2019 novel coronavirus (2019-nCoV) is widespread in China and other countries. The target of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV) is angiotensin-converting enzyme 2 (ACE2) positive cells. ACE2 is present in the salivary gland duct epithelium, and thus it could be the target of 2019-nCoV and SARS-CoV. SARS-CoV-related animal model experiments show that it can infect the epithelial cells on the salivary gland duct in Chinese rhesus macaques by targeting ACE2. Clinical studies confirmed that 2019-nCoV and SARS-CoV could be detected in saliva of human patients. We hypothesize that the infection of 2019-nCoV and SARS-CoV will lead to inflammatory pathological lesions in patients' target organs, and possibly inflammatory lesions in salivary glands. 2019-nCoV may cause acute sialoadenitis in the acute phase of infection. After the acute phase, chronic sialoadenitis may be caused by fibrosis repairment. Although there was no direct evidence to prove this, the available indirect evidence indicates a high probability of our hypothesis.

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is primarily transmitted through droplets. All human tissues with the angiotensin‐converting enzyme 2 (ACE2) and transmembrane protease serines 2 (TRMPRSS2) are potential targets of SARS‐CoV‐2. The role of saliva in SARS‐CoV‐2 transmission remains obscure. In this study, we attempted to reveal ACE2 and TRMPRSS2 protein expression in human parotid, submandibular, and sublingual glands (three major salivary glands). Then, the binding function of spike protein to ACE2 in three major salivary glands was detected. The expression of ACE2 and TMPRSS2 in human saliva from parotid glands were both examined. Exogenous recombined ACE2 and TMPRSS2 anchoring and fusing to oral mucosal epithelial cells in vitro were also unraveled. ACE2 and TMPRSS2 were found mainly to be expressed in the cytomembrane and cytoplasm of epithelial cells in the serous acinus cells in parotid and submandibular glands. Our research also discovered that the spike protein of SARS‐CoV‐2 binds to ACE2 in salivary glands in vitro. Furthermore, exogenous ACE2 and TMPRSS2 can anchor and fuse to oral mucosa in vitro. Thus, the expression of ACE2 and TMPRSS2 in human saliva might have implications for SARS‐CoV‐2 infection.

Background Endoplasmic reticulum (ER) stress has been found to foster the escape of cancer cells from immune surveillance and upregulate PD-L1 expression. However, the underlying mechanisms are unknown. Methods While analyzing the protein levels using immunofluorescence and Western blotting, the RNA levels were measured using qRT-PCR. Ten injection of exosomes into six-week-old nude mice was made through the tail vein once every other day in total. Results The expression of certain ER stress markers such as PERK (PKR-like endoplasmic reticulum kinase), ATF6 (activating transcription factor 6), and GRP78 (glucose-regulated protein 78), was found to be upregulated in the oral squamous cell carcinoma (OSCC) tissues and related to poor overall survival. There is a positive relationship between the extent of ER stress-related proteins and a cluster of PD-L1 expression and macrophage infiltration among the OSCC tissues. Further, incubation with exosomes derived from ER-stressed HN4 cells (Exo-ER) was found to upregulate PD-L1 extents in macrophages in vitro and in vivo, and macrophage polarization toward the M2 subtype was promoted by upregulating PD-L1. Conclusions ER stress causes OSCC cells to secrete exosomal PD-L1 and upregulates PD-L1 expression in macrophages to drive M2 macrophage polarization. The delineation of a new exosome-modulated mechanism was made for OSCC–macrophage crosstalk driving tumor development and to be examined for its therapeutic use. Graphical abstract Exosomal PD-L1 secreted by ER-stressed OSCC cells promoted M2 macrophage polarization.

Certain high-risk factors related to the death of COVID-19 have been reported, however, there were few studies on a death prediction model. This study was conducted to delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) of different degree and establish a death prediction model. In this multi-centered, retrospective, observational study, we enrolled 523 COVID-19 cases discharged before February 20, 2020 in Henan Province, China, compared clinical data, screened for high-risk fatal factors, built a death prediction model and validated the model in 429 mild cases, six fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan. Out of the 523 cases, 429 were mild, 78 severe survivors, 16 non-survivors. The non-survivors with median age 71 were older and had more comorbidities than the mild and severe survivors. Non-survivors had a relatively delay in hospitalization, with higher white blood cell count, neutrophil percentage, D-dimer, LDH, BNP, and PCT levels and lower proportion of eosinophils, lymphocytes and albumin. Discriminative models were constructed by using random forest with 16 non-survivors and 78 severe survivors. Age was the leading risk factors for poor prognosis, with AUC of 0.907 (95% CI 0.831-0.983). Mixed model constructed with combination of age, demographics, symptoms, and laboratory findings at admission had better performance (p = 0.021) with a generalized AUC of 0.9852 (95% CI 0.961-1). We chose 0.441 as death prediction threshold (with 0.85 sensitivity and 0.987 specificity) and validated the model in 429 mild cases, six fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan successfully. Mixed model can accurately predict clinical outcomes of COVID-19 patients.

