IL-23 Priming Enhances the Neuroprotective Effects of MSC-Derived Exosomes in Treating Retinal Degeneration.

Purpose: Neuroinflammation is a characteristic feature of neurodegenerative diseases. Mesenchymal stem cell-derived exosomes (MSC-exo) have shown neuroprotective effects through immunoregulation, but the therapeutic efficacy remains unsatisfactory. This study aims to enhance the neuroprotective capacity of MSC-exo through IL-23 priming for treating retinal degeneration in mice. Methods: MSC were primed with IL-23 stimulation in vitro, and subsequently, exosomes (MSC-exo and IL-23-MSC-exo) were isolated and characterized. Two retinal degenerative disease models (NaIO3-induced mice and rd10 mice) received intravitreal injections of these exosomes. The efficacy of exosomes was assessed by examining retinal structural and functional recovery. Furthermore, exosomal microRNA (miRNA) sequencing was conducted, and the effects of exosomes on the M1 and M2 microglial phenotype shift were evaluated. Results: IL-23-primed MSC-derived exosomes (IL-23-MSC-exo) exhibited enhanced capability in protecting photoreceptor cells and retinal pigment epithelium (RPE) cells against degenerative damage and fostering the restoration of retinal neural function in both NaIO3-induced retinal degeneration mice and rd10 mice when compared with MSC-exo. The exosomal miRNA suppression via Drosha knockdown in IL-23-primed MSC would abolish the neuroprotective role of IL-23-MSC-exo, highlighting the miRNA-dependent mechanism. Bioinformatic analysis, along with further in vivo biological studies, revealed that IL-23 priming induced a set of anti-inflammatory miRNAs in MSC-exo, prompting the transition of M1 to M2 microglial polarization. Conclusions: IL-23 priming presents as a potential avenue for amplifying the immunomodulatory and neuroprotective effects of MSC-exo in treating retinal degeneration.

Gamma-type immunoglobulin enhances phagocytosis of amyloid-beta fibrils by microglia.

The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer's disease. Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system, though the mechanisms are unclear. Here, we found that gamma-type immunoglobulin, a product originating from peripheral blood B cells, localized in the brain parenchyma of multiple mouse models with amyloid pathology, and was enriched on microglia but not on other brain cell types. Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes, including upregulation of pathways related to phagocytosis and immunity. Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc, but not Fab, fragment. Our data indicate that microglia, when exposed to gamma-type immunoglobulin, exhibit an enhanced capacity for clearing amyloid-beta fibrils, potentially via the gamma-type immunoglobulin Fc fragment signaling pathway. This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer's disease by enhancing microglial function.

PDCD4 triggers α-synuclein accumulation and motor deficits via co-suppressing TFE3 and TFEB translation in a model of Parkinson's disease.

TFE3 and TFEB, as the master regulators of lysosome biogenesis and autophagy, are well characterized to enhance the synaptic protein α-synuclein degradation in protecting against Parkinson's disease (PD) and their levels are significantly decreased in the brain of PD patients. However, how TFE3 and TFEB are regulated during PD pathogenesis remains largely vague. Herein, we identified that programmed cell death 4 (PDCD4) promoted pathologic α-synuclein accumulation to facilitate PD development via suppressing both TFE3 and TFEB translation. Conversely, PDCD4 deficiency significantly augmented global and nuclear TFE3 and TFEB distributions to alleviate neurodegeneration in a mouse model of PD with overexpressing α-synuclein in the striatum. Mechanistically, like TFEB as we reported before, PDCD4 also suppressed TFE3 translation, rather than influencing its transcription and protein stability, to restrain its nuclear translocation and lysosomal functions, eventually leading to α-synuclein aggregation. We proved that the two MA3 domains of PDCD4 mediated the translational suppression of TFE3 through binding to its 5'-UTR of mRNA in an eIF-4A dependent manner. Based on this, we developed a blood-brain barrier penetrating RVG polypeptide modified small RNA drug against pdcd4 to efficiently prevent α-synuclein neurodegeneration in improving PD symptoms by intraperitoneal injections. Together, we suggest PDCD4 as a PD-risk protein to facilitate α-synuclein neurodegeneration via suppressing TFE3 and TFEB translation and further provide a potential small RNA drug against pdcd4 to treat PD by intraperitoneal injections.

