Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive cardiopulmonary disease with a high mortality rate. Although growing evidence has revealed the importance of dysregulated energetic metabolism in the pathogenesis of PH, the underlying cellular and molecular mechanisms are not fully understood. In this study, we focused on ME1 (malic enzyme 1), a key enzyme linking glycolysis to the tricarboxylic acid cycle. We aimed to determine the role and mechanistic action of ME1 in PH. METHODS: Global and endothelial-specific ME1 knockout mice were used to investigate the role of ME1 in hypoxia- and SU5416/hypoxia (SuHx)-induced PH. Small hairpin RNA and ME1 enzymatic inhibitor (ME1*) were used to study the mechanism of ME1 in pulmonary artery endothelial cells. Downstream key metabolic pathways and mediators of ME1 were identified by metabolomics analysis in vivo and ME1-mediated energetic alterations were examined by Seahorse metabolic analysis in vitro. The pharmacological effect of ME1* on PH treatment was evaluated in PH animal models induced by SuHx. RESULTS: We found that ME1 protein level and enzymatic activity were highly elevated in lung tissues of patients and mice with PH, primarily in vascular endothelial cells. Global knockout of ME1 protected mice from developing hypoxia- or SuHx-induced PH. Endothelial-specific ME1 deletion similarly attenuated pulmonary vascular remodeling and PH development in mice, suggesting a critical role of endothelial ME1 in PH. Mechanistic studies revealed that ME1 inhibition promoted downstream adenosine production and activated A2AR-mediated adenosine signaling, which leads to an increase in nitric oxide generation and a decrease in proinflammatory molecule expression in endothelial cells. ME1 inhibition activated adenosine production in an ATP-dependent manner through regulating malate-aspartate NADH (nicotinamide adenine dinucleotide plus hydrogen) shuttle and thereby balancing oxidative phosphorylation and glycolysis. Pharmacological inactivation of ME1 attenuated the progression of PH in both preventive and therapeutic settings by promoting adenosine production in vivo. CONCLUSIONS: Our findings indicate that ME1 upregulation in endothelial cells plays a causative role in PH development by negatively regulating adenosine production and subsequently dysregulating endothelial functions. Our findings also suggest that ME1 may represent as a novel pharmacological target for upregulating protective adenosine signaling in PH therapy.

Members of the KCTD family are major regulators of cAMP signaling.

Cyclic adenosine monophosphate (cAMP) is a pivotal second messenger with an essential role in neuronal function. cAMP synthesis by adenylyl cyclases (AC) is controlled by G protein-coupled receptor (GPCR) signaling systems. However, the network of molecular players involved in the process is incompletely defined. Here, we used CRISPR/Cas9-based screening to identify that members of the potassium channel tetradimerization domain (KCTD) family are major regulators of cAMP signaling. Focusing on striatal neurons, we show that the dominant isoform KCTD5 exerts its effects through an unusual mechanism that modulates the influx of Zn2+ via the Zip14 transporter to exert unique allosteric effects on AC. We further show that KCTD5 controls the amplitude and sensitivity of stimulatory GPCR inputs to cAMP production by Gßγ-mediated AC regulation. Finally, we report that KCTD5 haploinsufficiency in mice leads to motor deficits that can be reversed by chelating Zn2+ Together, our findings uncover KCTD proteins as major regulators of neuronal cAMP signaling via diverse mechanisms.

Highly Efficient Photoelectrochemical Alkene Epoxidation on a Dye-Sensitized Photoanode.

