Cost-effectiveness of latent tuberculosis infection testing and treatment with 6-week regimen among key population in rural communities in China: a decision analysis study.

PURPOSE: Several model studies suggested the implementation of latent tuberculosis infection (LTBI) testing and treatment could greatly reduce the incidence of tuberculosis (TB) and achieve the 2035 target of the "End TB" Strategy in China. The present study aimed to evaluate the cost-effectiveness of LTBI testing and TB preventive treatment among key population (≥ 50 years old) susceptible to TB at community level in China. METHODS: A Markov model was developed to investigate the cost-effectiveness of LTBI testing using interferon gamma release assay (IGRA) and subsequent treatment with 6-month daily isoniazid regimen (6H) (as a standard regimen for comparison) or 6-week twice-weekly rifapentine and isoniazid regimen (6-week H2P2) in a cohort of 10,000 adults with an average initial age of 50 years. RESULTS: In the base-case analysis, LTBI testing and treatment with 6H was dominated (i.e., more expensive with a lower quality-adjusted life year (QALY)) by LTBI testing and treatment with 6-week H2P2. LTBI testing and treatment with 6-week H2P2 was more effective than no intervention at a cost of $20,943.81 per QALY gained, which was below the willingness-to-pay (WTP) threshold of $24,211.84 per QALY gained in China. The one-way sensitivity analysis showed the change of LTBI prevalence was the parameter that most influenced the results of the incremental cost-effectiveness ratios (ICERs). CONCLUSION: As estimated by a Markov model, LTBI testing and treatment with 6-week H2P2 was cost-saving compared with LTBI testing and treatment with 6H, and it was considered to be a cost-effective option for TB control in rural China.

Silver nanowires/cellulose flexible transparent conductive films for electromagnetic interference shielding and electrothermal conversion.

Currently, electromagnetic shielding materials need to meet the characteristics of lightweight, high transmittance, and robust conductivity. Silver nanowires (AgNWs) have progressively found applications in recent years owing to their excellent aspect ratio, conductivity, and flexibility. The properties of AgNWs vary with different aspect ratios, and the length and diameter of AgNWs often exert diverse influences on the photoelectric properties of conductive films. In this study, we combined AgNWs with hydroxypropyl methylcellulose (HPMC) and employed a directional stacking arrangement method to apply AgNWs onto the PET substrate, investigating the properties of four distinct aspect ratios of AgNWs (1000, 750, 625, and 531). Ultimately, the prepared four films achieved electromagnetic shielding capabilities ranging from 26.6 dB to 32.8 dB, with a transmittance range of 89.8% to 94.6%, showing excellent electromagnetic shielding properties. Moreover, the prepared films showed an exceedingly low roughness value (RMS = 7.07 nm), remarkable flexibility, and superior oxidation resistance with the facilitation of HPMC. The films also showed exceptional electrothermal conversion prowess, achieving saturation temperature within a mere 8 seconds, thereby displaying a rapid thermal response. Furthermore, when a voltage of 4 V was applied, the temperature of the thin film remained essentially constant for a duration of 2500 seconds, highlighting its admirable thermal stability, which is of great significance for the development of flexible and transparent electromagnetic shielding materials in the future.

Association between sleep patterns and galectin-3 in a Chinese community population.

