Accelerating the understanding of cancer biology through the lens of genomics.

A core mission of cancer genomics is to comprehensively chart molecular underpinnings of cancer-driving events and to provide personalized therapeutic strategies. Primarily focused on cancer cells, cancer genomics studies have successfully uncovered many drivers for major cancer types. Since the emergence of cancer immune evasion as a critical cancer hallmark, the paradigm has been elevated to the holistic tumor ecosystem, with distinct cellular components and their functional states elucidated. We highlight the milestones of cancer genomics, depict the evolving path of the field, and discuss future directions in completing the understanding of the tumor ecosystem and in advancing therapeutic strategies.

A pan-cancer single-cell panorama of human natural killer cells.

Natural killer (NK) cells play indispensable roles in innate immune responses against tumor progression. To depict their phenotypic and functional diversities in the tumor microenvironment, we perform integrative single-cell RNA sequencing analyses on NK cells from 716 patients with cancer, covering 24 cancer types. We observed heterogeneity in NK cell composition in a tumor-type-specific manner. Notably, we have identified a group of tumor-associated NK cells that are enriched in tumors, show impaired anti-tumor functions, and are associated with unfavorable prognosis and resistance to immunotherapy. Specific myeloid cell subpopulations, in particular LAMP3+ dendritic cells, appear to mediate the regulation of NK cell anti-tumor immunity. Our study provides insights into NK-cell-based cancer immunity and highlights potential clinical utilities of NK cell subsets as therapeutic targets.

Activation of ERß hijacks the splicing machinery to trigger R-loop formation in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with aggressive behavior and poor prognosis. Current therapeutic options available for TNBC patients are primarily chemotherapy. With our evolving understanding of this disease, novel targeted therapies, including poly ADP-ribose polymerase (PARP) inhibitors, antibody-drug conjugates, and immune-checkpoint inhibitors, have been developed for clinical use. Previous reports have demonstrated the essential role of estrogen receptor ß (ERß) in TNBC, but the detailed molecular mechanisms downstream ERß activation in TNBC are still far from elucidated. In this study, we demonstrated that a specific ERß agonist, LY500307, potently induces R-loop formation and DNA damage in TNBC cells. Subsequent interactome experiments indicated that the residues 151 to 165 of U2 small nuclear RNA auxiliary factor 1 (U2AF1) and the Trp439 and Lys443 of ERß were critical for the binding between U2AF1 and ERß. Combined RNA sequencing and ribosome sequencing analysis demonstrated that U2AF1-regulated downstream RNA splicing of 5-oxoprolinase (OPLAH) could affect its enzymatic activity and is essential for ERß-induced R-loop formation and DNA damage. In clinical samples including 115 patients from The Cancer Genome Atlas (TCGA) and 32 patients from an in-house cohort, we found a close correlation in the expression of ESR2 and U2AF1 in TNBC patients. Collectively, our study has unraveled the molecular mechanisms that explain the therapeutic effects of ERß activation in TNBC, which provides rationale for ERß activation-based single or combined therapy for patients with TNBC.

Recent Advances in DNA Origami-Engineered Nanomaterials and Applications.

DNA nanotechnology is a unique field, where physics, chemistry, biology, mathematics, engineering, and materials science can elegantly converge. Since the original proposal of Nadrian Seeman, significant advances have been achieved in the past four decades. During this glory time, the DNA origami technique developed by Paul Rothemund further pushed the field forward with a vigorous momentum, fostering a plethora of concepts, models, methodologies, and applications that were not thought of before. This review focuses on the recent progress in DNA origami-engineered nanomaterials in the past five years, outlining the exciting achievements as well as the unexplored research avenues. We believe that the spirit and assets that Seeman left for scientists will continue to bring interdisciplinary innovations and useful applications to this field in the next decade.

Comprehensive performance domain tolerance analysis methodology for freeform imaging spectrometers.

