DDAH1 promotes neurogenesis and neural repair in cerebral ischemia.

Choline acetyltransferase (ChAT)-positive neurons in neural stem cell (NSC) niches can evoke adult neurogenesis (AN) and restore impaired brain function after injury, such as acute ischemic stroke (AIS). However, the relevant mechanism by which ChAT+ neurons develop in NSC niches is poorly understood. Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a hydrolase for asymmetric NG,NG-dimethylarginine (ADMA), regulated genes responsible for the synthesis and transportation of acetylcholine (ACh) (Chat, Slc5a7 and Slc18a3) after stroke insult. The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT, possibly through hypoxia-inducible factor 1α (HIF-1α). KC7F2, an inhibitor of HIF-1α, abolished DDAH1-induced ChAT expression and suppressed neurogenesis. As expected, DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity. By comparing the results among Ddah1 general knockout (KO) mice, transgenic (TG) mice and wild-type (WT) mice, we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone (SGZ) under ischemic insult. As a result, DDAH1 may promote cognitive and motor function recovery against stroke impairment, while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

[Recent Advances in Diagnosis and Treatment Strategies for Multiple Primary Lung Cancer].

As the utilization of computed tomography in lung cancer screening becomes more prevalent in the post-pandemic era, the incidence of multiple primary lung cancer (MPLC) has surged in various countries and regions. Despite the continued application of advanced histologic and sequencing technologies in this research field, the differentiation between MPLC and intrapulmonary metastasis (IM) remains challenging. In recent years, the specific mechanisms of genetic and environmental factors in MPLC have gradually come to light. Lobectomy still predominates in the treatment of MPLC, but the observation that tumor-specific sublobar resection has not detrimentally impacted survival appears to be a viable option. With the evolution of paradigms, the amalgamated treatment, primarily surgical, is an emerging trend. Among these, stereotactic ablative radiotherapy (SABR) and lung ablation techniques have emerged as efficacious treatments for early unresectable tumors and control of residual lesions. Furthermore, targeted therapies for driver-positive mutations and immunotherapy have demonstrated promising outcomes in the postoperative adjuvant phase. In this manuscript, we intend to provide an overview of the management of MPLC based on the latest discoveries.
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Cold Case of Thrombolysis: Cold Recombinant Tissue Plasminogen Activator Confers Enhanced Neuroprotection in Experimental Stroke.

Background Thrombolysis and endovascular thrombectomy are the primary treatment for ischemic stroke. However, due to the limited time window and the occurrence of adverse effects, only a small number of patients can genuinely benefit from recanalization. Intraarterial injection of rtPA (recombinant tissue plasminogen activator) based on arterial thrombectomy could improve the prognosis of patients with acute ischemic stroke, but it could not reduce the incidence of recanalization-related adverse effects. Recently, selective brain hypothermia has been shown to offer neuroprotection against stroke. To enhance the recanalization rate of ischemic stroke and reduce the adverse effects such as tiny thrombosis, brain edema, and hemorrhage, we described for the first time a combined approach of hypothermia and thrombolysis via intraarterial hypothermic rtPA. Methods and Results We initially established the optimal regimen of hypothermic rtPA in adult rats subjected to middle cerebral artery occlusion. Subsequently, we explored the mechanism of action mediating hypothermic rtPA by probing reduction of brain tissue temperature, attenuation of blood-brain barrier damage, and sequestration of inflammation coupled with untargeted metabolomics. Hypothermic rtPA improved neurological scores and reduced infarct volume, while limiting hemorrhagic transformation in middle cerebral artery occlusion rats. These therapeutic outcomes of hypothermic rtPA were accompanied by reduced brain temperature, glucose metabolism, and blood-brain barrier damage. A unique metabolomic profile emerged in hypothermic rtPA-treated middle cerebral artery occlusion rats characterized by downregulated markers for energy metabolism and inflammation. Conclusions The innovative use of hypothermic rtPA enhances their combined, as opposed to stand-alone, neuroprotective effects, while reducing hemorrhagic transformation in ischemic stroke.

Linc00996 is a favorable prognostic factor in LUAD: Results from bioinformatics analysis and experimental validation.

