A novel adaptive filter with a heart-rate-based reference signal for esophageal pressure signal denoising.

Esophageal pressure (Peso) is one of the most common and minimally invasive methods used to assess the respiratory and lung mechanics in patients receiving mechanical ventilation. However, the Peso measurement is contaminated by cardiogenic oscillations (CGOs), which cannot be easily eliminated in real-time. The field of study dealing with the elimination of CGO from Peso signals is still in the early stages of its development. In this study, we present an adaptive filtering-based method by constructing a reference signal based on the heart rate and sine function to remove CGOs in real-time. The proposed technique is tested using clinical data acquired from 20 patients admitted to the intensive care unit. Lung compliance ( QUOTE ) and esophageal pressure swings (△Pes) are used to evaluate the performance and efficiency of the proposed technique. The CGO can be efficiently suppressed when the constructional reference signal contains the fundamental, and second and third harmonic frequencies of the heart rate signal. The analysis of the data of 8 patients with controlled mechanical ventilation reveals that the standard deviation/mean of the QUOTE is reduced by 28.4-79.2% without changing the QUOTE and the △Pes measurement is more accurate, with the use of our proposed technique. The proposed technique can effectively eliminate the CGOs from the measured Peso signals in real-time without requiring additional equipment to collect the reference signal.

Therapy of paraneoplastic pemphigus with Rituximab: A case report.

We report a case of 39-year-old female patient with paraneoplastic pemphigus (PNP) associated with thymoma treated with rituximab plus corticosteroids and methotrexate. After rituximab therapy for 8 weeks, oral ulcerations had cured, lesions on the trunk and limbs improved. Rituximab may be useful for PNP therapy, but further studies are necessary to confirm this hypothesis.

Tazarotene/Betamethasone Dipropionate Cream in Patients with Plaque Psoriasis: Results of a Prospective, Multicenter, Observational Study.

BACKGROUND: Topical agents are still the mainstay for the treatment of mild-to-moderate plaque psoriasis, in which fixed combinations play an important role. Tazarotene/betamethasone dipropionate (Taz/BD) cream is a novel fixed combination approved for treating plaque psoriasis in China, but its efficacy and safety have not been verified in a real-world environment. OBJECTIVES: The primary objective was to investigate the efficacy and safety of Taz/BD cream in treating plaque psoriasis. The secondary objectives were to assess its relapse after discontinuation and the efficacy and safety profiles during retreatment. METHODS: A prospective, multicenter, large-scale observational study was conducted. Adult patients with chronic plaque psoriasis involving <20% of the body surface area were enrolled. Taz/BD cream was applied once daily for 4 weeks. Patients who achieved ≥90% improvement in the Psoriasis Area and Severity Index (PASI) from baseline to week 4 were followed up to investigate relapse after drug withdrawal. Relapsed patients underwent another 4-week treatment. RESULTS: In total, 2,299 eligible patients were enrolled, and 2,095 patients (91.1%) completed the 4-week study. The mean PASI improvement at week 4 was 53.7%, and the PASI 50/75 response rates were 62.5 and 26.8%, respectively. The mean PASI reduction in plaque induration, desquamation and erythema were 58.3, 61.0 and 40.0%, respectively (p < 0.001). Adverse reactions occurred in 445 patients (20.8%) at week 4. The most frequently reported adverse reactions were local skin irritation, including pruritus (10%), pain (6.7%), erythema (6.1%) and desquamation (1.8%). During the post-treatment period, 47 patients (24.0%) relapsed within 8 weeks after drug discontinuation. Forty-five patients were retreated for another 4 weeks, and the PASI 50/75 response rates were 72.7 and 40.9%, respectively. There were no unexpected safety signals during retreatment. CONCLUSION: Taz/BD cream is effective and well tolerated in treating mild-to-moderate plaque psoriasis under near real-world conditions and demonstrates efficacy and safety during retreatment.

hsa_circ_0006916 promotes hepatocellular carcinoma progression by activating the miR-337-3p/STAT3 axis.

