Risk factors for ICU-acquired weakness in sepsis patients: A retrospective study of 264 patients.

Background: Sepsis is a common critical illness in intensive care unit (ICU) and an important risk factor for intensive care unit-acquired weakness (ICU-AW). The objective of the study is to analyze the risk factors of ICU-AW in septic patients. Methods: A total of 264 septic patients admitted to the General Hospital of the Western Theater Command from January 2018 to April 2022 were included in this study. The cohort was divided into 2 groups according to the presence or absence of ICU-AW. Clinical characteristics included age, sex, body mass index, length of ICU stay, multiple organ dysfunction syndrome, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), mechanical ventilation time, intubation, tracheotomy, protective constraint, lactic acid, fasting blood glucose, etc. The clinical characteristics of sepsis were evaluated using logistic regression analysis. Results: A total of 114 septic patients suffered ICU-AW during their ICU stay. Multivariate binary logistic regression analysis showed that APACHE Ⅱ score, mechanical ventilation time, protective constraint, and lactic acid were independent risk factors for ICU-AW in septic patients. The areas under the receiver operating characteristic curve (AUCs) were 0.791, 0.740 and 0.812, all P < 0.05, and the optimal cut-off values were 24 points, 5 days and 2.12 mmol/L, respectively. Conclusions: A high APACHE Ⅱ score, long mechanical ventilation time, protective constraint and high lactate concentration are independent risk factors for ICU-AW in septic patients. An APACHE Ⅱ score greater than 24 points, mechanical ventilation time longer than 5 days and lactate concentration higher than 2.12 mmol/L are likely to cause ICU-AW.

Naringenin mitigates cadmium-induced cell death, oxidative stress, mitochondrial dysfunction, and inflammation in KGN cells by regulating the expression of sirtuin-1.

The objective of this study was to examine the potential protective role of naringenin against the harmful effects induced by cadmium in KGN cell line. Cell viability was evaluated by cell counting kit-8 assay. Caspase-3/-9 activities were determined by caspase-3/-9 activity assay kits, respectively. Intracellular reactive oxygen species (ROS) level was detected by ROS-Glo™ H2O2 Assay, antioxidant capacity was determined by a total antioxidant capacity assay kit. Mitochondrial membrane potential (MMP), ATP level, and ATP synthase activity were determined by JC-1, ATP assay kit, and ATP synthase activity assay kit, respectively. The mRNA expression was determined by qRT-PCR. Cadmium reduced cell viability and increased caspase-3/-9 activities in a concentration-dependent manner. Naringenin improved cell viability and reduced caspase-3/-9 activities in cadmium-stimulated KGN cells in a concentration-dependent manner. Cadmium diminished the antioxidant capacity, increased ROS production, and induced mitochondrial dysfunction in KGN cells. These effects were ameliorated by naringenin treatment in a concentration-dependent manner. Furthermore, naringenin reduced the levels of pro-inflammatory cytokines in KGN cells exposed to cadmium. SIRT1 knockdown downregulated its expression in KGN cells and compromised the protective effects of naringenin on cell viability and caspase-3/-9 activities in cadmium-stimulated KGN cells. Naringenin prevented the reduction of MMP, ATP levels, and ATP synthase activity in cadmium-stimulated KGN cells in a concentration-dependent manner. However, these protective effects were significantly reversed by SIRT1 knockdown. In conclusion, this study suggests that naringenin protects against cadmium-induced damage by regulating oxidative stress, mitochondrial function, and inflammation in KGN cells, with SIRT1 playing a potential mediating role.

