Gut microbiome is associated with personality traits of free-ranging Tibetan macaques (Macaca thibetana).

Recent studies have emphasized that there is a strong link between the gut microbiome and the brain that affects social behavior and personality in animals. However, the interface between personality and the gut microbiome in wild primates remains poorly understood. Here, we used high-throughput sequencing and ethological methods in primate behavioral ecology to investigate the relationship between gut microbiome and personality in Tibetan macaques (Macaca thibetana). The behavioral assessment results indicated three personality dimensions including socialization, shyness, and anxiety. There was significant variation in alpha diversity only for shyness, with a significantly lower alpha diversity indices (including Shannon, Chao1, and PD) for bold individuals than for shy individuals. Using regression models to control for possible confounding factors, we found that the relative abundance of three genera, Akkermansia, Dialister, and Asteroleplasma, was significantly and positively correlated with the sociability scores in the macaques. In addition, Oscillospiraceae exhibited a positive correlation with scores for Shy Dimension. Furthermore, we found that the predicted functional genes for propionate and pyruvate, porphyrin and chlorophyll metabolic pathways related to animal behavior, were significant enriched in shyness group. We propose that the gut microbiome may play an important role in the formation of personality of Tibetan macaques.

Characteristics and immune functions of the endogenous CRISPR-Cas systems in myxobacteria.

The clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) system widely occurs in prokaryotic organisms to recognize and destruct genetic invaders. Systematic collation and characterization of endogenous CRISPR-Cas systems are conducive to our understanding and potential utilization of this natural genetic machinery. In this study, we screened 39 complete and 692 incomplete genomes of myxobacteria using a combined strategy to dispose of the abridged genome information and revealed at least 19 CRISPR-Cas subtypes, which were distributed with a taxonomic difference and often lost stochastically in intraspecies strains. The cas genes in each subtype were evolutionarily clustered but deeply separated, while most of the CRISPRs were divided into four types based on the motif characteristics of repeat sequences. The spacers recorded in myxobacterial CRISPRs were in high G+C content, matching lots of phages, tiny amounts of plasmids, and, surprisingly, massive organismic genomes. We experimentally demonstrated the immune and self-target immune activities of three endogenous systems in Myxococcus xanthus DK1622 against artificial genetic invaders and revealed the microhomology-mediated end-joining mechanism for the immunity-induced DNA repair but not homology-directed repair. The panoramic view and immune activities imply potential omnipotent immune functions and applications of the endogenous CRISPR-Cas machinery. IMPORTANCE: Serving as an adaptive immune system, clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) empower prokaryotes to fend off the intrusion of external genetic materials. Myxobacteria are a collective of swarming Gram-stain-negative predatory bacteria distinguished by intricate multicellular social behavior. An in-depth analysis of their intrinsic CRISPR-Cas systems is beneficial for our understanding of the survival strategies employed by host cells within their environmental niches. Moreover, the experimental findings presented in this study not only suggest the robust immune functions of CRISPR-Cas in myxobacteria but also their potential applications.

The bi-directional relationships between diversified leisure activity participation and cognitive function in older adults in China: separating between-person effects from within-person effects.

OBJECTIVE: To examine the bi-directorial association between diversified leisure activity participation and cognitive function over a 7-year period. METHODS: Data analyzed was from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a large-scale longitudinal national study. The baseline survey was conducted in 2011 with follow-up every three years. We traced a total of 2718 participants over a period of 7 years. We used adjusted random intercept cross-lagged panel models (RI-CLPMs) to examine the bi-directorial associations between diversified leisure activity participation and cognitive function. RESULTS: We observed bi-directorial associations between diversity of leisure activity and cognitive function across waves at the between-person and within-person levels. The adjusted random intercept cross-lagged panel models fitted the data appropriately, and the 3-year cross-lagged effects of prior diversified leisure activity participation on cognitive function (ß = 0.058, p < 0.01) and cognitive function on subsequent diversified leisure activity participation (ß = 0.047, p < 0.05) were significant. The results remained after adjusting the model for baseline sex, age, educational level, marital status and current residence, the number of chronic diseases, ADL, depressive symptoms, sleep quality, smoking, and drinking. CONCLUSION: This study suggests that a reciprocal causality relationship between diversified leisure activity participation and cognitive function, indicating a "positive circle" that further promotes cognition over time.

