The impact of integrating PRIMARY score or SUVmax with MRI-based risk models for the detection of clinically significant prostate cancer.

PURPOSE: An MRI-based risk calculator (RC) has been recommended for diagnosing clinically significant prostate cancer (csPCa). PSMA PET/CT can detect lesions that are not visible on MRI, and the addition of PSMA PET/CT to MRI may improve diagnostic performance. The aim of this study was to incorporate the PRIMARY score or SUVmax derived from [68Ga]Ga-PSMA-11 PET/CT into the RC and compare these models with MRI-based RC to assess whether this can further reduce unnecessary biopsies. METHODS: A total of 683 consecutive biopsy-naïve men who underwent both [68Ga]Ga-PSMA-11 PET/CT and MRI before biopsy were temporally divided into a development cohort (n = 552) and a temporal validation cohort (n = 131). Three logistic regression RCs were developed and compared: MRI-RC, MRI-SUVmax-RC and MRI-PRIMARY-RC. Discrimination, calibration, and clinical utility were evaluated. The primary outcome was the clinical utility of the risk calculators for detecting csPCa and reducing the number of negative biopsies. RESULTS: The prevalence of csPCa was 47.5% (262/552) in the development cohort and 41.9% (55/131) in the temporal validation cohort. In the development cohort, the AUC of MRI-PRIMARY-RC was significantly higher than that of MRI-RC (0.924 vs. 0.868, p < 0.001) and MRI-SUVmax-RC (0.924 vs. 0.904, p = 0.002). In the temporal validation cohort, MRI-PRIMARY-RC also showed the best discriminative ability with an AUC of 0.921 (95% CI: 0.873-0.969). Bootstrapped calibration curves revealed that the model fit was acceptable. MRI-PRIMARY-RC exhibited near-perfect calibration within the range of 0-40%. DCA showed that MRI-PRIMARY-RC had the greatest net benefit for detecting csPCa compared with MRI-RC and MRI-SUVmax-RC at a risk threshold of 5-40% for csPCa in both the development and validation cohorts. CONCLUSION: The addition of the PRIMARY score to MRI-based multivariable model improved the accuracy of risk stratification prior to biopsy. Our novel MRI-PRIMARY prediction model is a promising approach for reducing unnecessary biopsies and improving the early detection of csPCa.

Evaluating the Ability of External Electric Fields to Accelerate Reactions in Solution.

This study investigates the catalytic effects of external electric fields (EEFs) on two reactions in solution: the Menshutkin reaction and the Chapman rearrangement. Utilizing a scanning tunneling microscope-based break-junction (STM-BJ) setup and monitoring reaction rates through high-performance liquid chromatography connected to a UV detector (HPLC-UV) and ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-q-ToF-MS), we observed no rate enhancement for either reaction under ambient conditions. Density functional theory (DFT) calculations indicate that electric field-induced changes in reactant orientation and the minimization of activation energy are crucial factors in determining the efficacy of EEF-driven catalysis. Our findings suggest that the current experimental setups and field strengths are insufficient to catalyze these reactions, underscoring the importance of these criteria in assessing the reaction candidates.

Antagonistic Strain Bacillus velezensis JZ Mediates the Biocontrol of Bacillus altitudinis m-1, a Cause of Leaf Spot Disease in Strawberry.

Biofertilizers are environmentally friendly compounds that can enhance plant growth and substitute for chemically synthesized products. In this research, a new strain of the bacterium Bacillus velezensis, designated JZ, was isolated from the roots of strawberry plants and exhibited potent antagonistic properties against Bacillus altitudinis m-1, a pathogen responsible for leaf spot disease in strawberry. The fermentation broth of JZ exerted an inhibition rate of 47.43% against this pathogen. Using an optimized acid precipitation method, crude extracts of lipopeptides from the JZ fermentation broth were obtained. The crude extract of B. velezensis JZ fermentation broth did not significantly disrupt the cell permeability of B. altitudinis m-1, whereas it notably reduced the Ca2+-ATPase activity on the cell membrane and markedly elevated the intracellular reactive oxygen species (ROS) concentration. To identify the active compounds within the crude extract, QTOF-MS/MS was employed, revealing four antimicrobial compounds: fengycin, iturin, surfactin, and a polyene antibiotic known as bacillaene. The strain JZ also produced various plant-growth-promoting substances, such as protease, IAA, and siderophore, which assists plants to survive under pathogen infection. These findings suggest that the JZ strain holds significant potential as a biological control agent against B. altitudinis, providing a promising avenue for the management of plant bacterial disease.