BACKGROUND: Circular RNAs (circRNAs) are thought to be involved in the development of various malignancies. The expression and function of hsa_circ_0006916, a newly identified circRNA, in hepatocellular carcinoma remain unclear. METHODS: Quantitative RT-PCR was used to detect hsa_circ_0006916 in hepatocellular carcinoma. In vitro function assays were conducted to explore growth and invasion of hepatocellular carcinoma cells. Next, the mechanism of hsa_circ_0006916 function in hepatocellular carcinoma was determined by luciferase reporter and RIP assays. RESULTS: Hsa_circ_0006916 was substantially overexpressed in hepatocellular carcinoma tissues and cells. High levels of hsa_circ_0006916 in hepatocellular carcinoma patients were associated with advanced clinical characteristics. Down-regulation of hsa_circ_0006916 decreased the growth and invasion of hepatocellular carcinoma cells in vitro. The results suggested that hsa_circ_0006916 acted as a sponge of miR-337-3p and had an important functional use in the regulation of STAT3 levels in hepatocellular carcinoma cells. Moreover, miR-337-3p inhibition or STAT3 overexpression abolished the effect of hsa_circ_0006916 suppression on the progression of hepatocellular carcinoma cells. CONCLUSIONS: Our data suggest a novel hsa_circ_0006916/miR-337-3p/STAT3 axis in hepatocellular carcinoma, and provide a new target for treatment.

Development of a model to simulate soil heavy metals lateral migration quantity based on SWAT in Huanjiang watershed, China.

Lateral transportation of soil heavy metals in rainfall events could significantly increase the scope of pollution. Therefore, it is necessary to develop a model with high accuracy to simulate the migration quantity of heavy metals. A model for heavy metal migration simulation was developed based on the SWAT (Soil and Water Assessment Tool) model. This model took into consideration the influence of soil pH value, soil particle size, runoff volume, sediment amount, concentration of water-soluble heavy metals dissolved in runoff and insoluble absorbed to the soil particles. This model was reasonable in Huanjiang watershed, Guangxi Zhuang Autonomous Region, south China, covering an area of 273 km2. The optimal drainage area threshold was determined by analyzing the effects of watershed subdivision on the simulation results to ensure the simulation accuracy. The main conclusions of this paper were: (1) watershed subdivision could affect simulation migration quantity of heavy metals; (2) the quantity of heavy metals transported by sediment accounted for 97%-99% of the total migration quantity in the study watershed. Therefore, sediment played the most important role in heavy metal migration; (3) the optimal drainage area threshold percentage to ensure high simulation accuracy was determined to be 2.01% of the total watershed; (4) with the optimal threshold percentage, this model could simulate the migration quantity of As, Pb and Cd accurately at the total watershed and sub-watershed level. The results of this paper were useful for identifying the key regions with heavy metal migration.

Scoring systems used to predict mortality in patients with acute upper gastrointestinal bleeding in the ED.

OBJECTIVE: Acute upper gastrointestinal bleeding (UGIB) is a potentially life-threatening condition that requires rapid assessment in the emergency department (ED). We aimed to compare the performance of the AIMS65, Glasgow-Blatchford (Blatchford), preendoscopic Rockall (pre-Rockall), and preendoscopic Baylor bleeding (pre-Baylor) scores in predicting 30-day mortality in patients with acute UGIB in the ED setting. METHODS: Consecutive patients with acute UGIB who were admitted to the ED ward during 2012-2016 were retrospectively recruited. Data were retrieved from the admission list of the ED using international classification of disease codes via computer registration. The predictive accuracy of these four scores was compared using the area under the receiver operating characteristic curve (AUC) method. RESULTS: Among the 395 patients included during the study period, the total 30-day mortality rate was 10.4% (41/395). The AIMS65 and Glasgow-Blatchford scores performed better with an AUC of 0.907 (95% confidence interval (CI), 0.852-0.963; P<0.001) and 0.870 (95% confidence interval, 0.833-0.902; P<0.001) compared with other scoring systems (preendoscopic Rockall score: AUC, 0.709; 95% CI, 0.635-0.784; P<0.001; preendoscopic Baylor score: AUC, 0.523; 95% CI, 0.472-0.573; P>0.05). CONCLUSION: In patients with acute UGIB in the ED, the AIMS65 and Glasgow-Blatchford scores are clinically more useful for predicting 30-day mortality than the preendoscopic Rockall and preendoscopic Baylor scores. The AIMS65 score might be more ideal for risk stratification in the ED setting.

