Discovery of a first-in-class protein degrader for the c-ros oncogene 1 (ROS1).

The c-ros oncogene 1 (ROS1), an oncogenic driver, is known to induce non-small cell lung cancer (NSCLC) when overactivated, particularly through the formation of fusion proteins. Traditional targeted therapies focus on inhibiting ROS1 activity with ROS 1 inhibitors to manage cancer progression. However, a new strategy involving the design of protein degraders offers a more potent approach by completely degrading ROS1 fusion oncoproteins, thereby effectively blocking their kinase activity and enhancing anti-tumour potential. Utilizing PROteolysis-TArgeting Chimera (PROTAC) technology and informed by molecular docking and rational design, we report the first ROS1-specific PROTAC, SIAIS039. This degrader effectively targets multiple ROS1 fusion oncoproteins (CD74-ROS1, SDC4-ROS1 and SLC34A2-ROS1) in engineered Ba/F3 cells and HCC78 cells, demonstrating anti-tumour effects against ROS1 fusion-driven cancer cells. It suppresses cell proliferation, induces cell cycle arrest, and apoptosis, and inhibits clonogenicity. The anti-tumour efficacy of SIAIS039 surpasses two approved drugs, crizotinib and entrectinib, and matches that of the top inhibitors, including lorlatinib and taletrectinib. Mechanistic studies confirm that the degradation induced by 039 requires the participation of ROS1 ligands and E3 ubiquitin ligases, and involves the proteasome and ubiquitination. In addition, 039 exhibited excellent oral bioavailability in a mouse xenograft model, highlighting its potential for clinical application. In conclusion, our study presents a promising and novel therapeutic strategy for ROS1 fusion-positive NSCLC by targeting ROS1 fusion oncoproteins for degradation, laying the foundation for the development of further PROTAC and offering hope for patients with ROS1 fusion-positive NSCLC.

Melatonin regulates mitochondrial function to alleviate ferroptosis through the MT2/Akt signaling pathway in swine testicular cells.

Increasing evidence has shown that many environmental and toxic factors can cause testicular damage, leading to testicular ferroptosis and subsequent male reproductive disorders. Melatonin is a major hormone and plays an vital role in regulating male reproduction. However, there is a lack of research on whether Mel can alleviate testicular cell ferroptosis and its specific mechanism. In this study, the results indicated that Mel could enhance the viability of swine testis cells undergoing ferroptosis, reduce LDH enzyme release, increase mitochondrial membrane potential, and affect the expression of ferroptosis biomarkers. Furthermore, we found that melatonin depended on melatonin receptor 1B to exert these functions. Detection of MMP and ferroptosis biomarker protein expression confirmed that MT2 acted through the downstream Akt signaling pathway. Moreover, inhibition of the Akt signaling pathway can eliminate the protective effect of melatonin on ferroptosis, inhibit AMPK phosphorylation, reduce the expression of mitochondrial gated channel (VDAC2/3), and affect mitochondrial DNA transcription and ATP content. These results suggest that melatonin exerts a beneficial effect on mitochondrial function to mitigate ferroptosis through the MT2/Akt signaling pathway in ST cells.

Chromosome-level genome assembly and population genomics reveals crucial selection for subgynoecy development in chieh-qua.

