Predictors of Global Disparities in COVID-19 Vaccination Coverage - 219 Countries and Territories, December 2020-July 2022.

What is already known about this topic?: The significant disparities in global coronavirus disease 2019 (COVID-19) vaccine coverage hamper the pace of epidemic control. There is a need to better understand the factors contributing to disparities in COVID-19 vaccination rates across countries. What is added by this report?: This report revealed significant associations between vaccination coverage and various country-level indicators. Better pandemic preparedness, higher levels of trust, and a lower proportion of young population aged 0-14 were strongly correlated with higher COVID-19 vaccination coverage. What are the implications for public health practices?: Our findings emphasize the need for enhanced pandemic preparedness and governance, coupled with building trust in government and healthcare systems. It also needs to address the hesitancy of vaccinating children and adolescents aged 0-14 as the vaccination campaign progresses.

Effects of 15% Azelaic Acid Gel in the Management of Post-Inflammatory Erythema and Post-Inflammatory Hyperpigmentation in Acne Vulgaris.

INTRODUCTION: The aim of this study was to assess the efficacy and safety of 15% azelaic acid (AzA) gel in treating acne-induced post-inflammatory erythema (PIE) and post-inflammatory hyperpigmentation (PIH). The effects of 15% AzA gel on acne, skin barrier function, and quality of life were also evaluated. METHODS: A total of 72 patients with mild to moderate acne were enrolled in a randomized, double-blind, placebo-controlled trial. Patients were divided into two groups: patients in the AzA group applied 15% AzA gel twice daily for 12 weeks, and those in the placebo group applied AzA-free gel. Clinical evaluations using non-invasive skin detection technologies, including VISIA skin analysis, dermoscopy, and skin physiological function tests, were performed at 0, 4, 8, and 12 weeks. Main outcome measures included the post-acne hyperpigmentation index (PAHPI), melanin, hemoglobin, individual typology angle, water content, transepidermal water loss, and sebum. Investigator Global Assessment) and Dermatology Life Quality Index (DLQI) assessments were conducted at weeks 0 and 12. Adverse reactions were recorded. RESULTS: Of the 72 patients at study initiation, 60 completed the trial. At 8 and 12 weeks, patients in the AzA group showed significantly reduced PAHPI for PIE lesions compared to baseline and patients receiving placebo (P < 0.05). Patients in both groups exhibited reduced PIH lesions at weeks 8 and 12 that differed significantly from baseline (P < 0.05). Hemoglobin content decreased significantly in AzA-treated PIE lesions compared to those treated with placebo at week 12 (P < 0.05). Melanin content decreased significantly in AzA-treated PIH lesions at week 12 (P < 0.05). The AzA group showed higher improvement in DLQI (P < 0.05), and greater overall satisfaction (P < 0.05) compared to placebo. CONCLUSION: The results indicate that 15% AzA gel effectively improved acne-induced PIE and PIH with minimal adverse reactions, making it a viable clinical application. In the study population, it had no adverse effects on skin barrier function and contributed positively to acne improvement and patient quality of life. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (ChiCTR.org.cn) under the identifier ChiCTR2300076959. The registration date was 25 October 2023, retrospectively registered.

Application and mechanism of carbonate material in the treatment of heavy metal pollution: a review.

Among the many heavy metal pollution treatment agents, carbonate materials show strong flexibility and versatility by virtue of their high adsorption capacity for heavy metals and the characteristics of multiple and simple modification methods. It shows good potential for development. This review summarizes the application of carbonate materials in the treatment of heavy metal pollution according to the research of other scholars. It mainly relates to the application of surface-modified, activated, and nano-sized carbonate materials in the treatment of heavy metal pollution in water. Natural carbonate minerals and composite carbonate minerals solidify and stabilize heavy metals in soil. Solidification of heavy metals in hazardous waste solids is by MICP. There are four aspects of calcium carbonate oligomers curing heavy metals in fly ash from waste incineration. The mechanism of treating heavy metals by carbonate in different media was discussed. However, in the complex environment where multiple types of pollutants coexist, questions on how to maintain the efficient processing capacity of carbonate materials and how to use MICP to integrate heavy metal fixation and seepage prevention in solid waste base under complex and changeable natural environment deserve our further consideration. In addition, the use of carbonate materials for the purification of trace radioactive wastewater and the safe treatment of trace radioactive solid waste are also worthy of further exploration.

