Dysregulation of TNF-induced protein 3 and CCAAT/enhancer-binding protein ß in alveolar macrophages: Implications for systemic sclerosis-associated interstitial lung disease.

OBJECTIVES: This study investigates the role of TNF-induced protein 3 (TNFAIP3) and CCAAT/enhancer-binding protein ß (C/EBPß) in alveolar macrophages (AMs) of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) and their influence on pulmonary fibrosis. METHODS: Transfection of HEK293T cells and AMs with plasmids carrying TNFAIP3 and C/EBPß was performed, followed by co-culturing AMs with pulmonary fibroblasts. Immunoblotting analysis was then utilized to assess the expression of TNFAIP3, C/EBPß, and collagen type 1 (Col1). Quantitative PCR analysis was conducted to quantify the mRNA levels of C/EBPß, IL-10, and TGF-ß1. STRING database analysis, and immunoprecipitation assays were employed to investigate the interactions between TNFAIP3 and C/EBPß. RESULTS: TNFAIP3 expression was significantly reduced in SSc-ILD AMs, correlating with increased Col1 production in fibroblasts. Overexpression of TNFAIP3 inhibited this pro-fibrotic activity. Conversely, C/EBPß expression was elevated in SSc-ILD AMs, and its reduction through TNFAIP3 restoration decreased pro-fibrotic cytokines IL-10 and TGFß1 levels. Protein-protein interaction studies confirmed the regulatory relationship between TNFAIP3 and C/EBPß. CONCLUSIONS: This study highlights the important role of TNFAIP3 in regulating pulmonary fibrosis in SSc-ILD by modulating C/EBPß expression in AMs. These findings suggest that targeting TNFAIP3 could be a potential therapeutic strategy for managing SSc-ILD patients.

Recent advancements in mogrosides: A review on biological activities, synthetic biology, and applications in the food industry.

Mogrosides are low-calorie, biologically active sweeteners that face high production costs due to strict cultivation requirements and the low yield of monk fruit. The rapid advancement in synthetic biology holds the potential to overcome this challenge. This review presents mogrosides exhibiting antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, and liver protective activities, with their efficacy in diabetes treatment surpassing that of Xiaoke pills (a Chinese diabetes medication). It also discusses the latest elucidated biosynthesis pathways of mogrosides, highlighting the challenges and research gaps in this field. The critical and most challenging step in this pathway is the transformation of mogrol into a variety of mogrosides by different UDP-glucosyltransferases (UGTs), primarily hindered by the poor substrate selectivity, product specificity, and low catalytic efficiency of current UGTs. Finally, the applications of mogrosides in the current food industry and the challenges they face are discussed.

Structural disorder determines capacitance in nanoporous carbons.

The difficulty in characterizing the complex structures of nanoporous carbon electrodes has led to a lack of clear design principles with which to improve supercapacitors. Pore size has long been considered the main lever to improve capacitance. However, our evaluation of a large series of commercial nanoporous carbons finds a lack of correlation between pore size and capacitance. Instead, nuclear magnetic resonance spectroscopy measurements and simulations reveal a strong correlation between structural disorder in the electrodes and capacitance. More disordered carbons with smaller graphene-like domains show higher capacitances owing to the more efficient storage of ions in their nanopores. Our findings suggest ways to understand and exploit disorder to achieve highly energy-dense supercapacitors.

Asp-tRNAAsn/Glu-tRNAGln amidotransferase A subunit-like amidase mediates the degradation of insecticide flonicamid by Variovorax boronicumulans CGMCC 4969.

