Vibrationally-resolved RIXS reveals OH-group formation in oxygen redox active Li-ion battery cathodes.

Vibrationally-resolved resonant inelastic X-ray scattering (VR-RIXS) at the O K-edge is emerging as a powerful tool for identifying embedded molecules in lithium-ion battery cathodes. Here, we investigate two known oxygen redox-active cathode materials: the commercial LixNi0.90Co0.05Al0.05O2 (NCA) used in electric vehicles and the high-capacity cathode material Li1.2Ni0.13Co0.13Mn0.54O2 (LRNMC) for next-generation Li-ion batteries. We report the detection of a novel vibrational RIXS signature for Li-ion battery cathodes appearing in the O K pre-peak above 533 eV that we attribute to OH-groups. We discuss likely locations and pathways for OH-group formation and accumulation throughout the active cathode material. Initial-cycle behaviour for LRNMC shows that OH-signal strength correlates with the cathodes state of charge, though reversibility is incomplete. The OH-group RIXS signal strength in long-term cycled NCA is retained. Thus, VR-RIXS offers a path for gaining new insights to oxygen reactions in battery materials.

Enhancing Cancer Therapy: Boron-Rich Polyboronate Ester Micelles for Synergistic Boron Neutron Capture Therapy and PD-1/PD-L1 Checkpoint Blockade.

Malignant cancers, known for their pronounced heterogeneity, pose substantial challenges to monotherapeutic strategies and contribute to the risk of metastasis. Addressing this, our study explores the synergistic potential of combining boron neutron capture therapy (BNCT) with immune checkpoint blockade to enhance cancer treatment efficacy. We synthesized boron-rich block copolymer micelles as a novel boron drug for BNCT. Characterization was conducted using nuclear magnetic resonance, gel-permeation chromatography, transmission electron microscopy, and dynamic light scattering. These micelles, with an optimal size of 91.3 nm and a polydispersity index of 0.18, are suitable for drug delivery applications. In vitro assessments on B16-F10 melanoma cells showed a 13-fold increase in boron uptake with the micelles compared to borophenyl alanine (BPA), the conventional boron drug for BNCT. This resulted in a substantial increase in BNCT efficacy, reducing cell viability to 77% post-irradiation in micelle-treated cells, in contrast to 90% in BPA-treated cells. In vivo, melanoma-bearing mice treated with these micelles exhibited an 8-fold increase in boron accumulation in tumor tissues versus those treated with BPA, leading to prolonged tumor growth delay (5.4 days with micelles versus 3.3 days with BPA). Moreover, combining BNCT with anti-PD-L1 immunotherapy further extended the tumor growth delay to 6.6 days, and enhanced T-cell infiltration and activation at tumor sites, thereby indicating a boosted immune response. This combination demonstrates a promising approach by enhancing cytotoxic T-cell priming and mitigating the immunosuppressive effects of melanoma tumors.

A Prospective Cohort Study of Antimony Exposure and Cognitive Impairment in Older Adults - China, 2017-2021.

What is already known about this topic?: Antimony (Sb) has been identified as a new neurotoxicant that impacts neurological functions in animal studies. However, its effects on the human population remain unknown. What is added by this report?: The study reveals that there is an association between exposure to Sb and a higher incidence of cognitive impairment in older adults. The dose-response curve demonstrates that the risk of cognitive impairment consistently increased with higher levels of Sb exposure without a discernible threshold. What are the implications for public health practice?: Reducing exposure to Sb may have a beneficial effect in delaying or preventing the onset of cognitive impairment. This intervention has the potential to significantly decrease the disease burden associated with cognitive impairment, ultimately contributing to social development.

Understanding the Role of Low-Dose Polystyrene Microplastic in Copper Toxicity to Rice Seed (Oryza sativa L.).