Effects of Drought Stress on Photosynthesis and Chlorophyll Fluorescence in Blue Honeysuckle.

Blue honeysuckle (Lonicera caerulea L.) is a deciduous shrub with perennial rootstock found in China. The objectives of this study were to explore the drought tolerance of blue honeysuckle, determine the effect of drought stress on two photosystems, and examine the mechanism of acquired drought tolerance. In this study, blue honeysuckle under four levels of simulated field capacity (100%, 85%, 75%, and 65% RH) was grown in split-root pots for drought stress treatment, for measuring the changes in chlorophyll content, photosynthetic characteristics, and leaf chlorophyll fluorescence parameters. The chlorophyll content of each increased under mild stress and decreased under moderate and severe stress. The net photosynthetic rate, transpiration rate, intercellular carbon dioxide concentration, and stomatal conductance of blue honeysuckle decreased with the increase in water stress. However, the water utilization rate and stomatal limit system increased under mild and moderate stress and decreased under severe stress. The maximum fluorescence (Fm), maximum photochemical efficiency, and quantum efficiency of photosystem II decreased with the decrease in soil water content, and the initial fluorescence increased significantly (p < 0.01). With the decrease in soil water content, the energy allocation ratio parameters decreased under severe drought stress. The main activity of the unit reaction center parameters first increased and then decreased. ABS/CSm, TRo/CSm, ETo/CSm, and REo/CSm gradually declined. After a comprehensive analysis, the highest scores were obtained under adequate irrigation (CK). Overall, we concluded that the water irrigation system of blue honeysuckle should be considered adequate.

Transglutaminase 3 regulates cutaneous squamous carcinoma differentiation and inhibits progression via PI3K-AKT signaling pathway-mediated Keratin 14 degradation.

Cutaneous squamous carcinoma is the second most common epithelial malignancy, associated with significant morbidity, mortality, and economic burden. However, the mechanisms underlying cSCC remain poorly understood. In this study, we identified TGM3 as a novel cSCC tumor suppressor that acts via the PI3K-AKT axis. RT-qPCR, IHC and western blotting were employed to assess TGM3 levels. TGM3-overexpression/knockdown cSCC cell lines were utilized to detect TGM3's impact on epithelial differentiation as well as tumor cell proliferation, migration, and invasion in vitro. Additionally, subcutaneous xenograft tumor models were employed to examine the effect of TGM3 knockdown on tumor growth in vivo. Finally, molecular and biochemical approaches were employed to gain insight into the tumor-suppressing mechanisms of TGM3. TGM3 expression was increased in well-differentiated cSCC tumors, whereas it was decreased in poor-differentiated cSCC tumors. Loss of TGM3 is associated with poor differentiation and a high recurrence rate in patients with cSCC. TGM3 exhibited tumor-suppressing activity by regulating cell proliferation, migration, and invasion both in vitro and in vivo. As a novel cSCC tumor differentiation marker, TGM3 expression was positively correlated with cell differentiation. In addition, our results demonstrated an interaction between TGM3 and KRT14 that aids in the degradation of KRT14. TGM3 deficiency disrupts keratinocytes differentiation, and ultimately leads to tumorigenesis. Furthermore, RNA-sequence analysis revealed that loss of TGM3 enhanced EMT via the PI3K-AKT signaling pathway. Deguelin, a PI3K-AKT inhibitor, blocked cSCC tumor growth induced by TGM3 knockdown in vivo. Taken together, TGM3 inhibits cSCC tumor growth via PI3K-AKT signaling, which could also serve as a tumor differentiation marker and a potential therapeutic target for cSCC. Proposed model depicted the mechanism by which TGM3 suppress cSCC development. TGM3 reduces the phosphorylation level of AKT and degrades KRT14. In the epithelial cell layer, TGM3 exhibits a characteristic pattern of increasing expression from bottom to top, while KRT14 and pAKT are the opposite. Loss of TGM3 leads to reduced degradation of KRT14 and activation of pAKT, disrupting keratinocyte differentiation, and eventually resulting in the occurrence of low-differentiated cSCC.