Background: Linc00996 has been reported in a variety of malignant tumors, but its potential role and significance in lung adenocarcinoma (LUAD) are not fully understood. The authors investigated the expression and biological behavior of Linc00996 in LUAD and elucidated the function of its potential target genes. Materials and methods: The data of Linc00996 expression in cancers were derived from GEPIA. GEO and TCGA datasets were used to identify the differential expression of Linc00996 in LUAD and analyze the respective correlation between different expression levels and LUAD stage and survival prognosis. We further elucidated the potential biological processes and pathways involved with Linc00996 in LAUD by GSEA. ssGSEA was applied to explore the relationship between Linc00996 and immune activity. Finally, the clinical impact of Linc00996 was assessed in 61 patients with LUAD, and the biological functions of Linc00996 were determined by a series of experiments in vitro, such as CCK8, colony formation, migration, and invasion assays. Results: Compared with adjacent normal lung tissues, Linc00996 was significantly downregulated in LUAD, and its expression was negatively correlated with T stage, N stage, and pathological stage. An in vitro study suggested that enhanced Linc00996 expression could inhibit cell proliferation, clonal formation, migration, and invasion in LUAD cell lines. Via GSEA and ssGSEA, we observed that Linc00996 might be connected with immune infiltration in LUAD, and Linc00996 might inhibit tumorigenesis and metastasis by regulating antigen processing and presentation, JAK-STAT3, and cell adhesion molecular signaling pathways. Conclusion: Linc00996 is a novel tumor suppressor in LUAD and may suppress the tumorigenesis and metastasis of LUAD via the tumor-related signaling pathway, such as antigen processing and presentation, JAK-STAT3, and cell adhesion molecular signaling pathways.

Recycling of sewage sludge in clay-free thermal insulation brick: assessment of microstructure, performance, and environment impact.

Recycling municipal sewage sludge in fired bricks not only contributes to environmental protection, but is also an alternative to natural clay resource. The complex compositions of sludge have a great influence on the brick property. This work presents a systematical investigation on fired bricks made only with sludge and shale. The physicochemical properties of the raw mixtures, macroscopic performance, microstructure, and its evolution were quantitatively determined. The coordination between shale and sludge enables the blend of raw materials to achieve the desired gradation and plasticity. Although a reduction in compressive strength was observed, the open porosity was increased to 31.6% and thermal conductivity was reduced to 0.51 W·(m·K)-1, indicating the benefit to the performance of lightweight thermal insulation bricks. The fitting results confirm the pore-forming effect induced by the organic matter in the sludge. The obtained bricks possess good performance, especially in thermal insulation properties, and environmental and economic benefits.

A Multi-Omics Study of Familial Lung Cancer: Microbiome and Host Gene Expression Patterns.

Background: Inherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology. The lung microbiome is getting rising attention in carcinogenesis. The present work sought to investigate the microbiome in lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution (IAP); and further, to compare host gene expression patterns with their microbiome for potential links. Methods: Tissue sample pairs (cancer and adjacent nonmalignant tissue) were used for 16S rRNA (microbiome) and RNA-seq (host gene expression). Subgroup microbiome diversities and their matched gene expression patterns were analyzed. Significantly enriched taxa were screened out, based on different clinicopathologic characteristics. Results: Our FLC microbiome seemed to be smaller, low-diversity, and inactive to change; we noted microbiome differences in gender, age, blood type, anatomy site, histology type, TNM stage as well as IAP and smoking conditions. We also found smoking and IAP dramatically decreased specific-OTU biodiversity, especially in normal lung tissue. Intriguingly, enriched microbes were in three categories: opportunistic pathogens, probiotics, and pollutant-detoxication microbes; this third category involved Sphingomonas, Sphingopyxis, etc. which help degrade pollutants, but may also cause epithelial damage and chronic inflammation. RNA-seq highlighted IL17, Ras, MAPK, and Notch pathways, which are associated with carcinogenesis and compromised immune system. Conclusions: The lung microbiome can play vital roles in carcinogenesis. FLC and IAP subjects were affected by fragile lung epithelium, vulnerable host-microbes equilibrium, and dysregulated immune surveillance and response. Our findings provided useful information to study the triple interplay among environmental carcinogens, population genetic background, and diversified lung microbiome.

Effect of Vehicle-Bridge Coupled Vibration on the Performance of Magnesium Phosphate Cement Repair Materials.

This study evaluates the effect of vehicle-bridge coupled vibration on the mechanical properties of fiber-reinforced magnesium phosphate cement (FR-MPC) composites and the bonding properties of repaired systems. By means of compressive and flexural bond strengths, fiber pullout, mercury intrusion porosimeter (MIP) and backscattered electron imaging (BSE) analysis, an enhanced insight was gained into the evolution of FR-MPC performance before and after vibration. Experimental results showed that the compressive strength and flexural strength of FR-MPC was increased when it was subjected to vibration. However, the effects of vibration on the flexural strength of plain magnesium phosphate cement (MPC) mortars was insignificant. The increased flexural strength of FR-MPC after vibration could be due to the high average bond strength and pull-out energy between the micro-steel fiber and the MPC matrix. Moreover, BSE analysis revealed that the interface structure between FR-MPC and an ordinary Portland cement (OPC) substrate was more compacted after vibration, which could possibly be responsible for the better bonding properties of FR-MPC. These findings are beneficial for construction project applications of FR-MPC in bridge repairing and widening.

