Functional Divergence in Orthologous Transcription Factors: Insights from AtCBF2/3/1 and OsDREB1C.

Despite traditional beliefs of orthologous genes maintaining similar functions across species, growing evidence points to their potential for functional divergence. C-repeat binding factors/dehydration-responsive element binding protein 1s (CBFs/DREB1s) are critical in cold acclimation, with their overexpression enhancing stress tolerance but often constraining plant growth. In contrast, a recent study unveiled a distinctive role of rice OsDREB1C in elevating nitrogen use efficiency (NUE), photosynthesis, and grain yield, implying functional divergence within the CBF/DREB1 orthologs across species. Here, we delve into divergent molecular mechanisms of OsDREB1C and AtCBF2/3/1 by exploring their evolutionary trajectories across rice and Arabidopsis genomes, regulatomes, and transcriptomes. Evolutionary scrutiny shows discrete clades for OsDREB1C and AtCBF2/3/1, with the Poaceae-specific DREB1C clade mediated by a transposon event. Genome-wide binding profiles highlight OsDREB1C's preference for GCCGAC compared to AtCBF2/3/1's preference for A/GCCGAC, a distinction determined by R12 in the OsDREB1C AP2/ERF domain. Cross-species multiomic analyses reveal shared gene orthogroups (OGs) and underscore numerous specific OGs uniquely bound and regulated by OsDREB1C, implicated in NUE, photosynthesis, and early flowering, or by AtCBF2/3/1, engaged in hormone and stress responses. This divergence arises from gene gains/losses (∼16.7% to 25.6%) and expression reprogramming (∼62.3% to 66.2%) of OsDREB1C- and AtCBF2/3/1-regulated OGs during the extensive evolution following the rice-Arabidopsis split. Our findings illustrate the regulatory evolution of OsDREB1C and AtCBF2/3/1 at a genomic scale, providing insights on the functional divergence of orthologous transcription factors following gene duplications across species.

Comprehensive assessment of mRNA isoform detection methods for long-read sequencing data.

The advancement of Long-Read Sequencing (LRS) techniques has significantly increased the length of sequencing to several kilobases, thereby facilitating the identification of alternative splicing events and isoform expressions. Recently, numerous computational tools for isoform detection using long-read sequencing data have been developed. Nevertheless, there remains a deficiency in comparative studies that systemically evaluate the performance of these tools, which are implemented with different algorithms, under various simulations that encompass potential influencing factors. In this study, we conducted a benchmark analysis of thirteen methods implemented in nine tools capable of identifying isoform structures from long-read RNA-seq data. We evaluated their performances using simulated data, which represented diverse sequencing platforms generated by an in-house simulator, RNA sequins (sequencing spike-ins) data, as well as experimental data. Our findings demonstrate IsoQuant as a highly effective tool for isoform detection with LRS, with Bambu and StringTie2 also exhibiting strong performance. These results offer valuable guidance for future research on alternative splicing analysis and the ongoing improvement of tools for isoform detection using LRS data.

A Cross-Process Signal Integrity Analysis (CPSIA) Method and Design Optimization for Wafer-on-Wafer Stacked DRAM.

A multi-layer stacked Dynamic Random Access Memory (DRAM) platform is introduced to address the memory wall issue. This platform features high-density vertical interconnects established between DRAM units for high-capacity memory and logic units for computation, utilizing Wafer-on-Wafer (WoW) hybrid bonding and mini Through-Silicon Via (TSV) technologies. This 3DIC architecture includes commercial DRAM, logic, and 3DIC manufacturing processes. Their design documents typically come from different foundries, presenting challenges for signal integrity design and analysis. This paper establishes a lumped circuit based on 3DIC physical structure and calculates all values of the lumped elements in the circuit model with the transmission line model. A Cross-Process Signal Integrity Analysis (CPSIA) method is introduced, which integrates three different manufacturing processes by modeling vertical stacking cells and connecting DRAM and logic netlists in one simulation environment. In combination with the dedicated buffer driving method, the CPSIA method is used to analyze 3DIC impacts. Simulation results show that the timing uncertainty introduced by 3DIC crosstalk ranges from 31 ps to 62 ps. This analysis result explains the stable slight variation in the maximum frequency observed in vertically stacked memory arrays from different DRAM layers in the physical testing results, demonstrating the effectiveness of this CPSIA method.