In photoelectrochemical (PEC) cells, selective oxidation of organic substrates coupled with hydrogen evolution represents a promising approach for value-added chemical production and solar energy conversion. In this study, we report on PEC epoxidation of alkenes at a ruthenium dye-sensitized photoanode in a CH3CN/H2O mixed solvent with LiBr as a mediator and water as the oxygen source. The dye-sensitized photoanode was found to exhibit significant advantages in the simultaneous improvement of charge separation and suppression of charge recombination. First, LiBr as a redox mediator plays a critical role in charge separation, leading to an excellent excited electron injection efficiency of 95% and a high dye regeneration efficiency of 87%. Second, the predominant charge recombination pathway on the dye-sensitized photoanode is efficiently blocked by the reaction between alkene and the in situ generated bromine oxidant. As a result, the current system achieved a remarkable photocurrent density of over 4 mA cm-2 with a record-high incident photo-to-current efficiency (IPCE) of 51% and extraordinary selectivity of up to 99% for the epoxidation of a wide range of alkenes. Meanwhile, nearly 100% Faradaic efficiency for hydrogen evolution was obtained. The performance shown here exceeds that obtained by metal oxide-based semiconductor photoanodes under comparable conditions, demonstrating the great potential of dye-sensitized photoelectrodes for organic synthesis owing to their diversity and tunability.

Self-Assembly of Single-Virus SERS Hotspots for Highly Sensitive In Situ Detection of SARS-CoV-2 on Solid Surfaces.

Microbial surface transmission has aroused great attention since the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Developing a simple in situ detection method for viruses on solid surfaces is of great significance for timely public health surveillance. Taking advantage of the natural structure of SARS-CoV-2, we reported the assembly of Au@AgNPs on the surface of a single virus by the specific aptamer-spike protein interaction. Multiple hotspots can be created between the neighboring Au@AgNPs for the highly sensitive surface-enhanced Raman scattering (SERS) detection of SARS-CoV-2. Using two different aptamers labeled with Cy3 and Au@AgNPs, in situ SERS detection of pseudotyped SARS-CoV-2 (PSV) on packaging surfaces was achieved within 20 min, with a detection limit of 5.26 TCID50/mL. For the blind testing of 20 PSV-contaminated packaging samples, this SERS aptasensor had a sensitivity of 100% and an accuracy of 100%. This assay has been successfully applied to in situ detection of PSV on the surfaces of different packaging materials, suggesting its potential applicability.

Inorganic Polysulfide Chemistries for Better Energy Storage Systems.

ConspectusSulfur-based cathode materials have become a research hot spot as one of the most promising candidates for next-generation, high-energy lithium batteries. However, the insulating nature of elemental sulfur or organosulfides has become the biggest challenge that leads to dramatic degradation and hinders their practical application. The disadvantage is more obvious for all-solid-state battery systems, which require both high electronic and ionic migration at the same sites to realize a complete electrochemical reaction. In addition to adding conductive components into the cathode composites, another effective way to realize high-reversibility sulfur-based cathodes is by optimizing the inherent nature of sulfur-based materials to make them "conductive". Inorganic polysulfide materials including polysulfide molecules, selenium-sulfur solid solutions, and (lithium) metal polysulfides are promising, as they have different structures that can make them intrinsically conductive or becoming conductive during lithiation. They all contain at least one -S-S- bridged bond, which is the intrinsic structural characteristic and the source of the chemical properties of these polysulfide compounds. For example, by balancing the conductivity and reversible capacity, researchers in the US National Aeronautics and Space Administration (NASA) have shown that 500 Wh/kg solid-state Li-Se/S batteries can power cars and even electric aircraft.We have long been focusing on the inorganic polysulfide component, reported the selenium-sulfur solid solutions, the first sulfur-rich phosphorus polysulfide molecules, and followed the research of metal polysulfide components. The proposed Account summarizes our current knowledge of the fundamental aspects of inorganic polysulfides in energy storage systems based on state-of-the-art publications on this topic. Both fast electron and ion migrations within the electrode materials are vital to achieving high-energy batteries. We begin by illustrating effective approaches to enhance the electronic/ionic conductivity of sulfur-based electrode materials. We then present some basic observations and properties (especially the intrinsic high conductivities) of the inorganic polysulfide electrode materials. The key chemical and structural factors dictating their conductive and electrochemical behaviors will be discussed. Finally, we show the advantages and broad applications of inorganic polysulfides in energy storage areas. The proposed Account will provide an insightful perspective on the current knowledge of inorganic polysulfide materials, as well as their future research directions and development potential, serving as a keynote reference for researchers in the field of energy storage.

