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Objective: Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients. We aimed to develop and test 6-month, 1-, 2-, 3-, 5-, and 10-year overall survival (OS) and cancer-specific survival (CSS) prediction models for gastric cancer patients following gastrectomy. Methods: We derived and tested Survival Quilts, a machine learning-based model, to develop 6-month, 1-, 2-, 3-, 5-, and 10-year OS and CSS prediction models. Gastrectomy patients in the development set (n = 20,583) and the internal validation set (n = 5,106) were recruited from the Surveillance, Epidemiology, and End Results (SEER) database, while those in the external validation set (n = 6,352) were recruited from the China National Cancer Center Gastric Cancer (NCCGC) database. Furthermore, we selected gastrectomy patients without neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis (TNM) stage. Prognostic performances of these OS and CSS models were assessed using the Concordance Index (C-index) and area under the curve (AUC) values. Results: The machine learning model had a consistently high accuracy in predicting 6-month, 1-, 2-, 3-, 5-, and 10-year OS in the SEER development set (C-index = 0.861, 0.832, 0.789, 0.766, 0.740, and 0.709; AUC = 0.784, 0.828, 0.840, 0.849, 0.869, and 0.902, respectively), SEER validation set (C-index = 0.782, 0.739, 0.712, 0.698, 0.681, and 0.660; AUC = 0.751, 0.772, 0.767, 0.762, 0.766, and 0.787, respectively), and NCCGC set (C-index = 0.691, 0.756, 0.751, 0.737, 0.722, and 0.701; AUC = 0.769, 0.788, 0.790, 0.790, 0.787, and 0.788, respectively). The model was able to predict 6-month, 1-, 2-, 3-, 5-, and 10-year CSS in the SEER development set (C-index = 0.879, 0.858, 0.820, 0.802, 0.784, and 0.774; AUC = 0.756, 0.827, 0.852, 0.863, 0.874, and 0.884, respectively) and SEER validation set (C-index = 0.790, 0.763, 0.741, 0.729, 0.718, and 0.708; AUC = 0.706, 0.758, 0.767, 0.766, 0.766, and 0.764, respectively). In multivariate analysis, the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set (hazard ratio [HR] = 14.59, 95% confidence interval [CI]: 1.872–2.774, P < 0.001), SEER validation set (HR = 2.28, 95% CI: 13.089–16.293, P < 0.001), and NCCGC set (HR = 1.98, 95% CI: 1.617–2.437, P < 0.001). We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients, and found that high-risk group remained as an independent CSS factor in the SEER development set (HR = 12.81, 95% CI: 11.568–14.194, P < 0.001) and SEER validation set (HR = 1.61, 95% CI: 1.338–1.935, P < 0.001). Conclusion: Survival Quilts could allow accurate prediction of 6-month, 1-, 2-, 3-, 5-, and 10-year OS and CSS in gastric cancer patients following gastrectomy.

The rise of technology has heightened work demands, adversely impacting mental health and fitness. The COVID-19 pandemic exacerbates psychological stress, emphasizing the need for non-pharmacological interventions like yoga. Yoga positively influences the autonomic nervous system, benefiting cardio-respiratory health, metabolic efficiency, and conditions like Type-2 diabetes, Chronic Venous disease, and obesity. This study employs a dataset with 100 samples and 43 features related to Chronic Venous Insufficiency (CVI). Logistic and Random Forest classifiers are validated using K-fold cross-validation, with feature selection optimizing prediction accuracy. Hybrid models, enhanced with optimization algorithms, predict Venous Clinical Severity Score (VCSS) before, one, and three months after yoga practices. The Random Forest classifier, particularly RFGT, proves highly accurate in categorizing baseline severity and identifying Mild and Moderate CVI cases. RFGT demonstrated AUC score of 0.9072, 0.8714, 0.7709, and 0.7200 in Absent, Mild, Moderate, and Severe patient groups classification before yoga practices (VCSS-Pre). These values were 0.9158, 0.8644, 0.8142, and 0.6333 for VCSS-1 and reported as 0.9269, 0.8399, 0.7838, and 0.7500 for patients’ classification in VCSS-3. Predicting VCSS scores before yoga intervention assists in categorizing participants for personalized care and efficient resource allocation. The RFC-based models, notably RFGT, show high accuracy in identifying baseline severity, enabling early intervention for high-risk individuals. These models, especially RFGT, perform well in classifying Mild and Moderate CVI cases, informing lifestyle modifications. Predicting VCSS-1 scores evaluates the short-term impact of yoga practices, identifying individuals requiring additional support. RFGT aids in personalized recommendations based on specific factors, crucial for severe conditions. Predicting VCSS-3 scores assesses the sustained impact over three months, identifying intervention responders, particularly in Severe and Moderate groups. RFGT demonstrates optimal predictions, contributing to future interventions tailored to individual responses and improved outcomes.

Titanium-magnesium (Ti–Mg) composites have attracted increasing interest recently due to their partial degradability and excellent mechanical properties, which offers a new promise for medical bone implant and repair materials. Here we present a Ti–Mg composite fabricated by pressureless infiltration of pure Mg melt into the 3D-printed pure Ti scaffold. The spatially controllable distribution of phase structure and topology of Mg was achieved by 3D printing technology. The electrochemical corrosion and in vitro degradation behavior of Ti–Mg composite were investigated. The results exhibited that the composite's in vitro degradation rate in 0.9 wt% NaCl solution was faster in the first 48 h due to the influence of galvanic corrosion. After 14 days of immersion, the Mg inside the composite was completely degraded, and the porous Ti maintained its structural integrity throughout the in vitro degradation phase. Additionally, the electrochemical results show that the Ti–Mg composite is more susceptible to corrosion than pure Mg. The overall OCP of the composite tended to increase with increasing immersion time. During the first 24 h of immersion, the impedance value gradually increased due to the thickening of the corrosion product layer. Subsequently, the impedance started to decrease gradually after 3 days of immersion due to the thinning of the Mg(OH)2 film with the continuous degradation of Mg. This study may offer a theoretical reference for the feasibility of partially degradable Ti–Mg composites for long-term bone implants.

Porous asphalt concrete (PAC) is typically used as a paving material for porous asphalt pavement in rainy areas due to its abundant interconnected pores structure. Not all interconnected pores in PAC are valid for permeability, mainly influenced by the composition of aggregate gradation. The main purpose of this paper is to investigate the effect of aggregate gradation on pores structure distribution in PAC by X-ray computed tomography (CT) system and digital image processing (DIP) techniques. The distributions of porosity, number and average equivalent diameter of air voids in middle part are much more evenly compared to the both ends in PAC specimens, accounting for about 70 % of the total of specimen height. The average equivalent diameter of interconnected air voids mainly ranges from 0.5 mm to 5 mm in PAC, accounting for about 80 % of the total numbers. For PAC with similar porosity, the larger the normal maximum aggregate size (NMAS), the less the number and the larger the average equivalent diameter of air voids (interconnected air voids), the smaller the difference between the interconnected porosity and porosity. For PAC with same NMAS, as the porosity increase, the number and average equivalent diameter of air voids (interconnected air voids) are respectively decreased and increased gradually, the difference between the interconnected porosity and porosity is also showed a decreasing trend. And then, the correlated equation is established among porosity, interconnected porosity and the composition of aggregate gradation. The distribution of air voids (interconnected air voids) size could be well described by the two-parameter Weibull model, and the relationships are explored and developed between Weibull model parameters and the composition of aggregate gradation.