Chieh-qua is an important cucurbit crop and very popular in South China and Southeast Asia. Despite its significance, its genetic basis and domestication history are unclear. In this study, we have successfully generated a chromosome-level reference genome assembly for the chieh-qua 'A36' using a hybrid assembly strategy that combines PacBio long reads and Illumina short reads. The assembled genome of chieh-qua is approximately 953.3 Mb in size and is organized into 12 chromosomes, with contig N50 of 6.9 Mb and scaffold N50 of 68.2 Mb. Notably, the chieh-qua genome is comparable in size to the wax gourd genome. Through gene prediction analysis, we have identified a total of 24 593 protein-coding genes in the A36 genome. Additionally, approximately 56.6% (539.3 Mb) of the chieh-qua genome consists of repetitive sequences. Comparative genome analysis revealed that chieh-qua and wax gourd are closely related, indicating a close evolutionary relationship between the two species. Population genomic analysis, employing 129 chieh-qua accessions and 146 wax gourd accessions, demonstrated that chieh-qua exhibits greater genetic diversity compared to wax gourd. We also employed the GWAS method to identify related QTLs associated with subgynoecy, an interested and important trait in chieh-qua. The MYB59 (BhiCQ0880026447) exhibited relatively high expression levels in the shoot apex of four subgynoecious varieties compared with monoecious varieties. Overall, this research provides insights into the domestication history of chieh-qua and offers valuable genomic resources for further molecular research.

NAMPT-targeting PROTAC and nicotinic acid co-administration elicit safe and robust anti-tumor efficacy in NAPRT-deficient pan-cancers.

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the biosynthesis of nicotinamide adenine dinucleotide (NAD+), making it a potential target for cancer therapy. Two challenges hinder its translation in the clinic: targeting the extracellular form of NAMPT (eNAMPT) remains insufficient, and side effects are observed in normal tissues. We previously utilized proteolysis-targeting chimera (PROTAC) to develop two compounds capable of simultaneously degrading iNAMPT and eNAMPT. Unfortunately, the pharmacokinetic properties were inadequate, and toxicities similar to those associated with traditional inhibitors arose. We have developed a next-generation PROTAC molecule 632005 to address these challenges, demonstrating exceptional target selectivity and bioavailability, improved in vivo exposure, extended half-life, and reduced clearance rate. When combined with nicotinic acid, 632005 exhibits safety and robust efficacy in treating NAPRT-deficient pan-cancers, including xenograft models with hematologic malignancy and prostate cancer and patient-derived xenograft (PDX) models with liver cancer. Our findings provide clinical references for patient selection and treatment strategies involving NAMPT-targeting PROTACs.

Screening and effects of intestinal probiotics on growth performance, gut health, immunity, and disease resistance of Nile tilapia (Oreochromis niloticus) against Streptococcus agalactiae.

In the present study, 59 autochthonous bacteria were isolated from the intestine of tilapia. Following enzyme producing activity, antagonistic ability, hemolytic activity, drug sensitivity assessments, and in vivo safety evaluation, 7 potential probiotic strains were screened out: Bacillus tequilensis BT0825-2 (BT), Bacillus aryabhattai BA0829-3 (BA1), Bacillus megaterium BM0505-6 (BM), Bacillus velezensis BV0505-11 (BV), Bacillus licheniformis BL0505-18 (BL), B. aryabhattai BA0505-19 (BA2), and Lactococcus lactis LL0306-15 (LL). Subsequently, tilapia were fed basal diets (CT) and basal diets supplemented with 108 CFU/g of BT, BA1, BM, BV, BL, BA2 and LL, respectively. After 56 days of continuous feeding, the growth parameters (weight gain, final weight, and specific growth rate) showed significant improvement (p < 0.05) in both BM and BA2 groups. The total cholesterol and triglycerides of serum were significantly decreased in BV and LL groups (p < 0.05). The superoxide dismutase, glutathione reductase, and lysozyme of BV, BA2 and LL groups were increased, and the malondialdehyde of BV group was significantly decreased. The villous height and amylase of midgut were increased in BV, BA2 and LL groups. In addition, the expression levels of ZO-1 and occludin genes in the midgut of tilapia were enhanced in BM, BV, BA2 and LL groups. The supplementation of probiotics reduced the abundance of Cyanobacteria and increased the abundance of Actinobacteria at the phylum level. At the genus level, the addition of probiotics increased the abundance of Romboutsia. Furthermore, improvement in the expression of immune-related genes were observed, including interleukin 1ß, interleukin 10, tumor necrosis factor alpha, and transforming growth factor beta (p < 0.05). After challenging with S. agalactiae, the survival rates of BV, BA2 and LL groups were significantly higher than CT group (p < 0.05). Above results indicated that BM, BA2, BV and LL improved growth performance, gut health or immunity of tilapia, which can be applied in tilapia aquaculture.

