"Y-type” PEG modified liposomes could eliminate the accelerated blood clearance (ABC) phenomenon and improved tumor therapy

Poly(ethylene glycol) (PEG) is widely applied to decorate nanocarriers due to its "long circulation” characteristics. However, the applications of linear PEG-modified nanocarriers have been hindered by severe adverse effects due to the accelerated blood clearance (ABC) phenomenon. It was universally known that anti-PEG antibodies (APAs) were main culprits in ABC phenomenon which induced the significant change in pharmacokinetics, biological distributions of the second injection and triggered complement activation-related pseudoallergies (CARPA). Recent studies have illustrated that APAs triggered the ABC phenomenon of PEGylated protein drug and even related to the CARPA of COVID-19 vaccine. Therefore, it is urgent to inhibit the generation of APAs and eliminate the ABC phenomenon. Here, "Y-type” PEG was chosen to replace linear PEG due to its weak immunogenicity. "Y-type” PEG-lipid derivatives [DSPE-mPEG2,n (n = 2, 10, and 20 kDa)]-modified doxorubicin liposomes (DOX-PL2,n) and topotecan liposomes (TP-PL2,n) induced lower levels of APAs and could avoid activating complement system. In further research, we found that liposomes decorated with DSPE-mPEG2,n could avoid the ABC phenomenon after duplicate injections. Furthermore, pharmacodynamic tests indicated that DOX-PL2,n and TP-PL2,n improved the curative effect of S180 tumor than DOX-PL2k and TP-PL2k (linear PEGylated liposomes). For the first time, DOX-PL2,n and TP-PL2,n were used for in vivo pharmacokinetic and pharmacodynamic experiments. Liposomes ornamented with "Y-type” PEG may provide new approaches to maintaining long blood circulation time, eliminating the ABC phenomenon of encapsulated active compounds, and also could weaken CARPA and improve tumor therapeutic effect. Our research aims to promote the research and development of "Y-type” PEG-decorated nanocarriers and provide a substantial academic basis for its clinical application.

COVID-19 risk perception and tourist satisfaction: A mixed-method study of the roles of destination image and self-protection behavior.

This study aimed to examine the effects of COVID-19 risk perception on negative destination image and self-protection behavior, and the resultant effects on tourist satisfaction. Hence, this study applied a continuous interpretive mixed-method design combining quantitative and qualitative analyses. A quantitative survey (n = 486) in the cities of Ningbo, Huangshan, and Chengdu, China, and 19 qualitative interviews were conducted online. The results of the quantitative study show that: (1) Risk perception and negative destination image are antecedent variables influencing tourist satisfaction, and (2) there are significant positive correlations between risk perception and negative destination image, risk perception and tourist self-protection behavior, and negative destination image and tourist self-protection behavior. Moreover, (3) negative destination image had a partial mediating effect between risk perception and satisfaction. Furthermore, to supplement the research data and expand the quantitative findings, this study further examined whether the above variables are related to tourist satisfaction, through in-depth interviews with tourists. The findings showed that COVID-19 risk perception, negative destination image, and self-protection behavior all affect tourist satisfaction. The findings provide valuable crisis management suggestions for the government and should contribute to the efforts of tourist destinations to build a healthy and safe image, thereby contributing to the sustainable development of tourism industries in the post-epidemic era.

Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure.

The Omicron, or Pango lineage B.1.1.529, variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection against severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple BioNTech BNT162b2 messenger RNA-vaccinated health care workers (HCWs) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple-vaccinated individuals, but the magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCWs who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.

Perceived Benefits and Forest Tourists Consumption Intention: Environmental Protection Attitude and Resource Utilization Attitude as Mediators

Establishing a relationship model between environmental protection and resource utilization attitude and consumption intention is the key to promoting the sustainable development of forest tourism. From the standpoint of the Stimulus–Organism–Response (SOR) framework, the purpose of this study is to explore the complex causal relationships between perceived benefits, attitudes toward environmental protection, resource utilization attitudes, and consumption intentions in the context of forest tourism. The research data have been collected using a questionnaire survey of 436 tourists at Siming Mountain in the suburbs of Ningbo city, China. Furthermore, it is analyzed by structural equation modeling. The results indicate a positive correlation between the perceived benefits and tourists’ consumption intention that is mediated by the tourists’ attitude toward resource utilization. Although the independent mediating effect of environmental protection attitude is not supported in this study, both attitudes have played a chain-mediating role between perceived benefit and consumption intention. This study contributes to the existing knowledge by measuring the impact of perceived benefits and environmental attitudes of forest tourists on consumption intentions.

Adversity Tries Friends: A Multilevel Analysis of Corporate Philanthropic Response to the Local Spread of COVID-19 in China.

We examine corporate philanthropic decisions in response to the local spread of COVID-19. From a strategic perspective, firms may proactively undertake philanthropic efforts to limit the spread of the pandemic and avoid a degraded business environment. From the perspective of non-trivial costs, increased economic uncertainty can raise concerns about business survival and lead to conservative philanthropic strategies. Following the proverb "prosperity makes friends, adversity tries them," at the provincial level, our results support the second perspective. Specifically, when the spread of the pandemic worsens in a province, local firms are less likely to make COVID-19-related donations in terms of likelihood and amount. Investors also react negatively, not only to the local spread of COVID-19 but also to COVID-19-related philanthropic donations. At the organizational level, our evidence indicates that there is at least some level of cost-benefit analysis underlying corporate philanthropic decisions. Specifically, corporate philanthropic donations, especially those made to the local business environment, are significantly affected by organizational-level factors, such as pre-existing resource availability and motives to acquire political and reputational resources. Overall, our multilevel study presents a comprehensive picture of corporate philanthropic decisions amid the COVID-19 crisis.

Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants.

The impact of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOCs) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection plus two vaccine doses), S1 antibody, memory B cells, and heterologous neutralization of B.1.351, P.1, and B.1.617.2 plateaued, whereas B.1.1.7 neutralization and spike T cell responses increased. Serology using the Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over the 5 months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.

Opportunistic timing of management earnings forecasts during the COVID-19 crisis in China

Abstract This study assumes that the severity of local COVID-19 spread can capture the short-run fluctuation of macro-level uncertainty in business environments. Given capital-market pressure and incentives to obtain favourable considerations from the government and lenders, we hypothesise that COVID-19-induced uncertainty can lead managers to release (delay) preexisting firm-specific bad (good) news. Our baseline results show that firms are more likely to disclose unfavourable (favourable) 2019 forecasts in days when recent COVID-19 cases in headquarter provinces increase (decrease). Results in further analyses provide evidence on the aforementioned reporting incentives by showing that the opportunistic timing behaviour is more prominent in firms with higher managerial ownership, non-state ownership, and in firms under financial distress. In addition, we uncover the role of local marketisation level and medical resources in mitigating the opportunistic timing behaviour. Finally, the analysis of market reactions shows that the manipulation of disclosure dates can influence the market price in a favourable direction for firms. Overall, our paper presents a comprehensive picture of corporate opportunistic timing behaviour amid the COVID-19 crisis.