Characterizing genetic variation on the Z chromosome in Schistosoma japonicum reveals host-parasite co-evolution.

BACKGROUND: Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems. Schistosoma japonicum is endemic to Asia; the Z chromosome of S. japonicum comprises one-quarter of the entire genome. Detection of positive selection using resequencing data to understand adaptive evolution has been applied to a variety of pathogens, including S. japonicum. However, the contribution of the Z chromosome to evolution and adaptation is often neglected. METHODS: We obtained 1,077,526 high-quality SNPs on the Z chromosome in 72 S. japonicum using re-sequencing data publicly. To examine the faster Z effect, we compared the sequence divergence of S. japonicum with two closely related species, Schistosoma haematobium and S. mansoni. Genetic diversity was compared between the Z chromosome and autosomes in S. japonicum by calculating the nucleotide diversity (π) and Dxy values. Population structure was also assessed based on PCA and structure analysis. Besides, we employed multiple methods including Tajima's D, FST, iHS, XP-EHH, and CMS to detect positive selection signals on the Z chromosome. Further RNAi knockdown experiments were performed to investigate the potential biological functions of the candidate genes. RESULTS: Our study found that the Z chromosome of S. japonicum showed faster evolution and more pronounced genetic divergence than autosomes, although the effect may be smaller than the variation among genes. Compared with autosomes, the Z chromosome in S. japonicum had a more pronounced genetic divergence of sub-populations. Notably, we identified a set of candidate genes associated with host-parasite co-evolution. In particular, LCAT exhibited significant selection signals within the Taiwan population. Further RNA interference experiments suggested that LCAT is necessary for S. japonicum survival and propagation in the definitive host. In addition, we identified several genes related to the specificity of the intermediate host in the C-M population, including Rab6 and VCP, which are involved in adaptive immune evasion to the host. CONCLUSIONS: Our study provides valuable insights into the adaptive evolution of the Z chromosome in S. japonicum and further advances our understanding of the co-evolution of this medically important parasite and its hosts.

The Single Cell Immunogenomic Landscape after Neoadjuvant Immunotherapy combined Chemotherapy in Esophageal Squamous Cell Carcinoma.

Neoadjuvant immunotherapy represents promising strategy in the treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms underlying its impact on treatment sensitivity or resistance remain a subject of controversy. In this study, we conducted single-cell RNA and T/B cell receptor (scTCR/scBCR) sequencing of CD45+ immune cells on samples from 10 patients who received neoadjuvant immunotherapy and chemotherapy. We also validated our findings using multiplexed immunofluorescence and analyzed bulk RNA-seq from other cohorts in public database. By integrating analysis of 87357 CD45+ cells, we found GZMK+ effector memory T cells were relatively enriched and CXCL13+ exhausted T cells and regulator T cells decreased among responders, indicating a persistent anti-tumor memory process. Additionally, the enhanced presence of BCR expansion and somatic hypermutation process within TNFRSF13B+ memory B cells suggested their roles in antigen presentation. This was further corroborated by the evidence of the T-B co-stimulation pattern and CXCL13-CXCR5 axis. The complexity of myeloid cell heterogeneity was also particularly pronounced. The elevated expression of S100A7 in ESCC, as detected by bulk RNA-seq, was associated with an exhausted and immunosuppressive tumor microenvironment. In summary, this study has unveiled a potential regulatory network among immune cells and the clonal dynamics of their functions, and the mechanisms of exhaustion and memory conversion between GZMK+ Tem and TNFRSF13B+ Bmem from antigen presentation and co-stimulation perspectives during neoadjuvant PD-1 blockade treatment in ESCC.

