Primary Cilium-Autophagy-Nrf2 (PAN) Axis Activation Commits Human Embryonic Stem Cells to a Neuroectoderm Fate.

Under defined differentiation conditions, human embryonic stem cells (hESCs) can be directed toward a mesendoderm (ME) or neuroectoderm (NE) fate, the first decision during hESC differentiation. Coupled with lineage-specific G1 lengthening, a divergent ciliation pattern emerged within the first 24 hr of induced lineage specification, and these changes heralded a neuroectoderm decision before any neural precursor markers were expressed. By day 2, increased ciliation in NE precursors induced autophagy that resulted in the inactivation of Nrf2 and thereby relieved transcriptional activation of OCT4 and NANOG. Nrf2 binds directly to upstream regions of these pluripotency genes to promote their expression and repress NE derivation. Nrf2 suppression was sufficient to rescue poorly neurogenic iPSC lines. Only after these events had been initiated did neural precursor markers get expressed at day 4. Thus, we have identified a primary cilium-autophagy-Nrf2 (PAN) control axis coupled to cell-cycle progression that directs hESCs toward NE.

Loss of the m6A methyltransferase METTL3 in monocyte-derived macrophages ameliorates Alzheimer's disease pathology in mice.

Alzheimer's disease (AD) is a heterogeneous disease with complex clinicopathological characteristics. To date, the role of m6A RNA methylation in monocyte-derived macrophages involved in the progression of AD is unknown. In our study, we found that methyltransferase-like 3 (METTL3) deficiency in monocyte-derived macrophages improved cognitive function in an amyloid beta (Aß)-induced AD mouse model. The mechanistic study showed that that METTL3 ablation attenuated the m6A modification in DNA methyltransferase 3A (Dnmt3a) mRNAs and consequently impaired YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-mediated translation of DNMT3A. We identified that DNMT3A bound to the promoter region of alpha-tubulin acetyltransferase 1 (Atat1) and maintained its expression. METTL3 depletion resulted in the down-regulation of ATAT1, reduced acetylation of α-tubulin and subsequently enhanced migration of monocyte-derived macrophages and Aß clearance, which led to the alleviated symptoms of AD. Collectively, our findings demonstrate that m6A methylation could be a promising target for the treatment of AD in the future.

SOCS3 regulates pathological retinal angiogenesis through modulating SPP1 expression in microglia and macrophages.

Pathological ocular angiogenesis has long been associated with myeloid cell activation. However, the precise cellular and molecular mechanisms governing the intricate crosstalk between the immune system and vascular changes during ocular neovascularization formation remain elusive. In this study, we demonstrated that the absence of the suppressor of cytokine signaling 3 (SOCS3) in myeloid cells led to a substantial accumulation of microglia and macrophage subsets during the neovascularization process. Our single-cell RNA sequencing data analysis revealed a remarkable increase in the expression of the secreted phosphoprotein 1 (Spp1) gene within these microglia and macrophages, identifying subsets of Spp1-expressing microglia and macrophages during neovascularization formation in angiogenesis mouse models. Notably, the number of Spp1-expressing microglia and macrophages exhibited further elevation during neovascularization in mice lacking myeloid SOCS3. Moreover, our investigation unveiled the Spp1 gene as a direct transcriptional target gene of signal transducer and activator of transcription 3. Importantly, pharmaceutical activation of SOCS3 or blocking of SPP1 resulted in a significant reduction in pathological neovascularization. In conclusion, our study highlights the pivotal role of the SOCS3/STAT3/SPP1 axis in the regulation of pathological retinal angiogenesis.

Restoration of atypical protein kinase C ζ function in autosomal dominant polycystic kidney disease ameliorates disease progression.