N-glycosylation of the SARS-CoV-2 spike protein at Asn331 and Asn343 is involved in spike-ACE2 binding, virus entry, and regulation of IL-6.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global public health crisis. The causative agent, the SARS-CoV-2 virus, enters host cells via molecular interactions between the viral spike protein and the host cell ACE2 surface protein. The SARS-CoV-2 spike protein is extensively decorated with up to 66 N-linked glycans. Glycosylation of viral proteins is known to function in immune evasion strategies but may also function in the molecular events of viral entry into host cells. Here, we show that N-glycosylation at Asn331 and Asn343 of SARS-CoV-2 spike protein is required for it to bind to ACE2 and for the entry of pseudovirus harboring the SARS-CoV-2 spike protein into cells. Interestingly, high-content glycan binding screening data have shown that N-glycosylation of Asn331 and Asn343 of the RBD is important for binding to the specific glycan molecule G4GN (Galß-1,4 GlcNAc), which is critical for spike-RBD-ACE2 binding. Furthermore, IL-6 was identified through antibody array analysis of conditioned media of the corresponding pseudovirus assay. Mutation of N-glycosylation of Asn331 and Asn343 sites of the spike receptor-binding domain (RBD) significantly reduced the transcriptional upregulation of pro-inflammatory signaling molecule IL-6. In addition, IL-6 levels correlated with spike protein levels in COVID-19 patients' serum. These findings establish the importance of RBD glycosylation in SARS-CoV-2 pathogenesis, which can be exploited for the development of novel therapeutics for COVID-19.

Urban green space area mitigates the accumulation of heavy metals in urban soils.

Despite that the heavy metals in urban soils pose a threat to public health, the critical factors that influence their concentrations in urban soils are not well understood. In this study, we conducted a survey of surface soil samples from urban green spaces in Shanghai, to analyze the concentrations of the key heavy metals. The results showed that Zn was the most abundant metal with an average concentration of 122.99 mg kg-1, followed by Pb (32.72 mg kg-1) and Cd (0.23 mg kg-1). All concentrations were found to be below the risk screening values defined by the National Environmental Quality Standards for soils of development land in China (GB36600-2018), indicating no current risk in Shanghai. However, there was a clear accumulation of heavy metals, as the mean concentrations were significantly higher than the background values. Furthermore, we explored the relationships between key heavy metals with population density, GDP and green space area. Both Spearman correlation and Random Forest analysis indicated that per capita green space area (pGSA) and population density were the most crucial factors influencing the status of heavy metals in urban soils, unlike edaphic factors e.g. SOM content in farmland soils. Specifically, there was a significantly positive linear correlation between heavy metal concentrations and population density, with correlation coefficients ranging from 0.3 to 0.4. However, the correlation with pGSA was found to be non-linear. The nonlinear regression analysis revealed threshold values between heavy metals concentrations and pGSA (e.g Zn 22.22 m2, Pb 24.92 m2, and Cd 25.92 m2), with a sharp reduction in heavy metal concentrations below the threshold and a slow reduction above the threshold. It suggests that an increase in per capita green space area can mitigate the accumulation of heavy metals caused by growing population density, but the effect is limited after the threshold. Our findings not only provide insights into the distribution patterns of heavy metals in the urban soils at the local scale, but also contribute to the urban greening at the global scale and offer guidance for city planning in the face of increasing population densities over the coming decades.

Effects of intrauterine infusion of platelet-rich plasma on hormone levels and endometrial receptivity in patients with repeated embryo implantation failure.