Weight status changes from childhood to adulthood were associated with cardiometabolic outcomes in adulthood.

AIM: Few studies have assessed the association between weight changes from childhood to adulthood and cardiometabolic factors in adulthood. The aim of this study was to explore the relationships between weight changes from childhood to adulthood and cardiometabolic factors in adulthood using national Chinese data. METHODS: We included 649 participants from the China Health and Nutrition Survey from 1989 to 2009 and divided them into four groups by their body mass index from 6 to 37 years of age. They were selected using multistage random cluster sampling from 15 areas with large variations in economic and social development. Poisson regression models assessed associations between weight status changes and cardiometabolic outcomes in adulthood. RESULTS: The risk of multiple abnormal cardiometabolic outcomes in adulthood was increased in the 126 subjects with normal weight in childhood but overweight or obesity in adulthood and the 28 with obesity at both ages, compared to the 462 with normal weight at both ages. There was insufficient evidence to demonstrate that the 33 who had weight issues as children, but not as adults, had an increased risk. CONCLUSION: Being overweight or obese in both childhood and adulthood or during adulthood only increased the risk of abnormal cardiometabolic outcomes in adulthood. Larger studies need to investigate whether weight problems in childhood, but not adulthood, increase the risk.

CO2 Valorization in Deep Eutectic Solvents.

The deep eutectic solvent (DES) has emerged in recent years as a valuable medium for converting CO2 into valuable chemicals because of its easy availability, stability, and safety, and its capability to dissolve carbon dioxide. CO2 valorization in DES has evolved rapidly over the past 20 years. As well as being used as solvents for acid/base-promoted CO2 conversion for the production of cyclic carbonates and carbamates, DESs can be used as reaction media for electrochemical CO2 reduction for formic acid and CO. Among these products, cyclic carbonates can be used as solvents and electrolytes, carbamate derivatives include the core structure of many herbicides and pesticides, and formic acid and carbon monoxide, the C1 electrochemical products, are essential raw materials in the chemical industries. An overview of the application of DESs for CO2 valorization in recent years is presented in this review, followed by a compilation and comparison of product types and reaction mechanisms within the different types of DESs, and an outlook on how CO2 valorization will be developed in the future.

CRISPR-TE: a web-based tool to generate single guide RNAs targeting transposable elements.

BACKGROUND: The CRISPR/Cas systems have emerged as powerful tools in genome engineering. Recent studies highlighting the crucial role of transposable elements (TEs) have stimulated research interest in manipulating these elements to understand their functions. However, designing single guide RNAs (sgRNAs) that are specific and efficient for TE manipulation is a significant challenge, given their sequence repetitiveness and high copy numbers. While various sgRNA design tools have been developed for gene editing, an optimized sgRNA designer for TE manipulation has yet to be established. RESULTS: We present CRISPR-TE, a web-based application featuring an accessible graphical user interface, available at https://www.crisprte.cn/ , and currently tailored to the human and mouse genomes. CRISPR-TE identifies all potential sgRNAs for TEs and provides a comprehensive solution for efficient TE targeting at both the single copy and subfamily levels. Our analysis shows that sgRNAs targeting TEs can more effectively target evolutionarily young TEs with conserved sequences at the subfamily level. CONCLUSIONS: CRISPR-TE offers a versatile framework for designing sgRNAs for TE targeting. CRISPR-TE is publicly accessible at https://www.crisprte.cn/ as an online web service and the source code of CRISPR-TE is available at https://github.com/WanluLiuLab/CRISPRTE/ .

CAROTID ARTERY ULTRASOUND FOR ASSESSING FLUID RESPONSIVENESS IN PATIENTS UNDERGOING MECHANICAL VENTILATION WITH LOW TIDAL VOLUME AND PRESERVED SPONTANEOUS BREATHING.