Autosomal dominant polycystic kidney disease (ADPKD) affects more than 500,000 individuals in the United States alone. In most cases, ADPKD is caused by a loss-of-function mutation in the PKD1 gene, which encodes polycystin-1 (PC1). Previous studies reported that PC1 interacts with atypical protein kinase C (aPKC). Here we show that PC1 binds to the ζ isoform of aPKC (PKCζ) and identify two PKCζ phosphorylation sites on PC1's C-terminal tail. PKCζ expression is down-regulated in patients with ADPKD and orthologous and nonorthologous PKD mouse models. We find that the US Food and Drug Administration-approved drug FTY720 restores PKCζ expression in in vitro and in vivo models of polycystic kidney disease (PKD) and this correlates with ameliorated disease progression in multiple PKD mouse models. Importantly, we show that FTY720 treatment is less effective in PKCζ null versions of these PKD mouse models, elucidating a PKCζ-specific mechanism of action that includes inhibiting STAT3 activity and cyst-lining cell proliferation. Taken together, our results reveal that PKCζ down-regulation is a hallmark of PKD and that its stabilization by FTY720 may represent a therapeutic approach to the treat the disease.

An All-In-One Integrating Strategy for Designing Platinum(II)-Based Supramolecular Polymers for Photocatalytic Hydrogen Evolution.

Organic polymer photocatalysts have achieved significant progress in photocatalytic hydrogen evolution, while developing the integrated organic polymers possessing the functions of photosensitizer, electron transfer mediator, and catalyst simultaneously is urgently needed and presents a great challenge. Considering that chalcogenoviologens are able to act as photosensitizers and electron-transfer mediators, a series of chalcogenoviologen-containing platinum(II)-based supramolecular polymers is designed, which exhibited strong visible light-absorbing ability and suitable bandgap for highly efficient photocatalytic hydrogen evolution without the use of a cocatalyst. The hydrogen evolution rate (HER) increases steadily with the decrease in an optical gap of the polymer. Among these "all-in-one" polymers, Se-containing 2D porous polymer exhibited the best photocatalytic performance with a HER of 3.09 mmol g-1 h-1 under visible light (>420 nm) irradiation. Experimental and theoretical calculations reveal that the distinct intramolecular charge transfer characteristics and heteroatom N in terpyridine unit promote charge separation and transfer within the molecules. This work could provide new insights into the design of metallo-supramolecular polymers with finely tuned components for photocatalytic hydrogen evolution from water.

OptiComm-GPT: a GPT-based versatile research assistant for optical fiber communication systems.

With the increasing capacity and complexity of optical fiber communication systems, both academic and industrial requirements for the essential tasks of transmission systems simulation, digital signal processing (DSP) algorithms verification, system performance evaluation, and quality of transmission (QoT) optimization are becoming significantly important. However, due to the intricate and nonlinear nature of optical fiber communication systems, these tasks are generally implemented in a divide-and-conquer manner, which necessitates a profound level of expertise and proficiency in software programming from researchers or engineers. To lower this threshold and facilitate professional research easy-to-start, a GPT-based versatile research assistant named OptiComm-GPT is proposed for optical fiber communication systems, which flexibly and automatically performs system simulation, DSP algorithms verification, performance evaluation, and QoT optimization with only natural language. To enhance OptiComm-GPT's abilities for complex tasks in optical fiber communications and improve the accuracy of generated results, a domain information base containing rich domain knowledge, tools, and data as well as the comprehensive prompt engineering with well-crafted prompt elements, techniques, and examples is established and performs under a LangChain-based framework. The performance of OptiComm-GPT is evaluated in multiple simulation, verification, evaluation, and optimization tasks, and the generated results show that OptiComm-GPT can effectively comprehend the user's intent, accurately extract system parameters from the user's request, and intelligently invoke domain resources to solve these complex tasks simultaneously. Moreover, the statistical results, typical errors, and running time of OptiComm-GPT are also investigated to illustrate its practical reliability, potential limitations, and further improvements.

Gut microbial features may influence antiviral IgG levels after vaccination against viral respiratory infectious diseases: the evidence from two-sample bidirectional mendelian randomization.