Interaction between sulfur and lead in toxicity, iron plaque formation and lead accumulation in rice plant.

Human activities have resulted in lead and sulfur accumulation in paddy soils in parts of southern China. A combined soil-sand pot experiment was conducted to investigate the influence of S supply on iron plaque formation and Pb accumulation in rice (Oryza sativa L.) under two Pb levels (0 and 600 mg kg(-1)), combined with four S concentrations (0, 30, 60, and 120 mg kg(-1)). Results showed that S supply significantly decreased Pb accumulation in straw and grains of rice. This result may be attributed to the enhancement of Fe plaque formation, decrease of Pb availability in soil, and increase of reduced glutathione (GSH) in rice leaves. Moderate S supply (30 mg kg(-1)) significantly increased Fe plaque formation on the root surface and in the rhizosphere, whereas excessive S supply (60 and 120 mg kg(-1)) significantly decreased the amounts of iron plaque on the root surface. Sulfur supply significantly enhanced the GSH contents in leaves of rice plants under Pb treatment. With excessive S application, the rice root acted as a more effective barrier to Pb accumulation compared with iron plaque. Excessive S supply may result in a higher monosulfide toxicity and decreased iron plaque formation on the root surface during flooded conditions. However, excessive S supply could effectively decrease Pb availability in soils and reduce Pb accumulation in rice plants.

Hyperactivity and impaired attention in Gamma aminobutyric acid transporter subtype 1 gene knockout mice.

OBJECTIVES: Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder. It is conceivable that Gamma aminobutyric acid (GABA) neurotransmission is implicated in the pathophysiology of ADHD. This study investigated the effect of GABA transporter 1 (GAT-1) on the anxiety-like behaviours and cognitive function in knockout mice. METHODS: In all, 20 adult male mice were divided into two groups: wild-type (WT) group and GAT-1-/- group. The open field test, elevated O-maze (EZM) and Morris water maze were used to evaluate behavioural traits relevant to ADHD. RESULTS: Compared with WT mice, the GAT-1-/- mice travelled longer and displayed an enhanced kinematic velocity with the significant reduction of rest time in the open field test (p<0.05). The EZM showed that GAT-1-/- mice displayed a significant increase in total entries into the open sectors and the closed sectors compared with the WT mice. The WT mice showed shorter latencies after the training session (p<0.01), whereas the GAT-1-/- mice made no difference during probe test, the GAT-1-/- mice spent less time in the target quadrant (p<0.01). CONCLUSION: Our results demonstrated that GAT-1-/- mice have phenotypes of hyperactivity, impaired sustained attention and learning deficiency, and the performance of GAT-1-/- mice is similar to ADHD symptoms. So, the study of the GAT-1-/- mice may provide new insights into the mechanisms and the discovery of novel therapeutics for the treatment of ADHD.

Single-injection subunit vaccine for rabies prevention using lentinan as adjuvant.

