Lymphatic endothelial transcription factor Tbx1 promotes an immunosuppressive microenvironment to facilitate post-myocardial infarction repair.

The heart is an autoimmune-prone organ. It is crucial for the heart to keep injury-induced autoimmunity in check to avoid autoimmune-mediated inflammatory disease. However, little is known about how injury-induced autoimmunity is constrained in hearts. Here, we reveal an unknown intramyocardial immunosuppressive program driven by Tbx1, a DiGeorge syndrome disease gene that encodes a T-box transcription factor (TF). We found induced profound lymphangiogenic and immunomodulatory gene expression changes in lymphatic endothelial cells (LECs) after myocardial infarction (MI). The activated LECs penetrated the infarcted area and functioned as intramyocardial immune hubs to increase the numbers of tolerogenic dendritic cells (tDCs) and regulatory T (Treg) cells through the chemokine Ccl21 and integrin Icam1, thereby inhibiting the expansion of autoreactive CD8+ T cells and promoting reparative macrophage expansion to facilitate post-MI repair. Mimicking its timing and implementation may be an additional approach to treating autoimmunity-mediated cardiac diseases.

On-Site Computed Tomography-Derived Fractional Flow Reserve to Guide Management of Patients With Stable Coronary Artery Disease: The TARGET Randomized Trial.

BACKGROUND: Computed tomography-derived fractional flow reserve (CT-FFR) using on-site machine learning enables identification of both the presence of coronary artery disease and vessel-specific ischemia. However, it is unclear whether on-site CT-FFR improves clinical or economic outcomes when compared with the standard of care in patients with stable coronary artery disease. METHODS: In total, 1216 patients with stable coronary artery disease and an intermediate stenosis of 30% to 90% on coronary computed tomographic angiography were randomized to an on-site CT-FFR care pathway using machine learning or to standard care in 6 Chinese medical centers. The primary end point was the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease who did not undergo intervention within 90 days. Secondary end points included major adverse cardiovascular events, quality of life, symptoms of angina, and medical expenditure at 1 year. RESULTS: Baseline characteristics were similar in both groups, with 72.4% (881/1216) having either typical or atypical anginal symptoms. A total of 421 of 608 patients (69.2%) in the CT-FFR care group and 483 of 608 patients (79.4%) in the standard care group underwent invasive coronary angiography. Compared with standard care, the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease not undergoing intervention was significantly reduced in the CT-FFR care group (28.3% [119/421] versus 46.2% [223/483]; P<0.001). Overall, more patients underwent revascularization in the CT-FFR care group than in the standard care group (49.7% [302/608] versus 42.8% [260/608]; P=0.02), but major adverse cardiovascular events at 1 year did not differ (hazard ratio, 0.88 [95% CI, 0.59-1.30]). Quality of life and symptoms improved similarly during follow-up in both groups, and there was a trend towards lower costs in the CT-FFR care group (difference, -¥4233 [95% CI, -¥8165 to ¥973]; P=0.07). CONCLUSIONS: On-site CT-FFR using machine learning reduced the proportion of patients with stable coronary artery disease undergoing invasive coronary angiography without obstructive disease or requiring intervention within 90 days, but increased revascularization overall without improving symptoms or quality of life, or reducing major adverse cardiovascular events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03901326.

Decoupled responses of above- and below-ground beta-diversity to nitrogen enrichment in a typical steppe.

Increased atmospheric nitrogen (N) deposition affects biodiversity in terrestrial ecosystems. However, we do not know whether the effects of N on above-ground plant ß-diversity are coupled with changes occurring in the soil seed bank. We conducted a long-term N-addition experiment in a typical steppe and found that above-ground ß-diversity increased and then decreased with increasing N addition, whereas below-ground ß-diversity decreased linearly. This suggests decoupled dynamics of plant communities and their soil seed bank under N enrichment. Species substitution determined above- and below-ground ß-diversity change via an increasing role of deterministic processes with N addition. These effects were mostly driven by differential responses of the above-ground vegetation and the soil seed bank ß-diversities to N-induced changes in environmental heterogeneity, increased soil inorganic N concentrations and soil acidification. Our findings highlight the importance of considering above- and below-ground processes simultaneously for effectively conserving grassland ecosystems under N enrichment.