In recent years, attention has been directed towards cost-effective and compact freeform Schwarzschild imaging spectrometers with plane gratings. The utilization of tolerance analysis serves as a potent approach to facilitate the development of prototypes. Conventional tolerance analysis methods often rely solely on the modulation transfer function (MTF) criterion. However, for a spectrometer system, factors such as the keystone/smile distortion and spectral resolution performance also require consideration. In this study, a tailored comprehensive performance domain tolerance analysis methodology for freeform imaging spectrometers was developed, considering vital aspects such as the MTF, keystone/smile distortion, and spectral resolution. Through this approach, meticulous tolerance analysis was conducted for a freeform Schwarzschild imaging spectrometer, providing valuable insights for the prototype machining and assembly processes. Emphasis was placed on the necessity of precise control over the tilt and decenter between the first and third mirrors, whereas the other fabrication and assembly tolerances adhered to the standard requirements. Finally, an alignment computer-generated hologram (CGH) was employed for the preassembly of the first and third mirrors, enabling successful prototype development. The congruence observed between the measured results and tolerance analysis outcomes demonstrates the effectiveness of the proposed method.

Antipsychotic dose, dopamine D2 receptor occupancy and extrapyramidal side-effects: a systematic review and dose-response meta-analysis.

Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D2 receptor (D2R) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3-26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The D2R occupancy curves showed that the risk increased substantially when D2R occupancy exceeded 75-85%, except for D2R partial agonists that had smaller ORs albeit high D2R occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current D2R therapeutic window for EPS.

Moderating and mediating effects of resilience between childhood trauma and psychotic-like experiences among college students.

BACKGROUND: Extensive literature revealed that childhood trauma serves as a significant risk factor for developing psychotic-like experiences (PLEs) among the general population. Resilience has been regarded as a protective factor against PLEs. However, it remains unclear what role resilience plays in the relationship between childhood trauma and PLEs. METHODS: A total of 4302 college students completed the web-based survey in January 2021. Participants completed self-report measures of sample characteristics variables, childhood trauma, and PLEs. Moderation and mediation analyses were adopted to examine the associations linking childhood trauma, resilience, and PLEs. RESULTS: PLEs were positively associated with childhood trauma while negatively associated with resilience. Resilience played a partially mediating role in the relationship between childhood trauma and PLEs. Additionally, resilience moderated the association of childhood trauma with PLEs. CONCLUSIONS: These findings indicated that resilience plays a crucial role in mediating the relationship between childhood trauma and PLEs, suggesting the potential clinical implication of enhancing resilience for the prevention and intervention of PLEs among college students.

Employing Bayesian analysis to establish a cut-off point and assess stigma prevalence in substance use disorder: a comprehensive study of the Chinese version of the Substance Use Stigma Mechanism Scale.

PURPOSE: In China, individuals with substance use disorders (SUD) face severe stigma, but reliable stigma assessment tool is lacking. Therefore, this study aimed to validate the Chinese version of the Substance Use Stigma Mechanism Scale (SU-SMS-C) and set its cut-off point. METHODS: We recruited 1005 individuals with SUDs from Chinese rehabilitation centers. These participants completed a battery of questionnaires that included the SU-SMS-C, The Multidimensional Scale of Perceived Social Support (MSPSS), Center for Epidemiologic Studies Depression Scale (CES-D), General Self-Efficacy Scale (GSES), and Perceived Devaluation and Discrimination (PDD). Confirmatory factor analysis was used to assess the construct validity of the scale. Additionally, the Naive Bayes classifier was used to establish the cut-off point for the SU-SMS-C. We additionally explored the correlation between patient demographic characteristics and stigma. RESULTS: A confirmatory factor analysis was utilized, revealing a second-order five-factor model. Based on the Naive Bayes classifier, the area under the receiver operating characteristic (AUCROC) of 0.746, the cut-off point for the SU-SMS-C was established at 44.5. The prevalence of stigma observed in the study population was 49.05%. Significant disparities were observed in the distribution of stigma across genders, with males experiencing more pronounced stigma than females. Moreover, patients consuming different primary substances reported diverse levels of stigma. Notably, those primarily using heroin endured a higher degree of stigma than users of other substances. CONCLUSION: The study is the first to identify a cut-off point for the SU-SMS-C by Naive Bayes classifier, bridging a major gap in stigma measurement research. SU-SMS-C may help treat and manage SUDs by reducing stigma.

The therapeutic value of vacuum external fixation in polytrauma patients with multiple ribs fracture.