Identification of optimal feature genes in patients with thyroid associated ophthalmopathy and their relationship with immune infiltration: a bioinformatics analysis.

Background: Thyroid associated ophthalmopathy (TAO) is an organ-specific autoimmune disease that has a significant impact on individuals and society. The etiology of TAO is complicated and poorly understood. Thus, the goal of this study was to use bioinformatics to look into the pathogenesis of TAO and to identify the optimum feature genes (OFGs) and immune infiltration patterns of TAO. Methods: Firstly, the GSE58331 microarray data set was utilized to find 366 differentially expressed genes (DEGs). To find important modular genes, the dataset was evaluated using weighted gene coexpression network analysis (WGCNA). Then, the overlap genes of major module genes and DEGs were further assessed by applying three machine learning techniques to find the OFGs. The CIBERSORT approach was utilized to examine immune cell infiltration in normal and TAO samples, as well as the link between optimum characteristic genes and immune cells. Finally, the related pathways of the OFGs were predicted using single gene set enrichment analysis (ssGSEA). Results: KLB, TBC1D2B, LINC01140, SGCG, TMEM37, and LINC01697 were the six best feature genes that were employed to create a nomogram with high predictive performance. The immune cell infiltration investigation revealed that the development of TAO may include memory B cells, T cell follicular helper cells, resting NK cells, macrophages of type M0, macrophages of type M1, resting dendritic cells, active mast cells, and neutrophils. In addition, ssGSEA results found that these characteristic genes were closely associated with lipid metabolism pathways. Conclusion: In this research, we found that KLB, TBC1D2B, LINC01140, SGCG, TMEM37, and LINC01697 are intimately associated with the development and progression of TAO, as well as with lipid metabolism pathways.

Excitation localization/delocalization induced intramolecular singlet fission in cyclopentadithiophene-based quinoidal derivatives.

Two triplet excitons are generated through an ultrafast photophysical process, namely singlet fission (SF), providing a solution for efficient solar energy usage. In this work, we provide an effective guideline for designing SF materials by adjusting the planarity in cyclopentadithiophene (CPDT) derivatives. A practical strategy is proposed for tuning the quinoidal-biradical resonance structures by varying the electron push-pull groups of CPDTs for SF. The localized, delocalized, and intermediate charge-transfer excited configurations are predicted in the singlet excited state via computational simulations, which is further confirmed by ultrafast spectroscopy. Deduced from the potential energy surfaces in the low-lying excited states and transient absorption, the delocalized excited state is formed in 2.1 ps via postulated intramolecular SF in a polar solvent, followed by the ultrafast formation of the free triplet state with a lifetime of 6.8 ps. In comparison with different cross-conjugated chromophores, it is found that the increase in the charge separation could enhance the triplet-pair generation for iSF. We expect that by introducing symmetry-breaking modifications in the electronic configurations and adjusting the separation between the push-pull groups of CPDTs, it should be possible to prolong the duration of the free triplet state by preventing recombination within the triplet-pair excited configuration.

Ultrafast Photocontrolled Rotation in a Molecular Motor Investigated by Machine Learning-Based Nonadiabatic Dynamics Simulations.

