[Effect and mechanism of Compound Shougong Powder in attenuating triple-negative breast cancer progression by reversing epithelial-to-mesenchymal transition].

The study investigated the effect of Compound Shougong Powder(CSGP) on the biological functions of triple-negative breast cancer(TNBC) cells and whether its mechanism of action was related to the epithelial-mesenchymal transition(EMT) signaling pathway. TNBC cells(MDA-MB-231 and BT-549) were treated with different concentrations of CSGP-containing serum. MTS assay was used to detect the effect of CSGP on the proliferation of TNBC cells. The EdU staining was used to detect the effect of CSGP on the proliferation of TNBC cells. Flow cytometry was used to examine the impact of CSGP on apoptosis of TNBC cells. Wound-healing and Transwell assays were used to evaluate the effects of different concentrations of CSGP on the migration and invasion capabilities of TNBC cells. RNA sequencing technology was utilized to elucidate its mechanism. Subsequently, qRT-PCR was performed to measure the mRNA expression levels of E-cadherin, N-cadherin, Slug, Snail, Vimentin, Twist, Zinc finger E-box-Binding homeobox 1(Zeb1), and Zinc finger E-box-Binding homeobox 2(Zeb2). Western blot was used to assess the protein expression levels of Slug, Vimentin, and E-cadherin. After intervention with CSGP, the proliferation of MDA-MB-231 and BT-549 cells significantly decreased, while the apoptosis rate markedly increased. The expression levels of the epithelial marker protein E-cadherin significantly increased, while the expression levels of the EMT-related transcription factors Slug and Vimentin showed a decrease. In conclusion, CSGP inhibits the EMT, thereby suppressing the malignant progression of TNBC.

Targeting tumor-associated macrophage-derived CD74 improves efficacy of neoadjuvant chemotherapy in combination with PD-1 blockade for cervical cancer.

BACKGROUND: Cervical cancer has the second-highest mortality rate among malignant tumors of the female reproductive system. Immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1) blockade are promising therapeutic agents, but their efficacy when combined with neoadjuvant chemotherapy (NACT) has not been fully tested, and how they alter the tumor microenvironment has not been comprehensively elucidated. METHODS: In this study, we conducted single-cell RNA sequencing using 46,950 cells from nine human cervical cancer tissues representing sequential different stages of NACT and PD-1 blockade combination therapy. We delineated the trajectory of cervical epithelial cells and identified the crucial factors involved in combination therapy. Cell-cell communication analysis was performed between tumor and immune cells. In addition, THP-1-derived and primary monocyte-derived macrophages were cocultured with cervical cancer cells and phagocytosis was detected by flow cytometry. The antitumor activity of blocking CD74 was validated in vivo using a CD74 humanized subcutaneous tumor model. RESULTS: Pathway enrichment analysis indicated that NACT activated cytokine and complement-related immune responses. Cell-cell communication analysis revealed that after NACT therapy, interaction strength between T cells and cancer cells decreased, but intensified between macrophages and cancer cells. We verified that macrophages were necessary for the PD-1 blockade to exert antitumor effects in vitro. Additionally, CD74-positive macrophages frequently interacted with the most immunoreactive epithelial subgroup 3 (Epi3) cancer subgroup during combination NACT. We found that CD74 upregulation limited phagocytosis and stimulated M2 polarization, whereas CD74 blockade enhanced macrophage phagocytosis, decreasing cervical cancer cell viability in vitro and in vivo. CONCLUSIONS: Our study reveals the dynamic cell-cell interaction network in the cervical cancer microenvironment influenced by combining NACT and PD-1 blockade. Furthermore, blocking tumor-associated macrophage-derived CD74 could augment neoadjuvant therapeutic efficacy.

Tandem Protocol for Diversified Deuteration of Secondary Aliphatic Amines under Mild Conditions.