Linear morphea is the most disabling subtype of morphea, which may cause a series of excutaneous manifestations and sequelae. To futher explore the clinical characteristics of linear morphea, we conducted a retrospective study of 22 patients diagnosed with linear morphea in our department during the past 2 years. Their baseline clinical information, skin manifestations, complications and therapeutic effect were analyzed. Here, we report six cases of a special linear morphea, usually occurring on the unilateral upper limbs of young women, spreading along the distribution of the radial nerve and frequently progressing across the joint, which increases the incidence of neuromusculoskeletal disorders. Instead of traditional topical drugs, a combination of systemic prednisone and methotrexate improved their skin lesions and complications. Recognition of this special type of linear morphea enables earlier diagnosis and active treatment plan, which contributes to ameliorate the symptoms and avoid functional sequelae.

Background: This study aimed to explore the longitudinal associations of rumination with suicidal ideation and suicide attempts in individuals with major depressive disorder (MDD). Methods: Participants were derived from the Depression Cohort in China study (DCC). Those who completed at least one follow-up visit during the 12 months were included in the analysis. Dimensions of rumination including brooding and reflection were each measured using five items of the Ruminative Responses Scale. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation. Suicide attempts were also assessed and all were analyzed with generalized estimating equations. Results: Our final sample included 532 participants aged 18 to 59 years (mean [SD], 26.91 [6.94] years) consisting of 148 (27.8%) males and 384 (72.2%) females. After adjusting for temporal trend and potential confounders, individuals with higher levels of reflection were more likely to report suicidal ideation (AOR =1.11, 95% CI:1.01–1.22). However, no statistically significant association was found between brooding and suicidal ideation (AOR =1.06, 95% CI:0.96–1.17). Conversely, individuals with higher levels of brooding were more likely to report suicide attempts (AOR =1.13, 95% CI:1.02–1.24), while no statistically significant association was observed between reflection and suicide attempts (AOR =0.91, 95% CI:0.82–1.01). Conclusion: Rumination reflects a disturbance in cognitive emotional processing and manifests in different dimensions. Our findings suggest that high levels of reflection and brooding may be associated with a higher likelihood of having suicidal ideation and suicide attempts, respectively. However, it should be interpreted with caution, given that effect sizes are small.

Inter-provincial carbon compensation is an important means for a country to realize regional environmental protection and achieve coordinated regional development and realize the carbon neutral goal. It is easier to realize inter-provincial carbon compensation compared with the national level. Based on the multi-regional input-output model and the input–output data of 30 provinces in China, this study measured the carbon transfer in, carbon transfer out and net carbon transfer of each province, and based on the undesirable slacks-based measurement model under the common frontier, the provinces were given the shadow price of carbon emission in line with the situation of the local economic development, resource endowment, and industrial structure, and based on which, the amount of carbon compensation of each province was measured. The results show that: China's provinces and regions have a larger share of trade-implied carbon emissions; the net carbon transfer in areas mainly concentrated in the traditional energy provinces, which provide industrial products for other regions and undertake the transfer of carbon emissions, and become the main carbon compensation recipient areas; the net carbon transfer out is mainly concentrated in the economically developed and densely populated areas such as Beijing–Tianjin region and the eastern and southern coasts, which satisfy the end-consumption by purchasing a large number of industrial products and generate a large amount of carbon emissions. Transfer out; becoming the main carbon offset payment area. Based on the results of this study, it is proposed to improve the national provincial carbon offset mechanism and implement a differentiated and synergistic carbon emission reduction cooperation approach. The research program of this study can provide a reference for the development of inter-regional carbon offset programs.

We investigate the force sensing of a mechanical membrane in a dissipative cavity optomechanical system (OMS) driven by a squeezed vacuum field accompanying a strong pump laser. Specifically, the red-detuned laser exhibits a more significant improvement for force sensing compared to the blue-detuned laser. The optimal phase angle contributes to achieving much better force sensing. When injecting a squeezed vacuum field with appropriate squeezing parameter and squeezing phase, the standard quantum limit of force measurement can be easily beaten. Furthermore, the adverse effects of the increase in environment temperature and mechanical damping can be suppressed, simultaneously. This scheme provides a theoretical basics for force sensing of mechanical membranes in dissipative OMS and has potential applications in force feedback control, precision measurement, and force sensor design.

Bletilla striata polysaccharide (BSP) is an extract derived from the rare and valuable Chinese herb Bletilla striata [Thunb.] Reichb. f. Although BSP research has progressed considerably, producing portable BSP dressings with hemostatic efficacy remains challenging. This study describes a novel dressing with a reticulate structure. To create this structure, BSP sponges were cross-linked with chitosan and lyophilized. The resulting BSP sponges had excellent mechanical properties, a high density of pores, and an outstanding capacity for fluid absorption. Both in vitro and in vivo experiments demonstrated that the BSP sponges had excellent hemostatic, antibacterial, and anti-inflammatory properties; they also exhibited good stimulation of cell growth and wound healing properties. Furthermore, they were less likely to provoke complications than traditional materials. Cytocompatibility assays revealed that they also stimulated cell proliferation. Therefore, our study suggests that BSP sponges have promising clinical applications as wound dressings.

Rapid, universal and accurate identification of chemical composition changes in multi-component traditional Chinese medicine (TCM) decoction is a necessary condition for elucidating the effectiveness and mechanism of pharmacodynamic substances in TCM. In this paper, SERS technology, combined with grating-like SERS substrate and machine learning method, was used to establish an efficient and sensitive method for the detection of TCM decoction. Firstly, the grating-like substrate prepared by magnetron sputtering technology was served as a reliable SERS sensor for the identification of TCM decoction. The enhancement factor (EF) of 4-ATP probe molecules was as high as 1.90 × 107 and the limit of detection (LOD) was as low as 1 × 10−10 M. Then, SERS technology combined with support vector machine (SVM), decision tree (DT), Naive Bayes (NB) and other machine learning algorithms were used to classify and identify the three TCM decoctions, and the classification accuracy rate was as high as 97.78 %. In summary, it is expected that the proposed method combining SERS and machine learning method will have a high development in the practical application of multi-component analytes in TCM.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A–I (1, 4–11), and two known ones (2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Background: Enhanced levels of angiotensin-2 (Ang-II) causes hypertensive heart failure (HHF) through non-hemodynamical and hemodynamical alterations. 20(S)-ginsenoside Rh2 (20(S)-Rh2) is a natural ginseng compound with numerous cardiovascular benefits. This investigation elucidates the influence of 20(S)-Rh2 on Ang-II-induced heart failure and cardiac alterations. Methods: Ang-II was administered in C57BL/6 mice for 4 weeks to induce HHF. In the last 2 weeks of treatment, 20(S)-Rh2 was orally administered in mice to assess the potential 20(S)-Rh2 mechanism. Subsequently, RNA sequencing was carried out. Results: It was indicated that 20(S)-Rh2 suppresses myocardial fibrosis, hypertrophy, and inflammation, thereby inhibiting cardiac disruption in Ang-II-challenged mice without affecting blood pressure. According to the RNA sequencing data, this cardio-protective effect was linked with the (JNK)/AP 1 pathway. 20(S)-Rh2 alleviated heart tissue and cardiomyocytes inflammation by inhibiting the Ang-II-mediated JNK/AP-1 pathway. Within cardiomyocytes, JNK or AP-1 absence abolished the anti-inflammatory effects of 20(S)-Rh2. Conclusion: This study investigation indicated that 20(S)-Rh2 prevents cardiovascular dysfunction induced by Ang-II induced by decreasing JNK-regulated inflammatory responses, providing evidence for its use as an efficient regimen for HHF.

