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Abstract Background In previously published studies, oncolytic adenovirus-mediated gene therapy has produced good results in targeting cancer cells. However, safety and efficacy, the two most important aspects in cancer therapy, remain serious challenges. The specific expression or deletion of replication related genes in an adenovirus has been frequently utilized to regulate the cancer cell specificity of a virus. Accordingly, in this study, we deleted 24 bp in E1A (bp924-bp947) and the entirety of E1B, including those genes encoding E1B 55kDa and E1B19kDa. We used the survivin promoter (SP) to control E1A in order to construct a new adenovirus vector named Ad.SP.E1A(Δ24).ΔE1B (briefly Ad.SPDD). HCCS1 (hepatocellular carcinoma suppressor 1) is a novel tumor suppressor gene that is able to specifically induce apoptosis in cancer cells. The expression cassette AFP-HCCS1-WPRE-SV40 was inserted into Ad.SPDD to form Ad.SPDD-HCCS1, enabling us to improve the safety and efficacy of oncolytic-mediated gene therapy for liver cancer. Results Ad.SPDD showed a decreased viral yield and less toxicity in normal cells but enhanced toxicity in liver cancer cells, compared with the cancer-specific adenovirus ZD55 (E1B55K deletion). Ad.SPDD-HCCS1 exhibited a potent anti-liver-cancer ability and decreased toxicity in vitro. Ad.SPDD-HCCS1 also showed a measurable capacity to inhibit Huh-7 xenograft tumor growth on nude mice. The underlying mechanism of Ad.SPDD-HCCS1-induced liver cancer cell death was found to be via the mitochondrial apoptosis pathway. Conclusions These results demonstrate that Ad.SPDD-HCCS1 was able to elicit reduced toxicity and enhanced efficacy both in vitro and in vivo compared to a previously constructed oncolytic adenovirus. Ad.SPDD-HCCS1 could be a promising candidate for liver cancer therapy.

Polyhedral boranes are a class of well-known boron molecular clusters with unique physical and chemical properties, and great efforts have been made in the past decades to find more effective synthetic methods. However, the established synthetic methods suffer from low efficiency and low selectivity because the mechanism of the B–H bond condensation reaction, critical for the synthesis of the polyhedral boranes, is not well understood. Here we report highly selective and efficient synthetic methods of the salts of the tetradecahydridoundecaborate (1–) (B11H14−) and dodecahydrido-dodecaborates (2–) (B12H122−) anions by employing commercially available and inexpensive starting materials. Both theoretical and experimental investigations are carried out to elucidate the reaction mechanisms. We have found that the nature of the B–H bond condensation is the dihydrogen bonding interaction in which the positively charged hydrogens (bridged hydrogens) play a crucial role. The current study has not only led to more effective and selective synthetic methods for B11H14− and B12H122− but also unveiled the nature of the B–H bond condensation and the general formation mechanisms of polyhedral boranes. This finding will facilitate the development of more effective synthetic methods for polyhedral boranes and spur their wide application. [ABSTRACT FROM AUTHOR]

The goal of our study was to evaluate the potential role of sTNF-RI as a biomarker of renal involvement in SLE patients and active SLE. The study sample consisted of two cohorts. The discovery cohort included 16 SLE patients without renal involvement (non-LN), 60 lupus nephritis (LN) patients and 21 healthy controls (HCs) and the replication cohort included 18 SLE non-LN patients, 116 LN patients and 36 HCs. The sTNF-RI levels differed significantly in the discovery cohort. The plasma sTNF-RI levels were higher in LN patients than in non-LN patients (p =.009) and HCs (p = 4 × 10−6). Plasma sTNF-RI levels were significantly higher in non-LN patients than in HCs (p =.03). The finding was confirmed in independent replication cohort (LNs vs. non-LN, p = 4.053 × 10−7; LNs vs. HCs, p = 2.395 × 10−18; non-LN vs. HCs, p = 2.51 × 10−4). The plasma sTNF-RI levels were associated with disease activity, renal function in SLE patients and urine protein in LN patients. The multivariate analysis revealed that high sTNF-RI was an independent risk factor for renal involvement. The multivariate logistic regression results suggested that high TNF-RI, high systolic blood pressure, high serum creatinine, low C4 and positive anti-dsDNA were independent risks of active SLE patients. A nomogram was constructed based on the results of multivariate logistic regression analysis and it was practical in predicting the risk of the active SLE patients. Immunohistochemistry suggested that the expression of TNF-RI in the kidney was increased. Plasma sTNF-RI might be a good biomarker of renal involvement and disease activity in SLE patients. [ABSTRACT FROM AUTHOR]

UKRI/STFC’s Scientific Computing Department (SCD) has a long and rich history of delivering face to face public engagement and outreach, both on site and in public places, as part of the wider STFC programme. Due to the global COVID-19 pandemic, SCD was forced to abandon an extensive planned programme of public engagement, alongside altering the day-to-day working methods of the majority of its staff. SCD had to respond rapidly to create a new, remote only, programme for the summer and for the foreseeable future. This was initially an exercise in improvisation, identifying existing activities that could be delivered remotely with minimal changes. As the pandemic went on, SCD also created new resources specifically for a remote audience and adapted existing activities where appropriate, using our evaluation framework to ensure these activities continued to meet the aims of the in-person programme. This paper presents the process through which this was achieved, some of the benefits and challenges of remote engagement and the plans for 2021 and beyond.