Adolescent suicidal ideation: dissecting the role of sex in depression and NSSI predictors.

BACKGROUND: Suicidal ideation (SI) is increasingly prevalent among adolescents, often arising from depression and linked with non-suicidal self-injury (NSSI). Previous studies have noted significant sex differences in the manifestation and predictors of SI, depression, and NSSI. AIM: This study aims to analyze and compare the relationships between SI, depression, and NSSI among male and female adolescents, examining whether these associations differ based on sex. METHODS: A total of 368 adolescents (M = 15.43, SD = 1.22, about 56.2% female participants), both from clinical and school settings, were assessed for SI, depression, NSSI, and other related variables. Network analysis was utilized to explore the interconnections among these variables, focusing on identifying sex-specific patterns. Logistic regression was used to confirm the findings from the network analysis. RESULTS: The network analysis revealed significant sex differences in the relationships between SI, depression, and NSSI. In the female network, the edge weights between SI and NSSI (0.93) and between SI and depression (0.31) were much higher compared to the male network (0.29 and 0, respectively). Centrality indices (strength, betweenness, closeness, and expected influence) for SI, NSSI, and depression were also higher in the female network. Logistic regression confirmed these findings, with depression being a potential predictor of SI only in females (OR = 1.349, p = 0.001) and NSSI having a stronger influence on SI in females (OR = 13.673, p < 0.001) than in males (OR = 2.752, p = 0.037). CONCLUSION: The findings underscore the necessity of considering sex differences when predicting suicidal ideation from depression and NSSI in adolescents. Intervention and prevention strategies should be tailored to address these distinct patterns in male and female adolescents.

Plasma EBV quantification is associated with the efficacy of immune checkpoint blockade and disease monitoring in patients with primary pulmonary lymphoepithelioma-like carcinoma.

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein-Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC. Viral EBNA-1 and BamHI-W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results: Progression-free survival (PFS) was significantly longer in EBNA-1 high or BamHI-W high groups. A longer PFS was also observed in patients with both high plasma EBNA-1 or BamHI-W and PD-L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA-1 and BamHI-W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions: Plasma EBV DNA could be a useful and easy-to-use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.

Beyond monetary value: how reward type drives cheating in a gender-judgment task.

Background: Investigating the effects of monetary incentives on dishonest behavior provides valuable insights into human integrity and ethical decision-making processes. This study is conducted through the lens of self-concept maintenance theory. Aim: The aim of this study is to examine the influence of different types of rewards (score-based vs. monetary) and their magnitude on dishonest behavior within a gender judgment task. Method: Using a quantitative experimental design, this study involved 116 participants who were randomly assigned to conditions that differed in reward type (score or money) and magnitude (10 yuan vs. 50 yuan). Dishonest behavior was assessed using a gender judgment task with mechanisms to simulate conditions conducive to planned cheating. Results: Results revealed significant differences in dishonesty rates between score and money conditions, with a higher proportion of dishonest participants observed in the score condition compared to the money condition. The timing of initial cheating was earlier in the score condition compared to the money condition. No significant differences were found in the proportion of dishonest participants, the cheating rate, or the timing of initial cheating across reward levels within either condition. The rate of cheating increased over time, suggesting a temporal dynamic in unethical decision making. Conclusion: The study demonstrates that the nature of rewards significantly influences the likelihood of dishonest behavior, with intangible score-based rewards facilitating rationalizations for dishonesty more readily than tangible financial incentives. These findings enrich the understanding of moral psychology by highlighting the complex interplay between reward types, ethical rationalization, and the dynamics of dishonest behavior.

The m6A reader HNRNPC promotes glioma progression by enhancing the stability of IRAK1 mRNA through the MAPK pathway.

Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC-IRAK1-MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.

Root-to-shoot signaling positively mediates source-sink relation in late growth stages in diploid and tetraploid wheat.

Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat.

Defective Tungsten Oxides with Stacking Faults for Proton Exchange Membrane Green-Hydrogen Generation.

Defects can introduce atomic structural modulation and tailor performance of materials. Herein, it demonstrates that semiconductor WO3 with inert electrocatalytic behavior can be activated through defect-induced tensile strains. Structural characterizations reveal that when simply treated in Ar/H2 atmosphere, oxygen vacancies will generate in WO3 and cause defective structures. Stacking faults are found in defects, thus modulating electronic structure and transforming electrocatalytic-inert WO3 into highly active electrocatalysts. Density functional theory (DFT) calculations are performed to calculate *H adsorption energies on various WOx surfaces, revealing the oxygen vacancy composition and strain predicted to optimize the catalytic activity of hydrogen evolution reaction (HER). Such defective tungsten oxides can be integrated into commercial proton exchange membrane (PEM) electrolyser with comparable performance toward Pt-based PEM. This work demonstrates defective metal oxides as promising non-noble metal catalysts for commercial PEM green-hydrogen generation.

