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Alkali-activated slag and fly ash (FA)-blended seawater sea sand concrete (AASC) is a new type of concrete produced without Portland cement or river sand. The advantages of utilising industrial waste and marine resources are that they are not only eco-friendly but cost-saving. This study aimed to investigate the properties of AASC exposed to elevated temperatures. Slag and FA were activated using NaOH and water glass solutions for mixing AASC. Heating and compressive tests were conducted to analyse the thermal and compressive properties of the AASC. The results showed that the AASC with higher FA content (Type II) had fewer flaky structures and more integral interfacial transition zones than the other type of AASC (Type I) after exposure to 600 °C. Type I AASC had better mechanical performance at temperatures below 400 °C but was inferior to Type II AASC beyond 600 °C. A compressive constitutive model was proposed for AASC. [ABSTRACT FROM AUTHOR]

PD-1 signaling on T cells is the major pathway that limits T cell immunity, but the efficacy of anti-PD-1 therapy has been limited to a small proportion of patients with advanced cancers. We fortuitously observed that anti-PD-1 therapy depends on IL-2 signaling, which raises the possibility that a lack of IL-2 limits anti-PD-1-induced effector T cell expansion. To selectively deliver IL-2 to [PD-1.sup.+] [CD8.sup.+] tumor-infiltrating lymphocytes (TILs), we engineered a low-affinity IL-2 paired with anti-PD-1 (PD-1-laIL-2), which reduced affinity to peripheral Treg cells but enhanced avidity to [PD-1.sup.+] [CD8.sup.+] TILs. PD-1-laIL-2 exerted better tumor control and lower toxicity than single or mixed treatments. Mechanistically, PD-1-laIL-2 could effectively expand dysfunctional and tumor-specific [CD8.sup.+] T cells. Furthermore, we discovered that presumably dysfunctional [PD-1.sup.+] [TIM3.sup.+] TILs are the dominant tumor-specific T cells responding to PD-1-laIL-2. Collectively, these results highlight that PD-1-laIL-2 can target and reactivate tumor-specific TILs for tumor regression as a unique strategy with stronger efficacy and lower toxicity., Introduction Increased levels of tumor-infiltrating lymphocytes (TILs) are associated with improved survival in patients with cancer (1-3). Anti-PD-1/PD-L1-based cancer immunotherapies have revolutionized the treatment of cancers (4-8), and TIL abundance [...]

Background: Neuronal abnormalities are closely associated with major depressive disorder (MDD). Available evidence suggests a role for microRNAs (miRNAs) in regulating the expression of genes involved in MDD. Hence, miRNAs that can be potential therapeutic targets need to be identified. Methods: A mouse model of chronic unpredictable stress (CUS) was used to evaluate the function of miRNAs in MDD. miR‐144‐5p was screened from the hippocampi of CUS mice based on sequencing results. Adenovirus‐associated vectors were used to overexpress or knockdown miR‐144‐5p in mice. BpV(pic) and LY294002 were used to determine the relationship between miR‐144‐5p target genes PTEN and TLR4 in neuronal impairment caused by miR‐144‐5p deficiency. Western blotting, immunofluorescence, ELISA immunosorbent assay, and Golgi staining were used to detect neuronal abnormalities. Serum samples from healthy individuals and patients with MDD were used to detect miR‐144‐5p levels in the serum and serum exosomes using qRT‐PCR. Results: miR‐144‐5p expression was significantly decreased within the hippocampal dentate gyrus (DG) of CUS mice. Upregulation of miR‐144‐5p in the DG ameliorated depression‐like behavior in CUS mice and attenuated neuronal abnormalities by directly targeting PTEN and TLR4 expression. Furthermore, miR‐144‐5p knockdown in normal mice led to depression‐like behavior via inducing neuronal abnormalities, including abnormal neurogenesis, neuronal apoptosis, altered synaptic plasticity, and neuroinflammation. miR‐144‐5p deficiency‐mediated neuronal impairment was mediated by PI3K/Akt/FoxO1 signaling. Furthermore, miR‐144‐5p levels were downregulated in the sera of patients with MDD and associated with depressive symptoms. Consistently, serum exosome‐derived miR‐144‐5p levels were decreased in patients with MDD. Conclusion: miR‐144‐5p plays a vital role in regulating neuronal abnormalities in depression. Our findings provide translational evidence that miR‐144‐5p is a new potential therapeutic target for MDD. [ABSTRACT FROM AUTHOR]