Contrast Staining in Noninfarcted Tissue after Endovascular Treatment of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Contrast staining is a common finding after endovascular treatment of acute ischemic stroke. It typically occurs in infarcted tissue and is considered an indicator of irreversible brain damage. Contrast staining in noninfarcted tissue has not been systematically investigated. We sought to assess the incidence, risk factors, and clinical significance of contrast staining in noninfarcted tissue after endovascular treatment. MATERIALS AND METHODS: We conducted a retrospective review of consecutive patients who underwent endovascular treatment for anterior circulation large-vessel occlusion acute ischemic stroke. Contrast staining, defined as new hyperdensity on CT after endovascular treatment, was categorized as either contrast staining in infarcted tissue if the stained region demonstrated restricted diffusion on follow-up MR imaging or contrast staining in noninfarcted tissue if the stained region demonstrated no restricted diffusion. Baseline differences between patients with and without contrast staining in noninfarcted tissue were compared. Logistic regression was used to identify independent associations for contrast staining in noninfarcted tissue after endovascular treatment. RESULTS: Among 194 patients who underwent endovascular treatment for large-vessel occlusion acute ischemic stroke and met the inclusion criteria, contrast staining in infarcted tissue was noted in 52/194 (26.8%) patients; contrast staining in noninfarcted tissue, in 26 (13.4%) patients. Both contrast staining in infarcted tissue and contrast staining in noninfarcted tissue were noted in 5.6% (11/194). Patients with contrast staining in noninfarcted tissue were found to have a higher likelihood of having an ASPECTS of 8-10, to be associated with contrast staining in infarcted tissue, and to achieve successful reperfusion compared with those without contrast staining in noninfarcted tissue. In contrast staining in noninfarcted tissue regions, the average attenuation was 40 HU, significantly lower than the contrast staining in infarcted tissue regions (53 HU). None of the patients with contrast staining in noninfarcted tissue had clinical worsening during their hospital stay. The median discharge mRS was significantly lower in patients with contrast staining in noninfarcted tissue than in those without (3 versus 4; P = .018). No independent predictors of contrast staining in noninfarcted tissue were found. CONCLUSIONS: Contrast staining can be seen outside the infarcted tissue after endovascular treatment of acute ischemic stroke, likely attributable to the reversible disruption of the BBB in ischemic but not infarcted tissue. While generally benign, understanding its characteristics is important because it may mimic pathologic conditions such as infarcted tissue and cerebral edema.

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Oral AL01211 in Healthy Chinese Volunteers.

BACKGROUND AND OBJECTIVE: Aberrant accumulation of glycosphingolipids (GSLs) in the lysosome leads to GSL storage diseases. Glucosylceramide synthase inhibitors (GCSi) have the potential to treat several GSL storage diseases by reducing the synthesis of the disease-causing GSLs. AL01211 is a potent oral GCSi under investigation for Type 1 Gaucher disease and Fabry disease. Here, we evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of AL01211 in healthy Chinese volunteers. METHODS: AL01211 was tested in a Phase 1, single-center, randomized, double-blind, placebo-controlled study with single-dose (15 and 60 mg) and multiple-dose (30 mg) arms. RESULTS: Results of AL01211 demonstrated dose-dependent pharmacokinetics, rapid absorption (median time to maximum plasma concentration [tmax] 2.5-4 hours), relatively slow clearance rate (mean apparent total clearance from plasma [CL/F] 88.3-200 L/h) and the mean terminal half-life above 30 hours. Repeated once-daily oral administration of AL01211 for 14 days had an approximately 2-fold accumulation, reaching steady-state levels between 7 and 10 days, and led to a 73% reduction in plasma glucosylceramide (GL1) on Day 14. AL01211 was safe and well tolerated, with no identified serious adverse events. CONCLUSION: AL01211 showed a favorable pharmacokinetic, pharmacodynamics, safety, and tolerability profile in healthy Chinese volunteers. These data support the further clinical development of AL01211 as a therapy for GSL storage diseases. CLINICAL TRIAL REGISTRY: Clinical Trial Registry no. CTR20221202 ( http://www.chinadrugtrials.org.cn ) registered on 6 June 2022 and ChiCTR2200061431 ( http://www.chictr.org.cn ) registered on 24 June 2022.

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

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

Imaging HIV-1 Nuclear Import, Uncoating, and Proviral Transcription.

Live-cell imaging has become a powerful tool for dissecting the behavior of viral complexes during HIV-1 infection with high temporal and spatial resolution. Very few HIV-1 particles in a viral population are infectious and successfully complete replication (~1/50). Single-particle live-cell imaging enables the study of these rare infectious viral particles, which cannot be accomplished in biochemical assays that measure the average property of the entire viral population, most of which are not infectious. The timing and location of many events in the early stage of the HIV-1 life cycle, including nuclear import, uncoating, and integration, have only recently been elucidated. Live-cell imaging also provides a valuable approach to study interactions of viral and host factors in distinct cellular compartments and at specific stages of viral replication. Successful live-cell imaging experiments require careful consideration of the fluorescent labeling method used and avoid or minimize its potential impact on normal viral replication and produce misleading results. Ideally, it is beneficial to utilize multiple virus labeling strategies and compare the results to ensure that the virion labeling did not adversely influence the viral replication step that is under investigation. Another potential benefit of using different labeling strategies is that they can provide information about the state of the viral complexes. Here, we describe our methods that utilize multiple fluorescent protein labeling approaches to visualize and quantify important events in the HIV-1 life cycle, including docking HIV-1 particles with the nuclear envelope (NE) and their nuclear import, uncoating, and proviral transcription.