DNMT1/DNMT3a-mediated promoter hypermethylation and transcription activation of ICAM5 augments thyroid carcinoma progression.

Promoter methylation is one of the most studied epigenetic modifications and it is highly relevant to the onset and progression of thyroid carcinoma (THCA). This study investigates the promoter methylation and expression pattern of intercellular adhesion molecule 5 (ICAM5) in THCA. CpG islands with aberrant methylation pattern in THCA, and the expression profiles of the corresponding genes in THCA, were analyzed using bioinformatics. ICAM5 was suggested to have a hypermethylation status, and it was highly expressed in THCA tissues and cells. Its overexpression promoted proliferation, mobility, and tumorigenic activity of THCA cells. As for the downstream signaling, ICAM5 was found to activate the MAPK/ERK and MAPK/JNK signaling pathways. Either inhibition of ERK or JNK blocked the oncogenic effects of ICAM5. DNA methyltransferases 1 (DNMT1) and DNMT3a were found to induce promoter hypermethylation of ICAM5 in THCA cells. Knockdown of DNMT1 or DNMT3a decreased the ICAM5 expression and suppressed malignant properties of THCA cells in vitro and in vivo, which were, however, restored by further artificial ICAM5 overexpression. Collectively, this study reveals that DNMT1 and DNMT3a mediates promoter hypermethylation and transcription activation of ICAM5 in THCA, which promotes malignant progression of THCA through the MAPK signaling pathway.

Antigen specific VNAR screening in whitespotted bamboo shark (Chiloscyllium plagiosum) with next generation sequencing.

IgNAR exhibits significant promise in the fields of cancer and anti-virus biotherapies. Notably, the variable regions of IgNAR (VNAR) possess comparable antigen binding affinity with much smaller molecular weight (∼12 kDa) compared to IgNAR. Antigen specific VNAR screening is a changeling work, which limits its application in medicine and therapy fields. Though phage display is a powerful tool for VNAR screening, it has a lot of drawbacks, such as small library coverage, low expression levels, unstable target protein, complicating and time-consuming procedures. Here we report VANR screening with next generation sequencing (NGS) could effectively overcome the limitations of phage display, and we successfully identified approximately 3000 BAFF-specific VNARs in Chiloscyllium plagiosum vaccinated with the BAFF antigen. The results of modelling and molecular dynamics simulation and ELISA assay demonstrated that one out of the top five abundant specific VNARs exhibited higher binding affinity to the BAFF antigen than those obtained through phage display screening. Our data indicates NGS would be an alternative way for VNAR screening with plenty of advantages.

Recent Advances in Organic Small-Molecule Fluorescent Probes for the Detection of Zinc Ions (Zn2+).

Zinc(II) ions (Zn2g) play crucial roles in the growth, propagation, and metabolism of animals, plants, and humans. Abnormal concentrations of Zn2+ in the environment and living organisms pose potential risks to environmental protection and human health. Therefore, it is imperative to develop rapid, reliable and in-situ detection methods for Zn2+ in both environmental and biological contexts. Furthermore, effective analytical methods are required for diagnosing diseases and understanding physiological metabolic mechanisms associated with Zn2+ concentration levels. Organic small-molecule fluorescent probes offer advantages such as fast, reliable, convenient, non-destructive detection capabilities and have significant application potential in Zn2+ detection and bioimaging; thus garnering extensive attention. Over the past two years alone, various organic small-molecule probes for Zn2+ based on different detection mechanisms and fluorophores have been rapidly developed. However, these probes still exhibit several limitations that need further resolution. In light of this context, we provide a comprehensive summary of the detection mechanisms, performance characteristics, and application scope of Zn2+ fluorescence probes since year 2022 while highlighting their advantages. We also propose solutions to address existing issues with these probes and outline future directions for their advancement. This review aims to serve as a valuable reference source offering insights into the development of advanced organic small-molecule-based fluorescence probes specifically designed for detecting Zn2+.