ABSTRACT: Objective : This study aimed to investigate whether changes in carotid artery corrected flow time (ΔFTc bolus ) and carotid artery peak flow velocity respiratory variation (Δ V peak bolus ) induced by the fluid challenge could reliably predict fluid responsiveness in mechanically ventilated patients with a tidal volume < 8 mL/kg Predicted Body Weight while preserving spontaneous breathing. Methods : Carotid artery corrected flow time, Δ V peak, and hemodynamic data were measured before and after administration of 250 mL crystalloids. Fluid responsiveness was defined as a 10% or more increase in stroke volume index as assessed by noninvasive cardiac output monitoring after the fluid challenge. Results : A total of 43 patients with acute circulatory failure were enrolled in this study. Forty-three patients underwent a total of 60 fluid challenges. The ΔFTc bolus and Δ V peak bolus showed a significant difference between the fluid responsiveness positive group (n = 35) and the fluid responsiveness negative group (n = 25). Spearman correlation test showed that ΔFTc bolus and Δ V peak bolus with the relative increase in stroke volume index after fluid expansion ( r = 0.5296, P < 0.0001; r = 0.3175, P = 0.0135). Multiple logistic regression analysis demonstrated that ΔFTc bolus and Δ V peak bolus were significantly correlated with fluid responsiveness in patients with acute circulatory failure. The areas under the receiver operating characteristic curves of ΔFTc bolus and Δ V peak bolus for predicting fluid responsiveness were 0.935 and 0.750, respectively. The optimal cutoff values of ΔFTc bolus and Δ V peak bolus were 0.725 (sensitivity = 97.1%, specificity = 84%) and 4.21% (sensitivity = 65.7%, specificity = 80%), respectively. Conclusion : In mechanically ventilated patients with a tidal volume < 8 mL/kg while preserving spontaneous breathing, ΔFTc bolus and Δ V peak bolus could predict fluid responsiveness. The predictive performance of ΔFTc bolus was superior to Δ V peak bolus .

Suberoylanilide hydroxamic acid upregulates reticulophagy receptor expression and promotes cell death in hepatocellular carcinoma cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common clinical condition with a poor prognosis and few effective treatment options. Potent anticancer agents for treating HCC must be identified. Epigenetics plays an essential role in HCC tumorigenesis. Suberoylanilide hydroxamic acid (SAHA), the most common histone deacetylase inhibitor agent, triggers many forms of cell death in HCC. However, the underlying mechanism of action remains unclear. Family with sequence similarity 134 member B (FAM134B)-induced reticulophagy, a selective autophagic pathway, participates in the decision of cell fate and exhibits anticancer activity. This study focused on the relationship between FAM134B-induced reticulophagy and SAHA-mediated cell death. AIM: To elucidate potential roles and underlying molecular mechanisms of reticulophagy in SAHA-induced HCC cell death. METHODS: The viability, apoptosis, cell cycle, migration, and invasion of SAHA-treated Huh7 and MHCC97L cells were measured. Proteins related to the reticulophagy pathway, mitochondria-endoplasmic reticulum (ER) contact sites, intrinsic mitochondrial apoptosis, and histone acetylation were quantified using western blotting. ER and lysosome colocalization, and mitochondrial Ca2+ levels were characterized via confocal microscopy. The level of cell death was evaluated through Hoechst 33342 staining and propidium iodide colocalization. Chromatin immunoprecipitation was used to verify histone H4 lysine-16 acetylation in the FAM134B promoter region. RESULTS: After SAHA treatment, the proliferation of Huh7 and MHCC97L cells was significantly inhibited, and the migration and invasion abilities were greatly blocked in vitro. This promoted apoptosis and caused G1 phase cells to increase in a concentration-dependent manner. Following treatment with SAHA, ER-phagy was activated, thereby triggering autophagy-mediated cell death of HCC cells in vitro. Western blotting and chromatin immunoprecipitation assays confirmed that SAHA regulated FAM134B expression by enhancing the histone H4 lysine-16 acetylation in the FAM134B promoter region. Further, SAHA disturbed the Ca2+ homeostasis and upregulated the level of autocrine motility factor receptor and proteins related to mitochondria-endoplasmic reticulum contact sites in HCC cells. Additionally, SAHA decreased the mitochondrial membrane potential levels, thereby accelerating the activation of the reticulophagy-mediated mitochondrial apoptosis pathway and promoting HCC cell death in vitro. CONCLUSION: SAHA stimulates FAM134B-mediated ER-phagy to synergistically enhance the mitochondrial apoptotic pathway, thereby enhancing HCC cell death.