Development and characterisation of [18F]TTDP, a novel T cell immunoglobulin and ITIM domain tracer, in humanised mice and non-human primates.

PURPOSE: The T cell immunoglobulin and ITIM domain (TIGIT) blockade immunotherapy response is directly associated with individual differences of TIGIT expression on tumour-infiltrating lymphocytes (TILs) in tumour immune microenvironment (TIME) of non-small cell lung cancer (NSCLC). Here, we developed a TIGIT-targeted PET tracer to evaluate its feasibility in predicting immunotherapy efficacy, aiming to manage NSCLC patients accurately. METHODS: We synthesised a 18F-labeled TIGIT-targeted D-peptide, [18F]TTDP, and investigated the specificity of [18F]TTDP both to murine TIGIT and human TIGIT by a series of in vitro and in vivo assays. [18F]TTDP PET imaging was performed in humanised immune system (HIS) mice models bearing NSCLC patient-derived xenografts (PDXs) to evaluate the predictive value of FDA-approved combination immunotherapy of atezolizumab plus tiragolumab. Lastly, rhesus macaque was applied for [18F] TTDP PET to explore the tracer's in vivo distribution and translational potential in non-human primates. RESULTS: [18F]TTDP showed high specificity for both murine TIGIT and human TIGIT in vitro and in vivo. The HIS NSCLC PDX platform was successfully established for [18F]TTDP PET imaging, and tumour uptake of [18F]TTDP was significantly correlated with the TIGIT expression of TILs in the TIME. [18F]TTDP PET imaging, in predicting treatment response to the combination immunotherapy in NSCLC HIS-PDX models, showed a sensitivity of 83.33% and a specificity of 100%. In addition, [18F]TTDP PET also showed cross-species consistency of the tracer biodistribution between non-human primate and murine animals, and no adverse events were observed. CONCLUSION: The combined implementation of the [18F]TTDP and HIS-PDX model creates a state-of-the-art preclinical platform that will impact the identification and validation of TIGIT-targeted PET image-guided diagnosis, treatment response prediction, beneficial patient screening, novel immunotherapies, and ultimately the outcome of NSCLC patients. We first provided in vivo biodistribution of [18F]TTDP PET imaging in rhesus macaque, indicating its excellent translational potential in the clinic.

Permeation characteristics and cross-linking efficacy of iontophoresis-assisted riboflavin delivery for accelerated riboflavin-ultraviolet A scleral collagen cross-linking in porcine eyes.

The purpose of this study is to investigate whether the iontophoresis-assisted riboflavin delivery to posterior sclera with less delivery time, can achieve the same riboflavin permeation efficiency as the passive soaking way, and its effect on the mechanical properties of posterior sclera for accelerated scleral collagen cross-linking (A-SXL). In this study, 0.1% riboflavin solution was applied into the posterior sclera of porcine eyes either by the iontophoresis-assisted or passive soaking method, with delivery time of 5, 7.5, 10, 12.5, 15, 17.5, and 20 min, respectively. The fluorescence intensity and the distribution of riboflavin concentration in the 10 µm frozen sections of the sclera were evaluated by fluorescence inverted microscope. The posterior sclera with riboflavin treatment through either the iontophoresis-assisted or the passive soaking method for different durations ranging from 5 to 20 min was treated with ultraviolet A (UVA) irradiation at an intensity of 10 mW/cm2 for 9 min. The elastic modulus was determined at the physiological strain level using the uniaxial tensile test after ASXL. The results showed that the fluorescence intensity of riboflavin increased by prolonging the delivery time in both the iontophoresis and passive soaking groups, and the permeation depth of riboflavin remained constant over 15 min. The fluorescence intensity in the iontophoresis group was significantly higher than in the passive soaking group at 12.5 min and 15 min, respectively. The elastic modulus at 12.5 min in the iontophoresis group was significantly higher than in the passive soaking group at the same delivery time and showed no significant difference compared to the passive soaking group at 20 min. In conclusion, it indicated that iontophoresis-assisted delivery could not only shorten the surgery time but also achieve similar mechanical performance to the passive soaking method in ASXL.