Excimer laser coronary angioplasty combined with drug-coated balloon in the treatment of in-stent restenosis.

OBJECTIVES: The aim of this study is to investigate the safety and efficacy of excimer laser coronary angioplasty (ELCA) combined with drug-coated balloons (DCBs) in the treatment of in-stent restenosis (ISR), and to explore whether the contrast injection technique would improve the neointimal tissue ablation of ELCA. METHODS: We studied patients diagnosed with ISR between January 2019 and October 2022 at two medical centers. These patients underwent DCB angioplasty guided by optical coherence tomography (OCT). Based on whether ELCA was performed before DCB treatment, patients were categorized into two groups: the ELCA + DCB group and the DCB group. All patients underwent clinical follow-up 1 year after the procedure. The primary endpoint was the 1-year rate of target lesion revascularization (TLR), which was defined as any repeat percutaneous intervention or bypass surgery on the target vessel conducted to address restenosis or other complications related to the target lesion. The secondary endpoints including immediate luminal gain (ΔMLA, defined as the difference in minimum lumen area before and after the intervention). RESULTS: A total of 85 lesions in 75 patients were included. The mean age of the study population was 64.2 ± 12.0 years, with 81.3% male. Baseline clinical characteristics were well-balanced, and procedural success was 100% in both groups. The ELCA + DCB group (n = 24) exhibited a greater ΔMLA compared to the DCB group (n = 61) (3.57 ± 0.79 mm² vs. 2.50 ± 1.06 mm², [95% confidence interval, CI: 0.57-1.69], p < 0.001), The reduction in 1-year TLR was more frequently observed in patients from the ELCA + DCB group compared to the DCB group (hazard ratio 0.33 [95% CI: 0.11-0.99]; log-rank p = 0.048). The exploratory analysis showed that ELCA with contrast infusion is associated with greater acute lumen gain compared to ELCA with saline infusion (p < 0.001). CONCLUSIONS: The combination of ELCA and DCB is a safe and effective treatment strategy for in-stent stenosis. Additionally, compared with saline injection, ELCA with contrast injection is associated with greater acute lumen gain. However, the optimal contrast agent concentration and long-term outcome of the contrast injection technique need confirmation through larger sample sizes and prospective studies.

Lemneolemnanes A-D, Four Uncommon Sesquiterpenoids from the Soft Coral Lemnalia sp.

Four undescribed sesquiterpenoids, lemneolemnanes A-D (1-4), have been isolated from the marine soft coral Lemnalia sp. The absolute configurations of the stereogenic carbons of 1-4 were determined by single-crystal X-ray crystallographic analysis. Compounds 1 and 2 are epimers at C-3 and have an unusual skeleton with a formyl group on C-6. Compound 3 possesses an uncommonly rearranged carbon skeleton, while 4 has a 6/5/5 tricyclic system. Compound 1 showed significant anti-Alzheimer's disease (AD) activity in a humanized Caenorhabditis elegans AD pathological model.

Topological spin/structure couplings in layered chiral magnet Cr1/3TaS2: The discovery of spiral magnetic superstructure.

Chiral magnets have recently emerged as hosts for topological spin textures and related transport phenomena, which can find use in next-generation spintronic devices. The coupling between structural chirality and noncollinear magnetism is crucial for the stabilization of complex spin structures such as magnetic skyrmions. Most studies have been focused on the physical properties in homochiral states favored by crystal growth and the absence of long-ranged interactions between domains of opposite chirality. Therefore, effects of the high density of chiral domains and domain boundaries on magnetic states have been rarely explored so far. Herein, we report layered heterochiral Cr1/3TaS2, exhibiting numerous chiral domains forming topological defects and a nanometer-scale helimagnetic order interlocked with the structural chirality. Tuning the chiral domain density, we discovered a macroscopic topological magnetic texture inside each chiral domain that has an appearance of a spiral magnetic superstructure composed of quasiperiodic Néel domain walls. The spirality of this object can have either sign and is decoupled from the structural chirality. In weak, in-plane magnetic fields, it transforms into a nonspiral array of concentric ring domains. Numerical simulations suggest that this magnetic superstructure is stabilized by strains in the heterochiral state favoring noncollinear spins. Our results unveil topological structure/spin couplings in a wide range of different length scales and highly tunable spin textures in heterochiral magnets.

