Photodynamic therapy (PDT) combined with oxygenating strategies is widely employed in cancer treatment; however, oxygen-boosted PDT has failed to achieve an ideal effect due to the complexity, heterogeneity, and irreversible hypoxic environment generated by tumor tissues. With the emergence of Fe-dependent ferroptosis boasting reactive oxygen species (ROS) cytotoxicity as well, such a chemodynamic approach to cancer therapy has drawn extensive attention. In this study, hemoglobin (Hb) is connected with the photosensitizer chlorin e6 (Ce6) to construct a 2-in-1 nanoplatform (SRF@Hb-Ce6) with Sorafenib (SRF, ferroptosis promotor) loaded, combining oxygen-boosted PDT and potent ferroptosis. Benefiting from the intrinsic presence of Fe capable of binding oxygen, hemoglobin concurrently furnishes oxygen for oxygen-dependent PDT and Fe for Fe-dependent ferroptosis. Furthermore, amphiphilic MMP2-responsive peptide is incorporated into the skeleton of the nanoplatform to ensure drug-release specificity for safety improvement. Correlative measurements demonstrate the potentiation of PDT and ferroptosis with SRF@Hb-Ce6. More importantly, PDT strengthens ferroptosis by recruiting immune cells to secrete IFN-γ, which can sensitize the tumor to ferroptosis in our findings. The therapeutic effect of synergistic treatment with SRF@Hb-Ce6 in vitro and in vivo was proven significant, revealing the promising prospects of combined PDT and ferroptosis therapy with the 2-in-1 nanoplatform.

Objectives Withanolides are a group of modified C28 ergostane‐type steroids with a C‐22, C‐26 δ‐lactone side chain or a C‐23, C‐26 γ‐lactone side chain. They enjoy a limited distribution in the plant kingdom and predominantly occur in several genera of Solanaceae. Of which, the genus Physalis is an important resource for this type of natural molecules. The present review aims to comprehensively illustrate the structural characteristics and classification of withanolides, and particularly focus on the progression on phytochemical and pharmacological aspects of withanolides from Physalis ranging from January 2015 to June 2019. Key findings Approximately 351 natural withanolides with novel and unique structures have so far been identified from genus Physalis, mainly isolated from the species of P. angulata and P. peruviana. Withanolides demonstrated diverse biological activity, such as anticancer, anti‐inflammatory, antimicrobial, immunoregulatory, trypanocidal and leishmanicidal activity. Their observed pharmacological functions supported the uses of Physalis species in traditional or folk medicines. Summary Due to their unique structure skeleton and potent bioactivities, withanolides are regarded to be promising drug candidates, particularly for developing anticancer and anti‐inflammatory agents. Further investigations for discovering novel withanolides of genus Physalis, exploiting their pharmacological values and evaluating their potency as therapeutic agents are significant work.

Oxidative stress plays a central role in the pathogenesis of many human diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating the intracellular antioxidant response and is an emerging target for the prevention and therapy of oxidative stress-related diseases. Salviae Miltiorrhizae Radix et Rhizoma (SMRR) is a traditional Chinese medicine (TCM) and is commonly used for the therapy of cardiac cerebral diseases. Cumulative evidences indicated that the extract of SMRR and its constituents, represented by lipophilic diterpenoid quinones and hydrophilic phenolic acids, were capable of activating Nrf2 and inhibiting oxidative stress. These bioactive constituents demonstrated a therapeutic potential against human diseases, exemplified by cardiovascular diseases, neurodegenerative diseases, diabetes, nephropathy, and inflammation, based on the induction of Nrf2-mediated antioxidant response and the inhibition of oxidative stress. In the present review, we introduced the SMRR and Nrf2 signaling pathway, summarized the constituents with an Nrf2-inducing effect isolated from SMRR, and discussed the molecular mechanism and pharmacological functions of the SMRR extract and its constituents.

Anhedonia and amotivation, the hallmarks of negative symptoms in schizophrenia, are believed to be due to “emotion–behavior decoupling,” a failure in translating pleasure experience into appropriate goal‐directed behavior. A number of studies have reported that long‐term institutionalized schizophrenia patients suffer from more severe negative symptoms than community‐dwelling patients, but few studies have investigated pleasure experience and motivational behavior in schizophrenia patients who have experienced long‐term institutionalization. In this study, we recruited 26 long‐term institutionalized schizophrenia patients, 27 community‐dwelling schizophrenia patients, and 27 healthy controls. Participants were administered two specific computer‐based tasks to assess anhedonia and amotivation. The Anticipatory and Consummatory Pleasure (ACP) Task was used to measure emotion–behavior decoupling and the Effort‐Expenditure for Rewards Task (EEfRT) was used to measure amotivation related to rewards. Findings from the ACP Task showed that compared with healthy controls, the coupling between emotion experience and motivated behavior was significantly weaker in both clinical groups, suggesting that emotion–behavior decoupling could be a stable trait in schizophrenia patients. In the EEfRT, compared with both community‐dwelling patients and healthy controls, institutionalized patients with schizophrenia failed to expend more effort to gain potential rewards even when reward probability increased. These findings further reveal the underlying mechanism of anhedonia and amotivation and their potential relationships with long‐term institutionalization in patients with schizophrenia.