BACKGROUND: Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels. METHODS: We conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels. To make the results more reliable, we used four robust methods and performed comprehensive sensitivity analyses. RESULTS: The MR analyses revealed 26, 13, 20, and 18 causal associations of the gut microbial features influencing four IgG levels separately. ​Interestingly, ten microbial features, like genus Collinsella, species Bifidobacterium longum, and the biosynthesis of L-alanine have shown the capacity to regulate multiple IgG levels with consistent direction (rise or fall). The ​reverse MR analysis suggested several potential causal associations of IgG levels affecting microbial features. CONCLUSIONS: The human immune response against viral respiratory infectious diseases could be modulated by changing the abundance of gut microbes, which provided new approaches for the intervention of viral respiratory infections.

Maternal age-specific risks for adverse birth weights according to gestational weight gain: a prospective cohort in Chinese women older than 30.

BACKGROUND: It is unclear whether the effects of abnormal gestational weight gain (GWG) on birth outcomes are differently in women with different maternal ages. This study aimed to investigate maternal age-specific association between GWG and adverse birth weights in Chinese women older than 30. METHODS: 19,854 mother-child dyads were selected from a prospective cohort study in Southwest China between 2019 and 2022. Logistic regression model was used to assess the association between GWG, which defined by the 2009 Institute of Medicine guidelines, and adverse birth weights including large- and small-for-gestational-age (LGA and SGA), stratified by maternal age (31-34 years and ≥ 35 years). RESULTS: In both maternal age groups, excessive and insufficient GWG were associated with increased odds of LGA and SGA, respectively. After women were categorized by pre-pregnancy body mass index, the associations remained significant in women aged 31-34 years, whereas for women aged ≥ 35 years, the association between excessive GWG and the risk of LGA was only significant in normal weight and overweight/obese women, and the significant effect of insufficient GWG on the risk of SGA was only observed in underweight and overweight/obese women. Moreover, among overweight/obese women, the magnitude of the association between insufficient GWG and the risk of SGA was greater in those aged ≥ 35 years (31-34 years: OR 2.08, 95% CI 1.19-3.55; ≥35 years: OR 2.65, 95% CI 1.47-4.74), while the impact of excessive GWG on the risk of LGA was more pronounced in those aged 31-34 years (31-34 years: OR 2.18, 95% CI 1.68-2.88; ≥35 years: OR 1.71, 95% CI 1.30-2.25). CONCLUSIONS: The stronger associations between abnormal GWG and adverse birth weights were mainly observed in women aged 31-34 years, and more attention should be paid to this age group.

Six-month binocular stereopsis recovery and its influencing factors in children with intermittent exotropia.

OBJECTIVE: To investigate the recovery of binocular stereopsis recovery and its influencing factors in children with intermittent exotropia after successful correction of eye position. METHODS: Prospective clinical study. A total of 178 patients, aged 9 ∼ 14 (10.8 ± 1.7) years, who were successfully corrected after intermittent exotropia surgery at the Beijing Tongren Hospital Affiliated to Capital Medical University from October 2023 to September 2023 were collected, the follow-up duration was six-month or longer. Paired t test, Pearson correlation analysis and multivariable linear regression analysis were used to probe preoperative clinical features that may predict the stereopsis six months after surgery. RESULTS: Six months after surgery, the angle of deviation of the patients met the orthotopic standard, and there was significant difference compared with that before surgery (distant: -2.7△±3.2△ vs. -30.5△±8.4△, t=-25.3, P < 0.001. Near:-3.7△±4.1△ vs. -33.7△±8.0△, t=-26.1, P < 0.001). Distant stereopsis (3.0 ± 0.6 vs. 3.9 ± 0.4, t = 4.9, P < 0.05) and near stereopsis (2.3 ± 0.5 vs. 2.6 ± 0.4, t = 3.8, P < 0.05) were both significantly improved compared with that of before surgery. 17% and 22% patients rebuilt normal distant stereopsis and normal near stereopsis, respectively. Preoperative distant stereopsis (r=-0.26, P = 0.004) and near stereopsis (r=-0.23, P = 0.011) was significantly negatively correlated with convergence reserve. Multivariable analysis showed that patients' age (ß = 0.003, p = 0.037), anisometropia (ß = 0.015, p = 0.043), and preoperative distant stereopsis (ß = 0.456, p < 0.001) were significantly associated with postoperative distant stereopsis. Patients' age (ß = 0.005, p = 0.044), anisometropia (ß = 0.127, p = 0.034), angle of deviation (ß=-0.230, p = 0.020), and preoperative near stereopsis (ß = 0.136, p < 0.001) were significantly associated with postoperative near stereopsis. CONCLUSION: IXT patients could get eye position fixed after surgery, about 20% patients benefited from stereopsis improvement. Patient's age, binocular anisometropia, angle of deviation and preoperative stereopsis were independent factors influencing postoperative stereopsis.