Refined Sound Therapy in Combination with Cognitive Behavioural Therapy to Treat Tinnitus: A Randomized Controlled Trial.

Background: Post-auricular injection of lidocaine and methylprednisolone sodium succinate is a commonly used treatment for outpatient patients with tinnitus, but it is invasive, painful and has uncertain efficacy. We need to try to replace it with more non-invasive and effective treatments. The 2014 guidelines of the American Academy of Otolaryngology-Head and Neck Surgery recommend the use of cognitive behavioral therapy (CBT) to treat tinnitus. Some clinical doctors have also attempted sound therapy for tinnitus. It is unclear whether sound therapy combined with CBT y is more effective than local injection of lidocaine and methylprednisolone sodium succinate in treating tinnitus. Objective: To evaluate the efficacy and influencing factors of refined sound therapy combined with CBT in the treatment of tinnitus and compare it with post-auricular injection of lidocaine and methylprednisolone sodium succinate. Methods: We recruited 100 patients with tinnitus; ultimately, 81 patients completed the experiment and underwent follow-up. Patients were randomly assigned to either the treatment group (refined sound therapy combined with CBT) or the control group (post-auricular injections of lidocaine and methylprednisolone sodium succinate). Data was collected from 49 patients in the treatment group and 32 patients in the control group. Pre- and post-treatment data were collected using the Self-Rating Depression Scale (SDS), Hamilton Anxiety Rating Scale (HAM-A), Visual Analogue Score (VAS), Tinnitus loudness and Tinnitus Handicap Inventory (THI) score. Comparisons between groups were performed using the chi-square test, Fisher's exact test, or Wilcoxon rank-sum test. All tests were two-sided and considered statistically significant with P < .05. Results: The THI, SDS and HAM-A scores in the treatment group decreased significantly. In the control group, there was a significant reduction in THI scores, but not in SDS and HAM-A scores. In addition, tinnitus loudness and VAS scores were significantly decreased in the 2 groups. There was a significant difference in the reduction of THI, SDS, HAM-A and VAS scores between the 2 groups; the treatment group showed a greater reduction. However, there was no significant difference in the reduction of tinnitus loudness. There was no statistical difference in the reduction of THI scores, SDS scores, VAS scores and tinnitus loudness in different frequency groups, but there was a statistical difference in the reduction of HAM-A scores. There was no statistical difference in the reduction of THI scores, SDS scores, HAM-A scores, VAS scores and tinnitus loudness between patients with and without hearing loss. Conclusions: (1) This new combination is more effective than post-auricular injection of lidocaine and methylprednisolone sodium succinate in treating tinnitus and improving psychological symptoms. The latter had no effect on improving psychological indicators. (2) With this combination, patients with different tinnitus frequencies experienced different improvements in anxiety. (3) Low-frequency tinnitus seems have been more likely to cause sound adaptation. (4) The improvement in tinnitus and anxiety was the same regardless of whether or not there was hearing loss.

Effect of enzymatic hydrolysis of arabinoxylan on the quality of frozen dough during the subfreezing process.

