Goal-Guided Graph Attention Network with Interactive State Refinement for Multi-Agent Trajectory Prediction.

The accurate prediction of the future trajectories of traffic participants is crucial for enhancing the safety and decision-making capabilities of autonomous vehicles. Modeling social interactions among agents and revealing the inherent relationships is crucial for accurate trajectory prediction. In this context, we propose a goal-guided and interaction-aware state refinement graph attention network (SRGAT) for multi-agent trajectory prediction. This model effectively integrates high-precision map data and dynamic traffic states and captures long-term temporal dependencies through the Transformer network. Based on these dependencies, it generates multiple potential goals and Points of Interest (POIs). Through its dual-branch, multimodal prediction approach, the model not only proposes various plausible future trajectories associated with these POIs, but also rigorously assesses the confidence levels of each trajectory. This goal-oriented strategy enables SRGAT to accurately predict the future movement trajectories of other vehicles in complex traffic scenarios. Tested on the Argoverse and nuScenes datasets, SRGAT surpasses existing algorithms in key performance metrics by adeptly integrating past trajectories and current context. This goal-guided approach not only enhances long-term prediction accuracy, but also ensures its reliability, demonstrating a significant advancement in trajectory forecasting.

Association between the insufficient improvement of the quantitative flow ratio and worsening outcomes in ST-segment elevated myocardial infarction: a multicentre prospective cohort study.

Background: Improved coronary physiological function after percutaneous coronary intervention (PCI) has been shown to improve prognosis in stable ischaemic heart disease, but has not yet been explored in ST-segment elevated myocardial infarction (STEMI). The study sought to determine whether an improvement in the quantitative flow ratio (QFR) could improve the prognosis of STEMI patients undergoing primary PCI. Methods: Patients diagnosed with STEMI who were receiving primary PCI were recruited for the study. Those with thrombolysis in myocardial infarction (TIMI) flow <2 after wiring were excluded. The ΔQFR was calculated using the following formula: ΔQFR = post-PCI QFR - pre-stent QFR. The primary endpoint was the composite event, including recurrent myocardial infarction (MI) and acute heart failure (AHF). Results: In total, 515 STEMI patients with a median follow-up of 364 days were enrolled in the study. Based on the cut-off value from the receiver operator characteristic (ROC) curve, the patients were divided into the following two groups: the lower ΔQFR group (≤0.25, N=332); and the normal ΔQFR group (>0.25, N=183). Patients with a lower ΔQFR had a relatively higher rate of MI/AHF (10.5% vs. 4.4%, P=0.019) and AHF (7.2% vs. 2.7%, P=0.044). A lower ΔQFR was significantly associated with a higher incidence of MI/AHF [hazard ratio (HR) =2.962, 95% confidence interval (CI): 1.358-6.459, P=0.006, respectively] after adjusting for potential confounders. Pre-stent angiographic microvascular resistance [odds ratio (OR) =1.027, 95% CI: 1.022-1.033, P<0.001] and the stent-to-vessel diameter ratio <1.13 (OR =1.766, 95% CI: 1.027-3.071, P=0.04) were independent predictors of a lower ΔQFR. Conclusions: An insufficient improvement in the QFR contributes to worsening outcomes and might be a useful tool for risk stratification in STEMI.

Impaired autophagic flux in the human brain after traumatic brain injury.

Emerging evidence indicates that dysfunctional autophagic flux significantly contributes to the pathology of experimental traumatic brain injury (TBI). The current study aims to clarify its role post-TBI using brain tissues from TBI patients. Histological examinations, including hematoxylin and eosin, Nissl staining, and brain water content analysis, were employed to monitor brain damage progression. Electron microscopy was used to visualize autophagic vesicles. Western blotting and immunohistochemistry were performed to analyze the levels of important autophagic flux-related proteins such as Beclin1, autophagy-related protein 5, lipidated microtubule-associated protein light-chain 3 (LC3-II), autophagic substrate sequestosome 1 (SQSTM1/p62), and cathepsin D (CTSD), a lysosomal enzyme. Immunofluorescence assays evaluated LC3 colocalization with NeuN, P62, or CTSD, and correlation analysis linked autophagy-related protein levels with brain water content and Nissl bodies. Early-stage TBI results showed increased autophagic vesicles and LC3-positive neurons, suggesting autophagosome accumulation due to enhanced initiation and reduced clearance. As TBI progressed, LC3-II and P62 levels increased, while CTSD levels decreased. This indicates autophagosome overload from impaired degradation rather than increased initiation. The study reveals a potential association between worsening brain damage and impaired autophagic flux post-TBI, positioning improved autophagic flux as a viable therapeutic target for TBI.

