A supramolecular nanoplatform for imaging-guided phototherapies via hypoxia tumour microenvironment remodeling.

Photodynamic therapy (PDT) has emerged as an invasive and promising antitumour treatment, however, the hypoxia in deep tumour tissues and the poor water-solubility of photosensitizers as bottlenecks greatly hinder PDT efficiency. Herein, a tumour microenvironment (TME) activated supramolecular nanoplatform consisting of the pillar[5]arene-based amphiphilic polymer POPD, the phototherapeutic agent Cy7-CN, respiratory medication atovaquone (ATO) and chemotherapeutic drug pyridinyl camptothecin (CPT-Py) was constructed for imaging-guided hypoxia-ameliorated phototherapies. Owing to host-guest interaction, the photochemical and photophysical properties of cyanine were improved exceedingly due to the suppression of π-π stacking. Triggered by the acidic microenvironment in tumour sites, the supramolecular nanoplatform would dissociate and release CPT-Py and ATO which inhibits mitochondria-associated oxidative phosphorylation (OXPHOS) and encourages more oxygen to be used in enhanced PDT. In vitro and in vivo studies verified that the rational combination of ATO-enhanced PDT and PTT overcame the disadvantages of single phototherapy and formed mutual promotion, and simultaneously sensitized chemotherapeutic drugs, which resulted in high tumour inhibition. It is hoped that the supramolecular nanoplatform could shed light on the development of phototherapeutic agents.

Longitudinal study of mental health changes in residents affected by an initial outbreak of COVID-19 in China.

Introduction: The COVID-19 pandemic is ongoing, and the world continues to work to defeat it. We designed this study to understand the longitudinal change in the mental health of residents who experienced the initial disease outbreak in China and to explore the long-term influencing factors. Methods: The Perceived Stress Scale (PSS), Generalized Anxiety Scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) were administered to the same sample four times: during the initial outbreak (T1), 1 month later (T2), 18 months later (T3), and 26 months later (T4). Results: A total of 397 participants completed all of the follow ups. The mean PSS scores among the four time points showed significant differences (F = 183.98, P < 0.001), with the highest score at T1 (15.35 ± 7.14), a sharp decline at T2 (11.27 ± 6.27), an obvious rebound at T3 (15.17 ± 7.46), and finally a slight decrease at T4 (14.41 ± 7.99). Among the four mean GAD-7 scores, significant differences were also found (F = 242.0, P < 0.001), with the trend that from T1 (7.42 ± 6.03) to T2 (7.35 ± 5.88), the scores remained steady, while they showed an apparent decline at T3 (5.00 ± 5.30) and no obvious change at T4 (4.91 ± 4.81). There were no significant differences among the mean PHQ-9 scores (F = 1.256, P < 0.284). The long-term influencing factors differed for stress, anxiety and depression, but all three were influenced by a history of psychosis at T4, quarantine status and whether the participants' family members were infected during the initial outbreak. Discussion: The survey revealed that repeated outbreaks in other areas also had an impact on those who experienced the initial outbreak, with a return of stress, a decline in anxiety, and no change in depression, which provides direction for interventions in the future.

Psychosocial Factors Associated With Increased Adolescent Non-suicidal Self-Injury During the COVID-19 Pandemic.

Non-suicidal self-injury (NSSI) in adolescents hospitalized with psychiatric disorders continues to increase after the outbreak of COVID-19. This study aimed to explore the relationship between the pandemic and NSSI among adolescents and whether the composition of psychosocial factors related to NSSI has changed during the pandemic. Through the retrospective analysis of medical records retrieved from the electronic system of the psychiatric hospital located in Chengdu from January 2016 to March 2021, 609 medical records of adolescents were obtained. The main potential psychosocial factors were determined by deductive content analysis. Among the 609 adolescents, 420 subjects had engaged in NSSI, while 189 did not. We found that the percentage of adolescents who had engaged in NSSI in 2016 was only 29.2%, reaching 34.5% in 2017, 45.7% in 2018, 61.3% in 2019, 92.5% in 2020, and 95.9% in 2021. In the binary logistic regression model, female sex (OR = 0.073, 95% CI: 0.028-0.186), older age (OR = 1.234, 95% CI: 1.030-1.478), having a single parent (OR = 7.865, 95% CI: 3.997-15.476), having experienced trauma (OR = 2.192, 95% CI: 1.032-4.654), having experienced social isolation from peers (OR = 8.139, 95% CI: 4.037-16.408), having experienced body-focused bullying (OR = 3.078, 95% CI: 1.295-7.318), overuse of a mobile phone in the parents' opinions (OR = 4.354, 95% CI: 1.380-13.738), having attempted suicide (OR = 9.120, 95% CI: 4.492-18.512), and during the pandemic (time point is January 30, 2020) (OR = 5.399, 95% CI: 1.679-17.357) were the factors that were significantly associated with NSSI. When comparing the differences in psychosocial factors between the pre-pandemic and the during-pandemic groups, the results showed that the family constitution, parent-child relationships, mobile phone overuse, and stressful learning were important factors. Tailored interventions geared towards changed psychosocial factors should be formulated.

