Covalent targeted radioligands potentiate radionuclide therapy.

Targeted radionuclide therapy, in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation, has addressed unmet clinical needs and improved outcomes for patients with cancer1-4. A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue, which remains a major challenge5,6. A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution. Here we installed a sulfur (VI) fluoride exchange (SuFEx) chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance. When the engineered radiopharmaceutical binds to the tumour-specific protein, the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the 'click' SuFEx reaction. The application of this strategy to a fibroblast activation protein (FAP) inhibitor (FAPI) triggered more than 80% covalent binding to the protein and almost no dissociation for six days. In mice, SuFEx-engineered FAPI showed 257% greater tumour uptake than did the original FAPI, and increased tumour retention by 13-fold. The uptake in healthy tissues was rapidly cleared. In a pilot imaging study, this strategy identified more tumour lesions in patients with cancer than did other methods. SuFEx-engineered FAPI also successfully achieved targeted ß- and α-radionuclide therapy, causing nearly complete tumour regression in mice. Another SuFEx-engineered radioligand that targets prostate-specific membrane antigen (PSMA) also showed enhanced therapeutic efficacy. Considering the broad scope of proteins that can potentially be ligated to SuFEx warheads, it might be possible to adapt this strategy to other cancer targets.

Meta-ecosystem Frameworks Can Enhance Control of the Biotic Transport of Microplastics.

The lack of systematic approaches and analyses to identify, quantify, and manage the biotic transport of microplastics (MPs) along cross-ecosystem landscapes prevents the current goals of sustainable environmental development from being met. This Perspective proposes a meta-ecosystem framework, which considers organismal and resource flows among ecosystems to shed light on the research and management challenges related to both abiotic and biotic MP transport at landscape levels. We discuss MP transport pathways through species movements and trophic transfers among ecosystems and sub-ecosystems, and highlight these pathways in the mitigation of MP pollution. The integration of biotic pathways across landscapes prioritizes management actions for MP transport using diverse approaches such as wastewater treatment and plastic removal policies to mitigate contamination. In addition, our framework emphasizes the potential sink enhancement of MPs through habitat conservation and enhancement of riparian vegetation. By considering the mechanisms of meta-ecosystem dynamics through the processes of biotic dispersal, accumulation, and the ultimate fate of MPs, advances in the environmental impact assessment and management of MP production can proceed more effectively.

Maternal periconceptional environmental exposure and offspring with congenital heart disease: a case-control study in Guangzhou, China.

BACKGROUND: Congenital heart defects (CHDs) are a major global health problem, yet their crucial environmental risk factors are still unclear. We aimed to explore the associations between maternal periconceptional environmental exposures and all CHDs, isolated and multiple CHDs and CHDs subtypes. METHOD: A case-control study including 675 infants with CHDs and 1545 healthy controls was conducted. Participating mothers who delivered in Guangzhou from October 2019 to November 2021 were recruited. To examine the independent associations between maternal periconceptional environmental exposure and offspring with CHDs, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression model. RESULTS: Maternal exposure to living near main roads [adjusted OR (aOR) = 1.94, 95% CI = 1.06-3.56] and housing renovation (aOR = 1.94, 95% CI = 1.03-3.67) during the periconceptional period were positively related to a greater risk of all CHDs, similar results were also found in isolated CHDs rather than multiple CHDs. Additionally, living near main roads was positively associated with secundum atrial septal defect/patent foramen ovale (aOR = 2.65, 95% CI = 1.03-6.81) and housing renovation was strongly positively associated with ventricular septal defect (aOR = 5.08, 95% CI = 2.05-12.60). However, no association was observed between incense burning and family relationships and all CHDs, isolated and multiple CHDs and CHDs subtypes. CONCLUSION: Living near main roads and housing renovation during the periconceptional period are significantly associated with the increased risks for all CHDs and isolated CHDs. Further study is needed to extend sample size to explore the effects of time and frequency of burning incense and family relationships on CHDs in offspring.

Dietary Zinc, Copper, and Selenium Intake and High-Risk Human Papillomavirus Infection among American Women: Data from NHANES 2011-2016.

