Redundancy in microbiota-mediated suppression of the soybean cyst nematode.

BACKGROUND: Soybean cyst nematodes (SCN) as animal parasites of plants are not usually interested in killing the host but are rather focused on completing their life cycle to increase population, resulting in substantial yield losses. Remarkably, some agricultural soils after long-term crop monoculture show a significant decline in SCN densities and suppress disease in a sustainable and viable manner. However, relatively little is known about the microbes and mechanisms operating against SCN in such disease-suppressive soils. RESULTS: Greenhouse experiments showed that suppressive soils (S) collected from two provinces of China and transplantation soils (CS, created by mixing 10% S with 90% conducive soils) suppressed SCN. However, SCN suppressiveness was partially lost or completely abolished when S soils were treated with heat (80 °C) and formalin. Bacterial community analysis revealed that the specific suppression in S and CS was mainly associated with the bacterial phylum Bacteroidetes, specifically due to the enrichment of Chitinophaga spp. and Dyadobacter sp., in the cysts. SCN cysts colonized by Chitinophaga spp. showed dramatically reduced egg hatching, with unrecognizable internal body organization of juveniles inside the eggshell due to chitinase activity. Whereas, Dyadobacter sp. cells attached to the surface coat of J2s increased soybean resistance against SCN by triggering the expression of defence-associated genes. The disease-suppressive potential of these bacteria was validated by inoculating them into conducive soil. The Dyadobacter strain alone or in combination with Chitinophaga strains significantly decreased egg densities after one growing cycle of soybeans. In contrast, Chitinophaga strains alone required more than one growing cycle to significantly reduce SCN egg hatching and population density. CONCLUSION: This study revealed how soybean monoculture for decades induced microbiota homeostasis, leading to the formation of SCN-suppressive soil. The high relative abundance of antagonistic bacteria in the cyst suppressed the SCN population both directly and indirectly. Because uncontrolled proliferation will likely lead to quick demise due to host population collapse, obligate parasites like SCN may have evolved to modulate virulence/proliferation to balance these conflicting needs. Video Abstract.

6-shogaol against 3-Nitropropionic acid-induced Huntington's disease in rodents: Based on molecular docking/targeting pro-inflammatory cytokines/NF-κB-BDNF-Nrf2 pathway.

BACKGROUND: Huntington's disease (HD) is an extremely harmful autosomal inherited neurodegenerative disease. Motor dysfunction, mental disorder, and cognitive deficits are the characteristic features of this disease. The current study examined whether 6-shogaol has a protective effect against 3-Nitropropionic Acid (3-NPA)-induced HD in rats. METHODS: A total of thirty male Wistar rats received 6-shogaol (10 and 20 mg/kg, per oral) an hour before injection of 3-NPA (10 mg/kg i.p.) for 15 days. Behavioral tests were performed, including narrow beam walk, rotarod test, and grip strength test. Biochemical tests promoting oxidative stress were evaluated [superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and malondialdehyde (MDA)], including changes to neurotransmitters serotonin (5-HT), dopamine (DA), norepinephrine (NE), homovanillic acid (HVA), (3,4-dihydroxyphenylacetic acid (DOPAC), γ-aminobutyric acid (GABA), and 5-hydroxy indole acetic acid (5-HIAA), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukins-1ß (IL-1ß), IL-6, brain-derived neurotrophic factor (BDNF), and nuclear factor erythroid 2-related factor 2 (Nrf2). The 6-shogaol was docked to the active site of TNF-α (2AZ5), NF-κB (1SVC), BDNF) [1B8M], and Nrf2 [5FZN] proteins using AutoDock tools. RESULTS: The 6-shogaol group significantly improved behavioral activity over the 3-NPA-injected control rats. Moreover, 3-NPA-induced significantly altered neurotransmitters, biochemical and neuroinflammatory indices, which could efficiently be reversed by 6-shogaol. The 6-shogaol showed favorable negative binding energies at -9.271 (BDNF) kcal/mol. CONCLUSIONS: The present investigation demonstrated the neuroprotective effects of 6-shogaol in an experimental animal paradigm against 3-NPA-induced HD in rats. The suggested mechanism is supported by immunohistochemical analysis and western blots, although more research is necessary for definite confirmation.

Spontaneous Remission of Acute Lymphoblastic Leukemia Following Candida tropicalis Fungemia.