Multiparametric simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) incorporating intratumoral and peritumoral regions for grading of glioma.

Background: Preoperative grading gliomas is essential for therapeutic clinical decision-making. Current non-invasive imaging modality for glioma grading were primarily focused on magnetic resonance imaging (MRI) or positron emission tomography (PET) of the tumor region. However, these methods overlook the peritumoral region (PTR) of tumor and cannot take full advantage of the biological information derived from hybrid-imaging. Therefore, we aimed to combine multiparameter from hybrid 18F-fluorodeoxyglucose (18F-FDG) PET/MRI of the solid component and PTR were combined for differentiating high-grade glioma (HGG) from low-grade glioma (LGG). Methods: A total of 76 patients with pathologically confirmed glioma (41 HGG and 35 LGG) who underwent simultaneous 18F-FDG PET, arterial spin labelling (ASL), and diffusion-weighted imaging (DWI) with hybrid PET/MRI were retrospectively enrolled. The relative maximum standardized uptake value (rSUVmax), relative cerebral blood flow (rCBF), and relative minimum apparent diffusion coefficient (rADCmin) for the solid component and PTR at different distances outside tumoral border were compared. Receiver operating characteristic (ROC) curves were applied to assess the grading performance. A nomogram for HGG prediction was constructed. Results: HGGs displayed higher rSUVmax and rCBF but lower rADCmin in the solid component and 5 mm-adjacent PTR, lower rADCmin in 10 mm-adjacent PTR, and higher rCBF in 15- and 20-mm-adjacent PTR. rSUVmax in solid component performed best [area under the curve (AUC) =0.865] as a single parameter for grading. Combination of rSUVmax in the solid component and adjacent 20 mm performed better (AUC =0.881). Integration of all 3 indicators in the solid component and adjacent 20 mm performed the best (AUC =0.928). The nomogram including rSUVmax, rCBF, and rADCmin in the solid component and 5-mm-adjacent PTR predicted HGG with a concordance index (C-index) of 0.906. Conclusions: Multiparametric 18F-FDG PET/MRI from the solid component and PTR performed excellently in differentiating HGGs from LGGs. It can be used as a non-invasive and effective tool for preoperative grade stratification of patients with glioma, and can be considered in clinical practice.

High-purity La3-xTe4 Material with Superior Thermoelectric Performance Synthesized via Te-vapor Transport and Solid-State Diffusion.

La3-xTe4 is a very promising high-temperature candidate applied in next-generation Radioisotope Thermoelectric Generators (RTGs). Conventional synthesis of such materials is based on the mechanochemical method, which makes the sample difficult to purify due to the high-energy ball milling. In this report, a novel synthetic method is developed, which utilizes Te-vapor transport and solid-phase diffusion to efficiently produce the RE3-xTe4 phases (RE = La, Ce, Pr, Nd). Notably, this method obviates the requirement for high-energy ball-milling instruments, conventionally indispensable in the mechanochemical syntheses. For as-synthesized La2.74Te4 material, a high figure of merit of 1.5 is achieved at 1073 K, owning to the reduced electronic thermal conductivity with metal impurities well eliminated.

The Relationship Between Alcohol Consumption and Frailty Among Older Adults in China: Results From the Chinese Longitudinal Healthy Longevity Survey.

INTRODUCTION: Alcohol consumption has an impact on the frailty, but current research in China lacks a detailed classification of alcohol use. This study aimed to explore the relationship between different drinking patterns and frailty in older adults. METHODOLOGY: The data came from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) study, which included older adults (aged ≧ 60). Their demographic data, drinking status, and frailty index were collected in CLHLS. Through logistic regression models to analyze the correlation between alcohol consumption and frailty. RESULTS: A total of 14,931 participants were included in the analysis. The prevalence of frailty was 29.1%, 35.2%, and 14.9% among risk-free, past risky, and now risky drinkers, respectively. After adjusting for covariates, past risky drinking was a risk factor for frailty (p = .003). DISCUSSION: High-risk alcohol consumption is positively correlated with frailty. Prevention and reduction of risky drinking in older adults may help protect them from developing frailty.