Sulfur vacancy-rich bismuth sulfide nanowire derived from CAU-17 for radioactive iodine capture in complex environments: Performance and intrinsic mechanisms.

Effective capture and immobilization of volatile radioiodine from the off-gas of post-treatment plants is crucial for nuclear safety and public health, considering its long half-life, high toxicity, and environmental mobility. Herein, sulfur vacancy-rich Vs-Bi2S3@C nanocomposites were systematically synthesized via a one-step solvothermal vulcanization of CAU-17 precursor. Batch adsorption experiments demonstrated that the as-synthesized materials exhibited superior iodine adsorption capacity (1505.8 mg g-1 at 200 °C), fast equilibrium time (60 min), and high chemisorption ratio (91.7%), which might benefit from the nanowire structure and abundant sulfur vacancies of Bi2S3. Furthermore, Vs-Bi2S3@C composites exhibited excellent iodine capture performance in complex environments (high temperatures, high humidity and radiation exposure). Mechanistic investigations revealed that the I2 capture by fabricated materials primarily involved the chemical adsorption between Bi2S3 and I2 to form BiI3, and the interaction of I2 with electrons provided by sulfur vacancies to form polyiodide anions (I3-). The post-adsorbed iodine samples were successfully immobilized into commercial glass fractions in a stable form (BixOyI), exhibiting a normalized iodine leaching rate of 3.81 × 10-5 g m-2 d-1. Overall, our work offers a novel strategy for the design of adsorbent materials tailed for efficient capture and immobilization of volatile radioiodine.

Dysregulations of amino acid metabolism and lipid metabolism in urine of children and adolescents with major depressive disorder: a case-control study.

RATIONALE: The mechanisms underlying major depressive disorder (MDD) in children and adolescents are unclear. Metabolomics has been utilized to capture metabolic signatures of various psychiatric disorders; however, urinary metabolic profile of MDD in children and adolescents has not been studied. OBJECTIVES: We analyzed urinary metabolites in children and adolescents with MDD to identify potential biomarkers and metabolic signatures. METHODS: Here, liquid chromatography-mass spectrometry was used to profile metabolites in urine samples from 192 subjects, comprising 80 individuals with antidepressant-naïve MDD (AN-MDD), 37 with antidepressant-treated MDD (AT-MDD) and 75 healthy controls (HC). We performed orthogonal partial least squares discriminant analysis to identify differential metabolites and employed logistic regression and receiver operating characteristic analysis to establish a diagnostic panel. RESULTS: In total, 143 and 71 differential metabolites were identified in AN-MDD and AT-MDD, respectively. These were primarily linked to lipid metabolism, molecular transport, and small molecule biochemistry. AN-MDD additionally exhibited dysregulated amino acid metabolism. Compared to HC, a diagnostic panel of seven metabolites displayed area under the receiver operating characteristic curves of 0.792 for AN-MDD, 0.828 for AT-MDD, and 0.799 for all MDD. Furthermore, the urinary metabolic profiles of children and adolescents with MDD significantly differed from those of adult MDD. CONCLUSIONS: Our research suggests dysregulated amino acid metabolism and lipid metabolism in the urine of children and adolescents with MDD, similar to results in plasma metabolomics studies. This contributes to the comprehension of mechanisms underlying children and adolescents with MDD.

The Roles of CircRNAs in Mitochondria.

