A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice.

Innate immune cells are critical in antitumor immune surveillance and the development of antitumor adaptive cellular immunity. Trained innate immune cells demonstrate immune memory-like characteristics, producing more vigorous immune responses to secondary homologous or heterologous stimuli. This study aimed to investigate whether inducing trained immunity is beneficial when using a tumor vaccine to promote antitumor adaptive immune responses. A biphasic delivery system was developed with the trained immunity inducer Muramyl Dipeptide (MDP) and specific tumor antigen human papillomavirus (HPV) E7 peptide encapsulated by poly(lactide-co-glycolide)-acid(PLGA) nanoparticles (NPs), and the NPs along with another trained immunity agonist, ß-glucan, were further embedded in a sodium alginate hydrogel. The nanovaccine formulation demonstrated a depot effect for E7 at the injection site and targeted delivery to the lymph nodes and dendritic cells (DCs). The antigen uptake and maturation of DCs were significantly promoted. A trained immunity phenotype, characterized by increased production of IL-1ß, IL-6, and TNF-α, was induced in vitro and in vivo in response to secondary homologous or heterologous stimulation. Furthermore, prior innate immune training enhanced the antigen-specific INF-γ-expressing immune cell response elicited by subsequent stimulation with the nanovaccine. Immunization with the nanovaccine completely inhibited the growth of TC-1 tumors and even abolished established tumors in mice. Mechanistically, the inclusion of ß-glucan and MDP significantly enhanced the responses of tumor-specific effector adaptive immune cells. The results strongly suggest that the controlled release and targeted delivery of an antigen and trained immunity inducers with an NP/hydrogel biphasic system can elicit robust adaptive immunity, which provides a promising tumor vaccination strategy.

Polymerized porin as a novel delivery platform for coronavirus vaccine.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seriously threatens human life and health. The correct folding and polymerization of the receptor-binding domain (RBD) protein of coronavirus in Escherichia coli may reduce the cost of SARS-CoV-2 vaccines. In this study, we constructed this nanopore by using the principle of ClyA porin polymerization triggered by the cell membrane. We used surfactants to "pick" the ClyA-RBD nanopore from the bacterial outer membrane. More importantly, the polymerized RBD displayed on the ClyA-RBD polymerized porin (RBD-PP) already displays some correct spatial conformational epitopes that can induce neutralizing antibodies. The nanostructures of RBD-PP can target lymph nodes and promote antigen uptake and processing by dendritic cells, thereby effectively eliciting the production of anti-SARS-CoV-2 neutralizing antibodies, systemic cellular immune responses, and memory T cells. We applied this PP-based vaccine platform to fabricate an RBD-based subunit vaccine against SARS-CoV-2, which will provide a foundation for the development of inexpensive coronavirus vaccines. The development of a novel vaccine delivery system is an important part of innovative drug research. This novel PP-based vaccine platform is likely to have additional applications, including other viral vaccines, bacterial vaccines, tumor vaccines, drug delivery, and disease diagnosis.

RBD-Modified Bacterial Vesicles Elicited Potential Protective Immunity against SARS-CoV-2.

The disease caused by SARS-CoV-2 infection threatens human health. In this study, we used high-pressure homogenization technology not only to efficiently drive the bacterial membrane to produce artificial vesicles but also to force the fusion protein ClyA-receptor binding domain (RBD) to pass through gaps in the bacterial membrane to increase the contact between ClyA-RBD and the membrane. Therefore, the load of ClyA-RBD on the membrane is substantially increased. Using this technology, we constructed a "ring-like" bacterial biomimetic vesicle (BBV) loaded with polymerized RBD (RBD-BBV). RBD-BBVs injected subcutaneously can accumulate in lymph nodes, promote antigen uptake and processing, and elicit SARS-CoV-2-specific humoral and cellular immune responses in mice. In conclusion, we evaluated the potential of this novel bacterial vesicle as a vaccine delivery system and provided a new idea for the development of SARS-CoV-2 vaccines.

Initial Experience with Pediatrics Online Learning for Nonclinical Medical Students During the COVID-19 Pandemic (preprint)