Association of Human Whole-blood NAD + Levels with Nabothian Cyst.

Objective: Little is known about the association between whole-blood nicotinamide adenine dinucleotide (NAD +) levels and nabothian cysts. This study aimed to assess the association between NAD + levels and nabothian cysts in healthy Chinese women. Methods: Multivariate logistic regression analysis was performed to analyze the association between NAD + levels and nabothian cysts. Results: The mean age was 43.0 ± 11.5 years, and the mean level of NAD + was 31.3 ± 5.3 µmol/L. Nabothian cysts occurred in 184 (27.7%) participants, with single and multiple cysts in 100 (15.0%) and 84 (12.6%) participants, respectively. The total nabothian cyst prevalence gradually decreased from 37.4% to 21.6% from Q1 to Q4 of NAD + and the prevalence of single and multiple nabothian cysts also decreased across the NAD + quartiles. As compared with the highest NAD + quartile (≥ 34.4 µmol/L), the adjusted odds ratios with 95% confidence interval of the NAD + Q1 was 1.89 (1.14-3.14) for total nabothian cysts. The risk of total and single nabothian cysts linearly decreased with increasing NAD + levels, while the risk of multiple nabothian cysts decreased more rapidly at NAD + levels of 28.0 to 35.0 µmol/L. Conclusion: Low NAD + levels were associated with an increased risk of total and multiple nabothian cysts.

Self-assembled Au-CQDs nanofluids with excellent solar absorption and medium-high temperature stability for solar energy harvesting.

Nanofluids-based direct absorption solar collectors are promising candidates for medium-high-temperature solar energy harvesting. However, nanofluids' complicated preparation process and undesirable high-temperature stability have hindered their practical applications. Herein, we propose a facile method for synthesizing gold/carbon quantum dots (Au-CQDs) nanofluids by directly carbonizing the base fluid and spontaneously assembling with Au nanoparticles (AuNPs) triggered by high temperatures. The results indicate that the self-assembled Au-CQDs nanofluids can maintain high stability at 110 °C for 100 h without precipitation and keep excellent photothermal conversion performance under 10 sun irradiation. The concentration and particle size of AuNPs are crucial factors affecting the self-assembly process. By modulating the microscopic morphologies of the self-assembled nanoparticles, the extinction coefficient of the prepared nanofluids is up to 88.7 % at a low loading of 30 ppm. The nanofluids can reach an equilibrium temperature of 50 °C under 1 sun irradiation, 10.4 °C higher than the base fluid due to the enhanced plasmonic effects and stability resulting from the CQDs dotted AuNPs. This work offers a new strategy to fabricate highly stable nanofluids with excellent light absorption properties for efficient solar thermal applications.

IL-37d suppresses Rheb-mTORC1 axis independently of TCS2 to alleviate alcoholic liver disease.

Tuberous sclerosis complex 2 (TSC2) crucially suppresses Rheb activity to prevent mTORC1 activation. However, mutations in TSC genes lead to mTORC1 overactivation, thereby causing various developmental disorders and cancer. Therefore, the discovery of novel Rheb inhibitors is vital to prevent mTOR overactivation. Here, we reveals that the anti-inflammatory cytokine IL-37d can bind to lysosomal Rheb and suppress its activity independent of TSC2, thereby preventing mTORC1 activation. The binding of IL-37d to Rheb switch-II subregion destabilizes the Rheb-mTOR and mTOR-S6K interactions, further halting mTORC1 signaling. Unlike TSC2, IL-37d is reduced under ethanol stimulation, which results in mitigating the suppression of lysosomal Rheb-mTORC1 activity. Consequently, the recombinant human IL-37d protein (rh-IL-37d) with a TAT peptide greatly improves alcohol-induced liver disorders by hindering Rheb-mTORC1 axis overactivation in a TSC2- independent manner. Together, IL-37d emerges as a novel Rheb suppressor independent of TSC2 to terminate mTORC1 activation and improve abnormal lipid metabolism in the liver.

Perfluorooctane sulfonate induces ferroptosis-dependent non-alcoholic steatohepatitis via autophagy-MCU-caused mitochondrial calcium overload and MCU-ACSL4 interaction.