Baseline correction for Raman spectra using a spectral estimation-based asymmetrically reweighted penalized least squares method.

Baseline correction is necessary for the qualitative and quantitative analysis of samples because of the existence of background fluorescence interference in Raman spectra. The asymmetric least squares (ALS) method is an adaptive and automated algorithm that avoids peak detection operations along with other user interactions. However, current ALS-based improved algorithms only consider the smoothness configuration of regions where the signals are greater than the fitted baseline, which results in smoothing distortion. In this paper, an asymmetrically reweighted penalized least squares method based on spectral estimation (SEALS) is proposed. SEALS considers not only the uniform distribution of additive noise along the baseline but also the energy distribution of the signal above and below the fitted baseline. The energy distribution is estimated using inverse Fourier and autoregressive models to create a spectral estimation kernel. This kernel effectively optimizes and balances the asymmetric weight assigned to each data point. By doing so, it resolves the issue of local oversmoothing that is typically encountered in the asymmetrically reweighted penalized least squares method. This oversmoothing problem can negatively impact the iteration depth and accuracy of baseline fitting. In comparative experiments on simulated spectra, SEALS demonstrated a better baseline fitting performance compared to several other advanced baseline correction methods, both under moderate and strong fluorescence backgrounds. It has also been proven to be highly resistant to noise interference. When applied to real Raman spectra, the algorithm correctly restored the weak peaks and removed the fluorescence peaks, demonstrating the effectiveness of this method. The computation time of the proposed method was approximately 0.05 s, which satisfies the real-time baseline correction requirements of practical spectroscopy acquisition.

Summertime Urban Ammonia Emissions May Be Substantially Underestimated in Beijing, China.

Ammonia (NH3) is critical to the nitrogen cycle and PM2.5 formation, yet a great deal of uncertainty exists in its urban emission quantifications. Model-underestimated NH3 concentrations have been reported for cities, yet few studies have provided an explanation. Here, we explore reasons for severe WRF-Chem model underestimations of NH3 concentrations in Beijing in August 2018, including simulated gas-particle partitioning, meteorology, regional transport, and emissions, using spatially refined (3 km resolution) NH3 emission estimates in the agricultural sector for Beijing-Tianjin-Hebei and in the traffic sector for Beijing. We find that simulated NH3 concentrations are significantly lower than ground-based and satellite observations during August in Beijing, while wintertime underestimations are much more moderate. Further analyses and sensitivity experiments show that such discrepancies cannot be attributed to factors other than biases in NH3 emissions. Using site measurements as constraints, we estimate that both agricultural and non-agricultural NH3 emission totals in Beijing shall increase by ∼5 times to match the observations. Future research should be performed to allocate underestimations to urban fertilizer, power, traffic, or residential sources. Dense and regular urban NH3 observations are necessary to constrain and validate bottom-up inventories and NHx simulation.

T cell proliferation requires ribosomal maturation in nucleolar condensates dependent on DCAF13.

T cells require rapid proliferation to initiate adaptive immunity to prevent pathogen attacks. The nucleolus, a distinct subnuclear membrane-less compartment for ribosomal biogenesis, is indispensable for cell proliferation. However, specific nucleolar proteins involved in rapid T cell proliferation and their underlying molecular regulatory mechanism remain elusive. Here, we identified an essential nucleolar protein, DCAF13, in T cells and revealed its significant regulation of rapid T cell proliferation. Its depletion drastically impairs T cell proliferation due to severe 18S rRNA maturation failure, consequent abnormal ribosome assembly in nucleoli, and insufficient production of nascent proteins. Mechanistically, we propose that DCAF13 promotes NPM1 phase separation to accelerate pre-RNA enrichment and its endonuclease UTP23 for 18S rRNA maturation during T cell proliferation. Our findings reveal the modulatory effect of nucleolar NPM1/DCAF13 phase separation on ribosomal maturation to ensure rapid T cell proliferation and further pathogen clearance for the first time.

