Cognition-enhancing effect of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in the 5 × FAD transgenic mouse model of Alzheimer's pathology.

BACKGROUND: Intracerebral translocator protein 18 kDa (TSPO) mediates the transport of cholesterol from cytoplasm to mitochondria and activation of microglia. The change of TSPO and the dysfunction of microglia are closely related to the pathogenesis of Alzheimer's disease (AD). AIMS: This study aimed to investigate the effects of microglial TSPO and its selective ligand YL-IPA08 on the cognitive function of transgenic mice in 5 × familial Alzheimer's disease (FAD) mouse model of AD. METHODS: The TSPO knockout 5 × FAD transgenic mice were bred, and tested by Morris water maze. The effects of YL-IPA08 on cognitive abilities and expression of Aß in 5 × FAD mice were also explored into. RESULTS: The latency of escape by TSPO knockout 5 × FAD mice was significantly prolonged compared with the 5 × FAD group, indicating that the cognitive impairment of mice aggravated. With the attenuated phagocytic ability of microglia, the deposition of Aß in prefrontal cortex of TSPO knockout 5 × FAD mice increased, and the expression of proinflammatory factors (IL-1ß, TNF-α, IL-6) were upregulated. In addition, YL-IPA08 significantly reduced the latency of escape by 5 × FAD mice, increased the number of times of crossing over the platform by mice, and inhibited the deposition of Aß in the prefrontal cortex of 5 × FAD mice without affecting the cleavage of APP. CONCLUSION: Our findings suggested that TSPO knockout in 5 × FAD mice inhibited microglial phagocytosis, promoted Aß deposition and neuroinflammation, and aggravated cognitive dysfunction in AD mice. YL-IPA08 had a significant cognition-enhancing effect in 5 × FAD transgenic mice, which might provide a new basis for potential drug candidates in AD treatment.

Cinnamic acid hybrids as anticancer agents: A mini-review.

Cancer, as a long-lasting and dramatic disease, affects almost one-third of human beings globally. Chemotherapeutics play an important role in cancer treatment, but multidrug resistance and severe adverse effects have already become the main causes of failure in tumor chemotherapy. Therefore, it is an urgent need to develop novel chemotherapeutics. Cinnamic acid contains a ubiquitous α,ß-unsaturated acid moiety presenting potential therapeutic effects in the treatment of cancer as these derivatives could act on cancer cells by diverse mechanisms of action. Accordingly, cinnamic acid derivatives are critical scaffolds in discovering novel anticancer agents. This review provides a comprehensive overview of cinnamic acid hybrids as anticancer agents. The structure-activity relationship, as well as the mechanisms of action, are also discussed, covering articles published from 2012 to 2021.

Benzimidazole hybrids as anticancer drugs: An updated review on anticancer properties, structure-activity relationship, and mechanisms of action (2019-2021).

Cancer, characterized by a deregulation of the cell cycle which mainly results in a progressive loss of cellular differentiation and uncontrolled cellular growth, remains a prominent cause of death across the world. Almost all currently available anticancer agents used in clinical practice have developed multidrug resistance, creating an urgent need to develop novel chemotherapeutics. Benzimidazole derivatives could exert anticancer properties through diverse mechanisms, inclusive of the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, antiangiogenesis, and blockage of glucose transport. Moreover, several benzimidazole-based agents have already been approved for the treatment of cancers. Hence, benzimidazole derivatives are useful scaffolds for the development of novel anticancer agents. In particular, benzimidazole hybrids could exert dual or multiple antiproliferative activities and had the potential to overcome drug resistance, demonstrating the potential of benzimidazole hybrids as potential prototypes for clinical deployment in the control and eradication of cancers. The purpose of the present review article is to provide a comprehensive landscape of benzimidazole hybrids as potential anticancer agents, and the structure-activity relationship as well as mechanisms of action are also discussed to facilitate the further rational design of more effective candidates, covering articles published from 2019 to 2021.