The incidence of nonalcoholic steatohepatitis (NASH) is related with perfluorooctane sulfonate (PFOS), yet the mechanism remains ill-defined. Mounting evidence suggests that ferroptosis plays a crucial role in the initiation of NASH. In this study, we used mice and human hepatocytes L-02 to investigate the role of ferroptosis in PFOS-induced NASH and the effect and molecular mechanism of PFOS on liver ferroptosis. We found here that PFOS caused NASH in mice, and lipid accumulation and inflammatory response in the L-02 cells. PFOS induced hepatic ferroptosis in vivo and in vitro, as evidenced by the decrease in glutathione peroxidase 4 (GPX4), and the increases in cytosolic iron, acyl-CoA synthetase long-chain family member 4 (ACSL4) and lipid peroxidation. In the PFOS-treated cells, the increases in the inflammatory factors and lipid contents were reversed by ferroptosis inhibitor. PFOS-induced ferroptosis was relieved by autophagy inhibitor. The expression of mitochondrial calcium uniporter (MCU) was accelerated by PFOS, leading to subsequent mitochondrial calcium accumulation, and inhibiting autophagy reversed the increase in MCU. Inhibiting mitochondrial calcium reversed the variations in GPX4 and cytosolic iron, without influencing the change in ACSL4, induced by PFOS. MCU interacted with ACSL4 and the siRNA against MCU reversed the changes in ACSL4，GPX4 and cytosolic iron systemically. This study put forward the involvement of hepatic ferroptosis in PFOS-induced NASH and identified MCU as the mediator of the autophagy-dependent ferroptosis.

IDD10-NAC079 transcription factor complex regulates sheath blight resistance by inhibiting ethylene signaling in rice.

INTRODUCTION: Rhizoctonia solani Kühn is a pathogen causing rice sheath blight (ShB). Ammonium transporter 1 (AMT1) promotes resistance of rice to ShB by activating ethylene signaling. However, how AMT1 activates ethylene signaling remains unclear. OBJECTIVE: In this study, the indeterminate domain 10 (IDD10)-NAC079 interaction model was used to investigate whether ethylene signaling is modulated downstream of ammonium signaling and modulates ammonium-mediated ShB resistance. METHODS: RT-qPCR assay was used to identify the relative expression levels of nitrogen and ethylene related genes. Yeast two-hybrid assays, Bimolecular fluorescence complementation (BiFC) and Co-immunoprecipitation (Co-IP) assay were conducted to verify the IDD10-NAC079-calcineurin B-like interacting protein kinase 31 (CIPK31) transcriptional complex. Yeast one-hybrid assay, Chromatin immunoprecipitation (ChIP) assay, and Electrophoretic mobility shift assay (EMSA) were used to verify whether ETR2 was activated by IDD10 and NAC079. Ethylene quantification assay was used to verify ethylene content in IDD10 transgenic plants. Genetic analysis is used to detect the response of IDD10, NAC079 and CIPK31 to ShB infestation. RESULTS: IDD10-NAC079 forms a transcription complex that activates ETR2 to inhibit the ethylene signaling pathway to negatively regulating ShB resistance. CIPK31 interacts and phosphorylates NAC079 to enhance its transcriptional activation activity. In addition, AMT1-mediated ammonium absorption and subsequent N assimilation inhibit the expression of IDD10 and CIPK31 to activate the ethylene signaling pathway, which positively regulates ShB resistance. CONCLUSION: The study identified the link between ammonium and ethylene signaling and improved the understanding of the rice resistance mechanism.

Therapeutic intervention in neuroinflammation for neovascular ocular diseases through targeting the cGAS-STING-necroptosis pathway.

The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.

Brain Short-Chain Fatty Acids Induce ACSS2 to Ameliorate Depressive-Like Behavior via PPARγ-TPH2 Axis.

