Background Head and neck squamous cell carcinoma (HNSCC), the most common head and neck cancer, is highly aggressive and heterogeneous, resulting in variable prognoses and immunotherapeutic outcomes. Natural killer (NK) cells play essential roles in malignancies’ development, diagnosis, and prognosis. The purpose of this study was to establish a reliable signature based on genes related to NK cells (NRGs), thus providing a new perspective for assessing immunotherapy response and prognosis of HNSCC patients. Methods In this study, NRGs were used to classify HNSCC from the TCGA-HNSCC and GEO cohorts. The genes were evaluated using univariate cox regression analysis based on the differential analysis of normal and tumor samples in TCGA-HNSCC conducted using the “limma” R package. Thereafter, we built prognostic gene signatures using LASSO-COX analysis. External validation was carried out in the GSE41613 cohort. Immunity analysis based on NRGs was performed via several methods, such as CIBERSORT, and immunotherapy response was evaluated by TIP portal website. Results With the TCGA-HNSCC data, we established a nomogram based on the 17-NRGs signature and a variety of clinicopathological characteristics. The low-risk group exhibited a better effect when it came to immunotherapy. Conclusions 17-NRGs signature and nomograms demonstrate excellent predictive performance and offer new perspectives for assessing pre-immune efficacy, which will facilitate future precision immuno-oncology research.

/pdf/natural-killer-cell-related-prognosis-signature-260ipvkt.pdf

Natural killer cell-related prognosis signature characterizes immune landscape and predicts prognosis of HNSCC

Wildlife is reservoir of emerging viruses. Here we identified 27 families of mammalian viruses from 1981 wild animals and 194 zoo animals collected from south China between 2015 and 2022, isolated and characterized the pathogenicity of eight viruses. Bats harbor high diversity of coronaviruses, picornaviruses and astroviruses, and a potentially novel genus of Bornaviridae. In addition to the reported SARSr-CoV-2 and HKU4-CoV-like viruses, picornavirus and respiroviruses also likely circulate between bats and pangolins. Pikas harbor a new clade of Embecovirus and a new genus of arenaviruses. Further, the potential cross-species transmission of RNA viruses (paramyxovirus and astrovirus) and DNA viruses (pseudorabies virus, porcine circovirus 2, porcine circovirus 3 and parvovirus) between wildlife and domestic animals was identified, complicating wildlife protection and the prevention and control of these diseases in domestic animals. This study provides a nuanced view of the frequency of host-jumping events, as well as assessments of zoonotic risk. 

Virus diversity, wildlife-domestic animal circulation and potential zoonotic viruses of small mammals, pangolins and zoo animals

Therapeutic Implications of Targeting Pyroptosis in Cardiac-related Etiology of Heart Failure.

pdf/starting-the-journey-understanding-the-roles-of-complement-29vyb47y97.pdf

Starting the Journey: Understanding the Roles of Complement Proteins in Liver Diseases Through Mendelian Randomization.

Previous studies have identified multiple viruses in dead or severely diseased pangolins, but descriptions of the virome in healthy pangolins are lacking. This poses a greater risk of cross-species transmission due to poor preventive awareness and frequent interactions with breeders. In this study, we investigated the viral composition of 34 pangolins with no signs of disease at the time of sampling and characterized a large number of arthropod-associated viruses belonging to 11 families and vertebrate viruses belonging to eight families, including those with pathogenic potential in humans and animals. Several important vertebrate viruses were identified in the pangolins, including parvovirus, pestivirus, and picobirnavirus. The picobirnavirus was clustered with human and grey teal picobirnaviruses. Viruses with cross-species transmission ability were also identified, including circovirus, rotavirus, and astrovirus. Our study revealed that pangolins are frequently exposed to arthropod-associated viruses in the wild and can carry many vertebrate viruses under natural conditions. This study provides important insights into the virome of pangolins, underscoring the importance of monitoring potential pathogens in healthy pangolins to prevent outbreaks of infectious diseases in domesticated animals and humans.

https://doi.org/10.24272/j.issn.2095-8137.2022.246

Virome in healthy pangolins reveals compatibility with multiple potentially zoonotic viruses