Spontaneous remission (SR) in acute lymphoblastic leukemia (ALL) is a poorly understood phenomenon that has been sporadically reported in medical literature for over a century, and the molecular and immunologic mechanisms of remission pose interesting clinical questions. Furthermore, the often-transient nature of these remissions poses a challenge to physicians in formulating an approach to treatment. We report on a rare case of Candida tropicalis sepsis in a three-year-old female with high-risk ALL who received less than two months of treatment prior to sepsis and subsequent SR.

Characterization of anaerobic biotransformation of hexachlorocyclohexanes by novel microbial consortia enriched from channel and river sediments.

The microbial biotransformation of hexachlorocyclohexane (HCH) by novel anaerobic microbial consortia enriched from sediments of an industrial effluent channel and the river Ravi in Pakistan was examined. The anaerobic consortia were capable of biotransforming α-, ß-, γ-, and δ-HCH through reductive dichloroelimination, resulting in the formation of benzene and monochlorobenzene. Concerning γ-HCH biotransformation by the channel and river cultures, isotopic fractionations for carbon (εC) were - 5.3 ± 0.4 (‰) and - 10.6 ± 1.2 (‰), while isotopic fractionations for chlorine (εCl) were - 4.4 ± 0.4 (‰) and - 7.8 ± 0.9 (‰), respectively. Furthermore, lambda values (Λ), representing the correlation of δ13C and δ37Cl fractionation, were determined to be 1.1 ± 0.1 and 1.3 ± 0.1 for γ-HCH biotransformation, suggesting a reductive dichloroelimination as the initial step of HCH biotransformation in both cultures. Amplicon sequencing targeting the 16S rRNA genes revealed that Desulfomicrobium populations were considerably increased in both cultures, indicating their possible involvement in the degradation process. These findings suggest that Desulfomicrobium-like populations may have an important role in biotransformation of HCH and novel anaerobic HCH-degrading microbial consortia could be useful bioaugmentation agents for the bioremediation of HCH-contaminated sites in Pakistan.

Probing the Limit of the Number of Saturated Atoms for Achieving Hyperconjugative Aromaticity.

Aromaticity is a fundamental concept in organic chemistry. Hyperconjugative aromaticity, also known as hyperconjugation-induced aromaticity, has evolved from its origin from main group substituents to transition metal analogues, establishing itself as an important category of aromaticity. Additionally, aromatic compounds comprising two sp3-carbon atoms have recently been reported both experimentally and computationally. However, what is the maximum number of sp3-hybridized atoms needed to maintain hyperconjugative aromaticity? Here, we report that hyperconjugative aromaticity can be achieved in hexa-substituted indoliums and octa-substituted pyrroliums, possessing three-five sp3-hybridized carbon/nitrogen atoms by means of density functional theory (DFT) calculations. The aromaticity was confirmed by using various aromaticity indices, i.e., NICS, MCI, and EDDB. Notably, the strong electron-donating ability and aurophilicity of Au(I) substituents play a pivotal role in maintaining the aromaticity and structural integrity. In addition, increasing the number of hyperconjugative centers will decrease the aromaticity in these five-membered rings. Our findings highlight the significance of transition metal substituents in hyperconjugative aromaticity and offer a novel approach for designing aromatic organometallics.

The Pleural Origin of Retiform Hemangioendothelioma: An Unusual Origin of a Rare Diagnosis.

Introduction: Vascular malignancies are categorized into benign hemangiomas, malignant angiosarcomas, and tumors of intermediate malignancy. Retiform hemangioendothelioma (RH) is one of the rare diagnoses belonging to the class of intermediate malignancies that was initially diagnosed. Case Presentation: In this case report, we have reported a rare case of RH, a locally aggressive, vascular tumor of malignant potential presenting at an unusual site. The most observed locations of this soft tissue tumor are skin and subcutaneous tissues of extremities; however, this case of RH was observed in an unusual site called pleura, which is a rare occurrence related to this tumor. The presence of cell surface markers like CD31 and ERG of vascular and endothelial origin and the presence of hobnail appearance of endothelial channels on the biopsy profile supported the vascular origin of the tumor; the clinical features and imaging studies further confirmed the diagnosis of RH. Conclusion: In this case report, a rare case of RH with an unusual site of origin was highlighted. RH is a vascular neoplasm; commonly observed sites of this vascular tumor were skin and subcutaneous tissue of the extremities; however, in this case, the site was unusually different, which was the pleura of the left lung.