Short-chain fatty acids (SCFAs) have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse psychiatric or neurological disorders via the microbiota-gut-brain axis. However, the precise mechanism by which brain SCFAs extert multiple beneficial effects is not completely understood. Our previous research has demonstrated that the acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is a novel target of the rapid and long-lasting antidepressant responses. Here, we show that micromolar SCFAs significantly augment both total cellular and nuclear ACSS2 to trigger tryptophan hydroxylase 2 (TPH2) promoter histone acetylation and its transcription in SH-SY5Y cells. In chronic-restraint-stress-induced depression mice, neuronal ACSS2 knockdown by stereotaxic injection of adeno-associated virus in the hippocampus abolished SCFA-mediated improvements in depressive-like behaviors of mice, supporting that ACSS2 is required for SCFA-mediated antidepressant responses. Mechanistically, the peroxisome-proliferator-activated receptor gamma (PPARγ) is identified as a novel partner of ACSS2 to activate TPH2 transcription. Importantly, PPARγ is also responsible for SCFA-mediated antidepressant-like effects via ACSS2-TPH2 axis. To further support brain SCFAs as a therapeutic target for antidepressant effects, d-mannose, which is a naturally present hexose, can significantly reverse the dysbiosis of gut microbiota in the chronic-restraint-stress-exposure mice and augment brain SCFAs to protect against the depressive-like behaviors via ACSS2-PPARγ-TPH2 axis. In summary, brain SCFAs can activate ACSS2-PPARγ-TPH2 axis to play the antidepressive-like effects, and d-mannose is suggested to be an inducer of brain SCFAs in resisting depression.

Rheological characterization of chia seed gum as a thickening agent used for dysphagia management.

Dysphagia has emerged as a serious health issue facing contemporary society. Consuming thickened liquids is an effective approach for improving the swallowing safety for dysphagia patients. The thickening effect of chia seed gum (CSG), a novel thickener, in different dispersing media (water, orange juice, and skim milk) was investigated. Moreover, the potential application of CSG for dysphagia management was evaluated by comparison with xanthan gum (XG) and guar gum (GG). The thickened liquids prepared with 0.4 %-1.2 % (w/v) CSG, XG, and GG could be classified into levels 1-4, 2-4, and 1-3, respectively, according to the International Dysphagia Diet Standardization Initiative (IDDSI) framework. All the thickened liquids displayed shear-thinning characteristics that facilitated safe swallowing. The viscosities (η50) of CSG dissolved in water (0.202-1.027 Pa·s) were significantly greater than those of CSG dissolved in orange juice (0.070-0.690 Pa·s) and skim milk (0.081-0.739 Pa·s), indicating that CSG had a greater thickening effect in water than in orange juice and skim milk. Compared with those prepared with GG, the thickened liquids prepared with CSG and XG exhibited greater viscoelasticity, better water-holding capacity, and more compact networks. The findings suggested that CSG can be used as a potential thickener for thickening liquid foods to manage dysphagia.

The Heterogeneous Habitat of Taiga Forests Changes the Soil Microbial Functional Diversity.

The soil contains abundant and diverse microorganisms, which interrelate closely with the aboveground vegetation and impact the structure and function of the forest ecosystem. To explore the effect of vegetation diversity on soil microbial functional diversity in taiga forests, we selected significantly different important values of Larix gmelinii as experimental grouping treatments based on plant investigation from fixed plots in Da Xing'anling Mountains. Following that, we collected soil samples and applied the Biolog-ECO microplate method to investigate differences in carbon source utilization, features of functional diversity in soil microorganisms, and factors influencing them in taiga forests. The AWCD decreased as the important value of Larix gmelinii grew, and soil microorganisms preferred carboxylic acids, amino acids, and carbohydrates over polymers, phenolic acids, and amines. The Shannon and McIntosh indexes decreased significantly with the increase of the important value of Larix gmelinii (p < 0.05) and were positively correlated with soil SOC, MBC, C/N, and pH, but negatively with TN, AP, and AN. Redundancy analysis revealed significant effects on soil microbial functional diversity from soil C/N, SOC, AP, MBC, TN, pH, AN, and WC. To sum up, heterogeneous habitats of taiga forests with different important values altered soil microbial functional diversity.

S2VQ-VAE: Semi-Supervised Vector Quantised-Variational AutoEncoder for Automatic Evaluation of Trail Making Test.

