Proinflammatory Diet Increases the Risk of Irritable Bowel Syndrome: A Prospective Study of 129,408 UK Biobank Participants and Mendelian Randomization Analysis.

BACKGROUND: Patients with irritable bowel syndrome (IBS) often have chronic low-grade inflammation in the intestinal mucosa. Some dietary components are known to be associated with inflammation. However, there is currently limited research on the relationship between dietary inflammatory potential and the risk of IBS. METHODS: A total of 129,408 participants in the UK Biobank were included in this study. Energy-Adjusted Dietary Inflammatory Index (E-DII) based on 26 nutrients and the Empirical Dietary Inflammatory Pattern (EDIP) based on 17 food groups were constructed, and on the basis of the tertiles, the continuous score was categorized into proinflammatory, neutral, and antiinflammatory categories. Associations between IBS and E-DII and EDIP were investigated by multivariable Cox proportional hazard models. Potential confounders including sociodemographic, lifestyle, body mass index (BMI), psychological state, type 2 diabetes, and thyroiditis were adjusted. In addition, subgroup analysis and sensitivity analysis were also performed. Finally, a two-sample Mendelian randomization (MR) analysis was employed to explore the independent causality of nutrients and dietary-derived serum antioxidants with IBS. RESULTS: In the cohort study, over a median follow-up period of 13.26 years, 2421(1.87%) participants developed IBS. In the E-DII categories, after adjusting for the confounders, individuals in the proinflammatory diet category had a higher risk of IBS compared with the antiinflammatory category (HR 1.15, 95% CI 1.03-1.28, p = 0.015, p trend = 0.017) and neutral category (HR 1.13, 95% CI 1.01-1.26, p = 0.030, p trend = 0.017). In the EDIP categories, after adjusting for the confounders, individuals in the proinflammatory diet category had a higher risk of IBS compared with antiinflammatory category (HR 1.19, 95% CI 1.06-1.33, p = 0.002, p trend = 0.002) but no significant association compared with neutral category (HR 1.10, 95% CI 0.99-1.23, p = 0.067, p trend = 0.002). In the MR analysis, genetically determined intake levels of 16 nutrients and 6 dietary sources of circulating antioxidants did not have a causal effect on IBS. CONCLUSIONS: Our findings indicate that proinflammatory dietary components are independent risk factors for IBS. However, there is no causal relationship between individual nutrient intake or serum antioxidants from dietary sources and IBS.

Fibroblast growth factor 20 ameliorates cardiac hypertrophy via activation ErbB2.

Fibroblast growth factor 20 (FGF20) is a member of the fibroblast growth factor family and involved in embryonic development and cardiac repair. This study aimed to explore the role of FGF20 in cardiac hypertrophy and the underlying molecular mechanisms. FGF20 improved cardiac hypertrophy in vivo and in vitro. Furthermore, FGF20 increased expression of erythroblastic leukemia viral oncogene homolog 2 (ErbB2), which was negatively correlated with expression of the cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). In addition, FGF20 effectively protected cardiomyocytes against apoptosis and oxidative stress. To further investigate whether protective effect of FGF20 is mediated by ErbB2, neonatal rat cardiomyocytes (NRCMs) were treated with lapatinib, an inhibitor of ErbB2. Lapatinib largely abrogated the anti-hypertrophic effect of FGF20, accompanied by increases in cardiomyocyte apoptosis and oxidative stress. In summary, this study reveals that FGF20 prevents cardiac hypertrophy by inhibiting apoptosis and oxidative stress via activating ErbB2 and may be a promising therapeutic strategy for cardiac hypertrophy.

Long-term alterations of nutrient dynamics and phytoplankton communities in Daya Bay, South China Sea.

Dynamics of phytoplankton in coastal waters is a function of nutrient influx and the present study investigated the trend in nutrient dynamics and phytoplankton abundance of Daya Bay (DB), South China Sea, from 1986 to 2020. Dissolved inorganic nitrogen (DIN), Dissolved inorganic phosphate (DIP) and Silicates were measured. DIN concentration exhibited an increasing trend over the last decades, and it was above the threshold for the phytoplankton growth. DIP level showed a significant decreasing trend throughout the studied period, falling below the threshold for phytoplankton growth in the last decade, where harmful algal blooms were dominated by the dinoflagellates. Long-term anthropogenic influences severely change influx of DIN, DIP, and silicates which in turn shape the architecture of phytoplankton communities. Thus, the understanding of the complex interaction between nutrient influx, anthropogenic activities and dynamics of both water quality and biological elements are particularly important to decide criteria to manage coastal ecosystems.