There is still much to learn with respect to the potential for microplastics (MPs) to interact with environmental toxins and biota. In the present study, we investigated the effect of MPs on the toxicity of copper (Cu) to rice seeds (Oryza sativa L.). The 7-day median effective concentration (EC50) value of MPs on rice seed germination was 864 mg/L (95% confidence interval [CI] 839 to 897 mg/L). We found that MPs slightly reduced Cu toxicity to rice seeds. The 7-day EC50 of Cu on rice seed germination increased from 7.29 mg/L (95% CI 7.10-7.52 mg/L) to 7.93 mg/L (95% CI 7.58-8.08 mg/L) in the presence of 20 mg/L MPs. We examined this toxicity reduction phenomenon by investigating the role of MPs in the process of Cu transport, Cu accumulation, and metabolic responses. Further investigation found that the MPs used in the present study hardly adsorbed Cu, but these MPs accumulated on the coats of rice seeds and significantly reduced Cu accumulation in rice seedlings. When Cu concentration was 10 mg/L, the presence of MPs reduced the accumulation of Cu in rice seedlings by 34%. We also found that, compared with only Cu present, the addition of MPs resulted in lower reactive oxygen species accumulation and higher catalase activity and glutathione levels in rice seedlings, which also contributed to Cu toxicity reduction. Collectively, the present study shows that polystyrene MPs have the potential to form associations with plant structures which can ultimately impact heavy metal bioaccessibility and therefore toxicity. Environ Toxicol Chem 2024;00:1-10. © 2024 SETAC.

Development of a non-intercepting weak beam current measurement electronics for Heavy Ion Accelerator Facility in Lanzhou.

Non-destructive measurements of low-intensity charged particle beams are particularly challenging for beam diagnostics. At the Heavy Ion Accelerator Facility in Lanzhou (HIRFL), beams with weak currents below 1 µA are often provided for experiments. The detection of such low beam current is below the threshold of typical standard beam current transformers. Therefore, a low-intensity monitoring system is developed by using a sensitive capacitive pick-up (PU) and low-noise electronics. This device measures beam currents by digitally analyzing the amplitude of the PU signals using a homodyne detection scheme. During lab tests, the amplitude nonlinearity is <0.5% in the operational range of 1 nA-45 µA and the amplitude resolution is 0.94 nA. At present, four measurement systems for low beam currents are installed at HIRFL for the monitoring of standard operating conditions with low beam currents below 1 µA. After an absolute calibration with a Faraday cup, it can be used for accurate beam intensity measurement with a current resolution of about 1 nA.

Modulation format recognition in a UVLC system based on an ultra-lightweight model with communication-informed knowledge distillation.

Modulation format recognition (MFR) is a key technology for adaptive optical systems, but it faces significant challenges in underwater visible light communication (UVLC) due to the complex channel environment. Recent advances in deep learning have enabled remarkable achievements in image recognition, owing to the powerful feature extraction of neural networks (NN). However, the high computational complexity of NN limits their practicality in UVLC systems. This paper proposes a communication-informed knowledge distillation (CIKD) method that achieves high-precision and low-latency MFR with an ultra-lightweight student model. The student model consists of only one linear dense layer under a communication-informed auxiliary system and is trained under the guidance of a high-complexity and high-precision teacher model. The MFR task involves eight modulation formats: PAM4, QPSK, 8QAM-CIR, 8QAM-DIA, 16QAM, 16APSK, 32QAM, and 32APSK. Experimental results show that the student model based on CIKD can achieve comparable accuracy to the teacher model. After knowledge transfer, the prediction accuracy of the student model can be increased by up to 87%. Besides, it is worth noting that CIKD's inference accuracy can reach up to 100%. Moreover, the parameters constituting the student model in CIKD correspond to merely 18% of the parameters found in the teacher model, which facilitates the hardware deployment and online data processing of MFR algorithms in UVLC systems.

Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions.

BACKGROUND: Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. METHODS: A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). RESULTS: IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1ß). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. CONCLUSION: Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.

Positive Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Hypertension May Be Attenuated by Endogenous Sex Hormones: A Nationally Representative Cross-Sectional Study.

BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored. METHODS: This study included 10 794 adults aged ≥18 years from the China National Human Biomonitoring program. Weighted multiple logistic regression and linear regression were used to examine the associations of serum PFAS with hypertension, diastolic blood pressure, and systolic blood pressure. Joint effects of PFAS mixtures on hypertension, diastolic blood pressure, and systolic blood pressure were evaluated using quantile-based g-computation. Additive and multiplicative interactions were used to assess the role of PFAS with testosterone and estradiol on hypertension. RESULTS: The prevalence of hypertension in Chinese adults was 35.50%. Comparing the fourth quartile with the first quartile, odds ratio (95% CI) of hypertension were 1.53 (1.13-2.09) for perfluorononanoic acid, 1.40 (1.03-1.91) for perfluorodecanoic acid, 1.34 (1.02-1.78) for perfluoroheptane sulfonic acid, and 1.46 (1.07-1.99) for perfluorooctane sulfonic acid. Moreover, PFAS mixtures, with perfluorononanoic acid contributing the most, were positively associated with hypertension, diastolic blood pressure, and systolic blood pressure. PFAS and endogenous hormones had an antagonistic interaction in hypertension. For example, the relative excess risk ratio, attributable proportion, and synergy index for perfluorononanoic acid and estradiol were -3.61 (-4.68 to -2.53), -1.65 (-2.59 to -0.71), and 0.25 (0.13-0.47), respectively. CONCLUSIONS: Perfluorononanoic acid, perfluorodecanoic acid, perfluoroheptane sulfonic acid, perfluorooctane sulfonic acid, and PFAS mixtures showed positive associations with hypertension, systolic blood pressure, and diastolic blood pressure. Positive associations of PFAS with hypertension might be attenuated by increased levels of endogenous sex hormones.

Risk Perception and Maternal Prenatal Depressive Symptoms in the Early Stage of COVID-19 Pandemic in China: Role of Negative Emotions and Family Sense of Coherence.

BACKGROUND: Prenatal depression is associated with adverse health outcomes for both mothers and their children. The worldwide COVID-19 pandemic has presented new risks and challenges for expectant mothers. The aims of the study were to investigate the underlying mechanism between COVID-19 risk perception of Chinese pregnant women and their prenatal depressive symptoms and potential protective factors such as family sense of coherence (FSOC). METHOD: A total of 181 Chinese pregnant women (Mage = 31.40 years, SD = 3.67, ranged from 23 to 43) participated in an online survey from April 22 to May 16, 2020. Risk perception and negative emotions (fear and anxiety) related with COVID-19, FSOC, and prenatal depressive symptoms were assessed. RESULTS: The experience of maternal COVID-19 related negative emotion fully mediated the positive relationship between COVID-19 risk perception and prenatal depressive symptoms of pregnant women (ß = 0.12, 95% CI [0.06, 0.19]). When confronting COVID-19 related fear and anxiety, expectant mothers from higher coherent families experienced a significantly lower level of prenatal depressive symptoms. CONCLUSIONS: Contextual negative emotional experience was demonstrated to explain how risk perception impacts depressive symptoms during severe public health crisis for pregnant women. FSOC may be a psychological resource protecting pregnant women from experiencing adverse psychological outcomes during COVID-19 pandemic.

Boron Neutron Capture Therapy Enhanced by Boronate Ester Polymer Micelles: Synthesis, Stability, and Tumor Inhibition Studies.

Boron neutron capture therapy (BNCT) targets invasive, radioresistant cancers but requires a selective and high B-10 loading boron drug. This manuscript investigates boron-rich poly(ethylene glycol)-block-(poly(4-vinylphenyl boronate ester)) polymer micelles synthesized via atom transfer radical polymerization for their potential application in BNCT. Transmission electron microscopy (TEM) revealed spherical micelles with a uniform size of 43 ± 10 nm, ideal for drug delivery. Additionally, probe sonication proved effective in maintaining the micelles' size and morphology postlyophilization and reconstitution. In vitro studies with B16-F10 melanoma cells demonstrated a 38-fold increase in boron accumulation compared to the borophenylalanine drug for BNCT. In vivo studies in a B16-F10 tumor-bearing mouse model confirmed enhanced tumor selectivity and accumulation, with a tumor-to-blood (T/B) ratio of 2.5, surpassing BPA's T/B ratio of 1.8. As a result, mice treated with these micelles experienced a significant delay in tumor growth, highlighting their potential for BNCT and warranting further research.

From Intercalation to External Binding: Ru(II) Complexes with a Spiro Ligand for TAR RNA Selective Binding and HIV-1 Reverse Transcriptase Inhibition.