The thermal helix inversion (THI) of the overcrowded alkene-based molecular motors determines the speed of the unidirectional rotation due to the high reaction barrier in the ground state, in comparison with the ultrafast photoreaction process. Recently, a phosphine-based motor has achieved all-photochemical rotation experimentally, promising to be controlled without a thermal step. However, the mechanism of this photochemical reaction has not yet been fully revealed. The comprehensive computational studies on photoisomerization still resort to nonadiabatic molecular dynamics (NAMD) simulations based on electronic structure calculations, which remains a high computational cost for large systems such as molecular motors. Machine learning (ML) has become an accelerating tool in NAMD simulations recently, where excited-state potential energy surfaces (PESs) are constructed analytically with high accuracy, providing an efficient approach for simulations in photochemistry. Herein the reaction pathway is explored by a spin-flip time-dependent density functional theory (SF-TDDFT) approach in combination with ML-based NAMD simulations. According to our computational simulations, we notice that one of the key factors of fulfilling all-photochemical rotation in the phosphine-based motor is that the excitation energies of four isomers are similar. Additionally, a shortcut photoinduced transformation between unstable isomers replaces the THI step, which shares the conical intersection (CI) with photoisomerization. In this study, we provide a practical approach to speed up the NAMD simulations in photochemical reactions for a large system that could be extended to other complex systems.

Home confinement's impact on myopia control by using orthokeratology in school-aged children.

BACKGROUND: Home confinement during the epidemic has a significant impact on the lifestyle and behavior of school-aged children, who have exhibited an increase in the prevalence and development of myopia. Our research will look at if home confinement will affect school-aged children on myopia control with orthokeratology. METHOD: Data on axial length was gathered from school-aged children who had received OK lenses treatment. The entire data was separated into subgroups based on gender, age, and initial refraction, and the AL changes for each period were calculated using the formula defined in our study. Finally, the acquired data will be examined using various statistical approaches, and the ideas of slow, moderate, and rapid myopia progression will be applied to our study. RESULT: A total of 258 study subjects met the requirements to be included in the study. We discovered that the percentage of rapid myopia growth increased during the epidemic. In addition, the AL changes before and during the epidemic were found to be statistically significant in 171 subjects in the overall data. (P = 0.041) In the high age group, the AL changes before and during the epidemic、(P = 0.033) before and after the epidemic (P = 0.023) were found to be statistically significant. The AL changes before and during the epidemic (P = 0.035) were shown to be statistically significant in the moderate myopia group. Finally, we did not find statistically significant results for other groups. CONCLUSION: We cannot conclude that home confinement did have a negative impact on myopia control with orthokeratology in school-aged children. But we found there was an increase in the percentage of patients with OK treatment that had fast myopia progression during the confinement. We also observed that older children with higher initial refraction were more likely to be affected by home confinement.

Alkane Solvent-Derived Acylation Reaction Driven by Electric Fields.

Electric field acceleration of alkyl hydroperoxide activation to acylate amines in the scanning tunneling microscope-based break-junction is reported. Alkyl hydroperoxide mixtures, generated from hydrocarbon autoxidation in air, were found to be competent reagents for the functionalization of gold surfaces. Intermolecular coupling on the surface in the presence of amines was observed, yielding normal alkylamides. This novel mode of alkyl hydroperoxide activation to generate acylium equivalents was found to be responsive to the magnitude of the bias in the break junction, indicating an electric field influence on this novel reactivity.

Flavobacterium lacisediminis sp. nov., a bacterium isolated from lake sediment.

A taxonomic identification using polyphasic approach was performed on strain TH16-21T, which was isolated from the interfacial sediment of Taihu Lake, PR China. Strain TH16-21T was Gram-stain-negative, aerobic, rod-shaped and catalase-positive. Phylogenetic analysis based on the 16S rRNA gene and genomic sequences indicated that strain TH16-21T was classified within the genus of Flavobacterium. The 16S rRNA gene sequence of strain TH16-21T showed the highest similarity to Flavobacterium cheniae NJ-26T (98.9 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain TH16-21T and F. cheniae NJ-26T were 91.2 and 45.9 %, respectively. The respiratory quinone was menaquinone 6. The major cellular fatty acids (>10 %) comprised iso-C15 : 0, iso-C16 : 0, iso-C15 : 1 G and iso-C16 : 0 3-OH. The genomic DNA G+C content was 32.2 mol%. Phosphatidylethanolamine, six amino lipids and three phospholipids were the main polar lipids. Based on the phenotypic features and phylogenetic position, a novel species with the name Flavobacterium lacisediminis sp. nov. is proposed. The type strain is TH16-21T (=MCCC 1K04592T=KACC 22896T).