Mitochondria participate in varieties of cellular events. It is widely accepted that human mitochondrial genome encodes 13 proteins, 2 rRNAs, and 22 tRNAs. Gene variation derived from human nuclear genome cannot completely explain mitochondrial diseases. The advent of high-throughput sequencing coupled with novel bioinformatic analyses decode the complexity of mitochondria-derived transcripts. Recently, circular RNAs (circRNAs) from both human mitochondrial genome and nuclear genome have been found to be located at mitochondria. Studies about the roles and molecular mechanisms underlying trafficking of the nucleus encoded circRNAs to mitochondria and mitochondria encoded circRNAs to the nucleus or cytoplasm in mammals are only beginning to emerge. These circRNAs have been associated with a variety of diseases, especially cancers. Here, we discuss the emerging field of mitochondria-located circRNAs by reviewing their identification, expression patterns, regulatory roles, and functional mechanisms. Mitochondria-located circRNAs have regulatory roles in cellular physiology and pathology. We also highlight future perspectives and challenges in studying mitochondria-located circRNAs, as well as their potential biomedical applications.

Mosquito E-20-Monooxygenase Gene Knockout Increases Dengue Virus Replication in Aedes aegypti Cells.

E-20-monooxygenase (E20MO) is an enzymatic product of the shade (shd) locus (cytochrome p450, E20MO). Initially discovered in Drosophila, E20MO facilitates the conversion of ecdysone (E) into 20-hydroxyecdysone (20E) and is crucial for oogenesis. Prior research has implicated 20E in growth, development, and insecticide resistance. However, little attention has been given to the association between the E20MO gene and DENV2 infection. The transcriptome of Ae. aegypti cells (Aag2 cells) infected with DENV2 revealed the presence of the E20MO gene. The subsequent quantification of E20MO gene expression levels in Aag2 cells post-DENV infection was carried out. A CRISPR/Cas9 system was utilized to create an E20MO gene knockout cell line (KO), which was then subjected to DENV infection. Analyses of DENV2 copies in KO and wild-type (WT) cells were conducted at different days post-infection (dpi). Plasmids containing E20MO were constructed and transfected into KO cells, with pre- and post-transfection viral copy comparisons. Gene expression levels of E20MO increased after DENV infection. Subsequently, a successful generation of an E20MO gene knockout cell line and the verification of code-shifting mutations at both DNA and RNA levels were achieved. Furthermore, significantly elevated DENV2 RNA copies were observed in the mid-infection phase for the KO cell line. Viral RNA copies were lower in cells transfected with plasmids containing E20MO, compared to KO cells. Through knockout and plasmid complementation experiments in Aag2 cells, the role of E20MO in controlling DENV2 replication was demonstrated. These findings contribute to our understanding of the intricate biological interactions between mosquitoes and arboviruses.

Polyphyllin I induces rapid ferroptosis in acute myeloid leukemia through simultaneous targeting PI3K/SREBP-1/SCD1 axis and triggering of lipid peroxidation.

Acute myeloid leukemia (AML) is a malignant disease that is difficult to completely cure. Polyphyllin I (PPI), a steroidal saponin isolated from Paris polyphylla, has exhibited multiple biological activities. Here, we discovered the superior cytotoxicity of PPI on AML cells MOLM-13 with an IC50 values of 0.44 ± 0.09 µM. Mechanically, PPI could cause ferroptosis via the accumulation of intracellular iron concentration and triggering lipid peroxidation. Interestingly, PPI could induced stronger ferroptosis in a short time of about 6 h compared to erastin. Furthermore, we demonstrate that PPI-induced rapid ferroptosis is due to the simultaneous targeting PI3K/SREBP-1/SCD1 axis and triggering lipid peroxidation, and PI3K inhibitor Alpelisib can enhance the activity of erastin-induced ferroptosis. Molecular docking simulations and kinase inhibition assays demonstrated that PPI is a PI3K inhibitor. In addition, PPI significantly inhibited tumor progression and prolonged mouse survival at 4 mg/kg with well tolerance. In summary, our study highlights the therapeutic potential of PPI for AML and shows its unique dual mechanism.