This research aimed to investigate the expression and function of FAM83A in the proliferation and metastasis in head and neck squamous cell carcinoma (HNSCC). FAM83A mRNA and protein expressions in HNSCC were detected in primary HNSCC samples and cell lines. The associations between FAM83A expression and clinicopathologic variables were evaluated through tissue microarrays. Besides, FAM83A knockdown and overexpression cell lines were constructed to assess cell growth and metastasis in vitro and the relationship between FAM83A and epithelial-mesenchymal transition (EMT). Furthermore, two models of xenograft tumors in nude mice were used to assess the tumorigenicity and metastasis ability of FAM83A in vivo. In the present study, overexpression of FAM83A in HNSCC samples was significantly associated with tumor size, lymph node status and clinical tumor stages. Mechanically, FAM83A could promote HNSCC cell growth and metastasis by inducing EMT via activating Wnt/β-catenin signaling pathway. Rescue experiment demonstrated the inhibition of β-catenin could counteract the function of FAM83A. Also, the FAM83A knockdown could suppress tumor growth and distant metastasis in the xenograft animal models of HNSCC. In conclusion, this study identifies FAM83A as an oncogene of HNSCC. This study provides new insights into the molecular pathways that contribute to EMT in HNSCC. We revealed a previously unknown FAM83A-Wnt–β-catenin signaling axis involved in the EMT of HNSCC. There may be a potential bi-directional signaling loop between FAM83A and Wnt/β-catenin signaling pathway in HNSCC.

Long non-coding RNA (LncRNA) THOR (Lnc-THOR) is expressed in testis and multiple human malignancies. Lnc-THOR association with IGF2BP1 (IGF2 mRNA-binding protein 1) is essential for stabilization and transcription of IGF2BP1 targeted mRNAs. We tested its expression and potential functions in non-small cell lung cancer (NSCLC). In primary NSCLC cells and established cell lines, Lnc-THOR shRNA or CRISPR/Cas9-mediated knockout (KO) downregulated IGF2BP1 target mRNAs (IGF2, Gli1, Myc and SOX9), inhibiting cell viability, growth, proliferation, migration and invasion. Significant apoptosis activation was detected in Lnc-THOR-silenced/-KO NSCLC cells. Conversely, ectopic overexpression of Lnc-THOR upregulated IGF2BP1 mRNA targets and enhanced NSCLC cell proliferation, migration and invasion. RNA-immunoprecipitation and RNA pull-down assay results confirmed the direct binding between Lnc-THOR and IGF2BP1 protein in NSCLC cells. Lnc-THOR silencing and overexpression were ineffective in IGF2BP1-KO NSCLC cells. Forced IGF2BP1 overexpression failed to rescue Lnc-THOR-KO NSCLC cells. In vivo, intratumoral injection of Lnc-THOR shRNA adeno-associated virus potently inhibited A549 xenograft tumor growth in nude mice. At last we show that Lnc-THOR is overexpressed in multiple NSCLC tissues and established/primary NSCLC cells. Collectively, these results highlighted the ability of Lnc-THOR in promoting NSCLC cell growth by associating with IGF2BP1, suggesting that Lnc-THOR represents a promising therapeutic target of NSCLC.

Tumour-associated macrophages (TAMs) are thought to contribute to oral squamous cell carcinoma (OSCC) initiation and progression. However, the underlying mechanism through which TAMs foster OSCC progression is still unclear. This study intended to determine whether there are exclusively exosomal miRNAs-derived macrophages that are functionally necessary for OSCC progression. The phenotype of TAM recruitment in OSCC tissue samples was assessed, subsequently identifying the influence of M2 macrophages and exosomes derived from M2 macrophages on OSCC proliferation and tumorigenesis in vitro and in vivo. CD68 and CD163, the specific markers of M2 type macrophages, were upregulated in TAMs presented in intra-cancer tissues. M2 macrophages and M2 macrophage-derived exosomes (M2 exos) both can promote OSCC growth and tumorigenicity. An exosomal RNA-seq analysis was conducted to predict regulatory exosomal miRNAs related to OSCC growth, which determined miR-31-5p and LATS2 for subsequent experiments. Mechanistically, miR-31-5p was delivered to recipient OSCC cells through M2 exos and complementary pairing with the large tumor suppressor 2 (LATS2) coding sequence, thus suppressing the expression of LATS2 and inactivation the Hippo signaling pathway to support OSCC growth. Collectively, our findings demonstrate that M2 macrophage-derived exosomal miR- 31-5p can make tumor suppressor LATS2 gene inhibited and facilitate the progression of OSCC via inhibiting the Hippo signaling pathway, which possibly provides new targets for the molecular therapy of OSCC.