Early role for a Na+,K+-ATPase (ATP1A3) in brain development.

Osmotic equilibrium and membrane potential in animal cells depend on concentration gradients of sodium (Na+) and potassium (K+) ions across the plasma membrane, a function catalyzed by the Na+,K+-ATPase α-subunit. Here, we describe ATP1A3 variants encoding dysfunctional α3-subunits in children affected by polymicrogyria, a developmental malformation of the cerebral cortex characterized by abnormal folding and laminar organization. To gain cell-biological insights into the spatiotemporal dynamics of prenatal ATP1A3 expression, we built an ATP1A3 transcriptional atlas of fetal cortical development using mRNA in situ hybridization and transcriptomic profiling of ∼125,000 individual cells with single-cell RNA sequencing (Drop-seq) from 11 areas of the midgestational human neocortex. We found that fetal expression of ATP1A3 is most abundant to a subset of excitatory neurons carrying transcriptional signatures of the developing subplate, yet also maintains expression in nonneuronal cell populations. Moving forward a year in human development, we profiled ∼52,000 nuclei from four areas of an infant neocortex and show that ATP1A3 expression persists throughout early postnatal development, most predominantly in inhibitory neurons, including parvalbumin interneurons in the frontal cortex. Finally, we discovered the heteromeric Na+,K+-ATPase pump complex may form nonredundant cell-type-specific α-ß isoform combinations, including α3-ß1 in excitatory neurons and α3-ß2 in inhibitory neurons. Together, the developmental malformation phenotype of affected individuals and single-cell ATP1A3 expression patterns point to a key role for α3 in human cortex development, as well as a cell-type basis for pre- and postnatal ATP1A3-associated diseases.

Assessment of Measurement Uncertainty for S-Parameter Measurement Based on Covariance Matrix.

S-parameters are widely used to detail the scattering parameters of radio frequency (RF) components and microwave circuit modules. The vector network analyzer (VNA) is the most commonly used device for measuring S-parameters. Given the multiple frequency points, complex values, and intricate uncertainty propagation involved, accurately assessing the uncertainty of S-parameter measurements is difficult. In this study, we proposed a new method for assessing S-parameter uncertainty based on the covariance matrices, tracing back to the nominal uncertainty of calibration standards. First, we analyzed the relevant theory of uncertainty assessment using covariance matrices and subsequently deduced the mechanism of Type B uncertainty propagating from calibration standards to error model coefficients and S-parameter measurements to evaluate Type B measurement uncertainty. In this study, a novel measurement system was constructed for measuring grounded coplanar waveguides by using a VNA and calibration standards with 8- and 12-error models. Initially, the model assessed the Type B uncertainty of measuring four S-parameters of a grounded coplanar waveguide. Next, the VNA calibrated with the 12-error model was used to conduct multiple repeated measurements to assess the Type A uncertainty of the grounded coplanar waveguide. Finally, the composite uncertainty was constructed, which demonstrated that the proposed method can be used for assessing the uncertainty of S-parameters.

Clinical study of Microendoscopic Discectomy + Fibrous Ring Suture Versus Microendoscopic Discectomy alone in the treatment of lumbar disc herniation in young and middle-aged patients.