The main metabolic product of the pyridinecarboxamide insecticide flonicamid, N-(4-trifluoromethylnicotinyl)glycinamide (TFNG-AM), has been shown to have very high mobility in soil, leading to its accumulation in the environment. Catabolic pathways of flonicamid have been widely reported, but few studies have focused on the metabolism of TFNG-AM. Here, the rapid transformation of TFNG-AM and production of the corresponding acid product N-(4-trifluoromethylnicotinoyl) glycine (TFNG) by the plant growth-promoting bacterium Variovorax boronicumulans CGMCC 4969 were investigated. With TFNG-AM at an initial concentration of 0.86 mmol/L, 90.70 % was transformed by V. boronicumulans CGMCC 4969 resting cells within 20 d, with a degradation half-life of 4.82 d. A novel amidase that potentially mediated this transformation process, called AmiD, was identified by bioinformatic analyses. The gene encoding amiD was cloned and expressed recombinantly in Escherichia coli, and the enzyme AmiD was characterized. Key amino acid residue Val154, which is associated with the catalytic activity and substrate specificity of signature family amidases, was identified for the first time by homology modeling, structural alignment, and site-directed mutagenesis analyses. When compared to wild-type recombinant AmiD, the mutant AmiD V154G demonstrated a 3.08-fold increase in activity toward TFNG-AM. The activity of AmiD V154G was greatly increased toward aromatic L-phenylalanine amides, heterocyclic TFNG-AM and IAM, and aliphatic asparagine, whereas it was dramatically lowered toward benzamide, phenylacetamide, nicotinamide, acetamide, acrylamide, and hexanamid. Quantitative PCR analysis revealed that AmiD may be a substrate-inducible enzyme in V. boronicumulans CGMCC 4969. The mechanism of transcriptional regulation of AmiD by a member of the AraC family of regulators encoded upstream of the amiD gene was preliminarily investigated. This study deepens our understanding of the mechanisms of metabolism of toxic amides in the environment, providing new ideas for microbial bioremediation.

Interplay between Defects and Short-Range Disorder Manipulating the Oxygen Evolution Reaction on a Layered Double Hydroxide Electrocatalyst.

Improving the efficiency of the oxygen evolution reaction (OER) is crucial for advancing sustainable and environmentally friendly hydrogen energy. Layered double hydroxides (LDHs) have emerged as promising electrocatalysts for the OER. However, a thorough understanding of the impact of structural disorder and defects on the catalytic activity of LDHs remains limited. In this work, a series of NiAl-LDH models are systematically constructed, and their OER performance is rigorously screened through theoretical density functional theory. The acquired results unequivocally reveal that the energy increase induced by structural disorder is effectively counteracted at the defect surface, indicating the coexistence of defects and disorder. Notably, it is ascertained that the simultaneous presence of defects and disorder synergistically augments the catalytic activity of LDHs in the context of the OER. These theoretical findings offer valuable insights into the design of highly efficient OER catalysts while also shedding light on the efficacy of LDH electrocatalysts.

Computational simulations on the taste mechanism of steviol glycosides based on their interactions with receptor proteins.

Steviol glycoside (SG) is a potential natural sugar substitute. The taste of various SG structures differ significantly, while their mechanism has not been thoroughly investigated. To investigate the taste mechanism, molecular docking simulations of SGs with sweet taste receptor TAS1R2 and bitter taste receptor TAS2R4 were conducted. The result suggested that four flexible coils (regions) in TAS1R2 constructed a geometry open pocket in space responsible for the binding of sweeteners. Amino acids that form hydrogen bonds with sweeteners are located in different receptor regions. In bitterness simulation, fewer hydrogen bonds were formed with the increased size of SG molecules. Particularly, there was no interaction between RM and TAS2R4 due to its size, which explains the non-bitterness of RM. Molecular dynamics simulations further indicated that the number of hydrogen bonds between SGs and TAS1R2 was maintained during a simulation time of 50 ns, while sucrose was gradually released from the binding site, leading to the break of interaction. Conclusively, the high sweetness intensity of SG can be attributed to its durative concurrent interaction with the receptor's binding site, and such behavior was determined by the structure feature of SG.

Acid-induced conformation regulation of peanut polysaccharide and its effect on stability and digestibility of oil-in-water emulsion.

