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Furin is a proprotein convertase that activates different kinds of regulatory proteins, including SARS-CoV-2 spike protein which contains an additional furin-specific cleavage site. It is essential in predicting cancer patients' susceptibility to SARS-CoV-2 and the disease outcomes due to varying furin expressions in tumor tissues. In this study, we analyzed furin's expression, methylation, mutation rate, functional enrichment, survival rate and COVID-19 outcomes in normal and cancer tissues using online databases, and our IHC. As a result, furin presented with biased expression profiles in normal tissues, showing 12.25-fold higher than ACE2 in the lungs. The furin expression in tumors were significantly increased in ESCA and TGCT, and decreased in DLBC and THYM, indicating furin may play critical mechanistic functions in COVID-19 viral entry into cells in these cancer patients. Line with furin over/downexpression, furin promoter hypo-/hyper-methylation may be the regulatory cause of disease and lead to pathogenesis of ESCA and THYM. Furthermore, presence of FURIN−201 isoform with functional domains (P_proprotein, Peptidase_S8 and S8_pro-domain) is highest in all cancer types in comparison to other isoforms, demonstrating its use in tumorigenesis and SARS-Cov-2 entry into tumor tissues. Furin mutation frequency was highest in UCES, and its mutation might elevate ACE2 expression in LUAD and UCEC, reduce ACE2 expression in COAD, elevate HSPA5 expression in PAAD, and elevate TMPRSS2 expression in BRCA. These results showed that furin mutations mostly increased expression of ACE2, HSPA5, and TMPRSS2 in certain cancers, indicating furin mutations might facilitate COVID-19 cell entry in cancer patients. In addition, high expression of furin was significantly inversely correlated with long overall survival (OS) in LGG and correlated with long OS in COAD and KIRC, indicating that it could be used as a favorable prognostic marker for cancer patients' survival. GO and KEGG demonstrated that furin was mostly enriched in genes for metabolic and biosynthetic processes, retinal dehydrogenase activity, tRNA methyltransferase activity, and genes involving COVID-19, further supporting its role in COVID-19 and cancer metabolism. Moreover, Cordycepin (CD) inhibited furin expression in a dosage dependent manner. Altogether, furin's high expression might not only implies increased susceptibility to SARS-CoV-2 and higher severity of COVID-19 symptoms in cancer patients, but also it highlights the need for cancer treatment and therapy during the COVID-19 pandemic. CD might have a potential to develop an anti-SARS-CoV-2 drug through inhibiting furin expression.

HSPA5 (BiP, GRP78) has been reported as a potential host-cell receptor for SARS-Cov-2, but its expression profiles on different tissues including tumors, its susceptibility to SARS-Cov-2 virus and severity of its adverse effects on malignant patients are unclear. In the current study, HSPA5 has been found to be expressed ubiquitously in normal tissues and significantly increased in 14 of 31 types of cancer tissues. In lung cancer, mRNA levels of HSPA5 were 253-fold increase than that of ACE2 . Meanwhile, in both malignant tumors and matched normal samples across almost all cancer types, mRNA levels of HSPA5 were much higher than those of ACE2 . Higher expression of HSPA5 significantly decreased patient overall survival (OS) in 7 types of cancers. Moreover, systematic analyses found that 7.15% of 5,068 COVID-19 cases have malignant cancer coincidental situations, and the rate of severe events of COVID-19 patients with cancers present a higher trend than that for all COVID-19 patients, showing a significant difference (33.33% vs 16.09%, p <0.01). Collectively, these data imply that the tissues with high HSPA5 expression, not low ACE2 expression, are susceptible to be invaded by SARS-CoV-2. Taken together, this study not only indicates the clinical significance of HSPA5 in COVID-19 disease and cancers, but also provides potential clues for further medical treatments and managements of COVID-19 patients.