OBJECTIVE: To analyze the effect of intrauterine infusion on platelet-rich plasma on hormone levels and endometrial receptivity of patients with repeated embryo implantation failure (RIF). METHODS: A total of 64 patients with repeated implantation failure and re-fertilization-embryo transfer who were admitted to our hospital from January 2019 to December 2021 were analyzed retrospectively. Among them were 30 patients who did not receive the platelet-rich plasma perfusion therapy. This became the control group (CG). The 34 patients who received the therapy were regarded as the research group (RG). The changes of hormone levels before and after the treatment and endometrial receptivity after the treatment were evaluated. The outcomes of IVF assisted pregnancy, including rates of embryo implantation, clinical pregnancy, and early miscarriage, were compared after the treatment. Risk factors for clinical pregnancy were analyzed by logistic regression. RESULTS: After treatment, the estradiol (E2) level increased and the follicle stimulating hormone (FSH) level decreased (P<0.05), but there was no marked difference in luteinizing hormone (LH) before or after the treatment (P>0.05). The E2 level in the RG was higher than that in the CG, and FSH in the RG was lower (P<0.05). In comparison to CG, the endometrial thickness on the day of human chorionic gonadotropin (hCG) injection and embryo transfer in the RG increased dramatically (P<0.05). The uterine artery pulsation index (PI) and uterine artery resistance index (RI) decreased (P<0.05). The embryo implantation and clinical pregnancy rates in the RG increased markedly (P<0.01), and the early abortion rate decreased significantly (P<0.05). The logistic regression analysis identified that age, number of transplant failures, treatment regimens, and FSH were risk factors for clinical pregnancy outcomes in patients. CONCLUSION: Intrauterine infusion of platelet-rich plasma can improve the hormone levels in RIF patients, increase endometrial thickness, and enhance endometrial blood flow, increasing the pregnancy rate of patients and improving clinical pregnancy.

Data transforming: A concept analysis.

PURPOSE: The aims of this study are to clarify the concept of how data retrieved from electronic health records (EHR) are transformed into nurses' tacit knowledge for evidence-based practice from a cognitive perspective at a macro-organizational level, and to identify this concept's attributes, antecedents, and consequences in the nursing field. SOURCE: A literature review was conducted by performing a search on scientific databases using the key terms "data," "transform," "EHR," "nursing," "tacit knowledge," "organization," "data," "interpretation," and "healthcare." Forty-nine articles and four books were selected for the analysis. The process was audited by two independent experts to ensure neutrality and credibility. CONCLUSION: Data transforming is a complex cognitive process among different groups of data stakeholders at a macro-organizational level. The concept of data transforming has three attributes: analytical, respectful, and social. The antecedents of these attributes are skillful, immersive, and mission-driven. They have either positive or negative consequences for frontline nurses. These findings not only add to the body of knowledge but also serve as an important impetus for further theory development and research in nursing.

ORFV infection enhances CXCL16 secretion and causes oncolysis of lung cancer cells through immunogenic apoptosis.

Oncolytic viruses have been emerging as a promising therapeutic option for cancer patients, including lung cancer. Orf virus (ORFV), a DNA parapoxvirus, can infect its natural ungulate hosts and transmit into humans. Moreover, the ORFV has advantages of low toxicity, high targeted, self-amplification and can induce potent Th1-like immunity. This study explored the therapeutic potential of ORFV infection for human lung cancer therapy and investigated the molecular mechanisms. We used a previously described ORFV NA1/11 strain and tested the oncolysis of ORFV NA1/11 in two lines of lung cancer cells in vitro and in vivo. Treatment of both cell lines with ORFV NA1/11 resulted in a decrease in cell viability by inducing cell cycle arrest in G2/M phase, suppressing cyclin B1 expression and increasing their apoptosis in a caspase-dependent manner. The ORFV NA1/11-infected lung cancer cells were highly immunogenic. Evidently, ORFV NA1/11 infection of lung cancer cells induced oncolysis of tumor cells to release danger-associated molecular patterns, and promoted dendritic cell maturation, and CD8 T cell infiltration in the tumors by enhancing CXCL16 secretion. These findings may help to understand the molecular mechanisms of ORFV oncolysis and aid in the development of novel therapies for lung cancer.

Resveratrol regulates the inflammation and oxidative stress of granulosa cells in PCOS via targeting TLR2.