From Hit to Lead: Discovery of First-In-Class Furanone Glycoside D228 Derived from Chimonanthus salicifolius for the Treatment of Inflammatory Bowel Disease.

TNFα and related inflammatory factor antibody drugs have been orchestrated for the treatment of inflammatory bowel disease (IBD). However, antibody drugs elicited inevitable disadvantages and small molecule drugs are in an urgent need. Herein, we described the discovery, design, synthesis, and SAR studies from furanone glycoside compound Phoenicein (hit) isolated from Chimonanthus salicifolius to D228 (lead). Remarkably, D228 exhibited good inhibitory activity on B and T lymphocyte and excellent anti-IBD efficacy in vivo. Mechanistically, D228 alleviated the inflammation response by downregulating the MyD88/TRAF6/p38 signaling. Importantly, the relationship of D228, Phoenicein, and their aglycone 7a was deduced: D228 could be considered as a prodrug and metabolized to intermediate Phoenicein. In turn, Phoenicein released their shared active aglycone 7a. Additionally, D228 demonstrated good and balanced profiles of safety and efficacy both in vitro and in vivo. These results suggested that D228 could be used as an ideal lead and potentially utilized for IBD chemotherapy.

An "AND" logic gate-based supramolecular therapeutic nanoplatform for combatting drug-resistant non-small cell lung cancer.

Despite targeted therapies like epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), non-small cell lung cancer (NSCLC) remains a clinical challenge due to drug resistance hampering their efficacy. Here, we designed an "AND" logic gate-based supramolecular therapeutic platform (HA-BPY-GEF-NPs) for the treatment of EGFR-TKI resistant NSCLC. This system integrates both internal and external stimuli-responsive mechanisms that need to be activated in a preset sequence, enabling it to precisely control drug release behavior for enhancing therapeutic precision. By programming the system to respond to sequential near-infrared (NIR) irradiation and enzyme (cathepsin B) inputs, the release of gefitinib is effectively confined to the tumor region. Moreover, the NIR irradiation induces reactive oxygen species production, suppressing tumor growth and inhibiting bypass signaling pathways. The designed drug delivery system offers a highly controlled and targeted therapeutic approach, effectively inhibiting tumor growth, suppressing bypass signaling pathways, and overcoming EGFR-TKI resistance, thus offering a potential solution for maximizing therapeutic benefits.

Bufalin CaCO3 Nanoparticles Triggered Pyroptosis through Calcium Overload via Na+/Ca2+ Exchanger Reverse for Cancer Immunotherapy.

Bufalin is a promising active ingredient in traditional Chinese medicine but has shown limited anticancer applications due to its toxicity. Here, we report BCNPs@gel, a bufalin-containing CaCO3 nanoparticle hydrogel, for enhancing cancer treatment through inducing cellular pyroptosis. Under the tumor microenvironment's low pH conditions, bufalin and Ca2+ are released from the delivery system. Bufalin serves as a direct anticancer drug and a Na+/K+-ATPase inhibitor by forcing the Na+/Ca2+ exchanger to reverse its function, which transfers Ca2+ into cytoplasm and ultimately causes Ca2+ overload-triggered pyroptosis. Meanwhile, we found that bufalin can upregulate PD-L1 in tumor cells. In combination with the PD-1 antibody, the delivery system showed a greater performance during the cancer treatment. BCNPs@gel enhances antitumor efficiency, reduces systemic side effects, extends antitumor mechanism of bufalin, and provides new strategies for inducing pyroptosis and calcium overload in cancer immunotherapy via Na+/K+-ATPase inhibitor. This work provides an application model for numerous other traditional Chinese medicine ingredients.

Vascular Calcification: Where is the Cure?

With the progress of aging, the incidence of vascular calcification (VC) gradually increases, which is correlated with cardiovascular events and all-cause death, aggravating global clinical burden. Over the past several decades, accumulating approaches targeting the underlying pathogenesis of VC have provided some possibilities for the treatment of VC. Unfortunately, none of the current interventions have achieved clinical effectiveness on reversing or curing VC. The purpose of this review is to make a summary of novel perspectives on the interventions of VC and provide reference for clinical decision-making.