Hierarchical Ti3C2Tx@ZnO Hollow Spheres with Excellent Microwave Absorption Inspired by the Visual Phenomenon of Eyeless Urchins.

Ingenious microstructure design and rational composition selection are effective approaches to realize high-performance microwave absorbers, and the advancement of biomimetic manufacturing provides a new strategy. In nature, urchins are the animals without eyes but can "see", because their special structure composed of regular spines and spherical photosensitive bodies "amplifies" the light-receiving ability. Herein, inspired by the above phenomenon, the biomimetic urchin-like Ti3C2Tx@ZnO hollow microspheres are rationally designed and fabricated, in which ZnO nanoarrays (length: ~ 2.3 µm, diameter: ~ 100 nm) as the urchin spines are evenly grafted onto the surface of the Ti3C2Tx hollow spheres (diameter: ~ 4.2 µm) as the urchin spherical photosensitive bodies. The construction of gradient impedance and hierarchical heterostructures enhance the attenuation of incident electromagnetic waves. And the EMW loss behavior is further revealed by limited integral simulation calculations, which fully highlights the advantages of the urchin-like architecture. As a result, the Ti3C2Tx@ZnO hollow spheres deliver a strong reflection loss of - 57.4 dB and broad effective absorption bandwidth of 6.56 GHz, superior to similar absorbents. This work provides a new biomimetic strategy for the design and manufacturing of advanced microwave absorbers.

Ultralight Biomass Aerogels with Multifunctionality and Superelasticity Under Extreme Conditions.

Biomass aerogels are highly attractive candidates in various applications due to their intrinsic merits of high strength, high porosity, biodegradability, and renewability. However, under low-temperature harsh conditions, biomass aerogels suffer from weakened mechanical properties, become extremely brittle, and lose functionality. Herein, we report a multifunctional biomass aerogel with lamella nanostructures (∼1 µm) fabricated from cellulose nanofibers (∼200 nm) and gelatin, showing outstanding elasticity from room temperature to ultralow temperatures (repeatedly bent, twisted, or compressed in liquid nitrogen). The resultant aerogel exhibits excellent organic solvent absorption, thermal infrared stealth, and thermal insulation performance in both normal and extreme environments. Even at dry ice temperature (-78 °C), the aerogel can selectively and repeatedly absorb organic solvents in the same way as room temperature with high capacities (90-177 g/g). Excellent heat insulation and infrared stealth performances are achieved in a wide temperature range of -196 to 80 °C. Further, this aerogel combines with the advantages of ultralow density (∼6 mg/cm3), biodegradability, flame retardancy, and performance stability, making it a perfect candidate for multifunctional applications under harsh conditions. This work greatly broadens application temperature windows of biomass aerogels and sheds light on the development of mechanically robust biomass aerogels for various applications under extreme conditions.

Multifunctional Photothermal Conversion Nanocoatings Toward Highly Efficient and Safe High-Viscosity Oil Cleanup Absorption.

Efficient and safe cleanup for the high-viscosity heavy oil spill has been a worldwide challenge due to its sluggish flowability, while classic absorption methods by electric/solar heating are seriously limited by low efficiency and high fire hazards during heating of highly flammable oil. Facing this dilemma, we reported a novel flame-retardant photothermal conversion nanocoating to endow commercial foams with highly efficient and safe heavy oil cleanup absorption. This multifunctional nanocoating consisting of nano-Fe3O4 and reduced graphene oxide (rGO) that both showed photothermal conversion ability and non-flammable nature can be firmly deposited on the polymer foam skeletons via facile coprecipitation and dip-coating processes. The composite foam showed a tough morphology with high hydrophobicity and low density, thus leading to selective high absorption for various oils and organic solvents. Due to the double photothermal conversion effects of nano-Fe3O4 and rGO, the temperature of the foam can be rapidly heated at a rate of ∼103.5 °C/min (the fastest rate ever) under 1 sun irradiation. Consequently, the foam with a high absorption capacity of 75.1 times its weight demonstrated a rapid absorption rate of 9000 g m-2 min-1 for large-viscosity oil under 1 sun irradiation, which was 3 times faster than previously reported. Furthermore, benefitting from high flame retardancy, elasticity, and magnetism, the foam can be safely and repeatedly used for magnetically controllable oil cleanup absorption, which effectively avoids oil spill hazards.