Objective: To compare the clinical efficacy of microendoscopic discectomy + fibrous ring suture versus microendoscopic discectomy alone in the treatment of lumbar disc herniation (LDH) in young and middle-aged patients. Methods: A retrospective analysis was performed on the clinical data of 66 young and middle-aged patients with single-segment LDH diagnosed in Orthopedic Hospital of Henan Province from October 2019 to October 2022. All patients were divided into two groups: the microendoscopic discectomy + fibrous ring suture group and the microendoscopic discectomy alone group, with 33 cases in each group. The Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) scores of the two groups were recorded before surgery and six and twelve months after surgery. Results: Both groups completed the surgery and postoperative follow-up successfully and showed no statistically significant differences in terms of incision length, duration of surgery, intraoperative blood loss and length of hospital stay (all P>0.05). VAS, ODI and JOA scores were significantly improved in both groups at 6 and 12 months after surgery compared with those before surgery (all P<0.05). The two groups were similar in terms of excellent and good rates of postoperative modified MacNab Evaluation Criteria, with no statistically significant differences. No serious complications were observed in the two groups during and after surgery. Conclusion: Both of the two surgical methods are effective in the treatment of LDH in young and middle-aged patients, and microendoscopic discectomy + fibrous ring suture in particular may be preferred because it results in significant improvement in patients' VAS and ODI scores.

Hypoglycemic bioactivity of anthocyanins: A review on proposed targets and potential signaling pathways.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with complicated interrelationships responsible for initiating its pathogenesis. Novel strategies for the treatment of this devastating disease have attracted increasing attention worldwide. Anthocyanins are bioactive compounds that are widely distributed in the plant kingdom, and multiple studies have elucidated their beneficial role in preventing and managing T2DM. This review summarizes and comments on the hypoglycemic actions of anthocyanins from the perspective of molecular mechanisms and different target-related signaling pathways in vitro, in vivo, and clinical trials. Anthocyanins can ameliorate T2DM by functioning as carbohydrate digestive enzyme inhibitors, facilitating glucose transporter 4 (GLUT4) translocation, suppressing the effectiveness of dipeptidyl peptidase IV (DPP-IV), promoting glucagon-like peptide-1 (GLP-1) secretion, inhibiting protein tyrosine phosphatase 1B (PTP1B) overexpression, and interacting with sodium-glucose co-transporter (SGLT) to delay glucose absorption in various organs and tissues. In summary, anthocyanin is a promising and practical small molecule that can hyperglycemic symptoms and accompanying complications suffered by patients with diabetes. However, rational and potent doses for daily intake and clinical studies are required in the future.

Colon-targeted delivery of polyphenols: construction principles, targeting mechanisms and evaluation methods.

Polyphenols have received considerable attention for their promotive effects on colonic health. However, polyphenols are mostly sensitive to harsh gastrointestinal environments, thus, must be protected. It is necessary to design and develop a colon-targeted delivery system to improve the stability, colon-targeting and bioavailability of polyphenols. This paper mainly introduces research on colon-targeted controlled release of polyphenols. The physiological features affecting the dissolution, release and absorption of polyphenol-loaded delivery systems in the colon are first discussed. Simultaneously, the types of colon-targeted carriers with different release mechanisms are described, and colon-targeting assessment models that have been studied so far and their advantages and limitations are summarized. Based on the current research on polyphenols colon-targeting, outlook and reflections are proposed, with the goal of inspiring strategic development of new colon-targeted therapeutics to ensure that the polyphenols reach the colon with complete bioactivity.

Development of an efficient protein expression system in the thermophilic fungus Myceliophthora thermophila.

BACKGROUND: Thermophilic fungus Myceliophthora thermophila has been widely used in industrial applications due to its ability to produce various enzymes. However, the lack of an efficient protein expression system has limited its biotechnological applications. RESULTS: In this study, using a laccase gene reporting system, we developed an efficient protein expression system in M. thermophila through the selection of strong constitutive promoters, 5'UTRs and signal peptides. The expression of the laccase was confirmed by enzyme activity assays. The results showed that the Mtpdc promoter (Ppdc) was able to drive high-level expression of the target protein in M. thermophila. Manipulation of the 5'UTR also has significant effects on protein expression and secretion. The best 5'UTR (NCA-7d) was identified. The transformant containing the laccase gene under the Mtpdc promoter, NCA-7d 5'UTR and its own signal peptide with the highest laccase activity (1708 U/L) was obtained. In addition, the expression system was stable and could be used for the production of various proteins, including homologous proteins like MtCbh-1, MtGh5-1, MtLPMO9B, and MtEpl1, as well as a glucoamylase from Trichoderma reesei. CONCLUSIONS: An efficient protein expression system was established in M. thermophila for the production of various proteins. This study provides a valuable tool for protein production in M. thermophila and expands its potential for biotechnological applications.