Early-onset scoliosis in children aged 4-7 years in Nanjing, China: A cross-sectional study.

Background: This study aimed to investigate the potential variance in the prevalence of early-onset scoliosis among children aged 4-7 years and analyze the influencing factors. The goal was to establish a crucial reference point for monitoring and evaluating spinal curvature development in preschoolers, ultimately to reduce the occurrence of adverse health outcomes. Methods: Children aged 4-7 years within the main urban area of Nanjing were selected using a stratified random sampling method. A team of four senior therapists conducted screenings for spinal curvature among children using visual inspection, the Adams forward bending test, and an electronic scoliometer to measure the angle of trunk rotation (ATR) and identify children displaying signs of scoliosis. Children with suspected scoliosis in the initial screening underwent X-ray Cobb angle assessment for confirmation. The prevalence of early-onset scoliosis was then determined from the screening results. R version 4.2.0 software was used to analyze the factors associated with scoliosis among children using partial least squares structural equation modeling. Results: A total of 2281 children were included in this study, consisting of 1211 boys and 1070 girls, with a mean age of 5.44 ± 0.81 years (ranging from 4 to 7 years). Among them, 7.58% exhibited positive signs of scoliosis, 5.87% had early-onset scoliosis, and the positive predictive value was 77.5%. Significant differences in ATR were observed among children in different age groups (Kruskal-Wallis = 15, p = 0.0104) and by sex (t = 3.17, p = 0.00153). Significant variations in ATR were noted in children with scoliosis (t = -22.7, p < 0.001), with a cutoff at ATR = 4.5°, and auxiliary values of 0.947 and 0.990. Children diagnosed with early-onset scoliosis generally exhibited lower body mass index values, with a statistically significant difference (t = 2.99, p = 0.003). Conclusions: Using visual inspection, the Adams test, and an electronic scoliometer to measure the ATR, the present triad method is more sensitive for early scoliosis screening in children with abnormal posture aged 4-7 years. A full spine X-ray is advised in children with an ATR over 4.5° and poor posture.

Injectable polypeptide-polysaccharide depot for preventing postoperative tumor recurrence by concurrent in situ chemotherapy and brachytherapy.

Chemotherapy and radiotherapy in combination with sequence regimens are recognized as the current major strategy for suppressing postoperative tumor recurrence. However, systemic side effects and poor in-field cooperation of the two therapies seriously impair the therapeutic efficacy of patients. The combination of brachytherapy and chemotherapy through innovative biomaterials has proven to be an important strategy to achieve synergistic effects of radiotherapy and chemotherapy in-time and in-field. However, for postoperative chemoradiotherapy, as far as we know, there are few relevant reports. Herein, an injectable pH-responsive polypeptide-polysaccharide depot for concurrent in situ chemotherapy and brachytherapy was developed by encapsulating vincristine into iodine-125 radionuclide labeled hydrogel. This depot hydrogel was prepared by dynamic covalent bonds of Schiff base between aldehydeated hyaluronic acid and polyethylene glycol-polytyrosine. Therefore, this hydrogel enables smart response to tumor acidic microenvironment, rapid release of the encapsulated vincristine and an enhanced uptake effect by tumor cells, which significantly reduces IC50 of vincristine for the anaplasia Wilms' tumor cells in vitro. This depot hydrogel shows excellent stability and biocompatibility, and maintains for 14 days after in situ injection in a postoperative model of anaplasia Wilms' tumor. After injection at the cavity of tumor excision, responsively-released vincristine and the radioactive iodine-125 exerted excellent killing effects on residual tumor cells, inhibiting tumor relapse and liver metastasis of the recurrent tumor. Hence, this study proposes an effective therapeutic strategy for inhibiting anaplasia Wilms' tumor recurrence, which provides a new approach for concurrent postoperative chemo-radiotherapy and a desirable guidance in regimen execution of pediatric refractory tumors.

Lysophosphatidylcholine Impairs the Mitochondria Homeostasis Leading to Trophoblast Dysfunction in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications.

The mitochondrial genome of Bottapotamon fukienense (Brachiura: Potamidae) is fragmented into two chromosomes.