A Deep Learning Approach for Automated Extraction of Functional Status and New York Heart Association Class for Heart Failure Patients During Clinical Encounters.

Introduction: Serial functional status assessments are critical to heart failure (HF) management but are often described narratively in documentation, limiting their use in quality improvement or patient selection for clinical trials. We developed and validated a deep learning-based natural language processing (NLP) strategy to extract functional status assessments from unstructured clinical notes. Methods: We identified 26,577 HF patients across outpatient services at Yale New Haven Hospital (YNHH), Greenwich Hospital (GH), and Northeast Medical Group (NMG) (mean age 76.1 years; 52.0% women). We used expert annotated notes from YNHH for model development/internal testing and from GH and NMG for external validation. The primary outcomes were NLP models to detect (a) explicit New York Heart Association (NYHA) classification, (b) HF symptoms during activity or rest, and (c) functional status assessment frequency. Results: Among 3,000 expert-annotated notes, 13.6% mentioned NYHA class, and 26.5% described HF symptoms. The model to detect NYHA classes achieved a class-weighted AUROC of 0.99 (95% CI: 0.98-1.00) at YNHH, 0.98 (0.96-1.00) at NMG, and 0.98 (0.92-1.00) at GH. The activity-related HF symptom model achieved an AUROC of 0.94 (0.89-0.98) at YNHH, 0.94 (0.91-0.97) at NMG, and 0.95 (0.92-0.99) at GH. Deploying the NYHA model among 166,655 unannotated notes from YNHH identified 21,528 (12.9%) with NYHA mentions and 17,642 encounters (10.5%) classifiable into functional status groups based on activity-related symptoms. Conclusions: We developed and validated an NLP approach to extract NYHA classification and activity-related HF symptoms from clinical notes, enhancing the ability to track optimal care and identify trial-eligible patients.

Compliance and alternative behaviors of heavy gamers in adolescents to Chinese online gaming restriction policy.

Background and aims: In 2021, China implemented a policy to prevent adolescents from excessive online gaming, with the goal of encouraging healthier leisure activities. Methods: Three months after this policy was implemented, we conducted a study involving 430 Chinese adolescents who regularly played online games for over two hours daily before the policy. We collected their responses to the restriction, including their compliance with the policy, engagement in undesirable alternative behaviors (e.g., watching short videos), and engagement in desirable alternative behaviors (e.g., playing sports). We also collected data on individual factors, parental technology interference, and feelings of restriction to use as predictors for behaviors, including those related to violating the restriction or watching short videos. Results: A small percentage of heavy gamers violated the restriction by renting others' game accounts (3%) or using a family member's identity (14%), while 59% of the sample shifted to watching short videos. Heavy gamers who lived in rural areas, spent more time on online games prior to the policy, did not feel restricted from playing online games, and experienced parental technology interference were more likely to violate the restriction. Females or those lacking stable hobbies were more inclined to watch short videos. Conclusions: Although the policy restricted heavy gaming, it has also led to increased short video use. Policymakers could explore alternative approaches, such as developing infrastructure that supports outdoor leisure activities in rural areas, encouraging parents to model responsible technology use behaviors, and guiding adolescents to cultivate positive hobbies in their leisure time.

The S100 family is a prognostic biomarker and correlated with immune cell infiltration in pan-cancer.

