3-Methyl-4-nitrophenol Exposure Deteriorates Oocyte Maturation by Inducing Spindle Instability and Mitochondrial Dysfunction.

3-methyl-4-nitrophenol (PNMC), a well-known constituent of diesel exhaust particles and degradation products of insecticide fenitrothion, is a widely distributed environmental contaminant. PNMC is toxic to the female reproductive system; however, how it affects meiosis progression in oocytes is unknown. In this study, in vitro maturation of mouse oocytes was applied to investigate the deleterious effects of PNMC. We found that exposure to PNMC significantly compromised oocyte maturation. PNMC disturbed the spindle stability; specifically, it decreased the spindle density and increased the spindle length. The weakened spindle pole location of microtubule-severing enzyme Fignl1 may result in a defective spindle apparatus in PNMC-exposed oocytes. PNMC exposure induced significant mitochondrial dysfunction, including mitochondria distribution, ATP production, mitochondrial membrane potential, and ROS accumulation. The mRNA levels of the mitochondria-related genes were also significantly impaired. Finally, the above-mentioned alterations triggered early apoptosis in the oocytes. In conclusion, PNMC exposure affected oocyte maturation and quality through the regulation of spindle stability and mitochondrial function.

TRPC4 aggravates hypoxic pulmonary hypertension by promoting pulmonary endothelial cell apoptosis.

Pulmonary hypertension (PH) is a devastating disease that lacks effective treatment options and is characterized by severe pulmonary vascular remodeling. Pulmonary arterial endothelial cell (PAEC) dysfunction drives the initiation and pathogenesis of pulmonary arterial hypertension. Canonical transient receptor potential (TRPC) channels, a family of Ca2+-permeable channels, play an important role in various diseases. However, the effect and mechanism of TRPCs on PH development have not been fully elucidated. Among the TRPC family members, TRPC4 expression was markedly upregulated in PAECs from hypoxia combined with SU5416 (HySu)-induced PH mice and monocrotaline (MCT)-treated PH rats, as well as in hypoxia-exposed PAECs, suggesting that TRPC4 in PAECs may participate in the occurrence and development of PH. In this study, we aimed to investigate whether TRPC4 in PAECs has an aggravating effect on PH and elucidate the molecular mechanisms. We observed that hypoxia treatment promoted PAEC apoptosis through a caspase-12/endoplasmic reticulum stress (ERS)-dependent pathway. Knockdown of TRPC4 attenuated hypoxia-induced apoptosis and caspase-3/caspase-12 activity in PAECs. Accordingly, adeno-associated virus (AAV) serotype 6-mediated pulmonary endothelial TRPC4 silencing (AAV6-Tie-shRNA-TRPC4) or TRPC4 antagonist suppressed PH progression as evidenced by reduced right ventricular systolic pressure (RVSP), pulmonary vascular remodeling, PAEC apoptosis and reactive oxygen species (ROS) production. Mechanistically, unbiased RNA sequencing (RNA-seq) suggested that TRPC4 deficiency suppressed the expression of the proapoptotic protein sushi domain containing 2 (Susd2) in hypoxia-exposed mouse PAECs. Moreover, TRPC4 activated hypoxia-induced PAEC apoptosis by promoting Susd2 expression. Therefore, inhibiting TRPC4 ameliorated PAEC apoptosis and hypoxic PH in animals by repressing Susd2 signaling, which may serve as a therapeutic target for the management of PH.

The genus Ranunculus L. (Ranunculus) in Asia: a review of its botany, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations.

OBJECTIVES: Ranunculus L. genus contains 413 species, and it is the biggest genus in the family Ranunculaceae Juss. This review is to provide botanical characteristics, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations of the genus Ranunculus. KEY FINDINGS: The genus Ranunculus contains flavonoids, organic acids, coumarins, lactones, glycosides, sterols, polysaccharides, and trace elements. These chemical constituents complement the pharmacological actions and work together to exert anti-inflammatory, anticancer, antitubercular, antibacterial, antimalarial, etc. Those traditional Chinese medicine characteristics, like clearing away heat and detoxification, make this genus significant in ethnic medicine. The progress in research and the development of various pharmaceutical preparations made it appear in epidemiological and clinical studies. SUMMARY: The genus Ranunculus has attracted the attention of experts and scholars in many fields due to its unique advantages. However, there are many species that are not scientifically investigated. The toxicity issues are also a huge concern. Fortunately, the toxicity can be overcome via special processes like drying or heating and by choosing a safe extraction solvent, such as water thus ensuring the safety of medication. Pharmaceutical preparations containing the plants from Ranunculus have gratifying clinical value, but they are not promoted sufficiently. Therefore, further research should be carried out to promote the genus for its health benefits to humans.