Targeting MDM2-p53 interaction in Glioblastoma: Transcriptomic analysis and Peptide-Based inhibition strategy.

MDM2 is a gene that encodes a protein involved in cell survival, growth, and DNA repair. It has been implicated in the development and progression of glioblastoma (GBM). Inhibition of the MDM2-p53 interaction has emerged as a promising strategy for treating GBM. In this study, we performed comprehensive transcriptomic expression analysis from diverse datasets and observed MDM2 overexpression in a subset of GBM cases. MDM2 negatively regulates the major onco-suppressor p53. The interaction between MDM2 and p53 is a promising target for cancer therapy, as it can trigger p53-mediated cell death in response to different stress conditions, such as oncogene activation or DNA damage. In this study, we have identified a peptide-based inhibition of MDM2 as a therapeutic strategy for GBM. We have further validated the stability of the MDM2-peptide interaction using a molecular structural dynamics approach. The major trajectories, including root mean square of deviation (RMSD), root mean square of fluctuation (RMSF), and radius of gyration (RoG), indicate that the candidate peptides have a more stable binding compared to the native ligand and control drug. The stability of the binding interaction was further estimated by MMGBSA analysis, which also suggests that MDM2 has a stable binding with both peptide molecules. Based on these results, peptides P-1843 and P-3837 could be tested further for experimental validation to confirm their targeted inhibition of MDM-2. This approach could provide a highly selective and efficient inhibitor with potentially fewer side effects and less toxicity compared to small drug-based molecules.

One stone two birds: Endophytes alleviating trace elements accumulation and suppressing soilborne pathogen by stimulating plant growth, photosynthetic potential and defense related gene expression.

In the present investigation, we utilized zinc nanoparticles (Zn-NPs) and bacterial endophytes to address the dual challenge of heavy metal (HM) toxicity in soil and Rhizoctonia solani causing root rot disease of tomato. The biocontrol potential of Bacillus subtilis and Bacillus amyloliquefaciens was harnessed, resulting in profound inhibition of R. solani mycelial growth and efficient detoxification of HM through strong production of various hydrolytic enzymes and metabolites. Surprisingly, Zn-NPs exhibited notable efficacy in suppressing mycelial growth and enhancing the seed germination (%) while Gas chromatography-mass spectrometry (GC-MS) analysis unveiled key volatile compounds (VOCs) crucial for the inhibition of pathogen. Greenhouse trials underscored significant reduction in the disease severity (%) and augmented biomass in biocontrol-mediated plants by improving photosynthesis-related attributes. Interestingly, Zn-NPs and biocontrol treatments enhanced the antioxidant enzymes and mitigate oxidative stress indicator by increasing H2O2 concentration. Field experiments corroborated these findings, with biocontrol-treated plants, particularly those receiving consortia-mediated treatments, displayed significant reduction in disease severity (%) and enhanced the fruit yield under field conditions. Root analysis confirmed the effective detoxification of HM, highlighting the eco-friendly potential of these endophytes and Zn-NPs as fungicide alternative for sustainable production that foster soil structure, biodiversity and promote plant health.

A versatile functional interaction between electrically silent KV subunits and KV7 potassium channels.

Voltage-gated K+ (KV) channels govern K+ ion flux across cell membranes in response to changes in membrane potential. They are formed by the assembly of four subunits, typically from the same family. Electrically silent KV channels (KVS), however, are unable to conduct currents on their own. It has been assumed that these KVS must obligatorily assemble with subunits from the KV2 family into heterotetrameric channels, thereby giving rise to currents distinct from those of homomeric KV2 channels. Herein, we show that KVS subunits indeed also modulate the activity, biophysical properties and surface expression of recombinant KV7 isoforms in a subunit-specific manner. Employing co-immunoprecipitation, and proximity labelling, we unveil the spatial coexistence of KVS and KV7 within a single protein complex. Electrophysiological experiments further indicate functional interaction and probably heterotetramer formation. Finally, single-cell transcriptomic analyses identify native cell types in which this KVS and KV7 interaction may occur. Our findings demonstrate that KV cross-family interaction is much more versatile than previously thought-possibly serving nature to shape potassium conductance to the needs of individual cell types.

Improving prediction of blood cancer using leukemia microarray gene data and Chi2 features with weighted convolutional neural network.