Studies have shown that the micronutrients, zinc (Zn), copper (Cu), and selenium (Se) are associated with the HPV-associated cervical cancer, yet between dietary Zn/Cu/Se intake and high-risk HPV (hrHPV) infection remain unclear. We obtained publicly available data in the present cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) performed between 2011 and 2016. Dietary Zn, Cu, and Se intakes were assessed from two 24-h diet recalls. A total of 4628 female with the age of 18-59 years were included in this secondary analysis. Comparing the highest with the lowest quartiles of Zn intake, the adjusted odds ratio (aOR) for hrHPV infection was 0.72 (95% CI, 0.54-0.98). The aOR upon comparison of the quartile three with the lowest quartile of Cu intake was 0.67 (95% CI, 0.50-0.90). Whereas no significant association was found between intakes of Se and hrHPV infection in multivariate analysis. Moreover, compared with those below the Recommended Dietary Allowance (RDA), hrHPV infection risk was significantly decreased among women who met the RDA for Cu (aOR: 0.74; 95% CI = 0.60-0.92), but not for Zn and Se. In conclusion, high dietary Zn and moderate copper intakes were independently and negatively associated with hrHPV infection in addition to Se.

Cascading effects of benthic fish impede reinstatement of clear water conditions in lakes: A mesocosm study.

In shallow eutrophic lakes, submersed macrophytes are essential for maintaining a clear water state, and they are affected markedly by fishes directly through herbivory and indirectly by fish-invertebrate-periphyton complexity, a pathway that presently is not well understood in subtropical lakes but probably vital to lake managements. We conducted a mesocosm study involving benthic fish (Misgurnus anguillicaudatus), snails (Radix swinhoei) and submersed macrophyte (Vallisneria natans), aiming to examine whether benthic fish is detrimental to reestablishment of clear-water macrophyte-dominated state in eutrophic degraded lakes. In addition, we aimed to investigate the cascading effect that benthic fish might have on periphyton and phytoplankton and to what extent snails can alleviate this effect. Our results showed that benthic fish promoted nutrient release from the sediment and thereby facilitated the growth of phytoplankton and periphyton, leading to reduced growth of submerged macrophytes due to shading. Snails consumed the periphyton attached on the leaves of macrophytes, thereby being beneficial to the plant growth, albeit it could not fully counteract the adverse effects from benthic fish. The water quality indicators in terms of nutrients concentrations, phytoplankton biomass and light extinction coefficient along the water column was affected primarily by benthic fish, followed by macrophytes and snails. To target a clear-water condition, the water quality was best at the presence of macrophytes alone or in combination with snails, and worst at the presence of benthic fish. Our results implied that the removal of benthic fish should be a useful ecological restoration method for rehabilitation of submersed macrophytes and water quality improvement in subtropic, eutrophic, shallow lakes following external nutrient loading reduction.

Silica nanoparticles as an enhancer in the IL-1ß-induced inflammation cycle of A549 cells.

Objective: The industrial production and combustion of coal can produce silica nanoparticles (nano-SiO2). It enters the human body mainly through the respiratory tract and exerts a toxic effect. However, whether nano-SiO2 can increase the IL-1ß-induced inflammatory expression in A549 cells has not been tested. Therefore, the synergistic toxicity of nano-SiO2 and IL-1ß to A549 was observed in our study. Materials and methods: We exposed A549 cells to nano-SiO2 (0, 100, 500, and 1000 µg/ml) for 12 and 24 h. The effect of nano-SiO2 on the viability of A549 cells was observed by the CCK-8 method. The A549 cells were exposed to nano-SiO2 (1 mg/mL) and cytokine IL-1ß (10 ng/mL) for 4 h, and we detected the expression of IL-1ß and IL-6 cytokines by real time quantitative polymerase chain (RT-qPCR) and enzyme linked immunosorbent assay (ELISA). The expression of ß-Actin, I-κB, phospho-ERK1/2 (P-ERK1/2), total-ERK1/2 (T-ERK1/2), phospho-JNK (P-JNK), total-JNK (T-JNK), phospho-P38 (P-P38), and total-P38 (T-P38) in A549 cells was detected by the Western Blot method. Results: The nano-SiO2 treatment resulted in a time-dependent decrease in the viability of A549 cells. The synergistic effect of nano-SiO2 and IL-1ß was observed on the new production of IL-1ß and IL-6 in A549 cells. The Western blot results showed that nano-SiO2 can increase the expression of IL-1ß and IL-6 by promoting the phosphorylation of ERK1/2 and elevating the phosphorylation of I-κB by IL-1ß. IL-1ß and IL-6 were induced by nano-SiO2, and the IL-1ß treatment with 20 µM of I-κBα phosphorylation inhibitor (PD98059) and 20 µM of ERK1/2 inhibitor (BAY11-7082) for 1 h was significantly lower than that of the control group in A549 cells. Discussion and conclusion: These results indicated that nano-SiO2 had a toxic effect on A549 cells, and this effect could increase IL-1ß on the A549 cell-induced inflammatory response. The results suggested that the release of IL-1ß and IL-6 in A549 was enhanced by the synergistic IL-1ß-induced phosphorylation of ERK1/2 and I-κB. This process is similar to a snowball, and it is possible that IL-1ß is continuously produced and repeatedly superimposed in A549 cells to produce an inflammatory effect; then, a vicious circle occurs, and an inflammatory storm is accelerated.