BACKGROUND: The S100 protein family is a group of small molecular EF-hand calcium-binding proteins that play critical roles in various biological processes, including promotion of growth, metastasis and immune evasion of tumor. However, the potential roles of S100 protein family expression in tumor microenvironment (TME) cell infiltration in pan-cancer remain elusive. METHODS: Herein, we conducted a comprehensive assessment of the expression patterns of the S100 protein family in pan-cancer, meticulously examining their correlation with characteristics of TME cell infiltration. The S100 score was constructed to quantify S100 family expression patterns of individual tumors. RESULTS: The S100 family was a potent risk factor in many cancers. Clustering analysis based on the transcriptome patterns of S100 protein family identified two cancer clusters with distinct immunophenotypes and clinical characteristics. Cluster A, with lower S100 expression, exhibited lower immune infiltration, whereas, Cluster B, with higher S100 expression, featured higher immune infiltration. Interestingly, Cluster B had a poorer prognosis, likely due to an immune-excluded phenotype resulting from stromal activation. The analysis revealed robust enrichment of the TGFb and EMT pathways in the cohort exhibiting high S100 score, alongside a positive correlation between the S100 score and Treg levels, suggesting the manifestation of an immune-excluded phenotype in this group. Moreover, S100 families were associated with the prognosis of 22 different cancers and a noteworthy association was observed between high S100 score and an unfavorable response to anti-PD-1/L1 immunotherapy. Consistent findings across two independent immunotherapy cohorts substantiated the advantageous therapeutic outcomes and clinical benefits in patients displaying lower S100score. CONCLUSION: Our analysis demonstrated the role of S100 family in formation of TME diversity and complexity, enabling deeper cognition of TME infiltration characterization and the development of personalized immunotherapy strategies targeting S100 family for unique tumor types.

Adolescent male rats show altered gut microbiota composition associated with depressive-like behavior after chronic unpredictable mild stress: Differences from adult rats.

Accumulating evidence reveals the metabolism and neurotransmitter systems are different in major depressive disorder (MDD) between adolescent and adult patients; however, much is still unknown from the gut microbiome perspective. To minimize confounding factors such as geographical location, ethnicity, diet, and drugs, we investigated the gut microbial differences between adolescent and adult male Sprague-Dawley rats. We exposed the adolescent rats to chronic unpredictable mild stress (CUMS) for 3 weeks and assessed their behavior using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). We collected and sequenced fecal samples after the behavioral tests and compared them with our previous data on adult rats. Both adolescent and adult CUMS rats exhibited reduced sucrose preference in SPT, reduced total distance in OFT, and increased immobility time in FST. Moreover, compared to their respective controls, the adolescent CUMS rats had distinct amplicon sequence variants (ASVs) mainly in the Muribaculaceae family, Bacteroidetes phylum, while the adult CUMS rats had those in the Lachnospiraceae family, Firmicutes phylum. In the adolescent group, the Muribaculaceae negatively correlated with FST and positively correlated with SPT and OFT. In the adult group, the different genera in the Lachnospiraceae showed opposite correlations with FST. Furthermore, the adolescent CUMS rats showed disrupted microbial functions, such as "Xenobiotics biodegradation and metabolism" and "Immune system", while the adult CUMS rats did not. These results confirmed the gut microbiota differences between adolescent and adult rats after CUMS modeling and provided new insight into the age-related influence on depression models.

Inhibition of lysyl oxidase by pharmacological intervention and genetic manipulation alleviates epilepsy-associated cognitive disorder.

Epilepsy-associated cognitive disorder (ECD), a prevalent comorbidity in epilepsy patients, has so far uncharacterized etiological origins. Our prior work revealed that lysyl oxidase (Lox) acted as a novel contributor of ferroptosis, a recently discovered cell death mode in the regulation of brain function. However, the role of Lox-mediated ferroptosis in ECD remains unknown. ECD mouse model was established 2 months later following a single injection of kainic acid (KA) for. After chronic treatment with KA, mice were treated with different doses (30 mg/kg, 100 mg/kg and 300 mg/kg) of Lox inhibitor BAPN. Additionally, hippocampal-specific Lox knockout mice was also constructed and employed to validate the role of Lox in ECD. Cognitive functions were assessed using novel object recognition test (NOR) and Morris water maze test (MWM). Protein expression of phosphorylated cAMP-response element binding (CREB), a well-known molecular marker for evaluation of cognitive performance, was also detected by Western blot. The protein distribution of Lox was analyzed by immunofluorescence. In KA-induced ECD mouse model, ferroptosis process was activated according to upregulation of 4-HNE protein and a previously discovered ferroptosis in our group, namely, Lox was remarkably increased. Pharmacological inhibition of Lox by BAPN at the dose of 100 mg/kg significantly increased the discrimination index following NOR test and decreased escape latency as well as augmented passing times within 60 s following MWM test in ECD mouse model. Additionally, deficiency of Lox in hippocampus also led to pronounced improvement of deficits in ECD model. These findings indicate that the ferroptosis regulatory factor, Lox, is activated in ECD. Ablation of Lox by either pharmacological intervention or genetic manipulation ameliorates the impairment in ECD mouse model, which suggest that Lox serves as a promising therapeutic target for treating ECD in clinic.