Current rabies vaccines require 5 doses to provide full protection from the deadly virus, which significantly reduce the compliance of recipients. To minimize the number of immunizations herein single injection vaccines were developed. First a single injection vaccine was designed using rabies virus glycoprotein (G protein) as antigen. A time-controlled release system which uses dynamic layer-by-layer films as erodible coating was employed to accomplish multiply pulsatile releases of G protein. The single-injection vaccine elicits potent humoral and cellular immune responses comparable to the corresponding multi-dose ordinary vaccines because of their similar release pattern of G protein. To further improve its performance, a second single injection vaccine, in which lentinan was added as adjuvant, was designed. This single-injection vaccine again elicits humoral and cellular immune responses comparable to the corresponding multi-dose ordinary vaccines because of their similar release pattern of antigen and adjuvant. In addition, the second single-injection vaccine elicits higher level immune response and provides higher efficiency on virus inhibition than the first one because lentinan can booster immune response.

Time-series analysis of meteorological factors and emergency department visits due to dog/cat bites in Jinshan area, China.

Background: Meteorological factors play an important role in human health. Clarifying the occurrence of dog and cat bites (DCBs) under different meteorological conditions can provide key insights into the prevention of DCBs. Therefore, the objective of the study was to explore the relationship between meteorological factors and DCBs and to provide caution to avoid the incidents that may occur by DCBs. Methods: In this study, data on meteorological factors and cases of DCBs were retrospectively collected at the Shanghai Climate Center and Jinshan Hospital of Fudan University, respectively, in 2016-2020. The distributed lag non-linear and time series model (DLNM) were used to examine the effect of meteorological elements on daily hospital visits due to DCBs. Results: A total of 26,857 DCBs were collected ranging from 1 to 39 cases per day. The relationship between ambient temperature and DCBs was J-shaped. DCBs were positively correlated with daily mean temperature (rs = 0.588, P < 0.01). The relative risk (RR) of DCBs was associated with high temperature (RR = 1.450; 95% CI [1.220-1.722]). Female was more susceptible to high temperature than male. High temperature increased the risk of DCBs. Conclusions: The extremely high temperature increased the risk of injuries caused by DCBs, particularly for females. These data may help to develop public health strategies for potentially avoiding the occurrence of DCBs.

Effectiveness of Ixekizumab in Chinese Patients with Moderate-Severe Plaque Psoriasis with Special Area Involvement: Subanalysis of a Prospective, Multicenter, Observational Real-World Study.

INTRODUCTION: Ixekizumab, a monoclonal antibody against interleukin-17A, demonstrated effectiveness in the treatment of psoriasis in a Chinese real-world study that was consistent with previous randomized controlled trials. Here, we report further analyses from this study to explore the effectiveness of ixekizumab for treating patients with psoriasis and the involvement of special body areas (scalp, nail, joint, palmoplantar, or genital areas). METHODS: A multicenter, prospective, observational, single-arm, post-marketing surveillance study was conducted in patients aged ≥ 18 years with moderate-to-severe plaque psoriasis and prescribed with ixekizumab in 26 Chinese hospitals. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were compared between patients with versus without psoriasis in special body areas in the overall study population and across subgroups by body area. RESULTS: In total, 612 patients were included. At baseline, most patients (93.6%) had psoriasis involvement in at least one special body area. Overall, patients with psoriasis in special body areas reported a worse quality of life (QoL) than those without. Patients with versus without psoriasis in special body areas achieved a comparable mean reduction from baseline in PASI score (10.9 vs. 9.2 at week 2, and 16.9 vs. 14.7 at week 12, respectively) and DLQI score (6.0 vs. 4.4 at week 2, and 9.9 vs. 7.5 at week 12, respectively); a similar proportion of patients also achieved PASI 50 at week 2, and PASI 75 and PASI 90 at week 12, and a DLQI (0/1) at weeks 2 and 12. Several significantly different results were reported between subgroups, the majority of which favored patients with special body area involvement. CONCLUSION: Most patients had psoriasis involvement in a special body area which was associated with worse QoL. Ixekizumab is similarly effective in reducing disease severity and improving QoL in patients with plaque psoriasis across different special body areas.

Three cases of refractory bullous pemphigoid in the elderly treated successfully with ultra-low-dose rituximab.