Rapid in-situ aerobic biodegradation of high salt and oily food waste employing constructed synthetic microbiome.

The high salt content of food waste (FW) severely limits microbial physiological activity and reduces its biodegradability. In this study, a salt-tolerant thermophilic bacterial agent that consists of four different substrate degradation functional strains was evaluated for efficient high salt and oily FW in solid-state aerobic biodegradation disposers. The phy-chemical properties, enzyme activities, microbial community structure, and function during the biodegradation process were evaluated under high salt (5%) stress. The results showed that the agent promoted the degradation rate, increased the matrix temperature, decreased the moisture content (MC), and enhanced enzyme activities without putrid smell. High-throughput sequencing indicated community structure succession between different groups and the positive contribution of the inoculated functional strains. During the FW biodegradation process, the Bacillus sp. inoculated was the dominant genus in the agent group. Furthermore, CCA further confirmed the positive effects of the four inoculated strains on high salt and oily FW aerobic biodegradation. Functional prediction and metabolite results both confirmed that the agent was more efficient in carbon, amino acid, and lipid metabolism, which demonstrated that the synthetic microbial consortium holds a potential advantage for efficiency and subsequent resource utilization for organic fertilizer.

Addressing adsorption and catalysis of lithium polysulfide via electronic distribution of molybdenum carbide host.

Heterostructure engineering is considered a crucial strategy to modulate the intrinsic charge transfer behavior of materials, enhance catalytic activity, and optimize sulfur electrochemical processes. However, parsing the role of heterogeneous interface-structure-property relationships in heterostructures is still a key scientific issue to realize the efficient catalytic conversion of polysulfides. Based on this, molybdenum carbide (Mo2C) was successfully partial reduced to molybdenum metal (Mo) via a thermal reduction at high-temperature and the typical Mo-Mo2C-based Mott-Schottky heterostructures were simultaneously constructed, which realized the modulation of the electronic structure of Mo2C and optimized the conversion process of lithium polysulfides (LPS). Compared with single molybdenum carbide, the modulated molybdenum carbide acts as an electron donor with stronger Mo-S bonding strength as well as higher polysulfide adsorption energy, faster Li2S conversion kinetics, and greatly facilitates the adsorption → catalysis process of LPS. As a result, yolk-shell Mo-Mo2C heterostructure (C@Mo-Mo2C) exhibits excellent cycling performance as a sulfur host, with a discharge specific capacity of 488.41 mAh g-1 for C@Mo-Mo2C/S at 4 C and present an excellent high-rate cyclic performance accompanied by capacity decay rate of 0.08 % per cycle after 400 cycles at 2 C. Heterostructure-acting Mo2C electron distribution modulation engineering may contributes to the understanding of the structure-interface-property interaction law in heterostructures and further enables the efficient modulation of the chemical behavior of sulfur.

Role of maternal-fetal immune tolerance in the establishment and maintenance of pregnancy.

ABSTRACT: Normal pregnancy is a contradictory and complicated physiological process. Although the fetus carries the human leukocyte antigen (HLA) inherited from the paternal line, it does not cause maternal immune rejection. As the only exception to immunological principles, maternal-fetal immune tolerance has been a reproductive immunology focus. In early pregnancy, fetal extravillous trophoblast cells (EVTs) invade decidual tissues and come into direct contact with maternal decidual immune cells (DICs) and decidual stromal cells (DSCs) to establish a sophisticated maternal-fetal crosstalk. This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal-fetal tolerance based on maternal-fetal crosstalk. Insights into maternal-fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion, pre-eclampsia, and premature birth.

Correction: Establishment of a prediction model for prehospital return of spontaneous circulation in out-of-hospital patients with cardiac arrest.

[This corrects the article on p. 508 in vol. 15, PMID: 37900904.].

A Child With Concomitant Neuroblastoma and IgA Nephropathy: A Case Report and Literature Review.