BACKGROUND: Multiple displaced rib fractures often result in a poor prognosis. Open reduction and internal fixation has been shown to provide benefits for patients with displaced rib fractures and flail chest. Nevertheless, for patients who are unwilling or unsuitable for surgery, the therapeutic options are limited. We developed a novel plastic vacuum device for rib fractures external stabilization. This study aims to compare the therapeutic efficacy of this device against a traditional chest strap in polytrauma patients with multiple rib fractures. METHODS: A retrospective investigation was conducted on polytrauma patients with multiple rib fractures admitted to our trauma center between March 2020 and March 2023. Patients were categorized into two groups: vacuum external fixation and chest strap. Comparative analysis was conducted on baseline parameters, injury characteristics, and clinical outcomes between the two groups. RESULTS: In this study, 54 patients were included, with 28 receiving chest strap and 26 undergoing vacuum external fixation. Results showed that, at 3 days and 7 days postintervention, the vacuum external fixation group had significantly lower visual analog scale scores during deep breathing and coughing (P < .05). Vacuum external fixation also reduced pleural drainage duration and volume, as well as lowered the risk of pneumonia and other complications (P < .05). Furthermore, the vacuum external fixation group demonstrated notable improvements in vital capacity, tidal volume, blood-gas test results, and a shorter hospital length of stay. CONCLUSIONS: According to the study findings, vacuum external fixation appears to offer benefits to patients with multiple rib fractures, potentially reducing the risk of complications and improving overall clinical outcomes.

Bidirectional associations between short sleep duration, insomnia symptoms, and psychotic-like experiences in adolescents.

This study investigates the prospective associations between short sleep duration, insomnia symptoms, and psychotic-like experiences (PLEs) in a large sample of Chinese adolescents. This study utilized a three-timepoint repeated cross-sectional survey with two nested longitudinal subsamples. A total of 17,722 adolescents were assessed at baseline (April 21 to May 12, 2021) and six months later (December 17 to 26, 2021). Out of these, 15,694 adolescents provided complete responses to the questions at baseline and one year later (May 17 - June 6, 2022). A self-administered questionnaire was used to measure sample characteristics (at baseline), sleep duration, insomnia symptoms, and PLEs (at each assessment), and negative life events (at two follow-ups). Baseline short sleep duration and insomnia symptoms predicted frequent PLEs at both follow-up assessments. Additionally, baseline frequent PLEs also predicted insomnia symptoms at six months and one year later. However, when controlling for confounders, PLEs at baseline only predicted short sleep duration at six months, and not at one year. This study reveals bidirectional prospective relationships between short sleep duration, insomnia symptoms, and PLEs, even after controlling for covariates. Therefore, it is crucial to assess both sleep patterns and PLEs in order to promote optimal sleep and mental health among adolescents.

Concurrent and longitudinal associations of dissatisfaction with height and weight, body mass index with sleep disturbance among adolescents in China.

Sleep disturbance in adolescents is a significant global public health issue that can result in various physical and mental disorders. Height and weight dissatisfaction, as subjective perceptions of body shape, are common in adolescence and may affect individuals' sleep situations. However, the association of them is unclear. This study aimed to examine the cross-sectional and longitudinal associations among height dissatisfaction, weight dissatisfaction, body mass index (BMI), and sleep disturbance in adolescents. A total of 27,260 participants completed measures of sleep disturbance, height and weight satisfaction, and BMI. The cross-sectional and longitudinal effects of height satisfaction, weight satisfaction, and BMI as well as their changes in sleep disturbance over time were tested. Height satisfaction (ps < 0.001) and weight satisfaction (ps < 0.001) were negatively associated with concurrent sleep disturbance after adjusting for socio-demographic covariates and previous sleep disturbance. Height satisfaction (ps < 0.001) and weight satisfaction (ps < 0.001) at T1 as well as their increases (ps < 0.001) over 6 months predicted decreases in sleep disturbance over time. The cross-sectional and longitudinal associations between BMI and sleep disturbance were not significant (ps > 0.42). Moreover, height dissatisfaction (ORs = 1.06 to 1.34) and weight dissatisfaction (ORs = 1.21 to 1.36) were risk factors for concurrent and long-term sleep disturbance while adjusting socio-demographic covariates and previous sleep disturbance. Greater attention to subjective perception of height satisfaction and weight satisfaction, instead of BMI is needed.