BACKGROUND: Developing the stable and healthy emulsion-based food is in accord with the needs of people for health. In the present study, acidification at pH 3.0 of peanut polysaccharide (APPSI) was employed to regulate its conformation and further improve its advantages in preparing oil-in-water emulsion. RESULTS: The results indicated that acidification induced conversion of PPSI aggregates into linear chains. Increasing concentration promoted formation of cross-linked network structure shown in transmission electron microscopy images. Consequently, the viscosity, yield stress, storage modulus and flow activation energy significantly increased, further fabricating gel structure. Moreover, aggregation behavior suggested that more exposed proteins were involved in gel structure, thereby forming many hydrophobic cores as verified by fluorescence spectroscopy of pyrene. Afterwards, emulsion characteristics indicated that APPSI produced strong and thick steric hindrance around oil droplets and the coil-like interweaved chains locked the continuous phase, bringing strong elasticity and resistance to stress and creaming. Meanwhile, the lower fatty acid in APPSI-emulsion was released after simulated gastrointestinal digestion, mainly as a result of the high retention ratio of emulsion droplets. Furthermore, the elastic and viscous Lissajous curves suggested that the structure strength of APPSI-emulsion was similar to that of the salad dressing within the strain 53.22%. CONCLUSION: The conformation of PPSI after acidification at pH 3.0 was suitable for preparing the stable emulsion. The obtained emulsion could resist digestion and maintain a strong structure, comprising a cholesterol-free and low-fat salad dressing substitute. © 2023 Society of Chemical Industry.

Cell-Permeable Stimuli-Responsive Ubiquitin Probe for Time-Resolved Monitoring of Substrate Ubiquitination in Live Cells.

Dynamic monitoring of intracellular ubiquitin (Ub) conjugates is instrumental to understanding the Ub regulatory machinery. Although many biochemical approaches have been developed to characterize protein ubiquitination, chemical tools capable of temporal resolution probing of ubiquitination events remain to be developed. Here, we report the development of the first cell-permeable and stimuli-responsive Ub probe and its application for the temporal resolution profiling of ubiquitinated substrates in live cells. The probe carrying the photolabile group N-(2-nitrobenzyl)-Gly (Nbg) on the amide bond between Ub Gly75 and Gly76 is readily prepared through chemical synthesis and can be delivered to live cells by conjugation via a disulfide bond with the cyclic cell-penetrating peptide cR10D (i.e., 4-((4-(dimethylamino)phenyl)-azo)-benzoic acid-modified cyclic deca-arginine). Both in vitro and in vivo experiments showed that Ub-modifying enzymes (E1, E2s, and E3s) could not install the Ub probe onto substrate proteins prior to removal of the nitrobenzyl group, which was easily accomplished via photoirradiation. The utility and practicality of this probe were exemplified by the time-resolved biochemical and proteomic investigation of ubiquitination events in live cells during a H2O2-mediated oxidative stress response. This work shows a conceptually new family of chemical Ub tools for the time-resolved studies on dynamic protein ubiquitination in different biological processes and highlights the utility of modern chemical protein synthesis in obtaining custom-designed tools for biological studies.

The digestive behavior of pectin in human gastrointestinal tract: a review on fermentation characteristics and degradation mechanism.

Pectin is widely spread in nature and it develops an extremely complex structure in terms of monosaccharide composition, glycosidic linkage types, and non-glycosidic substituents. As a non-digestible polysaccharide, pectin exhibits resistance to human digestive enzymes, however, it is easily utilized by gut microbiota in the large intestine. Currently, pectin has been exploited as a novel functional component with numerous physiological benefits, and it shows a promising prospect in promoting human health. In this review, we introduce the regulatory effects of pectin on intestinal inflammation and metabolic syndromes. Subsequently, the digestive behavior of pectin in the upper gastrointestinal tract is summarized, and then it will be focused on pectin's fermentation characteristics in the large intestine. The fermentation selectivity of pectin by gut bacteria and the effects of pectin structure on intestinal microecology were discussed to highlight the interaction between pectin and bacterial community. Meanwhile, we also offer information on how gut bacteria orchestrate enzymes to degrade pectin. All of these findings provide insights into pectin digestion and advance the application of pectin in human health.

Production of high-purity lactulose via an integrated one-pot boronate affinity adsorbent based adsorption-assisted isomerization and simultaneous purification.

High-purity lactulose is mandatory for its medical uses and food applications. This work developed an efficient lab-scale strategy for the synthesis of high-purity lactulose by combining lactose-to-lactulose isomerization with simultaneous recovery of lactulose, which was conducted concurrently and semi-continuously in a boronate affinity adsorbent-packed column. The first step covers the boronate affinity adsorbent-based adsorption-assisted lactose-to-lactulose isomerization. Under optimized conditions, in situ selectively binding of the newly formed lactulose onto the boronate affinity adsorbent enables a much-enhanced lactulose yield up to 80.20% with the lowest byproducts yield of 6.30%. Afterward, over 90% of the adsorbed lactulose can be recovered through sequential desorption with purity >98%. The net outcome of the applied strategy was the yield of high-purity lactulose up to 72.31%, the highest value ever reported. Moreover, the packed column displayed excellent operational stability. The encouraging results validate the high potential of this approach in the sustainable production of high-purity lactulose.

