Ciwujianoside E inhibits Burkitt lymphoma cell proliferation and invasion by blocking ENO1-plasminogen interaction and TGF-ß1 activation.

Burkitt's lymphoma (BL) is a rare and highly aggressive B-cell non-Hodgkin lymphoma. Although the outcomes of patients with BL have greatly improved, options for patients with relapsed and refractory BL are limited. Therefore, there is an urgent need to improve BL therapeutics and to develop novel drugs with reduced toxicity. In this study, we demonstrated that enolase 1 (ENO1) is a potential novel drug target for BL treatment. We determined that ENO1 was aberrantly upregulated in BL, which was closely related to its invasiveness and poor clinical outcomes. Furthermore, using RNA interference, we demonstrated that ENO1 depletion significantly inhibited cell proliferation and invasion both in vitro and in vivo. Mechanistically, we established that ENO1 knockdown suppressed the PI3K-AKT and epithelial-mesenchymal transition (EMT) signaling pathways by reducing plasminogen (PLG) recruitment, plasmin (PL) generation, and TGF-ß1 activation. Addition of activated TGF-ß1 protein to the culture medium of shENO1 cells reversed the inhibitory effects on cell proliferation and invasion, as well as those on the PI3K-AKT and EMT signaling pathways. Notably, our research led to the discovery of a novel ENO1-PLG interaction inhibitor, Ciwujianoside E (L-06). L-06 effectively disrupts the interaction between ENO1 and PLG, consequently reducing PL generation and suppressing TGF-ß1 activation. In both in vitro and in vivo experiments, L-06 exerted impressive antitumor effects. In summary, our study elucidated the critical role of ENO1 in BL cell proliferation and invasion and introduced a novel ENO1 inhibitor, which holds promise for improving the treatment of patients with BL in the future.

Distinct drivers of bacterial community assembly processes in riverine islands in the middle and lower reaches of the Yangtze River.

Riverine islands are widespread alluvium wetlands developed in large rivers, and bacterial communities are crucial to their ecological function, yet their assembly processes are rarely addressed. The ecosystem services provided by the middle and the lower Yangtze are primarily threatened by pollution discharge from agricultural land use, and resource overutilization (e.g., embankments), respectively. Here, we assessed bacterial community assembly processes and their drivers within riverine islands in the middle Yangtze River (MR islands) and those in the lower reach (LR islands). A significant distance-decay relationship was observed, although the turnover rate was lower than that of the terrestrial ecosystem with less connectivity. Deterministic and stochastic processes jointly shaped community patterns, and the influence of stochastic increased from 26% in MR islands to 59% for those in LR islands. Meanwhile, the bacterial community in MR islands was controlled more by inorganic nitrogen availability, whereas those in LR islands were governed by pH and EC, although those factors explained a limited fraction of variation in the bacterial community. Potential indicator taxa (affiliated with Nocardioides and Lysobacter) characterized the waterway transport pollution. Overall, our study demonstrated that bacterial community dissimilarity and the importance of dispersal limitation increased concurrently along the flow direction, while distinct local factors further determined bacterial community compositions by selecting habitat-specificity taxa and particularly metabolism function. These findings enhanced our understanding of the mechanisms driving changes in bacterial communities of riverine islands subject to increased anthropogenic impacts.IMPORTANCERivers are among the most threatened ecosystems globally and face multiple stressors related to human activity. However, linkages between microbial diversity patterns and assembly processes in rivers remain unclear, especially in riverine islands developed in large rivers. Our findings reveal that distinct factors result in divergent bacterial community compositions and functional profiles in the riverine islands in the middle Yangtze and those in the lower Yangtze, with substantial differentiation in deterministic and stochastic processes that jointly contribute to bacterial community assemblages. Additionally, keystone species may play important metabolic roles in coping with human-related disturbances. This study provides an improved understanding of relationships between microbial diversity patterns and ecosystem functions under environmental changes in large river ecosystems.

Biosynthetic MnSe nanobomb with low Mn content activates the cGAS-STING pathway and induces immunogenic cell death to enhance antitumour immunity.