Adaptive locating foveated ghost imaging based on affine transformation.

Ghost imaging (GI) has been widely used in the applications including spectral imaging, 3D imaging, and other fields due to its advantages of broad spectrum and anti-interference. Nevertheless, the restricted sampling efficiency of ghost imaging has impeded its extensive application. In this work, we propose a novel foveated pattern affine transformer method based on deep learning for efficient GI. This method enables adaptive selection of the region of interest (ROI) by combining the proposed retina affine transformer (RAT) network with minimal computational and parametric quantities with the foveated speckle pattern. For single-target and multi-target scenarios, we propose RAT and RNN-RAT (recurrent neural network), respectively. The RAT network enables an adaptive alteration of the fovea of the variable foveated patterns spot to different sizes and positions of the target by predicting the affine matrix with a minor number of parameters for efficient GI. In addition, we integrate a recurrent neural network into the proposed RAT to form an RNN-RAT model, which is capable of performing multi-target ROI detection. Simulations and experimental results show that the method can achieve ROI localization and pattern generation in 0.358 ms, which is a 1 × 105 efficiency improvement compared with the previous methods and improving the image quality of ROI by more than 4 dB. This approach not only improves its overall applicability but also enhances the reconstruction quality of ROI. This creates additional opportunities for real-time GI.

An Assessment of Trends in HIV-1 Prevalence and Incidence and Spatio-Temporal Analyses of HIV-1 Recent Infection Among MSM During the Surveillance Period Between 2018 and 2022 in Sichuan, China.

Background: Men who have sex with men (MSM) is one main type of high-risk activities facilitating HIV-1 transmission in Sichuan province. Previous works on HIV-1 incidence and prevalence among MSM only concentrated before 2018, the situation after that is unknown. In addition, the distribution of hot-spots related to current HIV-1 epidemic is also rarely known among MSM in Sichuan. Objective: To update trends of HIV-1 prevalence and incidence and to visualize hot-spots of ongoing transmission in Sichuan province during surveillance period among MSM between 2018 and 2022. Methods: Limiting Antigen Avidity assay was performed to detect recent infection within new HIV-1 diagnoses founded during surveillance period among MSM. The HIV-1 prevalence and incidence were calculated according to an extrapolation method proposed by publications and guidelines. Trend tests were performed using χ2 tests with linear-by-linear association. The spatial analysis was conducted with ArcGIS 10.7 to figure hot-spots of HIV-1 recent infections among MSM. Results: Between 2018 and 2022, 16,697 individuals participated in HIV-1 MSM sentinel surveillance program, of which 449 samples (98.25%) were tested with LAg-Avidity EIA, and 230 samples were classified as recent infection. Respectively, the overall prevalence and incidence were 2.74% and 3.69% (95% CI: 3.21, 4.16) and both had significant declining trends (p < 0.001). Luzhou city had a highest HIV-1 incidence (10.74%, 95% CI: 8.39, 13.10) over the study period and was recognized as a hot-spot for recent HIV-1 infection among MSM. Conclusion: During the surveillance period, both HIV-1 prevalence and incidence were declining. However, Luzhou city had an unusually high HIV-1 incidence and became an emerging hot-spot of recent HIV-1 infection among MSM. This finding suggested focused attention, cross-regional intervention strategies, and prevention programs are urgently required to curb the spread of ongoing transmission.

Effects of Kiwifruit Dietary Fibers on Pasting Properties and In Vitro Starch Digestibility of Wheat Starch.