Highly efficient isolation and purification of high-purity tea saponins from industrial camellia oil production by porous polymeric adsorbents.

BACKGROUND: Recovery of high-purity tea saponin (TS), a promising non-ionic surfactant with well-documented properties, is one of the major challenges to broadening its industrial applications. In this study, an innovative and sustainable strategy for the highly-efficient purification of TS was developed by using well-designed highly-porous polymeric adsorbents. RESULTS: The prepared Pp-A with controllable macropores (~96 nm) and appropriate surface hydrophobic properties was found more favorable for achieving high adsorption efficiency towards TS/TS-micelles. Kinetic results showed the adsorption follows the pseudo-second-order model (R2 = 0.9800), and the Langmuir model is more qualified to explicate the adsorption isotherms with Qe-TS ~ 675 mg g-1 . Thermodynamic studies revealed the monolayer adsorption of TS was an endothermic process that was conducted spontaneously. Interestingly, ethanol-driven desorption (90% v/v ethanol) of TS was rapidly (< 30 min) complete due to the possible ethanol-mediated disassembling of TS-micelles. A possible mechanism that involves the interactions between the adsorbents and TS/TS-micelles, the formation and disassembling of TS-micelles was proposed to account for the highly efficient purification of TS. Afterwards, Pp-A-based adsorption method was developed to purify TS directly from industrial camellia oil production. Through selective adsorption, pre-washing, and ethanol-driven desorption, the applied Pp-A enabled the direct isolation of high-purity TS (~96%) with a recovery ratio > 90%. Notably, Pp-A exhibited excellent operational stability and is of high potential for long-term industrial application. CONCLUSION: Results ensured the practical feasibility of the prepared porous adsorbents in purifying TS, and the proposed methodology is a promising industrial-scale purification strategy. © 2023 Society of Chemical Industry.

Automated detection of myopic maculopathy using five-category models based on vision outlooker for visual recognition.

Purpose: To propose a five-category model for the automatic detection of myopic macular lesions to help grassroots medical institutions conduct preliminary screening of myopic macular lesions from limited number of color fundus images. Methods: First, 1,750 fundus images of non-myopic retinal lesions and four categories of pathological myopic maculopathy were collected, graded, and labeled. Subsequently, three five-classification models based on Vision Outlooker for Visual Recognition (VOLO), EfficientNetV2, and ResNet50 for detecting myopic maculopathy were trained with data-augmented images, and the diagnostic results of the different trained models were compared and analyzed. The main evaluation metrics were sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), area under the curve (AUC), kappa and accuracy, and receiver operating characteristic curve (ROC). Results: The diagnostic accuracy of the VOLO-D2 model was 96.60% with a kappa value of 95.60%. All indicators used for the diagnosis of myopia-free macular degeneration were 100%. The sensitivity, NPV, specificity, and PPV for diagnosis of leopard fundus were 96.43, 98.33, 100, and 100%, respectively. The sensitivity, specificity, PPV, and NPV for the diagnosis of diffuse chorioretinal atrophy were 96.88, 98.59, 93.94, and 99.29%, respectively. The sensitivity, specificity, PPV, and NPV for the diagnosis of patchy chorioretinal atrophy were 92.31, 99.26, 97.30, and 97.81%, respectively. The sensitivity, specificity, PPV, and NPV for the diagnosis of macular atrophy were 100, 98.10, 84.21, and 100%, respectively. Conclusion: The VOLO-D2 model accurately identified myopia-free macular lesions and four pathological myopia-related macular lesions with high sensitivity and specificity. It can be used in screening pathological myopic macular lesions and can help ophthalmologists and primary medical institution providers complete the initial screening diagnosis of patients.

[Research progress on the modulation mechanism of electroacupuncture for learning and memory impairment after ischemic stroke].