Development and application of whole-chromosome painting of chromosomes 7A and 8A of Arachis duranensis based on chromosome-specific single-copy oligonucleotides.

For peanut, the lack of stable cytological markers is a barrier to tracking specific chromosomes, elucidating the genetic relationships between genomes and identifying chromosomal variations. Chromosome mapping using single-copy oligonucleotide (oligo) probe libraries has unique advantages for identifying homologous chromosomes and chromosomal rearrangements. In this study, we developed two whole-chromosome single-copy oligo probe libraries, LS-7A and LS-8A, based on the reference genome sequences of chromosomes 7A and 8A of Arachis duranensis. Fluorescence in situ hybridization (FISH) analysis confirmed that the libraries could specifically paint chromosomes 7 and 8. In addition, sequential FISH and electronic localization of LS-7A and LS-8A in A. duranensis (AA) and A. ipaensis (BB) showed that chromosomes 7A and 8A contained translocations and inversions relative to chromosomes 7B and 8B. Analysis of the chromosomes of wild Arachis species using LS-8A confirmed that this library could accurately and effectively identify A genome species. Finally, LS-7A and LS-8A were used to paint the chromosomes of interspecific hybrids and their progenies, which verified the authenticity of the interspecific hybrids and identified a disomic addition line. This study provides a model for developing specific oligo probes to identify the structural variations of other chromosomes in Arachis and demonstrates the practical utility of LS-7A and LS-8A.

Improved high-performance liquid chromatography tandem mass spectrometry method for quantification of infliximab in pediatric plasma and its application in therapeutic drug monitoring.

RATIONALE: The application of infliximab (IFX) to immune-mediated disease is limited by the significant individual variability and associated clinical nonresponse, emphasizing the importance of therapeutic drug monitoring (TDM). Because of the cross-reactivity, limited linear range, and high costs, the clinical application of the previous reported methods was limited. Here, an improved high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to address the issues. METHODS: This study developed an improved bioanalytical HPLC-MS/MS method coupling nanosurface and molecular-orientation limited proteolysis technology. The commercially available compound P14R was selected as the internal standard. This method was developed with fewer volume of reagents and was thoroughly validated. The validated method was applied to TDM in pediatric inflammatory bowel disease (IBD). RESULTS: Chromatography was performed using a Shim-pack GISS-HP C18 metal-free column (3 µm, 2.1 × 100 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile at 0.4 mL/min. Detection and quantitation were performed using electrospray ionization (ESI) and multiple reaction monitoring in the positive ion mode. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect, and stability. The method exhibited a linear dynamic range of 0.3-100 µg/mL, with intra- and inter-day precision and relative errors below 15%. The recovery and matrix effect were measured as 87.28%-89.72% and 41.98%-67.17%, respectively, which were effectively compensated by the internal standard. A total of 32 samples collected from 24 pediatric patients with IBD were analyzed using the validated method, and only 46.9% achieved the reported targeted trough level. CONCLUSION: This study developed an improved HPLC-MS/MS method for the quantitative determination of IFX concentration in human plasma. The accurate, reliable, and cost-effective method was validated and utilized in the analysis of clinical samples. The results confirmed the importance of TDM on IFX and the clinical application prospects of the improved method.