In this study, the roles of kiwifruit soluble/insoluble dietary fiber (SDF/IDF, respectively) in the pasting characteristics and in vitro digestibility of wheat starch were explored. According to RVA and rheological tests, the IDF enhanced the wheat starch viscosity, decreased the gelatinization degree of the starch granules, and exacerbated starch retrogradation. The addition of SDF in high quantities could reduce the starch gelatinization level, lower the system viscosity, and exacerbate starch retrogradation. Through determining the leached amylose content and conducing scanning electron microscopy, the IDF and SDF added in high quantities was combined with the leached amylose wrapped around the starch granules, which reduced the leached amylose content and decreased the gelatinization degree of the starch granules. The Fourier transform infrared results showed that the addition of both the IDF and SDF resulted in an enhancement in hydrogen bonding formed by the hydroxyl groups of the system. The in vitro digestion results strongly suggested that both the IDF and SDF reduced the wheat starch digestibility. The above findings are instructive for the application of both IDF and SDF in starchy functional foods.

A new Cinygmula McDunnough, 1933 species with distinct imaginal frontal fold from eastern Chinese Himalaya (Ephemeroptera: Heptageniidae).

In the family Heptageniidae (Ephemeroptera), Cinygmula hutchinsoni (Traver, 1939) from central Asia is the only species known to possess pointed claws and a distinct frontal fold. Here, a second similar species with the same combination of characters is described. Cinygmula longissima sp. nov. is found in the eastern Himalaya of China, shows stouter imaginal penes, darker wingbases, and narrower nymphal gills than the previous one. This discovery indicates that this species of Heptageniidae are not limited to central Asia but live in high-altitude alpine habitats.

Leaching kinetics and bioaccumulation potential of additive-derived organophosphate esters in microplastics.

Considerable research has been conducted to evaluate microplastics (MPs) as vehicles for the transfer of hazardous pollutants in organisms. However, little effort has been devoted to the chemical release of hazardous additive-derived pollutants from MPs in gut simulations. This study looked at the leaching kinetics of organophosphate esters (OPFRs) from polypropylene (PP) and polystyrene (PS) MPs in the presence of gut surfactants, specifically sodium taurocholate, at two biologically relevant temperatures for marine organisms. Diffusion coefficients of OPFRs ranged from 1.71 × 10-20 to 4.04 × 10-18 m2 s-1 in PP and 2.91 × 10-18 to 1.51 × 10-15 m2 s-1 in PS. The accumulation factors for OPFRs in biota-plastic and biota-sediment interactions ranged from 1.52 × 10-3-69.1 and 0.02-0.7, respectively. Based on B3LYP/6-31G (d,p) calculations, the biodynamic model analysis revealed a slight increase in the bioaccumulation of OPFRs at a minor dose of 0.05% MPs. However, at higher concentrations (0.5% and 5% MPs), there was a decrease in bioaccumulation compared to the lower concentration for most OPFR compounds. In general, the ingestion of PE MPs notably contributed to the bioaccumulation of OPFRs in lugworms, whereas the contribution of PP and PS MPs was minimal. This could vary among sites exhibiting varying levels of MP concentrations or MPs displaying stronger affinities towards chemicals.

Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases: Recent advancements and prospects.

Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide. For diverse disease conditions, the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung diseases. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) isolated from the human UC have the capacity for self-renewal and multilineage differentiation. Moreover, in recent years, these cells have been demonstrated to have unique advantages in the treatment of lung diseases. We searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases, including coronavirus disease 2019, acute respiratory distress syndrome, bronchopulmonary dysplasia, chronic obstructive pulmonary disease, and pulmonary fibrosis. In this review, we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical application. Moreover, the underlying molecular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in depth. In brief, this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.

Comprehensive analysis of anoikis-related genes in diagnosis osteoarthritis: based on machine learning and single-cell RNA sequencing data.

