Multi-omic and comparative analyses revealed monocyte-derived alpha-defensin-1 correlated with COVID-19 severity and inhibited SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological pathogen of coronavirus disease 2019 (COVID-19), a highly contagious disease, spreading quickly and threatening global public health. The symptoms of COVID-19 vary from mild reactions to severe respiratory distress or even fatal outcomes probably due to the different status of host immunity against the virus. Here in the study, we unveiled plasma proteomic signatures and transcriptional patterns of peripheral blood mononuclear cells (PBMCs) using blood samples of 10 COVID-19 patients with different severity. Through systemic analysis, α-defensin-1 (DEFA1) was identified to be elevated in both plasma and PBMCs, and correlated with disease severity and stages. In vitro study demonstrated that DEFA1 was secreted from immunocytes and suppressed SARS-CoV-2 infection of both original and mutated strains with dose dependency. By using sequencing data, we discovered that DEFA1 was activated in monocytes through NF-κB signaling pathway after infection, and secreted into circulation to perturb SARS-CoV-2 infection by interfering protein kinase C expression. It worked mainly during virus replication instead of entry in host cells. Together, the anti-SARS-CoV-2 mechanism of DEFA1 has unveiled a corner of how innate immunity is against SARS-CoV-2 and explored its clinical potential in disease prognosis and therapeutic intervention.

Prevalence of mental health problems and associated risk factors among military healthcare workers in specialized COVID-19 hospitals in Wuhan, China: A cross-sectional survey.

INTRODUCTION: China has been severely affected by coronavirus disease 2019 (COVID-19) since December 2019. Military healthcare workers in China have experienced many pressures when combating COVID-19. This study aimed to investigate the current psychological status and associated risk factors among military healthcare workers. METHODS: We collected data from 194 military healthcare workers from three inpatient wards in two specialized COVID-19 hospitals using a web-based cross-sectional survey. The survey covered demographic information, the patient health questionnaire-9, the Generalized Anxiety Disorder-7, and the patient health questionnaire-15. Hierarchical regression analysis was used to explore potential risk factors for mental health problems. RESULTS: The overall prevalence rates of depressive, generalized anxiety, and somatic symptoms were 37.6%, 32.5%, and 50%, respectively. Rates of severe depression, generalized anxiety, and somatic symptoms were 5.2%, 3.6%, and 15.5%, respectively. In 22.7% of cases, comorbidities existed between depression, generalized anxiety, and somatization. A junior-grade professional title was associated with depression, older age was associated with generalized anxiety and somatization, and short sleep duration and poor sleep quality were associated with all three symptoms. DISCUSSION: The prevalence of depression, generalized anxiety, and somatic symptoms among military healthcare workers in specialized COVID-19 hospitals is high during the current COVID-19 outbreak. A junior-grade professional title, older age, short sleep duration, and poor sleep quality significantly affect military healthcare workers' mental health. Continuous surveillance and monitoring of the psychological consequences of the COVID-19 outbreak should be routine to promote mental health among military healthcare workers.

Inhibitory Effect of Bovine Adipose-Derived Mesenchymal Stem Cells on Lipopolysaccharide Induced Inflammation of Endometrial Epithelial Cells in Dairy Cows.

Endometritis is a disease that affects reproductive health in dairy cows and causes serious economic damage to the dairy industry world-wide. Although in recent years, the application of mesenchymal stem cell (MSC) therapy for the treatment of inflammatory diseases has attracted much attention, there are few reports of the use of MSCs in dairy cows. In the present study, our objective was to explore the inhibitory effects of bovine adipose-derived mesenchymal stem cells (bAD-MSCs) on lipopolysaccharide (LPS) induced inflammation in bovine endometrial epithelial cells (bEECs) along with the potential underlying molecular mechanisms. We characterized isolated bAD-MSCs using cell surface marker staining and adipogenic/osteogenic differentiation, and analyzed them using immunofluorescence, flow cytometry (surface marker staining), and adipogenic and osteogenic differentiation. Furthermore, to understand the anti-inflammatory effects of bAD-MSCs on LPS induced bEEC inflammation, we used a bAD-MSC/bEEC co-culture system. The results showed that bAD-MSC treatments could significantly decrease LPS induced bEEC apoptosis and pro-inflammatory cytokine expression levels, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Furthermore, our results showed that bAD-MSC treatments could also significantly downregulate LPS induced p38, IkB-a, and JAK1 phosphorylation and Bax protein expression levels, which are closely related to inflammatory progress and cellular apoptosis in bEECs. Our findings demonstrate that bAD-MSCs play an inhibitory role in LPS induced bEEC inflammation and provide new insights for the clinical therapy of endometritis in dairy cows.

Blood urea nitrogen may serve as a predictive indicator of retained placenta in dairy cows.