As a typical RNA virus, the genetic information on HIV-1 is entirely stored in RNA. The reverse transcription activity of HIV-1 reverse transcriptase (RT) plays a crucial role in the replication and transmission of the virus. Non-nucleoside RT inhibitors (NNRTIs) block the function of RT by binding to the RNA binding site on RT, with very few targeting viral RNA. In this study, by transforming planar conjugated ligands into a spiro structure, we convert classical Ru(II) DNA intercalators into a nonintercalator. This enables selective binding to HIV-1 transactivation response (TAR) RNA on the outer side of nucleic acids through dual interactions involving hydrogen bonds and electrostatic attraction, effectively inhibiting HIV-1 RT and serving as a selective fluorescence probe for TAR RNA.

Dense Polarized Positrons from Beam-Solid Interaction.

Relativistic positron sources with high spin polarization have important applications in nuclear and particle physics and many frontier fields. However, it is challenging to produce dense polarized positrons. Here we present a simple and effective method to achieve such a positron source by directly impinging a relativistic high-density electron beam on the surface of a solid target. During the interaction, a strong return current of plasma electrons is induced and subsequently asymmetric quasistatic magnetic fields as high as megatesla are generated along the target surface. This gives rise to strong radiative spin flips and multiphoton processes, thus leading to efficient generation of copious polarized positrons. With three-dimensional particle-in-cell simulations, we demonstrate the production of a dense highly polarized multi-GeV positron beam with an average spin polarization above 40% and nC-scale charge per shot. This offers a novel route for the studies of laserless strong-field quantum electrodynamics physics and for the development of high-energy polarized positron sources.

Systematic Quantitative Analysis of Fetal Dexamethasone Exposure and Fetal Lung Maturation in Pregnant Animals: Model Informed Dexamethasone Precision Dose Study.

Dexamethasone (DEX) was applied in neonatal respiratory distress syndrome treatment of pregnant women. We established a pharmacokinetics (PK)/pharmacodynamics(PD)/end point model of pregnant animals based on published data and then extrapolated to simulate fetal exposure and lung maturation in pregnant women. We first established the PK/PD/end point model for DEX in pregnant sheep. We considered the competitive effect of cortisol (Cort) and DEX binding with glucocorticoid receptor and then used the indirect response model to describe disaturated-phosphatidylcholine (DSPC) dynamics. Based on that, we established a regression relationship between DSPC and fetal lung volume (V40). We then extrapolated the PD/end point model of pregnant sheep to pregnant monkeys by corrected stages of morphologic lung maturation in two species. Finally, we utilized the interspecies extrapolation strategy to simulate fetal exposure (AUC0-48h) and V40 relationship in pregnant women. The current model could well describe the maternal-fetal PK of DEX in pregnant animals. Simulated DEX AUC0-24h values of the umbilical venous to maternal plasma ratio in pregnant sheep and monkeys were 0.31 and 0.27, respectively. The simulated Cort curve and V40 in pregnant sheep closely matched the observed data within a 2-fold range. For pregnant monkeys, model-simulated V40 were well fitted with external verification data, which showed good interspecies extrapolation performance. Finally, we simulated fetal exposure-response relationship in pregnant women, which indicated that the fetal AUC0-48h of DEX should not be less than 300 and 100 ng/mL·hr at GW28 and GW34 to ensure fetal lung maturity. The current model preliminarily provided support for clinical DEX dose optimization.

Characteristics and utility of high-resolution optical coherence microscopy images of endocervical canal lesions.

OBJECTIVES: To investigate optical coherence microscopy (OCM) imaging features and the application value of these high-resolution images for identifying endocervical canal lesions (ECLs), which is a clinical dilemma in cervical cancer screening programs. METHODS: In total, 520 OCM images were obtained by scanning the cervical canal lesions with an ultra-high-resolution OCM system (204 specimens from 73 patients). The OCM morphologic characteristics of ECLs were observed and summarized, and then 3 researchers performed a diagnostic test of OCM images of cervical canal lesions. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, 95% confidence interval of each parameter, and interinvestigator agreement (κ) were calculated. RESULTS: Normal endocervix, cysts, squamous metaplasia, high-grade squamous intraepithelial lesions involving glands, and invasive carcinoma had distinct OCM characteristics, which correlated well with corresponding H&E histologic sections. The accuracy, sensitivity, and specificity of the 3 researchers were 90.6%, 89.3% (95% CI, 86.5%-91.7%) and 91.6% (95% CI, 89.2%-93.5%), respectively. The positive predictive value was 90.1% (95% CI, 87.3%-92.4%), and the negative predictive value was 90.9% (95% CI, 88.5%-92.9%), with almost perfect agreement (κ = 0.874). CONCLUSIONS: The application of the OCM system in cervical canal lesions is feasible and could help improve detection of occult ECLs in cervical cancer screening programs. This study lays the foundation for further research on OCM in cervical canal lesions in vivo, which also has a potential impact on projecting pathologic evaluation beyond what is currently possible, perhaps globally.