Aptamer-Based Detection of Circulating Targets for Precision Medicine.

The past decade has witnessed ongoing progress in precision medicine to improve human health. As an emerging diagnostic technique, liquid biopsy can provide real-time, comprehensive, dynamic physiological and pathological information in a noninvasive manner, opening a new window for precision medicine. Liquid biopsy depends on the sensitive and reliable detection of circulating targets (e.g., cells, extracellular vesicles, proteins, microRNAs) from body fluids, the performance of which is largely governed by recognition ligands. Aptamers are single-stranded functional oligonucleotides, capable of folding into unique tertiary structures to bind to their targets with superior specificity and affinity. Their mature evolution procedure, facile modification, and affinity regulation, as well as versatile structural design and engineering, make aptamers ideal recognition ligands for liquid biopsy. In this review, we present a broad overview of aptamer-based liquid biopsy techniques for precision medicine. We begin with recent advances in aptamer selection, followed by a summary of state-of-the-art strategies for multivalent aptamer assembly and aptamer interface modification. We will further describe aptamer-based micro-/nanoisolation platforms, aptamer-enabled release methods, and aptamer-assisted signal amplification and detection strategies. Finally, we present our perspectives regarding the opportunities and challenges of aptamer-based liquid biopsy for precision medicine.

Phosphatase and tensin homologue determine inflammatory status by differentially regulating the expression of Akt1 and Akt2 in macrophage alternative polarization of periodontitis.

AIM: Macrophages are closely involved in periodontitis. However, the molecular mechanism by which macrophages influence periodontitis is not well understood. We investigated the effects of phosphatase and tensin homologue (PTEN) on macrophage polarization, the underlying mechanism and the regulatory roles in periodontium regeneration. MATERIALS AND METHODS: PTEN expression in periodontitis macrophages was detected ex vivo. The effects of PTEN on macrophage polarization and the underlying mechanisms were investigated in vitro. We also analysed the ability of PTEN inhibitors to repair periodontitis in vivo in a ligature-induced mouse model of periodontitis. RESULTS: Macrophage PTEN expression in periodontitis patients was significantly higher than that of controls. PTEN inhibition in macrophages induced alternative macrophage polarization, whereas PTEN overexpression facilitated classical polarization. PTEN inhibition facilitated activation of Akt1 while inhibiting expression of Akt2. Furthermore, Akt2 overexpression could rescue the effects of PTEN inhibition on NF-κB. Treatment with a PTEN inhibitor significantly attenuated the local inflammatory status and prevented alveolar bone resorption in the mouse model. CONCLUSIONS: Our findings suggest that PTEN inhibition could induce alternative macrophage polarization by differentially regulating Akt1 and Akt2. This also changed a pro-inflammatory microenvironment to an anti-inflammatory environment by subsequently regulating the expression of NF-κB, thereby attenuating inflammatory alveolar bone resorption induced by ligature.

Maternal diets affected ceramides and fatty acids in brain regions of neonatal rats with prenatal ethanol exposure.