Global food loss and waste embodies unrecognized harms to air quality and biodiversity hotspots.

Global food loss and waste (FLW) undermines the resilience and sustainability of food systems and is closely tied to the United Nation's Sustainable Development Goals on climate, resource use and food security. Here we reveal strong yet under-discussed interconnections between FLW and two other Sustainable Development Goals of Human Health and Life on Land via the nitrogen cycle. We find that eliminating global FLW in 2015 would have reduced anthropogenic NH3 emissions associated with food production by 11.4 Tg (16%), decreased local PM2.5 concentrations by up to 5 µg m-3 and PM2.5-related years of life lost by 1.5 million years, and mitigated nitrogen critical load exceedances in global biodiversity hotspots by up to 19%. Halving FLW in 2030 will reduce years of life lost by 0.5-0.8 million years and nitrogen deposition by 4.7-6.0 Tg N per year (4%) (range for socioeconomic pathways). Complementary to near-term NH3 mitigation potential via technological measures, our study emphasizes incentivizing FLW reduction efforts from air quality and ecosystem health perspectives.

Optimal reactive nitrogen control pathways identified for cost-effective PM2.5 mitigation in Europe.

Excess reactive nitrogen (Nr), including nitrogen oxides (NOx) and ammonia (NH3), contributes strongly to fine particulate matter (PM2.5) air pollution in Europe, posing challenges to public health. Designing cost-effective Nr control roadmaps for PM2.5 mitigation requires considering both mitigation efficiencies and implementation costs. Here we identify optimal Nr control pathways for Europe by integrating emission estimations, air quality modeling, exposure-mortality modeling, Nr control experiments and cost data. We find that phasing out Nr emissions would reduce PM2.5 by 2.3 ± 1.2 µg·m-3 in Europe, helping many locations achieve the World Health Organization (WHO) guidelines and reducing PM2.5-related premature deaths by almost 100 thousand in 2015. Low-ambition NH3 controls have similar PM2.5 mitigation efficiencies as NOx in Eastern Europe, but are less effective in Western Europe until reductions exceed 40%. The efficiency for NH3 controls increases at high-ambition reductions while NOx slightly decreases. When costs are considered, strategies for both regions uniformly shift in favor of NH3 controls, as NH3 controls up to 50% remain 5-11 times more cost-effective than NOx per unit PM2.5 reduction, emphasizing the priority of NH3 control policies for Europe.

Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids.

Studies of cultured embryos have provided insights into human peri-implantation development. However, detailed knowledge of peri-implantation lineage development as well as underlying mechanisms remains obscure. Using 3D-cultured human embryos, herein we report a complete cell atlas of the early post-implantation lineages and decipher cellular composition and gene signatures of the epiblast and hypoblast derivatives. In addition, we develop an embryo-like assembloid (E-assembloid) by assembling naive hESCs and extraembryonic cells. Using human embryos and E-assembloids, we reveal that WNT, BMP and Nodal signaling pathways synergistically, but functionally differently, orchestrate human peri-implantation lineage development. Specially, we dissect mechanisms underlying extraembryonic mesoderm and extraembryonic endoderm specifications. Finally, an improved E-assembloid is developed to recapitulate the epiblast and hypoblast development and tissue architectures in the pre-gastrulation human embryo. Our findings provide insights into human peri-implantation development, and the E-assembloid offers a useful model to disentangle cellular behaviors and signaling interactions that drive human embryogenesis.

Efficacy and safety of esketamine for sedation among patients undergoing gastrointestinal endoscopy: a systematic review and meta-analysis.