Background The Personality Inventory for DSM-5 Brief Form (PID-5-BF) is a 25-item measuring tool evaluating maladaptive personality traits for the diagnosis of personality disorders(PDs). As a promising scale, its impressive psychometric properties have been verified in some countries, however, there have been no studies about the utility of the PID-5-BF in Chinese settings. The current study aimed to explore the maladaptive personality factor model which was culturally adapted to China and to examine psychometric properties of the PID-5-BF among Chinese undergraduate students and clinical patients. Methods Seven thousand one hundred fifty-five undergraduate students and 451 clinical patients completed the Chinese version of the PID-5-BF. Two hundered twenty-eight students were chosen randomly for test-retest reliability at a 4-week interval. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to discover the most suitable factor structure in China, measurement invariance(MI), internal consistency, and external validity were also calculated. Results The theoretical five-factor model was acceptable, but the exploratory six-factor model was more applicable in both samples (Undergraduate sample: CFI = 0.905, TLI = 0.888, RMSEA = 0.044, SRMR = 0.039; Clinical sample: CFI = 0.904, TLI = 0.886, RMSEA = 0.047, SRMR = 0.060). In the Chinese six-factor model, the Negative Affect domain was divided into two factors and the new factor was named “Interpersonal Relationships”, which was in line with the Big-Six Personality model in Chinese. Measurement invariance across non-clinical and clinical sample was established (configural, weak, strong MI, and partial strict MI). Aside from acceptable internal consistency (Undergraduate sample: alpha = 0.84, MIC = 0.21; Clinical sample: alpha = 0.86, MIC = 0.19) and test-retest reliability(0.73), the correlation between the 25-item PID-5-BF and the 220-item PID-5 was significant(p < 0.01). The six PDs measured by Personality diagnostic questionnaire-4+ (PDQ-4+) were associated with and predicted by expected domains of PID-5-BF. Conclusions Both the theoretical five-factor model and the exploratory six-factor model of the PID-5-BF were acceptable to the Chinese population. The five-factor model could allow for comparison and integration with other work on the original theoretical model. However, the Chinese six-factor structure may be more culturally informed in East Asian settings. In sum, the PID-5-BF is a convenient and useful screening tool for personality disorders.

Resilience plays an important role in the health of the elderly. The 10-item Connor-Davidson Resilience Scale (CD-RISC-10) is widely used to evaluate resilience, but its factorial invariance has not been evaluated in the Chinese elders. In the current study, 1,238 Chinese elders aged 60 years and above completed the Chinese CD-RISC-10, yielding good reliability (Cronbach’s α = 0.936, Omega coefficient = 0.83, and test-retest reliability coefficient of 0.665 after 6 months). Confirmatory factor analysis indicated that a single-factor model fitted our CD-RISC-10 data well, both for the total sample and for each gender group. Furthermore, factorial invariance across genders was supported by multigroup confirmatory factor analysis. Finally, the current study revealed greater resilience levels in Chinese elderly women than in Chinese elderly men.

CTSL is expressed by cancerous tissues and encodes a lysosomal cysteine proteinase that regulates cancer progression and SARS-CoV-2 entry. Therefore, it is critical to predict the susceptibility of cancer patients for SARS-CoV-2 and evaluate the correlation between disease outcomes and the expression of CTSL in malignant cancer tissues. In the current study, we analyzed CTSL expression, mutation rate, survival and COVID-19 disease outcomes in cancer and normal tissues, using online databases. We also performed immunohistochemistry (IHC) to test CTSL expression and western blot to monitor its regulation by cordycepin (CD), and N6, N6-dimethyladenosine (m 6 2 A), respectively. We found that CTSL is conserved across different species, and highly expressed in both normal and cancer tissues from human, as compared to ACE2 or other proteinases/proteases. Additionally, the expression of CTSL protein was the highest in the lung tissue. We show that the mRNA expression of CTSL is 66.4-fold higher in normal lungs and 54.8-fold higher in cancer tissues, as compared to ACE2 mRNA expression in the respective tissues. Compared to other proteases/proteinases/convertases such as TMPRSS2 and FURIN, the expression of CTSL was higher in both normal lungs and lung cancer samples. All these data indicate that CTSL might play an important role in COVID-19 pathogenesis in normal and cancer tissues of the lungs. Additionally, the CTSL-002 isoform containing both the inhibitor_I29 and Peptidase_C1 domains was highly prevalent in all cancers, suggesting its potential role in tumor progression and SARS-CoV-2 entry in multiple types of cancers. Further analysis of the expression of CTSL mutant showed a correlation with FURIN and TMPRSS2, suggesting a potential role of CTSL mutations in modulating SARS-CoV-2 entry in cancers. Moreover, high expression of CTSL significantly correlated with a short overall survival (OS) in lung cancer and glioma. Thus, CTSL might play a major role in the susceptibility of lung cancer and glioma patients to SARS-CoV-2 uptake and COVID-19 severity. Furthermore, CD or m 6 2 A inhibited CTSL expression in the cancer cell lines A549, MDA-MB-231, and/or PC3 in a dose dependent manner. In conclusion, we show that CTSL is highly expressed in normal tissues and increased in most cancers, and CD or m 6 2 A could inhibit its expression, suggesting the therapeutic potential of targeting CTSL for cancer and COVID-19 treatment.

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