Surface Activity, Wettability, and Aggregation Behavior of Ecofriendly Fluorocarbon Surfactant Based on Double Perfluorinated Branched Short Chains.

This article reports the synthesis of a novel sulfonated fluorocarbon surfactant (SFDC) containing double C6 perfluorinated branched short chains and compares its surface properties with a similar structured compound (SFDC-L) in solutions. The critical micelle concentration (CMC) and the corresponding surface tension (γCMC) of SFDC aqueous solution are 9.77 × 10-3 mmol/L and 22.15 mN/m, respectively, indicating that SFDC has excellent surface properties. Besides, the addition of n-hexyltrimethylammonium bromide (HTAB) could further enhance the surface properties of SFDC. Meanwhile, the micellization, aggregation behavior, wettability, and adsorption at the air-water interface of SFDC and SFDC/HTAB mixture aqueous solutions are systematically investigated. Both SFDC and SFDC/HTAB show excellent wettability at low concentrations. The aggregation of SFDC and SFDC/HTAB mixtures in aqueous solution could be clearly seen as vesicles and rod-like micelles on TEM micrographs.

Prediction of rhinitis with class imbalance based on heterogeneous ensemble learning.

Common clinical rhinitis is characterized by different types of cases and class imbalance. Its prediction belongs to multiple output classification. Low recognition rate and poor generalization performance often occur for minority class. Therefore, we propose a novel integrated classification model, ARF-OOBEE, which transforms the multi-output classification to multi-label classification and multi-class classification. The multi-label classifier automatically adjusts the number and depth of integrated forest learners according to the imbalance ratio of single class label in a subset. It can effectively reduce the impact of class imbalance on classification and improve prediction performance of both majority or minority class concurrently. Also, we build a multi-class classification based on out-of-bag Extra-Tree to accomplish finer classification for the predicted labels. In addition, we calculate the feature importance for rhinitis on the grounds of the purity of nodes in decision-making tree inside Random Forest and study the correlation between rhinitis features. We conduct 12 folds cross-validation experiments on 461 cases of clinical rhinitis. The outcomes show that the evaluation indicators of ARF-OOBEE, such as Sensitivity, Specificity, Accuracy, F1-Score, AUC, and G-Mean are 74.9%,86.5%,92.0%,78.3%,95.3%, and 79.9%, respectively. In comparison to the other methods, ARF-OOBEE has better evaluation indicator and is more effective for the early clinical diagnosis of rhinitis.

A nonsynonymous mutation in BhLS, encoding an acyl-CoA N-acyltransferase leads to fruit and seed size variation in wax gourd (Benincasa hispida).

Wax gourd (Benincasa hispida (Thunb.) Cogn., 2n = 2x = 24) is an economically important vegetable crop cultivated widely in many tropical and subtropical regions, including China, India, and Japan. Both fruit and seeds are prized agronomic attributes in wax gourd breeding and production. However, the genetic mechanisms underlying these traits remain largely unexplored. In this study, we observed a strong correlation between fruit size and seed size variation in our mapping population, indicating genetic control by a single gene, BhLS, with large size being dominant over small. Through bulk segregant analysis sequencing and fine mapping with a large F2 population, we precisely located the BhLS gene within a 47.098-kb physical interval on Chromosome 10. Within this interval, only one gene, Bhi10M000649, was identified, showing homology to Arabidopsis HOOKLESS1. A nonsynonymous mutation (G to C) in the second exon of Bhi10M000649 was found to be significantly associated with both fruit and seed size variation in wax gourd. These findings collectively highlight the pleiotropic effect of the BhLS gene in regulating fruit and seed size in wax gourd. Our results offer molecular insights into the variation of fruit and seed size in wax gourd and establish a fundamental framework for breeding wax gourd cultivars with desired traits.