Deuteration of amine compounds has been widely of concern because of its practical role in organic reaction mechanisms and drug research; however, only limited deuteration label methods are accessible with D2O as a deuterium source. Herein, we propose a convenient deuteration protocol, including preparing D2 by the AlGa activation method, using PtRu nanowires as catalysts, and utilizing the elementary step in the couple reaction involving an imine unit, to realize the rapid preparation of a secondary amine with a diversified deuteration label. The self-coupling between nitriles not only provides a symmetric secondary amine with four α-D atoms but also produces high-valued ND3 in an atomic-economic way.

Association between the copy number variations of Methyl-CpG binding domain family and schizophrenia.

Schizophrenia is recognized as one of the most severe psychiatric disorders, with its pathogenesis likely involving genetic, epigenetic, developmental, and environmental factors. Members of the Methyl-CpG Binding Domain (MBD) Family play a crucial role in the regulation of genomic DNA methylation, and studies have implicated the association between MBD family and neurodevelopmental disorders. Copy number variations (CNVs) are a significant genetic basis for human genomic variation, also playing a critical role in the genetic processes of schizophrenia. Therefore, we aimed to evaluate the susceptibility of MBD family CNVs to schizophrenia by exploring and validating them in two separate populations using CNVplex™ and qPCR methods, and to explore the relationship between MBD family CNVs and clinical phenotypes in the overall population using chi-square tests and Fisher's exact tests. Results suggest that an increase in MBD1 gene copy number and a deficiency in MBD2 gene copy number may be associated with the risk of schizophrenia. The deficiency in MBD2 gene copy number may increase the risk of delusion of reference and delusion of persecutory in the overall sample, as well as in males. This research provides preliminary evidence supporting the association between MBD family CNVs and schizophrenia, highlighting the potential role of the MBD family in the pathogenesis of schizophrenia.

Prevalence and genotype distribution of human papillomavirus infection among 66000 women from 2014 to 2023 in the plateau region of Southwest China.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

Hydroxychloroquine blood concentrations and effects in Chinese patients with IgA nephropathy.

BACKGROUND: Hydroxychloroquine (HCQ) is recommended for Chinese patients with immunoglobulin A nephropathy (IgAN). However, the relationship between HCQ blood concentration and the therapeutic effect for IgAN has not yet been defined. This study investigates the optimal and efficacious range of HCQ blood concentrations in Chinese patients with IgAN. METHODS: Seventy-three patients with biopsy-proven IgAN who were at risk of progression were included in this study. Thirty-eight patients with IgAN were treated with HCQ plus an optimized renin-angiotensin-aldosterone system inhibitor (RAASi), and thirty-five patients received only RAASi. Blood HCQ concentration and 24-h proteinuria were examined at three and six months after treatment. RESULTS: The baseline proteinuria levels were comparable between the RAASi and HCQ groups. The HCQ group had lower 24-h proteinuria than the RAASi group three months after treatment, though the difference was not significant (p = 0.38). After six months, the median proteinuria level was significantly lower in the HCQ group than in the RAASi group (p < 0.05). The percentage reduction in 24-h proteinuria in the HCQ group was greater than that in the RAASi group at three (p < 0.05) and six months (p < 0.05). Hydroxychlorquine blood concentration and efficacy were positively correlated at three months (r = 0.428, p < 0.05) and six months (r = 0.48, p < 0.05). Moreover, the optimal blood concentration of HCQ for three-month efficacy was 418.96 ng/mL and that for six-month efficacy was 582.48 ng/mL. No serious adverse events were reported during HCQ treatment. CONCLUSIONS: Hydroxyhloroquine safely reduces proteinuria in Chinese patients with IgAN. The efficacy of HCQ is positively correlated with its blood concentration.