BACKGROUND: Irregular sleep patterns have been associated with inflammation. Galectin-3, a novel biomarker, plays an important role in inflammation. We investigated the relationship between sleep patterns and galectin-3 in a Chinese population. METHODS: A total of 1,058 participants from the Shenzhen-Hong Kong United Network on Cardiovascular Disease study were included in the analysis. Age and sex-adjusted linear regression models were employed to investigate the relationship between galectin-3 level and traditional metabolic biomarkers. Logistic regression models were used to estimate the association among sleep disturbance, nighttime sleep duration, and daytime napping duration and elevated galectin-3, with elevated galectin-3 defined as galectin-3 level > 65.1 ng/ml. RESULTS: Of study participants, the mean age was 45.3 years and 54.3% were women. Waist circumference, natural logarithm (ln)-transformed triglyceride, and ln-transformed high sensitivity C-reactive protein were positively associated with galectin-3 level (age and sex-adjusted standardized ß [95% confidence interval (CI)], 0.12 [0.04, 0.21], 0.11 [0.05, 0.17], and 0.08 [0.02, 0.14], respectively). Sleep disturbance was associated with elevated galectin-3 (odds ratio [95% CI], 1.68 [1.05, 2.68], compared to those without sleep disturbance) after adjusting for traditional metabolic biomarkers. No interaction was observed between galectin-3 and age, sex, obesity, hypertension, and diabetes on sleep disturbance. No association was found between nighttime sleep duration or daytime napping duration and elevated galectin-3. CONCLUSIONS: Our study provides evidence of a significant association between sleep disturbance and elevated galectin-3 level, independent of traditional metabolic biomarkers. Screening and interventions on galectin-3 could assist in preventing sleep disturbance-induced inflammatory disease.

Multilayer directionally arranged silver nanowire networks for flexible transparent conductive films.

Silver nanowire (AgNW) networks have excellent optoelectronic properties and have important applications in various optoelectronic devices. However, the random distribution of AgNWs coated on the substrate will cause problems such as uneven resistance and high surface roughness, which will affect the properties of the film. In order to solve these problems, this paper adopts the method of directional arrangement of AgNWs to prepare conductive films, by mixing AgNW aqueous solution with hydroxypropyl methyl cellulose (HPMC) to prepare conductive ink, and then the AgNWs are oriented on the flexible substrate by using the shear force generated during the Mayer rod coating process. The multilayer crossed three-dimensional (3D) AgNW conductive network is prepared, achieving a sheet resistance of 12.9 Ω sq-1 and a transmittance of 92.2% (λ = 550 nm). In addition, the roughness RMS value of the layered and ordered AgNW/HPMC composite film is only 6.96 nm, which is much lower than that of the randomly arranged AgNW film (RMS = 19.8 nm), and the composite film also has excellent bending resistance and environmental stability. This adjustable coating method is simple to prepare and can realize the large-scale manufacturing of conductive films, which is important for the future development of flexible transparent conductive films.

Interface-engineered Co3S4/CoMo2S4nanosheets as efficient bifunctional electrocatalysts for alkaline overall water splitting.

Exploring bifunctional electrocatalysts with high efficiency, inexpensive, and easy integration is still the daunt challenge for the production of hydrogen on a large scale by means of water electrolysis. In this work, a novel free-standing Co3S4/CoMo2S4heterostructure on nickel foam by a facial hydrothermal method is demonstrated to be an effective bifunctional electrocatalyst for overall water splitting (OWS). The synthesized Co3S4/CoMo2S4electrocatalyst achieves ultralow overpotentials of 143 mV@10 mA cm-2for hydrogen evolution reaction (HER) and 221 mV@25 mA cm-2for oxygen evolution reaction (OER), respectively, in 1 M KOH. Moreover, it presents a greatly improved durability and stability under operando electrochemical conditions. When used as catalysts for OWS, the Co3S4/CoMo2S4-3//Co3S4/CoMo2S4-3 electrodes just need 1.514 V to make it to the current density of 10 mA cm-2. It is supposed that the introduction of heterogeneous interface between Co3S4and CoMo2S4could give rise to plentiful active sites and enhanced conductivity, and thus boost excellent catalytic performances. Moreover, the porous feature of free-standing nanosheets on nickel foam could benefits catalytic performances by accelerating charge transport and releasing bubbles rapidly. This work proposes a bifunctional catalyst system with the heterogeneous interface, which could be used in a sustainable green energy system.

Gear-Shaped High-g Combustion Chamber for Micro Turbojet Engine Applications.