Triple-negative breast cancer (TNBC) is a relatively "cold" tumour with low immunogenicity compared to other tumour types. Especially, the immune checkpoint inhibitors to treat metastatic TNBC only shows the modest immune response rates. Here, we used Chlorella vulgaris as a bioreactor to synthesize an efficient nanobomb (Bio-MnSe) aimed at eliciting systemic anti-tumour immune response. Despite possessing extremely low Mn content, Bio-MnSe effectively produced more ROS and activated stronger cGAS-STING signal pathway compared to pure Se nanoparticles and free Mn2+ ions, promoting the infiltration of natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) in tumour, effectively turning "cold" tumour into "hot" tumour, and achieving strong antitumour immunotherapy. Additionally, the use of αPD-L1 as an immune checkpoint antagonist further increased the anti-tumour immune response of Bio-MnSe, resulting in enhanced anti-tumour effects. Doxorubicin (Dox), an immunogenic cell death (ICD) inducer, was combined with Bio-MnSe to form Bio-MnSe@Dox. This Bio-MnSe@Dox not only directly damaged tumour cells and induced tumour ICD but also promoted dendritic cell maturation, cytotoxic T lymphocyte infiltration, and NK cell recruitment, synergistically intensifying anti-tumour immune responses and suppressing tumour relapse and lung metastasis. Collectively, our findings propose an effective strategy for transforming 'cold' tumours to 'hot' ones, thereby advancing the development of anti-tumour immune drugs. STATEMENT OF SIGNIFICANCE: A biogenic MnSe (Bio-MnSe) nanocomposite was synthesized using Chlorella vulgaris as a bioreactor for enhanced immunotherapy of TNBC. Bio-MnSe demonstrated a stronger ability to activate the cGAS-STING signalling pathway and generate more ROS compared to pure Se nanoparticles and free Mn2+ ions. Apoptotic cells induced by Bio-MnSe released a significant amount of interferon, leading to the activation of T and natural killer (NK) cells, ultimately transforming immunologically 'cold' breast tumours to 'hot' tumours and enhancing the tumour's response to immune checkpoint inhibitors. The combination of Bio-MnSe with Dox or αPD-L1 further enhanced the anti-tumour immune response, fostering dendritic cell maturation, infiltration of cytotoxic T lymphocytes, and recruitment of NK cells, thereby enhancing the anti-tumour immunotherapy of TNBC.

A homologous-targeting cGAS-STING agonist multimodally activates dendritic cells for enhanced cancer immunotherapy.

Herein, we developed a doxorubicin (Dox)-loaded and 4T1 cancer cell membrane-modified hydrogenated manganese oxide nanoparticles (mHMnO-Dox) to elicit systemic antitumor immune responses. The results revealed that mHMnO-Dox actively recognized tumor cells and then effectively delivered Dox into the cells. Upon entering tumor cells, the mHMnO-Dox underwent rapid degradation and abundant release of Mn2+ and chemotherapeutic drugs. The released Mn2+ not only catalysed a Fenton-type reaction to produce excessive reactive oxygen species (ROS) but also activated the cGAS-STING pathway to boost dendritic cell (DC) maturation. This process increased cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment into the tumor site. In addition, the released Dox could contribute to a chemotherapeutic effect, while activating DC cells and subsequently intensifying immune responses through immunogenic cell death (ICD) of tumor cells. Consequently, the mHMnO-Dox suppressed the primary and distal tumor growth and inhibited tumor relapse and metastasis, as well as prolonged the lifespan of tumor-bearing mice. Thus, the mHMnO-Dox multimodally activated DC cells to demonstrate synergistic antitumor activity, which was mediated via the activation of the cGAS-STING signalling pathway to regulate tumor microenvironment, ICD-mediated immunotherapy and ROS-mediated CDT. These findings suggest the therapeutic potential of mHMnO-Dox in cancer immunotherapy. STATEMENT OF SIGNIFICANCE: A cancer cell membrane-camouflaged hydrogenated mesoporous manganese oxide (mHMnO) has been developed as a cGAS-STING agonist and ICD inducer. The mHMnO effectively induced abundance of ROS production in cancer cells, which caused cancer cell death and then promoted DC maturation via tumour-associated antigen presentation. Meanwhile, the mHMnO significantly activated cGAS-STING pathway to facilitate DC maturation and cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment, which further enhanced tumour immune response. In addition, the combination of the mHMnO and Dox could synergistically promote tumour ICD and then multimodally induce DC maturation, achieving an enhanced CIT. Overall, this study provides a potential strategy to design novel immunologic adjuvant for enhanced CIT.