BACKGROUND: The objective of this investigation was to examine the impact of enzymatic hydrolysis of arabinoxylan (AX) on frozen dough quality under subfreezing conditions. The dough was subjected to freezing at -40 °C for 2 h and then stored at -9, -12, and -18 °C for 15 days. The water loss, freezable water content, water migration, and microstructure of the dough were measured. RESULTS: The dough containing 0.8% cellulase enzymatically hydrolyzed AX (CAX) required the shortest duration when traversing the maximum ice-crystal formation zone (6.5 min). The dough with xylanase enzymatically hydrolyzed AX (XAX) demonstrated a faster freezing rate than the dough with CAX. The inclusion of both XAX and CAX in the dough resulted in the lowest freezable water loss and reduced freezable water content and free-water content levels, whereas the inclusion of xylanase-cellulase combined with enzymatically hydrolyzed AX resulted in higher free-water content levels. The textural properties of the subfreezing temperature dough were not significantly different from the dough stored at -18 °C and sometimes even approached or surpassed the quality observed in the control group rather than the dough stored at -18 °C. In addition, the gluten network structure remains well preserved in XAX- and CAX-containing doughs with minimal starch damage. CONCLUSION: The enzymatic hydrolysis of AX from wheat bran can be used as a useful additive to improve the quality of frozen dough. © 2024 Society of Chemical Industry.

Temperature-Gradient Solution Deposition Amends Unfavorable Band Structure of Sb2(S,Se)3 Film for Highly Efficient Solar Cells.

Band structure of a semiconducting film critically determines the charge separation and transport efficiency. In antimony selenosulfide (Sb2(S,Se)3) solar cells, the hydrothermal method has achieved control of bandgap width of Sb2(S,Se)3 thin film through tuning the atomic ratio of S/Se, resulting in an efficiency breakthrough towards 10%. However, the obtained band structure exhibits an unfavorable gradient distribution in terms of carrier transport, which seriously impedes the device efficiency improvement. To solve this problem, here we develop a strategy by intentionally regulating hydrothermal temperature to control the chemical reaction kinetics between S and Se sources with Sb source. This approach enables the control over vertical distribution of S/Se atomic ratio in Sb2(S,Se)3 films, forming a favorable band structure which is conducive to carrier transport. Meanwhile, the adjusted element distribution not only ensures the uniformity of grain structure, but also increases the Se content of the films and suppress sulfur vacancy defects. Ultimately, the device delivers a high efficiency of 10.55%, which is among the highest reported efficiency of Sb2(S,Se)3 solar cells. This study provides an effective strategy towards manipulating the element distribution in mixed-anion compound films prepared by solution-based method to optimize their optical and electrical properties.

EISA-EXPOSOME: One Highly Sensitive and Autonomous Exposomic Platform with Enhanced in-Source Fragmentation/Annotation.

Lacking a highly sensitive exposome screening technique is one of the biggest challenges in moving exposomic research forward. Enhanced in-source fragmentation/annotation (EISA) has been developed to facilitate molecular identification in untargeted metabolomics and proteomics. In this work, with a mixture of 50 pesticides at three concentration levels (20, 4, and 0.8 ppb), we investigated the analytical performance of the EISA technique over the well-accepted targeted MS/MS mode (TMM) in the detection and identification of chemicals at low levels using a quadrupole time-of-flight (qTOF) instrument. Compared with the TMM method, the EISA technique can recognize additional 1, 20, and 23 chemicals, respectively, at the three concentration levels (20, 4, and 0.8 ppb, respectively) investigated. At the 0.8 ppb level, intensities of precursor ions and fragments observed using the EISA technique are 30-1,154 and 3-80 times higher, respectively, than those observed at the TMM mode. A higher matched fragment ratio (MFR) between the EISA technique and the TMM method was recognized for most chemicals. We further developed a chemical annotation informatics algorithm, EISA-EXPOSOME, which can automatically search each precursor ion (m/z) in the MS/MS library against the EISA MS1 spectra. This algorithm then calculated a weighted score to rank the candidate features by comparing the experimental fragment spectra to those in the library. The peak intensity, zigzag index, and retention time prediction model as well as the peak correlation coefficient were further adopted in the algorithm to filter false positives. The performance of EISA-EXPOSOME was demonstrated using a pooled dust extract with a pesticide mixture (n = 200) spiked at 5 ppb. One urine sample spiked with a contaminant mixture (n = 50) at the 5 ppb level was also used for the validation of the pipeline. Proof-of-principal application of EISA-EXPOSOME in the real sample was further evaluated on the pooled dust sample with a modified T3DB database (n = 1650). Our results show that the EISA-EXPOSOME algorithm can remarkably improve the detection and annotation coverage at trace levels beyond the traditional approach as well as facilitate the high throughput screening of suspected chemicals.