Electric fields drive bond homolysis.

Electric fields have been used to control and direct chemical reactions in biochemistry and enzymatic catalysis, yet directly applying external electric fields to activate reactions in bulk solution and to characterize them ex situ remains a challenge. Here we utilize the scanning tunneling microscope-based break-junction technique to investigate the electric field driven homolytic cleavage of the radical initiator 4-(methylthio)benzoic peroxyanhydride at ambient temperatures in bulk solution, without the use of co-initiators or photochemical activators. Through time-dependent ex situ quantification by high performance liquid chromatography using a UV-vis detector, we find that the electric field catalyzes the reaction. Importantly, we demonstrate that the reaction rate in a field increases linearly with the solvent dielectric constant. Using density functional theory calculations, we show that the applied electric field decreases the dissociation energy of the O-O bond and stabilizes the product relative to the reactant due to their different dipole moments.

Effect of void-carbon on blue-shifted luminescence in TADF molecules by theoretical simulations.

Thermally activated delayed fluorescence (TADF) molecules have a theoretical 100% photoluminescence quantum yield in comparison with traditional fluorescent materials, leading to broad application in organic light-emitting diode (OLED). However, the application of TADF molecules with conjugated donor-acceptor structures in blue OLED remains a challenge due to their generally narrow energy gap between frontier molecular orbitals. Recently, a strategy has been approved in the improvement of the performance in TADF, in which void-carbon atoms between donor and acceptor fragments (donor-void-acceptor (D-v-A)) could regulate blue light emission. In this study, we first select three reported isomers followed by two proposed D-v-A TADF isomers to verify the feasibility of the void-carbon strategy through evaluation of the electronic structures in the excited state and photophysical properties. We further proposed a series of TADF molecules by replacing different donor and acceptor fragments to assess the applicability of the void-carbon strategy from the aspect of simulations in electronic structures, different properties of donor and acceptor fragments, photophysical properties, and analysis in the molecular conjugation. The results indicate that void-carbon strategy has conditional feasibility and applicability. Donor-acceptor molecular properties could be tuned through void-carbon strategy on aromatic acceptor fragments during the selection of promising candidates of TADF molecules. However, the void-carbon strategy does not work for the molecules with antiaromatic acceptor fragments, where the steric hindrance of the molecules plays a dominant role. Our work provides insightful guidance for the design of the blue-emission TADF molecules.

Cost-effectiveness analysis of atezolizumab plus chemotherapy as first-line treatment for patients with advanced nonsquamous non-small-cell lung cancer in China.

OBJECTIVE: The aim of the study was to evaluate the cost-effectiveness of adding atezolizumab to first-line chemotherapy for advanced nonsquamous non-small-cell lung cancer (NSCLC) from Chinese healthcare system. METHODS: A partitioned survival model (PSM) was established to simulate 3-week patients transition in a 20-year time horizon to estimate the health and economic outcomes of adding atezolizumab to first-line chemotherapy for advanced nonsquamous NSCLC. Costs and utility values were obtained from the local charges and published studies. Sensitivity analyses were conducted to confirm the robustness of the model results. RESULTS: Atezolizumab plus chemotherapy yielded additional 0.36 life years (LYs) and 0.23 quality-adjusted life-years (QALYs), and the marginal cost was $60,154.48, resulting in an ICER of atezolizumab plus chemotherapy versus chemotherapy was $267,264.85/QALY. One-way sensitivity analyses revealed that the cost of atezolizumab was the main driver of the model outcomes, and the probabilistic sensitivity analyses suggested that atezolizumab plus chemotherapy had 0% probability of being cost-effective first-line option at the willingness-to-pay (WTP) threshold of $37,652/QALY in China. CONCLUSIONS: Atezolizumab plus chemotherapy could not be considered cost-effective compared with chemotherapy alone as the first-line strategy for patients with advanced nonsquamous NSCLC in China. And appropriately reduce the price of atezolizumab is necessary.