The effect of artificial light at night (ALAN) on the characteristics of diapause of Aedes albopictus.

BACKGROUND: Recently, the effect of artificial light at night (ALAN) on the physiology and behavior of insects has gradually attracted the attention of researchers and has become a new research topic. Aedes albopictus is an important vector that poses a great public health risk. Further studies on the diapause of Ae. albopictus can provide a basis for new vector control, and it is also worth exploring whether the effect of ALAN on the diapause of Ae. albopictus will provide a reference for the prevention and control of infectious diseases mediated by Ae. albopictus. METHODS: In this study, we experimentally studied the diapause characteristics of different geographical strains of Ae. albopictus under the interference of ALAN, explored the effect of ALAN on the diapause of Ae. albopictus and explored the molecular mechanism of ALAN on the diapause process through RNA-seq. RESULTS: As seen from the diapause incidence, Ae. albopictus of the same geographic strain showed a lower diapause incidence when exposed to ALAN. The differentially expressed genes (DEGs) were mainly enriched in signaling and metabolism-related pathways in the parental females and diapause eggs of the ALAN group. CONCLUSIONS: ALAN inhibits Ae. albopictus diapause. In the short photoperiod induced diapause of Ae. albopictus in temperate strain Beijing and subtropical strain Guangzhou, the disturbance of ALAN reduced the egg diapause rate and increased the egg hatching rate of Ae. albopictus, and the disturbance of ALAN also shortened the life cycle of Ae. albopictus eggs after hatching.

Macrophage-Capturing Self-Assembly Photosensitizer Nanoparticles Induces Immune Microenvironment Re-Programming and Golgi-Responsive Immunogenic Cell Death in Head and Neck Carcinoma.

Head and neck carcinoma treatment is shifted toward the combination of therapy causing immune checkpoint blockade (ICB) and immunogenic cell death. In this study, a CSFRi-chimeric TAMCSFR+-targeting extracellular vesicle (EV@CSFRi) platform is developed and designed an intracellular protoporphyrin conjugated with RVRR peptide sequence for furin-cleavage to perform Golgi-targeting and generating ROS (GT-RG). The graphical abstract illustrates the self-assembly of GT-RG nanoparticles into nanofiber through the hydrophily of RVRR and hydrophobicity of RG, and the red line indicates the site of furin cleavage. As is shown in the Graphical abstract, the Golgi-targeting Protoporphyrin-RVRR platform is composed with CSFRi-chimeric extracellular vesicles and forms the tumor-responsive TAM-reprogramming bilayers (GT-RGEV@CSFRi). The GT-RGEV@CSFRi acted as a multifunctional theranostic platform, which can induce immunogenic cell death and further help modulate TAM, thus suppressing the HNC xenograft model by combination therapy with anti-PD-1.

Distribution and protection of Thesium chinense Turcz. under climate and land use change.