1,2,4-Trimethoxybenzene selectively inhibits NLRP3 inflammasome activation and attenuates experimental autoimmune encephalomyelitis.

NOD-like receptor (NLR) family pyrin domain-containing-3 (NLRP3) inflammasome is implicated in inflammation-associated diseases such as multiple sclerosis, Parkinson's disease, and stroke. Targeting the NLRP3 inflammasome is beneficial to these diseases, but few NLRP3 inflammasome-selective inhibitors are identified to date. Essential oils (EOs) are liquid mixtures of volatile and low molecular-weight organic compounds extracted from aromatic plants, which show various pharmacological activities, including antibacterial, antifungal, antiviral, antioxidant, and anti-inflammatory properties. In this study we screened active ingredients from essential oils, and identified 1,2,4-trimethoxybenzene (1,2,4-TTB) as a selective NLRP3 inflammasome inhibitor. We showed that 1,2,4-TTB (1 mM) markedly suppressed nigericin- or ATP-induced NLRP3 inflammasome activation, thus decreased caspase-1 activation and IL-1ß secretion in immortalized murine bone marrow-derived macrophages (iBMDMs) and in primary mouse microglia. Moreover, 1,2,4-TTB specifically inhibited the activation of NLRP3 inflammasome without affecting absent in melanoma 2 (AIM2) inflammasome activation. We further demonstrated that 1,2,4-TTB inhibited oligomerization of the apoptosis-associated speck-like protein containing a CARD (ASC) and protein-protein interaction between NLRP3 and ASC, thus blocking NLRP3 inflammasome assembly in iBMDMs and in primary mouse macrophages. In mice with experimental autoimmune encephalomyelitis (EAE), administration of 1,2,4-TTB (200 mg · kg-1 · d-1, i.g. for 17 days) significantly ameliorated EAE progression and demyelination. In conclusion, our results demonstrate that 1,2,4-TTB is an NLRP3 inflammasome inhibitor and attenuates the clinical symptom and inflammation of EAE, suggesting that 1,2,4-TTB is a potential candidate compound for treating NLRP3 inflammasome-driven diseases, such as multiple sclerosis.

Fully bio-based, low fire-hazard and superelastic aerogel without hazardous cross-linkers for excellent thermal insulation and oil clean-up absorption.

Elastic biomass aerogels have attracted widespread attention but are seriously hindered by environmentally unfriendly cross-linkers and fire hazards for functional applications. This study outlines the fabrication of a fully bio-based, low fire-hazard and superelastic aerogel without any cross-linkers for excellent thermal insulation and oil absorption, via creating highly oriented wave-shaped layer microstructures and subsequently depositing nonflammable siloxane coating on the surface of the aerogel skeleton. The resultant environmental-safety aerogel showed the combined advantages of anisotropic super-elasticity, hydrophobicity, low density and high flame retardancy (limiting oxygen index value of 42%, UL-94 V-0 rating, and extremely low heat release), thus leading to many benefits for solving environmental hazards. For instance, this fire-safety biomass aerogel can be used as the high-performance thermal insulator with low thermal conductivity and high shielding efficiency. The aerogel also exhibited a great selectively oil clean-up absorption with a high absorption capacity of 117 times its own weight and excellent recyclability. Especially, due to the highly oriented microstructures, the aerogel as a filter showed the fastest separation rates of oil/water mixture (flux rate of 145.78 L h-1 g-1) ever reported. Such a method of preparing super-elastic biomass aerogels will provide new insights into their multifunctional applications with high environmental safety.