Polycystic ovary syndrome (PCOS) is featured as a common endocrine disorder in reproductive-aged women, while its pathophysiology is not fully illustrated. This study examined potential actions of resveratrol in PCOS cellular model and explored the underlying interaction between resveratrol and toll-like receptor 2 (TLR2). This study performed the bioinformatics analysis on two microarray datasets (GSE34526 and GSE138518). We found that TLR2 was one of potential hub genes that may be associated with PCOS. Further examination showed that TLR2 was highly expressed in granulosa cells from PCOS group compared with control. The in vitro studies showed that LPS intervention caused an increased expression of TLR2 and the pro-inflammatory mediators, and induced oxidative stress in the granulosa cells, which was concentration-dependently antagonized by resveratrol treatment. TLR2 silence significantly attenuated LPS-induced increase TNF-α, IL-1ß, IL-6 and IL-8 expression and oxidative stress of granulosa cells. Furthermore, TLR2 overexpression promoted inflammatory response and oxidative stress in the granulosa cells, which was antagonized by resveratrol treatment. In conclusion, resveratrol could attenuate LPS-induced inflammation and oxidative stress in granulosa cells, and the underlying mechanisms may be related to the inhibitory effect of resveratrol on TLR2 expression in granulosa cells.

Efficacy of Letrozole Combined with Urinary Gonadotropin for Ovulation Induction in Endocrine Abnormal Infertility Patients: A Retrospective Single-Center, Case-Control Study.

Aims: To ask lots of questions and try to find the truth about the medicine-based effectiveness of letrozole (LE) combined with human menopausal gonadotropin (HMG) in the treatment of inability to have children crops patients with endocrine (things that are different from what is usually expected and the effect on ovulation-related chemicals produced by the body). Materials and Methods: A total of 160 unable to have children crops patients with endocrine things that are different from what is usually expected who were treated in our hospital from March 2019 to March 2022 were selected as the subjects of this look at how things were in the past study and were divided into instance of watching, making a statement group was treated with human menopausal gonadotropin on the basis of the control group. The differences in serum related to the process of making children, chemical produced by the body levels, ovarian function, and ovulation induction effect between the two groups were watched and compared. Results: After treatment, LH, FSH, PRL, and E2 in the observation group were better than those in the control group. The ovarian volume, follicle size, follicle diameter, and endometrial thickness of the two groups of patients were significantly improved, and the observation group was better than the control group. Significance is P < 0.05. After treatment, the ovarian volume, follicle size, follicle diameter, and endometrial thickness in the two groups were significantly improved, and the observation group was better than the control group, and the difference was statistically significant (P < 0.05). The ovulation rate, pregnancy rate, singleton pregnancy rate, and multiple pregnancy rate of the observation group were higher than those of the control group, and the difference was statistically significant by the chi-square test (P < 0.05). Conclusion: Letrozole can promote the improvement of sex hormones in infertile patients. After being combined with human menopausal gonadotropin treatment, the follicle development and ovulation of patients are significantly improved, and infertility is improved to a certain extent. It has a certain reference value in the clinical treatment of endocrine abnormal infertility.

Development and evaluation of time-resolved fluorescent immunochromatographic assay for quantitative detection of SARS-CoV-2 spike antigen.

BACKGROUND: The spread of COVID-19 worldwide caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated efficient, sensitive diagnostic methods to identify infected people. We report on the development of a rapid 15-minute time-resolved fluorescent (TRF) lateral flow immunochromatographic assay for the quantitative detection of the SARS-CoV-2 spike protein receptor-binding domain (S1-RBD). OBJECTIVES: Our objective was to develop an efficient method of detecting SARS-CoV-2 within 15 min of sample collection. METHODS: We constructed and evaluated a portable, disposable lateral flow device, which detected the S1-RBD protein directly in nasopharyngeal swab samples. The device emits a fluorescent signal in the presence of S1-RBD, which can be captured by an automated TRF instrument. RESULTS: The TRF lateral flow assay signal was linear from 0 to 20 ng/ml and demonstrated high accuracy and reproducibility. When evaluated with clinical nasopharyngeal swabs, the assay was performed at >80% sensitivity, >84% specificity, and > 82% accuracy for detection of the S1-RBD antigen. CONCLUSION: The new S1-RBD antigen test is a rapid (15 min), sensitive, and specific assay that requires minimal sample preparation. Critically, the assay correlated closely with PCR-based methodology in nasopharyngeal swab samples, showing that the detected S1-RBD antigen levels correlate with SARS-CoV-2 virus load. Therefore, the new TRF lateral flow test for S1-RBD has potential application in point-of-care settings.

