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BackgroundTo mitigate the cardiotoxicity of anthracycline antibiotics without compromising their anticancer activities is still an issue to be solved. We previously demonstrated that schisandrin B (Sch B) could protect against doxorubicin (Dox)-induced acute cardiotoxicity via enhancing cardiomyocytic glutathione redox cycling that could attenuate oxidative stress generated from Dox. In this study, we attempted to prove if Sch B could also protect against Dox-induced chronic cardiotoxicity, a more clinically relevant issue, without compromising its anticancer activity.MethodologyRat was given intragastrically either vehicle or Sch B (50 mg/kg) two hours prior to i.p. Dox (2.5 mg/kg) weekly over a 5-week period with a cumulative dose of Dox 12.5 mg/kg. At the 6th and 12th week after last dosing, rats were subjected to cardiac function measurement, and left ventricles were processed for histological and ultrastructural examination. Dox anticancer activity enhanced by Sch B was evaluated by growth inhibition of 4T1, a breast cancer cell line, and S180, a sarcoma cell line, in vitro and in vivo.Principal FindingsPretreatment with Sch B significantly attenuated Dox-induced loss of cardiac function and damage of cardiomyocytic structure. Sch B substantially enhanced Dox cytotoxicities toward S180 in vitro and in vivo in mice, and increased Dox cytotoxcity against 4T1 in vitro. Although we did not observe this enhancement against the implanted 4T1 primary tumor, the spontaneous metastasis to lung was significantly reduced in combined treatment group than Dox alone group.ConclusionSch B is capable of protecting Dox-induced chronic cardiotoxicity and enhancing its anticancer activity. To the best of our knowledge, Sch B is the only molecule ever proved to function as a cardioprotective agent as well as a chemotherapeutic sensitizer, which is potentially applicable for cancer treatment.

Introduction The increased use of telehealth to maintain ambulatory care during the COVID-19 pandemic had potential to exacerbate or diminish disparities in access to care. Objective The purpose of this study was to describe patient characteristics associated with successful transition from in-person to virtual care, and video vs audio-only participation. Methods This was a retrospective analysis of electronic health record data from all patients with ambulatory visits from 1 October 2019–30 September 2020 in a large integrated health system in the Northeast USA. The outcome of interest was receipt of virtual care, and video vs audio-only participation. We matched home addresses with census-tract level area social vulnerability index (SVI) and Internet access. Among ambulatory care patients, we used logistic regression to identify characteristics associated with virtual participation. Among virtual participants, we identified characteristics associated with video vs audio-only visits. Results Among 1,241,313 patients, 528,542 (42.6%) were virtual participants. Relative to in-person only, virtual participants were older, more often English-proficient and with activated patient portal. Characteristics associated with virtual participation included patients with: only behavioural health visits, COVID patients, highest quartile of visit frequency, and multiple visit types. Characteristics associated with video participation (relative to audio-only) included being younger and patients with: only behavioural health visits, highest quartile of visit frequency, non-Hispanic black race, limited English proficiency and inactivated portal account. Discussion In our regional healthcare system, the transition to virtual care during COVID was vital for continued access to care, but substantial inequity remained. Without audio-only visits, access to care would have been even more limited for our most vulnerable patients.

Heat stress seriously threatens the growth of Pleurotus ostreatus. Various studies have been performed to study the resistance of P. ostreatus to heat stress. Here, the metabolome was evaluated to determine the response of P. ostreatus mycelia to heat stress at different times (6, 12, 24, 48 h). More than 70 differential metabolites were detected and enriched in their metabolic pathways. Dynamic metabolites changes in enrichment pathways under heat stress showed that heat stress enhanced the degradation of unsaturated fatty acids and nucleotides, increased the content of amino acids and vitamins, and accelerated glycolysis and the tricarboxylic acid cycle in P. ostreatus. The time course changes of P. ostreatus metabolites under continuous heat stress demonstrated that amino acids continuously changed with heat stress, nucleotides clearly changed with heat stress at 12 and 48 h, and lipids exhibited an increasing trend with prolonged heat stress, while few types saccharides and vitamins changed under heat stress. Additionally, heat-treated P. ostreatus produced salicylic acid and other stress-resistant substances that were reported in plants. This study first reported the metabolites changes in P. ostreatus mycelia during 48 h of heat stress. The metabolic pathways and substances that changed with heat stress in this research will aid future studies on the resistance of P. ostreatus and other edible fungi to heat stress.

The link between carcinogen exposure and cancer immunogenicity is unclear. Single exposure to 12-dimethylbenz[a]anthracene (DMBA) at puberty accelerated spontaneous breast carcinogenesis in mouse mammary tumor virus-polyoma middle tumor-antigen transgenic (MMTV-PyMTtg or PyMT) and MMTV-Her2/neutg (Her2) mice. Paradoxically, DMBA-treated PyMT and Her2 animals were protected from metastasis. CD8+ T cells significantly infiltrated DMBA-exposed breast cancers. CD8+ T cell depletion resulted in severe lung and liver metastasis in DMBA-treated PyMT mice. Besides increasing tumor mutational burden, DMBA exposure up-regulated Chemokine (C-C motif) ligand 21 (CCL21) in cancer cells and heightened antigen presentation. CCL21 injection suppressed breast cancer growth, and CCL21 receptor deletion attenuated T cell immunity against cancer metastasis in DMBA-treated PyMT animals. CCL21 expression correlated with increased mutational burden and cytolytic activity across human cancers. Higher CCL21 levels correlated with increased CD8+ T cell infiltrates in human breast cancer and predicted lower breast cancer distant recurrence rate. Collectively, carcinogen exposure induces immune-activating factors within cancer cells that promote CD8+ T cell immunity against metastasis.