Single-cell RNA sequencing in cancer research: discovering novel biomarkers and therapeutic targets for immune checkpoint blockade.

Immune checkpoint blockade (ICB) has become a promising strategy in treating advanced cancers, providing significant survival benefits for patients with various cancer types. However, among the vast population of cancer patients, only a small fraction are able to respond to and derive benefits from ICB therapy. Numerous factors contribute to the diminished efficacy of ICB, with the complex tumor microenvironment (TME) playing an important role. Therefore, comprehensively understanding the intricate composition of the TME is critical for elucidating the mechanisms that underlie distinct responses to ICB in patients. Single-cell RNA sequencing (scRNA-seq) is a novel technique that reveals gene expression profiles of individual cells, facilitating the investigation of TME heterogeneity at a high resolution and the identification of key cell subsets participating in the response to ICB. This review emphasizes the importance of scRNA-seq in studying ICB and summarizes recent findings in the discovery of biomarkers that predict ICB response and novel potential therapeutic targets for immunotherapy. These findings suggest future directions for the clinical implementation of cancer immunotherapy, facilitating further advancements in precision medicine.

Pharmacomicrobiomics and type 2 diabetes mellitus: A novel perspective towards possible treatment.

Type 2 diabetes mellitus (T2DM), a major driver of mortality worldwide, is more likely to develop other cardiometabolic risk factors, ultimately leading to diabetes-related mortality. Although a set of measures including lifestyle intervention and antidiabetic drugs have been proposed to manage T2DM, problems associated with potential side-effects and drug resistance are still unresolved. Pharmacomicrobiomics is an emerging field that investigates the interactions between the gut microbiome and drug response variability or drug toxicity. In recent years, increasing evidence supports that the gut microbiome, as the second genome, can serve as an attractive target for improving drug efficacy and safety by manipulating its composition. In this review, we outline the different composition of gut microbiome in T2DM and highlight how these microbiomes actually play a vital role in its development. Furthermore, we also investigate current state-of-the-art knowledge on pharmacomicrobiomics and microbiome's role in modulating the response to antidiabetic drugs, as well as provide innovative potential personalized treatments, including approaches for predicting response to treatment and for modulating the microbiome to improve drug efficacy or reduce drug toxicity.

Atorvastatin prevents endoplasmic reticulum stress-mediated apoptosis via the Nrf2/HO-1 signaling pathway in TBI mice.

BACKGROUND: Our present study evaluated the neuroprotection effects of atorvastatin by inhibiting TBI-induced ER stress, as well as the potential role of the Nrf2/HO-1 pathway in experimental TBI. METHODS: First, the mice were divided into four groups:sham, TBI, TBI+Vehicle and TBI+atorvastatin groups. The mice received atorvastatin (10 mg/kg/day) through intragastric gavage once a day for 3 days before TBI. In addition, Nrf2 WT and Nrf2 knockout mice were randomly divided into four groups: Nrf2+/+ TBI, Nrf2+/+ TBI+atorvastatin, Nrf2-/- TBI, and Nrf2-/- TBI+atorvastatin groups. Several neurobehavioral parameters were assessed post-TBI using mNSS, brain edema and the rotarod test, and the brain was isolated for molecular and biochemical analysis conducted through TUNEL staining and western blotting. . RESULTS: The results showed that atorvastatin treatment significantly improved neurological deficits, alleviated brain edema, and apoptosis caused by TBI. Western blotting analysis showed that atorvastatin significantly suppressed ER stress and its related apoptotic pathway after TBI, which may be associated with the further activation of the Nrf2/HO-1 pathway. However, compared with the Nrf2+/+ TBI+Vehicle group, Nrf2 deficiency further aggravated neurological deficits and promoted ER stress-mediated apoptosis induced by TBI. Interestingly, atorvastatin failed to improve neurological deficits but reversed apoptosis, and the loss of the beneficial properties of anti-ER stress in the Nrf2-/- TBI mice. . CONCLUSIONS: The results indicated that atorvastatin improves the neurologic functions and protects the brain from injury in the Nrf2+/+ TBI mice, primarily by counteracting ER stress-mediated apoptosis, which may be achieved through the activation of the Nrf2/HO-1 signaling pathway.