The Failure Mechanisms of Precast Geopolymer after Water Immersion.

Precast geopolymers with lower water/binder (0.14), which mainly consists of alkali solution, fly ash (FA) and steel slag (SS), were manufactured through molding pressing technology. The failure mechanisms of precast geopolymers after water immersion were studied by testing the loss of compressive strength, the pH of the leaching solution, the concentration of ions (Na+, Ca2+, Si4+ and Al3+), the evolution of phases, pore structure and morphology, and further discussion of the regulation evolution was performed. The results show that the harmful pores (>50 nm) of geopolymers progressively decrease from 70% to 50% after 28 days of water immersion when the content of steel slag increases from 0 to 80 wt.%. Compressive strength of geopolymers sharply reduces in the first 3 days and then increases during the water immersion process, but the phase composition varies slightly. Furthermore, increasing the content of steel slag could decrease the total porosity and further prevent the water resistance.

Influence of Mineral Additives on the Efflorescence of Ettringite-Rich Systems.

Efflorescence is aesthetically undesirable to all cementitious materials products and mainly results from the carbonation of hydrates and salt precipitation. Alternative binders without portlandite formation theoretically have much lower efflorescence risk, but in practice, the efflorescence of ettringite-rich systems is still serious. This study reports the impacts of mineral additives on the efflorescence of ettringite-rich systems and the corresponding microstructural evolution. The effects of silica fume, limestone powder, and diatomite on efflorescence and the capillary pore structure of mortars were investigated from a multi-scale analysis. The composition and microstructure of efflorescent phases were revealed by optical microscope (O.M.), in-situ Raman spectroscopy, and Scanning Electron Microscopy (SEM). Results indicate that the addition of mineral additives can efficiently inhibit the efflorescence of reference, especially with silica fume. Similar to the ettringite-rich system, the efflorescence substances of all modifies are composed of ettringite and CaCO3, indicating that the addition of mineral admixture does not lead to chemical reactions, lower capillary absorption coefficient of mineral additives modified specimen, the denser pore structure and the lower efflorescence degree.

A Comprehensive Study on the Hardening Features and Performance of Self-Compacting Concrete with High-Volume Fly Ash and Slag.

The main concern of this work is to evaluate the influences of supplementary cementitious materials (fly ash, slag) and a new type of polycarboxylate superplasticizer containing viscosity modifying agents (PCE-VMA) on the performance of self-compacting concrete (SCC). The workability, hydration process, mechanical property, chloride permeability, degree of hydration and pore structure of SCC were investigated. Results indicate that the addition of fly ash and slag slows down early hydration and decreases the hydration degree of SCC, and thus leads to a decline in compressive strengths, especially within the first 7 days. The addition of slag refines pore structure and contributes to lower porosity, and thus the chloride permeability of SCC is decreased during the late hydration stage. Additionally, a new factor of calculated water-binder ratio is put forward, which can directly reflect the free water content of concrete mixture after mixing, and guide the mix proportion design of SCC.

Comparison of the Hydration Characteristics of UltraHighPerformance and Normal Cementitious Materials.

The hydration mechanism of ultrahighperformance cementitious materials (UHPC) departs considerably from that of normal cementitious materials (NC). In this study, the strength, isothermal calorimetry, chemical shrinkage, Xray diffraction (XRD), and thermogravimetry (TG) methods are used to determine the hydration characteristics of UHPC and NC that contain silica fume (SF). A simple device was modified to test the chemical shrinkage for longterm growth, and the ultimate chemical shrinkage is obtained by semiempirical formula fitting. It is found that the degree of hydration of UHPC is significantly lower than that of NC. The hydration kinetics analyzed using the KrstulovicDabic model shows that the hydration process of NC is type NGID, which is characterized by gentle and prolonged hydration. However, the hydration of UHPC is type NGD with the distinguishing features of early sufficiency and later stagnation. The growth of the strength, exothermic evolution, and phase development of UHPC is decelerated as the hydration process proceeds, which confirms the weak development tendency of hydration at the later stage. In addition, the effect of SF on the hydration of UHPC is minor, and the higher content of SF is beneficial to the hydration at the later stage.

Crack Extension and Possibility of Debonding in Encapsulation-Based Self-Healing Materials.