Single-Virion Analysis: A Method to Visualize HIV-1 Particle Content Using Fluorescence Microscopy.

HIV-1 virions incorporate viral RNA, cellular RNAs, and proteins during the assembly process. Some of these components, such as the viral RNA genome and viral proteins, are essential for viral replication, whereas others, such as host innate immune proteins, can inhibit virus replication. Therefore, analyzing the virion content is an integral part of studying HIV-1 replication. Traditionally, virion contents have been examined using biochemical assays, which can provide information on the presence or absence of the molecule of interest but not its distribution in the virion population. Here, we describe a method, single-virion analysis, that directly examines the presence of molecules of interest in individual viral particles using fluorescence microscopy. Thus, this method can detect both the presence and the distribution of molecules of interest in the virion population. Single-virion analysis was first developed to study HIV-1 RNA genome packaging. In this assay, HIV-1 unspliced RNA is labeled with a fluorescently tagged RNA-binding protein (protein A) and some of the Gag proteins are labeled with a different fluorescent protein (protein B). Using fluorescence microscopy, HIV-1 particles can be identified by the fluorescent protein B signal and the presence of unspliced HIV-1 RNA can be identified by the fluorescent protein A signal. Therefore, the proportions of particles that contain unspliced RNA can be determined by the fraction of Gag particles that also have a colocalized RNA signal. By tagging the molecule of interest with fluorescent proteins, single-virion analysis can be easily adapted to study the incorporation of other viral or host cell molecules into particles. Indeed, this method has been adapted to examine the proportion of HIV-1 particles that contain APOBEC3 proteins and the fraction of particles that contain a modified Gag protein. Therefore, single-virion analysis is a flexible method to study the nucleic acid and protein content of HIV-1 particles.

Metagenomics analysis reveals effects of salinity fluctuation on diversity and ecological functions of high and low nucleic acid content bacteria.

Salinity is a critical environmental factor in marine ecosystems and has complex and wide-ranging biological effects. However, the effects of changing salinity on diversity and ecological functions of high nucleic acid (HNA) and low nucleic acid (LNA) bacteria are not well understood. In this study, we used 16S rRNA sequencing and metagenomic sequencing analysis to reveal the response of HNA and LNA bacterial communities and their ecological functions to salinity, which was decreased from 26 ‰ to 16 ‰. The results showed that salinity changes had significant effects on the community composition of HNA and LNA bacteria. Among LNA bacteria, 14 classes showed a significant correlation between relative abundance and salinity. Salinity changes can lead to the transfer of some bacteria from HNA bacteria to LNA bacteria. In the network topology relationship, the complexity of the network between HNA and LNA bacterial communities gradually decreased with decreased salinity. The abundance of some carbon and nitrogen cycling genes in HNA and LNA bacteria varied with salinity. Overall, this study demonstrates the effects of salinity on diversity and ecological functions and suggests the importance of salinity in regulating HNA and LNA bacterial communities and functions.