NIR-IIb fluorescence antiangiogenesis copper nano-reaper for enhanced synergistic cancer therapy.

The formation of blood vessel system under a relatively higher Cu2+ ion level is an indispensable precondition for tumor proliferation and migration, which was assisted in forming the tumor immune microenvironment. Herein, a copper ions nano-reaper (LMDFP) is rationally designed not only for chelating copper ions in tumors, but also for combination with photothermal therapy (PTT) to improve antitumor efficiency. Under 808 nm laser irradiation, the fabricated nano-reaper converts light energy into thermal energy to kill tumor cells and promotes the release of D-penicillamine (DPA) in LMDFP. Photothermal properties of LMDFP can cause tumor ablation in situ, which further induces immunogenic cell death (ICD) to promote systematic antitumor immunity. The released DPA exerts an anti-angiogenesis effect on the tumor through chelating copper ions, and inhibits the expression of programmed death ligand 1 (PD-L1), which synergizes with PTT to enhance antitumor immunity and inhibit tumor metastasis. Meanwhile, the nanoplatform can emit near-infrared-IIb (NIR-IIb) fluorescence under 980 nm excitation, which can be used to track the nano-reaper and determine the optimal time point for PTT. Thus, the fabricated nano-reaper shows powerful potential in inhibiting tumor growth and metastasis, and holds great promise for the application of copper nanochelator in precise tumor treatment.

Current situation and influence factors of scientific integrity in China: A multicenter survey.

Objective: Cases of scientific misconduct have occurred frequently, especially in the field of medical research. We collected electronic questionnaires from 1257 medical staff in 43 cities and obtained a cross-sectional data set of their understanding of scientific integrity in research. This study aims to propose recommendations for establishing a mature oversight system for research integrity. Methods: The study employed multiple regression analysis to explore the effect of different factors on the perception of four types of research integrity. Results: Female participants had a higher understanding of project application integrity than men (P < â€‹ 0.001). Participants in clinical departments had a lower understanding of project application integrity than those in nursing departments (clinical vs. nursing, P â€‹= 0.046). Participants with a junior college degree or below had a lower understanding than those who had a postgraduate degree and doctoral degree (junior college or below vs. postgraduate degree, P â€‹< â€‹0.001; junior college or below vs. doctoral degree, P â€‹< â€‹0.001). Conclusions: We found that female, medical technology department, advanced education background, and advanced professional titles were significantly associated with a higher understanding of scientific integrity in research in China.

Depression and approach-avoidance achievement goals of Chinese undergraduate students: A four-wave longitudinal study.

OBJECTIVE: The study explored the prospective relations between depression and approach-avoidance achievement goals of undergraduate students in China. METHODS: 2473 full-time undergraduates reported their depression and achievement goals annually from the freshman to the senior year. Data were analysed using descriptive statistics, correlation analysis and cross-lagged models. RESULTS: Students' achievement goals decreased gradually during the first 3 years but rose in the fourth year, and the avoidance goals appeared to be less prevalent than the approach goals over time. Depression was negatively associated with approach goals, whereas positively correlated with avoidance goals. Depression in the freshman and sophomore years resulted in more avoidance goals 1 year later, and the depressive problems in the junior year predicted the decline of approach goals in the senior year. CONCLUSIONS: The present study highlighted the deleterious effects of depression on the achievement goals of college students.

Efficacy of traditional Chinese medicine external therapy on sleep quality in patients with cancer: A systematic review and network meta-analysis.