Intracranial penetrating injury by clothes fork in an infant: case report and review of the literature.

Nonmissile intracranial penetrating injury (IPI) in pediatric population is rare. Here, we report the exceedingly rare case of a 5-month-old infant sustained by a metallic clothes fork penetrating into his left forehead. The little baby was identified to carry a traumatic hemorrhagic shock, and a multidisciplinary team (MDT) was immediately established response for whole-course evaluation and decision-making. Computed tomography revealed that the clothes fork had impaled into the left frontal bone and brain parenchyma with about 3.2 cm inside the cranial vault. The infant underwent emergency surgery, and the clothes fork was removed jointly by MDT members under general anesthesia in the retrograde direction. His recovery was uneventful and was followed up 2 years without growth and developmental abnormality. As an extremely rare entity with distinct age-related characteristics, a MDT approach is a best choice and effective strategy to manage infant nonmissile IPI, including preoperative management, surgical treatment, and even following rehabilitation.

A novel necroptosis-related gene signature for predict prognosis of glioma based on single-cell and bulk RNA sequencing.

Background: Glioma is the most fatal neoplasm among the primary intracranial cancers. Necroptosis, a form of programmed cell death, is correlated with tumor progression and immune response. But, the role of necroptosis-related genes (NRGs) in glioma has not been well-uncovered. Methods: Single-cell and bulk RNA sequencing data, obtained from publicly accessed databases, were used to establish a necroptosis-related gene signature for predicting the prognosis of glioma patients. Multiple bioinformatics algorithms were conducted to evaluate the efficacy of the signature. The relative mRNA level of each signature gene was validated by quantitative real-time reverse transcription PCR (qRT-PCR) in glioma cell lines compared to human astrocytes. Results: In this predicted prognosis model, patients with a high risk score showed a shorter overall survival, which was verified in the testing cohorts. The signature risk score was positively related with immune cell infiltration and some immune check points, such as CD276 (B7-H3), CD152 (CTLA-4), CD223 (LAG-3), and CD274 (PD-L1). Single-cell RNA sequencing analysis confirmed that the glioma microenvironment consists of various immune cells with different markers. The eight NRGs of the signature were detected to be expressed in several immune cells. QRT-PCR results verified that all the eight signature genes were differentially expressed between human astrocytes and glioma cells. Conclusion: The eight NRGs correlate with the immune microenvironment of glioma according to our bioinformatics analysis. This necroptosis-related gene signature may evaluate the precise methodology of predicting prognosis of glioma and provide a novel thought in glioma investigation.

Preclinical Studies of Natural Products Targeting the Gut Microbiota: Beneficial Effects on Diabetes.

Diabetes mellitus (DM) is a serious metabolic disease characterized by persistent hyperglycemia, with a continuously increasing morbidity and mortality. Although traditional treatments including insulin and oral hypoglycemic drugs maintain blood glucose levels within the normal range to a certain extent, there is an urgent need to develop new drugs that can effectively improve glucose metabolism and diabetes-related complications. Notably, accumulated evidence implicates that the gut microbiota is unbalanced in DM individuals and is involved in the physiological and pathological processes of this metabolic disease. In this review, we introduce the molecular mechanisms by which the gut microbiota contributes to the development of DM. Furthermore, we summarize the preclinical studies of bioactive natural products that exert antidiabetic effects by modulating the gut microbiota, aiming to expand the novel therapeutic strategies for DM prevention and management.

Procollagen C-protease enhancer protein is a prognostic factor for glioma and promotes glioma development by regulating multiple tumor-related pathways and immune microenvironment.