Background: Both the accumulation of reactive oxygen species (ROS) and iron overload are significant variables that enhance the incidence of photoreceptor cell death and retinal degeneration. The discovery of ferroptosis, which is characterized by iron-dependent lipid peroxidation, has led to a new perspective on how retinal degeneration develops. As a natural phenolic acid, salvianic acid A (SAA) from Salvia miltiorrhiza has promise in treating eye diseases. The purpose of this research was to learn more about SAA and its function in the development of iron-overload-induced retinal degeneration. Methods: Models of iron overload in Kunming mice and the murine photoreceptor cell line 661 W were established, then the protective and antiferroptotic properties of SAA were assessed in vivo and in vitro. Results: Biochemical and histopathological findings on the retina confirmed that SAA successfully alleviated retinal injury. In photoreceptor cells, iron overload caused cell death, mitochondrial dysfunction, ROS generation, and iron deposition. Salvianic acid A relieved lipid peroxidation and decreased iron accumulation by modulating Acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, solute carrier family 7 member 11, and iron-metabolism-related proteins. The mitochondrial morphology suggests that the retinal protective effect of SAA is mediated via antiferroptotic action. Conclusion: Ferroptosis plays an important role in the pathogenesis of iron-overload-induced retinal degeneration. New roles of SAA in ferroptosis prevention via iron deposit inhibition, lipid peroxidation inhibition, and mitochondrial dysfunction reduction, were identified.

Summary: Hippocampal CA1 neurons generate single spikes and stereotyped bursts of spikes. However, it is unclear how individual neurons dynamically switch between these output modes and whether these two spiking outputs relay distinct information. We performed extracellular recordings in spatially navigating rats and cellular voltage imaging and optogenetics in awake mice. We found that spike bursts are preferentially linked to cellular and network theta rhythms (3–12 Hz) and encode an animal’s position via theta phase precession, particularly as animals are entering a place field. In contrast, single spikes exhibit additional coupling to gamma rhythms (30–100 Hz), particularly as animals leave a place field. Biophysical modeling suggests that intracellular properties alone are sufficient to explain the observed input frequency-dependent spike coding. Thus, hippocampal neurons regulate the generation of bursts and single spikes according to frequency-specific network and intracellular dynamics, suggesting that these spiking modes perform distinct computations to support spatial behavior.

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disorder, and it is unlikely that any single drug or intervention will be very successful. The pathophysiology of Alzheimer's disease involves a range of complicated biological processes, including the accumulation of beta-amyloid protein and tau protein. Given the complexity of AD and amyloid accumulation, a combination of interventions remains to be further explored. Here, we investigated the potential of combining β-asarone and cannabidiol (CBD) as a treatment for AD. The study analyzed the combined effects of these two phytochemicals on beta-amyloid (Aβ) protein aggregation and toxicity in bulk solution, in cells as well as in C.elegans. We detailed the morphological and size changes of Aβ40 aggregates in the presence of β-asarone and cannabidiol. More importantly, the presence of both compounds synergistically inhibited apoptosis and downregulated relative gene expression in cells, and that it may also slow aging, decrease the rate of paralysis, enhance learning capacity, and boost autophagy activity in C.elegans. Our studies suggest that multiple drugs, like β-asarone and CBD, may be potentially developed as a medicinal adjunct in the treatment of AD, although further clinical trials are needed to determine the efficacy and safety of this combination treatment in humans.

6-Gingerol (6G) is the main phenolic active component of ginger, which has a certain protective effect against liver injury induced by drugs, and chemical pollutants. However, the mechanism of protection of 6G against arsenic trioxide (ATO)-induced liver injury remains unclear. The network pharmacology and animal experiment results respectively indicated that oxidative stress and inflammatory responses were closely related to ATO-induced liver injury. 6G can alleviate ATO-induced liver injury and oxidative stress. Furthermore, 6G can attenuate the release of pro-inflammatory factors induced by ATO and reduce the expressions of NLRP3, ASC, Caspase-1 and gasdermin-D. The results showed that the activation of NLRP3 inflammatory and its induced pyroptosis play critical roles in liver injury caused by ATO. Furthermore, 6G can suppress the ROS-NLRP3 inflammasome signaling pathway, which may be an effective strategy for the treatment of ATO-induced liver injury.

Glioblastoma multiforme (GBM) is one of the most common primary malignant brain tumors in adults. Due to the poor prognosis of patients, the median survival time of GBM is often less than 1 year. Therefore, it is very necessary to find novel treatment options with a good prognosis for the treatment or prevention of GBM. In recent years, flavonoids are frequently used to treat cancer. It is a new attractive molecule that may achieve this promising treatment option. Flavonoids have been proved to have many biological functions, such as antioxidation, prevention of angiogenesis, anti-inflammation, inhibition of cancer cell proliferation, and protection of nerve cells. It has also shown the ability to regulate long non-coding RNA (LncRNA). Studies have confirmed that flavonoids can regulate epigenetic modification, transcription, and change microRNA (miRNA) expression of GBM through lncRNA at the gene level. It also found that flavonoids can induce apoptosis and autophagy of GBM cells by regulating lncRNA. Moreover, it can improve the metabolic abnormalities of GBM, interfere with the tumor microenvironment and related signaling pathways, and inhibit the angiogenesis of GBM cells. Eventually, flavonoids can block the tumor initiation, growth, proliferation, differentiation, invasion, and metastasis. In this review, we highlight the role of lncRNA in GBM cancer progression and the influence of flavonoids on lncRNA regulation. And emphasize their expected role in the prevention and treatment of GBM.