Latent profile analysis of Eysenck's personality dimensions and psychological constructs in university students.

Background: The exploration of personality traits in relation to psychological constructs has become increasingly relevant in understanding the mental health of university students (the emerging adulthood). Studies have focused on how dimensions intersect with various psychological parameters. Aim: The study aims to identify distinct personality profiles among university students based on Eysenck's personality dimensions and investigate how these profiles differ across psychological constructs. Method: A quantitative methodology was utilized, involving 708 university students from Wenzhou and Nanjing in China as participants. The research employed the Eysenck Personality Questionnaire along with other psychological measures. Latent Profile Analysis was applied to categorize the participants into distinct personality profiles. Results: Four distinct personality profiles emerged: 'The Reserved Analyst,' 'The Social Diplomat,' 'The Unconventional Pragmatist,' and 'The Impulsive Truth-Teller.' Significant differences were found among these profiles on various psychological constructs. 'The Social Diplomat' exhibited the most adaptive psychological profile, with higher cognitive reappraisal (F = 45.818, p < 0.001, η2 = 0.163), meaning in life (F = 17.764, p < 0.001, η2 = 0.070), and positive coping (F = 40.765, p < 0.001, η2 = 0.148) compared to other profiles. Conversely, 'The Reserved Analyst' showed higher intolerance of uncertainty (F = 13.854, p < 0.001, η2 = 0.056) and state anxiety (F = 26.279, p < 0.001, η2 = 0.101). Conclusion: This study enriches the understanding of personality traits in relation to psychological constructs within the context of university student populations. By identifying distinct personality profiles, it lays the groundwork for developing tailored mental health strategies that cater to the specific needs of different student groups.

Poor healthy lifestyle and life's essential 8 are associated with higher risk of new-onset migraine: a prospective cohort study.

BACKGROUND: Lifestyle are closely related to migraine. However, there is a lack of studies investigating the association between Healthy lifestyle or Life's Essential 8 (LE8) and the risk of migraine. The objective of this research was to investigate the relationship between Healthy lifestyle scores and Life's essential 8 scores, and migraine. METHODS: 332,895 UK Biobank participants without migraine were included. Healthy lifestyle were assessed using seven lifestyle factors, and categorized as poor, intermediate, or ideal. LE8, based on the American Heart Association (AHA) Guidelines for Cardiovascular Health (CVH), consist of eight indicators classified as low, moderate, or high CVH. The Cox proportional hazard model was employed to examine the association between Healthy lifestyle scores, LE8 scores, and migraine, with calculations for population-attributable fraction (PAF) and cumulative incidence. RESULTS: During a median follow-up of 13.58 years, participants in intermediate (HR: 0.91; 95% CI: 0.85, 0.99) or ideal category of Healthy lifestyle (HR: 0.81; 95% CI: 0.73, 0.91) significantly reduced migraine risk compared to the poor category. Similarly, high CVH (HR: 0.73; 95% CI: 0.58, 0.92) also lowered migraine risk, while moderate CVH (HR: 0.93; 95% CI: 0.85, 1.02) did not show a difference compared to low CVH. If all individuals adhered to higher categories of Healthy lifestyle and LE8, approximately 11.38% and 22.05% of migraine cases could be prevented. Among individual lifestyle factors, maintaining an ideal body mass index (BMI), physical activity, sleep duration, sleep pattern, and sedentary time were associated with substantial reductions in migraine risk, by 5.65%, 0.81%, 10.16%, 16.39%, and 6.57%, respectively. CONCLUSION: Our study provides evidence that poor Healthy lifestyle and Life's Essential 8 are associated with higher risk of new-onset migraine.

Root-zone regulation and longitudinal translocation cause intervarietal differences for phthalates accumulation in vegetables.