Association between Coronary Artery Disease Reporting and Data System-recommended Post-Coronary CT Angiography Management and Clinical Outcomes in Patients with Stable Chest Pain from a Chinese Registry.

Background Coronary Artery Disease Reporting and Data System (CAD-RADS) was developed to standardize and optimize disease management in patients after coronary CT angiography (CCTA), but the impact of CAD-RADS management recommendations on clinical outcomes remains unclear. Purpose To retrospectively assess the association between the appropriateness of post-CCTA management according to CAD-RADS version 2.0 and clinical outcomes. Materials and Methods From January 2016 to January 2018, consecutive participants with stable chest pain referred for CCTA were prospectively included in a Chinese registry and followed for 4 years. Retrospectively, CAD-RADS 2.0 classification and the appropriateness of post-CCTA management were determined. Propensity score matching (PSM) was used to adjust for confounding variables. Hazard ratios (HRs) for a major adverse cardiovascular event (MACE), relative risks for invasive coronary angiography (ICA), and the corresponding number needed to treat were estimated. Results Of the 14 232 included participants (mean age, 61 years ± 13 [SD]; 8852 male), 2330, 2756, and 2614 were retrospectively categorized in CAD-RADS 1, 2, and 3, respectively. Only 26% of participants with CAD-RADS 1-2 disease and 20% with CAD-RADS 3 received appropriate post-CCTA management. After PSM, appropriate post-CCTA management was associated with lower risk of MACEs (HR, 0.34; 95% CI: 0.22, 0.51; P < .001), corresponding to a number needed to treat of 21 in CAD-RADS 1-2 but not CAD-RADS 3 (HR, 0.86; 95% CI: 0.49, 1.85; P = .42). Appropriate post-CCTA management was associated with decreased use of ICA in CAD-RADS 1-2 (relative risk, 0.40; 95% CI: 0.29, 0.55; P < .001) and 3 (relative risk, 0.33; 95% CI: 0.28, 0.39; P < .001), resulting in a number needed to treat of 14 and 2, respectively. Conclusion In this retrospective secondary analysis, appropriate disease management after CCTA according to CAD-RADS 2.0 was associated with lower risk of MACEs and more prudent use of ICA. ClinicalTrials.gov registration no. NCT04691037 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Leipsic and Tzimas in this issue.

The two sides of resistance-resilience relationship in both aboveground and belowground communities in the Eurasian steppe.

The ongoing nitrogen (N) deposition has led to profound changes in aboveground and belowground ecosystems. However, the stability of plant and soil microbial community toward N addition in terms of resistance and resilience is less understood. We established a long-running field trial (2008-2018) in a series of N applications in combination with a mowing and fencing (unmown) treatment in a semiarid steppe. We assessed the resistance via ongoing N treatment of one subplot and the resilience via discontinuing N treatment in another to promote natural recovery since 2014. Plant resistance was negatively correlated with N application rate, while microbial resistance was independent of N rate. Mowing significantly reduced plant resistance and resilience, reduced soil microbial resistance but improved its resilience. Generally, plants are more resilient but less resistant to N than soil microbes. The two sides of resistance-resilience relationship were revealed: trade-offs exist between resistance and resilience for both plants and microbes at the community level; and trade-offs between resistance and resilience cannot be scaled down to species/group level. This study provided an important theoretical basis for the recovery and conservation of semiarid steppe and new insight into resistance-resilience relationship.

Identifying thresholds of nitrogen enrichment for substantial shifts in arbuscular mycorrhizal fungal community metrics in a temperate grassland of northern China.