Soluble sugar content in seeds is an important quality trait of soybean. In this study, 57 quantitative trait loci (QTLs) related to soluble sugar contents in soybean seeds were collected from databases and published papers. After meta-overview-collinearity integrated analysis to refine QTL intervals, eight consensus QTLs were identified. To further verify the consensus QTLs, a population of chromosome segment substitution lines (CSSLs) was analyzed. Two lines containing fragments covering the regions of consensus QTLs and the recurrent parent were selected: one line showed high soluble sugar contents associated with a consensus QTL fragment, and the other line showed low soluble sugar contents. Transcriptome sequencing was conducted for these two lines at the early, middle, and late stages of seed development, which identified 158, 109 and 329 differentially expressed genes, respectively. Based on the analyses of re-sequencing data of the CSSLs and the consensus QTL region, three candidate genes (Glyma.19G146800, Glyma.19G122500, and Glyma.19G128500) were identified in the genetic fragments introduced from wild soybean. Sequence comparisons between the two CSSL parents SN14 and ZYD00006 revealed a single nucleotide polymorphism (SNP) mutation in the coding sequence of Glyma.19G122500, causing a non-synonymous mutation in the amino acid sequence that affected the predicted protein structure. A Kompetitive allele-specific PCR (KASP) marker was developed based on this SNP and used to evaluate the CSSLs. These results lay the foundation for further research to identify genes related to soluble sugar contents in soybean seeds and for future soybean breeding.

Introduction: Sepsis is an infection-induced severe inflammatory disorder leading to multiple organ dysfunction. It remains a highly lethal condition for which early diagnosis and therapy achieve unsatisfactory results. Circulating exosomes containing biomarkers and mediators of sepsis have recently received attention, but the progress has been far from optimal. Objectives: The present study focuses on the profiles of molecular dynamics in serum exosomes and explores the potential molecular mechanisms on serum exosomes during the process of sepsis. Methods: We used high-performance liquid chromatography-tandem mass spectrometry and RNA-seq to detect the dynamic profiles of exosome proteins and RNAs (including mRNAs, lncRNAs and miRNAs) in serum exosomes from 3 healthy individuals and 9 septic patients at the different stages. Then integrative multiomics analyses were performed and the results were validated by qRT-PCR, LiquiChip assay and metabolomics analysis on mice subjected to cecal ligation and puncture (CLP) modeling. Results: A total of 354 proteins, 195 mRNAs, 82 lncRNAs and 55 miRNAs were identified as differentially expressed molecules in serum exosomes from septic patients. Integrative multiomics analysis showed that exosome components were associated with cytokine storm, complement and clotting cascades, the endothelial barrier, 20S proteasome-dependent protein degradation and vitamin metabolism. Importantly, pretreatment with serum exosomes derived from mice subjected to CLP significantly restrained proinflammatory cytokine expression and alleviated tissue injury in septic mice. Further metabolomics analysis demonstrated that pretreatment with septic serum exosomes significantly affected the metabolites associated with vitamin digestion and absorption in CLP mice. Conclusion: Our study for the first time describes the landscape of the molecular dynamics of serum exosomes during the development of sepsis and proposes some hypothetical molecular mechanisms by integrative multiomics analysis, which may provide helpful diagnostic and therapeutic insights for the ongoing battle against sepsis.

Objectives: To investigate the effect of aligner displacement on tooth movement and periodontal health to improve the efficiency of aligner treatment and explore the mechanism in vivo. Methods: A two-tooth site was established by a finite element (FE) model to virtually evaluate aligner staging. A randomized controlled experiment was conducted when the tooth sites in beagles were treated with fixed or aligner appliances with different movement and force, and tooth movement and internal structure were recorded during the alignment. After sacrificing five dogs, bone-periodontal ligament (PDL)-tooth specimens were removed and processed to conduct uniaxial compression and tensile tests as well as micro-CT imaging and histological analysis. Results: Three displacements of 0.25, 0.35 and 0.45 mm were obtained from FE analysis and applied in beagles. In general, aligners had poorer performance on movement compared to fixed systems in vivo, but the aligner with a staging of 0.35 mm had the highest accuracy (67.46%) (P

LncRNAs are involved in many physiological and pathological processes, including chromatin remodeling, transcription, posttranscriptional gene expression, mRNA stability, translation, and posttranslational modification, and their functions depend on subcellular localization. MIR503HG is a lncRNA as well as a host gene for the miRNAs miR-503 and miR-424. MIR503HG functions independently or synergistically with miR-503. MIR503HG affects cell proliferation, invasion, metastasis, apoptosis, angiogenesis, and other biological behaviors. The mechanism of MIR503HG in disease includes interaction with protein, sponging miRNA to regulate downstream target gene, and participation in NF-κB, TGF-β, ERK/MAPK, and PI3K/AKT signaling pathways. In this review, we summarize the molecular mechanisms of MIR503HG in disease and its potential applications in diagnosis, prognosis, and treatment. We also raise some unanswered questions in this area, providing insights for future research.

Apolipoprotein E (ApoE) is a multifunctional protein involved in lipid transport and lipoprotein metabolism, mediating lipid distribution/redistribution in tissues and cells. It can also regulate inflammation and immune function, maintain cytoskeleton stability, and improve neural tissue Function. Due to genetic polymorphisms of ApoE (ε2, ε3, and ε4), its three common structural isoforms (ApoE2, ApoE3, ApoE4) are also associated with the risk of many diseases, especially degenerative diseases, such as vascular degenerative diseases including atherosclerosis (AS), coronary heart disease (CHD), and neurodegenerative disease like Alzheimer's disease (AD). The frequency of the ε4 allele and APOE variants were significantly higher than that of the ε2 and ε3 alleles in the patients with CHD or AD. In recent years, ApoE has frequently appeared in tumor research and become a tumor biomarker gradually. It has been found that ApoE is highly expressed in most solid tumor tissues, such as glioblastoma, gastric cancer, pancreatic ductal cell carcinoma, etc. Studies illustrated that ApoE could regulate the polarization changes of macrophages, participate in the construction of tumor immune microenvironment, regulate tumor inflammation and immune response and play a role in tumor progression, invasion, and metastasis. Of course, many functions of ApoE and its relationship with diseases are still under research. By reviewing the structure and function of ApoE from degeneration diseases to tumor neoplasms, we hope to better understand such a biomarker and further explore the value of ApoE in later studies.

ABSTRACT: Objectives: The aim of this study was to explore the prevalence of blaCTX-M and elucidate the characteristics of transferable blaCTX-M-55 plasmids. Methods: Escherichia coli were isolated from 10 large-scale duck farms from nine counties and cities in Guizhou Province. They were identified, subjected to antimicrobial susceptibility testing and screened for antibiotic resistance genes. blaCTX-M-positive strains were subtyped, and blaCTX-M-55-containing strains were further analysed by multilocus sequence typing, conjugation experiments and polymerase chain reaction–based replicon typing. Three transferable plasmids were selected for whole genome sequencing sequencing and further analysis of genetic context. Results: In total, 128 E. coli strains were identified, and 23 were blaCTX-M-positive. Subtype analysis of blaCTX-M-positive strains revealed that 23 were blaCTX-M-55 and one of the strains contained both blaCTX-M-65 and blaCTX-M-55. They were divided into 12 multilocus sequence typing types, and 6 were undetermined. blaCTX-M-55-bearing plasmids in seven were transferred to E. coli C600 at frequencies between 10−6 and 10−9, and blaCTX-M-55 was found to be located on IncN, IncFⅡ and IncFII-N fusion type plasmids. Three plasmids (IncFⅡ plasmids pEC99_Plas3 and pS1_Plas2 and IncFII-N plasmid pD2_plas2) shared a homologous region of IS26-ARGs-IS26-blaTEM-orf477-blaCTX-M-55-ISEcp1△-IS26. Conclusion: Our study demonstrates the environmental presence of blaCTX-M-55 harbouring E. coli in Guizhou. Analysis of the genetic context of blaCTX-M-55 aids in understanding possible dissemination routes of ESBL genes and controlling widespread antibiotic resistance.