Enhancing combustion efficiency and optimizing the thrust-to-weight ratio are critical technical challenges encountered in the development, application, and growth of micro turbojet engines. The high-centrifugal (high-g) combustion chamber, as an innovative combustion chamber system, has the capability to replace the primary combustion chamber of the traditional turbojet engine, reducing the length of the combustion chamber while maintaining engine performance. Previous studies on the structure of the high-g combustor (HGC) have shown problems such as uneven temperature distribution of the turbojet rotor. To improve the feasibility of HGC integration into micro turbojet engines, this study conducts relevant experiments on a 120 N thrust engine. Subsequently, the results of these experiments were used to analyze the structural design of HGC through a simulation approach. Including six main configurations, the first four structural designs focused on establishing a suitable highly centrifugal environment to stabilize and improve the combustion performance, which was successfully achieved by designing the outer ring gear-shaped inlet with four different angles. Subsequent structural designs were based around improving the uniformity of the temperature distribution at the combustion chamber outlet. The final design of the HGC combustion efficiency is not much different from the original combustion chamber, and it can shorten the axial length of the combustion chamber by nearly 30%. The design of the air inlet holes and the baffle plate effectively improves the temperature uniformity at the outlet of the combustion chamber. Moreover, without changing the combustion chamber material, the corresponding engine weight can be reduced by about 10.7%, and the engine thrust-to-weight ratio can be improved by up to 12% with the same thrust, which provides design ideas for further lightweight applications.

Comparison of patient-controlled analgesia and sedation (PCAS) with remifentanil and propofol versus total intravenous anesthesia (TIVA) with midazolam, fentanyl, and propofol for colonoscopy.

BACKGROUND: Colonoscopy is a commonly performed gastroenterological procedure in patients associated with anxiety and pain. Various approaches have been used to provide sedation and analgesia during colonoscopy, including patient-controlled analgesia and sedation (PCAS). This study aims to evaluate the feasibility and efficiency of PCAS administered with propofol and remifentanil for colonoscopy. METHODS: This randomized controlled trial was performed in an authorized and approved endoscopy center. A total of 80 outpatients were recruited for the colonoscopy studies. Patients were randomly allocated into PCAS and total intravenous anesthesia (TIVA) groups. In the PCAS group, the dose of 0.1 ml/kg/min of the mixture was injected after an initial bolus of 3 ml mixture (1 ml containing 3 mg of propofol and 10 µg of remifentanil). Each 1 ml of bolus was delivered with a lockout time of 1 min. In the TIVA group, patients were administered fentanyl 1 µg/kg, midazolam 0.02 mg/kg, and propofol (dosage titrated). Cardiorespiratory parameters and auditory evoked response index were continuously monitored during the procedure. The recovery from anesthesia was assessed using the Aldrete scale and the Observer's Assessment of Alertness/Sedation Scale. The Visual Analogue Scale was used to assess the satisfaction of patients and endoscopists. RESULTS: No statistical differences were observed in the Visual Analogue Scale scores of the patients (9.58 vs 9.50) and the endoscopist (9.43 vs 9.30). A significant decline in the mean arterial blood pressure, heart rate, and auditory evoked response index parameters was recorded in the TIVA group (P < 0.05). The recovery time was significantly shorter in the PCAS group than in the TIVA group (P = 0.00). CONCLUSION: The combination of remifentanil and propofol could provide sufficient analgesia, better hemodynamic stability, lighter sedation, and faster recovery in the PCAS group of patients compared with the TIVA group.

CCR5 antagonist TD-0680 uses a novel mechanism for enhanced potency against HIV-1 entry, cell-mediated infection, and a resistant variant.