Simple and field-adapted species identification of biological specimens combining multiplex multienzyme isothermal rapid amplification, lateral flow dipsticks, and universal primers for initial rapid screening without standard PCR laboratory.

Species identification of biological specimens can provide the valuable clues and accelerate the speed of prosecution material processing for forensic investigation, especially when the case scene is inaccessible and the physical evidence is cumbersome. Thus, establishing a rapid, simple, and field-adapted species identification method is crucial for forensic scientists, particularly as first-line technology at the crime scene for initial rapid screening. In this study, we established a new field-adapted species identification method by combining multiplex multienzyme isothermal rapid amplification (MIRA), lateral flow dipstick (LFD) system, and universal primers. Universal primers targeting COX I and COX II genes were used in multiplex MIRA-LFD system for seven species identification, and a dedicated MIRA-LFD system primer targeting CYT B gene was used to detect the human material. DNA extraction was performed by collecting DNA directly from the centrifuged supernatant. Our study found that the entire amplification process took only 15 min at 37 °C and the results of LFDs could be visually observed after 10 min. The detection sensitivity of human material could reach 10 pg, which is equivalent to the detection of single cell. Different common animal samples mixed at the ratio of 1 ng:1 ng, 10 ng:1 ng, and 1 ng:10 ng could be detected successfully. Furthermore, the damaged and degraded samples could also be detected. Therefore, the convenient, feasible, and rapid approach for species identification is suitable for popularization as first-line technology at the crime scene for initial rapid screening and provides a great convenient for forensic application.

Prenatal Exposure of PFAS in Cohorts of Pregnant Women: Identifying the Critical Windows of Vulnerability and Health Implications.

Cohorts of pregnant women in 2018 and 2020 were selected to explore prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS). Maternal serum during the whole pregnancy (first to third trimesters) and matched cord serum were collected for the analysis of 50 PFAS. Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and 6:2 fluorotelomer sulfonic acid (6:2 FTS) were the dominant PFAS in both the maternal and cord serum. The median ∑PFAS concentration was 14.18 ng/mL, and the ∑PFAS concentration was observed to decline from the first trimester to the third trimester. The transplacental transfer efficiencies (TTE) of 29 PFAS were comprehensively assessed, and a "U"-shaped trend in TTE values with increasing molecular chain length of perfluoroalkyl carboxylic acid (PFCA) was observed in this study. Moreover, the maternal concentrations of 9-chlorohexadecafluoro-3-oxanonane-1-sulfonic acid (6:2 Cl-PFESA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), PFOS, and hexafluoropropylene oxide dimer acid (HFPO-DA) in the 2020 cohort were significantly lower than those in the 2018 cohort, declining by about 23.85-43.2% from 2018 to 2020 (p < 0.05). Higher proportions of emerging PFAS were observed in fetuses born in 2020. This birth cohort was collected during the COVID-19 epidemic period. The change in the PFAS exposure scene might be in response to the different exposure profiles of the 2018 and 2020 cohorts, which are attributed to the impact of COVID-19 on the social activities and environment of pregnant women. Finally, by application of a multiple informant model, the third trimester was identified as the critical window of vulnerability to PFAS exposure that affects birth weight and birth length.

CO Oxidation Promoted by NO Adsorption on RhMn2O3- Cluster Anions.

CO oxidation represents an important model reaction in the gas phase to provide a clear structure-reactivity relationship in related heterogeneous catalysis. Herein, in combination with mass spectrometry experiments and quantum-chemical calculations, we identified that the RhMn2O3- cluster cannot oxidize CO into gas-phase CO2 at room temperature, while the NO preadsorbed products RhMn2O3-[(NO)1,2] are highly reactive in CO oxidation. This discovery is helpful to get a fundamental understanding on the reaction behavior in real-world three-way catalytic conditions where different kinds of reactants coexist. Theoretical calculations were performed to rationalize the crucial roles of preadsorbed NO where the strongly attached NO on the Rh atom can greatly stabilize the products RhMn2O2-[(NO)1,2] during CO oxidation and at the same time works together with the Rh atom to store electrons that stay originally in the attached CO2- unit. The leading result is that the desorption of CO2, which is the rate-determining step of CO oxidation by RhMn2O3-, can be greatly facilitated on the reactions of RhMn2O3-[(NO)1,2] with CO.