Wetting and evaporation behavior of dilute sodium dodecyl sulfate droplets on soft substrates under a direct current electric field.

Wetting and evaporation behavior of dilute sodium dodecyl sulfate (SDS) droplets on planar polydimethylsiloxane (PDMS) surfaces under a direct current (DC) electric field were experimentally investigated. Two characteristic voltages-actuation voltage and saturation voltage were observed in the electrowetting of dilute SDS droplets on PDMS surfaces. It was found that for dilute SDS droplets with a fixed SDS concentration substrate elasticity has an obvious influence on actuation voltage, and saturation voltage increased with the increase of mass ratio of PDMS surfaces. SDS concentration was also found to obviously influence actuation voltage and saturation voltage when SDS concentration was in a certain range. For the case of evaporation of sessile dilute SDS droplets on PDMS surfaces with the application of a DC electric field, substrate elasticity, SDS concentration and the magnitude of applied voltage were all found to have an influence on the duration of CCR stage. Moreover, contact angle hysteresis for dilute SDS droplets on a planar PDMS 10:1 surface under different applied voltage was measured and it was found that the magnitude of applied voltage greatly influenced contact angle hysteresis, which also depends on SDS concentration and KCl concentration.

Hypothalamic-Pituitary-Adrenal Axis and Epilepsy.

Epilepsy is a recurrent, transient seizure disorder of the nervous system that affects the intellectual development, life and work, and psychological health of patients. People with epilepsy worldwide experience great suffering. Stressful stimuli such as infection, mental stress, and sleep deprivation are important triggers of epilepsy, and chronic stressful stimuli can lead to frequent seizures and comorbidities. The hypothalamic-pituitary-adrenal (HPA) axis is the most important system involved in the body's stress response, and dysfunction thereof is thought to be associated with core epilepsy symptoms and related psychopathology. This article explores the intrinsic relationships of corticotropin-releasing hormone, adrenocorticotropic hormone, and glucocorticoids with epilepsy in order to reveal the role of the HPA axis in the pathogenesis of epilepsy. We hope that this information will yield future possible directions and ideas for fully understanding the pathogenesis of epilepsy and developing antiepileptic drugs.

Structural Modification of Noscapine via Photoredox/Nickel Dual Catalysis for the Discovery of S-Phase Arresting Agents.

Herein, we disclose a powerful strategy for the functionalization of the antitumor natural alkaloid noscapine by utilizing photoredox/nickel dual-catalytic coupling technology. A small collection of 37 new noscapinoids with diverse (hetero)alkyl and (hetero)cycloalkyl groups and enhanced sp3 character was thus synthesized. Further in vitro antiproliferative activity screening and SAR study enabled the identification of 6o as a novel, potent, and less-toxic anticancer agent. Furthermore, 6o exerts superior cellular activity via an unexpected S-phase arrest mechanism and could significantly induce cell apoptosis in a dose-dependent manner, thereby further highlighting its potential in drug discovery as a promising lead compound.

Chemical reagents for the enrichment of modified peptides in MS-based identification.

Chemical reagents with special groups as enrichable handles have empowered the ability to label and enrich modified peptides. Here is an overview of different chemical reagents with affinity tags to isolate labeled peptides and the latest developments of enrichment strategies. Biotin is the most used affinity tag due to its high interaction with avidin. To decrease the unfavorable influence of biotin for its poor efficiency in ionization and fragmentation in downstream MS analysis, cleavable moieties were installed between the reactive groups and biotin to release labeled peptides from the biotin. To minimize the steric hindrance of biotin, a two-step method was developed, for which alkyne- or azide-tagged linkers were firstly used to label peptides and then biotin was installed through click chemistry. Recently, new linkers using a small phosphonic acid as the affinity tag for IMAC or TiO2 enrichment have been developed and successfully used to isolate chemically labeled peptides in XL-MS. A stable P-C instead of P-O bond was introduced to linkers to differentiate labeled and endogenous phosphopeptides. Furthermore, a membrane-permeable phosphonate-containing reagent was reported, which facilitated the study of living systems. Taking a cue from classic chemical reactions, stable metal-complex intermediates, including cobalt and palladium complexes, have been developed as peptide purification systems. Advanced enrichment strategies have also been proposed, such as the two-stage IMAC enrichment method and biotin-based two-step reaction strategy, allowing the reduction of unwanted peptides and improvements for the analysis of specific labeled peptides. Finally, future trends in the area are briefly discussed.

