperature programmed desorption (TPD) experiments were performed to get desorption activation energy of acetone on SAC samples, and the results ranged from 23.54 to 38.71 kJ mol-1. The results of the molecular simulation show that the introduction of sulfur element can increase the binding energy between acetone molecule and carbon surface, and the tri-oxidized sulfur (sulfonic acid) functional group has the highest binding energy of - 0.4765 eV. Graphical abstract.

Serendipitous Detection of Hodgkin Lymphoma by 18F-NaF PET/CT.

A 17-year-old girl underwent F-NaF PET/CT to evaluate bone pain after an accident. The images did not identify any osseous lesion. However, there was a focally increased activity in the left upper chest, which corresponded to a partially calcified soft tissue mass in the mediastinum, suggestive of malignancy. The result led to subsequent F-FDG PET/CT imaging, which demonstrated intense activity in the mediastinal mass and in multiple cervical, supraclavicular, and mediastinal lymph nodes. Hodgkin lymphoma was diagnosed histopathologically following the biopsy.

Single dose vaccination of the ASO3-adjuvanted A(H1N1)pdm09 monovalent vaccine in health care workers elicits homologous and cross-reactive cellular and humoral responses to H1N1 strains.

Healthcare workers (HCW) were prioritized for vaccination during the 2009 influenza A(H1N1)pdm09 pandemic. We conducted a clinical trial in October 2009 where 237 HCWs were immunized with a AS03-adjuvanted A(H1N1)pdm09 monovalent vaccine. In the current study, we analyzed the homologous and cross-reactive H1N1 humoral responses using prototype vaccine strains dating back to 1977 by the haemagglutinin inhibition (HI), single radial hemolysis SRH), antibody secreting cell (ASC) and memory B cell (MBC) assays. The cellular responses were assessed by interferon-γ (IFN-γ) ELISPOT and by intracellular staining (ICS) for the Th1 cytokines IFN-γ, interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α). All assays were performed using blood samples obtained prior to (day 0) and 7, 14 and 21 d post-pandemic vaccination, except for ASC (day 7) and ICS (days 0 and 21). Vaccination elicited rapid HI, SRH and ASC responses against A(H1N1)pdm09 which cross reacted with seasonal H1N1 strains. MBC responses were detected against the homologous and seasonal H1N1 strains before vaccination and were boosted 2 weeks post-vaccination. An increase in cellular responses as determined by IFN-γ ELISPOT and ICS were observed 1-3 weeks after vaccination. Collectively, our data show that the AS03-adjuvanted A(H1N1)pdm09 vaccine induced rapid cellular and humoral responses against the vaccine strain and the response cross-reacted against prototype H1N1 strains dating back to 1977.