Simultaneous removal of tetracycline hydrochloride and hexavalent chromium by heterogeneous Fenton in a photocatalytic fuel cell system.

In this work, a novel double-chamber system (PFC-Fenton), combined photocatalytic fuel cell (PFC) with Fenton, was constructed for tetracycline hydrochloride (TCH) and hexavalent chromium (Cr(VI)) removal and electricity production. Therein, Zn5(OH)6(CO3)2/Fe2O3/BiVO4/fluorine-doped SnO2 (ZIO/BiVO4/FTO) and carboxylated carbon nanotubes/polypyrrole/graphite felt (CCNTs/Ppy/GF) were served as photoanode and cathode, respectively. Under light irradiation, the removal efficiencies of TCH and Cr(VI) with the addition of H2O2 (2 mL) could reach 93.1% and 80.4%, respectively. Moreover, the first-order kinetic constants (7.37 × 10-3 min-1 of TCH and 3.94 × 10-3 min-1 of Cr(VI)) were 5.26 and 5.57 times as much as the absence of H2O2. Simultaneously, the maximum power density could be obtained 0.022 mW/cm2 at a current density of 0.353 mA/cm2. Therein, the main contribution of TCH degradation was ·OH and holes in anode chamber. The synergistic effect of photoelectrons, generated ·O2-, and H2O2 played a crucial role in the reduction of Cr(VI) in cathode chamber. The high-performance liquid chromatography-mass spectrometry indicated that TCH could be partially mineralized into CO2 and H2O. X-ray photoelectron spectroscope and X-ray absorption near-edge structure spectra showed that Cr(VI) could be reduced to Cr(III). After 5 times of cycling, the removal efficiencies of TCH and Cr(VI) were still greater than 70%, indicating the remarkable stability of the PFC-Fenton system. Overall, this system could remove TCH/Cr(VI) and generate power simultaneously without iron sludge formation, demonstrating a promising method to further develop PFC-Fenton technology.

Review on physical performance, modification mechanisms, carbon emissions and economic costs of recycled aggregates modified with physical enhancement technologies.

With the continuous advancement of urban renewal, the application of recycled aggregates (RA) is a win-win measure to solve the treatment of construction waste and provide the required building materials. However, the existence of a large amount of old adhesive mortar (OAM) makes it difficult for RA to equivalently replace natural aggregates (NA) due to their higher water absorption and crushing index, as well as a lower apparent density. From the published literature on enhancing RA, the most mature and easiest method for construction is physical enhancement technology. Therefore, through a review of recent related researches, this article summarizes and compares the modification effects of mechanical grinding technology, traditional heating and grinding technology, and microwave heating technology on the physical properties of RA, including water absorption, apparent density, and crushing value. The related modification mechanisms were discussed. Additionally, the impacts of different physical enhancement technologies on the environment and economy effects are assessed from the perspectives of carbon emissions and cost required during processing. Based on multi-criteria analysis, microwave heating technology is more efficient and cleaner, which is the most recommended in the future.

scCancer: a package for automated processing of single-cell RNA-seq data in cancer.

Molecular heterogeneities and complex microenvironments bring great challenges for cancer diagnosis and treatment. Recent advances in single-cell RNA-sequencing (scRNA-seq) technology make it possible to study cancer cell heterogeneities and microenvironments at single-cell transcriptomic level. Here, we develop an R package named scCancer, which focuses on processing and analyzing scRNA-seq data for cancer research. Except basic data processing steps, this package takes several special considerations for cancer-specific features. Firstly, the package introduced comprehensive quality control metrics. Secondly, it used a data-driven machine learning algorithm to accurately identify major cancer microenvironment cell populations. Thirdly, it estimated a malignancy score to classify malignant (cancerous) and non-malignant cells. Then, it analyzed intra-tumor heterogeneities by key cellular phenotypes (such as cell cycle and stemness), gene signatures and cell-cell interactions. Besides, it provided multi-sample data integration analysis with different batch-effect correction strategies. Finally, user-friendly graphic reports were generated for all the analyses. By testing on 56 samples with 433 405 cells in total, we demonstrated its good performance. The package is available at: http://lifeome.net/software/sccancer/.