BACKGROUND: China is the hotspot of global freshwater crab diversity, but their wild populations are facing severe pressures associated with anthropogenic factors, necessitating the need to map their taxonomic and genetic diversity and design conservation policies. RESULTS: Herein, we sequenced the mitochondrial genome of a Chinese freshwater crab species Bottapotamon fukienense, and found that it is fragmented into two chromosomes. We confirmed that fragmentation was not limited to a single specimen or population. Chromosome 1 comprised 15,111 base pairs (bp) and there were 26 genes and one pseudogene (pseudo-nad1) encoded on it. Chromosome 2 comprised 8,173 bp and there were 12 genes and two pseudogenes (pseudo-trnL2 and pseudo-rrnL) encoded on it. Combined, they comprise the largest mitogenome (23,284 bp) among the Potamidae. Bottapotamon was the only genus in the Potamidae dataset exhibiting rearrangements of protein-coding genes. Bottapotamon fukienense exhibited average rates of sequence evolution in the dataset and did not differ in selection pressures from the remaining Potamidae. CONCLUSIONS: This is the first experimentally confirmed fragmentation of a mitogenome in crustaceans. While the mitogenome of B. fukienense exhibited multiple signs of elevated mitogenomic architecture evolution rates, including the exceptionally large size, duplicated genes, pseudogenisation, rearrangements of protein-coding genes, and fragmentation, there is no evidence that this is matched by elevated sequence evolutionary rates or changes in selection pressures.

Triggering of endoplasmic reticulum stress via ATF4-SPHK1 signaling promotes glioblastoma invasion and chemoresistance.

Despite advances in therapies, glioblastoma (GBM) recurrence is almost inevitable due to the aggressive growth behavior of GBM cells and drug resistance. Temozolomide (TMZ) is the preferred drug for GBM chemotherapy, however, development of TMZ resistance is over 50% cases in GBM patients. To investigate the mechanism of TMZ resistance and invasive characteristics of GBM, analysis of combined RNA-seq and ChIP-seq was performed in GBM cells in response to TMZ treatment. We found that the PERK/eIF2α/ATF4 signaling was significantly upregulated in the GBM cells with TMZ treatment, while blockage of ATF4 effectively inhibited cell migration and invasion. SPHK1 expression was transcriptionally upregulated by ATF4 in GBM cells in response to TMZ treatment. Blockage of ATF4-SPHK1 signaling attenuated the cellular and molecular events in terms of invasive characteristics and TMZ resistance. In conclusion, GBM cells acquired chemoresistance in response to TMZ treatment via constant ER stress. ATF4 transcriptionally upregulated SPHK1 expression to promote GBM cell aggression and TMZ resistance. The ATF4-SPHK1 signaling in the regulation of the transcription factors of EMT-related genes could be the underlying mechanism contributing to the invasion ability of GBM cells and TMZ resistance. ATF4-SPHK1-targeted therapy could be a potential strategy against TMZ resistance in GBM patients.

Screening, epidemic trends and drug sensitivity analysis of nontuberculous mycobacteria in a local area of China.

OBJECTIVE: To analyze the isolation rate, prevalence trends, species distribution, and drug sensitivity of non-tuberculous mycobacteria (NTM) in Anhui Province, providing a reference for diagnosis and treatment strategies. METHODS: Specimens from suspected mycobacterial infection patients at Anhui Chest Hospital (including outpatients and inpatients) from January 2021 to December 2023 were cultured. Identified NTM strains were analyzed for species distribution and drug sensitivity. RESULTS: Of 10,519 mycobacteria strains cultured, 1,589 were NTM (15.11%). The top four species were Mycobacterium intracellulare (75.36%), Mycobacterium abscessus (11.78%), Mycobacterium kansasii (7.09%), and Mycobacterium avium (2.85%). NTM strains showed high sensitivity to amikacin and clarithromycin (≥90%) and significant sensitivity to rifabutin, moxifloxacin, and rifampicin (89.03%-79.61%). They exhibited high resistance to imipenem/cilastatin, sulfamethoxazole, minocycline, and doxycycline (≥95%). CONCLUSION: NTM isolation rates in Anhui have remained stable, with the predominant species being M. intracellulare, M. kansasii, M. abscessus, and M. avium. NTM strains are highly sensitive to amikacin, clarithromycin, rifabutin, moxifloxacin, and rifampicin. These findings can guide diagnosis, treatment strategies, and drug selection for NTM disease in Anhui Province.