Wild medicinal plants are prominent in the field of Traditional Chinese Medicine (TCM), but their availability is being impacted by human activities and ecological degradation in China. To ensure sustainable use of these resources, it is crucial to scientifically plan areas for wild plant cultivation. Thesium chinense, a known plant antibiotic, has been overharvested in recent years, resulting in a sharp reduction in its wild resources. In this study, we employed three atmospheric circulation models and four socio-economic approaches (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) to investigate the primary environmental factors influencing the distribution of T. chinense. We also examined changes in its suitable area using the Biomod2 package. Additionally, we utilized the PLUS model to project and analyze future land use changes in climate-stable regions for T. chinense. Our planning for wild tending areas of T. chinense was facilitated by the ZONATION software. Over the next century, the climate-stable regions for T. chinense in China is approximately 383.05 × 104 km2, while the natural habitat in this region will progressively decline. Under the current climate conditions, about 65.06% of the habitats in the high suitable areas of T. chinense are not affected by future land use changes in China. Through hotspot analysis, we identified 17 hotspot cities as ideal areas for the wild tending of T. chinense, including 6 core hotspot cities, 6 sub-hotspot cities, and 5 fringe hotspot cities. These findings contribute to a comprehensive research framework for the cultivation planning of T. chinense and other medicinal plants.

Reconfiguration of Structural and Functional Connectivity Coupling in Patient Subgroups With Adolescent Depression.

Importance: Adolescent major depressive disorder (MDD) is associated with serious adverse implications for brain development and higher rates of self-injury and suicide, raising concerns about its neurobiological mechanisms in clinical neuroscience. However, most previous studies regarding the brain alterations in adolescent MDD focused on single-modal images or analyzed images of different modalities separately, ignoring the potential role of aberrant interactions between brain structure and function in the psychopathology. Objective: To examine alterations of structural and functional connectivity (SC-FC) coupling in adolescent MDD by integrating both diffusion magnetic resonance imaging (MRI) and resting-state functional MRI data. Design, Setting, and Participants: This cross-sectional study recruited participants aged 10 to 18 years from January 2, 2020, to December 28, 2021. Patients with first-episode MDD were recruited from the outpatient psychiatry clinics at The First Affiliated Hospital of Chongqing Medical University. Healthy controls were recruited by local media advertisement from the general population in Chongqing, China. The sample was divided into 5 subgroup pairs according to different environmental stressors and clinical characteristics. Data were analyzed from January 10, 2022, to February 20, 2023. Main Outcomes and Measures: The SC-FC coupling was calculated for each brain region of each participant using whole-brain SC and FC. Primary analyses included the group differences in SC-FC coupling and clinical symptom associations between SC-FC coupling and participants with adolescent MDD and healthy controls. Secondary analyses included differences among 5 types of MDD subgroups: with or without suicide attempt, with or without nonsuicidal self-injury behavior, with or without major life events, with or without childhood trauma, and with or without school bullying. Results: Final analyses examined SC-FC coupling of 168 participants with adolescent MDD (mean [mean absolute deviation (MAD)] age, 16.0 [1.7] years; 124 females [73.8%]) and 101 healthy controls (mean [MAD] age, 15.1 [2.4] years; 61 females [60.4%]). Adolescent MDD showed increased SC-FC coupling in the visual network, default mode network, and insula (Cohen d ranged from 0.365 to 0.581; false discovery rate [FDR]-corrected P < .05). Some subgroup-specific alterations were identified via subgroup analyses, particularly involving parahippocampal coupling decrease in participants with suicide attempt (partial η2 = 0.069; 90% CI, 0.025-0.121; FDR-corrected P = .007) and frontal-limbic coupling increase in participants with major life events (partial η2 ranged from 0.046 to 0.068; FDR-corrected P < .05). Conclusions and Relevance: Results of this cross-sectional study suggest increased SC-FC coupling in adolescent MDD, especially involving hub regions of the default mode network, visual network, and insula. The findings enrich knowledge of the aberrant brain SC-FC coupling in the psychopathology of adolescent MDD, underscoring the vulnerability of frontal-limbic SC-FC coupling to external stressors and the parahippocampal coupling in shaping future-minded behavior.