Concurrent malignancy and IgA nephropathy are rare. Despite the lack of solid experimental evidence, there are theoretical hypotheses of pathophysiology for the development of glomerular damage in cancer patients, like aberrant immune activities. Here, we describe a nine-year-old child who was admitted due to nephrotic syndrome. Abdominal imaging examination accidentally revealed a retroperitoneal tumor, and surgical resection was performed with a pathological diagnosis of neuroblastoma. However, complete removal of the tumor had no impact on the clinical manifestation of nephrotic syndrome, like proteinuria. The use of corticosteroids alone only led to a partial resolution of proteinuria, and resistance developed after one month of treatment. A further kidney biopsy was performed, which suggested IgA nephropathy. Clinical remission of IgA nephropathy was achieved after standard combination treatment of corticosteroids and mycophenolate mofetil for 10 months. This study represented the first case report of neuroblastoma associated with IgA nephropathy. We postulated that IgA nephropathy pathogenesis might be associated with neuroblastoma, though a coincidence of these two conditions cannot be fully excluded. Standard treatment for IgA nephropathy is applicable for patients with concomitant cancer.

Exploring the regulatory role of non-coding RNAs in fiber development and direct regulation of GhKCR2 in the fatty acid metabolic pathway in upland cotton.

Cotton fiber holds immense importance as the primary raw material for the textile industry. Consequently, comprehending the regulatory mechanisms governing fiber development is pivotal for enhancing fiber quality. Our study aimed to construct a regulatory network of competing endogenous RNAs (ceRNAs) and assess the impact of non-coding RNAs on gene expression throughout fiber development. Through whole transcriptome data analysis, we identified differentially expressed genes (DEGs) regulated by non-coding RNA (ncRNA) that were predominantly enriched in phenylpropanoid biosynthesis and the fatty acid elongation pathway. This analysis involved two contrasting phenotypic materials (J02-508 and ZRI015) at five stages of fiber development. Additionally, we conducted a detailed analysis of genes involved in fatty acid elongation, including KCS, KCR, HACD, ECR, and ACOT, to unveil the factors contributing to the variation in fatty acid elongation between J02-508 and ZRI015. Through the integration of histochemical GUS staining, dual luciferase assay experiments, and correlation analysis of expression levels during fiber development stages for lncRNA MSTRG.44818.23 (MST23) and GhKCR2, we elucidated that MST23 positively regulates GhKCR2 expression in the fatty acid elongation pathway. This identification provides valuable insights into the molecular mechanisms underlying fiber development, emphasizing the intricate interplay between non-coding RNAs and protein-coding genes.

Barriers and facilitators to using ophthalmic clinical health services following school vision screening: a mixed-methods study.

OBJECTIVE: To identify determinants of the utilisation of ophthalmic clinical health services among students who failed school vision screening. METHODS: This study employed a sequential explanatory mixed methods design, underpinned by Andersen's Behavioural Model of Health Service Utilisation. Data were initially gathered through interviews with 27 stakeholders-comprising 5 ophthalmologists, 7 community doctors, 7 public health professionals and 8 teachers. The qualitative insights informed the construction of a questionnaire, which subsequently garnered responses from 6215 participants. Qualitative data underwent thematic analysis with NVivo V.12, while quantitative data were analysed using multivariable multinomial logistic regression in SAS V.9.4. Data integration was performed using the Pillar Integration Process for a deductive, evidence-based synthesis of findings. RESULTS: The research revealed that students attending vision demonstration schools and receiving encouragement from schools or communities to access clinical ophthalmic services demonstrated higher adherence to referral (OR=1.66, 95% CI 1.30 to 2.12; OR=1.54, 95% CI 1.33 to 1.80). Conversely, older students and those from higher-income families exhibited lower adherence rates (OR=0.31, 95% CI 0.23 to 0.44; OR=0.34, 95% CI 0.25 to 0.46). Moreover, students with less urgent medical needs were more likely to adhere to referrals compared with those needing immediate referrals (OR=1.24, 95% CI 1.06 to 1.45).Four pillars emerged: (a) adherence decreased with age, (b) financial constraints did not pose an obstacle, (c) public health services played a critical role, (d) referral urgency did not linearly correlate with adherence. CONCLUSION: The utilisation of ophthalmic clinical health services following vision screening failure in students is significantly influenced by public health services provided by schools or communities, such as prompting those with abnormal screening results to access ophthalmic clinical health services.

Centrifugo-Pneumatic Reciprocating Flowing Coupled with a Spatial Confinement Strategy for an Ultrafast Multiplexed Immunoassay.