Investigation on the Influencing Factors of Mental Health of Healthcare Workers for Aid in Hubei during the Outbreak of COVID-19.

BACKGROUND: This study aimed to determine the factors that were related to the psychological health status of healthcare workers aid for Hubei after the COVID-19 outbreak. METHODS: A total of 1260 participants completed the Self-Rating Scale of Sleep (SRSS), the Generalized Anxiety Scale (GAD-7), and the 9-item patient health questionnaire (PHQ-9) via the online questionnaires, and their related experiences with COVID-19 were collected. RESULTS: The average SRSS score of all participants (25.13 ± 6.41) indicated a mild sleep problem, and the factors that influenced their sleep were the respondent's gender, whether they had patients who died under their care, their history of psychosis and whether their family members were infected with COVID-19. The average GAD-7 score of all participants (12.37 ± 4.89) indicated a moderate anxiety level. The main factors that influenced anxiety were the respondent's gender, years of work, history of psychosis, self-perceived health status, and whether their family members were infected with COVID-19. The average PHQ-9 score of all participants (8.90 ± 5.42) indicated a mild depression level. The primary factors that influenced depression were whether the respondent had nursed/treated severely ill patients in Hubei and whether they had a history of psychosis. CONCLUSIONS: During the outbreak of COVID-19, the symptoms of anxiety were prominent among healthcare workers in Hubei. Moreover, male workers, those whose patients died during treatment, those with a history of anxiety disorders and those whose family members were infected with COVID-19 reported more serious problems. Therefore, this particular group of healthcare workers needs to be monitored and provided with tailored psychological support.

The qualitative analysis of characteristic of callers to a psychological hotline at the early stage of COVID-19 in China.

BACKGROUND: As the outbreak of COVID-19, traditional face-to-face psychological intervention are difficult to achieve, so hotline becomes available and recommended strategies. The callers' characteristic could help us to study their experiences of emotional distress, as well as the reasons for calling during the pandemic, which can be used to inform future service design and delivery. METHODS: The information of 1558 callers called our hospital' s hotline for help from February 3, 2020, to March 16, 2020 were collected in the form of Tick-box and Free text, and the inductive content analysis was undertaken focusing on the reasons for caller engagement. RESULTS: It was indicated that more than half of the callers are female (59.7%), mostly between the age of 18-59 (76.5%). The average age was 37.13 ± 13.76 years old. The average duration of a call to the hotline was 10.03 ± 9.84 min. The most frequent description emotional state were anxious (45.1%) and calm (30.3%), with the sub-sequence of scared (18.2%), sad (11.9%), and angry (6.9%). All callers displayed a wide range of reasons for calling, with needing support around their emotion (64.6%), seeking practical help (44.0%), and sleep problems (20.3%) constituting the majority of calls. Among the subthemes, 314 callers thought the epidemic has made them upset, 198 asked questions about the epidemic, and 119 reported their life routines were disrupted. The prevalence of key reasons does not appear to differ over time. Through their feedback, 79.1% agreed that they felt emotionally better after calling, and 95.0% agreed that hotline had helped them. CONCLUSIONS: During the epidemic, the most concern of the public is still related to epidemics and its adverse effects. Fortunately, the hotline can be an active and effective rescue measure after an emergency happened.

Zeolitic Imidazolate Framework Platform for Combinational Starvation Therapy and Oxygen Self-Sufficient Photodynamic Therapy against a Hypoxia Tumor.