Electroacupuncture may play a role in treatment of learning and memory impairment after ischemic stroke by regulating phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway, nerve growth factor (NGF)/tyrosine kinase-A (TrkA) signaling pathway, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, Notch signaling pathway, erythropoietin-producing hepatocyte (Eph)/ephrin signaling pathway. The interactions among these pathways should be further explored in treatment of learning and memory impairment after ischemic stroke.

Prediction model for successful induction of labor by cervical strain elastography diagnosed at late-term pregnancy in nulliparous women: a prospective cohort study.

BACKGROUND: The use of cervical strain elastography for nulliparous women during late-term pregnancy remains unclear. This study assesses the predictive value of late-term cervical strain elastography for successful induction of labor (IOL) in nulliparous women. METHODS: This single-centered, prospective study included 86 patients undergoing IOL between January 2020 and March 2022. Univariate and multivariate analyses were conducted to identify predictive factors for successful IOL. The predictive values were assessed using the area under receiver operating characteristic (ROC) curves. RESULTS: IOL was successful in 58 patients. The hardness ratio and cervical length were significantly associated with successful late-term IOL in nulliparous women. The predictive value of the combination of hardness ratio and cervical length was higher than that of cervical length alone. CONCLUSIONS: The hardness ratio and cervical length assessed by cervical strain elastography during late-term pregnancy are predictors of the success of IOL in nulliparous women. The predictive value of the combination of hardness ratio and cervical length was higher than that of cervical length alone.

Acyl azide modification of the ubiquitin C-terminus enables DUB capture.

Deubiquitinating enzyme (DUB) abnormalities are associated with many diseases. Previous attempts have been made to introduce various chemical groups such as alkynes, unsaturated olefins and alkyl halides to the C-terminus of ubiquitin (Ub) to capture the active-site cysteine residue in DUBs for structural and biochemical studies. Here, we find that a Ub C-terminal acyl azide can capture DUBs, thereby forming thioester bonds in buffers and cell lysates. This finding not only makes ubiquitin acyl azide a chemical probe for capturing DUBs, but also extends the utility of azide groups in biological applications.

Regulatory effects and mechanisms of branched chain amino acids and metabolic intermediates on insulin resistance / 生理学报

Branched chain amino acids, as essential amino acids, can be used to synthesize nitrogen-containing compounds and also act as signal molecules to regulate substance metabolism. Studies have shown that the elevated level of branched chain amino acids is closely related to insulin resistance and type 2 diabetes. It can affect insulin signal transduction by activating mammalian target of rapamycin (mTOR) signal pathway, and regulate insulin resistance by damaging lipid metabolism and affecting mitochondrial function. In addition, abnormal catabolism of branched amino acids can lead to the accumulation of metabolic intermediates, such as branched chain α-keto acids, 3-hydroxyisobutyrate and β-aminoisobutyric acid. Branched chain α-keto acids and 3-hydroxyisobutyrate can induce insulin resistance by affecting insulin signaling pathway and damaging lipid metabolism. β-aminoisobutyric acid can improve insulin resistance by reducing lipid accumulation and inflammatory reaction and enhancing fatty acid oxidation. This paper systematically reviewed the regulatory effects and mechanisms of branched chain amino acids and their metabolic intermediates on insulin resistance, which will provide a new direction for the prevention and treatment of insulin resistance and type 2 diabetes.

Effects of primary acquired nasolacrimal duct obstruction on tear film and ocular surface / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of primary acquired nasolacrimal duct obstruction(PANDO)on the tear film and ocular surface using LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer.METHODS: A self-controlled clinical trials. A total of 40 patients diagnosed with unilateral PANDO for at least 6mo who were admitted to our department from September 2021 to March 2022 were enrolled in the study, and the healthy eyes of the patients were assessed as control group. The LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer were used to measure the changes in related parameters of the tear film and ocular surface in both eyes.RESULTS: The non-invasive tear meniscus height(NITMH), stimulated NITMH, loss rate of upper meibomian gland, nasal and temporal ciliary redness index, temporal conjunctival redness index of the affected eyes were higher than healthy eyes(P&#x003C;0.05), but there were no statistical differences in the non-invasive break-up time(NIBUT), loss rate of lower meibomian gland, nasal conjunctival redness index, dry eye grading, blink responses, partial blink rate and lipid layer thickness(LLT)between the both eyes(P&#x003E;0.05).CONCLUSION: PANDO may lead to the aggravation of ocular surface inflammation and the loss of upper meibomian gland, and damage the ocular surface of patients. Attention should be paid to the early treatment of PANDO.