Blood cancer has emerged as a growing concern over the past decade, necessitating early diagnosis for timely and effective treatment. The present diagnostic method, which involves a battery of tests and medical experts, is costly and time-consuming. For this reason, it is crucial to establish an automated diagnostic system for accurate predictions. A particular field of focus in medical research is the use of machine learning and leukemia microarray gene data for blood cancer diagnosis. Even with a great deal of research, more improvements are needed to reach the appropriate levels of accuracy and efficacy. This work presents a supervised machine-learning algorithm for blood cancer prediction. This work makes use of the 22,283-gene leukemia microarray gene data. Chi-squared (Chi2) feature selection methods and the synthetic minority oversampling technique (SMOTE)-Tomek resampling is used to overcome issues with imbalanced and high-dimensional datasets. To balance the dataset for each target class, SMOTE-Tomek creates synthetic data, and Chi2 chooses the most important features to train the learning models from 22,283 genes. A novel weighted convolutional neural network (CNN) model is proposed for classification, utilizing the support of three separate CNN models. To determine the importance of the proposed approach, extensive experiments are carried out on the datasets, including a performance comparison with the most advanced techniques. Weighted CNN demonstrates superior performance over other models when coupled with SMOTE-Tomek and Chi2 techniques, achieving a remarkable 99.9% accuracy. Results from k-fold cross-validation further affirm the supremacy of the proposed model.

The C-terminal proline-rich repeats of Enteropathogenic E. coli effector EspF are sufficient for the depletion of tight junction membrane proteins and interactions with early and recycling endosomes.

BACKGROUND: Enteropathogenic E. coli (EPEC) causes acute infantile diarrhea accounting for significant morbidity and mortality in developing countries. EPEC uses a type three secretion system to translocate more than twenty effectors into the host intestinal cells. At least four of these effectors, namely EspF, Map, EspG1/G2 and NleA, are reported to disrupt the intestinal tight junction barrier. We have reported earlier that the expression of EspF and Map in MDCK cells causes the depletion of the TJ membrane proteins and compromises the integrity of the intestinal barrier. In the present study, we have examined the role of the proline-rich repeats (PRRs) within the C-terminus of EspF in the depletion of the tight junction membrane proteins and identified key endocytosis markers that interact with EspF via these repeats. RESULTS: We generated mutant EspF proteins which lacked one or more proline-rich repeats (PRRs) from the N-terminus of EspF and examined the effect of their expression on the cellular localization of tight junction membrane proteins. In lysates derived from cells expressing the mutant EspF proteins, we found that the C-terminal PRRs of EspF are sufficient to cause the depletion of TJ membrane proteins. Pull-down assays revealed that the PRRs mediate interactions with the TJ adaptor proteins ZO-1 and ZO-2 as well as with the proteins involved in endocytosis such as caveolin-1, Rab5A and Rab11. CONCLUSIONS: Our study demonstrates the direct role of the proline-rich repeats of EspF in the depletion of the TJ membrane proteins and a possible involvement of the PRRs in the endocytosis of host proteins. New therapeutic strategies can target these PRR domains to prevent intestinal barrier dysfunction in EPEC infections.

Harnessing the Power of Big Data Analytics-Estimation of Reference Intervals for Neonatal Serum TSH in Pakistan Using RefineR Algorithm.

OBJECTIVE: To estimate the population-specific reference intervals (RIs) for neonatal thyroid stimulating hormone (TSH) in Pakistani neonates, utilising the refineR algorithm. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, Pakistan, from 17th May to 30th November 2023. METHODOLOGY: A data mining analysis was conducted on serum TSH results of neonates (≤1 month) over a period of six years, following approval from the Institutional Ethical Review Committee. Two subgroups were assessed based on the age as 0 - 5 days and 6 - 30 days. The refineR algorithm was implemented using refineR package (version 1.0.0), ensuring accurate analysis and insights. RESULTS: A total of non-duplicate 82,299 neonatal serum TSH tests were retrieved, including 70,788 (88%) aged 0 - 5 days and 11,511 (12%) aged ranging from 6 - 30 days. The estimated RI was from 0.67 µIU/mL (90% CI 0.641 - 0.72) to 15.0 µIU/mL (90% CI 13.2 - 17.3) for the first age group and 0.65 µIU/mL (90% CI 0.6 - 0.84) to 8.6 µIU/mL (90% CI 8.05 - 9.71) for the second age group. CONCLUSION: Reference intervals for neonatal serum TSH of the Pakistani population were estimated, considering the genetic differences of this demographic in comparison to the Western population. Results aligned with global literature, validating the refineR indirect approach's applicability. KEY WORDS: Reference intervals, Neonatal, Thyroid stimulating hormone, RefineR algorithm, Big data, Pakistan.