The Combined Use of Orf Virus and PAK4 Inhibitor Exerts Anti-tumor Effect in Breast Cancer.

The parapoxvirus Orf virus (ORFV) has long been recognized as one of the valuable vectors in researches of oncolytic virus. In order to develop a potential therapeutic strategy for breast cancer based on the oncolytic virotherapy via ORFV, firstly we explore the oncolytic effects of ORFV. Our research showed that ORFV exerts anti-tumor effects in vitro by inducing breast cancer cell G2/M phase arrest and cell apoptosis. In vivo experiments were carried out, in which we treated 4T1 tumor-bearing BALB/C mice via intratumoral injection of ORFV. ORFV can exert anti-tumor activity by regulating tumor microenvironment (TME) and inducing a host immune response plus directly oncolytic effect. The CRISPR-Cas9 knockout library targeting 507 kinases was used to screen out PAK4, which is beneficial to the anti-tumor effect of ORFV on breast cancer cells. PF-3758309 is a potent PAK4-targeted inhibitor. Co-using of ORFV and PF-3758309 as a combination treatment produces its anti-tumor effects through inhibition of cell viability, induction of apoptosis and suppression of cell migration and invasion in vitro. The results of in vivo experiments showed that the tumor growth of mice in the combination treatment group was significantly inhibited, which proved that the combination treatment exerts an effective anti-tumor effect in vivo. In summary, we have clarified the oncolytic effect of ORFV on breast cancer, and found that the combination of ORFV and PAK4 inhibitor can effectively improve the oncolytic effect of ORFV. We hope our research could provide a new idea for the development of new treatment strategies for breast cancer.

The spike-ACE2 binding assay: An in vitro platform for evaluating vaccination efficacy and for screening SARS-CoV-2 inhibitors and neutralizing antibodies.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has become a worldwide pandemic, and there is a pressing need for the rapid development of novel therapeutic strategies. SARS-CoV-2 viral entry is mediated by interaction between the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein and host cellular receptor, human angiotensin converting enzyme 2 (ACE2). The lack of a high throughput screening (HTS) platform for candidate drug screening means that no targeted COVID-19 treatments have been developed to date. To overcome this limitation, we developed a novel, rapid, simple, and HTS binding assay platform to screen potential inhibitors of the RBD-ACE2 complex. Three "neutralizing" mouse monoclonal antibodies capable of blocking the RBD-ACE2 interaction were identified using our binding assay and pseudovirus neutralization assay followed by further validation with the Focus Reduction Neutralization Test (FRNT), which analyzes the neutralization capacity of samples in the presence of live SARS-CoV-2. Furthermore, the consistency of our binding assay and FRNT results (R2 = 0.68) was demonstrated by patients' serum, of which were COVID-19 positive (n = 34) and COVID-19 negative (n = 76). Several small molecules selected for their potential to inhibit the Spike-ACE2 complex in silico were also confirmed with the binding assay. In addition, we have evaluated vaccine efficacy using binding assay platform and validated through pseudovirus neutralization assay. The correlation between binding assay & psuedovirus assay of the post vaccinated serum showed well correlated (R2 = 0.09) Moreover, our binding assay platform successfully validated different Spike RBD mutants. These results indicate that our binding assay can be used as a platform for in vitro screening of small molecules and monoclonal antibodies, and high-throughput assessment of antibody levels after vaccination. When conducting drug screening, computer virtual screening lacks actual basis, construction of pseudoviruses is relatively complicated, and even FRNT requires a P3 laboratory. There are few methods to determine the competitiveness of the target drug and SRBD or ACE2. Our binding assay can fill this gap and accelerate the process and efficiency of COVID-19 drug screening.