Rituximab has proven effective for the treatment of steroid-refractory bullous pemphigoid (BP), but there is controversy over the dosing protocol. We report three cases of refractory BP treated successfully with ultra-low-dose rituximab (100 mg weekly for 4 weeks). Our cases confirmed the efficacy and good follow-up outcomes of this treatment strategy for refractory BP. The ultra-low-dose rituximab regimen (100 mg weekly for 4 weeks) may be a useful alternative therapy in patients with refractory BP.

Inhibition of p38 MAPK diminishes doxorubicin-induced drug resistance associated with P-glycoprotein in human leukemia K562 cells.

BACKGROUND: Several studies have shown that multidrug transporters, such as P-glycoprotein (PGP), are involved in cell resistance to chemotherapy and refractory epilepsy. The p38 mitogen-activated protein kinase (MAPK) signaling pathway may increase PGP activity. However, p38-mediated drug resistance associated with PGP is unclear. Here, we investigated p38-mediated doxorubicin-induced drug resistance in human leukemia K562 cells. MATERIAL/METHODS: The expression of PGP was detected by RT-PCR, Western blot, and immunocytochemistry. Cell viability and half-inhibitory concentrations (IC50) were determined by CCK-8 assay. The intracellular concentration of drugs was measured by HPLC. RESULTS: A doxorubicin-induced PGP overexpression cell line, K562/Dox, was generated. The p38 inhibitor SB202190 significantly decreased MDR1 mRNA expression, as well as PGP, in K562/Dox cells. The IC50 of phenytoin sodium and doxorubicin in K562/Dox cells was significantly higher than that in wild-type K562 cells, indicating the drug resistance of K562/Dox cells. During the blocking of p38 activity in the presence of SB202190, cell number was significantly reduced after the phenytoin sodium and doxorubicin treatment, and the IC50 of phenytoin sodium and doxorubicin was decreased in K562/Dox cells. HPLC showed that the intracellular levels of phenytoin sodium and doxorubicin were significantly lower in K562/Dox cells than those in K562 cells. The decrease of the intracellular level of these drugs was significantly abolished in the presence of SB202190. CONCLUSIONS: Our study demonstrated that p38 is, at least in part, involved in doxorubicin-induced drug resistance. The mechanistic study of MAPK-mediated PGP and the action of SB202190 need further investigation.

Can second language metaphorical competence be taught through instructional intervention? A meta-analysis.

Background: For a long time, the traditional view regarded metaphor as merely a rhetorical device that served to enrich linguistic expression. With the continuous development of cognitive linguistics, foreign language educators began to realize the vital role of metaphor in foreign language education. Objectives: This study looked at how well pedagogical interventions improve metaphorical competence by looking at how well teachers teach metaphors. Methods: After a rigorous literature search and selection process from the Chinese and English databases, 13 Chinese and 7 international studies with 51 effect sizes were included in this meta-analysis. With the help of the meta-analysis 3.0 software, the literature and heterogeneity tests were performed to ensure that the meta-analysis results were as accurate and valid as possible. Results: The effect size tests revealed that the metaphorical instructional intervention was significantly effective in general and produced a large effect size (d = 0.888) on improving learners' metaphorical abilities. Meta-regression analyses were also conducted to examine how other factors might change the effects of the interventions. Findings: Research has shown that instructional interventions that combine prolonged input of metaphorical concepts with reinforcement of metaphorical practice can help second language learners develop metaphorical competence. Teaching puts more pressure on teachers and the learning environment, and the results of this study could help teachers teach metaphors in the future.

Asiaticoside delays senescence and attenuate generation of ROS in UV­exposure cells through regulates TGF­ß1/Smad pathway.