Hybrid deep spatial and statistical feature fusion for accurate MRI brain tumor classification.

The classification of medical images is crucial in the biomedical field, and despite attempts to address the issue, significant challenges persist. To effectively categorize medical images, collecting and integrating statistical information that accurately describes the image is essential. This study proposes a unique method for feature extraction that combines deep spatial characteristics with handmade statistical features. The approach involves extracting statistical radiomics features using advanced techniques, followed by a novel handcrafted feature fusion method inspired by the ResNet deep learning model. A new feature fusion framework (FusionNet) is then used to reduce image dimensionality and simplify computation. The proposed approach is tested on MRI images of brain tumors from the BraTS dataset, and the results show that it outperforms existing methods regarding classification accuracy. The study presents three models, including a handcrafted-based model and two CNN models, which completed the binary classification task. The recommended hybrid approach achieved a high F1 score of 96.12 ± 0.41, precision of 97.77 ± 0.32, and accuracy of 97.53 ± 0.24, indicating that it has the potential to serve as a valuable tool for pathologists.

Exploring Ubiquitin-specific proteases as therapeutic targets in Glioblastoma.

Glioblastoma (GB) remains a formidable challenge and requires new treatment strategies. The vital part of the Ubiquitin-proteasome system (UPS) in cellular regulation has positioned it as a potentially crucial target in GB treatment, given its dysregulation oncolines. The Ubiquitin-specific proteases (USPs) in the UPS system were considered due to the garden role in the cellular processes associated with oncolines and their vital function in the apoptotic process, cell cycle regulation, and autophagy. The article provides a comprehensive summary of the evidence base for targeting USPs as potential factors for neoplasm treatment. The review considers the participation of the UPS system in the development, resulting in the importance of p53, Rb, and NF-κB, and evaluates specific goals for therapeutic administration using midnight proteasomal inhibitors and small molecule antagonists of E1 and E2 enzymes. Despite the slowed rate of drug creation, recent therapeutic discoveries based on USP system dynamics hold promise for specialized therapies. The review concludes with an analysis of future wanderers and the feasible effects of targeting USPs on personalized GB therapies, which can improve patient hydration in this current and unattractive therapeutic landscape. The manuscript emphasizes the possibility of USP oncogene therapy as a promising alternative treatment line for GB. It stresses the direct creation of research on the medical effectiveness of the approach.

A Comparison of Machine Learning Approaches for predicting Hepatotoxicity potential using Chemical Structure and Targeted Transcriptomic Data.

Animal toxicity testing is time and resource intensive, making it difficult to keep pace with the number of substances requiring assessment. Machine learning (ML) models that use chemical structure information and high-throughput experimental data can be helpful in predicting potential toxicity . However, much of the toxicity data used to train ML models is biased with an unequal balance of positives and negatives primarily since substances selected for in vivo testing are expected to elicit some toxicity effect. To investigate the impact this bias had on predictive performance, various sampling approaches were used to balance in vivo toxicity data as part of a supervised ML workflow to predict hepatotoxicity outcomes from chemical structure and/or targeted transcriptomic data. From the chronic, subchronic, developmental, multigenerational reproductive, and subacute repeat-dose testing toxicity outcomes with a minimum of 50 positive and 50 negative substances, 18 different study-toxicity outcome combinations were evaluated in up to 7 ML models. These included Artificial Neural Networks, Random Forests, Bernouilli Naïve Bayes, Gradient Boosting, and Support Vector classification algorithms which were compared with a local approach, Generalised Read-Across (GenRA), a similarity-weighted k-Nearest Neighbour (k-NN) method. The mean CV F1 performance for unbalanced data across all classifiers and descriptors for chronic liver effects was 0.735 (0.0395 SD). Mean CV F1 performance dropped to 0.639 (0.073 SD) with over-sampling approaches though the poorer performance of KNN approaches in some cases contributed to the observed decrease (mean CV F1 performance excluding KNN was 0.697 (0.072 SD)). With under-sampling approaches, the mean CV F1 was 0.523 (0.083 SD). For developmental liver effects, the mean CV F1 performance was much lower with 0.089 (0.111 SD) for unbalanced approaches and 0.149 (0.084 SD) for under-sampling. Over-sampling approaches led to an increase in mean CV F1 performance (0.234, (0.107 SD)) for developmental liver toxicity. Model performance was found to be dependent on dataset, model type, balancing approach and feature selection. Accordingly tailoring ML workflows for predicting toxicity should consider class imbalance and rely on simpler classifiers first.