Semaglutide for the prevention of atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is reported to have cardiac benefits, but its effects on preventing atrial fibrillation (AF) remain inconclusive. This study aimed to investigate whether semaglutide can prevent AF occurrence in patients with type 2 diabetes mellitus (T2DM), obesity, or overweight. METHODS: We searched MEDLINE, EMBASE, the Cochrane CENTRAL database, and clinicaltrials.gov from inception to December 29, 2023. Randomized controlled trials of semaglutide in patients with T2DM, obesity, or overweight were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for the overall population and subgroups. RESULTS: Twenty-one trials comprising 25957 patients were included. In the overall pooled analysis, semaglutide decreased AF occurrence compared to control drugs (RR 0.70, 95 % CI 0.52-0.95). This result was consistent in trials using other antihyperglycemic medications as controls (RR 0.43, 95 % CI 0.21-0.89), but not in placebo-controlled trials (RR 0.77, 95 % CI 0.56-1.07). The outcome was favorable for patients with T2DM (RR 0.71, 95 % CI 0.52-0.97), but not for patients with overweight or obesity (RR 0.56, 95 % CI 0.18-1.73). Results varied by type of semaglutide, with oral semaglutide showing an RR of 0.49 (95 % CI 0.25-0.97) and subcutaneous semaglutide showing an RR of 0.77 (95 % CI 0.55-1.07). CONCLUSION: Semaglutide was associated with a reduced risk of AF occurrence in the overall analysis. Favorable outcomes were observed in subsets using other antihyperglycemic medications as controls, in patients with T2DM, and with oral semaglutide.

Coherent control on the generation and annihilation of a pseudospin-induced optical vortex in a honeycomb photonic lattice.

We experimentally investigate the coherently controllable generation and annihilation of a pseudospin-induced optical vortex in an optically induced honeycomb photonic lattice in a Λ-type 85Rb atomic vapor cell. Three Gaussian coupling beams are coupled into the atomic gases to form a hexagonal interference pattern, which can induce a honeycomb photonic lattice under electromagnetically induced transparency. Then, two probe beams interfere with each other to form periodical fringes and cover one set of sublattice in the honeycomb lattice, corresponding to excite the K or K' valleys in momentum space. By properly adjusting the experimental parameters, the generation and annihilation of the induced optical vortex can be effectively controlled. The theoretical simulations based on the Dirac and Schrödinger equations are performed to explore the underlying mechanisms, which will support the observations. The demonstrated properties of such controllable optical vortex may lay the foundation for the design of vortex-based optical devices with multidimensional tunability.

A highly sensitive and colorimetric fluorescent probe for visualizing hydroxylamine in immune cells.

BACKGROUND: Hydroxylamine (HA) is vital industrial raw material and pharmaceutical intermediate. In addition, HA is an important cellular metabolite, which is intermediate in the formation of nitric oxide and nitroxide. However, excessive amounts of HA are toxic to both animals and plants. Conventional methods for the detection of HA are cumbersome and complicated. The detection of HA with fluorescent probes is convenient and sensitive. There are few probes available for the detection of hydroxylamine. Therefore, a fluorescent probe for the sensitive and selective detection of HA was developed in this work. RESULTS: A coumarin derivative SWJT-22 was synthesized as a colorimetric fluorescent probe to detect hydroxylamine (HA), with high sensitivity and selectivity. The detection limit of the probe to HA was 0.15 µM, which was lower than most probes of HA. Upon the addition of HA to aqueous solution containing SWJT-22, the color of the solution changed from orange to yellow, and the fluorescence color also changed from orange to green. The reaction mechanism of SWJT-22 to HA was confirmed by 1H NMR titrations, mass spectrometry and round bottom flask experiments. Moreover, SWJT-22 had been fabricated into portable test strips for the detection of HA. SWJT-22 had been successfully used in cellular imaging and could detect both endogenous and exogenous HA in HeLa cells and RAW 264.7 cells. SIGNIFICANCE: Due to the physiological role of hydroxylamine in organisms, it is crucial to detect hydroxylamine selectively and sensitively. This work provided a convenient tool for the detection of hydroxylamine, not only to detect endogenous and exogenous HA in cells, but also made into portable test strips. The HA fluorescent probe SWJT-22 is expected to promote the study of HA in physiological processes.

Photosynthetic performance of glumes of oat spikelets is more stable for grain-filling stage under drought stress.