Objective: This network meta-analysis aims to assess and compare the effectiveness of various external therapies from traditional Chinese medicine (TCM) in enhancing sleep quality among patients with cancer. Methods: We systematically searched nine electronic databases, encompassing five English and four Chinese databases, for randomized controlled trials (RCTs) from their inception up to August 10, 2023. The random effects model was utilized for effect size analysis, and the standardized mean difference (SMD) along with its corresponding 95% confidence interval (CI) were computed. Network meta-analysis and comparative effects ranking were executed utilizing STATA 14.0. Results: We included thirty-four RCTs involving seven distinct external TCM therapies. Among these, Chinese medicine pillow (SMD = -3.27; 95% CI: -6.03 to -0.51), auricular acupressure (SMD = -2.33; 95% CI: -3.36 to -1.29), moxibustion (SMD = -2.28; 95% CI: -3.63 to -0.94), acupressure (SMD = -1.67; 95% CI: -2.64 to -0.70), and acupuncture (SMD = -1.43; 95% CI: -2.65 to -0.21) demonstrated significant effects in improving sleep quality when compared to usual care or waitlist. The cumulative ranking curve values revealed that the Chinese medicine pillow exhibited the highest potential for effectively enhancing sleep quality in patients with cancer, followed by auricular acupressure, moxibustion, acupressure, acupuncture, Tuina, and electroacupuncture. Conclusions: Our study highlights the Chinese medicine pillow as an optimal external TCM therapy for ameliorating sleep quality in cancer patients, but more RCTs are needed to validate this conclusion. These findings serve as valuable support for future clinical trials and research endeavors. Systematic review registration: CRD42022381370.

Inhibitive effects of phytic acid combined with glutathione on the browning and oxidation of King Oyster mushroom (Pleurotus eryngii) slices during drying and storage.

Phytic acid and glutathione can inhibit polyphenoloxidase (PPO) activity and suppress browning. This study investigated the effects of phytic acid alone (Treatment-1) or combined with glutathione (Treatment-2) on inhibiting browning and oxidation resistance of King Oyster mushroom (Pleurotus eryngii) slices during drying and storage. In King Oyster mushroom slices, 0.08% phytic acid combined with 0.1% glutathione inhibited the PPO activity by 97.6%, suppressed browning by 78.09% after 6 h of drying at 60 °C and inhibited browning by 69.93% and oxidation by 78.75% after 12 months of storage at âˆ¼ 20 °C. Results indicated that using phytic acid combined with glutathione may inhibit browning and suppress the oxidation of King Oyster mushroom slices during drying and storage.

Proteomics and ß-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice.

Aging is widely accepted as an independent risk factor for cardiovascular disease (CVD), which contributes to increasing morbidity and mortality in the elderly population. Lysine ß-hydroxybutyrylation (Kbhb) is a novel post-translational modification (PTM), wherein ß-hydroxybutyrate is covalently attached to lysine ε-amino groups. Recent studies have revealed that histone Kbhb contributes to tumor progression, diabetic cardiomyopathy progression, and postnatal heart development. However, no studies have yet reported a global analysis of Kbhb proteins in aging hearts or elucidated the mechanisms underlying this modification in the process. Herein, we conducted quantitative proteomics and Kbhb PTM omics to comprehensively elucidate the alterations of global proteome and Kbhb modification in the hearts of aged mice. The results revealed a decline in grip strength and cardiac diastolic function in 22-month-old aged mice compared to 3-month-old young mice. High-throughput liquid chromatogram-mass spectrometry analysis identified 1710 ß-hydroxybutyrylated lysine sites in 641 proteins in the cardiac tissue of young and aged mice. Additionally, 183 Kbhb sites identified in 134 proteins exhibited significant differential modification in aged hearts (fold change (FC) > 1.5 or <1/1.5, p < 0.05). Notably, the Kbhb-modified proteins were primarily detected in energy metabolism pathways, such as fatty acid elongation, glyoxylate and dicarboxylate metabolism, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, these Kbhb-modified proteins were predominantly localized in the mitochondria. The present study, for the first time, provides a global proteomic profile and Kbhb modification landscape of cardiomyocytes in aged hearts. These findings put forth novel possibilities for treating cardiac aging and aging-related CVDs by reversing abnormal Kbhb modifications.