The breakage of capsules upon crack propagation is crucial for achieving crack healing in encapsulation-based self-healing materials. A mesomechanical model was developed in this study to simulate the process of crack propagation in a matrix and the potential of debonding. The model used the extended finite element method (XFEM) combined with a cohesive zone model (CZM) in a two-dimensional (2D) configuration. The configuration consisted of an infinite matrix with an embedded crack and a capsule nearby, all subjected to a uniaxial remote tensile load. A parametric study was performed to investigate the effect of geometry, elastic parameters and fracture properties on the fracture response of the system. The results indicated that the effect of the capsule wall on the fracture behavior of the matrix is insignificant for tc/Rc ≤ 0.05. The matrix strength influenced the ultimate crack length, while the Young's modulus ratio Ec/Em only affected the rate of crack propagation. The potential for capsule breakage or debonding was dependent on the comparative strength between capsule and interface (Sc/Sint), provided the crack could reach the capsule. The critical value of Sc,cr/Sint,cr was obtained using this model for materials design.

Investigation on the potential of waste cooking oil as a grinding aid in Portland cement.

Although there are several methods for managing waste cooking oil (WCO), a significant result has not been achieved in China. A new method is required for safe WCO management that minimizes the environmental threat. In this context, this work was developed in which cement clinker and gypsum were interground with various WCOs, and their properties, such as grindability, water-cement ratio required to achieve a normal consistency, setting times, compressive strength, contents of calcium hydroxide and ettringite in the hardened paste, microstructure and economic and environmental considerations, were addressed in detail. The results show that, overall, WCO favorably improves cement grinding. WCO prolonged the cement setting times and resulted in longer setting times. Additionally, more remarkable effects were found in cements in which WCO contained more unsaturated fatty acid. WCOs increased the cement strength. However, this enhancement was rated with respect to the WCO contents and components. WCOs decreased the CH and AFt contents in the cement hardened paste. Even the AFt content at later ages was reduced when WCO was used. WCO also densify microstructure of the hardened cement paste. It is economically and environmentally feasible to use WCOs as grinding aids in the cement grinding process. These results contribute to the application of WCOs as grinding aids and to the safe management of WCO.

Self-healing efficiency of cementitious materials containing microcapsules filled with healing adhesive: mechanical restoration and healing process monitored by water absorption.

Autonomous crack healing of cementitious composite, a construction material that is susceptible to cracking, is of great significance to improve the serviceability and to prolong the longevity of concrete structures. In this study, the St-DVB microcapsules enclosing epoxy resins as the adhesive agent were embedded in cement paste to achieve self-healing capability. The self-healing efficiency was firstly assessed by mechanical restoration of the damaging specimens after being matured. The flexural and compressive configurations were both used to stimulate the localized and distributed cracks respectively. The effects of some factors, including the content of microcapsules, the curing conditions and the degree of damage on the healing efficiency were investigated. Water absorption was innovatively proposed to monitor and characterize the evolution of crack networks during the healing process. The healing cracks were observed by SEM-EDS following. The results demonstrated that the capsule-containing cement paste can achieve the various mechanical restorations depending on the curing condition and the degree of damage. But the voids generated by the surfactants compromised the strength. Though no noticeable improved stiffness obtained, the increasing fracture energy was seen particularly for the specimen acquiring 60% pre-damage. The sorptivity and amount of water decreased with cracks healing by the adhesive, which contributed to cut off and block ingress of water. The micrographs by SEM-EDS also validated that the cracks were bridged by the hardened epoxy as the dominated elements of C and O accounted for 95% by mass in the nearby cracks.

Flies cope with uncontrollable stress by learned helplessness.

In a wide range of animals, uncontrollable stressful events can induce a condition called "learned helplessness." In mammals it is associated with low general activity, poor learning, disorders of sleep and feeding, ulcers, and reduced immune status, as well as with increased serotonin in parts of the brain. It is considered an animal model of depression in humans. Here we investigate learned helplessness in Drosophila, showing that this behavioral state consists of a cognitive and a modulatory, possibly mood-like, component. A fly, getting heated as soon as it stops walking, reliably resumes walking to escape the heat. If, in contrast, the fly is not in control of the heat, it learns that its behavior has no effect and quits responding. In this state, the fly walks slowly and takes longer and more frequent rests, as if it were "depressed." This downregulation of walking behavior is more pronounced in females than in males. Learned helplessness in Drosophila is an example of how, in a certain situation, behavior is organized according to its expected consequences.

A lanthanide metal-organic framework with high thermal stability and available Lewis-acid metal sites.

A lanthanide metal-organic framework, Dy(BTC)(H2O).DMF, with excellent thermal stability shows a high surface area, 655 m(2) g(-1), high hydrogen and carbon dioxide storage capability, and available Lewis-acid metal sites which could be anticipated to use in catalysis and metal-site specific chemical sensor.