Retained placentae (RP) results in significant economic losses to dairy farmers. In Experiment 1, to screen biochemical indicators of RP, 21 cows with RP and 21 cows with no retained placenta (NRP) were selected as a control group, and blood was collected at -7 d, 0 h (parturition) and 12 h. Serum biochemical indicators were ascertained. Results indicate serum concentrations of phosphorus (P) and blood urea nitrogen (BUN) in cows of the RP group were markedly greater than in cows of the NRP group at -7 d (P < 0.01). In Experiment 2, to evaluate predictive indicators for RP, 34 cows with RP and 34 cows with NRP were selected, and there was blood sampling at -15 d, -10 d, -7 d, -4 d, and -1 d. Serum P, BUN, and total protein (TP) were evaluated. Associations of values among the three indicators and occurrence of RP were analyzed using binary logistic regression. Results indicate there was a negative correlation between only the values for BUN and RP (P = 0.016). In Experiment 3, to test hypothesis that relatively greater concentrations of BUN effects immune function in placental tissues, four cows were selected, placentae were collected at 0 and 12 h, and hematoxylin-eosin (HE) staining was performed. Results indicated that the extent of inflammatory cell infiltration and vascular proliferation were less at the 12 than 0-hour timepoint. Taken together, BUN at -7 d may serve as a predictive indicator of RP in cows.

[Association of the tumor necrosis factor-alpha -1031T/C and its combination with interleukin-6 -634C/G gene polymorphisms with susceptibility to endometriosis].

OBJECTIVE: To investigate the association of tumor necrosis factor-alpha (TNF-α) gene promoter region -1031T/C and its combination with interleukin-6 (IL-6) gene promoter region -634C/G single nucleotide polymorphisms (SNP) with the genetic susceptibility to endometriosis. METHODS: Total of 432 endometriosis patients and 499 non-endometriosis women who had received an operation due to tubal ligation, tubal recanalization, laparoscopic hydrotubation, ovarian simple cyst and teratoma were collected and separated into endometriosis group and control group, that all cases were confirmed by operation and pathology. A case-control study was performed in endometriosis and control group to evaluate the association of these SNP with the susceptibility to endometriosis by using a fluorescent quantitative PCR-based high resolution melting (HRM) method. RESULTS: (1) TNF-α -1031T/C genotype:the T and C of TNF-α -1031T/C allele frequencies in the endometriosis group and control group were 79.2% (684/864), 20.8% (180/864) and 81.8% (816/998), 18.2% (182/998), respectively. The TT, TC and CC of TNF-α -1031T/C genotype frequencies in the two groups were 63.7% (275/432), 31.0% (134/432), 5.3% (23/432) and 66.5% (332/499), 30.5% (152/499), 3.0% (15/499), respectively. There were no statistical significances in the TNF-α -1031T/C alleles and genotypes distributions between the two groups (P = 0.158, P = 0.186). (2) TNF-α -1031T/C and IL-6 -634C/G conjoint genotypes: to research on the TNF-α -1031T/C and IL-6 -634C/G genotypes for conjoint analysis, the TT+CC, TC+CC, CC+CC, TT+CG, TC+CG, CC+CG, TT+GG, TC+GG and CC+GG combination genotype frequencies in the two groups were 39.4% (170/432), 19.4% (84/432), 4.6% (20/432), 20.6% (89/432), 8.8% (38/432), 0.9% (4/432), 3.5% (15/432), 2.3% (10/432), 0.5% (2/432) and 36.7% (183/499), 17.4% (87/499), 1.4% (7/499), 26.1% (130/499), 10.4% (52/499), 1.2% (6/499), 3.8% (19/499), 2.6% (13/499), 0.4% (2/499), respectively. There were no statistical significances in the combination genotypes distributions between the two groups (P = 0.107). As compared with carriers of TT+CC combination genotype, the endometriosis risk of carriers of CC+CC combination genotype enhanced 3.076 times (95%CI: 1.268 - 7.457, P = 0.009), and the endometriosis risk of carriers of other combination genotypes were no statistical significances (all P > 0.05). CONCLUSIONS: The study demonstrates that there are no significant association between the SNP of TNF-α -1031T/C and genetic susceptibility to endometriosis. However the results indicate that there are significant association between genetic susceptibility to endometriosis and the combination polymorphisms of TNF-α -1031T/C and IL-6 -634C/G.

Distribution of Candida albican genotype and Candida species is associated with the severity of vulvovagianl candidiasis.

OBJECTIVE: To investigate the distribution of pathogenic C.albican genotype and Candida species in association with the severity of vulvovaginal candidiasis (VVC). METHODS: Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) of the internal transcribed spacer analysis was employed to identify the Candida species isolated from the vaginal secretions of 198 patients with acute VVC. SSCP and GeneScan analyses of microsatellite locus I polymorphism were used to determine the genotypes of the clinical isolates of C. albican associated with VVC. All the patients were scored for clinical signs and symptoms to evaluate the severity of VVC. RESULTS: A total of 198 Candida strains were isolated from VVC patients, including 140 (70.7%) C. albicans strains and 58 (29.3%) non-albicans strains. In the 95 patients with severe VVC and 103 with mild-moderate VVC, C.albican was detected in 62.1% and 76.6% of the patients, respectively (P=0.011). Thirty-eight microsatellite locus I genotypes were detected in 140 unrelated C. albican strains, among which the dominant genotypes 30-45 (44 strians, 31.43%) and 32-46 (23 strains, 16.43%) were the most common, followed by genotypes 30-46 (4 strains, 2.86%) and 32-47 (9 strains, 6.42%). The overall frequencies of the 4 genotypes were significantly higher in severe VVC than in mild-moderate VVC cases (77.9% vs 42.0%, P<0.001). CONCLUSION: C. albicans remains the most common pathogenic Candia species in patients with VVC, but the non-alibcans species seem more likely to cause severe VVC. The dominant genotypes of C. albicans with a tropism for the vagina are correlated to the severity of VVC.