OBJECTIVES: Glioma is a common type of brain tumor with high incidence and mortality rates. Procollagen C-protease enhancer protein (PCOLCE) has been shown to regulate tumor growth and metastasis in several cancers. However, the role of PCOLCE in glioma is unknown. This study aims to assess the association between PCOLCE and prognosis of glioma, and investigated the potential mechanisms. METHODS: The prognostic value of PCOLCE was determined using data from nine publicly available glioma cohorts. We also investigated the relationship between PCOLCE and glioma immune microenvironment and predicted response to immunotherapy based on the expression levels of PCOLCE. The potential roles of PCOLCE in glioma were also explored and validated in cell experiment. RESULTS: Survival analysis suggested that high-PCOLCE expression was associated with poor prognosis in glioma. Upregulation of PCOLCE enhanced an immune suppressive microenvironment in glioma by regulating immunocyte infiltration and Cancer-Immunity Cycle. Cox and ROC analysis revealed that PCOLCE was a prognostic factor for glioma and could be used to predict survival of the patients. Patients with low-PCOLCE expression were more likely to respond to Immunotherapy with ICI (immune checkpoint inhibitor) and survive longer. Enrichment analysis showed that PCOLCE was associated with multiple tumor-related pathways. Finally, we demonstrated that the knockdown of PCOLCE inhibited glioma development by regulating cell cycle and promoting apoptosis in in vitro experiments. CONCLUSION: PCOLCE promotes glioma progression by regulating multiple tumor-related pathways and immune microenvironment and can be used as a prognostic factor for glioma.

Microvascular and Prognostic Effect in Lesions With Different Stent Expansion During Primary PCI for STEMI: Insights From Coronary Physiology and Intravascular Ultrasound.

Background: While coronary stent implantation in ST-elevation myocardial infarction (STEMI) can mechanically revascularize culprit epicardial vessels, it might also cause distal embolization. The relationship between geometrical and functional results of stent expansion during the primary percutaneous coronary intervention (pPCI) is unclear. Objective: We sought to determine the optimal stent expansion strategy in pPCI using novel angiography-based approaches including angiography-derived quantitative flow ratio (QFR)/microcirculatory resistance (MR) and intravascular ultrasound (IVUS). Methods: Post-hoc analysis was performed in patients with acute STEMI and high thrombus burden from our prior multicenter, prospective cohort study (ChiCTR1800019923). Patients aged 18 years or older with STEMI were eligible. IVUS imaging, QFR, and MR were performed during pPCI, while stent expansion was quantified on IVUS images. The patients were divided into three subgroups depending on the degree of stent expansion as follows: overexpansion (>100%), optimal expansion (80%-100%), and underexpansion (<80%). The patients were followed up for 12 months after PCI. The primary endpoint included sudden cardiac death, myocardial infarction, stroke, unexpected hospitalization or unplanned revascularization, and all-cause death. Results: A total of 87 patients were enrolled. The average stent expansion degree was 82% (in all patients), 117% (in overexpansion group), 88% (in optimal expansion), and 75% (in under-expansion). QFR, MR, and flow speed increased in all groups after stenting. The overall stent expansion did not affect the final QFR (p = 0.08) or MR (p = 0.09), but it reduced the final flow speed (-0.14 cm/s per 1%, p = 0.02). Under- and overexpansion did not affect final QFR (p = 0.17), MR (p = 0.16), and flow speed (p = 0.10). Multivariable Cox analysis showed that stent expansion was not the risk factor for MACE (hazard ratio, HR = 0.97, p = 0.13); however, stent expansion reduced the risk of MACE (HR = 0.95, p = 0.03) after excluding overexpansion patients. Overexpansion was an independent risk factor for no-reflow (HR = 1.27, p = 0.02) and MACE (HR = 1.45, p = 0.007). Subgroup analysis shows that mild underexpansion of 70%-80% was not a risk factor for MACE (HR = 1.11, p = 0.08) and no-reflow (HR = 1.4, p = 0.08); however, stent expansion <70% increased the risk of MACE (HR = 1.36, p = 0.04). Conclusions: Stent expansion does not affect final QFR and MR, but it reduces flow speed in STEMI. Appropriate stent underexpansion of 70-80% does not seem to be associated with short-term prognosis, so it may be tolerable as noninferior compared with optimal expansion. Meanwhile, overexpansion and underexpansion of <70% should be avoided due to the independent risk of MACEs and no-reflow events.

Comprehensive pan-cancer analysis on CBX3 as a prognostic and immunological biomarker.