Preclinical efficacy and involvement of mTOR signaling in the mechanism of Orf virus against nasopharyngeal carcinoma cells.

AIMS: Orf virus (ORFV) is a parapoxvirus causing contagious ecthyma in sheep and goats. With inhibitory role of ORFV reported by previous studies, ORFV can be a candidate of oncolytic virus. However, few studies reported the application and mechanism of ORFV in nasopharyngeal carcinoma (NPC). We aimed to elucidate the anti-tumor mechanism of ORFV against NPC cells. MATERIALS AND METHODS: The anti-tumor effect of ORFV in NPC cells was confirmed by cell counting kit 8 (CCK-8) assay, flow cytometry and Western blot. In vitro and in vivo experiments were adopted to evaluate the inhibitory effect of ORFV in NPC cells. Western blot was used to determine the down-regulation of rapamycin (mTOR) signaling and autophagy enhancement induced by ORFV. To explore the mechanism of ORFV on NPC cells, mTOR signaling agonist and autophagy inhibitors were used to rescue the effects of ORFV. KEY FINDINGS: The results indicated that ORFV replicates in NPC cells, thus induces the apoptosis of NPC cells. Moreover, ORFV can effectively inhibit NPC cell growth in vivo. ORFV infection in NPC cells leads to the mTOR signaling inhibition and up-regulated autophagy, which might be the specific mechanism of ORFV in killing tumor cells. As to safety confirmation, normal nasopharyngeal epithelial cells NP69 are insensitive to ORFV. More importantly, ORFV would not cause organ damage in vivo. SIGNIFICANCES: Our data clarified that ORFV induces autophagy of NPC cells via inhibiting mTOR signaling, thus further inducing apoptosis. The anti-tumor role of ORFV might provide a preclinical strategy for NPC treatment.

Quantitative Detection of Anti-SARS-CoV-2 Antibodies Using Indirect ELISA.

OBJECTIVE: Real-time reverse transcription-polymerase chain reaction is the gold standard for the diagnosis of COVID-19, but it is necessary to utilize other tests to determine the burden of the disease and the spread of the outbreak such as IgG-, IgM-, and IgA-based antibody detection using enzyme-linked immunosorbent assay (ELISA). MATERIALS AND METHODS: We developed an indirect ELISA assay to quantitatively measure the amount of COVID-19 IgG, IgM, and IgA antibodies present in patient serum, dried blood, and plasma. RESULTS: The population cutoff values for positivity were determined by receiver operating characteristic curves to be 1.23 U/mL, 23.09 U/mL, and 6.36 U/mL for IgG, IgM, and IgA, respectively. After albumin subtraction, the specificity remained >98% and the sensitivity was 95.72%, 83.47%, and 82.60%, respectively, for IgG, IgM, and IgA antibodies to the combined spike subunit 1 receptor binding domain and N proteins in serum. Plasma and dried blood spot specimens were also validated on this assay. CONCLUSION: This assay may be used for determining the seroprevalence of SARS-CoV-2 in a population exposed to the virus or in vaccinated individuals.

Comprehensive Profiling of Inflammatory Factors Revealed That Growth Differentiation Factor-15 Is an Indicator of Disease Severity in COVID-19 Patients.