Identifying plasma metabolic characteristics of major depressive disorder, bipolar disorder, and schizophrenia in adolescents.

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are classified as major mental disorders and together account for the second-highest global disease burden, and half of these patients experience symptom onset in adolescence. Several studies have reported both similar and unique features regarding the risk factors and clinical symptoms of these three disorders. However, it is still unclear whether these disorders have similar or unique metabolic characteristics in adolescents. We conducted a metabolomics analysis of plasma samples from adolescent healthy controls (HCs) and patients with MDD, BD, and SCZ. We identified differentially expressed metabolites between patients and HCs. Based on the differentially expressed metabolites, correlation analysis, metabolic pathway analysis, and potential diagnostic biomarker identification were conducted for disorders and HCs. Our results showed significant changes in plasma metabolism between patients with these mental disorders and HCs; the most distinct changes were observed in SCZ patients. Moreover, the metabolic differences in BD patients shared features with those in both MDD and SCZ, although the BD metabolic profile was closer to that of MDD than to SCZ. Additionally, we identified the metabolites responsible for the similar and unique metabolic characteristics in multiple metabolic pathways. The similar significant differences among the three disorders were found in fatty acid, steroid-hormone, purine, nicotinate, glutamate, tryptophan, arginine, and proline metabolism. Interestingly, we found unique characteristics of significantly altered glycolysis, glycerophospholipid, and sphingolipid metabolism in SCZ; lysine, cysteine, and methionine metabolism in MDD and BD; and phenylalanine, tyrosine, and aspartate metabolism in SCZ and BD. Finally, we identified five panels of potential diagnostic biomarkers for MDD-HC, BD-HC, SCZ-HC, MDD-SCZ, and BD-SCZ comparisons. Our findings suggest that metabolic characteristics in plasma vary across psychiatric disorders and that critical metabolites provide new clues regarding molecular mechanisms in these three psychiatric disorders.

Label-Free Optical Imaging of Nanoscale Single Entities.

The advancement of optical microscopy technologies has achieved imaging of nanoscale objects, including nanomaterials, virions, organelles, and biological molecules, at the single entity level. Recently developed plasmonic and scattering based optical microscopy technologies have enabled label-free imaging of single entities with high spatial and temporal resolutions. These label-free methods eliminate the complexity of sample labeling and minimize the perturbation of the analyte native state. Additionally, these imaging-based methods can noninvasively probe the dynamics and functions of single entities with sufficient throughput for heterogeneity analysis. This perspective will review label-free single entity imaging technologies and discuss their principles, applications, and key challenges.

Correspondence-based Generative Bayesian Deep Learning for semi-supervised volumetric medical image segmentation.

Automated medical image segmentation plays a crucial role in diverse clinical applications. The high annotation costs of fully-supervised medical segmentation methods have spurred a growing interest in semi-supervised methods. Existing semi-supervised medical segmentation methods train the teacher segmentation network using labeled data to establish pseudo labels for unlabeled data. The quality of these pseudo labels is constrained as these methods fail to effectively address the significant bias in the data distribution learned from the limited labeled data. To address these challenges, this paper introduces an innovative Correspondence-based Generative Bayesian Deep Learning (C-GBDL) model. Built upon the teacher-student architecture, we design a multi-scale semantic correspondence method to aid the teacher model in generating high-quality pseudo labels. Specifically, our teacher model, embedded with the multi-scale semantic correspondence, learns a better-generalized data distribution from input volumes by feature matching with the reference volumes. Additionally, a double uncertainty estimation schema is proposed to further rectify the noisy pseudo labels. The double uncertainty estimation takes the predictive entropy as the first uncertainty estimation and takes the structural similarity between the input volume and its corresponding reference volumes as the second uncertainty estimation. Four groups of comparative experiments conducted on two public medical datasets demonstrate the effectiveness and the superior performance of our proposed model. Our code is available on https://github.com/yumjoo/C-GBDL.