SSR identification and phylogenetic analysis in four plant species based on complete chloroplast genome sequences.

The effective utilization of traditional Chinese medicine (TCM) has been challenged by the difficulty to accurately distinguish between similar plant varieties. The stability and conservation of the chloroplast genome can aid in resolving genotypes. Previous studies using nuclear sequences and molecular markers have not effectively differentiated the species from related taxa, such as Machilus leptophylla, Hanceola exserta, Rubus bambusarum, and Rubus henryi. This study aimed to characterize the chloroplast genomes of these four plant species, and analyze their simple sequence repeats (SSRs) and phylogenetic positions. The results demonstrated the four chloroplast genomes consisted of 152.624 kb, 153.296 kb, 156.309 kb, and 158.953 kb in length, involving 124, 130, 129, and 131 genes, respectively. They also contained four specific regions with mononucleotide being the class with the most members. Moreover, these repeating types of SSR were various in individual class. Phylogenetic analysis showed that M. leptophylla was clustered with M. yunnanensis, and H. exserta was confirmed as belonging to the family Ocimeae. Additionally, R. bambusarum and R. henryi were grouped together but differed in their SSR features, indicating that they were not the same species. This research provides evidence for resolving species and contributes new genetic information for further studies.

A network meta-analysis of efficacy, acceptability, and tolerability of antipsychotics in treatment-resistant schizophrenia.

OBJECTIVE: Clozapine is considered as the standard treatment for this subgroup, but the evidence is not unequivocal. There are several potential alternatives being used because of the possible adverse effects of clozapine. We aimed to examine the efficacy and adverse events of different antipsychotics in treatment-resistant schizophrenia by performing a network meta-analysis. METHODS: We searched the Cochrane Schizophrenia Group register for randomized-controlled trials (up to March 06, 2022) and MEDLINE (up to January 20, 2023). We included blinded and open studies and participants with a broad definition of treatment resistance. The primary outcome was overall symptoms of schizophrenia; secondary outcomes were response to treatment, positive and negative symptoms of schizophrenia, discontinuation, side effects, quality of life, and functioning. The study was registered in Open Science Framework ( https://osf.io/9nf2y/ ). RESULTS: We included 60 studies involving 6838 participants in the network meta-analysis. In the primary outcome, clozapine and olanzapine were more efficacious than risperidone, haloperidol, fluphenazine, sertindole, chlorpromazine, and quetiapine (range of mean SMDs, - 0.11 to - 0.48). The difference between clozapine and olanzapine was trivial and uncertain (SMD - 0.05, 95% CI, - 0.21 to 0.11). The result of other efficacy outcomes as well as subgroup and sensitivity analyses were consistent with the primary analysis. Clozapine and olanzapine were associated with more weight gain, and clozapine was associated with more sedation events compared to many other antipsychotics. CONCLUSIONS: Clozapine remains the gold standard for patients with treatment-resistant schizophrenia. Olanzapine seems to be second-best and could be tried before switching to clozapine.

The predictive role of psychotic-like experiences in suicidal ideation among technical secondary school and college students during the COVID-19 pandemic.

BACKGROUND: Previous research has shown the strong association between psychotic-like experiences (PLEs) and suicide. However, the predictive role of PLEs in suicidal ideation (SI) during the COVID-19 pandemic remains unclear. AIMS: This study aimed to explore the association between PLEs before the pandemic and SI during the pandemic among late adolescents. METHODS: A total of 938 technical secondary school and college students completed both waves of the online survey before and during the pandemic. PLEs were assessed through the 15-item Positive Subscale of the Community Assessment of Psychic Experiences. SI was evaluated by the frequency of SI during the pandemic. RESULTS: In early stage of the pandemic, most students had low frequent SI, and only 3.3% students showed high frequent SI. Compared to the low frequent group, the high frequent group exhibited significantly higher levels of PLEs (p < 0.001) and scored lower in resilience (p = .001) and perceived social support (p = .008) across the two timepoints. PLEs were significantly associated with higher risk of high frequent SI (OR = 2.56, 95%: 1.07-6.13), while better resilience (OR: 0.93, 95% CI: 0.88-0.99) and stronger perceived social support (OR: 0.96, 95% CI: 0.93-0.99) appeared to be protective factors. No interactions were found among PLEs and other psychosocial and psychological factors. CONCLUSIONS: PLEs may increase the risk of SI in early stage of the pandemic, while good resilience and adequate social support can help weaken the risk.