Immunoassays serve as powerful diagnostic tools for early disease screening, process monitoring, and precision treatment. However, the current methods are limited by high costs, prolonged processing times (>2 h), and operational complexities that hinder their widespread application in point-of-care testing. Here, we propose a novel centrifugo-pneumatic reciprocating flowing coupled with spatial confinement strategy, termed PRCM, for ultrafast multiplexed immunoassay of pathogens on a centrifugal microfluidic platform. Each chip consists of four replicated units; each unit allows simultaneous detection of three targets, thereby facilitating high-throughput parallel analysis of multiple targets. The PRCM platform enables sequential execution of critical steps such as solution mixing, reaction, and drainage by coordinating inherent parameters, including motor rotation speed, rotation direction, and acceleration/deceleration. By integrating centrifugal-mediated pneumatic reciprocating flow with spatial confinement strategies, we significantly reduce the duration of immune binding from 30 to 5 min, enabling completion of the entire testing process within 20 min. As proof of concept, we conducted a simultaneous comparative test on- and off-the-microfluidics using 12 negative and positive clinical samples. The outcomes yielded 100% accuracy in detecting the presence or absence of the SARS-CoV-2 virus, thus highlighting the potential of our PRCM system for multiplexed point-of-care immunoassays.

Research strategies of small molecules as chemotherapeutics to overcome multiple myeloma resistance.

Multiple myeloma (MM), a cancer of plasma cells, is the second most common hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities. Over the past two decades, novel treatment strategies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved the relative survival rate of MM patients. However, the development of drug resistance results in the majority of MM patients suffering from relapse, limited treatment options and uncontrolled disease progression after relapse. There are urgent needs to develop and explore novel MM treatment strategies to overcome drug resistance and improve efficacy. Here, we review the recent small molecule therapeutic strategies for MM, and introduce potential new targets and corresponding modulators in detail. In addition, this paper also summarizes the progress of multi-target inhibitor therapy and protein degradation technology in the treatment of MM.

Interlayer Entropy Engineering Inducing the Symmetry-Broken Layered Oxide Cathodes to Activate Reversible High-Voltage Redox Reaction.

The as-reported doping entropy engineering of electrode materials that are usually realized by the sharing of multiple metal elements with the metal element from the lattice body, potentially has three shortages of stringent synthesis conditions, large active element loss, and serious lattice distortion. Herein, an interlayer entropy engineering of layered oxide cathodes is proposed, where the multiple metal ions are simultaneously intercalated into the same interlayer sites, thus avoiding the three shortages. Concretely, a novel interlayer medium-entropy V2O5 ((MnCoNiMgZn)0.26V2O5∙0.84H2O) is successfully constructed by a one-step hydrothermal method. The interlayer medium-entropy effect is revealed to be that five metal ions pre-intercalation induces the local symmetry-broken [VO6] octahedra in bilayer V2O5, thus activating the reversible high-voltage redox reaction, inhibiting the layer slip and following phase transformation by its pinning effect, and enhancing the charge transfer kinetics. As a result, the medium-entropy cathode realizes the trade-off between specific capacity and structural stability with a discharge capacity of 152 mAh g-1 at 0.1 A g-1 after 100 cycles, and a capacity retention rate of 98.7% at 0.5 A g-1 after 150 cycles for Li+ storage. This engineering provides a new guideline for the rational design of high-performance layered oxide cathodes.

Inhibitory Properties of Cinnamon Bark Oil against Postharvest Pathogen Penicillium digitatum In Vitro.

Penicillium digitatum is a major postharvest pathogen that threatens the global citrus fruit industry and causes great economic losses annually. In the present study, inhibitory properties of cinnamon bark oil (CBO) against P. digitatum in vitro were investigated. Results indicated that 0.03% CBO could efficiently inhibit the spore germination, germ tube elongation, mycelial growth, colonial expansion and conidial accumulation of P. digitatum. The results of fluorescein diacetate (FDA) and MitoTraker Orange (MTO) staining also proved the suppression effects of CBO against P. digitatum. Meanwhile, CBO could inhibit green mold rots induced by P. digitatum in citrus fruit when the working concentration of CBO exceeded 0.06%. In addition, the expressions of 12 genes critical for the growth and virulence of P. digitatum were also significantly regulated under CBO stress. Through a transcriptomic analysis, a total of 1802 common differentially expressed genes (DEGs) were detected in P. digitatum after 4 h and 8 h of CBO treatment. Most of the DEG products were associated with carbohydrate, amino acid and lipid metabolism. They directly or indirectly led to the disturbance of the membrane and the generation of reactive oxygen species (ROS). Our results may deepen the understanding of antifungal properties of CBO against P. digitatum and provide the theoretical foundation to uncover the antifungal mechanism of CBO at the molecular level.