Chemical compositions and cryo-adhesive probing of the epicuticular wax crystals on fruit surface of wax gourd (Benincasa hispida).

Surface wax crystals play important roles in protecting plants from pest and disease invasions, and UV irradiation. The wax crystals are less probed individually from the fruit surfaces. Herein the morphologies, chemicals and an efficient method to sample the wax blooms of white wax gourd were addressed. Various crystalloids such as rodlets, platelets, fragments, and granules were observed, which stacked as fine wax film covering on wax gourd fruit surface. The wax blooms were effectively removed by cryo-adhesive after consecutive manipulating set by a high-end device with cylinders. Wax crystals were dominated by triterpenols and triterpenol acetates over 61 % of total crystals, followed by vey-long-chain aliphatics. Accordingly, the high-end device with cryo-adhesive provides an efficient approach to selectively probe the wax crystals from those fruits covering wax blooms. The elucidation of morphologies and chemical compositions of wax crystals may help to better understand their regulations on fruit quality traits.

A novel defensin-like peptide C-13326 possesses protective effect against multidrug-resistant Aeromonas schubertii in hybrid snakehead (Channa maculate ♀ × Channa argus ♂).

The purpose of this study was to investigate whether a defensin-like antimicrobial peptide (C-13326 peptide) identified in Hermetia illucens could possess protective effect against multidrug-resistant Aeromonas schubertii in hybrid snakehead (Channa maculate ♀ × Channa argus ♂). The cDNA of C-13326 peptide comprised 243 nucleotides encoding 80 amino acids, with six conserved cysteine residues and the classical CSαß structure. The recombinant expression plasmid pPIC9K-C-13326 was constructed and transformed into GS115 Pichia pastoris, and the C-13326 peptide was expressed by induction with 1% methanol. The crude extract of C-13326 peptide was precipitated by ammonium sulfate, assayed by Braford method, detected by tricine-SDS-PAGE, evaluated by BandScan software and identified by liquid chromatography-mass spectrometry. The C-13326 peptide was shown to have inhibitory activity against the growth of multidrug-resistant A. schubertii DM210910 by using the minimum growth inhibitory concentration and Oxford cup method. In addition, scanning electron microscopy analysis suggested that C-13326 peptide inhibited the growth of A. schubertii DM210910 by damaging the bacterial cell membrane. To explore the role of peptide C-13326 in vivo, hybrid snakehead was fed with peptide C-13326 as feed additives for 7 days. The results revealed that C-13326 peptide could significantly down-regulate the expression levels of IL-1ß, IL-8, IL-12 and TNF-α (p < .05), and significantly improved the survival rate of hybrid snakehead after challenging with A. schubertii DM210910. Therefore, the C-13326 peptide is a promising antimicrobial agent for A. schubertii treatment in aquaculture.

The pathway of Edwardsiella piscicida infecting Lateolabrax maculatus via the immersion bath.