Serum lipid reference values recommended during a twin pregnancy and evaluating its association with perinatal outcomes.

BACKGROUND: Maternal lipid metabolism fluctuations have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus over what constitutes normal maternal lipid values during twin pregnancy. Therefore, the aim of this study was to establish a serum lipid reference range for a twin pregnancy. METHODS: A retrospective survey was conducted, from 2011 to 2021, at the Peking University Third Hospital. A total of 881 twin pregnancies, with lipid data from early and middle pregnancies, were included. After excluding those with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), and low-density lipid cholesterol (LDL-C) levels, using the mean and standard deviation to determine appropriate percentiles. We later determined the lipid reference range in early and middle pregnancy based on the initial results. We evaluated Inappropriate lipid levels associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, small for gestational age. RESULTS: (1) Serum levels of TC, TG, LDL-C, and HDL-C increased significantly from early to late pregnancy, where the greatest increase was observed in TG. (2) Based on the results, we recommend that TC, TG, and LDL-C serum reference values during early and middle pregnancy should be less than the 95th percentile. On the other hand, HDL-C should be greater than the 5th percentile. During early pregnancy, the values recommended are TC < 5.31 mmol/L, TG < 2.25 mmol/L, HDL > 1.02 mmol/L and LDL < 3.27 mmol/L, and those during middle pregnancy are TC < 8.74 mmol/L, TG < 4.89 mmol/L, HDL > 1.25 mmol/L and LDL < 5.49 mmol/L, while the values during late pregnancy are TC < 9.11 mmol/L, TG < 6.70 mmol/L, HDL > 1.10 mmol/L and LDL < 5.81 mmol/L. Higher levels of blood lipids were associated with GDM, PE, SGA. CONCLUSIONS: We suggested a reference ranges for blood lipids during the twin pregnancy in a Chinese population. The reference ranges recommended by this study can be used to identify women with twin pregnancies using unfavorable lipid values. Higher levels of blood lipids were associated with adverse pregnancy outcomes.

Situation and associated factors of needle stick and sharps injuries among health-care workers in a tertiary hospital: a cross-sectional survey.

PURPOSE: This study aimed to assess the prevalence of and factors associated with needle stick and sharps injuries (NSSIs) among health-care workers (HCWs) in a tertiary hospital in China. MATERIALS AND METHODS: This retrospective survey was conducted with 562 HCWs at a tertiary hospital in China in July 2023. Information was collected using a self-designed questionnaire, and all enrolled members were required to fill in the demographic characteristics, occurrence of NSSIs and other associated factors in the past year. Logistic analysis was used to identify variables associated with NSSIs. RESULTS: The proportion of participants with at least one injury within the year preceding the investigation was 21.2%. Male (AOR = 2.116 [1.265, 3.538]), working hours per week > 40 (AOR = 1.718 [1.056,2.796]), rarely checking blood-borne infections before invasive operations (AOR = 2.219 [1.303,3.782]) were significantly associated with NSSIs. CONCLUSION: The prevalence of NSSIs was not low in the survey area, especially in male, individuals with longer working hours, and rarely checking blood-borne infections before invasive operations. Therefore, it is necessary to promote educational programs to enhance awareness of standard prevention measures, especially for key populations, and reduce heavy workloads to decrease the occurrence of such injuries.

Chemical Synthesis of Fucosylated Chondroitin Sulfate Tetrasaccharide with Fucosyl Branch at the 6-OH of GalNAc Residue.