Development and validation of a smartwatch algorithm for differentiating physical activity intensity in health monitoring.

To develop and validate a machine learning based algorithm to estimate physical activity (PA) intensity using the smartwatch with the capacity to record PA and determine outdoor state. Two groups of participants, including 24 adults (13 males) and 18 children (9 boys), completed a sequential activity trial. During each trial, participants wore a smartwatch, and energy expenditure was measured using indirect calorimetry as gold standard. The support vector machine algorithm and the least squares regression model were applied for the metabolic equivalent (MET) estimation using raw data derived from the smartwatch. Exercise intensity was categorized based on MET values into sedentary activity (SED), light activity (LPA), moderate activity (MPA), and vigorous activity (VPA). The classification accuracy was evaluated using area under the ROC curve (AUC). The METs estimation accuracy were assessed via the mean absolute error (MAE), the correlation coefficient, Bland-Altman plots, and intraclass correlation (ICC). A total of 24 adults aged 21-34 years and 18 children aged 9-13 years participated in the study, yielding 1790 and 1246 data points for adults and children respectively for model building and validation. For adults, the AUC for classifying SED, MVPA, and VPA were 0.96, 0.88, and 0.86, respectively. The MAE between true METs and estimated METs was 0.75 METs. The correlation coefficient and ICC were 0.87 (p < 0.001) and 0.89, respectively. For children, comparable levels of accuracy were demonstrated, with the AUC for SED, MVPA, and VPA being 0.98, 0.89, and 0.85, respectively. The MAE between true METs and estimated METs was 0.80 METs. The correlation coefficient and ICC were 0.79 (p < 0.001) and 0.84, respectively. The developed model successfully estimated PA intensity with high accuracy in both adults and children. The application of this model enables independent investigation of PA intensity, facilitating research in health monitoring and potentially in areas such as myopia prevention and control.

Pharmacokinetics and safety of EVER206, a novel polymyxin antimicrobial, in healthy Chinese subjects.

EVER206 (also known as SPR206) is a novel polymyxin analog that has shown in vitro potency and in vivo efficacy against multidrug-resistant (MDR) Gram-negative pathogens. This randomized, double-blinded, placebo-controlled, Phase I study evaluated the safety, tolerability, and pharmacokinetics of EVER206 in healthy Chinese subjects. After single administration of 50-300 mg EVER206, the Cmax ranged from 3.94 to 25.82 mg/L, and the AUC0-inf ranged from 12.42 to 101.67 h·mg/L. The plasma exposure displayed a linear relationship with the dose administered. After administration of 75 and 100 mg of EVER206 every 8 hours (q8 hour), a steady state was achieved on Day 2. The accumulation ratios of Cmax and AUC from Day 1 to Day 7 were in the range of 1.12 to 1.3. The elimination half-lives ranged from 2.86 to 4.32 hours in the single-ascending-dose (SAD) study and 4.71 to 6.18 hours in the multiple-ascending-dose (MAD) study. The urinary excretion of unchanged EVER206 increased with the dose, with the mean cumulative fraction ranging from 23.70% to 47.10%. EVER206 was safe and well-tolerated in Chinese healthy subjects. No severe treatment emerging adverse events (TEAEs), serious adverse events, or TEAEs leading to discontinuation were reported. The results of the present study demonstrated a similar safety profile of EVER206 with data reported in an earlier study on SPR206-101. The exposure of EVER206 in Chinese healthy subjects was higher than that in Australian healthy subjects. These results could enable further clinical development of EVER206 in Chinese patients with severe MDR Gram-negative pathogen infections.CLINICAL TRIALSThis study was registered at the Chinese Clinical Trial Registry under identifier ChiCTR2200056692.

Engineering Photothermal Catalytic CO2 Nanoreactor for Osteomyelitis Treatment by In Situ CO Generation.