A Chinese family of autosomal recessive polycystic kidney disease identified by whole exome sequencing.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is an autosomal recessive hepatorenal fibrocystic syndrome. The majority of ARPKD patients progress to end-stage renal disease. Precise molecular diagnosis of ARPKD has proven valuable for understanding its mechanism and selecting optimal therapy. METHODS: A Chinese family with ARPKD was recruited in current study. The clinical characteristics of ARPKD patient were collected from medical records and the potential responsible genes were studied by the whole exome sequencing (WES). Candidate pathogenic variants were validated by Sanger sequencing. RESULTS: Both renal manifestation and hepatobiliary phenotype were observed. WES revealed compound heterozygous mutations of polycystic kidney and hepatic disease 1 genes, NM_138694: c.751G>T, (p.Asp251Tyr) and c.3998_4004delACCTGAA (p.Asn1333Thr fs × 13), which were confirmed by Sanger sequencing. Moreover, the mutations in the proband and its affected sib were co-segregated with the phenotype. CONCLUSIONS: The novel mutation in polycystic kidney and hepatic disease 1 gene identified by WES might be molecular pathogenic basis of this disorder.

Banana Leaflike C-Doped MoS2 Aerogels toward Excellent Microwave Absorption Performance.

We describe the design and manufacturing method of a lightweight C-doped MoS2 aerogel with a special regular banana leaflike microstructure used for high-performance microwave absorbers. The aerogel precursor was first fabricated by a self-assembly process between alginate (Alg) and ammonium thiomolybdate (ATM), where Alg as a template was assembled with ATM into regular banana leaflike architectures along the ice growth direction during oriented freezing. After pyrolysis at 900 °C, the C-doped MoS2 aerogels maintained low densities and porous hierarchal banana leaflike structures, where the banana leaves ranged in diameter from about 2 to 5 µm with the growth of small branches. Benefitting from these features, the C-doped MoS2 aerogel possessed excellent microwave absorption performance in the frequency range of 2-18 GHz. The minimum reflection loss (RL) reached -43 dB at 5.4 GHz with a matching thickness of 4 mm, and the effective microwave absorption band (RL < -10 dB) reached 4 GHz (14-18 GHz) at a thickness of 1.5 mm. Our findings also provide strategies for designing MoS2 aerogel nanostructures for electronic devices, catalysis, and other potential applications.

Hierarchically porous SiO2/polyurethane foam composites towards excellent thermal insulating, flame-retardant and smoke-suppressant performances.

Polyurethane foam (PUF) is widely used in building insulation field but highly flammable. In an effort to develop an efficient way to reduce flammability and smoke release of PUF without sacrificing its inherent merits, a novel strategy has been proposed to decorate silica aerogels onto the surface of PUF to fabricate hierarchically porous SiO2/PUF composites. Due to the unique hierarchically porous structure, the resultant composites showed superior thermal insulation with a lower thermal conductivity of 0.0282 W/(m K). The introduction of silica aerogels also effectively improved the compressive strength, almost 220% of that of neat PUF. Notably, the SiO2/PUF composites were rendered self-extinguishing in vertical burning tests and had a high limiting oxygen index (LOI) value of 32.5%. Cone calorimetry (CC) tests revealed that the peak heat release rate (PHRR) and peak smoke production release (PSPR) of the SiO2/PUF composites were reduced by 40.4% and 45.6%, respectively. Particularly, the specific optical density (Ds) of the composites displayed as 55.7% reduction in the smoke density chamber tests, showing excellent smoke-suppression. The mechanism analysis suggested that a compact silica-rich hybrid barrier formed, preventing thermal degradation products and energy transfer during combustion. These results indicate SiO2/PUF composites have enormous potential as building insulation materials.