BACKGROUND: Increased evidence supports the relationship between chromobox protein homolog 3 (CBX3) and tumorigenesis of some cancers. However, the role of CBX3 in pan-cancers remains poorly defined. In the research, we aimed to investigate the prognostic value and the immunological functions of CBX3. RESULTS: We explored the potential oncogenic roles of CBX3 in mRNA and protein levels based on the diverse databases, including the expression, the correlation with prognosis, tumor microenvironment (TME), DNA methylation, protein phosphorylation and enrichment analysis across all TCGA tumors. The results show that CBX3 is overexpressed in multiple cancers, and significant correlations exist between high expression and adverse prognosis in most tumor patients. We observed an enhanced phosphorylation level in uterine corpus endometrial carcinoma, colon cancer and lung adenocarcinoma. A distinct relationship was also found between CBX3 expression and TME, including immune infiltration of tumor-infiltrating lymphocytes and cancer-associated fibroblasts, immune score or matrix score, immune checkpoints. The correlative transcription factors and miRNAs of CBX3-binding hub genes were analyzed to investigate the molecular mechanism. Moreover, alcoholism and alteration of DNA cellular biology may be involved in the functional mechanisms of CBX3. CONCLUSION: The first pan-cancer study offers a relatively comprehensive cognition on the oncogenic roles of CBX3 as a prognostic and immunological marker in various malignant tumors.

Nrf2 loss of function exacerbates endoplasmic reticulum stress-induced apoptosis in TBI mice.

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in neuroprotection and recover. Our studies have showed that endoplasmic reticulum (ER) stress-induced apoptosis aggravates secondary damage following traumatic brain injury (TBI). Whether Nrf2 involved in ER stress and ER stress-mediated apoptosis is not clearly investigated. This present study explored the effect of Nrf2 knockout on ER stress and ER stress-induced apoptosis in TBI mice. A lateral fluid percussion injury (FPI)model of TBI was built based on Nrf2 knockout (Nrf2(-/-)) mice and wild-type (Nrf2(+/+)) mice, and the expressions of marker proteins of ER stress and ER stress-induced apoptosis were checked at 24 h following TBI. We found that Nrf2(-/-) mice presented more severe neurological deficit, brain edema and neuronal cell apoptosis compared with Nrf2(+/+) mice. And, the TBI Nrf2(-/-) mice were significantly increased expression of marker proteins of ER stress and ER stress-induced apoptotic pathway including glucose regulated protein (GRP78), protein kinase RNA-like ER kinase (PERK), inositol requiring enzyme (IRE1), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), caspase-12 and caspase-3, compared with that in WT mice. These results suggest that Nrf2 could ameliorate TBI-induced second brain injury partly through ER stress signal pathway.

Non-stenting strategy is not inferior to stent implantation in patients with acute ST-segment elevated myocardial infarction and high thrombus burden and intermediate stenotic culprit lesion.

BACKGROUND: According to European Society of Cardiology (ESC) as well as American College of Cardiology/American Heart Association (ACC/AHA) guidelines, primary stenting is recommended for patients with acute ST-segment elevation myocardial infarction (STEMI); however, in-stent thrombosis is a life-threatening early adverse event that could lead to acute myocardial infarction (AMI) or even cardiac death. On the other hand, in-stent restenosis is a late adverse event that could result in recurrent readmission and revascularization. We compared a non-stenting (NS) strategy to a stenting (S) strategy in terms of incidence of major adverse cardiac events (MACEs) for patients with acute STEMI and high thrombus burden. METHODS: We performed a post hoc analysis of our prior multicenter, prospective cohort study (ChiCTR1800019923) among 51 eligible patients with acute STEMI and high thrombus burden. All participants received percutaneous coronary intervention (PCI) with a deferred-stenting strategy (second procedure performed within 48-72 h after primary PCI). Either NS or S strategies were carried out among patients. Primary outcomes were follow-ups of MACEs at 1, 3, 6, and 12 months. Intravenous ultrasound (IVUS) and quantitative flow ratio (QFR) evaluation were performed. RESULTS: In our post hoc analysis of 51 patients (21 with NS and 30 with S), baseline clinical and interventional characteristics were well matched between the 2 groups, to the exception of culprit lesion length. Incidence of MACEs was not significantly different between the 2 strategies in-hospital (P=0.56) and in follow-ups at 1 (P=0.41), 3 (free of events), 6 (P=0.71), and 12 (P=0.68) months. Culprit lesions of NS tended to be "low-risk" [minimum lumen area (MLA) 4.27±1.02 vs. 3.80±1.32 mm2, P=0.36] and plaque burden (70.79%±6.46% vs. 76.97%±6.76%, P=0.03) when compared with culprit lesions of S in IVUS evaluation. Evaluation of QFR showed more sufficient physiological reperfusion improvement with NS than with S [two-dimensional (2D) QFR: 0.85±0.09 vs. 0.79±0.13, P=0.10 and 3D QFR: 0.86±0.08 vs. 0.78±0.15, P=0.02]. CONCLUSIONS: The NS strategy did not increase MACEs in-hospital and at 1, 3, 6, and 12 months. The NS can be a safe option when meeting certain criteria for patients with STEMI and a high thrombus burden.