Objectives: Ceramide (Cer), known as apoptotic markers, increases with prenatal ethanol (EtOH) exposure, resulting in neuroapoptosis. Whether maternal nutrition can impact Cer concentrations in brain, via altering plasma and brain fatty acid compositions have not been examined. This study compared a standard chow with a formulated semi-purified energy dense (E-dense) diet on fatty acid composition, Cer concentrations, and apoptosis in plasma and brain regions (cortex, cerebellum, and hippocampus) of pups exposed to EtOH during gestation. Methods: Pregnant Sprague-Dawley rats were randomized into four groups: chow (n = 6), chow + EtOH (20% v/v) (n = 7), E-dense (n = 6), and E-dense + EtOH (n = 8). At postnatal day 7, representing the peak brain growth spurt in rats, lipids, and apoptosis were analyzed by gas chromatography and a fluorometric caspase-3 assay kit, respectively. Results: Maternal E-dense diet increased total fatty acid concentrations (p < 0.0001), including docosahexaenoic acid (DHA) (p < 0.0001) in plasma, whereas DHA concentrations were decreased in the cerebellum (p < 0.03) of pups than those from chow-fed dams. EtOH-induced Cer elevations in the hippocampus of pups born to dams fed chow were reduced by an E-dense diet (p < 0.02). No significant effects of maternal diet quality and EtOH were observed on caspase-3 activity. No significant correlations existed between plasma/brain fatty acids and Cer concentrations. Discussions: Maternal diet quality affected fatty acid compositions and Cer concentrations of pups with prenatal EtOH exposure, differently. Maternal nutrition has the potential to prevent or alleviate some of the adverse effects of prenatal EtOH exposure.

Charge equilibration model with shielded long-range Coulomb for reactive molecular dynamics simulations.

Atomic description of electrochemical systems requires reactive interaction potential to explicitly describe the chemistry between atoms and molecules and the evolving charge distribution and polarization effects. Calculating Coulomb electrostatic interactions and polarization effects requires a better estimate of the partial charge distribution in molecular systems. However, models such as reactive force fields and charge equilibration (QEq) include Coulomb interactions up to a short-distance cutoff for better computational speeds. Ignoring long-distance electrostatic interaction affects the ability to describe electrochemistry in large systems. We studied the long-range Coulomb effects among charged particles and extended the QEq method to include long-range effects. By this extension, we anticipate a proper account of Coulomb interactions in reactive molecular dynamics simulations. We validate the approach by computing charges on a series of metal-organic frameworks and some simple systems. Results are compared to regular QEq and quantum mechanics calculations. The study shows slightly overestimated charge values in the regular QEq approach. Moreover, our method was combined with Ewald summation to compute forces and evaluate the long-range effects of simple capacitor configurations. There were noticeable differences between the calculated charges with/without long-range Coulomb interactions. The difference, which may have originated from the long-range influence on the capacitor ions, makes the Ewald method a better descriptor of Coulomb electrostatics for charged electrodes. The approach explored in this study enabled the atomic description of electrochemical systems with realistic electrolyte thickness while accounting for the electrostatic effects of charged electrodes throughout the dielectric layer in devices like batteries and emerging solid-state memory.

A prospective analysis of optimal total weight gain ranges and trimester-specific weight gain rates for Chinese pregnant women.

BACKGROUND: Gestational weight gain (GWG) criteria recommended by the Institute of Medicine may not be appropriate for Asians. Our aims are to investigate the association between GWG and adverse pregnancy outcomes, and to propose optimal total GWG and rates of GWG for Chinese women. METHODS: Prospective data of 51,125 mother-child pairs from 27 hospitals and community health care centers from Guizhou, Yunnan and Sichuan provinces in China between 2014 and 2018 were analyzed. Generalized Additive Models were performed to determine the associations of GWG with the risk of aggregated adverse outcomes (gestational diabetes mellitus, preeclampsia, cesarean delivery, stillbirth, preterm birth, macrosomia, large for gestational age, and small for gestational age). The range that did not exceed a 2.5% increase from the lowest risk of aggregated adverse outcomes was defined as the optimal GWG range. RESULTS: Among all participants, U-shaped prospective association was found between GWG and the risk of aggregated adverse pregnancy outcomes. The optimal GWG range of 8.2-13.0 kg was proposed for underweight, 7.3-12.5 kg for normal weight, and 2.0-9.4 kg for overweight/obese women. Meanwhile, a higher GWG rate in the first two trimesters than that in the last trimester was suggested, except for overweight/obese women. After stratified by maternal age, mothers ≥35 years were suggested to gain less weight compared to younger mothers. CONCLUSIONS: To keep a balance between maternal health and neonatal growth, optimal GWG ranges based on Asia-specific BMI categories was suggested for Chinese women with different pre-gravid BMIs and maternal ages.