Regardless of the route of transmission, R5-tropic HIV-1 predominates early in infection, rendering C-C chemokine receptor type 5 (CCR5) antagonists as attractive agents not only for antiretroviral therapy but also for prevention. Here, we report the specificity, potency, and underlying mechanism of action of a novel small molecule CCR5 antagonist, TD-0680. TD-0680 displayed the greatest potency against a diverse group of R5-tropic HIV-1 and SIV strains when compared with its prodrug, TD-0232, the Food and Drug Administration-approved CCR5 antagonist Maraviroc, and TAK-779, with EC(50) values in the subnanomolar range (0.09-2.29 nm). Importantly, TD-0680 was equally potent at blocking envelope-mediated cell-cell fusion and cell-mediated viral transmission as well as the replication of a TAK-779/Maraviroc-resistant HIV-1 variant. Interestingly, TD-0232 and TD-0680 functioned differently despite binding to a similar transmembrane pocket of CCR5. Site-directed mutagenesis, drug combination, and antibody blocking assays identified a novel mechanism of action of TD-0680. In addition to binding to the transmembrane pocket, the unique exo configuration of this molecule protrudes and sterically blocks access to the extracellular loop 2 (ECL2) region of CCR5, thereby interrupting the interaction between virus and its co-receptor more effectively. This mechanism of action was supported by the observations of similar TD-0680 potency against CD4-dependent and -independent SIV strains and by molecular docking analysis using a CCR5 model. TD-0680, therefore, merits development as an anti-HIV-1 agent for therapeutic purposes and/or as a topical microbicide for the prevention of sexual transmission of R5-tropic HIV-1.

Optimization of injection molding process parameters for the lining of IV hydrogen storage cylinder.

The hydrogen storage cylinder lining was taken as the research object. The injection model of the cylinder liner was developed employing 3D software, a two-cavity injection molding system was built, and Moldflow was utilized for analysis to determine the best combination of injection molding process parameters. The effects of injection process parameters (melt temperature, mold temperature, holding pressure, holding time and cooling time) on the evaluation index were analyzed by orthogonal experiment L16(45). The prediction data of IV hydrogen storage cylinder lining under different parameters were obtained by the range analysis method. The multi-objective optimization problem of injection molding process was transformed into a single-objective optimization problem by using the grey correlation analysis method. The optimal parameters such as melt temperature 270 °C, mold temperature 80 °C, packing pressure 55 MPa, packing time 20 s and cooling time 13 s were obtained. Taguchi method was adopted to obtain SNR (signal-to-noise ratio), while range and variance methods were used for analysis. The results showed that warpage was 0.4892 mm, the volume shrinkage was 12.31%, the residual stress in the first direction was 98.13 MPa, and the residual stress in the second direction was 108.1 MPa. The comprehensive index was simultaneously most impacted by the melt temperature.

Prediction and Verification of Performance and Emission Characteristics of Diesel/Natural Gas Dual-Fuel Engine Based on Intelligent Algorithm.

With the development of computer application technologies, intelligent algorithm has been widely used in various fields. In this study, a coupled Gaussian process regression and feedback neural network (GPR-FNN) algorithm is proposed, and it is used to predict the performance and emission characteristics of a six-cylinder heavy-duty diesel/natural gas (NG) dual-fuel engine. Using the engine speed, torque, NG substitution rate, diesel injection pressure, and injection timing as inputs, an GPR-FNN model is established to predict the crank angle corresponding to 50% heat release, brake-specific fuel consumption, brake thermal efficiency, and carbon monoxide, carbon dioxide, total unburned hydrocarbon, nitrogen oxides, and soot emissions. Subsequently, its performance is evaluated using experimental results. The results show that the regression correlation coefficients of all output parameters are greater than 0.99, and the mean absolute percentage error is less than 5.9%. In addition, a contour plot is used to compare the experimental results with the GPR-FNN prediction data in detail, and the results show that the prediction model has high accuracy. The results of this study can provide new ideas for the research on diesel/natural gas dual-fuel engines.

Experimental Study of Curing Temperature Effect on Mechanical Performance of Carbon Fiber Composites with Application to Filament Winding Pressure Vessel Design.