Ultrastrong and High Thermal Insulating Porous High-Entropy Ceramics up to 2000 °C.

High mechanical load-carrying capability and thermal insulating performance are crucial to thermal-insulation materials under extreme conditions. However, these features are often difficult to achieve simultaneously in conventional porous ceramics. Here, for the first time, it is reported a multiscale structure design and fast fabrication of 9-cation porous high-entropy diboride ceramics via an ultrafast high-temperature synthesis technique that can lead to exceptional mechanical load-bearing capability and high thermal insulation performance. With the construction of multiscale structures involving ultrafine pores at the microscale, high-quality interfaces between building blocks at the nanoscale, and severe lattice distortion at the atomic scale, the materials with an ≈50% porosity exhibit an ultrahigh compressive strength of up to ≈337 MPa at room temperature and a thermal conductivity as low as ≈0.76 W m-1 K-1. More importantly, they demonstrate exceptional thermal stability, with merely ≈2.4% volume shrinkage after 2000 °C annealing. They also show an ultrahigh compressive strength of ≈690 MPa up to 2000 °C, displaying a ductile compressive behavior. The excellent mechanical and thermal insulating properties offer an attractive material for reliable thermal insulation under extreme conditions.

Butane Tetracarboxylic Acid Grafted on Polymeric Nanofibrous Aerogels for Highly Efficient Protein Absorption and Separation.

Developing high-performance and low-cost protein purification materials is of great importance to meet the demands for highly purified proteins in biotechnological industries. Herein, a facile strategy was developed to design and construct high-efficiency protein absorption and separation media by combining aerogels' molding techniques and impregnation processes. Poly (ethylene-co-vinyl alcohol) (EVOH) nanofibrous aerogels (NFAs) were modified by grafting butane tetracarboxylic acid (BTCA) over them in situ. This modification was carried out using polyphosphoric acid as a catalyst. The resulting EVOH/BTCA NFAs exhibited favorable comprehensive properties. Benefiting from the highly interconnected porous structure, good underwater compressive properties, and abundant absorption ligands, the obtained EVOH/BTCA NFAs possessed a high static absorption capacity of 1082.13 mg/g to lysozyme and a short absorption equilibrium time of about 6 h. A high saturated dynamic absorption capacity for lysozyme (716.85 mg/g) was also realized solely by gravity. Furthermore, EVOH/BTCA NFAs displayed excellent reusability, good acid and alkaline resistance, and unique absorption selectivity performance. The successful synthesis of such aerogels can provide a potential candidate for next-generation protein absorbents for bio-separation and purification engineering.

MICAL-L2, as an estrogen-responsive gene, is involved in ER-positive breast cancer cell progression and tamoxifen sensitivity via the AKT/mTOR pathway.