Retrospective Investigation and Research on Fall Events Among Hospitalized Patients in the Rehabilitation Department.

Objective: We investigated the clinical characteristics, fall outcomes, and related factors of falls in patients who were hospitalized in the rehabilitation department, and explored strategies to reduce the incidence of falls and prevent falls in patients. Methods: Data from 60 patients who fell in the rehabilitation department between 2016 and 2021 were analyzed for clinical characteristics, associated factors, incidence of falls, injuries, and patient demographics. Under the random stratified sampling method, 60 patients who did not fall during the same period were selected as the control group, and relevant data was collected. Measurement data were compared using an independent sample t-test. Enumeration data were compared using chi-squared (χ2) test was employed to compare these data between the two groups. Non-parametric data were analyzed using the Mann-Whitney U-test. Factors potentially influencing falls were scrutinized through both univariate and binary logistic regression analyses. Results: The median annual incidence of falls among patients who were hospitalized in the rehabilitation department was 0.04%, while the overall fall injury rate was 60%. Falls were most prevalent within 30 days of hospitalization (71.67%). The most common fall-related condition was craniocerebral disease (83.33%). The incidents of falls location of fall were mainly reported in nearby areas of rehabilitation ward (70%). Most accidents occurred between 7:00 a.m.-12:00 p.m. and 3:01 p.m.-6:00 p.m. (63.33%), and dyskinesia was the most common cause of falls (71.67%). There were 39 patients (65.00%) with Barthel Index (BI) scores ranging between 40-60. Conclusion: Patients in the rehabilitation department had a greater incidence of falls and fall injuries. Within 30 days of admission, patients with moderately dependent craniocerebral disorders and dyskinesia frequently experienced falls during typical daytime shifts in areas characterized by endemic conditions.

Cisplatin-activated and hemoglobin-mediated injectable hydrogel system for antitumor chemodynamic and chemotherapy.

Low specificity and hypoxia-induced drug resistance are significant challenges in traditional cancer treatment. To enhance the anticancer efficacy, an injectable hydrogel system is developed through the formation of dynamic covalent bonds in hyaluronic acid, allowing for localized controlled release of drugs. This system also utilizes double-stranded DNA sequences for the intercalation delivery of the chemotherapeutic drug, enabling a multifaceted approach to therapy. Cisplatin not only serves as a chemotherapy drug but also acts as a catalyst for chemodynamic therapy (CDT) to initiate CDT cascades by creating hydrogen peroxide for the Fenton reaction. Hemoglobin, enclosed in PLGA nanoparticles, provides ferrous ions that react with hydrogen peroxide in an acidic environment, yielding hydroxyl radicals that induce cancer cell death. Additionally, oxygen released from hemoglobin mitigates hypoxia-induced chemoresistance, bolstering overall anticancer efficacy. Results demonstrate the shear-thinning properties and injectability of the hydrogel. Cisplatin elevates intracellular hydrogen peroxide levels in tumor cells, while hemoglobin efficiently releases ferrous ions and generates reactive oxygen species (ROS) in the presence of hydrogen peroxide. In in vitro and in vivo study, the combinational use of chemo- and chemodynamic therapies achieves a synergistic anticancer effect on combating glioblastoma. In summary, our CDT-based hydrogel, activated by endogenous cues and mediated by chemo drugs, spontaneously produces ROS and ameliorates the adverse tumor microenvironment with rational and selective antitumor strategies.

Pro-inflammatory macrophage activation does not require inhibition of mitochondrial respiration.