BACKGROUND: Computer-aided detection of cognitive impairment garnered increasing attention, offering older adults in the community access to more objective, ecologically valid, and convenient cognitive assessments using multimodal sensing technology on digital devices. METHODOLOGY: In this study, we aimed to develop an automated method for screening cognitive impairment, building on paper- and electronic TMTs. We proposed a novel deep representation learning approach named Semi-Supervised Vector Quantised-Variational AutoEncoder (S2VQ-VAE). Within S2VQ-VAE, we incorporated intra- and inter-class correlation losses to disentangle class-related factors. These factors were then combined with various real-time obtainable features (including demographic, time-related, pressure-related, and jerk-related features) to create a robust feature engineering block. Finally, we identified the light gradient boosting machine as the optimal classifier. The experiments were conducted on a dataset collected from older adults in the community. RESULTS: The experimental results showed that the proposed multi-type feature fusion method outperformed the conventional method used in paper-based TMTs and the existing VAE-based feature extraction in terms of screening performance. CONCLUSIONS: In conclusion, the proposed deep representation learning method significantly enhances the cognitive diagnosis capabilities of behavior-based TMTs and streamlines large-scale community-based cognitive impairment screening while reducing the workload of professional healthcare staff.

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

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

Suppression of Pseudomonas aeruginosa type III secretion system by a novel calcium-responsive signaling pathway.

Expression of the type III secretion system (T3SS) in Pseudomonas aeruginosa is exquisitely controlled by diverse environmental or host-related signals such as calcium (Ca2+), however, the signal transduction pathways remain largely elusive. In this study, we reported that FleR, the response regulator of the two-component system FleS/FleR, inhibits T3SS gene expression and virulence of P. aeruginosa uncoupled from its cognate histidine kinase FleS. Interestingly, FleR was found to repress T3SS gene expression under Ca2+-rich conditions independently of its DNA-binding domain. FleR activates the elevation of intracellular c-di-GMP contents and FleQ serves as the c-di-GMP effector to repress T3SS gene expression through the Gac/Rsm pathway. Remarkably, we found that AmrZ, a member of the FleR regulon, inhibits T3SS gene expression by directly targeting the promoter of exsCEBA in an expression level-dependent manner. This study revealed an intricate regulatory network that connects P. aeruginosa T3SS gene expression to the Ca2+ signal.

Structural deep multi-view clustering with integrated abstraction and detail.

Deep multi-view clustering, which can obtain complementary information from different views, has received considerable attention in recent years. Although some efforts have been made and achieve decent performances, most of them overlook the structural information and are susceptible to poor quality views, which may seriously restrict the capacity for clustering. To this end, we propose Structural deep Multi-View Clustering with integrated abstraction and detail (SMVC). Specifically, multi-layer perceptrons are used to extract features from specific views, which are then concatenated to form the global features. Besides, a global target distribution is constructed and guides the soft cluster assignments of specific views. In addition to the exploitation of the top-level abstraction, we also design the mining of the underlying details. We construct instance-level contrastive learning using high-order adjacency matrices, which has an equivalent effect to graph attention network and reduces feature redundancy. By integrating the top-level abstraction and underlying detail into a unified framework, our model can jointly optimize the cluster assignments and feature embeddings. Extensive experiments on four benchmark datasets have demonstrated that the proposed SMVC consistently outperforms the state-of-the-art methods.

Research on Determinants Affecting Users' Impulsive Purchase Intention in Live Streaming from the Perspective of Perceived Live Streamers' Ability.

As an innovative marketing pattern, live-streaming e-commerce supplies advantages over traditional e-commerce in stimulating impulsive purchases. This study developed a theoretical model that examines how perceived live streamers' abilities (perceived live interaction ability and perceived linguistic persuasion ability) affect impulsive purchase intention based on interaction theory, affective distance theory, trust theory, and Aristotle's rhetorical appeals. We conducted empirical research through a survey questionnaire to verify the effectiveness of the model. A total of 330 valid samples were gathered from live-streaming users, and partial least squares-structural equation modeling (PLS-SEM) was employed for data analysis. The results indicate that perceived live interaction ability, encompassing responsiveness, entertainment, and personalization, significantly impacts affective distance. Among the four dimensions of perceived linguistic persuasion ability, emotional contagion significantly influences affective distance, whereas expertise, logic, and morality significantly affect cognitive trust. Both affective distance and cognitive trust promote consumers' impulsive purchases through affective trust. Our research findings provide theoretical and practical recommendations for live-streaming platforms and merchants engaged in live marketing.