Fucosylated chondroitin sulfate is a unique glycosaminoglycan isolated from sea cucumbers, with excellent anticoagulant activity. The fucosyl branch in FCS is generally located at the 3-OH of D-glucuronic acid but, recently, a novel structure with α-L-fucose linked to the 6-OH of N-acetyl-galactosamine has been found. Here, using functionalized monosaccharide building blocks, we prepared novel FCS tetrasaccharides with fucosyl branches both at the 6-OH of GalNAc and 3-OH of GlcA. In the synthesis, the protective group strategy of selective O-sulfation, as well as stereoselective glycosylation, was established, which enabled the efficient synthesis of the specific tetrasaccharide compounds. This research enriches knowledge on the structural types of FCS oligosaccharides and facilitates the exploration of the structure-activity relationship in the future.

Toxic mechanism in Daphnia magna due to phthalic acid esters and CuO nanoparticles co-exposure: The insight of physiological, microbiomic and metabolomic profiles.

Various phthalic acid esters (PAEs) such as dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) co-exist with nanopollutants in aquatic environment. In this study, Daphnia magna was exposed to nano-CuO and DBP or BBP at environmental relevant concentrations for 21-days to investigate these combined toxic effects. Acute EC50 values (48 h) of nano-CuO, DBP, and BBP were 12.572 mg/L, 8.978 mg/L, and 4.785 mg/L, respectively. Results showed that co-exposure with nano-CuO (500 µg/L) for 21 days significantly enhanced the toxicity of DBP (100 µg/L) and BBP (100 µg/L) to Daphnia magna by 18.37% and 18.11%, respectively. The activities of superoxide dismutase, catalase, and glutathione S-transferase were enhanced by 10.95% and 14.07%, 25.63% and 25.91%, and 39.93% and 35.01% in nano-CuO+DBP and nano-CuO+BBP treatments as compared to the individual exposure groups, verifying that antioxidative defense responses were activated. Furthermore, the co-exposure of nano-CuO and PAEs decreased the population richness and diversity microbiota, and changed the microbial community composition in Daphnia magna. Metabolomic analysis elucidated that nano-CuO + PAEs exposure induced stronger disturbance on metabolic network and molecular function, including amino acid, nucleotides, and lipid metabolism-related metabolic pathways, as comparison to PAEs single exposure treatments. In summary, the integration of physiological, microflora, and untargeted metabolomics analysis offers a fresh perspective into the potential ecological risk associated with nanopollutants and phthalate pollution in aquatic ecosystems.

The disease recurrence perception scale for patients with inflammatory bowel disease: Instrument development and cross-sectional validation study.

Disease recurrence perception plays a key role in disease management and subsequent disease recurrence prevention. However, there are no specific tools for assessing disease recurrence perception in patients with inflammatory bowel disease (IBD) characterized by alternating remission and recurrence. To develop and validate an instrument for measuring disease recurrence perception of patients with IBD, the study was conducted in two steps: (1) instrument development and (2) psychometric tests. A total of 623 patients with IBD participated in the study. The common sense model of illness self-regulation (CSM) was used as a framework for instrument development. The administered version contained 48 items intended to be relevant to at least one of the six dimensions of the model. Based on preliminary analyzes, 12 items were deleted leaving 36 items for more detailed psychometric and factor analyzes. The Cronbach's alpha coefficient of the total 36-item instrument was 0.915. The content validity indexes at item and scale levels were satisfactory. The test-retest reliability of the total instrument was 0.870. Exploratory principal components analysis (n = 278) was used to identify six components congruent with intended CSM constructs that accounted for 62.6% of total item variance. Confirmatory factor analysis (n = 345) found acceptable fit for the six factor measurement model (χ2/df = 1.999, GFI = 0.846, NFI = 0.855, IFI = 0.922, TLI = 0.910, CFI = 0.921, RMSEA = 0.054). Overall, the DRPSIBD demonstrated satisfactory reliability and validity to warrant further development as a measure of disease recurrence perception of patients with IBD.