Noncontrast CT Selected Thrombectomy vs Medical Management for Late-Window Anterior Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window. METHODS: This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well (TSLW) from January 2014 to May 2022 were included. The primary end point was the 90-day ordinal shift in the modified Rankin Scale (mRS) score. Inverse probability treatment weighting (IPTW) and multivariable methods were used. RESULTS: Of 5,098 patients screened, 839 patients were included, with a median (interquartile range) age of 75 (64-83) years; 455 (54.2%) were women. There were 616 patients selected to undergo EVT by NCCT (73.4%) and 223 (26.6%) who were medically managed. In IPTW analyses, there was a more favorable 90-day ordinal mRS shift in patients selected by NCCT to EVT vs those who were medically managed (odds ratio [OR] 1.99, 95% CI 1.53-2.59; p < 0.001). There were higher rates of 90-day functional independence (mRS 0-2) in the EVT group (40.1% vs 18.4%, OR 3.31, 95% CI 2.11-5.20; p < 0.001). sICH was nonsignificantly higher in the EVT group (8.5% vs 1.4%, OR 3.77, 95% CI 0.72-19.7, p = 0.12). Mortality at 90 days was lower in the EVT vs MM group (23.9% vs 32.3%, OR 0.61, 95% CI 0.45-0.83, p = 0.002). DISCUSSION: In patients with proximal anterior LVO in the extended time window, there was a lower rate of disability and mortality in patients selected with NCCT and CTA to EVT compared with those who were medically managed. These findings support the use of NCCT as a simpler and more inclusive approach to patient selection in the extended window. TRIAL REGISTRATION INFORMATION: This study was registered at ClinicalTrials.gov under NCT04096248. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with proximal anterior circulation occlusion presenting with ischemic stroke from 6 to 24 hours, compared with medical management, those undergoing thrombectomy based on NCCT have reduced disability and mortality at 90 days.

Associations and Mediating Pathways between Childhood Adversity and Risk of Dementia: A Cohort Study in the UK Biobank.

BACKGROUND: While childhood adversity (CA) is known to be associated with multiple adverse outcomes, its link with dementia is an area with limited exploration and inconsistent agreement. The study aimed to examine the longitudinal associations of CA with incident all-cause dementia and to quantify the potential mediating pathways. METHODS: Data from the UK Biobank. CA, encompassing neglect and abuse, was evaluated retrospectively by an online mental health questionnaire. Physical performance, psychological factors, lifestyles, and biological indicators assessed at baseline were considered potential mediators. Incident all-cause dementia was defined by International Classification of Diseases, Tenth Revision codes obtained through self-reported medical conditions, primary care, hospital admission, and death registrations. Cox proportional hazard models were applied to estimate the longitudinal associations. Mediation analyses were conducted on potential mediators to examine their contribution. RESULTS: This cohort study comprised 150,152 non-demented individuals (mean [SD] age, 55.9 [7.7] years) at baseline (2006-2010). Compared to individuals who did not experience CA, those exposed to any CA exhibited a 30.0% higher risk of dementia (hazard ratio [HR] =1.300, 95% confidence interval [CI]: 1.129-1.496). Each additional CA was associated with a 15.5% (95% CI: 8.8-22.5%, P  for trend < 0.001) increased dementia risks. Depression, smoking, and low grip strength explained 8.7%, 2.4% and 0.9% of the associations, respectively. Biomarkers involving inflammation, erythrocytes, liver, and kidney function mediated the associations by 0.6% to 1.4%. CONCLUSIONS: The study revealed the detrimental effects of CA on dementia and identified some potential mediators, namely depression, smoking, low grip strength, and several targeted biomarkers. In addition to calling more attention to CA, the findings underscore the importance of interventions targeting modifiable mediators in preventing dementia.

Lipid matrix-specific pretreatment method for enhancing the extractability and allergenicity maintenance of bovine milk allergens in ELISA detection.

The presence of various components in the food matrix makes allergen detection difficult and inaccurate, and pretreatment is an innovative breakthrough point. Food matrices were categorised based on their composition. Subsequently, a pretreatment method was established using a combination of ultrasound-assisted n-hexane degreasing and weakly alkaline extraction systems to enhance the detection accuracy of bovine milk allergens. Results showed that more allergens were obtained with less structural destruction, as demonstrated using immunological quantification and spectral analysis. Concurrently, allergenicity preservation was confirmed through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, a KU812 cell degranulation model, and western blotting. The method exhibited good accuracy (bias, 8.47%), repeatability (RSDr, 1.52%), and stability (RSDR, 5.65%). In foods with high lipid content, such as chocolate, the allergen content was 2.29-fold higher than that of commercial kits. Laser confocal scanning microscopy (LCSM) and scanning electron microscopy (SEM) analyses revealed a significant decrease in fat content after post-pretreatment using our method. In addition, colloidal stability surpassed that achieved using commercial kits, as indicated through the PSA and zeta potential results. The results demonstrated the superiority of the extractability and allergenicity maintenance of lipid matrix-specific pretreatment methods for improving the accuracy of ELISA based allergen detection in real food.

A study on pulmonary function in children with obstructive sleep apnea hypopnea syndrome.