Career Education Skills and Career Adaptability among College Students in China: The Mediating Role of Career Decision-Making Self-Efficacy.

In the past, the shift in career patterns and the unprecedented disruptions caused by events such as COVID-19 have posed notable challenges for job seekers. This holds particularly true for college students who are preparing to enter the workforce. In this context, enhancing career adaptability plays a vital role in shaping their career development. The primary objective of this research was to investigate the relationship between career education skills and career adaptability among 273 undergraduate students in China. Additionally, the study aimed to explore the mediating effect of career decision-making self-efficacy in shaping this relationship. The findings of the correlation analysis indicate a significant positive correlation between career education skills and career adaptability. Moreover, the results of the mediation model revealed that career education skills significantly contribute to improving career adaptability along with the mediating effect of college students' self-efficacy in making career decisions. This study suggests that universities should prioritize the development and expansion of career education initiatives. They should not only help establish clear career goals for college students but also cultivate a positive and flexible career outlook to assist them in better adapting to various changes that may arise throughout their career journeys.

XPO1 is a new target of homoharringtonine (HHT): Making NPMc+ AML cells much more sensitive to HHT treatment.

Acute myeloid leukemia (AML) is a heterogeneous disease and about one third of AML patients carry nucleophosmin (NPM1) mutation. Because 95% mutations give NPM1 an additional nuclear export signaling (NES) and dislocate NPM1 in cytoplasm (NPMc+), relocating NPM1 in nucleus provide an innovative strategy for treating this type of AML. The nuclear export of NPM1 depends on the nuclear protein export receptor XPO1, which recognizes the NES sequence on NPM1. Homoharringtonine (HHT) is a first-line chemotherapy drug of AML, yet the exact mechanism of its anti-AML activity is elusive. In this study, we found that HHT can directly target XPO1 to its NES-binding cleft, bind to Cys528 of XPO1, and inhibits its nuclear transport function. In addition, HHT can block NPMc+ proteins nuclear export and thus make NPMc+ AML cells much more sensitive to HHT treatment. Furthermore, the sensitivity of NPMc+ AML cells to HHT is a universal phenomenon irrespective of the different genetic lesions of AML. Taken together, our findings suggest that XPO1 is a new target of HHT and provide a novel strategy for NPMc+ AML treatment.

Professional Identity and Career Adaptability among Chinese Engineering Students: The Mediating Role of Learning Engagement.

Due to the rapid development of science and technology, economic development has changed dramatically, resulting in the transformation of career characteristics. Individuals need to convey a higher career adaptability than ever before in order to face the rapid changes brought by development. Especially for college students in the critical period of career development, having good career adaptability is of great significance to their future career choice and development. This study conducted a cross-sectional survey of 692 engineering undergraduates at a top engineering university in China and used the data to investigate the relationship between the professional identity (professional interest, professional strength, career prospects, and professional satisfaction) and career adaptability of college students, as well as to discuss the mediating role of learning engagement in the relationship between professional identity and career adaptability. The results of the correlation analysis showed that professional identity was positively correlated with career adaptability. The mediation effect model indicated that learning engagement played a mediating role in the relationship between the professional identity and career adaptability of Chinese college students. In other words, professional identity had a direct positive impact on career adaptability, while professional identity, mediated by learning engagement, had a positive impact on career adaptability. The study recommends that colleges provide students with a more conducive academic environment and more opportunities for career practice. We also encourage educators to provide more emotional support and identity for students to enhance students' career adaptability by creating a favorable academic and emotional atmosphere.

Relationship between depression, smartphone addiction, and sleep among Chinese engineering students during the COVID-19 pandemic.