Asiaticoside, isolated from Centella asiatica, shows great improvement on wound healing and anti-oxidation function in vitro and in vivo. From previous research, asiaticoside possesses the potential capability to delay skin aging and reduce wrinkles clinically, but its underlying mechanism to regulate aging have not well-investigated. The present study found that asiaticoside could improve the viability and maintains a normal morphology in ultraviolet (UV)-exposure cells. In addition, ß-galactosidase release was inhibited by treatment of asiaticoside in UV damaged cells was observed. The present study confirmed that UV-induced ROS generation and SOD reduction could be attenuated by incubation of asiaticoside. By using RNA sequencing technology, differential genes between UV and asiaticoside treatment were demonstrated and enriched genes suggested that asiaticoside is able to negatively regulate cell cycle and MAPK pathways. Western blotting was employed to clarify the variation of key proteins in TGF-ß1/Smad pathway and cell cycle and the result implied that asiaticoside is capable of attenuating upregulation of TGF-ß1, Smad2 and Smad3 to reverse cell senescence. The present study investigated regulation of asiaticoside to TGF-ß1/Smad pathway in UV-induced HaCat cells, showing its potential to against photoaging.

Anthracene dimer cross-linked, washing- and sterilization-free hydrogel films for multicellular spheroid generation.

Three-dimensional multicellular spheroids are better in vitro cell models than two-dimensional cell monolayers; however, their applications are limited by their difficult production. PHEMA hydrogel films with honeycomb-like wrinkled patterns have been developed for high-throughput generation of multicellular spheroids with a uniform shape and size; however, the films are prepared by polymerization of the HEMA monomer, and should be washed extensively before use. Here to synthesize washing-free PHEMA hydrogel films, linear anthracene-functionalized PHEMA polymers were first synthesized by the free-radical copolymerization of HEMA and an anthracene-containing vinyl monomer. Smooth films were then prepared from the linear polymers in the wells of cell culture plates by solution casting. They were cross-linked via photo-dimerization of anthracene groups by exposing to 365 nm UV light, and patterned spontaneously by adding water to swell them. The swelling degree of the films and hence the shape of the wrinkled patterns could be facilely adjusted by adjusting the anthracene content in the linear polymers. If necessary, the cross-link density of the film and thus the shape of the wrinkled patterns could be callbacked by irradiating with 254 nm UV light, thanks to the reversibility of the photo-dimerization of anthracene. The as-prepared films exhibit a high biocompatibility and support cell growth well even without washing and sterilization. The high biocompatibility is attributed to the facts that no low molecular weight monomer, crosslinker and initiator were involved in the film preparation, and the photo-dimerization of anthracene groups produces no by-products. The films are sterilized simultaneously when cross-linked with UV irradiation, thus avoiding an additional sterilization step. PHEMA films with long-range ordered hexagonal wrinkled patterns were selected to generate multicellular spheroids of tumor cell lines. The resulting spheroids exhibit a narrow size distribution and high cell viability. Preliminary tests demonstrated their potential in the screening of anti-cancer drugs.

COVID-19, students satisfaction about e-learning and academic achievement: Mediating analysis of online influencing factors.

Background: The current study examines student satisfaction with e-learning, the adaption of online learning channels, digital competency of students' involvement, and academic achievement during COVID-19. Purpose: The purpose of this study is to examine the online influencing components for learning among University students in Pakistan during the COVID-19 Pandemic. Methods: The study population comprised Pakistani University students in Punjab province who tooke online lessons throughout the epidemic. In accordance with the study's purpose, a questionnaire survey was employed to gather primary data. SPSS-23 is used for analyzing the demographic data, and cleaning and preparing data for testing hypotheses. SmartPLS 3.0 was used to investigate the suggested study framework using structural equation modeling (SEM). Results: The analysis of the SEM model shows that all planned hypotheses (Adaptation of Online Education Channels -> Satisfaction about E-learning, COVID-19 Pandemic -> Adaptation of Online Education Channels, COVID-19 Pandemic -> Digital Competence, COVID-19 Pandemic -> Motivation for Online Learning, COVID-19 Pandemic -> Willingness for Online Learning, Digital Competence -> Satisfaction about E-learning, Motivation for Online Learning -> Satisfaction about E-learning, Satisfaction about E-learning -> Academic Achievement, Willingness for Online Learning -> Satisfaction about E-learning) are confirmed. Conclusion: The results linked e-learning satisfaction to academic success and Pakistani students who utilized e-learning throughout the outbreak reported higher levels of academic satisfaction and achievement.