Edwardsiella piscicida, an infectious bacterium, causes great economic losses to the aquaculture industry. Immersion bath which is the closest way to how the fish infect bacterial pathogens in the natural environment is an effective route of artificial infection. In this study, the dynamic process of E. piscicida infection, in the spotted sea bass (Lateolabrax maculatus) was evaluated via the immersion bath. The results showed that soaking the spotted sea bass with 3 × 106 CFU mL-1 E. piscicida for 30 min could artificially induce edwardsiellosis. The higher culture temperature (28.5 ± 0.5°C) or the longer bath time (30 min) would lead to higher mortality of fish. E.piscicida first invaded the gill, then entered the blood circulation to infect the spleen and kidney, where it is colonized, and gradually multiplied in the liver and brain. Meanwhile, the fluorescence in situ hybridization showed that the localization of E. piscicida in the gill and foregut after the immersion challenge proceeded from the exterior to the interior. The invasion of pathogens triggers the immune response of fish and causes tissue damage to the host. The quantitative real-time PCR results displayed an increase in the relative expression level of immune genes (NK-lysin, LZM, IgM and IgD). Otherwise, the most notable histopathological changes of the infected spotted sea bass were multifocal necrosis. Findings in this study broaden our understanding of the infection conditions of E. piscicida and its pathogenicity to the spotted sea bass.

White matter hyperintensities in cholinergic pathways correlates of cognitive impairment in moyamoya disease.

OBJECTIVE: To investigate the effect of cholinergic pathways damage caused by white matter hyperintensities (WMHs) on cognitive function in moyamoya disease (MMD). METHODS: We included 62 patients with MMD from a prospectively enrolled cohort. We evaluated the burden of cholinergic pathways damage caused by WMHs using the Cholinergic Pathways Hyperintensities Scale (CHIPS). Cognitive function was evaluated with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Cognitive impairment was determined according to the cut-off of MMSE and education. Multivariate linear and logistic regression models were used to analyze whether CHIPS was independently associated with cognition. Receiver operating characteristic curve analysis was performed to identify the ability of CHIPS in discriminating cognitive impairment and normal cognition. RESULTS: CHIPS was associated with both MMSE and MoCA (ß = - 0.601 and ß = - 0.672, both p < 0.001). After correcting age, sex, education, volumes of limbic areas, and other factors, CHIPS remained to be independently associated with both MMSE and MoCA (ß = - 0.388 and ß = - 0.334, both p < 0.001). In the logistic regression, only CHIPS was associated with cognitive impairment (odds ratio = 1.431, 95% confidence interval = 1.103 to 1.856, p = 0.007). The optimal cut-off of CHIPS score was 10, yielding a sensitivity of 87.5% and a specificity of 78.3% in identifying MMD patients with cognitive impairment. CONCLUSIONS: The damage of cholinergic pathways caused by WMHs plays an independent effect on cognition and CHIPS could be a useful method in identifying MMD patients likely to be cognitive impairment. CLINICAL RELEVANCE STATEMENT: This study shows that Cholinergic Pathways Hyperintensities Scale (CHIPS) could be a simple and reliable method in identifying cognitive impairment for patients with moyamoya disease. CHIPS could be helpful in clinical practice, such as guiding treatment decisions and predicting outcome. KEY POINTS: • Cholinergic Pathways Hyperintensities Scale was significantly associated with cognitive screening tests in patients with moyamoya disease. • Cholinergic Pathways Hyperintensities Scale plays an independent effect on cognitive impairment in patients with moyamoya disease. • Cholinergic Pathways Hyperintensities Scale shows higher accuracy than education, volumes of limbic areas, and sex in identifying cognitive impairment in moyamoya disease.

Genome-wide identification of bZIP gene family and expression analysis of BhbZIP58 under heat stress in wax gourd.