The outcomes in STEMI patients with high thrombus burden treated by deferred versus immediate stent implantation in primary percutaneous coronary intervention: a prospective cohort study.

BACKGROUND: No-/slow-reflow indicates worse outcomes in ST-elevation myocardial infarction (STEMI) patients with high thrombus burden. We examined whether deferred stenting (DS) strategy reduces no-/slow-reflow or major adverse cardiovascular events (MACEs) in primary percutaneous coronary intervention (pPCI) for patients with acute STEMI and high thrombus burden. METHODS: We performed an open-label, multi-center, prospective cohort study among eligible patients with acute STEMI and high thrombus burden who further received pPCI. All participants received PCI with DS (second procedure performed within 48-72 h) or immediate-stenting (IS) strategy. The primary outcome was the incidence of no-/slow-reflow. We evaluated MACEs and bleeding events during hospitalization and at 30- and 90-day follow-ups. RESULTS: We recruited 245 patients to this study, including 51 with DS and 194 with IS. Baseline clinical characters were comparable between the 2 strategies. Incidence of no-/slow-reflow defined by thrombolysis in myocardial infarction (TIMI) flow grade was not significantly different between the 2 strategies [DS: 5 (9.8%), IS: 33 (17.0%), P=0.21]. No-/slow-reflow by TIMI myocardial perfusion grade (TMPG) was less prevalent in DS [20 (39.2%) vs. 107 (55.2%), P=0.04]. No significant differences were found in recurrence of myocardial infarction (P=0.56), cardiac death (P=0.37), all-cause mortality (P=0.37), heart failure-induced readmission (P=0.35), or bleeding (P=0.61) between the 2 strategies in-hospital, and at 30- and 90-day follow-up. CONCLUSIONS: In STEMI patients with high thrombus burden who underwent pPCI, DS strategy reduced no-/slow-reflow of microcirculation. However, DS strategy did not reduce incidence of MACEs or bleeding.

Semen quality and windows of susceptibility: A case study during COVID-19 outbreak in China.

BACKGROUND: To evaluate the impact of air pollution exposure on semen quality parameters during COVID-19 outbreak in China, and to identify potential windows of susceptibility for semen quality. METHODS: A retrospective observational study was carried out on 1991 semen samples collected between November 23, 2019 and July 23, 2020 (a period covering COVID-19 lock-down in China) from 781 sperm donor candidates at University-affiliated Sichuan Provincial Human Sperm Bank. Multivariate mixed-effects regression models were constructed to investigate the relationship between pollution exposure, windows of susceptibility, and semen quality, while controlling for biographic and meteorologic confounders. RESULT(S): The results indicated multiple windows of susceptibility for semen quality, especially sperm motility, due to ambient pollution exposure. Exposure to particulate matters (PM2.5 and PM10), O3 and NO2 during late stages of spermatogenesis appeared to have weak but positive association with semen quality. Exposure to CO late in sperm development appeared to have inverse relationship with sperm movement parameters. Exposure to SO2 appeared to influence semen quality throughout spermatogenesis. CONCLUSION(S): Potential windows of susceptibility for semen quality varied depending on air pollutants. Sperm motility was sensitive to pollution exposure. Findings from current study further elucidate the importance of sensitive periods during spermatogenesis and provide new evidence for the determinants of male fertility.

Impact on Mechanical Properties and Microstructural Response of Nickel-Based Superalloy GH4169 Subjected to Warm Laser Shock Peening.

