Inside-out assembly of viral antigens for the enhanced vaccination.

Current attempts in vaccine delivery systems concentrate on replicating the natural dissemination of live pathogens, but neglect that pathogens evolve to evade the immune system rather than to provoke it. In the case of enveloped RNA viruses, it is the natural dissemination of nucleocapsid protein (NP, core antigen) and surface antigen that delays NP exposure to immune surveillance. Here, we report a multi-layered aluminum hydroxide-stabilized emulsion (MASE) to dictate the delivery sequence of the antigens. In this manner, the receptor-binding domain (RBD, surface antigen) of the spike protein was trapped inside the nanocavity, while NP was absorbed on the outside of the droplets, enabling the burst release of NP before RBD. Compared with the natural packaging strategy, the inside-out strategy induced potent type I interferon-mediated innate immune responses and triggered an immune-potentiated environment in advance, which subsequently boosted CD40+ DC activations and the engagement of the lymph nodes. In both H1N1 influenza and SARS-CoV-2 vaccines, rMASE significantly increased antigen-specific antibody secretion, memory T cell engagement, and Th1-biased immune response, which diminished viral loads after lethal challenge. By simply reversing the delivery sequence of the surface antigen and core antigen, the inside-out strategy may offer major implications for enhanced vaccinations against the enveloped RNA virus.

Effects of mindfulness decompression therapy on mental health and job burnout among nurses working in the frontline of the novel coronavirus pandemic: A retrospective study.

OBJECTIVES: As the coronavirus disease 2019 (COVID-19) pandemic continues to spread worldwide, nucleic acid detection is a key step in controlling it. Psychological issues and job burnout of nurses working in nucleic acid sampling roles for long periods have become apparent. This study aimed to explore the effects of mindfulness decompression therapy on mental health and job burnout in front-line nurses working in nucleic acid sampling during the pandemic. METHODS: Nucleic acid sampling frontline nurses who were positive for burnout on both the Symptom Checklist-90 (SCL-90) and the Maslach Burnout Inventory-General Scale (MBI-GS) were selected as the participants. Frontline nurses in the nucleic acid testing area who received routine psychological nursing intervention from June 2020 to April 2021 were used as the control group. Nurses who received both routine psychological nursing and mindfulness decompression therapy from May 2021 to December 2021 formed the "mindfulness" subject group. We compared the two groups' primary outcome measures of SCL-90 and MBI-GS scores. RESULTS: Before the intervention, there were no significant differences between the two groups in general data, SCL-90 scores, and MBI-GS scores. After the mindfulness decompression therapy, according to SCL-90 and MBI-GS scales, psychological distress and job burnout of nurses in the mindfulness group were significantly better than those in the control group. CONCLUSION: Mindfulness decompression therapy can effectively improve mental health and relieve job burnout in frontline nurses in nucleic acid sampling areas, which is worthy of clinical application. Randomized controlled trials are still needed, however, to fully confirm the effects of mindfulness decompression therapy.

Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility.

Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1, an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1- Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

Ubiquitin C-terminal hydrolase L1 (UCHL1), a double-edged sword in mammalian oocyte maturation and spermatogenesis.

BACKGROUND: Recent studies have shown that ubiquitin-mediated cell apoptosis can modulate protein interaction and involve in the progress of oocyte maturation and spermatogenesis. As one of the key regulators involved in ubiquitin signal, ubiquitin C-terminal hydrolase L1 (UCHL1) is considered a molecular marker associated with spermatogonia stem cells. However, the function of UCHL1 was wildly reported to regulate various bioecological processes, such as Parkinson's disease, lung cancer, breast cancer and colon cancer, how UCHL1 affects the mammalian reproductive system remains an open question. METHODS: We identified papers through electronic searches of PubMed database from inception to July 2022. RESULTS: Here, we summarize the important function of UCHL1 in controlling mammalian oocyte development, regulating spermatogenesis and inhibiting polyspermy, and we posit the balance of UCHL1 was essential to maintaining reproductive cellular and tissue homeostasis. CONCLUSION: This study considers the 'double-edged sword' role of UCHL1 during gametogenesis and presents new insights into UCHL1 in germ cells.

COVID-19 Vaccines: Particulate Alum via Pickering Emulsion for an Enhanced COVID-19 Vaccine Adjuvant (Adv. Mater. 40/2020)

For enhanced COVID-19 vaccines, in article number 2004210, Yufei Xia, Guanghui Ma, and co-workers pack licensed alum on a squalene/water interphase. Thereby, this century-old adjuvant ?travels through time? in a new form of alum-stabilized Pickering emulsion (PAPE), which not only inherits the clinically acknowledged biosafety, but also demonstrates enhanced cellular uptake and cross-presentation of antigens for potent humoral and cellular responses.

Particulate Alum via Pickering Emulsion for an Enhanced COVID-19 Vaccine Adjuvant.

For rapid response against the prevailing COVID-19 (coronavirus disease 19), it is a global imperative to exploit the immunogenicity of existing formulations for safe and efficient vaccines. As the most accessible adjuvant, aluminum hydroxide (alum) is still the sole employed adjuvant in most countries. However, alum tends to attach on the membrane rather than entering the dendritic cells (DCs), leading to the absence of intracellular transfer and process of the antigens, and thus limits T-cell-mediated immunity. To address this, alum is packed on the squalene/water interphase is packed, forming an alum-stabilized Pickering emulsion (PAPE). "Inheriting" from alum and squalene, PAPE demonstrates a good biosafety profile. Intriguingly, with the dense array of alum on the oil/water interphase, PAPE not only adsorbs large quantities of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antigens, but also harbors a higher affinity for DC uptake, which provokes the uptake and cross-presentation of the delivered antigens. Compared with alum-treated groups, more than six times higher antigen-specific antibody titer and three-fold more IFN-γ-secreting T cells are induced, indicating the potent humoral and cellular immune activations. Collectively, the data suggest that PAPE may provide potential insights toward a safe and efficient adjuvant platform for the enhanced COVID-19 vaccinations.