Catalytic activity of violet phosphorus-based nanosystems and the role of metabolites in tumor therapy.

Although nanocatalytic medicine has demonstrated its advantages in tumor therapy, the outcomes heavily relie on substrate concentration and the metabolic pathways are still indistinct. We discover that violet phosphorus quantum dots (VPQDs) can catalyze the production of reactive oxygen species (ROS) without requiring external stimuli and the catalytic substrates are confirmed to be oxygen (O2) and hydrogen peroxide (H2O2) through the computational simulation and experiments. Considering the short of O2 and H2O2 at the tumor site, we utilize calcium peroxide (CaO2) to supply catalytic substrates for VPQDs and construct nanoparticles together with them, named VPCaNPs. VPCaNPs can induce oxidative stress in tumor cells, particularly characterized by a significant increase in hydroxyl radicals and superoxide radicals, which cause substantial damage to the structure and function of cells, ultimately leading to cell apoptosis. Intriguingly, O2 provided by CaO2 can degrade VPQDs slowly, and the degradation product, phosphate, as well as CaO2-generated calcium ions, can promote tumor calcification. Antitumor immune activation and less metastasis are also observed in VPCaNPs administrated animals. In conclusion, our study unveils the anti-tumor activity of VPQDs as catalysts for generating cytotoxic ROS and the degradation products can promote tumor calcification, providing a promising strategy for treating tumors.

Myosin forces elicit an F-actin structural landscape that mediates mechanosensitive protein recognition.

Cells mechanically interface with their surroundings through cytoskeleton-linked adhesions, allowing them to sense physical cues that instruct development and drive diseases such as cancer. Contractile forces generated by myosin motor proteins mediate these mechanical signal transduction processes through unclear protein structural mechanisms. Here, we show that myosin forces elicit structural changes in actin filaments (F-actin) that modulate binding by the mechanosensitive adhesion protein α-catenin. Using correlative cryo-fluorescence microscopy and cryo-electron tomography, we identify F-actin featuring domains of nanoscale oscillating curvature at cytoskeleton-adhesion interfaces enriched in zyxin, a marker of actin-myosin generated traction forces. We next introduce a reconstitution system for visualizing F-actin in the presence of myosin forces with cryo-electron microscopy, which reveals morphologically similar superhelical F-actin spirals. In simulations, transient forces mimicking tugging and release of filaments by motors produce spirals, supporting a mechanistic link to myosin's ATPase mechanochemical cycle. Three-dimensional reconstruction of spirals uncovers extensive asymmetric remodeling of F-actin's helical lattice. This is recognized by α-catenin, which cooperatively binds along individual strands, preferentially engaging interfaces featuring extended inter-subunit distances while simultaneously suppressing rotational deviations to regularize the lattice. Collectively, we find that myosin forces can deform F-actin, generating a conformational landscape that is detected and reciprocally modulated by a mechanosensitive protein, providing a direct structural glimpse at active force transduction through the cytoskeleton.

A nitrile solvent structure induced stable solid electrolyte interphase for wide-temperature lithium-ion batteries.

Lithium-ion batteries (LIBs) are extensively employed in various fields. Nonetheless, LIBs utilizing ethylene carbonate (EC)-based electrolytes incur capacity degradation in a wide-temperature range, which is attributable to the slow Li+ transfer kinetics at low temperatures and solvent decomposition during high-rate cycling at high temperatures. Here, we designed a novel electrolyte by substituting nitrile solvents for EC, characterized by low de-solvation energy and high ionic conductivity. The correlation between the carbon chain length of nitrile solvents with reduction stability and the Li+-solvated coordination was investigated. The results revealed that the valeronitrile (VN) solvent displayed an enhanced lowest unoccupied molecular orbital energy level and low de-solvation energy, which helped construct robust SEI interfacial layers and improved kinetics of interfacial ion transfer in wide-temperature LIBs. The VN-based electrolyte employed in graphite‖NCM523 pouch cells achieved a discharge capacity of 89.84% at a 20C rate at room temperature. Meanwhile, the cell exhibited 3C rate cycling stability even at a high temperature of 55 °C. Notably, the VN-based electrolyte exhibited a high ionic conductivity of 1.585 mS cm-1 at -50 °C. The discharge capacity of pouch cells retained 75.52% and 65.12% of their room temperature capacity at -40 °C and -50 °C, respectively. Wide-temperature-range batteries with VN-based electrolytes have the potential to be applied in various extreme environments.

