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It is known that the main-group metals and their related materials show poor catalytic activity due to a broadened single resonance derived from the interaction of valence orbitals of adsorbates with the broad sp-band of main-group metals. However, Mg cofactors existing in enzymes are extremely active in biochemical reactions. Our density function theory calculations reveal that the catalytic activity of the main-group metals (Mg, Al and Ca) in oxygen reduction reaction is severely hampered by the tight-bonding of active centers with hydroxyl group intermediate, while the Mg atom coordinated to two nitrogen atoms has the near-optimal adsorption strength with intermediate oxygen species by the rise of p-band center position compared to other coordination environments. We experimentally demonstrate that the atomically dispersed Mg cofactors incorporated within graphene framework exhibits a strikingly high half-wave potential of 910 mV in alkaline media, turning a s/p-band metal into a highly active electrocatalyst. Although magnesium-based cofactors are highly active in biochemical reactions, magnesium-based materials generally exhibit poor catalytic activity for oxygen reduction. Here the authors enhance electrocatalytic activity of magnesium through atomic dispersion with a graphene framework.

When exposed to various microenvironmental stimuli, macrophages are highly plastic and primarily polarized into the pro-inflammatory M1-type and the anti-inflammatory M2-type, both of which perform almost entirely opposing functions. Due to this characteristic, macrophages perform different functions at different stages of immunity and inflammation. Inflammatory immune skin diseases usually show an imbalance in the M1/M2 macrophage ratio, and altering the macrophage polarization phenotype can either make the symptoms worse or better. Therefore, this review presents the mechanisms of macrophage polarization, inflammation-related signaling pathways (JAK/STAT, NF-κB, and PI3K/Akt), and the role of both in inflammatory immune skin diseases (psoriasis, AD, SLE, BD, etc.) to provide new directions for basic and clinical research of related diseases.

Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Long noncoding RNAs (lncRNAs) are thought to play a critical role in cancer development. Recently, lncRNA CASC9 was shown to be dysregulated in many cancer types, but the mechanisms whereby this occurs remain largely unknown. In this study, we found that CASC9 was significantly upregulated in ESCC tissues, with further analysis revealing that elevated CASC9 expression was associated with ESCC prognosis and metastasis. Furthermore, we found that CASC9 knockdown significantly repressed ESCC migration and invasion in vitro and metastasis in nude mice in vivo. A microarray analysis and mechanical experiments indicated that CASC9 preferentially affected gene expression linked to ECM–integrin interactions, including LAMC2, an upstream inducer of the integrin pathway. We demonstrated that LAMC2 was consistently upregulated in ESCC and promoted ESCC metastasis. LAMC2 overexpression partially compromised the decrease of cell migration and invasion capacity in CASC9 knockdowns. In addition, we found that both CASC9 and LAMC2 depletion reduced the phosphorylation of FAK, PI3K, and Akt, which are downstream effectors of the integrin pathway. Moreover, the reduction in phosphorylation caused by CASC9 depletion was rescued by LAMC2 overexpression, further confirming that CASC9 exerts a pro-metastatic role through LAMC2. Mechanistically, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assay indicated that CASC9 could bind with the transcriptional coactivator CREB-binding protein (CBP) in the nucleus. Chromatin immunoprecipitation (ChIP) assay additionally illustrated that CASC9 increased the enrichment of CBP and H3K27 acetylation in the LAMC2 promoter, thereby upregulating LAMC2 expression. In conclusion, we demonstrate that CASC9 upregulates LAMC2 expression by binding with CBP and modifying histone acetylation. Our research reveals the prognostic and pro-metastatic roles for CASC9 in ESCC, suggesting that CASC9 could serve as a biomarker for prognosis and a target for metastasis treatment.

High stiffness and strength carbon fibres are commonly used to reinforce epoxy-resin composites. While wild Antheraea pernyi silk fibres exhibit high toughness originating from their α-helix/random coil conformation structures and their micro-fibre morphology, their insufficient strength and stiffness hinders them from being used in similar structural composites. In this work, we use interply hybridization of silk and carbon fibres to reinforce epoxy-matrix composites. With increased carbon fibre content, the quasi-static tensile/flexural stiffness and strength increases following the rule of mixtures while more silk fibre acts to increase ductility and impact strength. This results in a composite comprising equal volumes of carbon and silk fibres achieving an impact strength of 98 kJ m −2 , which is twice that of purely carbon-fibre reinforced composites (44 kJ m −2 ). This work shows tough natural silk fibres and strong synthetic fibres can be successfully integrated into epoxy-resin composites for tailored mechanical properties. Natural silk fibres are tough, but they lack required strength and stiffness as a reinforcement for polymer matrix composites. Here, the authors hybridise silks produced by a wild caterpillar A. pernyi with high-performance carbon fibres to produce tough, strong and impact resistant composites.

Vx-770 (Ivacaftor), a Food and Drug Administration (FDA)-approved drug for clinical application to patients with cystic fibrosis (CF), shifts the paradigm from conventional symptomatic treatments to therapeutics directly tackling the root of the disease: functional defects of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel caused by pathogenic mutations. The underlying mechanism for the action of Vx-770 remains elusive partly because this compound not only increases the activity of wild-type (WT) channels whose gating is primarily controlled by ATP binding/hydrolysis, but also improves the function of G551D-CFTR, a disease-associated mutation that abolishes CFTR’s responsiveness to ATP. Here we provide a unified theory to account for this dual effect of Vx-770. We found that Vx-770 enhances spontaneous, ATP-independent activity of WT-CFTR to a similar magnitude as its effects on G551D channels, a result essentially explaining Vx-770’s effect on G551D-CFTR. Furthermore, Vx-770 increases the open time of WT-CFTR in an [ATP]-dependent manner. This distinct kinetic effect is accountable with a newly proposed CFTR gating model depicting an [ATP]-dependent “reentry” mechanism that allows CFTR shuffling among different open states by undergoing multiple rounds of ATP hydrolysis. We further examined the effect of Vx-770 on R352C-CFTR, a unique mutant that allows direct observation of hydrolysis-triggered gating events. Our data corroborate that Vx-770 increases the open time of WT-CFTR by stabilizing a posthydrolytic open state and thereby fosters decoupling between the gating cycle and ATP hydrolysis cycle. The current study also suggests that this unique mechanism of drug action can be further exploited to develop strategies that enhance the function of CFTR.

Chemodynamic therapy (CDT) catalyzed by transition metal and starvation therapy catalyzed by intracellular metabolite oxidases are both classic tumor treatments based on nanocatalysts. CDT monotherapy has limitations including low catalytic efficiency of metal ions and insufficient endogenous hydrogen peroxide (H 2 O 2 ). