Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common cancer in the world. However, there is no effective treatment for HNSCCs. More than 90% of HNSCCs overexpress epidermal growth factor receptors (EGFRs). Although small molecule inhibitors and monoclonal antibodies have been developed to target EGFRs, few EGFR-targeted therapeutics are approved for clinical use. Ferroptosis is a new kind of programmed death induced by the iron catalyzed excessive peroxidation of polyunsaturated fatty acids. A growing body of evidence suggests that ferroptosis plays a pivotal role in inhibiting the tumor process. However, whether and how ferroptosis-inducers (FINs) play roles in hindering HNSCCs are unclear. In this study, we analyzed the sensitivity of different HNSCCs to ferroptosis-inducers. We found that only tongue squamous cell carcinoma cells and laryngeal squamous cell carcinoma cells, but not nasopharyngeal carcinoma cells, actively respond to ferroptosis-inducers. The different sensitivities of HNSCC cells to ferroptosis induction may be attributed to the expression of KRAS and ferritin heavy chain (FTH1) since a high level of FTH1 is associated with the poor prognostic survival of HNSCCs, but knocked down FTH1 can promote HNSCC cell death. Excitingly, the ferroptosis-inducer RSL3 plays a synthetic role with EGFR monoclonal antibody Cetuximab to inhibit the survival of nasopharyngeal carcinoma cells (CNE-2), which are insensitive to both ferroptosis induction and EGFR inhibition due to a high level of FTH1 and a low level of EGFR, respectively. Our findings prove that FTH1 plays a vital role in ferroptosis resistance in HNSCCs and also provide clues to target HNSCCs resistant to ferroptosis induction and/or EGFR inhibition.

With the rapid global spread of the Coronavirus Disease 2019 (COVID-19) pandemic, a safe and effective vaccine against human coronaviruses (HCoVs) is believed to be a top priority in the field of public health. Due to the frequent outbreaks of different HCoVs, the development of a pan-HCoVs vaccine is of great value to biomedical science. The antigen design is a key prerequisite for vaccine efficacy, and we therefore developed a novel antigen with broad coverage based on the genetic algorithm of mosaic strategy. The designed antigen has a potentially broad coverage of conserved cytotoxic T lymphocyte (CTL) epitopes to the greatest extent, including the existing epitopes from all reported HCoV sequences (HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2). This novel antigen is expected to induce strong CTL responses with broad coverage by targeting conserved epitopes against multiple coronaviruses.

Characterizing the spatial transmission pattern is critical for better surveillance and control of human influenza. Here, we propose a mutation network framework that utilizes network theory to study the transmission of human influenza H3N2. On the basis of the mutation network, the transmission analysis captured the circulation pattern from a global simulation of human influenza H3N2. Furthermore, this method was applied to explore, in detail, the transmission patterns within Europe, the United States, and China, revealing the regional spread of human influenza H3N2. The mutation network framework proposed here could facilitate the understanding, surveillance, and control of other infectious diseases.

As dengue is an increasing global health threat, a better understanding of the global circulation dynamics and its determinants would be helpful for precise prevention and control of dengue. The dynamics of global circulation of the four dengue virus serotypes were explored utilizing genetic sequences through a network-based method. Four new circulation indicators, including local intensity, betweenness centrality, tip frequency, and persistence time, were defined. Three circulation roles, including source, hub, and destination, were proposed on the basis of new indicators. Spatial and temporal changes of the three circulation roles, along with the persistence time, were explored. Important determinants were also evaluated by machine learning models. Thailand, Indonesia, and Vietnam in Asia and Venezuela and Colombia in Americas were the sources for all four serotypes in different decades. Destinations were observed mostly in island regions. Over the decades, the number of regions with different circulation roles and persistence of DENV-1 increased significantly. Climate and airline factors were involved in the important determinants to circulation roles and persistence of dengue. The roles identified in the global circulation of dengue and important determinants, including climate and airline factors, provide new insights into global dynamics and are beneficial for controlling dengue.