Nitrogen (N) enrichment poses threats to biodiversity and ecosystem stability, while arbuscular mycorrhizal (AM) fungi play important roles in ecosystem stability and functioning. However, the ecological impacts, especially thresholds of N enrichment potentially causing AM fungal community shifts have not been adequately characterized. Based on a long-term field experiment with nine N addition levels ranging from 0 to 50 g N m-2 yr-1 in a temperate grassland, we characterized the community response patterns of AM fungi to N enrichment. Arbuscular mycorrhizal fungal biomass continuously decreased with increasing N addition levels. However, AM fungal diversity did not significantly change below 20 g N m-2 yr-1 , but dramatically decreased at higher N levels, which drove the AM fungal community to a potentially unstable state. Structural equation modeling showed that the decline in AM fungal biomass could be well explained by soil acidification, whereas key driving factors for AM fungal diversity shifted from soil nitrogen : phosphorus (N : P) ratio to soil pH with increasing N levels. Different aspects of AM fungal communities (biomass, diversity and community composition) respond differently to increasing N addition levels. Thresholds for substantial community shifts in response to N enrichment in this grassland ecosystem are identified.

Global trans-lesional computed tomography-derived fractional flow reserve gradient is associated with clinical outcomes in diabetic patients with non-obstructive coronary artery disease.

BACKGROUND: Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (CT-FFR) enables physiological assessment and risk stratification, which is of significance in diabetic patients with nonobstructive coronary artery disease (CAD). We aim to evaluate prognostic value of the global trans-lesional CT-FFR gradient (GΔCT-FFR), a novel metric, in patients with diabetes without flow-limiting stenosis. METHODS: Patients with diabetes suspected of having CAD were prospectively enrolled. GΔCT-FFR was calculated as the sum of trans-lesional CT-FFR gradient in all epicardial vessels greater than 2 mm. Patients were stratified into low-gradient without flow-limiting group (CT-FFR > 0.75 and GΔCT-FFR < 0.20), high-gradient without flow-limiting group (CT-FFR > 0.75 and GΔCT-FFR ≥ 0.20), and flow-limiting group (CT-FFR ≤ 0.75). Discriminant ability for major adverse cardiovascular events (MACE) prediction was compared among 4 models [model 1: Framingham risk score; model 2: model 1 + Leiden score; model 3: model 2 + high-risk plaques (HRP); model 4: model 3 + GΔCT-FFR] to determine incremental prognostic value of GΔCT-FFR. RESULTS: Of 1215 patients (60.1 ± 10.3 years, 53.7% male), 11.3% suffered from MACE after a median follow-up of 57.3 months. GΔCT-FFR (HR: 2.88, 95% CI 1.76-4.70, P < 0.001) remained independent risk factors of MACE in multivariable analysis. Compared with the low-gradient without flow-limiting group, the high-gradient without flow-limiting group (HR: 2.86, 95% CI 1.75-4.68, P < 0.001) was associated with higher risk of MACE. Among the 4 risk models, model 4, which included GΔCT-FFR, showed the highest C-statistics (C-statistics: 0.75, P = 0.002) as well as a significant net reclassification improvement (NRI) beyond model 3 (NRI: 0.605, P < 0.001). CONCLUSIONS: In diabetic patients with non-obstructive CAD, GΔCT-FFR was associated with clinical outcomes at 5 year follow-up, which illuminates a novel and feasible approach to improved risk stratification for a global hemodynamic assessment of coronary artery in diabetic patients.

Microglia play an important role in PRV infection-induced immune responses of the central nervous system.

Pseudorabies virus (PRV) can infect multiple hosts and lead to fatal encephalitis. There is a significant increase in the number of microglia in the brain of animals infected with PRV. However, whether and how microglia contribute to central nervous system damage in PRV infection remain unknown. In the present study, we elucidated that PRV infection can cause more severe inflammatory cell infiltration, thicker and more numerous vessel sleeve walls, and more severe inflammatory responses in the brains of natural hosts (pigs) than in those of nonnatural hosts (mice). In a mice infection model, activated microglia restricted viral replication in the early stage of infection. Acute neuroinflammation caused by microglia hyperactivation at late-stage of infection. Furthermore, in vitro experiments revealed that microglia restricted viral replication and decreased viral infectivity. This may be associated with the phagocytic ability of microglia because we observed a significant increase in the expression of the membrane receptor TREM2 in microglia, which is closely related to phagocytosis, we observed that depletion of microglia exacerbated neurological symptoms, blood-brain barrier breakdown, and peripheral lymphocyte infiltration. Taken together, we revealed the dual role of microglia in protecting the host and neurons from PRV infection.