BACKGROUND: Existing research has demonstrated that depression is positively related to smartphone addiction, but the role of sleep has not been discussed thoroughly, especially among engineering undergraduates affected by the coronavirus disease 2019 pandemic. AIM: To evaluate sleep as a mediator of the association between smartphone addiction and depression among engineering undergraduates. METHODS: Using a multistage stratified random sampling method, a cross-sectional survey was conducted among 692 engineering undergraduates from a top engineering university in China, and data were collected by self-reported electronic questionnaires. The data included demographic characteristics, such as age, gender, the Smartphone Addiction Scale-Short Version (SAS-SV), the 9-item Patient Health Questionnaire, and the Pittsburgh Sleep Quality Index. Pearson correlation and multiple linear regression analyses were used to examine the association between smartphone addiction and depression, while structural equation models were established to evaluate the possible mediating role of sleep. RESULTS: Based on the cutoffs of the SAS-SV, the rate of smartphone addiction was 63.58 percent, with 56.21 percent for women and 65.68 percent for men, among 692 engineering students. The prevalence of depression among students was 14.16 percent, with 17.65 percent for women, and 13.18 percent for men. Smartphone addiction was positively correlated with depression, and sleep played a significant mediating effect between the two, accounting for 42.22 percent of the total effect. In addition, sleep latency, sleep disturbances, and daytime dysfunction significantly mediated the relationship between depression and smartphone addiction. The mediating effect of sleep latency was 0.014 [P < 0.01; 95% confidence interval (CI): 0.006-0.027], the mediating effect of sleep disturbances was 0.022 (P < 0.01; 95%CI: 0.011-0.040), and the mediating effect of daytime dysfunction was 0.040 (P < 0.01; 95%CI: 0.024-0.059). The influence of sleep latency, sleep disturbances, and daytime dysfunction accounted for 18.42%, 28.95%, and 52.63% of the total mediating effect, respectively. CONCLUSION: The results of the study suggest that reducing excessive smartphone use and improving sleep quality can help alleviate depression.

Risk prediction of placenta previa based on the distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy.

OBJECTIVES: To explore the relationship between the distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy and placenta previa. MATERIAL AND METHODS: A prospective cohort study of women who underwent pregnancy examination in Weifang People's Hospital or Sunshine Union Hospital from January 2020 to June 2021. The distance from the lower edge of the gestational sac to the internal cervical os was measured at 5-6 weeks' gestation. There were 86 women with distance < 2.5 cm, and 105 women with distance ≥ 2.5 cm were randomly selected. There were 92 cases of scarred uterus and 99 cases of non-scarred uterus among the 191 women. They were divided into six groups according to the distance: (1) < 1.0 cm; (2) 1.0 cm to < 1.5 cm; (3) 1.5 cm to < 2.0cm; (4) 2.0 cm to < 2.5 cm; (5) 2.5 cm to < 3.0 cm; (6) ≥ 3.0 cm. All included women were followed-up during pregnancy and pregnancy outcome, and the likelihood ratio of different distances in early pregnancy was calculated and risk stratification was performed, and ROC curve was constructed. RESULTS: There were 15 women in the included studies who were lost to follow-up, 47 had a scarred uterus with placenta previa and 29 had a non-scarred uterus with placenta previa after delivery at 28 weeks or later. The distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy of the scarred uterus < 1.5 cm, and the likelihood ratio was ∞; and the distance ≥ 3.0 cm, the likelihood ratio was 0. The distance from the lower edge of the non-scarred gestational sac to the internal cervical os < 1.0 cm, and the likelihood ratio was ∞; and the distance ≥ 3.0 cm, the likelihood ratio was 0. The ROC curve showed that when the area AUC under the curve was 87%, the optimal diagnostic cut-off value was 2.4 cm. CONCLUSIONS: When the distance from the lower edge of the gestational sac to the internal cervical os was < 1.5 cm and the distance between the non-scarred uterus was < 1.0 cm, it eventually developed into placenta previa; the distance from the lower edge of the gestational sac to the internal cervical os in the first trimester of pregnancy between the scarred uterus and the non-scarred uterus was ≥ 3.0 cm, and it would hardly develop into placenta previa. When the distance from the lower edge of the gestational sac to the internal cervical os in early pregnancy was ≤ 2.4 cm, it could be used as a predictor of placenta previa.