The antitumor efficacy of photodynamic therapy (PDT) is greatly impeded by the nonspecific targeting of photosensitizers and limited oxygen supply in hypoxic tumors. Aiming to overcome the problem, a dual-locked porphyrin/enzyme-loading zeolitic imidazolate framework (ZIF) nanoplatform was constructed for starvation therapy and O2 self-sufficient PDT. The fluorescence recovery and PDT of photosensitizers could be cooperatively triggered by dual pathological parameters, the low pH and overexpressed GSH in tumor tissues, which makes the PDT process conduct precisely in a tumor microenvironment. The cascade catalysis of glucose oxidase and catalase promotes the nanoplatform dissociation, inhibits the energy supply of tumors (starvation therapy), and provides enough O2 to ameliorate the hypoxia and enhance PDT efficacy. In vitro and in vivo studies were performed to confirm the high antitumor efficacy of the porphyrin/enzyme-loading ZIF nanoplatform. Thus, this work offers a path for precise and efficient PDT-based combination therapy against a hypoxia tumor.

Pillar[5]arene-Based Switched Supramolecular Photosensitizer for Self-Amplified and pH-Activated Photodynamic Therapy.

Photodynamic therapy (PDT) has emerged as a promising and spatiotemporally controllable cancer treatment modality. However, serious skin photosensitization during the PDT process limits the clinical application of PDT. Thus, the construction of "smart" and multifunctional photosensitizers has attracted substantial interest. Herein, we develop a mitochondria-targeting and pH-switched hybrid supramolecular photosensitizer by the host-guest interaction. The PDT efficacy of supramolecular photosensitizers can be quenched by the Förster resonance energy transfer (FRET) effect during long circulation and activated by the dissociation of supramolecular photosensitizers in an acidic tumor microenvironment, benefitting from the dynamic feature of the host-guest interaction and pH responsiveness of the water-soluble pillar[5]arene on gold nanoparticles. The rational integration of mitochondria-targeting and reductive glutathione (GSH) elimination in the hybrid switchable supramolecular photosensitizer prolongs the lifetime of reactive oxygen species generated in the PDT near mitochondria and further amplifies the PDT efficacy. Thus, the facile and versatile construction of switchable supramolecular photosensitizer offers not only the targeted and precise phototherapy but also high therapeutic efficacy, which would provide a new path for the clinic application of PDT.

Water-Soluble Polymers with Appending Porphyrins as Bioinspired Catalysts for the Hydrogen Evolution Reaction.

Molecular design to improve catalyst performance is significant but challenging. In enzymes, residue groups that are close to reaction centers play critical roles in regulating activities. Using this bioinspired strategy, three water-soluble polymers were designed with appending Co porphyrins and different side-chain groups to mimic enzyme reaction centers and activity-controlling residue groups, respectively. With these polymers, high hydrogen evolution efficiency was achieved in neutral aqueous media for electro- (turnover frequency >2.3×104  s-1 ) and photocatalysis (turnover number >2.7×104 ). Porphyrin units are surrounded and protected by polymer chains, and more importantly, the activity can be tuned with different side-chain groups. Therefore, instead of revising molecular structures that is difficult from both design and synthesis points of view, polymers can be used to improve molecular solubility and stability and simultaneously regulate activity by using side-chain groups.

NIR-Triggered Multifunctional and Degradable Nanoplatform Based on an ROS-Sensitive Block Copolymer for Imaging-Guided Chemo-Phototherapy.

Imaging-guided chemo-phototherapy based on multifunctional nanocarriers has emerged as a promising and high-efficient cancer treatment because of the inevitable limitations of single therapy. Herein, a near-infrared (NIR) light-activated degradable polymeric nanoplatform was fabricated for chemo-phototherapy. An NIR photosensitizer, IR780, and a chemotherapeutic drug, doxorubicin (DOX), were efficiently coloaded within a reactive oxygen species (ROS)-sensitive polymeric micelle based on an amphiphilic copolymer with degradable thioketal (TK) linkages. The obtained spherical nanoparticles (denoted as (IR780/DOX)@PTK) exhibited a notable photodynamic and photothermal effect upon NIR light exposure. Furthermore, due to the rapid cleavage of TK linkers induced by ROS generated from NIR-activated IR780, (IR780/DOX)@PTK also showed an NIR light-induced degradable feature, which can be used for light-triggered tumor-specific drug release and lead to ignorable systematic toxicity after biodegradation and drug delivery. Under the guidance of NIR fluorescence and photothermal dual modal imaging, (IR780/DOX)@PTK exhibited excellent tumor accumulation after intravenously injection into 4T1-tumor-bearing mice. As verified in both in vitro and in vivo study, (IR780/DOX)@PTK presented a significant tumor suppression effect by synergistic chemo-phototherapy.