During the forming process of carbon fiber composite pressure vessels, the parameters of the curing and forming processes become one of the critical factors affecting the production cost and forming quality. The curing temperature of 4251 A4/B2 epoxy resin is measured in this research, and the effect of curing temperature on the mechanical properties of composite materials for winding is studied, which is finally verified in the test of pressure vessels. First, the actual curing temperature of the epoxy resin is tested and analyzed using differential scanning calorimetry (DSC). Second, under two different curing regimes, the tensile and flexural properties are tested by making pure epoxy resin matrix test pieces, Naval Ordnance Laboratory (NOL) rings, and carbon fiber composite unidirectional plates that affect the overall performance of composite pressure vessels. At the same time, the test results provide reliable process parameters for numerical simulation and manufacturing of pressure vessels. Finally, the filament-wound 35 MPa type III pressure vessel is cured and carried out using a hydraulic burst test. The results show the resin matrix has good fluidity and excellent interface bonding with carbon fiber when the curing temperature is 112 °C. Compared with the results in curing temperature of 100 °C, the tensile strength of the NOL ring reaches 2260.8 MPa, up by 22%. In the 90° direction, the tensile and flexural strengths of the unidirectional plates increase by 68.86% and 37.42%, respectively. In the 0° direction, the tensile and flexural strengths of the unidirectional plates increase by 5.82% and 1.16%, respectively. The pressure vessel bursting form is reasonable and meets the CGH2R standard. The bursting pressure of the vessel is up to 104.4 MPa, which verifies the rationality of the curing regime used in the curing process of the pressure vessel. Based on the results of this paper, the curing temperature affects the fluidity of the epoxy resin, which in turn affects the interfacial bonding properties of the composite, and the forming quality of the wound components and the pressure vessel, ultimately. When using 4251A4/B2 epoxy resin for wet winding pressure vessels, the choice of a 112 °C curing temperature will help improve the vessel's overall performance. This work could provide reliable experience and insight into the curing process analysis of pressure vessel manufacturing.

Association of beta-2-microglobulin, cystatin C and lipocalin-2 with stroke risk in the general Chinese population.

INTRODUCTION: Beta-2-microglobulin (B2M), cystatin C and lipocalin-2 (LCN-2) are established renal biomarkers, yet their roles in stroke have not been fully evaluated. We aimed to investigate the relationship of B2M, cystatin C, and LCN-2 with stroke risk in a general Chinese population. METHODS: We used ordinal regression to study the relationship between serum B2M, cystatin C, and LCN-2 with stroke risk in 1060 participants (mean age 45.4 ± 10.8 years, 46% male) from the Shenzhen-Hong Kong United Network on Cardiovascular Disease (SHUN-CVD) study. Stroke risk was classified into low-risk, middle-risk and high-risk groups according to the China National Stroke Screening Survey criteria. Serum biomarker levels were measured using immunoturbidimetric assays. Participants with valid data on serum biomarker levels and stroke risk were included in the analysis. RESULTS: The number of participants in the low-risk, middle-risk and high-risk stroke risk groups were 663, 143 and 254 respectively. Elevated serum B2M, cystatin C, and LCN-2 levels were associated with being male, overweight/obesity, hypertension, alcohol consumption and smoking. Serum B2M, cystatin C and LCN-2 levels were significantly associated with stroke risk in the overall population (B2M: ß = 0.595, p < .001; cystatin C: ß = 3.718, p < .001; LCN-2: ß = 0.564, p < .001) after adjustment for age. CONCLUSION: Elevated serum B2M, cystatin C and LCN-2 levels are associated with stroke risk. They may be novel biomarkers for clinicians to assess stroke risk.Key messagesSerum beta-2-microglobulin, cystatin C and lipocalin-2 levels are significantly associated with stroke risk.Beta-2-microglobulin, cystatin C and lipocalin-2 may serve as useful biomarkers for stroke risk stratification in the general population.