BACKGROUND: The basic leucine zipper (bZIP) transcription factor family is one of the most abundant and evolutionarily conserved gene families in plants. It assumes crucial functions in the life cycle of plants, including pathogen defense, secondary metabolism, stress response, seed maturation, and flower development. Although the genome of wax gourd has been published, little is known about the functions, evolutionary background, and gene expression patterns of the bZIP gene family, which limits its utilization. RESULTS: A total of 61 bZIP genes (BhbZIPs) were identified from wax gourd (Benincasa hispida) genome and divided into 12 subgroups. Whole-genome duplication (WGD) and dispersed duplication (DSD) were the main driving forces of bZIP gene family expansion in wax gourd, and this family may have undergone intense purifying selection pressure during the evolutionary process. We selected BhbZIP58, only one in the member of subgroup B, to study its expression patterns under different stresses, including heat, salt, drought, cold stress, and ABA treatment. Surprisingly, BhbZIP58 had a dramatic response under heat stress. BhbZIP58 showed the highest expression level in the root compared with leaves, stem, stamen, pistil, and ovary. In addition, BhbZIP58 protein was located in the nucleus and had transcriptional activation activity. Overexpression of BhbZIP58 in Arabidopsis enhanced their heat tolerance. CONCLUSIONS: In this study, bZIP gene family is systematically bioinformatically in wax gourd for the first time. Particularly, BhbZIP58 may have an important role in heat stress. It will facilitate further research on the bZIP gene family regarding their evolutionary history and biological functions.

Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry.

Since 2019, SARS-CoV-2 has evolved rapidly and gained resistance to multiple therapeutics targeting the virus. Development of host-directed antivirals offers broad-spectrum intervention against different variants of concern. Host proteases, TMPRSS2 and CTSL/CTSB cleave the SARS-CoV-2 spike to play a crucial role in the two alternative pathways of viral entry and are characterized as promising pharmacological targets. Here, we identify compounds that show potent inhibition of these proteases and determine their complex structures with their respective targets. Furthermore, we show that applying inhibitors simultaneously that block both entry pathways has a synergistic antiviral effect. Notably, we devise a bispecific compound, 212-148, exhibiting the dual-inhibition ability of both TMPRSS2 and CTSL/CTSB, and demonstrate antiviral activity against various SARS-CoV-2 variants with different viral entry profiles. Our findings offer an alternative approach for the discovery of SARS-CoV-2 antivirals, as well as application for broad-spectrum treatment of viral pathogenic infections with similar entry pathways.

Effect of SMOF lipid emulsion on physical growth and extrauterine growth retardation in very preterm infants: Insights from a multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to investigate the effects of soybean, medium-chain triacylglycerols (MCTs), olive oil, and fish oil (SMOF) on short-term clinical outcomes, physical growth, and extrauterine growth retardation (EUGR) in very preterm infants. METHODS: This was a multicenter retrospective cohort study of very preterm infants hospitalized in neonatal intensive care units at five tertiary hospitals in China between January 2021 and December 2021. According to the type of fat emulsion used in parenteral nutrition (PN), eligible very preterm infants were divided into the MCTs/long-chain triacylglycerol (MCT/LCT) group and SMOF group. Change in weight z-score (weight Δz) between measurements at birth and at 36 wk of postmenstrual age or at discharge, the incidence of EUGR, and short-term clinical outcomes between the two groups were compared and analyzed. RESULTS: We enrolled 409 very preterm infants, including 205 in the MCT/LCT group and 204 in the SMOF group. Univariate analysis showed that infants in the SMOF group had significantly longer duration of invasive mechanical ventilation and PN, longer days to reach total enteral nutrition, and a higher proportion of maximum weight loss than those in MCT/LCT group (all P < 0.05). After adjusting for the confounding variables, multifactorial logistic regression analysis of short-term clinical outcomes showed that SMOF had protective effects on PN-associated cholestasis (odds ratio [OR], 0.470; 95% confidence interval [CI], 0.266-0.831) and metabolic bone disease of prematurity (OR, 0.263; 95% CI, 0.078-0.880). Additionally, SMOF was an independent risk factor for lower weight growth velocity (ß = -0.733; 95% CI, -1.452 to -0.015) but had no effect on the incidence of EUGR (OR, 1.567; 95% CI, 0.912 to -2.693). CONCLUSION: Compared with MCT/LCT, SMOF can reduce the risk for PN-associated cholestasis and metabolic bone disease of prematurity in very preterm infants and has a negative effect on growth velocity but has no effect on the incidence of EUGR.