The role of PP2A /NLRP3 signaling pathway in ambient particulate matter 2.5 induced lung injury.

Ambient particulate matter 2.5 (PM2.5) exposure has been linked to pulmonary fibrosis. However, the key signaling pathways remained unclear. In the present study, we applied a mouse model with myeloid-specific deletion of Ppp2r1a gene (encoding protein phosphatase 2 A (PP2A) A subunit) to identify the key signaling pathways involved in PM2.5-induced pulmonary fibrosis. PP2A Aα-/- homozygote mice and matched wild-type (WT) littermates were exposed to filtered air (FA), unfiltered air (UA), and concentrated PM2.5 (CA) in a real-ambient PM exposure system for 8 weeks and 16 weeks, respectively. The mice exposed to PM2.5 displayed a progressive inflammation and pulmonary fibrosis. Moreover, the expressions of NLRP3, pro-caspase-1, caspase-1, ASC and IL-1ß were increased in mice lung following PM2.5 exposure, indicating PM2.5 exposure caused pulmonary inflammation by the NLRP3 pathways activation. Furthermore, the effects of PM exposure on pulmonary inflammation, pulmonary fibrosis, oxidative stress, and pulmonary function damage were significantly enhanced in PP2A-/- mice compared to WT mice, indicating the role of PP2A in the regulation of pulmonary injury induced by PM exposure. In vitro study confirmed that PP2A was involved in the PM2.5-induced inflammation response and NLRP3 inflammasome activation. Importantly, we identified PP2A regulated the activation of NLRP3 pathways by direct dephosphorylating IRE1α in response to PM2.5 exposure. Taken together, our results demonstrated that PP2A-IRE1α-NLRP3 signaling pathway played a crucial role in regulating the inflammation response, triggering the lung fibrogenesis upon PM2.5 exposure. Our findings provide new insights into regulatory role of PP2A in human diseases upon the PM exposure.

[Introduction of legislation of disciplinary system for acupuncturists in various states in the United States: taking Ohio and other 11 states as examples].

With 12 representative states such as Ohio and Illinois as examples, the disciplinary system for acupuncturists in the United States is introduced. The disciplinary system mainly covers several aspects such as the subject of the implementation, the types of illegal acts, the form of disciplinary responsibility, and the hearing procedure. The acupuncture industry association has the responsibility of disciplinary action in most states. Corresponding disciplinary measures will be taken depending on the illegal activities of acupuncturists according to the types of illegal practice specified by each state. The hearing procedure provides procedural guarantee for the subsequent rights protection activities of acupuncturists.

Analysis on Time-Series Data from Movie Using MF-DCCA Method and Recurrent Neural Network Model Under the Internet of Things.

The present work aims to analyze the time-series data (TSD) from movies and support constructing the movie recommendation system. Referencing the Internet of Things (IoT) technology as the framework, a time-series data analysis system for movies is built based on the recurrent neural network (RNN) and multifractal detrended mobility cross-correlation analysis (MF-DCCA) method. First, the traditional RNN model is improved by replacing the conventional convolution operation with spatial adaptive convolution. Specifically, an additional convolution layer is used to obtain the position parameters required for adaptive convolution to improve the model performance to capture the characteristics of spatial-temporal transformation. Then, the MF-DCCA method is optimized to reduce the interference of noise signals to the analysis processing of TSD from movies. Finally, the TSD analysis system is tested for performance verification. The test results indicate that the method proposed here has outstanding stability and runs smoothly. When the prediction scheme is long short-term memory (LSTM) (L = 20), the similarity of the LSTM (L = 20) network under one frame is 0.977; the similarity of the LSTM (L = 20) network under nine frames is 0.727. This system provides a specific idea for applying the RNN model and MF-DCCA method in analyzing TSD from movies.

Increased Molecular Conductance in Oligo[n]phenylene Wires by Thermally Enhanced Dihedral Planarization.