OBJECTIVE: To investigate the pulmonary function of children with obstructive sleep apnea syndrome. METHODS: A total of 328 children aged 3 to 12 years old who were evaluated for a sleep disorder from January 2022 to June 2023 were selected as the observation group, classified into mild, moderate, and severe categories based on the apnea hypopnea index. The number of children with mild, moderate, and severe obstructive sleep apnea is 228, 62, and 28 respectively. Additionally, 126 healthy individuals aged 3 to 13 years old undergoing health examinations during the same period were selected as the control group. All subjects underwent sleep respiratory monitoring, pulmonary function tests, and impulse oscillometry. Comparative analysis was performed on pulmonary function indices (forced vital capacity, maximum ventilation, inspiratory capacity, total lung capacity, and inspiratory reserve volume), and respiratory impedance indices (resonant frequency, total respiratory impedance, viscous resistance at 5 Hz, 20 Hz, and 35 Hz). Pulmonary function indices were also compared among patients in the observation group with mild, moderate, and severe conditions. RESULTS: In the observation group, the FVC pre% of patients decreased by 10.5 ± 5.99 compared to the control group. The MVV of the control group decreased by 28.10 ± 2.22 compared to patients in the observation group. The IC of the control group decreased by 0.68 ± 0.44 compared to patients in the observation group. The TLC of the control group decreased by 1.354 ± 0.51 compared to patients in the observation group. The ERV of the control group decreased by 0.53 ± 0.30 compared to patients in the observation group. Additionally, the Fres, Zrs, R5, R20, and R35 of the observation group were higher than those of the control group by 10.73 ± 0.18, 1.78 ± 0.24, 0.11 ± 0.17, 0.86 ± 0.13, and 0.02 ± 0.21, respectively. In sum, the pulmonary function indices of the observation group were significantly lower than those of the control group, while the respiratory impedance indices were higher (P < 0.05). Within the observation group, the pulmonary function indices of severe patients were lower than those of moderate and mild patients, and moderate patients had lower pulmonary function indices than mild patients (P < 0.05). CONCLUSION: The pulmonary function of children with obstructive sleep apnea syndrome is impaired and varies in severity. There are significant differences in pulmonary function, underscoring the importance of monitoring pulmonary function in these children for clinical assessment and treatment prognosis.

Epigenome-wide association study of lung cancer among never smokers in two prospective cohorts in Shanghai, China.

BACKGROUND: The aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted. METHODS: We conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women's Health Study and Shanghai Men's Health Study. DNAm was measured in prediagnostic oral rinse samples using Illumina MethylationEPIC array. Initially, we conducted an EWAS to identify differentially methylated positions (DMPs) associated with lung cancer in the discovery sample of 101 subjects. The top 50 DMPs were further evaluated in a replication sample of 62 subjects, and results were pooled using fixed-effect meta-analysis. RESULTS: Our study identified three DMPs significantly associated with lung cancer at the epigenome-wide significance level of p<8.22×10-8. These DMPs were identified as cg09198866 (MYH9; TXN2), cg01411366 (SLC9A10) and cg12787323. Furthermore, examination of the top 1000 DMPs indicated significant enrichment in epithelial regulatory regions and their involvement in small GTPase-mediated signal transduction pathways. Additionally, GrimAge acceleration was identified as a risk factor for lung cancer (OR=1.19 per year; 95% CI 1.06 to 1.34). CONCLUSIONS: While replication in a larger sample size is necessary, our findings suggest that DNAm patterns in prediagnostic oral rinse samples could provide novel insights into the underlying mechanisms of lung cancer in never smokers.

Partial root-zone drying irrigation improves intrinsic water-use efficiency and maintains high photosynthesis by uncoupling stomatal and mesophyll conductance in cotton leaves.