The drinking water quality index (DWQI) transforms multiple water quality parameters into a dimensionless number, thus, presenting comprehensive status of drinking water in an intuitive manner. However, there are very few studies summarize the current progress of DWQI. Thus, we systematically reviewed 514 articles to evaluated the methods used in each DWQI developmental step with the aim of helping environmental workers choose the most appropriate index-generation model for local application. We observed that existing studies usually select 10–15 (55.4% of the studies) physicochemical parameters (such as Cl, pH, SO4, Ca, Mg etc.) to develop a DWQI. The weights of selected parameters are most often assigned using the five-scale method (53.7%), but these values varied considerably among the different studies due to the lack of clear evaluation standards. Semiquantitative and quantitative methods have been applied to overcome the subjectivity involved in these steps, including the analytical hierarchy process, information entropy, and factor analysis etc. The measurement results are normalized using the permissible limit, and multiplied by the corresponding weight, then added up to get the final DWQI result. Specifically, two distinct approaches, fuzzy logic and WQI adopted by Canadian Council of Ministers of the Environment (CCME-WQI) are discussed. Comparing with the more common approach based on classic set theory, fuzzy logic can better resolve the inherent uncertainty in the assessment of DWQI, whereas, the CCME-WQI is more appropriate for evaluating the spatiotemporal variations in DWQI over a given period. Some studies have assessed the robustness of the developed DWQI by conducting sensitivity analyses and its effectiveness was validated by comparisons with expert scores, existing WQIs or toxicological endpoints. Fifty-seven predefined classification schemes have been proposed to interpret DWQI value. As no one-size-fits-all approach exists for DWQI development, we recommended here to clarify the principles to be followed at each step, disclose the details of each method, and validate the developed index in future research. Meanwhile, additional efforts are required to develop new water quality monitoring methods and conduct DWQI studies on central water supply system.

A study has been made of the effect of heat-treatment on the microstructures of commercial quality AISI4340 steel after austenitizing at 1128 K and austempering at temperatures ranging from 561 K to 644 K. The morphologies of the bainite structure were observed after etching using optical microscopy. The “Avrami” equation was used to determine the relationship between the transformed fraction and different austempering temperature. The activation energy was determined by using the “Arrhenius” equation. The results show the bainite sheaves and bainite width grow as the austempering temperature increases. High temperature results in fast bainite transformation and the bainite activation energy is 5.302 × 103 J/mol. The bainite microstructures highly enhanced tribological performance as compared to tempered martensite microstructures at the same hardness.

Hedgehog (HH), a conserved signaling pathway, is involved in embryo development, organogenesis, and other biological functions. Dysregulation and abnormal activation of HH are involved in tumorigenesis and tumor progression. With the emergence of interest in noncoding RNAs, studies on their involvement in abnormal regulation of biological processes in tumors have been published one after another. In this review, we focus on the crosstalk between noncoding RNAs and the HH pathway in tumors and elaborate the mechanisms by which long noncoding RNAs and microRNAs regulate or are regulated by HH signaling in cancer. We also discuss the interaction between noncoding RNAs and the HH pathway from the perspective of cancer hallmarks, presenting this complex network as concisely as possible and organizing ideas for cancer diagnosis and treatment.

Cardiac inflammation is an important pathological process in diabetic cardiomyopathy (DCM). Curcumin is a natural compound found in the rhizome of Curcuma longa and has been shown to possess multifunctional bioactivities. In the present study, we identified a new curcumin-derived compound, JM-2, and investigated its therapeutic effects against DCM in mouse models of streptozotocin-induced type 1 diabetes mellitus (T1DM) and HFD-induced type 2 diabetes (T2DM). Treatment with JM-2 (10 mg/kg) prevented cardiac functional and structural deficits effectively and reduced cardiac inflammation and fibrosis. JM-2 administration attenuated DCM by inhibiting nuclear factor kappa-B (NF-κB) activation in the heart of both models. In addition, treatment with JM-2 completely prevented the increase in proinflammatory factors and macrophage infiltration in T1DM and T2DM mice. RNA-seq analysis showed that the anti-inflammatory activity of JM-2 was associated with the inhibition of NF-κB activation. In vitro, JM-2 suppressed high glucose (HG)-induced myocardial hypertrophy and fibrosis in H9c2 cells, accompanied by inhibition of HG-induced NF-κB activation. Collectively, our results showed that JM-2, a new curcumin analog, provides strong protection against DCM via inhibition of the NF-κB-mediated inflammation. In summary, our data suggest that the curcumin analog JM-2 may be a potential therapeutic agent for DCM.

ABSTRACT: Fatty liver hemorrhagic syndrome (FLHS) is a chronic hepatic disease which occurs when there is a disorder in lipid metabolism. FLHS is often observed in caged laying hens and characterized by a decrease in egg production and dramatic increase of mortality. Salidroside (SDS) is an herbal drug which has shown numerous pharmacological activities, such as protecting mitochondrial function, attenuating cell apoptosis and inflammation, and promoting antioxidant defense system. We aimed to determine the therapeutic effects of SDS on FLHS in laying hens and investigate the underlying mechanisms through which SDS operates these functions. We constructed oleic acid (OA)-induced fatty liver model in vitro and high-fat diet-induced FLHS of laying hens in vivo. The results indicated that SDS inhibited OA-induced lipid accumulation in chicken primary hepatocytes, increased hepatocyte activity, elevated the mRNA expression of proliferation related genes PCNA, CDK2, and cyclinD1 and increased the protein levels of PCNA and CDK2 (P < 0.05), as well as decreased the cleavage levels of Caspase-9, Caspase-8, and Caspase-3 and apoptosis in hepatocytes (P < 0.05). Moreover, SDS promoted the phosphorylation levels of PDK1, AKT, and Gsk3-β, while inhibited the PI3K inhibitor (P < 0.05). Additionally, we found that high-fat diet-induced FLHS hens had heavier body weight, liver weight, and abdominal fat weight, and severe steatosis in histology, compared with the control group (Con). However, hens fed with SDS maintained lighter body weight, liver weight, and abdominal fat weight, as well as normal liver without hepatic steatosis. In addition, high-fat diet-induced FLHS hens had high levels of serum total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), and aspartate aminotransferase (AST) compared to the Con group, however, in the Model+SDS group, the levels of TC, TG, ALT, and AST decreased significantly, whereas the level of superoxide dismutase (SOD) increased significantly (P < 0.05). We also found that SDS significantly decreased the mRNA expression abundance of PPARγ, SCD, and FAS in the liver, as well as increased levels of PPARα and MTTP, and decreased the mRNA expression of TNF-α, IL-1β, IL-6, and IL-8 in the Model+SDS group (P < 0.05). In summary, this study showed that 0.3 mg/mL SDS attenuated ROS generation, inhibited lipid accumulation and hepatocyte apoptosis, and promoted hepatocyte proliferation by targeting the PI3K/AKT/Gsk3-β pathway in OA-induced fatty liver model in vitro, and 20 mg/kg SDS alleviated high-fat-diet-induced hepatic steatosis, oxidative stress, and inflammatory response in laying hens in vivo.