Laser shock peening (LSP), as an innovative surface treatment technology, can effectively improve fatigue life, surface hardness, corrosion resistance, and residual compressive stress. Compared with laser shock peening, warm laser shock peening (WLSP) is a newer surface treatment technology used to improve materials' surface performances, which takes advantage of thermal mechanical effects on stress strengthening and microstructure strengthening, resulting in a more stable distribution of residual compressive stress under the heating and cyclic loading process. In this paper, the microstructure of the GH4169 nickel superalloy processed by WLSP technology with different laser parameters was investigated. The proliferation and tangling of dislocations in GH4169 were observed, and the dislocation density increased after WLSP treatment. The influences of different treatments by LSP and WLSP on the microhardness distribution of the surface and along the cross-sectional depth were investigated. The microstructure evolution of the GH4169 alloy being shocked with WLSP was studied by TEM. The effect of temperature on the stability of the high-temperature microstructure and properties of the GH4169 alloy shocked by WLSP was investigated.

Access to dihydropyrano[3,2-b]pyrrol-5-ones skeletons by N-heterocyclic carbene-catalyzed [3+3] annulations.

A novel and efficient NHC-catalyzed [3+3] annulation of enals with pyrrol-4-ones was developed, thus providing the dihydropyrano[3,2-b]pyrrol-5-one core structures with broad scope and good to excellent enantioselectivities. Notably, this strategy could also expand to the synthesis of axially chiral compounds and polysubstituted indoles.

Loss of histone deacetylase 2 inhibits oxidative stress induced by high glucose via the HO-1/SIRT1 pathway in endothelial progenitor cells.

Chronic diabetic foot ulcer (DFU) is a major cause of disability and mortality in patients with diabetes. Dysfunctional endothelial progenitor cells (EPCs) play important roles in preventing vascular complications in these patients. Our results determined the elevated expression of histone deacetylase 2 (HDAC2) both in patients with DFU and in high glucose (HG) induced EPCs. In this study, HDAC2 siRNA (si-HDAC2) was transfected to investigate the effects of HDAC2 on EPCs. Cell proliferation decreased in HG-induced EPCs, but it was upregulated after si-HDAC2 transfection. Tube formation of EPCs also decreased with HG, which was reversed by si-HDAC2 transfection. Furthermore, inflammatory factors and reactive oxygen species (ROS) in EPCs were detected, showing that HG increased TNF-α, IL-1ß, IL-6, and ROS production in EPCs. However, si-HDAC2 reversed these effects. These results indicate that HDAC2 inhibitor may resist HG-induced EPC injury. Finally, reduced expression of HO-1-Sirt1 signaling in HG-induced EPCs also was reversed by HDAC2 siRNA. In conclusion, these findings indicate that HDAC2 inhibitor may prevent impaired cell proliferation, tube formation, inflammation, and ROS production in high-glucose EPCs.

[Chicory extract's influence on gut bacteria of abdominal obesity rat].

OBJECTIVE: To investigate the efficacy mechanisme of chicory extract interventing abdominal obesity rat from the aspect of gut bacteria. METHOD: Male SD rats were randomly divided into five groups, namely the normal group, model group, large and small dose group of chicory and the fenofibrate group. Normal group was given deionized water, the other group was given fructose water and give the medical treatment of chicory and fenofibrate. Assay triglycerides, total cholesterol, LDL and HDL by biochemical methods and measure body weight and abdominal circumference and microscopicly observe the count changes of gut bacteria through real-time PCR method. RESULT: Compared with normal group, the triglyceride level and abdominal circumference were significantly higher (P < 0.05), weight and high-density lipoprotein increased but no significant changes and E. coli, lactobacillus increased significantly. Compared with model group, chicory extract large and small dose group and the fenofibrate group can significantly reduce triglyceride levels (P < 0.05), reduce the number of E. coli and Lactobacillus and increase the number of bifidobacteria. The fenofibrate group can significantly reduce total cholesterol and high-density lipoprotein levels. CONCLUSION: The chicory's treatment effect on abdominal obesity is significant. The efficacy mechanisme intervention abdominal obesity may be related to the reduction of the number of lactic acid bacteria and E. coli and the increase of bifidobacteria.