Photocatalytic carbon dioxide (CO2) reduction is an effective method for in vivo carbon monoxide (CO) generation for antibacterial use. However, the available strategies mainly focus on utilizing visible-light-responsive photocatalysts to achieve CO generation. The limited penetration capability of visible light hinders CO generation in deep-seated tissues. Herein, a photothermal CO2 catalyst (abbreviated as NNBCs) to achieve an efficient hyperthermic effect and in situ CO generation is rationally developed, to simultaneously suppress bacterial proliferation and relieve inflammatory responses. The NNBCs are modified with a special polyethylene glycol and further embellished by bicarbonate (BC) decoration via ferric ion-mediated coordination. Upon exposure to 1064 nm laser irradiation, the NNBCs facilitated efficient photothermal conversion and in situ CO generation through photothermal CO2 catalysis. Specifically, the photothermal effect accelerated the decomposition of BC to produce CO2 for photothermal catalytic CO production. Benefiting from the hyperthermic effect and in situ CO production, in vivo assessments using an osteomyelitis model confirmed that NNBCs can simultaneously inhibit bacterial proliferation and attenuate the photothermal effect-associated pro-inflammatory response. This study represents the first attempt to develop high-performance photothermal CO2 nanocatalysts to achieve in situ CO generation for the concurrent inhibition of bacterial growth and attenuation of inflammatory responses.

Cadmium aggravates liver injury by activating ferroptosis and neutrophil extracellular traps formation in Nile tilapia (Oreochromis niloticus).

Cadmium (Cd) is a pervasive environmental contaminant and a significant risk factor for liver injury. The present study was undertaken to evaluate the involvement of ferroptosis and neutrophil extracellular traps (NETs) in Cd-induced liver injury in Nile tilapia (Oreochromis niloticus), and to explore its underlying mechanism. Cd-induced liver injury was associated with increased total iron, malondialdehyde (MDA), and Acyl-CoA synthetase long-chain family member 4 (ACSL4), together with reduced levels of glutathione, glutathione peroxidase-4a (Gpx4a), and solute carrier family 7 member 11 (SLC7A11), which are all hallmarks of ferroptosis. Moreover, liver hyperemia, neutrophil infiltration, increased inflammatory factors and myeloperoxidase, as well as elevated serum DNA content in Cd-stimulated Nile tilapia suggested that a considerable number of neutrophils were recruited to the liver. Furtherly, in vitro experiments demonstrated that Cd induced the formation of NETs, and the possible mechanism was related to the generation of reactive oxygen species and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, along with the P38 and extracellular regulated protein kinase (ERK) signaling pathways. We concluded that ferroptosis and NETs are the critical mechanisms contributing to Cd-induced liver injury in Nile tilapia. These findings will contribute to Cd toxicological studies in aquatic animals.

Association of maternal weight gain in early pregnancy with congenital heart disease in offspring: a China birth cohort study.

OBJECTIVES: Little study has reported the association of maternal weight gain in early pregnancy with fetal congenital heart disease (CHD). We aimed to explore the potential relationship based on a China birth cohort while adjusting by multiple factors. DESIGN: Cohort study. SETTING: China birth cohort study conducted from 2017 to 2021. PARTICIPANTS: The study finally included 114 672 singleton pregnancies in the 6-14 weeks of gestation, without missing data or outliers, loss to follow-up or abnormal conditions other than CHD. The proportion of CHD was 0.65% (749 cases). PRIMARY AND SECONDARY OUTCOME MEASURES: Association between maternal pre-pregnancy weight gain and CHD in the offspring were analysed by multivariate logistic regression, with the unadjusted, minimally adjusted and maximally adjusted methods, respectively. RESULTS: The first-trimester weight gain showed similar discrimination of fetal CHD to that period of maternal body mass index (BMI) change (DeLong tests: p=0.091). Compared with weight gain in the lowest quartile (the weight gain less than 0.0 kg), the highest quartile (over 2.0 kg) was associated with a higher risk of fetal CHD in unadjusted (OR 1.36, 95% CI: 1.08 to 1.72), minimally adjusted (adjusted OR (aOR) 1.29, 95% CI: 1.02 to 1.62) and maximally adjusted (aOR 1.29, 95% CI: 1.02 to 1.63) models. The association remains robust in pregnant women with morning sickness, normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with folic acid (FA) and/or multivitamin supplementation. CONCLUSIONS AND RELEVANCE: Although the association of maternal pre-pregnancy weight gain on fetal CHD is weak, the excessive weight gain may be a potential predictor of CHD in the offspring, especially in those with morning sickness and other conditions that are routine in the cohort, such as normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with FA and/or multivitamin supplementation.