Visible-light-promoted selenylation/cyclization of o-(1-alkynyl) benzoates to access seleno-substituted isocoumarins.

A simple and efficient method to access 4-selenyl-isocoumarin derivatives through visible-light-promoted selenylation/cyclization of o-(1-alkynyl) benzoates has been developed. This transformation is performed under mild conditions and has the advantages of functional group tolerance and broad substrate scope.

Interpenetrating LiB/Li3BN2 phases enabling stable composite lithium metal anode.

Host-less lithium metal anode generally suffers from large volume changes and serious dendrite growth during cycling, which poses challenges for its practical application. Interpenetrating phase composites with continuous architectures offer a solution to enhance mechanical properties of materials. Herein, a robust composite Li anode (LBN) material is fabricated through the metallurgical reaction between Li and hexagonal boron nitride (h-BN) with the formation of interpenetrating LiB/Li3BN2 phases. As LiB fibers are anchored by Li3BN2 granules, the collapse and slippage of LiB fibers are suppressed whilst the mechanical strength and structural stability of LBN are reinforced. By rolling, ultrathin (15 µm), freestanding, and electrochemically stable LBN foil can be obtained. The LBN anode exhibits a high average Coulombic efficiency of 99.69% (1 mA cm-2, 3 mAh cm-2) and a long lifespan of 2500 h (1 mA cm-2, 1 mAh cm-2). Notably, the LiCoO2 (with double-sided load 40 mg cm-2)|LBN pouch cell can operate over 450 cycles with a capacity retention of 90.1%. The exceptional cycling stability of LBN can be ascribed to the interpenetrating reinforcement architectures and synergistic electronic/ionic conductivity of the LiB/Li3BN2 dual-lithiophilic-phases. This work provides a new methodology for thin Li strip processing and reinforced-architecture design, with implications beyond battery applications.

Predictors of alcohol and other drug treatment completion among young people accessing residential and community-based treatment: A retrospective analysis of routinely collected service data.

BACKGROUND AND AIMS: Young people accessing alcohol and other drug (AOD) treatment experience high rates of treatment disengagement, contributing to poorer outcomes. To improve outcomes, it is important to identify factors associated with treatment retention. This study measured the relationships between client characteristics, treatment characteristics, clinical severity measures and completion of treatment among young people. DESIGN, SETTING AND PARTICIPANTS: This study was a retrospective analysis of routinely collected data set in residential- and community-based AOD services in New South Wales, Australia. Routinely collected data from the Network of Alcohol and Other Drug Agencies' (NADA) database were used. Included individuals were aged 10-24 years and accessed treatment between 2012 and 2023 (n = 17 474). MEASUREMENTS: Variables included client-related characteristics, service characteristics and baseline measures of clinical severity [Kessler-10 (K10), EUROHIS-QoL, severity of dependence scale (SDS)]. Multivariable binary logistic regression models assessed the relationships between these characteristics and treatment completion. FINDINGS: Rates of treatment completion were highest among adolescents in community-based treatment (57%) and lowest among young adults in residential treatment (35%). Polysubstance use was negatively associated with treatment completion among adolescents [adjusted odds ratio (adjOR) = 0.71, P < 0.001] and adults (adjOR = 0.70, P < 0.001) in community-based treatment, and adolescents in residential treatment (adjOR = 0.62, P = 0.006), as was housing insecurity (adolescents in community treatment, adjOR = 0.61, P = 0.001; adults in community treatment, adjOR = 0.77, P = 0.002; adolescents in residential treatment, adjOR = 0.42, P = 0.005). Attending youth-specific services was associated with higher treatment completion rates among adults in community-based (adjOR = 1.81, P < 0.001) and residential treatment (adjOR = 1.72, P < 0.001). Varying correlates of treatment completion were identified throughout treatment groups, reflecting the differences in population and/or needs across contexts. CONCLUSIONS: In New South Wales, Australia, fewer than half of young people accessing alcohol and other drug treatment between 2012 and 2023 completed treatment, and completion rates were lower among those facing barriers such as polysubstance use and housing insecurity.