BACKGROUND: Patients who undergo gastrointestinal endoscopy often require propofol-based sedation combined with analgesics. At present, the efficacy and safety of esketamine as an adjunct to propofol for sedation during endoscopic procedures in patients remains controversial. Moreover, there is no universal agreement regarding the appropriate dose of esketamine supplementation. This study aimed to assess the efficacy and safety of esketamine as an adjunct to propofol for sedation during endoscopic procedures in patients. METHODS: Seven electronic databases and three clinical trial registry platforms were searched and the deadline was February 2023. Randomized controlled trials (RCTs) evaluating the efficacy of esketamine for sedation were included by two reviewers. Data from the eligible studies were combined to calculate the pooled risk ratio or standardized mean difference. RESULTS: Eighteen studies with 1962 esketamine participants were included in the analysis. As an adjunct to propofol, the administration of esketamine reduced the recovery time compared to normal saline (NS). However, there was no significant difference between the opioids group and ketamine group. For propofol dosage, the administration of esketamine required a lower propofol dosage compared to the NS group and opioids group].For complications, the esketamine group had fewer complications compared to the NS group and opioid group in patients, but there were no significant differences between the esketamine group and ketamine group. Notably, the coadministration of esketamine was associated with a higher risk of visual disturbance compared to the NS group. In addition, we used subgroup analysis to investigate whether 0.2-0.5 mg/kg esketamine was effective and tolerable for patients. CONCLUSION: Esketamine as an adjunct to propofol, is an appropriate effective alternative for sedation in participants undergoing gastrointestinal endoscopy. However, considering the possibility of its psychotomimetic effects, esketamine should be used with caution.

Bibliometric analysis of worldwide research trends on breast cancer about inflammation.

Background: The most prevalent cancer and the second-leading cause of cancer-related mortality in women is breast cancer. Growing interest has been shown in recent years in learning more about the processes behind the development of breast cancer. It has been shown that persistent inflammation may play a significant role in the advancement of breast cancer. However, a comprehensive and objective analysis on the state of inflammation in breast cancer research is still lacking. This study was aim to undertake a bibliometric analysis of breast cancer research associated with inflammation between 2013 and 2022 in order to identify the trends, dynamics, and scientific outputs in the field. Methods: From 2013 to 2022, original and review publications on breast cancer and inflammation-associated research were retrieved from the Web of Science Core Collection (WOSCC) database. To examine the position of yearly publications, journals, nations, institutions, and authors, we employed two bibliometric tools (CiteSpace and VOSviewer). After that, by examining keyword visualization and keyword bursts, we determined the hot research fields related to inflammation in breast cancer. Results: we discovered 6902 publications regarding inflammation in breast cancer by using our retrieval approach. In terms of the number of publications, The United States ranked first in the global study, followed by China and Italy. In terms of institutions, the University of Texas System, UT MD Anderson Cancer Center, and University of California System are in the top 3 for the quantity of publications published. The most popular journal for this field research is "CANCERS." Ueno NT, Woodward WA, Cristofanilli M, and others have made significant contributions to the understanding of inflammation in breast cancer. In the end, we conducted a biclustering analysis on keywords and discovered three clusters that represent research hotspots. Conclusion: According to the global trend, the research output of inflammation in breast cancer is increasing. The information provided in this article, including the cooperation network information of authors, nations, journals, and institutions, may help researchers to better understand hotspots and developing patterns in this discipline. At present, the focus of study gradually shifts from "phenotype study" to "therapeutic research". It is recommended to pay attention to the latest hot spots, such as targeted therapy, antimicrobial activity and nanoparticle.

Breast Milk Constituents and the Development of Breast Milk Jaundice in Neonates: A Systematic Review.

Breast milk is tailored for optimal growth in all infants; however, in some infants, it is related to a unique phenomenon referred to as breast milk jaundice (BMJ). BMJ is a type of prolonged unconjugated hyperbilirubinemia that is often late onset in otherwise healthy-appearing newborns, and its occurrence might be related to breast milk itself. This review aims to systematically evaluate evidence regarding breast milk composition and the development of BMJ in healthy neonates. PubMed, Scopus and Embase were searched up to 13 February 2023 with key search terms, including neonates, hyperbilirubinemia, and breastfeeding. A total of 678 unique studies were identified and 12 were ultimately included in the systematic review with narrative synthesis. These included studies covered both nutritional compositions (e.g., fats and proteins) and bioactive factors (e.g., enzymes and growth factors) of breast milk and formally assessed the difference in the concentration (or presence) of various endogenous components of breast milk collected from mothers of BMJ infants and healthy infants. The results were inconsistent and inconclusive for most of the substances of interest, and there was only a single study available (e.g., total energy and mineral content, bile salts and cytokines); conflicting or even contradictory results arose when there were two or more studies on the subject matter (e.g., fats and free fatty acids contents and epidermal growth factor). The etiology of BMJ is likely multifactorial, and no single constituent of breast milk could explain all the BMJ cases observed. Further well-designed studies are warranted to investigate the complex interaction between maternal physiology, the breast milk system and infant physiology before this field could be progressed to uncover the etiology of BMJ.