Osteoarthritis (OA) is a degenerative disease closely associated with Anoikis. The objective of this work was to discover novel transcriptome-based anoikis-related biomarkers and pathways for OA progression.The microarray datasets GSE114007 and GSE89408 were downloaded using the Gene Expression Omnibus (GEO) database. A collection of genes linked to anoikis has been collected from the GeneCards database. The intersection genes of the differential anoikis-related genes (DEARGs) were identified using a Venn diagram. Infiltration analyses were used to identify and study the differentially expressed genes (DEGs). Anoikis clustering was used to identify the DEGs. By using gene clustering, two OA subgroups were formed using the DEGs. GSE152805 was used to analyse OA cartilage on a single cell level. 10 DEARGs were identified by lasso analysis, and two Anoikis subtypes were constructed. MEgreen module was found in disease WGCNA analysis, and MEturquoise module was most significant in gene clusters WGCNA. The XGB, SVM, RF, and GLM models identified five hub genes (CDH2, SHCBP1, SCG2, C10orf10, P FKFB3), and the diagnostic model built using these five genes performed well in the training and validation cohorts. analysing single-cell RNA sequencing data from GSE152805, including 25,852 cells of 6 OA cartilage.

A quality grade classification method for fresh tea leaves based on an improved YOLOv8x-SPPCSPC-CBAM model.

In light of the prevalent issues concerning the mechanical grading of fresh tea leaves, characterized by high damage rates and poor accuracy, as well as the limited grading precision through the integration of machine vision and machine learning (ML) algorithms, this study presents an innovative approach for classifying the quality grade of fresh tea leaves. This approach leverages an integration of image recognition and deep learning (DL) algorithm to accurately classify tea leaves' grades by identifying distinct bud and leaf combinations. The method begins by acquiring separate images of orderly scattered and randomly stacked fresh tea leaves. These images undergo data augmentation techniques, such as rotation, flipping, and contrast adjustment, to form the scattered and stacked tea leaves datasets. Subsequently, the YOLOv8x model was enhanced by Space pyramid pooling improvements (SPPCSPC) and the concentration-based attention module (CBAM). The established YOLOv8x-SPPCSPC-CBAM model is evaluated by comparing it with popular DL models, including Faster R-CNN, YOLOv5x, and YOLOv8x. The experimental findings reveal that the YOLOv8x-SPPCSPC-CBAM model delivers the most impressive results. For the scattered tea leaves, the mean average precision, precision, recall, and number of images processed per second rates of 98.2%, 95.8%, 96.7%, and 2.77, respectively, while for stacked tea leaves, they are 99.1%, 99.1%, 97.7% and 2.35, respectively. This study provides a robust framework for accurately classifying the quality grade of fresh tea leaves.

Streptococcus suis subtilisin-like serine proteases SspA-1 and SspA-2 interplay with complement C3a and C5a to facilitate bacterial immune evasion and infection.

Streptococcus suis (S. suis), a significant zoonotic bacterial pathogen impacting swine and human, is associated with severe systemic diseases such as streptococcal toxic shock-like syndrome, meningitis, septicaemia, and abrupt fatality. The multifaceted roles of complement components C5a and C3a extend to orchestrating inflammatory cells recruitment, oxidative burst induction, and cytokines release. Despite the pivotal role of subtilisin-like serine proteases in S. suis pathogenicity, their involvement in immune evasion remains underexplored. In the present study, we identify two cell wall-anchored subtilisin-like serine proteases in S. suis, SspA-1 and SspA-2, as binding partners for C3a and C5a. Through Co-Immunoprecipitation, Enzyme-Linked Immunosorbent and Far-Western Blotting Assays, we validate their interactions with the aforementioned components. However, SspA-1 and SspA-2 have no cleavage activity against complement C3a and C5a performed by Cleavage assay. Chemotaxis assays reveal that recombinant SspA-1 and SspA-2 effectively attenuate monocyte chemotaxis towards C3a and C5a. Notably, the ΔsspA-1, ΔsspA-1, and ΔsspA-1/2 mutant strains exhibit compromised survival in blood, and resistance of opsonophagocytosis, alongside impaired survival in blood and in vivo colonization compared to the parental strain SC-19. Critical insights from the murine and Galleria mellonella larva infection models further underscore the significance of sspA-1 in altering mortality rates. Collectively, our findings indicate that SspA-1 and SspA-2 are novel binding proteins for C3a and C5a, thereby shedding light on their pivotal roles in S. suis immune evasion and the pathogenesis.

Improved LEACH Protocol Based on Underwater Energy Propagation Model, Parallel Transmission, and Replication Computing for Underwater Acoustic Sensor Networks.