Drought stress affects plant photosynthesis, leading to a reduction in the quality and yield of crop production. Non-foliar organs play a complementary role in photosynthesis during plant growth and development and are important sources of energy. However, there are limited studies on the performance of non-foliar organs under drought stress. The photosynthetic-responsive differences of oat spikelet organs (glumes, lemmas and paleas) and flag leaves to drought stress during the grain-filling stage were examined. Under drought stress, photosynthetic performance of glume is more stable. Intercellular CO2 concentration (Ci), chlorophyll b, maximum photochemical efficiency of photosystem II. (Fv/Fm), and electron transport rate (ETR) were significantly higher in the glume compared to the flag leaf. The transcriptome data revealed that stable expression of the RCCR gene under drought stress was the main reason for maintaining higher chlorophyll content in the glume. Additionally, no differential expression genes (DEGs) related to Photosystem Ⅰ (PSI) reaction centers were found, and drought stress primarily affects the Photosystem II (PSII) reaction center. In spikelets, the CP43 and CP47 subunits of PSII and the AtpB subunit of ATP synthase were increased on the thylakoid membrane, contributing to photosynthetic stabilisation of spikelets as a means of supplementing the limited photosynthesis of the leaves under drought stress. The results enhanced understanding of the photosynthetic performance of oat spikelet during the grain-filling stage, and also provided an important basis on improving the photosynthetic capacity of non-foliar organs for the selection and breeding new oat varieties with high yield and better drought resistance.

Integrated Pristine van der Waals Homojunctions for Self-Powered Image Sensors.

Van der Waals junctions hold significant potentials for various applications in multifunctional and low-power electronics and optoelectronics. The multistep device fabrication process usually introduces lattice mismatch and defects at the junction interfaces, which deteriorate device performance. Here the layer engineering synthesis of van der Waals homojunctions consisting of 2H-MoTe2 with asymmetric thickness to eliminate heterogenous interfaces and thus obtain clean interfaces is reported. Experimental results confirm that the homostructure nature gives rise to the formation of pristine van der Waals junctions, avoiding chemical disorders and defects. The ability to tune the energy bands of 2H-MoTe2 continuously through layer engineering enables the creation of adjustable built-in electric field at the homojunction boundaries, which leads to the achievement of self-powered photodetection based on the obtained 2H-MoTe2 films. Furthermore, the successful integration of 2H-MoTe2 homojunctions into an image sensor with 10 × 10 pixels, brings about zero-power consumption and near-infrared imaging functions. The pristine van der Waals homojunctions and effective integration strategies shed new insights into the development of large-scale application for two-dimensional materials in advanced electronics and optoelectronics.

Identifying influencing factors of metabolic syndrome in patients with major depressive disorder: A real-world study with Bayesian network modeling.

BACKGROUND: The bidirectional relationships between metabolic syndrome (MetS) and major depressive disorder (MDD) were discovered, but the influencing factors of the comorbidity were barely investigated. We aimed to fully explore the factors and their associations with MetS in MDD patients. METHODS: The data were retrieved from the electronic medical records of a tertiary psychiatric hospital in Beijing from 2016 to 2021. The influencing factors were firstly explored by univariate analysis and multivariate logistic regressions. The propensity score matching was used to reduce the selection bias of participants. Then, the Bayesian networks (BNs) with hill-climbing algorithm and maximum likelihood estimation were preformed to explore the relationships between influencing factors with MetS in MDD patients. RESULTS: Totally, 4126 eligible subjects were included in the data analysis. The proportion rate of MetS was 32.6 % (95 % CI: 31.2 %-34.1 %). The multivariate logistic regression suggested that recurrent depression, uric acid, duration of depression, marriage, education, number of hospitalizations were significantly associated with MetS. In the BNs, number of hospitalizations and uric acid were directly connected with MetS. Recurrent depression and family history psychiatric diseases were indirectly connected with MetS. The conditional probability of MetS in MDD patients with family history of psychiatric diseases, recurrent depression and two or more times of hospitalizations was 37.6 %. CONCLUSION: Using the BNs, we found that number of hospitalizations, recurrent depression and family history of psychiatric diseases contributed to the probability of MetS, which could help to make health strategies for specific MDD patients.

Highly Efficient Spin Injection and Readout Across Van Der Waals Interface.