Endocrine treatment, particularly tamoxifen, has shown significant improvement in the prognosis of patients with estrogen receptor-positive (ER-positive) breast cancer. However, the clinical utility of this treatment is often hindered by the development of endocrine resistance. Therefore, a comprehensive understanding of the underlying mechanisms driving ER-positive breast cancer carcinogenesis and endocrine resistance is crucial to overcome this clinical challenge. In this study, we investigated the expression of MICAL-L2 in ER-positive breast cancer and its impact on patient prognosis. We observed a significant upregulation of MICAL-L2 expression in ER-positive breast cancer, which correlated with a poorer prognosis in these patients. Furthermore, we found that estrogen-ERß signaling promoted the expression of MICAL-L2. Functionally, our study demonstrated that MICAL-L2 not only played an oncogenic role in ER-positive breast cancer tumorigenesis but also influenced the sensitivity of ER-positive breast cancer cells to tamoxifen. Mechanistically, as an estrogen-responsive gene, MICAL-L2 facilitated the activation of the AKT/mTOR signaling pathway in ER-positive breast cancer cells. Collectively, our findings suggest that MICAL-L2 could serve as a potential prognostic marker for ER-positive breast cancer and represent a promising molecular target for improving endocrine treatment and developing therapeutic approaches for this subtype of breast cancer.

Water depth affects submersed macrophyte more than herbivorous snail in mesotrophic lakes.

Introduction: Water depth (WD) and snail abundance (SA) are two key factors affecting the growth of submersed aquatic plants in freshwater lake ecosystems. Changes in WD and SA drive changes in nutrients and other primary producers that may have direct or indirect effects on submersed plant growth, but which factor dominates the impact of both on aquatic plants has not been fully studied. Methods: To investigate the dominant factors that influence aquatic plant growth in plateau lakes, a one-year field study was conducted to study the growth of three dominant submersed macrophyte (i.e., Vallisneria natans, Potamogeton maackianus, and Potamogeton lucens) in Erhai Lake. Results: The results show that, the biomass of the three dominant plants, P.maackianus, is the highest, followed by P.lucens, and V.natans is the lowest. Meanwhile, periphyton and snails attached to P.maackianus are also the highest. Furthermore, WD had a positive effect on the biomass of two submersed macrophyte species of canopy-type P.maackianus and P.lucens, while it had a negative effect on rosette-type V.natans. Snail directly inhibited periphyton attached on V.natans and thereby increasing the biomass of aquatic plants, but the effect of snails on the biomass of the other two aquatic plants is not through inhibition of periphyton attached to their plants. Discussion: The dominant factors affecting the biomass of submersed macrophyte in Erhai Lake were determined, as well as the direct and indirect mechanisms of WD and snails on the biomass of dominant submersed macrophyte. Understanding the mechanisms that dominate aquatic plant change will have implications for lake management and restoration.

Anti-Toxoplasma gondii antibodies as a risk factor for the prevalence and severity of systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the presence of numerous autoantibodies. The interaction of infectious agents (viruses, bacteria and parasites) and a genetically susceptible host may be a key mechanism for SLE. Toxoplasma gondii is a widespread intracellular parasite that has been implicated in the pathogenesis of autoimmune diseases. However, the relationship between T. gondii infection and the increased risk of SLE in Chinese populations remains unclear. METHODS: The seroprevalence of T. gondii infection was assessed in 1771 serum samples collected from Chinese individuals (908 healthy controls and 863 SLE patients) from different regions of China using an enzyme-linked immunosorbent assay. Serum autoantibodies and clinical information were obtained and analysed. RESULTS: Our observations revealed a higher prevalence of anti-T. gondii antibodies (ATxA) immunoglobulin G (IgG) in serum samples from SLE patients (144/863, 16.7%) than in those from the healthy controls (53/917, 5.8%; P < 0.0001), indicating a 2.48-fold increased risk of SLE in the ATxA-IgG+ population, after adjustment for age and sex (95% confidence interval [CI] 1.70-3.62, P < 0.0001). ATxA-IgG+ SLE patients also showed a 1.75-fold higher risk of developing moderate and severe lupus symptoms (95% CI 1.14-2.70, P = 0.011) compared to ATxA-IgG- patients. Relative to ATxA-IgG- patients, ATxA-IgG+ patients were more likely to develop specific clinical symptoms, including discoid rash, oral ulcer, myalgia and alopecia. Seven antibodies, namely anti-ribosomal RNA protein (rRNP), anti-double stranded DNA (dsDNA), anti-cell membrane DNA (cmDNA), anti-scleroderma-70 (Scl-70), anti-cardiolipin (CL), anti-beta2-glycoprotein-I (B2GPI) and rheumatoid factor (RF), occurred more frequently in ATxA-IgG+ patients. When combined with anti-dsDNA and RF/anti-rRNP/anti-cmDNA/ESR, ATxA-IgG significantly increased the risk for severe lupus. CONCLUSIONS: Our results suggest that ATxA-IgG may be a significant risk factor for SLE prevalence and severity in Chinese populations.