Underwater acoustic sensor networks (UASNs) are critical to a range of applications from oceanographic data collection to submarine surveillance. In these networks, efficient energy management is critical due to the limited power resources of underwater sensors. The LEACH protocol, a popular cluster-based protocol, has been widely used in UASNs to minimize energy consumption. Despite its widespread use, the conventional LEACH protocol faces challenges such as an unoptimized cluster number and low transmission efficiency, which hinder its performance. This paper proposes an improved LEACH protocol for cluster-based UASNs, where the cluster number is optimized with an underwater energy propagation model to reduce energy consumption, and a transmission scheduling algorithm is also employed to achieve conflict-free parallel data transmission. Replication computing is introduced to the LEACH protocol to reduce the signaling in the clustering and data transmission phases. The simulation results show that the proposed protocol outperforms several conventional methods in terms of normalized average residual energy, average number of surviving nodes, average round when the first death node occurs, and the number of packets received by the base station.

Synergistic Interfacial Optimization for High-Sulfur-Content All-Solid-State Lithium-Sulfur Batteries.

Improving the sulfur content in the cathode is essential for achieving high-energy-density all-solid-state lithium-sulfur batteries (ASSLSBs). However, the complex multiinterfaces, akin to the short wooden planks that consist of the cask, severely limit the performance of ASSLSBs with high sulfur content. Since singular approaches fail to optimize these interfaces simultaneously, we propose a synergistic approach using a dual-doped sulfide solid electrolyte (Y2S3 and LiI) and an SbSn alloy sulfur host in this work. The incorporation of Y2S3 in the solid electrolyte serves to improve the electrolyte-electrolyte interfaces and enhance the ionic conductivity, while the inclusion of LiI helps stabilize the electrolyte-anode interface and suppress dendrite formation. Meanwhile, the SbSn alloy sulfur host facilitates the transfer of Li+ at the electrolyte-cathode interfaces. Consequently, the solid-solid interfaces are significantly improved, leading to impressive specific capacities in ASSLSBs with high sulfur content (>44% in the cathode composite) at room temperature (1163.5 mAh g-1) and at 60 °C (1408.7 mAh g-1) during the 50th cycle at 0.05C. This work presents a promising strategy for achieving practical high-performance ASSLSBs.

Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice.

OBJECTIVE: The function of Bcl-6 in T follicular helper (Tfh) cell maturation is indispensable, and Tfh cells play a pivotal role in asthma. This study investigated the impact of Bcl-6 on asthmatic traits. METHODS: The microscopic pathological alterations, airway resistance (AR), and lung compliance (LC) were determined in asthmatic mice and Bcl-6 interference mice. The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) were determined. RESULTS: Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone (DXM). Asthmatic mice exhibited an increased AR and a decreased LC, while Bcl-6 siRNA or DXM mitigated these changes. The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice, and they significantly decreased after Bcl-6 inhibition or DXM treatment. RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice, and it decreased following Bcl-6 inhibition or DXM treatment. The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend. In asthmatic mice, the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF, but not with the IgG1 levels. CONCLUSION: The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression, which effectively hinders Tfh cell differentiation, ultimately resulting in a concurrent reduction in IgE production.

Correlation analysis of hypertension, traditional Chinese medicine constitution, and LPL gene polymorphism in the elderly in communities in Shanghai.