Beneficial Effects and Potential Mechanisms of Tai Chi on Lower Limb Osteoarthritis: A Biopsychosocial Perspective / 中国结合医学杂志

Lower limb osteoarthritis (OA) is a chronic, multifactorial disease characterized by impaired physical function, chronic pain, compromised psychological health and decreased social functioning. Chronic inflammation plays a critical role in the pathophysiology of OA. Tai Chi is a type of classical mind-body exercise derived from ancient Chinese martial arts. Evidence supports that Tai Chi has significant benefits for relieving lower limb OA symptoms. Using a biopsychosocial framework, this review aims to elucidate the beneficial effects of Tai Chi in lower limb OA and disentangle its potential mechanisms from the perspective of biology, psychology, and social factors. Complex biomechanical, biochemical, neurological, psychological, and social mechanisms, including strengthening of muscles, proprioception improvement, joint mechanical stress reduction, change of brain activation and sensitization, attenuation of inflammation, emotion modulation and social support, are discussed.

[Efficacy Analysis of Bendamustine-Based Combination Regimen in Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma].

OBJECTIVE: To investigate the efficacy and safety of bendamustine combined with gemcitabine, vinorelbine，glucocorticoids (BeGEV)±X regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma. METHODS: A total of 18 relapsed/ refractory non-Hodgkin lymphoma patients at the age of 18 years or older hospitalized in the First People's Hospital of Changzhou from March 2020 to March 2021 were selected. They received two or more cycles of BeGEV±X regimen. X could be anti-CD20 monoclonal antibody, PD-1-blocking antibodies, lenalidomide, BTK inhibitor, Bcl-2 inhibitor and so on according to patients' disease feature. The clinical efficacy and adverse effects were observed. RESULTS: In total, 18 patients completed two or more cycles of BeGEV±X regimen, including 14 with diffuse large B-cell lymphoma, one with low-grade follicular lymphoma, one with follicular lymphoma grade 3b, one with angioimmunoblastic T-cell lymphoma and one with peripheral T-cell lymphoma, not otherwise specified. 11 patients were male. The median age of the patients was 64 years old. 17 patients had modified Ann Arbor stage Ⅲ/Ⅳ disease. 13 patients had high- intermediate risk or high risk IPI score, while 15 patients had high-intermediate high risk or high risk NCCN-IPI score. 14 cases had extranodal sites of disease. And 6 cases had bulky disease. 12 patients experienced refractory disease, while 8 patients had received 3 line or more prior treatment. After two or three cycles of chemotherapy, the complete response rate was 6/18, the partial response rate was 3/18, and the objective response rate was 9/18. From the beginning of salvage chemotherapy to the end of follow-up, the median progression-free survival time was 130 days, and the median overall survival was 152 days. The most common grade 3 to 4 adverse events were hematologic toxicities, infection and febrile neutropenia. CONCLUSION: BeGEV±X is an effective salvage regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma, while adverse events such as hematologic toxicities and infection should be closely monitored.

White matter alterations associated with lifetime and current depression in adolescents: Evidence for cingulum disruptions.

INTRODUCTION: Compared to research on adults with depression, relatively little work has examined white matter microstructure differences in depression arising earlier in life. Here we tested hypotheses about disruptions to white matter structure in adolescents with current and past depression, with an a priori focus on the cingulum bundles, uncinate fasciculi, corpus collosum, and superior longitudinal fasciculus. METHODS: One hundred thirty-one children from the Preschool Depression Study were assessed using a Human Connectome Project style diffusion imaging sequence which was processed with HCP pipelines and TRACULA to generate estimates of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). RESULTS: We found that reduced FA, reduced AD, and increased RD in the dorsal cingulum bundle were associated with a lifetime diagnosis of major depression and greater cumulative and current depression severity. Reduced FA, reduced AD, and increased RD in the ventral cingulum were associated with greater cumulative depression severity. CONCLUSION: These findings support the emergence of white matter differences detected in adolescence associated with earlier life and concurrent depression. They also highlight the importance of connections of the cingulate to other brain regions in association with depression, potentially relevant to understanding emotion dysregulation and functional connectivity differences in depression.