Pro-inflammatory macrophage activation is a hallmark example of how mitochondria serve as signaling organelles. Upon classical macrophage activation, oxidative phosphorylation sharply decreases and mitochondria are repurposed to accumulate signals that amplify effector function. However, evidence is conflicting as to whether this collapse in respiration is essential or largely dispensable. Here we systematically examine this question and show that reduced oxidative phosphorylation is not required for pro-inflammatory macrophage activation. Only stimuli that engage both MyD88- and TRIF-linked pathways decrease mitochondrial respiration, and different pro-inflammatory stimuli have varying effects on other bioenergetic parameters. Additionally, pharmacologic and genetic models of electron transport chain inhibition show no direct link between respiration and pro-inflammatory activation. Studies in mouse and human macrophages also reveal accumulation of the signaling metabolites succinate and itaconate can occur independently of characteristic breaks in the TCA cycle. Finally, in vivo activation of peritoneal macrophages further demonstrates that a pro-inflammatory response can be elicited without reductions to oxidative phosphorylation. Taken together, the results suggest the conventional model of mitochondrial reprogramming upon macrophage activation is incomplete.

Advancing elastomer performance with dynamic bond networks in polymer-grafted single-chain nanoparticles: a molecular dynamics exploration.

This research introduces a method to enhance the mechanical properties of elastomers by grafting polymer chains onto single-chain flexible nanoparticles (SCNPs) and incorporating dynamic functional groups. Drawing on developments in grafting polymers onto hard nanoparticle fillers, this method employs the distinct flexibility of SCNPs to diminish heterogeneity and enhance core size control. We use molecular dynamics (MD) simulations for a mesoscale analysis of structural properties, particularly the effects of dynamic functional group quantities and their distribution. The findings demonstrate that increased quantities of functional groups are correlated with enhanced mechanical strength and toughness, showing improved stress-strain responses and energy dissipation capabilities. Moreover, the uniformity in the distribution of these functional groups is crucial, promoting a more cohesive and stable dynamic bonding network. The insights gained from MD simulations not only advance our understanding of the microstructural control necessary for optimizing macroscopic properties, but also provide valuable guidance for the design and engineering of advanced polymer nanocomposites, thereby enhancing the material performance through strategic molecular design.

Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia.

BACKGROUND: Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. RESULTS: By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. CONCLUSIONS: Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal-fetal interface formation.

Effects of MhMYB1 and MhMYB2 transcription factors on the monoterpenoid biosynthesis pathway in l-menthol chemotype of Mentha haplocalyx Briq.

MAIN CONCLUSION: Transcription factors MhMYB1 and MhMYB2 correlate with monoterpenoid biosynthesis pathway in l-menthol chemotype of Mentha haplocalyx Briq, which could affect the contents of ( -)-menthol and ( -)-menthone. Mentha haplocalyx Briq., a plant with traditional medicinal and edible uses, is renowned for its rich essential oil content. The distinct functional activities and aromatic flavors of mint essential oils arise from various chemotypes. While the biosynthetic pathways of the main monoterpenes in mint are well understood, the regulatory mechanisms governing different chemotypes remain inadequately explored. In this investigation, we identified and cloned two transcription factor genes from the M. haplocalyx MYB family, namely MhMYB1 (PP236792) and MhMYB2 (PP236793), previously identified by our research group. Bioinformatics analysis revealed that MhMYB1 possesses two conserved MYB domains, while MhMYB2 contains a conserved SANT domain. Yeast one-hybrid (Y1H) analysis results demonstrated that both MhMYB1 and MhMYB2 interacted with the promoter regions of MhMD and MhPR, critical enzymes in the monoterpenoid biosynthesis pathway of M. haplocalyx. Subsequent virus-induced gene silencing (VIGS) of MhMYB1 and MhMYB2 led to a significant reduction (P < 0.01) in the relative expression levels of MhMD and MhPR genes in the VIGS groups of M. haplocalyx. In addition, there was a noteworthy decrease (P < 0.05) in the contents of ( -)-menthol and ( -)-menthone in the essential oil of M. haplocalyx. These findings suggest that MhMYB1 and MhMYB2 transcription factors play a positive regulatory role in ( -)-menthol biosynthesis, consequently influencing the essential oil composition in the l-menthol chemotype of M. haplocalyx. This study serves as a pivotal foundation for unraveling the regulatory mechanisms governing monoterpenoid biosynthesis in different chemotypes of M. haplocalyx.