Transparent Oil-Water Separating Hydrophobic Sponge Prepared from a Pickering High Internal Phase Emulsion Stabilized by Octadecyltrichlorosilane Grafting Carbon Nanotubes.

Increasingly, oil spills and industrial discharges are wreaking havoc on the water environment; in order to efficiently separate oil and water from sewage containing oil or organic solvents, a novel porous polymer (P(EHA-co-BA)) was prepared by Pickering high internal phase emulsion (HIPE) template method. To obtain polyHIPE with better oil/water separation capacities, octadecyltrichlorosilane (OTS)-modified carbon nanotubes (CNTs) and surfactants were used as costabilizers for HIPE, which improved the stability of HIPE as well as the mechanical properties and the separation efficiency of polyHIPE. In the presence of 1 wt % OTS-CNT adding in the oil phase, 1%OTS-CNT polyHIPE has high porosity (92.21%), favorable hydrophobicity (a water contact angle of 128°), and excellent mechanical properties. As a result, 1%OTS-CNT polyHIPE has high absorption of oils and oily solvents, e.g., dichloromethane up to 36 g/g, and maintains an absorption efficiency of >97% after 20 reapplications. In the formulation of polyHIPE, cinnamaldehyde (CA) has been added to provide superior antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). It appears that the novel polyHIPE proposed in this work is a reusable antibacterial porous polymer with promising applications for oil-water separation.

Prediction of high-grade patterns of stage IA lung invasive adenocarcinoma based on high-resolution CT features: a bicentric study.

OBJECTIVES: This study aims to predict the high-grade pattern (HGP) of stage IA lung invasive adenocarcinoma (IAC) based on the high-resolution CT (HRCT) features. METHODS: The clinical, pathological, and HRCT imaging data of 457 patients (from bicentric) with pathologically confirmed stage IA IAC (459 lesions in total) were retrospectively analyzed. The 459 lesions were classified into high-grade pattern (HGP) (n = 101) and non-high-grade pattern (n-HGP) (n = 358) groups depending on the presence of HGP (micropapillary and solid) in pathological results. The clinical and pathological data contained age, gender, smoking history, tumor stage, pathological type, and presence or absence of tumor spread through air spaces (STAS). CT features consisted of lesion location, size, density, shape, spiculation, lobulation, vacuole, air bronchogram, and pleural indentation. The independent predictors for HGP were screened by univariable and multivariable logistic regression analyses. The clinical, CT, and clinical-CT models were constructed according to the multivariable analysis results. RESULTS: The multivariate analysis suggested the independent predictors of HGP, encompassing tumor size (p = 0.001; OR = 1.090, 95% CI 1.035-1.148), density (p < 0.001; OR = 9.454, 95% CI 4.911-18.199), and lobulation (p = 0.002; OR = 2.722, 95% CI 1.438-5.154). The AUC values of clinical, CT, and clinical-CT models for predicting HGP were 0.641 (95% CI 0.583-0.699) (sensitivity = 69.3%, specificity = 79.2%), 0.851 (95% CI 0.806-0.896) (sensitivity = 79.2%, specificity = 79.6%), and 0.852 (95% CI 0.808-0.896) (sensitivity = 74.3%, specificity = 85.8%). CONCLUSION: The logistic regression model based on HRCT features has a good diagnostic performance for the high-grade pattern of stage IA IAC. KEY POINTS: • The AUC values of clinical, CT, and clinical-CT models for predicting high-grade patterns were 0.641 (95% CI 0.583-0.699), 0.851 (95% CI 0.806-0.896), and 0.852 (95% CI 0.808-0.896). • Tumor size, density, and lobulation were independent predictive markers for high-grade patterns. • The logistic regression model based on HRCT features has a good diagnostic performance for the high-grade patterns of invasive adenocarcinoma.