A Multiscale Study of CFRP Based on Asymptotic Homogenization with Application to Mechanical Analysis of Composite Pressure Vessels.

The application of composites is increasingly extensive due to their advanced properties while the analysis still remains complex on different scales. In this article, carbon fiber reinforced polymer (CFRP) is modeled via asymptotic homogenization employing a representative volume element (RVE) with periodic boundary conditions. A multiscale mechanical model of CFRP is established to bridge the microscopic model, mesoscopic model, and macroscopic model. According to asymptotic homogenization, the coefficients of the material constitutive equation are calculated with volume-averaged stress and strain. Using the homogenized materials properties of CFRP, the tensile experiments of composite layers with the layout of [(0∘/60∘/0∘/-60∘)4] are carried out to validate asymptotic homogenization method. The results indicated that the asymptotic homogenization approach can be used to calculate the homogenized elastic moduli and Poisson's ratio of the whole structure, where the numerical results are basically consistent with test data. The sequent homogenized CFRP laminate model is applied to the mechanical analysis of type III composite pressure vessels, whereby burst pressure is accurately predicted. This work might shed some light on multiscale analysis of composite pressure vessels.

Facile Synthesis of 4,4'-biphenyl Dicarboxylic Acid-Based Nickel Metal Organic Frameworks with a Tunable Pore Size towards High-Performance Supercapacitors.

Metal-organic frameworks (MOFs) have attracted significant research interest for supercapacitor applications due to their high-tunable conductivity and their structure's pore size. In this work, we report a facile one-step hydrothermal method to synthesize nickel-based metal-organic frameworks (MOF) using organic linker 4,4'-biphenyl dicarboxylic acid (BPDC) for high-performance supercapacitors. The pore size of the Ni-BPDC-MOF nanostructure is tuned through different synthesization temperatures. Among them, the sample synthesized at 180 °C exhibits a nanoplate morphology with a specific surface area of 311.99 m2·g-1, a pore size distribution of 1-40 nm and an average diameter of ~29.2 nm. A high specific capacitance of 488 F·g-1 has been obtained at a current density of 1.0 A·g-1 in a 3 M KOH aqueous electrolyte. The electrode shows reliable cycling stability, with 85% retention after 2000 cycles. The hydrothermal process Ni-BPDC-MOF may provide a simple and efficient method to synthesize high-performance hybrid MOF composites for future electrochemical energy storage applications.

Flexible Piezoelectric and Pyroelectric Nanogenerators Based on PAN/TMAB Nanocomposite Fiber Mats for Self-Power Multifunctional Sensors.

Self-powered wearable electronics to convert mechanical and thermal energy into electrical energy are important for biomedical monitoring, which highly require good flexibility, comfortability, signal sensitivity, and accuracy. In this work, composite nanofiber mats of polyacrylonitrile (PAN) and trimethylamine borane (TMAB) were prepared by electrospinning, which exhibited excellent piezoelectric and pyroelectric abilities in harvesting mechanical and thermal energy. The PAN/TMAB-4 nanofiber mats not only generated a high voltage of up to 2.56 V and a high power of 0.19 µW upon shape deformation but also exhibited linear voltage response to thermal gradient. The hybrid piezoelectric and pyroelectric output signals were successfully integrated together and have been applied to precisely monitor human vital signs, including elbow bending angles, foot posture, and breathing status, in real time by attaching the flexible sensors to proper human body parts. Overall, good flexibility, bifunctional sensing ability, and self-power make PAN-/TMAB-type sensors very attractive in fabricating high-performance electronics for detecting motion, monitoring health, and making portable microelectronics.

Field-testing of a rapid survey method to assess the prevalence and causes of hearing loss in Gao'an, Jiangxi province, China.