Carbon-economic inequality in global ICT trade.

The expansion of information and communications technology (ICT) trade has contributed to rising trade imbalances and international tensions. A detailed assessment of the potential carbon and economic impacts of ICT trade is pertinent. We assess to what extent and how the carbon costs and economic benefits embodied in ICT trade were unevenly distributed among global regions in the period 2000-2018 using multiregional input-output models. We show that in 2018, emerging economies received 82% of the CO2 emissions while developed economies gained 42% of the value-added in ICT exports. This carbon-economic inequality (CEI) decreased (i.e., improved) by 16% from 2000 to 2018, arising from global production fragmentation, with developed economies retaining downstream high value-added ICT marketing but outsourcing upper- and middle-stream carbon-intensive material extraction and manufacturing to emerging economies. This study provides insights for enhancing negotiations and cooperation among global regions to light a path toward sustainable ICT trade.

Single-injection COVID-19 subunit vaccine elicits potent immune responses.

Current vaccination schedules, including COVID-19 vaccines, require multiple doses to be administered. Single injection vaccines eliciting equivalent immune response are highly desirable. Unfortunately because unconventional release kinetics are difficult to achieve it still remains a huge challenge. Herein a single-injection COVID-19 vaccine was designed using a highly programmable release system based on dynamic layer-by-layer (LBL) films. The antigen, S1 subunit of SARS-CoV-2 spike protein, was loaded in CaCO3 microspheres, which were further coated with tannic acid (TA)/polyethylene glycol (PEG) LBL films. The single-injection vaccine was obtained by mixing the microspheres coated with different thickness of TA/PEG films. Because of the unique constant-rate erosion behavior of the TA/PEG coatings, this system allows for distinct multiple pulsatile release of antigen, closely mimicking the release profile of antigen in conventional multiple dose vaccines. Immunization with the single injection vaccine induces potent and persistent S1-specific humoral and cellular immune responses in mice. The sera from the vaccinated animal exhibit robust in vitro viral neutralization ability. More importantly, the immune response and viral inhibition induced by the single injection vaccine are as strong as that induced by the corresponding multiple dose vaccine, because they share the same antigen release profile. STATEMENT OF SIGNIFICANCE: Vaccines are the most powerful and cost-effective weapons against infectious diseases such as COVID-19. However, current vaccination schedules, including the COVID-19 vaccines, require multiple doses to be administered. Herein a single-injection COVID-19 vaccine is designed using a highly programmable release system. This vaccine releases antigens in a pulsatile manner, closely mimicking the release pattern of antigens in conventional multiple dose vaccines. As a result, one single injection of the new vaccine induces an immune response and viral inhibition similar to that induced by the corresponding multiple-dose vaccine approach.

Construction of single-injection vaccine using new time-controlled release system.

Single-injection vaccines may overcome issues, such as high cost and poor patient compliance, of the multi-bolus regimes dominantly used in vaccination. However no such vaccine has been commercialized because time-controlled release, an unconventional release kinetics, is difficult to achieve. Here a new time-controlled release system using dynamic layer-by-layer (LBL) film as erodible coating was used to design single-injection vaccine. Unlike commonly used degradable polymers, dynamic LBL film disintegrates at a constant rate, thus allowing distinct pulsatile release of antigen at predetermined intervals. The release pattern of the single-injection vaccine mimics closely to that of ordinary multi-dose regimes. It elicits both humoral and cellular immune responses which are comparable to or even stronger than the corresponding multi-dose regime. In addition, it inhibits tumor growth more effectively. The new vaccine will not only improve patient compliance but also therapeutic outcome.