Spin injection, transport, and detection across the interface between a ferromagnet and a spin-carrying channel are crucial for energy-efficient spin logic devices. However, interfacial conductance mismatch, spin dephasing, and inefficient spin-to-charge conversion significantly reduce the efficiency of these processes. In this study, it is demonstrated that an all van der Waals heterostructure consisting of a ferromagnet (Fe3GeTe2) and Weyl semimetal enables a large spin readout efficiency. Specifically, a nonlocal spin readout signal of 150 mΩ and a local spin readout signal of 7.8 Ω is achieved, which reach the signal level useful for practical spintronic devices. The remarkable spin readout signal is attributed to suppressed spin dephasing channels at the vdW interfaces, long spin diffusion, and efficient charge-spin interconversion in Td-MoTe2. These findings highlight the potential of vdW heterostructures for spin Hall effect-enabled spin detection with high efficiency, opening up new possibilities for spin-orbit logic devices using vdW interfaces.

MRI versus Dual-Energy CT in Local-Regional Staging of Gastric Cancer.

Background Preoperative local-regional tumor staging of gastric cancer (GC) is critical for appropriate treatment planning. The comparative accuracy of multiparametric MRI (mpMRI) versus dual-energy CT (DECT) for staging of GC is not known. Purpose To compare the diagnostic accuracy of personalized mpMRI with that of DECT for local-regional T and N staging in patients with GC receiving curative surgical intervention. Materials and Methods Patients with GC who underwent gastric mpMRI and DECT before gastrectomy with lymphadenectomy were eligible for this single-center prospective noninferiority study between November 2021 and September 2022. mpMRI comprised T2-weighted imaging, multiorientational zoomed diffusion-weighted imaging, and extradimensional volumetric interpolated breath-hold examination dynamic contrast-enhanced imaging. Dual-phase DECT images were reconstructed at 40 keV and standard 120 kVp-like images. Using gastrectomy specimens as the reference standard, the diagnostic accuracy of mpMRI and DECT for T and N staging was compared by six radiologists in a pairwise blinded manner. Interreader agreement was assessed using the weighted κ and Kendall W statistics. The McNemar test was used for head-to-head accuracy comparisons between DECT and mpMRI. Results This study included 202 participants (mean age, 62 years ± 11 [SD]; 145 male). The interreader agreement of the six readers for T and N staging of GC was excellent for both mpMRI (κ = 0.89 and 0.85, respectively) and DECT (κ = 0.86 and 0.84, respectively). Regardless of reader experience, higher accuracy was achieved with mpMRI than with DECT for both T (61%-77% vs 50%-64%; all P < .05) and N (54%-68% vs 51%-58%; P = .497-.005) staging, specifically T1 (83% vs 65%) and T4a (78% vs 68%) tumors and N1 (41% vs 24%) and N3 (64% vs 45%) nodules (all P < .05). Conclusion Personalized mpMRI was superior in T staging and noninferior or superior in N staging compared with DECT for patients with GC. Clinical trial registration no. NCT05508126 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Méndez and Martín-Garre in this issue.

A network analysis of the interrelationships between depression, anxiety, insomnia and quality of life among fire service recruits.