Isoprocarb is a widely used carbamate insecticide in agriculture and aquaculture. Overuse of isoprocarb always leaves toxic residues in soil and water, however, the potential ecotoxicity of isoprocarb to organisms is still confusing. In this study, zebrafish embryo was used as a model to evaluate the toxicity of isoprocarb. Zebrafish embryos (96 hpf) were separately exposed at different concentrations of isoprocarb. The mortality rate, hatchability rate, average heart beat of the zebrafish embryo were separately calculated. Our results suggested that exposure to isoprocarb induced developmental toxicity in zebrafish embryos. HE staining showed that exposure to isoprocarb caused developmental defect in the hindbrain of zebrafish embryos. As expected, the behavioral analysis also showed that the motor ability of zebrafish embryos were significantly inhibited following exposure to isoprocarb. In terms of mechanism, The expressions of genes involved in neurodevelopment signaling pathways, such as foxo3a, gfap, syn2a, elavl3 and sox19b, were inhibited in zebrafish embryos after exposure to isoprocarb. The acetylcholinesterase (AChE) activity was also reduced in isoprocarb-treated zebrafish embryos. Moreover, oxidative stress was induced by increasing the reactive oxygen species (ROS) level and decreasing the activity of antioxidant enzyme (SOD) after exposure to isoprocarb. Expectedly, acridine orange (AO) staining and the detection of some apoptosis-related genes revealed that oxidative stress resulted in apoptosis. In short, the expressions of genes associated with the neurodevelopmental signaling pathway are inhibited, and oxidative stress is also induced in zebrafish embryos after exposure to isoprocarb, which may be the molecular basics of isoprocarb-induced neurotoxicity in zebrafish embryos.

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis and high mortality due to lack of effective treatment. The tendency of TNBC to metastasize to distinct organs is caused by cancer cells undergoing a particular mesenchymal phenotypic shift and enriched cancer stem cells (CSCs) in tumors. Pterostilbene (PTE), a bioactive phytoalexin naturally found in blueberries or grapes, has attracted considerable attention in terms of superior potential in cancer chemoprevention and chemotherapy applications. However, whether PTE can inhibit the metastasis of TNBC via regulating epithelial to mesenchymal transition (EMT) and stemness is still explored. In the present study, we found that PTE possessed the abilities of reversing EMT by upregulation of E-cadherin and downregulation of ZEB1 and SNAI1 and suppression of stemness by inhibiting the self-renewal capacity of mammosphere on tumor cells. Furthermore, PTE could inhibit the lung metastases of TNBC with therapeutic safety by suppressing the nuclear translocation of β-catenin to decrease the expression of target protein of CD44, MMPs. Our data demonstrated PTE possessed the effect against the metastasis of TNBC by suppression of β-catenin-mediated EMT and stemness, which may further enhance its dietary benefit and possibly contribute to a valuable clinical effect.

10-Gingerol (10-Gin), an active ingredient extracted from ginger, has been reported to have beneficial effects on the cardiovascular system. However, its protective effects on myocardial ischemia (MI) and the underlying cellular mechanisms are still unclear. To investigate the protection conferred by 10-Gin against MI injury and its potential mechanisms in cardiomyocytes via patch-clamp and molecular biology techniques. A rat MI model was established using the subcutaneous injection of isoproterenol (85 mg/kg) administered on two consecutive days. 10-Gin was pre-administered to rats for seven days to assess its cardio-protection. The patch-clamp and IonOptix Myocam detection techniques were used to investigated 10-Gin’s effects on L-type Ca2+ channels (LTCCs), Ca2+ transients and cell contractility in isolated rat cardiomyocytes. 10-Gin administration alleviated MI injury, improved cardiac function and myocardial histopathology, reduced myocardial infarct area, downregulated oxidative stress and Ca2+ levels, and decreased the expression of apoptotic factors. Importantly, 10-Gin led to an increase in phosphorylated Janus kinase 2 and signal transducer and activator of transcription 3 (JAK2 and STAT3, respectively) expressions. Furthermore, 10-Gin inhibited LTCCs in a concentration-dependent manner with a half-maximal inhibitory concentration of 75.96 μM. Moreover, 10-Gin administration inhibited Ca2+ transients and cell contractility. Our results suggest that 10-Gin exerts cardioprotective effects on MI in vivo and in vitro in connection with the inhibition of oxidative stress and apoptosis via activation of the JAK2/STAT3 signalling pathway, and regulation of Ca2+ homeostasis by LTCCs.

Heart failure is a fairly common outcome of hypertension. Recent studies have highlighted the key role of the non-hemodynamic activity of angiotensin II (Ang II) in hypertensive heart failure via inducing cardiac inflammation. Drugs that disrupt Ang II-induced cardiac inflammation may have clinical utility in the treatment of hypertensive heart failure. A naturally occurring compound, corynoline, exhibit anti-inflammatory activities in other systems. C57BL/6 mice were injected with Ang II via a micro-osmotic pump for four weeks to develop hypertensive heart failure. The mice were treated with corynoline by gavage for two weeks. RNA-sequencing analysis was performed to explore the potential mechanism of corynoline. We found that corynoline could inhibit inflammation, myocardial fibrosis, and hypertrophy to prevent heart dysfunction, without the alteration of blood pressure. RNA-sequencing analysis indicates that the PPARα pathway is involved Ang II-induced cardiac fibrosis and cardiac remodeling. Corynoline reversed Ang II-induced PPARα inhibition both in vitro and in vivo. We further found that corynoline increases the interaction between PPARα and P65 to inhibit the NF-κB pro-inflammatory pathway in H9c2 cells. Our studies show that corynoline relieves Ang II-induced hypertensive heart failure by increasing the interaction between PPARα and P65 to inhibit the NF-κB pathway.

In situ measurement of particle flow is a promising tool to visualize how the particles affect the power feeding laser additive manufacturing (PFLAM). A simple and robust platform based on optical feedback interferometry (OFI) was implemented in this study. The diameters of particles, the change of particle density, and the agglomeration behavior of particles in the powder stream generated by the powder feeder can be measured through in situ measurements based on the OFI. Signal detection and data processing became more difficult when the particle diameter was much larger or much smaller than the detection laser wavelength. The distribution of particles in fiber laser-induced plume with a diameter ranging from 0.3 μm to 4 μm can be measured using the OFI in laser additive manufacturing with powder feeding. The percentage of particles with a diameter of about 0.65 μm in plume decreased significantly with the increase of laser power.