Selecting and cultivating low-accumulating crop varieties (LACVs) is the most effective strategy for the safe utilization of di-(2-ethylhexyl) phthalate (DEHP)-contaminated soils, promoting cleaner agricultural production. However, the adsorption-absorption-translocation mechanisms of DEHP along the root-shoot axis remains a formidable challenge to be solved, especially for the research and application of LACV, which are rarely reported. Here, systematic analyses of the root surface ad/desorption, root apexes longitudinal allocation, uptake and translocation pathway of DEHP in LACV were investigated compared with those in a high-accumulating crop variety (HACV) in terms of the root-shoot axis. Results indicated that DEHP adsorption was enhanced in HACV by root properties, elemental composition and functional groups, but the desorption of DEHP was greater in LACV than HACV. The migration of DEHP across the root surface was controlled by the longitudinal partitioning process mediated by root tips, where more DEHP accumulated in the root cap and meristem of LACV due to greater cell proliferation. Furthermore, the longitudinal translocation of DEHP in LACV was reduced, as evidenced by an increased proportion of DEHP in the root apoplast. The symplastic uptake and xylem translocation of DEHP were suppressed more effectively in LACV than HACV, because DEHP translocation in LACV required more energy, binding sites and transpiration. These results revealed the multifaceted regulation of DEHP accumulation in different choysum (Brassica parachinensis L.) varieties and quantified the pivotal regulatory processes integral to LACV formation.

Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment.

Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.

Minimum-Consumption Discrimination of Quantum States via Globally Optimal Adaptive Measurements.

Reducing the average resource consumption is the central quest in discriminating non-orthogonal quantum states for a fixed admissible error rate ϵ. The globally optimal fixed local projective measurement for this task is found to be different from that for previous minimum-error discrimination tasks [S. Slussarenko et al., Phys. Rev. Lett. 118, 030502 (2017)PRLTAO0031-900710.1103/PhysRevLett.118.030502]. To achieve the ultimate minimum average consumption, here we develop a general globally optimal adaptive strategy (GOA) by subtly using the updated posterior probability, which works under any error rate requirements and any one-way measurement restrictions, and can be solved by a convergent iterative relation. First, under the local measurement restrictions, our GOA is solved to serve as the local bound, which saves 16.6 copies (24%) compared with the previously best globally optimal fixed local projective measurement. When the more powerful two-copy collective measurements are allowed, our GOA is experimentally demonstrated to beat the local bound by 3.9 copies (6.0%). By exploiting both adaptivity and collective measurements, our Letter marks an important step toward minimum-consumption quantum state discrimination.

Mental toughness in adolescents: bridging family relationships and depression across personality traits.

BACKGROUND: Adolescence is a pivotal stage vulnerable to mental health issues like anxiety and depression. While family relationships, mental toughness, and personality traits are known to impact adolescent mental health, their interactive and moderating roles are not fully understood. AIM: This study aims to investigate the mediating role of mental toughness in the relationship between family relationships and depression among high school students, and to examine the varying impacts of personality traits on this mediation. METHOD: A cross-sectional study was conducted on a sample of 734 adolescents. Participants completed measures assessing family relationships, mental toughness, personality traits, and mental health outcomes (depression). Latent Profile Analysis, Multiple Regression Analysis, and Structural Equation Modeling, to investigate these relationships. RESULTS: The study found that mental toughness significantly mediates the relationship between family relationships and depression. Notably, this mediating effect varied between personality type; it was more pronounced in the moderate-reserved type compared to the proactive-engaged type. LPA identified two distinct personality types of students based on their personality traits, with differential patterns of family relationships, mental toughness, and depression. Multiple regression analysis indicated that character and adaptability, components of mental toughness, were significant negative predictors of depression. CONCLUSION: The study contributes to understanding the dynamics of adolescent mental health, particularly in the context of Chinese high school students. It underscores the importance of considering family dynamics, personality traits, and mental toughness in developing effective mental health interventions for adolescents.

Gene expression prognostic of early relapse risk in low-risk B-cell acute lymphoblastic leukaemia in children.

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low-risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low-risk ETV6::RUNX1-positive B-cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome-wide transcriptome and single-nucleotide variants. We found high TIMD4 expression (> 85th-percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low-risk ETV6::RUNX1-positive B-cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ETV6::RUNX1-negative B-cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.

Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. METHODS: This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-index) and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA sequencing (RNA-seq) analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: An MRI-based radiomic signature predicted OS more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for lrNPC patients.

Development and trends in metabolomics studies in psoriasis: A bibliometric analysis of related research from 2011 to 2024.