The Risk of Infection-Caused Mortality in Gastric Adenocarcinoma: A Population-Based Study.

Background: Gastric adenocarcinoma (GAC) is a deadly tumor. Postoperative complications, including infections, worsen its prognosis and may affect overall survival. Little is known about perioperative complications as well as modifiable and non-modifiable risk factors. Early detection and treatment of these risk factors may affect overall survival and mortality. Methods: We extracted GAC patient's data from the Surveillance, Epidemiology, and End Results (SEER) database and analyzed using Pearson's Chi-square, Cox regression, Kaplan-Meier, and binary regression methods in SPSS. Results: At the time of analysis, 59,580 GAC patients were identified, of which 854 died of infection. Overall, mean survival in months was better for younger patients, age < 50 years vs. ≥ 50 years (60.45 vs. 56.75), and in females vs. males (65.23 vs. 53.24). The multivariate analysis showed that the risk of infectious mortality was higher in patients with age ≥ 50 years (hazard ratio (HR): 3.137; 95% confidence interval (CI): 2.178 - 4.517), not treated with chemotherapy (HR: 1.669; 95% CI: 1.356 - 2.056), or surgery (HR: 1.412; 95% CI:1.132 - 1.761) and unstaged patients (HR: 1.699; 95% CI: 1.278 - 2.258). In contrast, the mortality risk was lower in females (HR: 0.658; 95% CI: 0.561 - 0.773) and married patients (HR: 0.627; 95% CI: 0.506 - 0.778). The probability of infection was higher in older patients (odds ratio (OR) of 2.094 in ≥ 50 years), other races in comparison to Whites and Blacks (OR: 1.226), lesser curvature, not other specified (NOS) as a primary site (OR: 1.325), and patients not receiving chemotherapy (OR: 1.258). Conclusion: Older, unmarried males with GAC who are not treated with chemotherapy or surgery are at a higher risk for infection-caused mortality and should be given special attention while receiving treatment.

Specialized nutritious foods and behavior change communication interventions during the first 1,000 days of life to prevent stunting: A quasi-experimental study in Afghanistan.

BACKGROUND: Considerable evidence supports the effectiveness of nutritional supplementation with or without nutrition education in preventing stunting in developing countries, but evidence from Afghanistan is scarce. OBJECTIVE: This project aimed to assess the effectiveness of specialized nutritious food (SNF), social and behavior change communication (SBCC) intervention to prevent stunting among children under 2 years during the first 1,000 days of life in Badakhshan, Afghanistan. METHODS: We used a community-based quasi-experimental pre-post study design with a control group. Pregnant and lactating women received a monthly ration of 7.5 kg of Super Cereal (250g/day) during pregnancy and the first 6 months of breastfeeding. Children aged 6-23 months received 30 sachets of medium-quantity lipid-based nutrient supplement (50g/sachet/day) monthly. We compared pre- and post-intervention assessments of the intervention and control groups to isolate the effect of the intervention on key study outcomes at the endline by difference-in-differences (DID) estimates. RESULTS: A total of 2,928 and 3,205 households were surveyed at baseline and endline. DID estimates adjusted for child, maternal, and household characteristics indicated a significant reduction in stunting (DID: -5% (95% CI: -9.9, -0.2) and underweight (DID: -4.6% (95% CI: -8.6, -0.5) among children <2 years of age. However, DID estimates for wasting among children in the intervention and control groups were not significantly different (DID: -1.7 (95% CI: -5.1,1.6). Furthermore, exposure to the SBCC messages was associated with improvements in the early initiation of breastfeeding (DID: 19.6% (95% CI: 15.6,23.6), exclusive breastfeeding under 6-months (DID: 11.0% (95% CI: 2.3,19.7), minimum meal frequency (MMF) (DID: 23% (95% CI: 17.7,28.2), minimum acceptable diet (MAD) (DID: 13% (95% CI: 9.8,16.3). CONCLUSIONS: The provision of SNF in combination with SBCC during the first 1,000 days of life was associated with reduction in stunting and underweight and improvements in IYCF practices among children under 2 years of age. CLINICAL TRIAL REGISTRY NUMBER: Clinicaltrials.gov, NCT04581993.