The Spherical Evolutionary Multi-Objective (SEMO) Algorithm for Identifying Disease Multi-Locus SNP Interactions.

Single-nucleotide polymorphisms (SNPs), as disease-related biogenetic markers, are crucial in elucidating complex disease susceptibility and pathogenesis. Due to computational inefficiency, it is difficult to identify high-dimensional SNP interactions efficiently using combinatorial search methods, so the spherical evolutionary multi-objective (SEMO) algorithm for detecting multi-locus SNP interactions was proposed. The algorithm uses a spherical search factor and a feedback mechanism of excellent individual history memory to enhance the balance between search and acquisition. Moreover, a multi-objective fitness function based on the decomposition idea was used to evaluate the associations by combining two functions, K2-Score and LR-Score, as an objective function for the algorithm's evolutionary iterations. The performance evaluation of SEMO was compared with six state-of-the-art algorithms on a simulated dataset. The results showed that SEMO outperforms the comparative methods by detecting SNP interactions quickly and accurately with a shorter average run time. The SEMO algorithm was applied to the Wellcome Trust Case Control Consortium (WTCCC) breast cancer dataset and detected two- and three-point SNP interactions that were significantly associated with breast cancer, confirming the effectiveness of the algorithm. New combinations of SNPs associated with breast cancer were also identified, which will provide a new way to detect SNP interactions quickly and accurately.

Ultrasound meets the cell membrane: for enhanced endocytosis and drug delivery.

Endocytosis plays a crucial role in drug delivery for precision therapy. As a non-invasive and spatiotemporal-controllable stimulus, ultrasound (US) has been utilized for improving drug delivery efficiency due to its ability to enhance cell membrane permeability. When US meets the cell membrane, the well-known cavitation effect generated by US can cause various biophysical effects, facilitating the delivery of various cargoes, especially nanocarriers. The comprehension of recent progress in the biophysical mechanism governing the interaction between ultrasound and cell membranes holds significant implications for the broader scientific community, particularly in drug delivery and nanomedicine. This review will summarize the latest research results on the biological effects and mechanisms of US-enhanced cellular endocytosis. Moreover, the latest achievements in US-related biomedical applications will be discussed. Finally, challenges and opportunities of US-enhanced endocytosis for biomedical applications will be provided.

Interphase Engineering for Stabilizing Ni-Rich Cathode in Lithium-Ion Batteries by a Nucleophilic Reaction-Based Additive.

Ni-rich cathode materials are considered promising candidates for next-generation lithium-ion batteries because of their high energy density and low cost. However, interphase failure at the surface of Ni-rich cathodes negatively impacts cycling performance, making it challenging to meet the requirements of long-term applications. In this study, a strategy is developed to improve interphase properties through introduction of a nucleophilic reaction-based additive, using an appropriate amount of the inducer lithium isopropoxide (LIP) in the commercial electrolyte to achieve long-term cycling stability of Li||LiNi0.83 Co0.11 Mn0.06 O2 (NCM83) cells. This strategy enables Li||NCM83 cells to maintain a capacity of 148.7 mAh g-1 with a retention of 83.3 % even after 500 cycles. This outstanding cycling stability is attributed to a robust cathode-electrolyte interphase (CEI) constructed on NCM83 surface LIP-induce ring-opening polymerization of ethylene carbonate (EC). As a result, the organic-inorganic components of the CEI effectively constrain gas evolution and the corresponding phase transformation behavior. Furthermore, the CEI also suppresses microcrack formation and eventually sustains the Ni valence and coordination environment at high voltage.

How does turions production of Potamogeton crispus L. respond to parental population biomass and living environment.