Partial root-zone drying irrigation (PRD) can improve water-use efficiency (WUE) without reductions in photosynthesis; however, the mechanism by which this is attained is unclear. To amend that, PRD conditions were simulated by polyethylene glycol 6000 in a root-splitting system and the effects of PRD on cotton growth were studied. Results showed that PRD decreased stomatal conductance (gs) but increased mesophyll conductance (gm). Due to the contrasting effects on gs and gm, net photosynthetic rate (AN) remained unaffected, while the enhanced gm/gs ratio facilitated a larger intrinsic WUE. Further analyses indicated that PRD-induced reduction of gs was related to decreased stomatal size and stomatal pore area in adaxial and abaxial surface which was ascribed to lower pore length and width. PRD-induced variation of gm was ascribed to the reduced liquid-phase resistance, due to increases in chloroplast area facing to intercellular airspaces and the ratio of chloroplast surface area to total mesophyll cell area exposed to intercellular airspaces, as well as to decreases in the distance between cell wall and chloroplast, and between adjacent chloroplasts. The above results demonstrate that PRD, through alterations to stomatal and mesophyll structures, decoupled gs and gm responses, which ultimately increased intrinsic WUE and maintained AN.

A "dual-key-and-lock" platform for distinguishing autophagy during neuroinflammation.

Autophagy is an essential degradative process that governs the renewal of organelle and maintains the homeostasis of cellular microenvironment. Its dysregulation has been demonstrated to be an indicator for neuroinflammation. To elucidate the interrelationship between neuroinflammation and autophagy, optical probes are ideal tools as they offer a number of advantages such as high spatiotemporal resolution and non-invasive sensing, which help to visualize the physiological and pathological functions of interested analytes. However, single autophagy parameter-response probes may generate false-positive results since they cannot distinguish between neuroinflammation and other autophagic stimuli. In contrast, chemosensors that respond to two (or more) targets can improve selectivity by qualifying response conditions. Herein, a "dual-key-and-lock" strategy was applied to construct probe (Vis-NO) to selectively recognize autophagy under inflammation out of other stimuli. The red fluorescence of Vis-NO was lit up only in the simultaneously presence of high viscosity and nitric oxide (NO) in lysosome. Due to the characteristics of high viscosity and overexpressed NO within lysosomes, Vis-NO could be used to selectively identify autophagy during neuroinflammation, providing expanding insights into the interrelationship between autophagy, neuroinflammation and stroke in pathology, and informing about the mechanisms through which autophagy regulates inflammation.

A risk warning method for steady-state power quality based on VMD-LSTM and fuzzy model.

The risk warning for steady-state power quality in the power grid is essential for its prevention and management. However, current risk warning methods fall short in predicting the power quality trend while accounting for potential risks. Consequently, this study introduces a novel steady-state power quality risk warning method utilizing VMD-LSTM and a fuzzy model. Firstly, a power quality index prediction method based on variational mode decomposition (VMD) and long short-term memory (LSTM) is proposed. This approach significantly enhances prediction accuracy. Secondly, a power quality risk warning method incorporating kernel density estimation (KDE) and a fuzzy model is proposed, which systematically addresses the uncertainty associated with power quality risks. To validate the effectiveness and practicality of the proposed method, experiments are conducted using field monitoring data from a residential load in southern China. The results affirm the reliability and applicability of the proposed method. The simulation results show that the median error of prediction of power quality indexes by the proposed method is 5.03 % during the evaluated time period, and the prediction accuracy is mostly maintained above 90 %.

Potential Strategy to Control the Organic Components of Condensable Particulate Matter: A Critical Review.

More and more attention has been paid to condensable particulate matter (CPM) since its emissions have surpassed that of filterable particulate matter (FPM) with the large-scale application of ultralow-emission reform. CPM is a gaseous material in the flue stack but instantly turns into particles after leaving the stack. It is composed of inorganic and organic components. Organic components are an important part of CPM, and they are an irritant, teratogenic, and carcinogenic, which triggers photochemical smog, urban haze, and acid deposition. CPM organic components can aggravate air pollution and climate change; therefore, consideration should be given to them. Based on existing methods for removing atmospheric organic pollutants and combined with the characteristics of CPM organic components, we provide a critical overview from the aspects of (i) fundamental cognition of CPM, (ii) common methods to control CPM organic components, and (iii) catalytic oxidation of CPM organic components. As one of the most encouraging methods, catalytic oxidation is discussed in detail, especially in combination with selective catalytic reduction (SCR) technology, to meet the growing demands for multipollutant control (MPC). We believe that this review is inspiring for a fuller understanding and deeper exploration of promising approaches to control CPM organic components.

High-efficiency and economical uranium extraction from seawater with easily prepared supramolecular complexes.