This study aimed to propose the in situ measurement of particles based on the self-mixing interferometry (SMI) effect for monitoring the dynamic behaviors of the plume. This method was verified through the in situ measurement of tiny moving metal objects. The signal acquisition rate of the method was about 100%. The SMI signal of the detection laser had a waveform similar to the sawtooth waveform, and its intensity positively correlated with the detection laser power density. A focused detection laser was used to accurately measure the sizes of the tiny moving objects at the laser focus position. The measuring range of this method was limited by the half-wavelength and numerical aperture of the detection laser. The distribution of the plume particles with a diameter ranging from 0.3 μm to 4 μm was obtained using the in situ measurement method based on a detection laser with a wavelength of 1.31 μm in the 1-kW fiber laser keyhole welding. By quantitative statistical analysis, the number proportion of particles ranging from 0.3 to 0.65 μm diameter is more than 70% in all the detected particles.

This research presents an experimental study on the tribological behavior and plastic deformation layer response of quenched-tempered AISI 6150 steel and austempered AISI 6150 steel under sliding with a ball-on-disk type apparatus. Worn surfaces were analyzed by micro-hardness, 3D profilometer, microscopy and scanning electron microscope (SEM). The results showed that the disk surfaces were hardened after tribo-tests due to fresh-martensite formation caused by frictional heating/self-quenching during the sliding tests. The wear loss of the disk specimens was due to smearing plastic deformation resulting in material pile-up along the wear track and debris inside the wear track. The quenched-tempered disk specimens generated more debris than the austempered specimens. The greater amount of wear debris in the quench-tempered samples led to more severe contact stresses between the ball and disk samples which accelerated the smearing of material. As the tempering temperature increases, more cracks were observed for all quenched-tempered disk specimens. More voids and cracks was developed in the near surface region of tempered martensite leading to accelerated material loss through smearing and delamination. Also, more plate-like wear particles were observed on the disks of tempered martensite due to greater surface and subsurface crack fomation and propagation.

This study describes the laser surface hardening process effect on microstructures produced and their wear behavior. Ductile iron samples were austempered at three different austempering temperatures: 232 °C/288 °C/398 °C respectively. Then, the laser surface hardening process was applied on each sample. Different laser gaps were designed: 1.5mm/3mm/4 mm. The microstructures were observed using optical microscopy and tribo-tests were run using a UMT-3 tribo tester. A Rockwell hardness tester was used to measure the hardness after heat-treatment. Optical microscopy and SEM were used to observe the different microstructures and their distribution on the worn surface. The results showed that the laser processing generated ledeburite, martensite, or tempered bainite microstructures. Vickers hardness tests were carried out on these microstructures. The original needle-like microstructures were observed on the samples with 4 mm laser gap but not with 1.5 mm or 3 mm laser gap. This is because part of the 4 mm laser gap is beyond the laser heat effected zone. Generally, severe ploughing wear and smearing wear were observed on the tempered bainite zone but not the bainite zone. Debris was generated during the tribo-tests and led to three body abrasive wear which not only resulted in higher wear loss, but also polished the worn surface.

To investigate the protection of cinnamic aldehyde (CA) against myocardial ischemia/hypoxia (I/H) injury and its potential mechanisms in vivo and in vitro. Mice were pretreated with CA for 7 days, and then isoproterenol (85 mg/kg) was administered for 2 consecutive days to assess its cardioprotection. Furthermore, an in vitro myocardial I/H model was established by administering CoCl2 (600 μM) to H9c2 cells for 24 h. H9c2 cells were pretreated with CA for 12 h to assess its protection. We observed that CA improved electrocardiogram and histopathological changes and decreased creatine kinase and lactate dehydrogenase activities and oxidative stress levels. The TUNEL results showed that CA reduced the degree of apoptosis. Furthermore, CA could lead to a down-regulation of the Caspase-3 and Bax protein expressions, but an up-regulation of the Bcl-2 protein expressions. Importantly, CA increased p-PI3K and p-AKT protein expressions, indicating the activation of the PI3K/AKT signaling pathway. Moreover, treatment with CA improved the cell viability rate and mitochondrial membrane potential while markedly decreasing apoptosis and oxidative stress levels in vitro. Our results suggested that CA exerts cardioprotection on myocardial I/H injury, which possibly occurred in connection with inhibition of oxidative stress and apoptosis via activation of the PI3K/AKT signaling pathway.

Trace in situ nanocrystals crystallized from metallic glasses as innovative microstructure manipulation agents were proposed to manipulate the multilevel microstructure configuration of eutectic Al–Si13.0–Cu5.0–Mg0.6 alloy. And the manipulation effect by nanocrystals for different times was compared with Sr, nanocrystals + Sr and Ni alloying. The calculations indicated that NiTi nanocrystals had an ideal mismatch with α-Al and silicon; thus, nanocrystals can stimulate their nucleation and hinder their growth. Sr and Ni alloying were found to only refine the silicon phases, but nanocrystals refined both α-Al and silicon phases. Moreover, the inhibition of nanocrystals and Sr was verified. After the manipulation by nanocrystals for 20 min, the optimum microstructure configuration and mechanical properties were realized. The results showed that the size of α-Al was reduced by 86.7%, and the size and aspect ratio of eutectic silicon were decreased by 27.7% and 50.0% compared with that of the unmanipulated alloy. Primary silicon was distributed more evenly and reduced in number. In addition, the size of Al2Cu and Mg2Si was decreased by 57.7% and 90.6%. Accordingly, a prominent microstructure configuration comprised of refined α-Al, silicon phases and precipitations was established successfully via nanocrystals. Moreover, the ultimate tensile strength (UTS) and fracture strain (FS) were increased by 17.8% and 73.3% compared with that of the unmanipulated alloy at ambient temperature, and the yield strength (σ0.2) and UTS were increased by 21.5% and 14.4% at 250 °C. The specific strengthening mechanisms were revealed, as well. Therefore, in situ nanocrystals have great application potential and developmental value.

Based on the principle of bionics, the lightweight and high-strength the Neptune’s shell was chosen as a bionic model for this study due to its light weight and high strength. Micro-nano mixed-scale dual-phase reinforced aluminum matrix composites were prepared by one-step densification of combustion synthesis combined with hot pressing. We aimed to control the particle size of the ceramic and the ratio of the soft and hard phases by controlling the composition of the composite, and to study the mechanical properties of the biomimetic structure of the composite at normal and high temperatures. The results showed that as the aluminum content in the composite decreased, the ceramic particle size increased and the ceramic particles became evenly distributed in the matrix. Compression testing showed that as the ceramic volume fraction increased the ultimate compressive strength (σUCS) and fracture strain (εf) first increased and then decreased, both at room temperature and at 473 K and 523 K. (TiB2-TiCx)/Al-Cu-Mg composites of 40 vol.% exhibited optimal compressive properties at room temperature and at high temperatures. The increase in the size of the ceramic particles caused an increase in the spacing between the particles, which also weakened the bonding strength between the ceramic particles and the aluminum matrix. Therefore, when the ceramic volume fraction exceeded 40% by volume, the compression properties of the composite tended to decrease. The coupling effect of the layered structure and the soft-hardened structure played a key role in the stability of the biomimetic composite.