Turions production is the dominant means of propagation in Potamogeton crispus L. To understand how parental population and their living environmental factors influence the turions production of P. crispus L., a field research was conducted in Nansi Lake in Yellow River Flood Plain and southwestern Shandong Province, China. This study showed that P. crispus biomass and asexual turions showed an almost uniform spatial distribution pattern. Water depth, attenuation coefficient of light, sediment water content, sediment organic matter content, and pH were significantly related to P. crispus biomass, turions weight, and turions number. Single turion weight was determined only by P. crispus biomass, while turions number was simultaneously determined by P. crispus biomass and sediment water content. Turions weight mainly depended on turions number rather than single turion weight, and maternal biomass and sediment water content determined turions weight by affected turions number rather than single turion weight.

Laser Ablation Mechanism and Performance of Carbon Fiber-Reinforced Poly Aryl Ether Ketone (PAEK) Composites.

The ablation mechanism and performance of carbon fiber (CF)-reinforced poly aryl ether ketone (PAEK) thermoplastic composites were studied in this paper. The results show that the ablation damaged area is controlled by the irradiation energy, while the mass loss rate is controlled by the irradiation power density. In the ablation center, the PAEK resin and CFs underwent decomposition and sublimation in an anaerobic environment. In the transition zone, the resin experienced decomposition and remelting in an aerobic environment, and massive char leaves were present in the cross section. In the heat-affected zone, only remelting of the resin was observed. The fusion and decomposition of the resin caused delamination and pores in the composites. Moreover, oxygen appeared crucial to the ablation morphology of CFs. In an aerobic environment, a regular cross section formed, while in an anaerobic environment, a cortex-core structure formed. The cortex-core structure of CF inside the ablation pit was caused by the inhomogeneity of fibers along the radial direction and the residual carbon layer generated by resin decomposition in an anoxic environment. The description of the ablation mechanism presented in this study broadens our understanding of damage evolution in thermoplastic composites subjected to high-energy CW laser irradiation.

Discovery of Pyridone-Substituted Triazolopyrimidine Dual A2A/A1 AR Antagonists for the Treatment of Ischemic Stroke.

Ischemic stroke is a complex systemic disease characterized by high morbidity, disability, and mortality. The activation of the presynaptic adenosine A2A and A1 receptors modifies a variety of brain insults from excitotoxicity to stroke. Therefore, the discovery of dual A2A/A1 adenosine receptor (AR)-targeting therapeutic compounds could be a strategy for the treatment of ischemic stroke. Inspired by two clinical phase III drugs, ASP-5854 (dual A2A/A1 AR antagonist) and preladenant (selective A2A AR antagonist), and using the hybrid medicinal strategy, we characterized novel pyridone-substituted triazolopyrimidine scaffolds as dual A2A/A1 AR antagonists. Among them, compound 1a exerted excellent A2A/A1 AR binding affinity (K i = 5.58/24.2 nM), an antagonistic effect (IC50 = 5.72/25.9 nM), and good metabolic stability in human liver microsomes, rat liver microsomes, and dog liver microsomes. Importantly, compound 1a demonstrated a dose-effect relationship in the oxygen-glucose deprivation/reperfusion (OGD/R)-treated HT22 cell model. These findings support the development of dual A2A/A1 AR antagonists as a potential treatment for ischemic stroke.

Interpregnancy interval and subsequent perinatal risk of congenital heart disease in Guangzhou, Southern China: a retrospective cohort study, 2014-2019.