Developing effective adsorbents for uranium extraction from natural seawater is strategically significant for the sustainable fuel supply of nuclear energy. Herein, stable and low-cost supramolecular complexes (PA-bPEI complexes) were facilely constructed through the assembly of phytic acid and hyperbranched polyethyleneimine based on the multiple modes of electrostatic interaction and hydrogen bonding. The PA-bPEI complexes exhibited not only high uptake (841.7 mg g-1) and selectivity (uranium/vanadium selectivity = 84.1) toward uranium but also good antibacterial ability against biofouling. Mechanism analysis revealed that phosphate chelating groups and amine assistant groups coordinated the uranyl ions together with a high affinity. To be more suitable for practical applications, powdery PA-bPEI complexes were compounded with sodium alginate to fabricate various macroscopic adsorbents with engineered forms, which achieved an extraction capacity of 9.0 mg g-1 in natural seawater after 50 days of testing. Impressively, the estimated economic cost of the macroscopic adsorbent for uranium extraction from seawater ($96.5 âˆ¼ 138.1 kg-1 uranium) was lower than that of all currently available uranium adsorbents. Due to their good uranium extraction performance and low economic cost, supramolecular complex-based adsorbents show great potential for industrial uranium extraction from seawater.

Targeted delivery of MerTK protein via cell membrane engineered nanoparticle enhances efferocytosis and attenuates atherosclerosis in diabetic ApoE-/- Mice.

BACKGROUND: Clearance of apoptotic cells by efferocytosis is crucial for prevention of atherosclerosis progress, and impaired efferocytosis contributes to the aggravated atherosclerosis. RESULTS: In this study, we found that diabetic ApoE-/- mice showed aggravated atherosclerosis as hyperglycemia damaged the efferocytosis capacity at least partially due to decreased expression of Mer tyrosine kinase (MerTK) on macrophages. To locally restore MerTK in the macrophages in the plaque, hybrid membrane nanovesicles (HMNVs) were thus developed. Briefly, cell membrane from MerTK overexpressing RAW264.7 cell and transferrin receptor (TfR) overexpressing HEK293T cell were mixed with DOPE polymers to produce nanovesicles designated as HMNVs. HMNVs could fuse with the recipient cell membrane and thus increased MerTK in diabetic macrophages, which in turn restored the efferocytosis capacity. Upon intravenous administration into diabetic ApoE-/- mice, superparamagnetic iron oxide nanoparticles (SMN) decorated HMNVs accumulated at the aorta site significantly under magnetic navigation, where the recipient macrophages cleared the apoptotic cells efficiently and thus decreased the inflammation. CONCLUSIONS:  Our study indicates that MerTK decrease in macrophages contributes to the aggravated atherosclerosis in diabetic ApoE-/- mice and regional restoration of MerTK in macrophages of the plaque via HMNVs could be a promising therapeutic approach.

Association and biological pathways between lung function and incident depression: a prospective cohort study of 280,032 participants.

BACKGROUND: Lung health is increasingly recognized as an essential factor in mental health. However, prospective evidence on lung function with incident depression remains to be determined. The study aimed to examine the prospective association between impaired lung function and incident depression and the underlying biological mechanisms. METHODS: This prospective cohort study comprised 280,032 non-depressed individuals with valid lung function measurements from the UK Biobank. Lung function was assessed through the forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1). Cox proportional hazard models were applied to estimate the associations between lung function and incident depression. Mediation analyses were fitted to investigate the potential mediating role of biomarkers and metabolites in the association. RESULTS: A total of 9514 participants (3.4%) developed depression during a median follow-up of 13.91 years. Individuals in the highest quartile had a lower risk of depression (FVC % predicted: HR = 0.880, 95% CI = 0.830-0.933; FEV1% predicted: HR = 0.854, 95% CI = 0.805-0.905) compared with those in the lowest quartile of the lung function indices. Additionally, the restricted cubic splines suggested lung function indices had reversed J-shaped associations with incident depression (nonlinear P < 0.05 for FVC % predicted and FEV1% predicted). Impaired lung function yielded similar risk estimates (HR = 1.124, 95% CI = 1.074-1.176). Biomarkers involving systemic inflammation, erythrocytes, and liver and renal function may be potential mediators in the lung function-depression association. CONCLUSIONS: This study revealed that the higher risk of developing depression was associated with impaired lung function. Also, the association might be partially mediated by biomarkers including systemic inflammation, erythrocytes, and liver and renal function, though these mediation findings should be interpreted with caution due to potential temporal ambiguity.