BACKGROUND: The Rapid Assessment of Hearing Loss (RAHL) survey protocol aims to measure the prevalence and causes of hearing loss in a low cost and rapid manner, to inform planning of ear and hearing services. This paper reports on the first field-test of the RAHL in Gao'an County, Jiangxi Province, China. This study aimed to 1) To report on the feasibility of RAHL; 2) report on the estimated prevalence and causes of hearing loss in Gao'an. METHODS: A cross-sectional population-based survey was conducted in September-October 2018. Forty-seven clusters in Gao'an County were selected using probability-proportionate-to-size sampling. Within clusters, compact segment sampling was conducted to select 30 people aged 50+. A questionnaire was completed covering sociodemographics, hearing health, and risk factors. Automated pure-tone audiometry was completed for all participants, using smartphone-based audiometry (hearTest), at 0.5, 1, 2, 4 kHz (kHz). All participants had their ears examined by an Ear Nose and Throat (ENT) doctor, using otoscopy, and probable causes of hearing loss assigned. Prevalence estimates were age and sex standardised to the Jiangxi population. Feasibility of a cluster size of 30 was examined by assessing the response rate, and the proportion of clusters completed in 1 day. RESULTS: 1344 of 1421 eligible participants completed the survey (94.6%). 100% of clusters were completed in 1 day. The survey was completed in 4.5 weeks. The prevalence of moderate or greater hearing loss (pure-tone average of 0.5, 1, 2, 4 kHz of > = 41dBHL in the better ear) was 16.3% (95% CI = 14.3, 18.5) and for any level of hearing loss (pure-tone average of > = 26dBHL in the better ear) the prevalence was 53.2% (95% CI = 49.2, 57.1). The majority of hearing loss was due to acquired sensorineural causes (91.7% left; 92.1% right). Overall 54.0% of the population aged 50+ (108,000 people) are in need of diagnostic audiology services, 3.4% were in need of wax removal (7000 people), and 4.8% were in need of surgical services (9500 people). Hearing aid coverage was 0.4%. CONCLUSION: The RAHL survey protocol is feasible, demonstrated through the number of people examined per day, and the high response rate. The survey was completed in a much shorter period than previous all-age surveys in China. Some remaining challenges included assignment of causes of probable sensorineural loss. The data obtained from this survey can be used to scale-up hearing services in Gao'an.

Persistent lentivirus infection induces early myeloid suppressor cells expansion to subvert protective memory CD8 T cell response✰,✰✰.

BACKGROUND: Memory CD8+T cell responses play an essential role in protection against persistent infection. However, HIV-1 evades vaccine-induced memory CD8+T cell response by mechanisms that are not fully understood. METHODS: We analyzed the temporal dynamics of CD8+T cell recall activity and function during EcoHIV infection in a potent PD1-based vaccine immunized immunocompetent mice. FINDINGS: Upon intraperitoneal EcoHIV infection, high levels of HIV-1 GAG-specific CD8+T lymphocytes recall response reduced EcoHIV-infected cells significantly. However, this protective effect diminished quickly after seven days, followed by a rapid reduction of GAG-specific CD8+T cell number and activity, and viral persistence. Mechanistically, EcoHIV activated dendritic cells (DCs) and myeloid cells. Myeloid cells were infected and rapidly expanded, exhibiting elevated PD-L1/-L2 expression and T cell suppressive function before day 7, and were resistant to CD8+T cell-mediated apoptosis. Depletion of myeloid-derived suppressor cells (MDSCs) reduced EcoHIV infection and boosted T cell responses. INTERPRETATION: This study provides an overview of the temporal interplay of persistent virus, DCs, MDSCs and antigen-specific CD8+T cells during acute infection. We identify MDSCs as critical gatekeepers that restrain antiviral T cell memory responses, and highlight MDSCs as an important target for developing effective vaccines against chronic human infections. FUNDING: Hong Kong Research Grant Council (T11-709/18-N, HKU5/CRF/13G), General Research Fund (17122915 and 17114114), Hong Kong Health and Medical Research Fund (11100752, 14130582, 16150662), Grant RGC-ANR A-HKU709/14, the San-Ming Project of Medicine (SZSM201512029), University Development Fund of the University of Hong Kong and Li Ka Shing Faculty of Medicine Matching Fund to HKU AIDS Institute.