Background: Research on the mental health and quality of life (hereafter QOL) among fire service recruits after the end of the COVID-19 restrictions is lacking. This study explored the network structure of depression, anxiety and insomnia, and their interconnections with QOL among fire service recruits in the post-COVID-19 era. Methods: This cross-sectional study used a consecutive sampling of fire service recruits across China. We measured the severity of depression, anxiety and insomnia symptoms, and overall QOL using the nine-item Patient Health Questionnaire (PHQ-9), seven-item Generalized Anxiety Disorder scale (GAD-7), Insomnia Severity Index (ISI) questionnaire, and World Health Organization Quality of Life-brief version (WHOQOL-BREF), respectively. We estimated the most central symptoms using the centrality index of expected influence (EI), and the symptoms connecting depression, anxiety and insomnia symptoms using bridge EI. Results: In total, 1,560 fire service recruits participated in the study. The prevalence of depression (PHQ-9 ≥ 5) was 15.2% (95% CI: 13.5-17.1%), while the prevalence of anxiety (GAD-7 ≥ 5) was 11.2% (95% CI: 9.6-12.8%). GAD4 ("Trouble relaxing") had the highest EI in the whole network model, followed by ISI5 ("Interference with daytime functioning") and GAD6 ("Irritability"). In contrast, PHQ4 ("Fatigue") had the highest bridge EI values in the network, followed by GAD4 ("Trouble relaxing") and ISI5 ("Interference with daytime functioning"). Additionally, ISI4 "Sleep dissatisfaction" (average edge weight = -1.335), which was the central symptom with the highest intensity value, had the strongest negative correlation with QOL. Conclusion: Depression and anxiety were important mental health issues to address among fire service recruits in the post-COVID-19 era in China. Targeting central and bridge symptoms identified in network analysis could help address depression and anxiety among fire service recruits in the post-COVID-19 era.

Abnormal resting-state functional connectivity in subregions of amygdala in adults and adolescents with major depressive disorder.

BACKGROUND: The different symptoms of major depressive disorder (MDD) in adolescents compared to adults suggested there may be differences in the pathophysiology between adolescents and adults with MDD. However, despite the amygdala being considered critical in the pathophysiology, there was limited knowledge about the commonalities and differences in the resting-state functional connectivity (rsFC) of amygdala subregions in MDD patients of different age groups. METHODS: In the current study, 65 adolescents (46 with MDD and 19 controls) and 91 adults (35 with MDD and 56 controls) were included. A seed-based functional connectivity analysis was performed for each of the amygdala subregions. A 2 × 2 ANOVA was used to analyze the main effect of age, diagnosis, and their interaction on the rsFC of each subregion. RESULTS: A significant main effect of age was revealed in the rsFC of bilateral centromedial (CM) subregions and right laterobasal (LB) subregion with several brain regions in the limbic system and frontoparietal network. The significant main effect of diagnosis showed MDD patients of different ages showed higher connectivity than controls between the right LB and left middle frontal gyrus (MFG). CONCLUSIONS: The rsFC of specific amygdala subregions with brain regions in the limbic system and frontoparietal network is affected by age, indicating a distinct amygdala connectivity profile in adolescents. The decreased rsFC between the right LB and the left MFG in adolescents and adults with MDD could serve as a diagnostic biomarker and a target of nonpharmacological treatment for MDD.

Shared and unique alterations of large-scale network connectivity in drug-free adolescent-onset and adult-onset major depressive disorder.

Differences in clinical manifestations and biological underpinnings between Major Depressive Disorder (MDD) onset during adolescence and adulthood have been posited in previous studies, implying an influential role of age of onset (AOO) in the clinical subtyping and therapeutic approaches to MDD. However, direct comparisons between the two cohorts and their age-matched controls have been lacking in extant investigations. In this investigation, 156 volunteers participated, comprising 46 adolescents with MDD (adolescent-onset group), 35 adults with MDD (adult-onset group), 19 healthy adolescents, and 56 healthy adults. Resting-state functional MRI scans were undergone by all participants. Large-scale network analyses were applied. Subsequently, a 2 × 2 ANOVA was employed to analyze the main effects of diagnosis, age, and their interaction effect on functional connectivity (FC). Furthermore, regression analysis was employed to scrutinize the association between anomalous FC and HAMD sub-scores. Increased FC in visual network (VN), limbic network (LN), VN-dorsal attention network (DAN), VN-LN, and LN-Default Mode (DMN) was found in both adolescent-onset and adult-onset MDD; however, the increased FC in DAN and LN were only found in adult-onset MDD and the decreased FC in DAN was only found in adolescent-onset MDD. Additionally, the relationship between HAMD factor 1 anxiety somatization and altered FC of DAN, VN, and VN-DAN was moderated by AOO. In conclusion, shared and distinctive large-scale network alterations in adolescent-onset and adult-onset MDD patients were suggested by our findings, providing valuable contributions towards refining clinical subtyping and treatment approaches for MDD.