Human tongue squamous cell carcinoma (TSCC), the most prevalent type of oral cancer, is associated with human papillomavirus (HPV) infection. Our previous work showed Karyopherin α2 (KPNA2), as an oncogene of TSCC, by relegating the p53/autophagy signaling pathway. Nevertheless, the significance of KPNA2 in TSCC pathogenesis has not been established. KPNA2 levels were evaluated via the TCGA database, and its effects on survival outcomes were assessed by LASSO, Kaplan‐Meier, and COX regression analyses. CIBERSORT and ESTIMATE investigated the relationships between KPNA2 and immune infiltration. At the same time, KPNA2 and HPV infection was analyzed by immunohistochemistry. In addition, the association between downstream molecular regulation pathways and KPNA2 levels was determined by GO, GSEA, and WGCNA. In TSCC, KPNA2 levels were associated with clinical prognosis and tumor grade. Moreover, KPNA2 may be involved in cancer cell differentiation and facilitates tumor-related genes and signaling pathways, such as Cell Cycle, Mitotic G1 phase, G1/S transition, DNA Repair, and Transcriptional Regulation TP53 signaling pathways. Nevertheless, regulatory B cells, follicular helper B cells, and immune and stromal scores between low- and high-KPNA2 expression groups were insignificant. These results imply that KPNA2 is highly involved in tumor grade and prognosis of TSCC. KPNA2 levels correct with HPV 16 markedly regulated cell differentiation, several oncogenes, and cancer‐related pathways.

/pdf/oncogenic-kpna2-serves-as-a-biomarker-and-immune-1kmafud6.pdf

Oncogenic KPNA2 Serves as a Biomarker and Immune Infiltration in Patients With HPV Positive Tongue Squamous Cell Carcinoma

ABSTRACT Pangolins have gained increasing global attention owing to their public health significance as potential zoonotic hosts since the identification of SARS-CoV-2-related viruses in them. Moreover, these animals could carry other respiratory viruses. In this study, we investigated the virome composition of 16 pangolins that died in 2018 with symptoms of pneumonia using metagenomic approaches. A total of eight whole virus sequences belonging to the Paramyxoviridae or Pneumoviridae families were identified, including one human parainfluenza virus 3, one human respiratory syncytial virus A, and six human respiratory syncytial virus B. All of these sequences showed more than 99% nucleotide identity with the virus isolated from humans at the whole-genome level and clustered with human viruses in the phylogenetic tree. Our findings provide evidence that pangolins are susceptible to HPIV3 and HRSV infection. Therefore, public awareness of the threat of pangolin-borne pathogens is essential to stop their human consumption and to prevent zoonotic viral transmission.

https://www.tandfonline.com/doi/pdf/10.1080/22221751.2022.2086071?needAccess=true

Human parainfluenza 3 and respiratory syncytial viruses detected in pangolins

Objective Prostatitis is a common disease of the male genitourinary system, which seriously disturbs the physical and mental health of male patients. It is related to many factors such as living habits, age, and race, but the etiology has not been fully elucidated. This study investigated whether there is a causal relationship between clinical biochemical indicators (i.e., intermediate phenotype) and prostatitis through Mendelian randomization. The subjects of the study were prostatitis patients and related SNPs in the Guangxi Fangchenggang health examination cohort. Methods According to the requirements of Mendelian randomization (MR), the single nucleotide polymorphisms (SNPs) related to prostatitis patients and 29 common SNPs related to clinical biochemical indicators were analyzed by linkage disequilibrium, and the calculated SNPs were selected. Finally, the related SNPs were analyzed by Mendelian randomization method. Results 15 biochemical indicators such as complement C4, FOL, CRP, HCY, and estradiol have shared chronic prostatitis SNP sites, and five qualified SNPs were finally screened for complement C4. Finally, complement C4 was obtained by Mendelian randomization method (P = 0.039), which was statistically significant. The other 28 clinical endophenotypes were all negative. Conclusion The results show that there was a causal relationship between complement C4 and prostatitis, and the more consistent SNP is rs2075799.

/pdf/investigating-causal-relations-between-genetic-related-1r9xbqro.pdf

Investigating Causal Relations between Genetic-Related Intermediate Endophenotype and Risk of Chronic Prostatitis: Mendelian Randomization Study

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Oncogenic KPNA2 Serves as a Biomarker and Immune Infiltration in Patients With HPV Positive Tongue Squamous Cell Carcinoma

Human parainfluenza 3 and respiratory syncytial viruses detected in pangolins

Investigating Causal Relations between Genetic-Related Intermediate Endophenotype and Risk of Chronic Prostatitis: Mendelian Randomization Study