Biodegradable nanoplatform upregulates tumor microenvironment acidity for enhanced cancer therapy via synergistic induction of apoptosis, ferroptosis, and anti-angiogenesis.

Chemodynamic therapy of cancer is limited by insufficient endogenous H2O2 generation and acidity in the tumor microenvironment (TME). Herein, we developed a biodegradable theranostic platform (pLMOFePt-TGO) involving composite of dendritic organosilica and FePt alloy, loaded with tamoxifen (TAM) and glucose oxidase (GOx), and encapsulated by platelet-derived growth factor-B (PDGFB)-labeled liposomes, that effectively uses the synergy among chemotherapy, enhanced chemodynamic therapy (CDT), and anti-angiogenesis. The increased concentration of glutathione (GSH) present in the cancer cells induces the disintegration of pLMOFePt-TGO, releasing FePt, GOx, and TAM. The synergistic action of GOx and TAM significantly enhanced the acidity and H2O2 level in the TME by aerobiotic glucose consumption and hypoxic glycolysis pathways, respectively. The combined effect of GSH depletion, acidity enhancement, and H2O2 supplementation dramatically promotes the Fenton-catalytic behavior of FePt alloys, which, in combination with tumor starvation caused by GOx and TAM-mediated chemotherapy, significantly increases the anticancer efficacy of this treatment. In addition, T2-shortening caused by FePt alloys released in TME significantly enhances contrast in the MRI signal of tumor, enabling a more accurate diagnosis. Results of in vitro and in vivo experiments suggest that pLMOFePt-TGO can effectively suppress tumor growth and angiogenesis, thus providing an exciting potential strategy for developing satisfactory tumor theranostics.

Self-Assembly Mitochondria-Targeting Donor-Acceptor Type Theranostic Nanosphere Activates ROS Storm for Multimodal Cancer Therapy.

The rational design of cancer theranostics with natural diagnostic information and therapeutic behavior has been considered to be a big challenge, since common theranostics from photothermal and photodynamic therapy need to be activated with external stimuli of photoirradiation to enable the chemotherapeutic effects. In this contribution, we have designed and synthesized a series of simple theranostic agents, TPA-N-n (n = 4, 8, 12), which could accumulate at the tumor site over 48 h and indicate superior antiproliferative performance in vivo. TPA-N-n was constructed with electron donor triphenylamine-acceptor benzothiadiazole-mitochondria-targeting moiety pyridinium. Complex TPA-N-8 indicated the best cytotoxicity to cancerous HeLa cells, with an IC50 value of 4.3 µM, and could self-assemble to a nanosphere with a size of 161.2 nm in the DMSO/PBS solution. It is worth noting that TPA-N-8 could accumulate in the mitochondria and produce major ROS species O2•- and OH• as well as small amounts of 1O2 without photoirradiation. Oxidative DNA damage is initiated due to the imbalance of intracellular redox homeostasis from the significant ROS storm. Multimodal synergistic therapy for HeLa cells was activated, as the PINK1-mediated mitophagy from the damaged mitochondria and DNA damage responsive (DDR) induced necroptosis and autophagy. This work not only provided a successful D-A type theranostic agent with superior anticancer performance from multimodal synergistic therapy but also further demonstrated the high efficacy of a mitochondria-targeting strategy for cancer treatment.

Co-Culturing Rat Dorsal Root Ganglion Neurons With Rat Schwann Cells Protects Them Against the Cytotoxic Effects of Silver and Gold Nanoparticles.