In this study, the thermal stability of Ni–Nb–Ti metallic glasses was investigated under isothermal and non-isothermal conditions. The effectiveness of NiTi phases, one of the nanosized crystallized phases, as grain refiners for Al–Cu alloys was also investigated from a crystallographic point of view using the edge-to-edge matching (E2EM) model. Thermal analysis showed that NiTi phases promote solidification of α-Al, and these nanocrystalline phases also promote an Al–Cu eutectic reaction and inhibit the growth of eutectic phases. A significant refining effect of α-Al grains from 402.7 μm to 69.1 μm was achieved with 0.05 wt.% nanocrystalline phases. Simultaneously, values for yield strength, ultimate tensile strength and fracture strain of inoculated Al–Cu alloys were increased by 18%, 13% and 78% to 363.2 MPa, 534.3 MPa and 11.92%, respectively, when compared with those of uninoculated Al–Cu alloys. Strengthening mechanisms of Al–Cu alloys manipulated by the nanocrystalline phases are grain boundary strengthening and precipitation strengthening.

This research studies the kinetic transformation and austempering temperature effect on the morphologies of bainite for AISI 6150 steel. A minimum of 10 different holding times for each austempering temperature were utilized. All the AISI 6150 steel samples with original spheroidal pearlite were austenized at 855 °C for 20 min, followed by a lower temperature salt bath for austempering at various holding times. The hardness for each austempered temperature and holding time was measured, and the microstructures were observed by optical microscopy. The kinetic energy for needle like lower bainite and granular like upper bainite was analyzed by using kinetic transformation equations. The aim of this research was to study the transformation of bainite, in particular lower bainite, to obtain improved mechanical properties and higher ductility of AISI 6150 steel, and then apply AISI 6150 steel to more applications. Keywords: Bainite morphologies, Austempering process, Microstructures, Transformation kinetics, Phase activation energy

Epilepsy biomarkers from electroencephalogram recordings are routinely used to assess seizure risk and localization. Two widely adopted biomarkers include: (i) interictal spikes, and (ii) high frequency ripple oscillations. The combination of these two biomarkers, ripples co-occurring with spikes (spike ripples), has been proposed as an improved biomarker for the epileptogenic zone and epileptogenicity in humans and rodent models. Whether spike ripples translate to predict seizure risk in rodent seizure models is unknown. Further, recent evidence suggests ictal networks can include deep gray nuclei in humans. Whether pathologic spike ripples and seizures are also observed in the basal ganglia in rodent models has not been explored. We addressed these questions using local field potential recordings from mice with and without striatal seizures after carbachol or 6-hydroxydopamine infusions into the striatum. We found increased spike ripples in the interictal and ictal periods in mice with seizures compared to pre-infusion and post-infusion seizure-free recordings. These data provide evidence of electrographic seizures involving the striatum in mice and support the candidacy of spike ripples as a translational biomarker for seizure risk in mouse models.

Ethoprophos is an effective and widely pesticide that used in controlling nemathelminth and soil insect. However, ethoprophos has been frequently detected in environment and freshwater. The potential toxicity to aquatic organisms is still not be explored. In this study, zebrafish embryo model was used to evaluated the toxicity of ethoprophos during cardiovascular developmental process of zebrafish. Zebrafish embryos were separately exposed to 10 mg/L, 20 mg/L, 30 mg/L, 40 mg/L and 50 mg/L of ethoprophos exposure at 96 h post-fertilization (hpf), which induced cardiac defects, such as low heart rate, pericardium edema and long SV-BA distance, but had no influence to vascular development. Mechanistically, the expression of cardiac-related genes were abnormal. Moreover, ethoprophos exposure significantly increased oxidative stress in zebrafish embryos by inhibiting the production of antioxidant enzyme (SOD) and activating reactive oxygen species. Expectedly, some apoptosis genes were induced and the apoptotic cardiomyocytes were detected by acridine orange staining. In addition, ethoprophos exposure also inhibited the expression of genes in wnt signaling pathway, such as β-catenin, Axin2, GSK3β and Sox9b. BML284, an activator of wnt signaling pathway, can rescue the cardiotoxic effect of embryos. These results indicated that oxidative stress and blocking wnt signaling pathway were molecular basis of ethoprophos-induced injure in zebrafish. Generally, our study showed that ethoprophos exposure led to severe cardiotoxicity to zebrafish embryo.

Liquiritigenin (LQ) has protective effects against various hepatotoxicities. However, its specific role on arsenic trioxide (ATO)-induced hepatotoxicity and the related biomolecular mechanisms remain unclear. The purpose of this study is to explore the protective actions of LQ on ATO-induced hepatotoxicity and its biomolecular mechanisms in mice. LQ was administered orally at 20 and 40 mg/kg per day for seven consecutive days with an intraperitoneal injection of ATO (5 mg/kg). Liver injury was induced by ATO and was alleviated by treatment with LQ as reflected by reduced histopathological damage of liver and decreased serum ALT, AST, and ALP levels. The generation of intracellular ROS induced by ATO was attenuated after LQ treatment. The levels of SOD, CAT, and GSH were elevated with LQ administration while MDA levels decreased. LQ mitigated elevated TNF-α and IL-6 levels as well as the hepatic mitochondrial damage caused by ATO. Moreover, LQ upregulated the expression of LC3-II and enhanced autophagy in the liver of ATO-induced mice. Further studies indicated that LQ significantly suppressed the expression of p-PI3K, p-AKT, and p-mTOR in ATO-induced mice. In conclusion, our findings show that LQ protects against ATO-induced hepatotoxicity due to its antioxidant and anti-inflammatory activities and enhancement of autophagy mediated by the PI3K/AKT/mTOR signaling pathway in mice.

Summary: Recent improvements in genetically encoded voltage indicators enabled optical imaging of action potentials and subthreshold transmembrane voltage in vivo. To perform high-speed voltage imaging of many neurons simultaneously over a large anatomical area, widefield microscopy remains an essential tool. However, the lack of optical sectioning makes widefield microscopy prone to background cross-contamination. We implemented a digital-micromirror-device-based targeted illumination strategy to restrict illumination to the cells of interest and quantified the resulting improvement both theoretically and experimentally with SomArchon expressing neurons. We found that targeted illumination increased SomArchon signal contrast, decreased photobleaching, and reduced background cross-contamination. With the use of a high-speed, large-area sCMOS camera, we routinely imaged tens of spiking neurons simultaneously over minutes in behaving mice. Thus, the targeted illumination strategy described here offers a simple solution for widefield voltage imaging of many neurons over a large field of view in behaving animals.

Summary: Ultrasound modulates brain activity. However, it remains unclear how ultrasound affects individual neurons in the brain, where neural circuit architecture is intact and different brain regions exhibit distinct tissue properties. Using a high-resolution calcium imaging technique, we characterized the effect of ultrasound stimulation on thousands of individual neurons in the hippocampus and the motor cortex of awake mice. We found that brief 100-ms-long ultrasound pulses increase intracellular calcium in a large fraction of individual neurons in both brain regions. Ultrasound-evoked calcium response in hippocampal neurons exhibits a rapid onset with a latency shorter than 50 ms. The evoked response in the hippocampus is shorter in duration and smaller in magnitude than that in the motor cortex. These results demonstrate that noninvasive ultrasound stimulation transiently increases intracellular calcium in individual neurons in awake mice, and the evoked response profiles are brain region specific.