The first antimicrobial peptide from sea amphibian.

The crab-eating frog, Rana cancrivora, is one of only a handful of amphibians worldwide that tolerates saline waters. It typically inhabits brackish water of mangrove forests of Southeast Asia. A large amount of antimicrobial peptides belonging to different families have been identified from skins of amphibians inhabiting freshwater. No antimicrobial peptide from sea amphibians has been reported. In this paper, we firstly reported the antimicrobial peptide and its cDNA cloning from skin secretions of the crab-eating frog R. cancrivora. The antimicrobial peptide was named cancrin with an amino acid sequence of GSAQPYKQLHKVVNWDPYG. By BLAST search, cancrin had no significant similarity to any known peptides. The cDNA encoding cancrin was cloned from the cDNA library of the skin of R. cancrivora. The cancrin precursor is composed of 68 amino acid residues including a signal peptide, acidic spacer peptide, which are similar to other antimicrobial peptide precursors from Ranid amphibians and mature cancrin. The overall structure is similar to other amphibian antimicrobial peptide precursors although mature cancrin is different from known peptides. The current results reported a new family of amphibian antimicrobial peptide and the first antimicrobial peptide from sea amphibian.

In vivo electroporation of a codon-optimized BERopt DNA vaccine protects mice from pathogenic Mycobacterium tuberculosis aerosol challenge.

DNA vaccines have been extensively studied as preventative and therapeutic interventions for various infectious diseases such as tuberculosis, HIV/AIDS and influenza. Despite promising progresses made, improving the immunogenicity of DNA vaccine remains a technical challenge for clinical development. In this study, we investigated a tuberculosis DNA vaccine BERopt, which contained a codon-optimized fusion immunogen Ag85B-ESAT-6-Rv2660c for enhanced mammalian cell expression and immunogenicity. BERopt immunization through in vivo electroporation in BALB/c mice induced surprisingly high frequencies of Ag85B tetramer+ CD8+ T cells in peripheral blood and IFN-γ-secreting CD8+ T cells in splenocytes. Meanwhile, the BERopt vaccine-induced long-lasting T cell immunity protected BALB/c mice from high dose viral challenge using a modified vaccinia virus Tiantan strain expressing mature Ag85B protein (MVTT-m85B) and the virulent M. tb H37Rv aerosol challenge. Since the BERopt DNA vaccine does not induce anti-vector immunity, the strong immunogenicity and protective efficacy of this novel DNA vaccine warrant its future development for M. tb prevention and immunotherapy to alleviate the global TB burden.

A bactericidal homodimeric phospholipases A2 from Bungarus fasciatus venom.

Group IIA secretory phospholipases A(2) (sPLA(2)-II) is generally known to display potent gram-positive bactericidal activity, while group IA sPLA(2) (sPLA(2)-I) reportedly is not. In this work, a novel sPLA(2)-I named BFPA was identified from Bungarus fasciatus venom, and its antimicrobial activity was studied as well. The amino acid sequence of the venomous protein precursor was 145-amino acid in length, and contained a predicted 27-amino acid signal peptide and a 118-amino acid mature protein. Unlike the well-known sPLA(2)-Is, which have 14 half-cysteines forming 7 intramolecular disulfide bridges, BFPA possesses 15 half-cysteines. The additional cysteine might contribute to the formation of an intermolecular disulfide bridge of the homodimeric protein. In the biological activities assays, BFPA displayed the activities of anticoagulation and bactericidal against Escherichia coli and Staphylococcus aureus. This study is the first report about gram-positive bactericidal activity of sPLA(2)-I.