Modeling global oceanic nitrogen deposition from food systems and its mitigation potential by reducing overuse of fertilizers.

Growing population and consumption pose unprecedented demands on food production. However, ammonia emissions mainly from food systems increase oceanic nitrogen deposition contributing to eutrophication. Here, we developed a long-term oceanic nitrogen deposition dataset (1970 to 2018) with updated ammonia emissions from food systems, evaluated the impact of ammonia emissions on oceanic nitrogen deposition patterns, and discussed the potential impact of nitrogen fertilizer overuse. Based on the chemical transport modeling approach, oceanic ammonia-related nitrogen deposition increased by 89% globally between 1970 and 2018, and now, it exceeds oxidized nitrogen deposition by over 20% in coastal regions including China Sea, India Coastal, and Northeastern Atlantic Shelves. Approximately 38% of agricultural nitrogen fertilizer was excessive, which corresponds to 15% of global oceanic ammonia-related nitrogen deposition. Policymakers and water quality managers need to pay increasingly more attention to ammonia associated with food production if the goal of reducing coastal nitrogen pollution is to be achieved for Sustainable Development Goals.

50 Hz Magnetic Field Exposure Inhibited Spontaneous Movement of Zebrafish Larvae through ROS-Mediated syn2a Expression.

Extremely low frequency electromagnetic field (ELF-EMF) exists widely in public and occupational environments. However, its potential adverse effects and the underlying mechanism on nervous system, especially behavior are still poorly understood. In this study, zebrafish embryos (including a transfected synapsin IIa (syn2a) overexpression plasmid) at 3 h post-fertilization (hpf) were exposed to a 50-Hz magnetic field (MF) with a series of intensities (100, 200, 400 and 800 µT, respectively) for 1 h or 24 h every day for 5 days. Results showed that, although MF exposure did not affect the basic development parameters including hatching rate, mortality and malformation rate, yet MF at 200 µT could significantly induce spontaneous movement (SM) hypoactivity in zebrafish larvae. Histological examination presented morphological abnormalities of the brain such as condensed cell nucleus and cytoplasm, increased intercellular space. Moreover, exposure to MF at 200 µT inhibited syn2a transcription and expression, and increased reactive oxygen species (ROS) level as well. Overexpression of syn2a could effectively rescue MF-induced SM hypoactivity in zebrafish. Pretreatment with N-acetyl-L-cysteine (NAC) could not only recover syn2a protein expression which was weakened by MF exposure, but also abolish MF-induced SM hypoactivity. However, syn2a overexpression did not affect MF-increased ROS. Taken together, the findings suggested that exposure to a 50-Hz MF inhibited spontaneous movement of zebrafish larvae via ROS-mediated syn2a expression in a nonlinear manner.

Adaptive Stimulations in a Biophysical Network Model of Parkinson's Disease.

Deep brain stimulation (DBS)-through a surgically implanted electrode to the subthalamic nucleus (STN)-has become a widely used therapeutic option for the treatment of Parkinson's disease and other neurological disorders. The standard conventional high-frequency stimulation (HF) that is currently used has several drawbacks. To overcome the limitations of HF, researchers have been developing closed-loop and demand-controlled, adaptive stimulation protocols wherein the amount of current that is delivered is turned on and off in real-time in accordance with a biophysical signal. Computational modeling of DBS in neural network models is an increasingly important tool in the development of new protocols that aid researchers in animal and clinical studies. In this computational study, we seek to implement a novel technique of DBS where we stimulate the STN in an adaptive fashion using the interspike time of the neurons to control stimulation. Our results show that our protocol eliminates bursts in the synchronized bursting neuronal activity of the STN, which is hypothesized to cause the failure of thalamocortical neurons (TC) to respond properly to excitatory cortical inputs. Further, we are able to significantly decrease the TC relay errors, representing potential therapeutics for Parkinson's disease.