BACKGROUND: Research on the genetic mechanisms of hypertension has been a hot topic in the cardiovascular field. OBJECTIVE: To study the correlation between senile hypertension and traditional Chinese medicine (TCM) constitution and lipoprotein lipase (LPL) gene polymorphism and to provide the theoretical basis for TCM prevention and treatment of hypertension. METHODS: The elderly population in communities in Shanghai (hypertensive: 264 cases; non-hypertensive: 159 cases) was taken as the research object. Essential data and information on TCM constitution were collected. The LPL gene mutation was detected using the second-generation sequencing method. Statistical analysis was performed to clarify the relationship between hypertension and senile hypertension. The correlation of TCM constitution with risk factors and LPL gene polymorphisms was studied. RESULTS: The primary TCM constitutions in the hypertension group were phlegm-dampness constitution (51.52%), yin-deficiency constitution (17.42%), balanced constitution (15.53%), and yin-deficiency (9.43%). Logistic regression analysis showed that the phlegm-dampness constitution (P< 0.05, OR = 2.587) and yin-deficiency constitution (P< 0.01, OR = 2.693) were the risk constitutions of hypertension in the elderly. A total of 37 LPL gene mutation loci (SNP: 22; new discovery: 15) were detected in the LPL gene, and the mutation rates of rs254, rs255, rs3208305, rs316, rs11570891, rs328, rs11570893, and rs13702 were relatively high, which were 26.24%, 26.24%, 16.08%, 14.66%, 13.24%, 12.06%, and 10.64%. In the phlegm-dampness group, the proportion of rs254 CC type, rs255 TT type, and rs13702 TT type in the hypertensive group (77.21%, 77.21%, and 93.38%) was higher than that in the non-hypertensive group (56.41%, 56.41%, and 82.05%), The difference was statistically significant (P< 0.05). CONCLUSION: The phlegm-dampness constitution and yin-deficiency constitution are the risk factors of hypertension in the elderly; in the phlegm-dampness population, rs254 CC type, rs255 TT type, and rs13702 TT type are the risk factors for elderly hypertension.

FFR CT and Static Computed Tomography Myocardial Perfusion Imaging for Therapeutic Decision-making and Prognosis in Patients With Coronary Artery Disease.

PURPOSE: The purpose of this study was to investigate the effect of integrated evaluation of resting static computed tomography perfusion (CTP) and coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFR CT ) on therapeutic decision-making and predicting major adverse cardiovascular events (MACEs) in patients with suspected coronary artery disease. MATERIALS AND METHODS: In this post hoc analysis of a prospective trial of CCTA in patients assigned to either CCTA or CCTA plus FFR CT arms, 500 patients in the CCTA plus FFR CT arm were analyzed. Both resting static CTP and FFR CT were evaluated by using the conventional CCTA. Perfusion defects in the myocardial segments with ≥50% degree of stenosis in the supplying vessels were defined as resting static CTP positive, and any vessel with an FFR CT value of ≤0.80 was considered positive. Patients were divided into 3 groups: (1) negative CTP-FFR CT match group (resting static CTP-negative and FFR CT -negative group); (2) mismatch CTP-FFR CT group (resting static CTP-positive and FFR CT -negative or resting static CTP-negative and FFR CT -positive group); and (3) positive CTP-FFR CT match group (resting static CTP-positive and FFR CT -positive group). We compared the revascularization-to-invasive coronary angiography ratio and the MACE rate among 3 subgroups at 1- and 3-year follow-ups. The adjusted Cox hazard proportional model was used to assess the prognostic value of FFR CT and resting static CTP to determine patients at risk of MACE. RESULTS: Patients in the positive CTP-FFR CT match group were more likely to undergo revascularization at the time of invasive coronary angiography compared with those in the mismatch CTP-FFR CT group (81.4% vs 57.7%, P =0.033) and the negative CTP-FFR CT match group (81.4% vs 33.3%, P= 0.001). At 1- and 3-year follow-ups, patients in the positive CTP-FFR CT match group were more likely to have MACE than those in the mismatch CTP-FFR CT group (10.5% vs 4.2%, P= 0.046; 35.6% vs 9.4%, P <0.001) and the negative CTP-FFR CT match group (10.5% vs 0.9%, P <0.001; 35.6% vs 5.4%, P <0.001). A positive CTP-FFR CT match was strongly related to MACE at 1-year (hazard ratio=8.06, P= 0.003) and 3-year (hazard ratio=6.23, P <0.001) follow-ups. CONCLUSION: In patients with suspected coronary artery disease, the combination of FFR CT with resting static CTP could guide therapeutic decisions and have a better prognosis with fewer MACE in a real-world scenario.

Gypenoside Pretreatment Alleviates the Cerebral Ischemia Injury via Inhibiting the Microglia-Mediated Neuroinflammation.