BACKGROUND: The association between maternal interpregnancy interval (IPI) and congenital heart disease (CHD) in neonates remains inconclusive. This study aimed to examine the effect of maternal IPI on birth risk of CHD. METHODS: Chinese women with two consecutive singleton deliveries in Guangzhou between January 2014 and December 2019 were selected as participants. Information on IPI and CHD was extracted from the Guangzhou Perinatal Health Care and Delivery Registry and the Guangzhou Birth Defects Surveillance Program. We stratified IPI into four categories: <24 months, 24-35 months, 36-59 months, and ≥60 months. A multivariate logistic regression model was used to examine the association between IPI and CHD. Subgroup analysis was also performed to assess whether the associations differed across top three CHD subtypes. RESULTS: For 119,510 women enrolled in this study, the mean ages at two consecutive deliveries were 26.2 ± 3.8 and 28.8 ± 4.0 years, which yielded a median IPI of 51.2 (interquartile range, 32.1-77.2) months. Among them, 828 delivered infants with CHD during their second pregnancy. There was a J-shaped curve relationship between IPI and CHD with the lowest birth prevalence (5.33‰) at 24-35-month interval. Compared to women with an IPI of 24-35 months, those with an IPI ≥60 had an increased risk of delivering infants with CHD (adjusted odds ratio (OR), 1.41; 95% confidence interval (CI), 1.19-1.64). However, for those with an IPI <24 months (adjusted OR, 1.24; 95% CI, 0.97-1.51), IPI was statistically insignificant associated with the risk of delivering infants with CHD (p = .12). There were different patterns of associations for different CHD subtypes. CONCLUSIONS: Longer maternal IPI (≥60 months) was associated with an increased risk of delivering infants with CHD in the Chinese population.

Biodiversity buffers the impact of eutrophication on ecosystem functioning of submerged macrophytes on the Yunnan-Guizhou Plateau, Southwest China.

Increasing eutrophication poses a considerable threat to freshwater ecosystems, which are closely associated with human well-being. As important functional entities for freshwater ecosystems, submerged macrophytes have suffered rapidly decline with eutrophication. However, it is unclear whether and how submerged macrophytes maintain their ecological functions under increasing eutrophication stress and the underlying patterns in the process. In the current study, we conducted an extensive survey of submerged macrophytes in 49 lakes and reservoirs (67% of them are eutrophic) on the Yunnan-Guizhou Plateau of southwestern China to reveal the relationship between submerged macrophyte biodiversity and ecosystem functioning (BEF) under eutrophication stress. Results showed that submerged macrophytes species richness, functional diversity (FD), and ß diversity had positive effects on ecosystem functioning, even under eutrophication. Functional diversity was a stronger predictor of community biomass than species richness and ß diversity, while species richness explained higher coverage variability than FD and ß diversity. This suggests that species richness was a reliable indicator when valid functional traits cannot be collected in considering specific ecological process. With increasing eutrophication in water bodies, the mechanisms underlying biodiversity-ecosystem functioning evolved from "niche complementarity" to "selection effects", as evidenced by decreased species turnover and increased nestedness. Furthermore, the relative growth rate, specific leaf area, and ramet size in trade-off of community functional composition became smaller along eutrophication while flowering duration and shoot height became longer. This study contributes to a better understanding of positive BEF in freshwater ecosystems, despite increasing anthropogenic impacts. Protecting the environment remained the effective way to protect biodiversity and corresponding ecological functions and services. It will be important to consider different facets of biodiversity on ecosystem functioning in future studies to improve effective management plans.

Seasonal patterns of taxonomic and functional beta diversity in submerged macrophytes at a fine scale.

Spatiotemporal variation in community composition is of considerable interest in ecology. However, few studies have focused on seasonal variation patterns in taxonomic and functional community composition at the fine scale. As such, we conducted seasonal high-density sampling of the submerged macrophyte community in Hongshan Bay of Erhai Lake in China and used the generalized dissimilarity model (GDM) to evaluate the effects of environmental factors and geographic distance on taxonomic and functional beta diversity as well as corresponding turnover and nestedness components. At the fine scale, taxonomic turnover and nestedness as well as functional turnover and nestedness showed comparable contributions to corresponding taxonomic and functional beta diversity, with different importance across seasons. All taxonomic and functional dissimilarity metrics showed seasonal variation. Of note, taxonomic beta diversity was highest in summer and lowest in winter, while functional beta diversity showed the opposite pattern. Taxonomic and functional turnover showed similar change patterns as taxonomic and functional beta diversity. Taxonomic nestedness was low in summer and high in winter. Functional nestedness was also lower in summer. These results suggest that under extreme environmental conditions, both turnover and nestedness can exist at the fine scale and seasonal community composition patterns in submerged macrophytes should be considered. Future investigations on community assembly mechanisms should pay greater attention to long-term dynamic characteristics and functional information.