Design and preliminary evaluation of a multi-channel multi-energy point integrated Wolter microscope.

In inertial confinement fusion, high-precision x-ray imaging is crucial for understanding the states of matter under extreme conditions. To observe the target asymmetry during compression, multiple imaging spots with varying energy responses are necessary. However, integrating multiple imaging channels in a grazing incidence x-ray imaging scheme is challenging, and there is an urgent need for effective combination of multi-color and high-throughput diagnostics. This study presents a design method for a multi-channel integrated Wolter microscope with high spatial resolution, wide-band response, and high throughput. The basic optical configuration, adjustment method, and multi-channel integration scheme are discussed in detail. A 10 keV-class three-channel integrated Wolter microscope is proposed for verification, with an estimated spatial resolution better than 4.0 µm in a field of view of ±500µm. The peak response efficiencies for each imaging channel are calculated as 5.2×10-5 s r, 8.6×10-5 s r, and 2.2×10-4 s r, respectively.

Profiles of depressive symptoms and influential factors among people living with HIV in China.

BACKGROUND: Depressive symptoms are highly prevalent among people living with HIV (PLWH). We leveraged Latent Profile Analysis (LPA) to identify profiles of depressive symptoms among PLWHs. We also investigated differences in psychological factors of interest, demographic characteristics, and HIV-related factors across patients' profiles. METHODS: A cross-sectional study was conducted at one hospital and two designated prison facilities in Hunan province, China. A total sample of 533 PLWHs (320 recruited from the hospital, 213 recruited from prisons) completed the survey. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9). Family function, resilience, childhood trauma, demographic characteristics, and HIV-related factors were also evaluated. We conducted LPA and multinomial logistic regression analyses to: 1) identify distinct profiles for depressive symptoms; 2) identify demographic characteristics, and HIV-related, and psychological factors predicting PLWHs' likelihood to express a specific profile. RESULTS: We identified three distinct profiles of depressive symptoms among PLWHs: severe symptoms (11.8%), moderate symptoms (40.5%), and low/no symptoms (47.7%). Moderate/ severe family dysfunction, low resilience, experiencing emotional abuse and neglect were more likely to fall in the "severe symptoms" rather than the "low/no symptoms" profile. In addition, severe family dysfunction, low resilience, and experiencing emotional neglect indicated a higher likelihood of being classified in the "moderate symptoms" profile, compared to the "low/no symptoms" profile. CONCLUSION: Identifying profiles of depressive symptoms among PLWHs using the PHQ-9 items allows for understanding of the distinct paths of development of depressive symptoms and for developing tailored prevention and intervention programs for PLWHs.

Integrated pathway and network analyses of metabolomic alterations in peripheral blood of patients with depression.

Depression is a serious mental illness, but the molecular mechanisms of depression remain unclear. Previous research has reported metabolomic changes in the blood of patients with depression, while integrated analysis based on these altered metabolites was still lacking. The objective of this study was to integrate metabolomic changes to reveal the underlying molecular alternations of depression. We retrieved altered metabolites in the blood of patients with depression from the MENDA database. Pathway analysis was conducted to explore enriched pathways based on candidate metabolites. Pathway crosstalk analysis was performed to explore potential correlations of these enriched pathways, based on their shared candidate metabolites. Moreover, potential interactions of candidate metabolites with other biomolecules such as proteins were assessed by network analysis. A total of 854 differential metabolite entries were retrieved in peripheral blood of patients with depression, including 555 unique candidate metabolites. Pathway analysis identified 215 significantly enriched pathways, then pathway crosstalk analysis revealed that these pathways were clustered into four modules, including amino acid metabolism, nucleotide metabolism, energy metabolism and others. Additionally, eight molecular networks were identified in the molecular network analysis. The main functions of these networks involved amino acid metabolism, molecular transport, inflammatory responses and others. Based on integrated analysis, our study revealed pathway-based modules and molecular networks associated with depression. These results will contribute to the underlying knowledge of the molecular mechanisms in depression.