Previous studies using monotypic nerve cell cultures have shown that nanoparticles induced neurotoxic effects on nerve cells. Interactions between neurons and Schwann cells may protect against the neurotoxicity of nanoparticles. In this study, we developed a co-culture model consisting of immortalized rat dorsal root ganglion (DRG) neurons and rat Schwann cells and employed it to investigate our hypothesis that co-culturing DRG neurons with Schwann cells imparts protection on them against neurotoxicity induced by silver or gold nanoparticles. Our results indicated that neurons survived better in co-cultures when they were exposed to these nanoparticles at the higher concentrations compared to when they were exposed to these nanoparticles at the same concentrations in monotypic cultures. Synapsin I expression was increased in DRG neurons when they were co-cultured with Schwann cells and treated with or without nanoparticles. Glial fibrillary acidic protein (GFAP) expression was increased in Schwann cells when they were co-cultured with DRG neurons and treated with nanoparticles. Furthermore, we found co-culturing with Schwann cells stimulated neurofilament polymerization in DRG neurons and produced the morphological differentiation. Silver nanoparticles induced morphological disorganization in monotypic cultures. However, there were more cells displaying normal morphology in co-cultures than in monotypic cultures. All of these results suggested that co-culturing DRG neurons with Schwann cells imparted some protection on them against neurotoxicity induced by silver or gold nanoparticles, and altering the expression of neurofilament-L, synapsin I, and GFAP could account for the phenomenon of protection in co-cultures.

An Evidence-Based Nursing Intervention Decreases Anxiety, Depression, Sleep Quality and Somatic Symptoms of Patients with Acute Ischemic Stroke.

Purpose: This study aimed to explore the effects of evidence-based nursing (EBN) intervention on anxiety, depression, sleep quality and somatic symptoms of patients with acute ischemic stroke (AIS). Methods: The eligible AIS patients were randomized into the intervention group and control group in a 1:1 ratio. Patients in both groups received routine nursing care. On the basis of routine nursing, patients in the intervention group also received EBN. Self-rating anxiety scale (SAS), self-rating depression scale (SDS), Pittsburgh Sleep Quality Index (PSQI), and the Patient Health Questionnaire-15 (PHQ-15) were used to assess patients' anxiety, depression, sleep quality, and somatic symptoms at baseline (T0) and 6 months after intervention (T1), respectively. Results: There was no difference in SAS, SDS, PSQI, and PHQ-15 scores at T0 between the 2 groups (all P > 0.05). Comparing to the control group, the intervention group had significantly lower SAS and SDS scores at T1 (P = 0.002, P < 0.001, respectively). The SAS and SDS score changes (T1-T0) were more evident in the intervention group than in the control group (all P < 0.001). No difference of PSQI or PHQ-15 score between the 2 groups was observed at T1. However, the PSQI and PHQ-15 score changes were more evident in the intervention group than in the control group (P = 0.044 and P = 0.007, respectively). Conclusion: EBN invention significantly improved anxiety, depression, sleep quality and somatic symptoms of patients with AIS.

Influencing factors, prediction and prevention of depression in college students: A literature review.

The high prevalence of depression among college students has a strong negative impact on individual physical and mental health, academic development, and interpersonal communication. This paper reviewed the extant literature by identifying nonpathological factors related to college students' depression, investigating the methods of predicting depression, and exploring nonpharmaceutical interventions for college students' depression. The influencing factors of college students' depression mainly fell into four categories: biological factors, personality and psychological state, college experience, and lifestyle. The outbreak of coronavirus disease 2019 has exacerbated the severity of depression among college students worldwide and poses grave challenges to the prevention and treatment of depression, given that the coronavirus has spread quickly with high infection rates, and the pandemic has changed the daily routines of college life. To predict and measure mental health, more advanced methods, such as machine algorithms and artificial intelligence, have emerged in recent years apart from the traditional commonly used psychological scales. Regarding nonpharmaceutical prevention measures, both general measures and professional measures for the prevention and treatment of college students' depression were examined in this study. Students who experience depressive disorders need family support and personalized interventions at college, which should also be supplemented by professional interventions such as cognitive behavioral therapy and online therapy. Through this literature review, we insist that the technology of identification, prediction, and prevention of depression among college students based on big data platforms will be extensively used in the future. Higher education institutions should understand the potential risk factors related to college students' depression and make more accurate screening and prevention available with the help of advanced technologies.