Alveolar Macrophages-Mediated Translocation of Intratracheally Delivered Perfluorocarbon Nanoparticles to Achieve Lung Cancer 19F-MR Imaging.

Recent advances in intratracheal delivery strategies have sparked considerable biomedical interest in developing this promising approach for lung cancer diagnosis and treatment. However, there are very few relevant studies on the behavior and mechanism of imaging nanoparticles (NPs) after intratracheal delivery. Here, we found that nanosized perfluoro-15-crown-5-ether (PFCE NPs, ∼200 nm) exhibite significant 19F-MRI signal-to-noise ratio (SNR) enhancement than perfluorooctyl bromide (PFOB NPs) up to day 7 after intratracheal delivery. Alveolar macrophages (AMs) engulf PFCE NPs, become PFCE NPs-laden AMs, and then migrate into the tumor margin, resulting in increased tumor PFCE concentration and 19F-MRI signals. AMs-mediated translocation of PFCE NPs to lung draning lymph nodes (dLNs) decreases the background PFCE concentration. Our results shed light on the dynamic AMs-mediated translocation of intratracheally delivered PFC NPs for effective lung tumor visualization and reveal a pathway to develop and promote the clinical translation of an intratracheal delivery-based imaging strategy.

[Anisotropy and viscoelasticity of different corneal regions in rabbit corneal ectasia model].

The mechanical properties of the cornea in corneal ectasia disease undergo a significant reduction, yet the alterations in mechanical properties within distinct corneal regions remain unclear. In this study, we established a rabbit corneal ectasia model by employing collagenase II to degrade the corneal matrix within a central diameter of 6 mm. Optical coherence tomography was employed for the in vivo assessment of corneal morphology (corneal thickness and corneal curvature) one month after operation. Anisotropy and viscoelastic characteristics of corneal tissue were evaluated through biaxial and uniaxial testing, respectively. The results demonstrated a marked decrease in central corneal thickness, with no significant changes observed in corneal curvature. Under different strains, the elastic modulus of the cornea exhibited no significant differences in the up-down and naso-temporal directions between the control and model groups. However, the cornea in the model group displayed a significantly lower elastic modulus compared to the control group. Specifically, the elastic modulus of the central region cornea in the model group was significantly lower than that of the entire cornea within the same group. Moreover, in comparison to the control group, the cornea in the model group exhibited a significant increase in both creep rate and overall deformation rate. The instantaneous modulus and equilibrium modulus were significantly reduced in the model cornea. No significant differences were observed between the entire cornea and the central cornea concerning these parameters. The results indicate that corneal anisotropy remains unchanged in collagenase-induced ectatic cornea. However, a significant reduction in viscoelastic properties is noticed. This study provides valuable insights for investigating changes in corneal mechanical properties within different regions of ectatic corneal disease.

[Study on methods measuring mechanical properties of arterial wall by macroscopic indentation].

Accurately evaluating the local biomechanics of arterial wall is crucial for diagnosing and treating arterial diseases. Indentation measurement can be used to evaluate the local mechanical properties of the artery. However, the effects of the indenter's geometric structure and the analysis theory on measurement results remain uncertain. In this paper, four kinds of indenters were used to measure the pulmonary aorta, the proximal thoracic aorta and the distal thoracic aorta in pigs, and the arterial elastic modulus was calculated by Sneddon and Sirghi theory to explore the influence of the indenter geometry and analysis theory on the measured elastic modulus. The results showed that the arterial elastic modulus measured by cylindrical indenter was lower than that measured by spherical indenter. In addition, compared with the calculated results of Sirghi theory, the Sneddon theory, which does not take adhesion forces in account, resulted in slightly larger elastic modulus values. In conclusion, this study provides parametric support for effective measurement of arterial local mechanical properties by millimeter indentation technique.