Neuroinflammation is closely related to prognosis in ischemic stroke. Microglia are the main immune cells in the nervous system. Under physiological conditions, microglia participate in clearance of dead cells, synapse pruning and regulation of neuronal circuits to maintain the overall health of the nervous system. Once ischemic stroke occurs, microglia function in the occurrence and progression of neuroinflammation. Therefore, the regulation of microglia-mediated neuroinflammation is a potential therapeutic strategy for ischemic stroke. The anti-inflammatory activity of gypenosides (GPs) has been confirmed to be related to the activity of microglia in other neurological diseases. However, the role of GPs in neuroinflammation after ischemic stroke has not been studied. In this study, we investigated whether GPs could reduce neuroinflammation by regulating microglia and the underlying mechanism through qRT-PCR and western blot. Results showed that GPs pretreatment mitigated blood-brain barrier (BBB) damage in the mice subjected to middle cerebral artery occlusion (MCAO) and improved motor function. According to the results of immunofluorescence staining, GPs pretreatment alleviated neuroinflammation in MCAO mice by reducing the number of microglia and promoting their phenotypic transformation from M1 to M2. Furthermore, GPs pretreatment reduced the number of astrocytes in the penumbra and inhibited their polarization into the A1 type. We applied oxygen and glucose deprivation (OGD) on BV2 cells to mimic ischemic conditions in vitro and found similar effect as that in vivo. At the molecular level, the STAT-3/HIF1-α and TLR-4/NF-κB/HIF1-α pathways were involved in the anti-inflammatory effects of GPs in vitro and in vivo. Overall, this research indicates that GPs are potential therapeutic agents for ischemic stroke and has important reference significance to further explore the possibility of GPs application in ischemic stroke.

Compromise Optimized Superior Energy Storage Performance in Lead-Free Antiferroelectrics by Antiferroelectricity Modulation and Nanodomain Engineering.

Lead-free antiferroelectrics with excellent energy storage performance can become the core components of the next-generation advanced pulse power capacitors. However, the low energy storage efficiency caused by the hysteresis of antiferroelectric-ferroelectric transition largely limits their development toward miniaturization, lightweight, and integration. In this work, an ultrahigh recoverable energy storage density of ≈11.4 J cm-3 with a high efficiency of ≈80% can be realized in La-modified Ag0.5 Na0.5 NbO3 antiferroelectric ceramics at an ultrahigh breakdown electric field of ≈67 kV mm-1 by the compromise optimization between antiferroelectricity enhancement and nanodomain engineering, resulting in the transformation of large-size ferrielectric antipolar stripe domains into ultrasmall antiferroelectric nanodomains or polarization nanoregions revealing as Moiré fringe structures. In addition, the enhanced transparency with increasing La content can also be clearly observed. This work not only develops new lead-free antiferroelectric energy storage materials with high application potential but also demonstrates that the strategy of compromise optimization between antiferroelectricity modulation and nanodomain engineering is an effective avenue to enhance the energy storage performance of antiferroelectrics.

Maternal exposure to 4-vinylcyclohexene diepoxide during pregnancy leads to disorder of gut microbiota and bile acid metabolism in offspring.

Our previous study reveals that maternal exposure to 4-vinylcyclohexene diepoxide (VCD) during pregnancy causes insufficient ovarian follicle reserve and decreased fertility in offspring. The present study aims to further explore the reasons for the significant decline of fecundity in mice caused by VCD, and to clarify the changes of gut microbiota and microbial metabolites in F1 mice. The ovarian metabolomics, gut microbiota and microbial metabolites were analyzed. The results of ovarian metabolomics analysis showed that maternal VCD exposure during pregnancy significantly reduced the concentration of carnitine in the ovaries of F1 mice, while supplementation with carnitine (isovalerylcarnitine and valerylcarnitine) significantly increased the number of ovulation. The results of 16 S rDNA-seq and microbial metabolites analysis showed that maternal VCD exposure during pregnancy caused disordered gut microbiota, increased abundance of Parabacteroides and Flexispira bacteria that are involved in secondary bile acid synthesis. The concentrations of NorDCA, LCA-3S, DCA and other secondary bile acids increased significantly. Our results indicate that maternal exposure to VCD during pregnancy leads to disorder in gut microbiota and bile acid metabolism in F1 mice, accompanying with decreased ovarian function, providing further evidence that maternal exposure to VCD during pregnancy has intergenerational deleterious effects on offspring.