Coherent tunneling electron transport through molecular wires has been theoretically established as a temperature-independent process. Although several experimental studies have shown counter examples, robust models to describe this temperature dependence have not been thoroughly developed. Here, we demonstrate that dynamic molecular structures lead to temperature-dependent conductance within coherent tunneling regime. Using a custom-built variable-temperature scanning tunneling microscopy break-junction instrument, we find that oligo[n]phenylenes exhibit clear temperature-dependent conductance. Our calculations reveal that thermally activated dihedral rotations allow these molecular wires to have a higher probability of being in a planar conformation. As the tunneling occurs primarily through π-orbitals, enhanced coplanarization substantially increases the time-averaged tunneling probability. These calculations are consistent with the observation that more rotational pivot points in longer molecular wires leads to larger temperature-dependence on conductance. These findings reveal that molecular conductance within coherent and off-resonant electron transport regimes can be controlled by manipulating dynamic molecular structure.

The proteasome-dependent degradation of ALKBH5 regulates ECM deposition in PM2.5 exposure-induced pulmonary fibrosis of mice.

Long-term inhalation of fine particulate matter (PM2.5) can cause serious effects on the respiratory system. It might be attributed to the fact that PM2.5 could directly enter and deposit in lung tissues. We established models of PM2.5 exposure in vivo and in vitro to explore the adverse effects of ambient PM2.5 on pulmonary and its potential pathogenic mechanisms. Our results showed that PM2.5 exposure promoted the deposition of ECM and the increased stiffness of the lungs, and then led to pulmonary fibrosis in time- and dose- dependent manners. Pulmonary function test showed restrictive ventilation function in mice after PM2.5 exposure. After PM2.5 exposure, ALKBH5 was recognized by TRIM11 and then degraded through the proteasome pathway. ALKBH5 deficiency (ALKBH5-/-) aggravated restrictive ventilatory disorder and promoted ECM deposition in lungs of mice induced by PM2.5. And the YAP1 signaling pathway was more activated in ALKBH5-/- than WT mice after PM2.5 exposure. In consequence, decreased ALKBH5 protein levels regulated miRNAs and then the miRNAs-targeted YAP1 signaling was activated to promote pulmonary fibrosis induced by PM2.5.

Right Ventricular Ejection Fraction Assessed by Three-Dimensional Echocardiography Is Associated with Long-Term Adverse Clinical Cardiac Events in Patients with Anthracycline-Induced Cardiotoxicity.

BACKGROUND: Patients with cancer treated with chemotherapy are at risk for cardiovascular toxicity. Global longitudinal strain has been reported to play important roles in predicting cardiovascular adverse events (CAEs) in patients treated with anthracycline. In addition to various left ventricular indicators, the authors hypothesized that right ventricular (RV) parameters might be associated with CAEs related to anthracycline treatment. METHODS: In this retrospective study, 96 patients diagnosed with diffuse large B-cell lymphoma who received chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) were studied using three-dimensional transthoracic echocardiography. Baseline demographic data and oncologic and echocardiographic parameters were analyzed. The main outcome was the proportion of patients with grade 3 to 5 CAEs. The association of all three-dimensional transthoracic echocardiographic parameters with long-term CAEs was analyzed using Cox proportional-hazard analysis. RESULTS: Over a median follow-up period of 6.1 years (range, 4.9-7.6 years) after the completion of anthracycline chemotherapy, 18 of 96 patients (19%) experienced CAEs. Percentage changes (%Δ) in left ventricular global longitudinal strain (LVGLS), global circumferential strain, RV ejection fraction (RVEF), and RV end-systolic volume were associated with CAEs (P < .05). A relative reduction of RVEF (hazard ratio, 0.847; 95% CI, 0.785-0.915; P < .001) was the strongest associated factor for CAEs. An increase in CAEs was also observed in patients with impaired %ΔLVGLS > 15% and impaired %ΔRVEF > 12.7% compared with those with impaired %ΔLVGLS > 15% and impaired %ΔRVEF < 12.7% (P = .032). CONCLUSIONS: Three-dimensional echocardiography-based assessments of %ΔRVEF and %Δ in RV end-systolic volume were significantly associated with CAEs in patients with lymphoma treated with anthracycline chemotherapy.