To systematically explore potential biomarkers which can predict disease severity in COVID-19 patients and prevent the occurrence or development of severe COVID-19, the levels of 440 factors were analyzed in patients categorized according to COVID-19 disease severity; including asymptomatic, mild, moderate, severe, convalescent and healthy control groups. Factor candidates were validated by ELISA and functional relevance was uncovered by bioinformatics analysis. To identify potential biomarkers of occurrence or development of COVID-19, patient sera from three different severity groups (moderate, severe, and critical) at three time points (admission, remission, and discharge) and the expression levels of candidate biomarkers were measured. Eleven differential factors associated with disease severity were pinpointed from 440 factors across 111 patients of differing disease severity. The dynamic changes of GDF15 reflect the progression of the disease, while the other differential factors include TRAIL R1, IGFBP-1, IGFBP-4, VCAM-1, sFRP-3, FABP2, Transferrin, GDF15, IL-1F7, IL-5Rα, and CD200. Elevation of white blood cell count, neutrophil count, neutrophil-lymphocyte ratio (NLR), Alanine aminotransferase and Aspartate aminotransferase, low lymphocyte and eosinophil counts in the severe group were associated with the severity of COVID-19. GDF15 levels were observed to be associated with the severity of COVID-19 and the dynamic change of GDF15 levels was closely associated with the COVID-19 disease progression. Therefore, GDF15 might serve as an indicator of disease severity in COVID-19 patients.

Identification of in vitro and in vivo oncolytic effect in colorectal cancer cells by Orf virus strain NA1/11.

Orf virus (ORFV) is a favorable oncolytic viral carrier in research, and ORFV strain NZ2 has been revealed to have antitumor effects in animal models mediated by immunoregulation profile. However, the antitumor effects triggered by the ORFV in colorectal cancer (CRC) cells is poorly characterized. The in vivo and in vitro roles of ORFV in CRC were determined using western blotting, colony formation, CCK­8, wound scratch assay, qPCR, and animal models. Furthermore, cytokine antibody chip assay, flow cytometry, western blotting, and immunohistochemical (IHC) assays were conducted to explore the potential mechanism of ORFV. The present data revealed that ORFV strain NA1/11 infected and inhibited the in vitro growth and migration of CRC cells. By establishing a CRC model in Balb/c mice, it was revealed that ORFV strain NA1/11 significantly inhibited the in vivo growth and migration of CRC cells. A cytokine antibody array was utilized to obtain a more comprehensive profile revealing the differentially expressed cytokines in ORFV infection. Cytokines, such as IL­7, IL­13, IL­15, CD27, CD30, pentraxin 3, and B lymphocyte chemoattractant (BLC), were upregulated. Axl, CXCL16, ANG­3, MMP10, IFN­Î³ R1 and VEGF­B were downregulated. The results indicated that ORFV played roles in the regulation of key factors relevant to apoptosis, autoimmunity/inflammation, angiogenesis, and the cell cycle. Finally, data was presented to validate that ORFV infection induces oncolytic activity by enhancing apoptosis in vivo and in vitro. In conclusion, ORFV could be an oncolytic virus for CRC therapy.

Confronting the threat of SARS-CoV-2: Realities, challenges and therapeutic strategies (Review).

The novel coronavirus (SARS-CoV-2) appeared in2019 in Wuhan, China, and rapidly developed into a global pandemic. The disease has affected not only health care systems and economies worldwide but has also changed the lifestyles and habits of the majority of the world's population. Among the potential targets for SARS-CoV-2 therapy, the viral spike glycoprotein has been studied most intensely, due to its key role in mediating viral entry into target cells and inducing a protective antibody response in infected individuals. In the present manuscript the molecular mechanisms that are responsible for SARS-CoV-2 infection are described and a progress report on the status of SARS-CoV-2 research is provided. A brief review of the clinical symptoms of the condition and current diagnostic methods and treatment plans for SARS-CoV-2 are also presented and the progress of preclinical research into medical intervention against SARS-CoV-2 infection are discussed.

Using Antibody Arrays for Biomarker Discovery.

Biomarkers for diseases are important for the development of clinical diagnostic tests and can provide early intervention for cancer or cardiovascular patients. Over the past decade, antibody array technology has achieved significant technological improvement in the quantitative measurement of more than a thousand proteins simultaneously and has been utilized to screen and identify unique proteins as disease biomarkers. However, few biomarkers have been translated into clinical application. This chapter will discuss the protocol for the screening and validation of unique proteins that create a new avenue for biomarker discovery.