Background: To minimize the risk of infection during the COVID-19 pandemic, the learning mode of universities in China has been adjusted, and the online learning of clinical medicine is facing great challenges. This study preliminarily discusses the experience of express team-based learning (eTBL) combined with a flipped classroom (FC) and case-based learning (CBL) online for nonclinical medical students and addresses the distribution of online learning resources used in pediatrics. This study helps to document additional experience in online learning during the global trend of digital learning. Methods: When online learning was fully launched at Sichuan University in the spring of 2020, 236 penultimate-year students of nonclinical medicine majors were selected as the research objects. The penultimate-year students of the same majors in the spring of 2019 were taken as the reference objects. The research objects successively used the methods of eTBL combined with FC and CBL methods to conduct online learning in pediatrics, and students were encouraged to search and share online learning resources. The reference objects used the method of eTBL combined with CBL for offline face-to-face learning, and the test results of the two learning environments were compared. At the end of the pediatrics course in the spring of 2020, the research objects were invited to participate anonymously in an online questionnaire survey involving 12 items on a 5-point Likert scale (1 = strongly disagree, 5 = strongly agree) to evaluate the participation, satisfaction, and distribution of online learning resources used in pediatrics. Results: 1. Student participation and test scores: i. A total of 75.8% (179/236) of the respondents completed the questionnaire effectively, and 7 items on the Likert scale indicated that online learning with eTBL + FC had higher student participation than eTBL + CBL (4.64 vs 4.27, P < 0.001). ii. In the spring of 2019 and 2020, the average scores of the last four subjects were higher than those of the first four subjects (P < 0.001). The average scores of online learning courses in the spring of 2020 were higher than those of offline learning in the spring of 2019 (P < 0.001). 2. Online learning resources: i. The main motivations for students to use online learning resources were pre-class preparation (4.83), class discussion (4.28) and pre-class testing (3.79). ii. A total of 72.9% (129/179) of the students “most or all of the time” searched online learning resources in the pre-class preparation stage. iii. Students' online learning resources mainly included Chinese academic databases, search engines, teaching platforms and foreign databases. iv. The information retrieval ability of students was improved after the above online learning methods (after versus before, Mdn 5 VS 4, U = 591.0, P = 0.007). 3. More students thought that the online learning method of eTBL + CBL was more beneficial for understanding than that of eTBL + FC (P = 0.044), while the online learning method of eTBL + FC was more conducive for online learning resource retrieval than that of eTBL + CBL (P = 0.034), and the workload was greater (P = 0.001). Both of the online learning methods were conducive to online learning resource sharing (P = 0.298). 4. The results of five items on the Likert scale in the questionnaire showed that students' satisfaction with the online learning mode was high (4.16). Conclusion: i. During the COVID-19 pandemic, online eTBL shortened the learning time of typical TBL. After online learning with eTBL, in combination with FC, CBL and the use of online learning resources, students had high rates of participation and satisfaction. ii. Online learning test results were as good as offline test results. iii. The main motivation for students to use online learning resources came from learning tasks. Chinese academic databases and search engines were the main learning resources for nonclinical medical students. iv. Both online combined learning methods were helpful for students to share online learning resources. eTBL + FC was more helpful in retrieving online learning resources, and the workload was also larger, while eTBL + CBL was more helpful for students to understand course content.

SARS-CoV-2 and the reproductive system: assessment of risk and recommendations for infection control in reproductive departments.

The World Health Organization has declared the outbreak of the coronavirus disease COVID-19, caused by SARS-CoV-2, a pandemic. This novel infectious disease has rapidly become a global health threat. Currently, there are limited data on the extent of reproductive system damage caused by COVID-19. We reviewed the potential risks for complications in the reproductive system caused by COVID-19 infection. In addition, based on the latest American Society for Reproductive Medicine (ASRM), and European Society of Human Reproduction and Embryology (ESHRE), recommendations regarding clinical and patient management, we provide a series of suggestions for infection control measures in reproductive medicine departments. With the gradual restoration of reproductive care services, reproductive departments in epidemic areas should actively seek to minimize COVID-19 infection of both healthcare workers and patients.

Challenges in the Practice of Sexual Medicine in the Time of COVID-19 in China

BACKGROUND: In March 2020, the World Health Organization declared coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Currently, data on changes in sexual behavior during the COVID-19 outbreak are limited. AIM: The present study aimed to obtain a preliminary understanding of the changes in people's sexual behavior, as a result of the pandemic, and explore the context in which they manifest. METHODS: A convenience sample of 270 men and 189 women who completed an online survey consisting of 12 items plus an additional question were included in the study. OUTCOMES: The study outcomes were obtained using a study-specific questionnaire to assess the changes in people's sexual behavior. RESULTS: While there was a wide range of individual responses, our results showed that 44% of participants reported a decrease in the number of sexual partners and about 37% of participants reported a decrease in sexual frequency. Multiple regression analysis showed that age, partner relationship, and sexual desire were closely related to sexual frequency. In addition, we found that most individuals with risky sexual experiences had a rapid reduction in risky sexual behavior. CLINICAL IMPLICATIONS: The current findings contribute to identifying another potential health implication associated with the COVID-19 pandemic and report preliminary evidence of the need to provide potential interventions for the population. STRENGTH & LIMITATIONS: This study is the first to perform a preliminary exploration of sexual behavior during the COVID-19 outbreak. The generalizability of the results is limited, given that only a small convenience sample was used. CONCLUSION: During the height of the COVID-19 outbreak, overall sexual activity, frequency, and risky behaviors declined significantly among young men and women in China. Li W, Li G, Xin C, et al. Challenges in the Practice of Sexual Medicine in the Time of COVID-19 in China. J Sex Med 2020;17:1225-1228.