Background: Psoriasis is a chronic, inflammatory skin disease with autoimmune characteristics. Recent research has made significant progress in the field of psoriasis metabolomics. However, there is a lack of bibliometric analysis on metabolomics of psoriasis. The objective of this study is to utilize bibliometrics to present a comprehensive understanding of the knowledge structure and research hotspots in psoriasis within the field of metabolomics. Methods: We conducted a bibliometric analysis by searching the Web of Science Core Collection database for publications on metabolomics in psoriasis from 2011 to 2024. To perform this analysis, we utilized tools such as VOSviewers, CiteSpace, and the R package "bibliometrix". Results: A total of 307 articles from 47 countries, with the United States and China leading the way, were included in the analysis. The publications focusing on metabolomics in psoriasis have shown a steady year-on-year growth. The Medical University of Bialystok is the main research institution. The International Journal of Molecular Sciences emerges as the prominent journal in the field, while the Journal of Investigative Dermatology stands out as the highly co-cited publication. A total of 2029 authors contributed to these publications, with Skrzydlewska Elzbieta, Baran Anna, Flisiak Iwona, Murakami Makoto being the most prolific contributors. Notably, Armstrong April W. received the highest co-citation. Investigating the mechanisms of metabolomics in the onset and progression of psoriasis, as well as exploring therapeutic strategies, represents the primary focus of this research area. Emerging research hotspots encompass inflammation, lipid metabolism, biomarker, metabolic syndrome, obesity, and arthritis. Conclusion: The results of this study indicate that metabolism-related research is thriving in psoriasis, with a focus on the investigation of metabolic targets and interventions within the metabolic processes. Metabolism is expected to be a hot topic in future psoriasis research.

Phenotypic comparison and the potential antitumor function of immortalized bone marrow-derived macrophages (iBMDMs).

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.

Congener-specific fate and impact of microcystins in the soil-earthworm system.

Microcystins (MCs) have a significant influence on aquatic ecosystems, but little is known about their terrestrial fate and impact. Here, we investigated the fate of two MCs (MC-LR and MC-RR) in the soil-earthworm system, with consideration of their congener-specific impact on earthworm health, soil bacteria, and soil metabolome. Although MCs had little acute lethal effect on earthworms, they caused obvious growth inhibition and setae rupture. Relative to MC-RR, MC-LR exhibited higher bioaccumulation and the resulting dermal lesions and deformation of longitudinal muscles. While the incorporation of both MCs into soils stimulated pathogenic bacteria and depressed oxidative stress tolerant bacteria, the response among soil nitrification and glutathione metabolism differed between the two congeners. The dissipation kinetics of MCs obeyed the first-order model. Earthworms stimulated soil N-cycling enzyme activities, increased the abundance of MC-degrading bacteria, and promoted bacterial metabolic functions related to glutathione metabolism, xenobiotics biodegradation, and metabolism of amino acids that comprise MCs, which accelerated the dissipation of MC-LR and MC-RR by 227% and 82%, respectively. These results provide evidence of significant congener differences in the terrestrial fate and impact of MCs, which will enable a better understanding of their role in mediating soil functions and ecosystem services.

Engineered protein cages with enhanced extracellular drug release for elevated antitumor efficacy.

Human heavy chain ferritin (HFn) protein cage has been explored as a nanocarrier for targeted anticancer drug delivery. Here, we introduced a matrix metalloproteinases (MMPs)-cleavable sequence into the DE loop of HFn, creating an MMP-responsive variant, MR-HFn, for localized and extracellular drug release. The crystal structure of MR-HFn revealed that the addition of the MMPs recognition sequence did not affect the self-assembly of HFn but presented a surface-exposed loop susceptible to MMPs cleavage. Biochemical analysis indicated that this engineered protein cage is responsive to MMPs, enabling the targeted release of encapsulated drugs. To evaluate the therapeutic potential of this engineered protein cage, monosubstituted ß-carboxy phthalocyanine zinc (CPZ), a type of photosensitizer, was loaded inside this protein cage. The prepared CPZ@MR-HFn showed higher uptake and stronger phototoxicity in MMPs overexpressed tumor cells, as well as enhanced penetration into multicellular tumor spheroids compared with its counterpart CPZ@HFn in vitro. In vivo, CPZ@MR-HFn displayed a higher tumor inhibitory rate than CPZ@HFn under illumination. These results indicated that MR-HFn is a promising nanocarrier for anticancer drug delivery and the MMP-responsive strategy here can also be adapted for other stimuli.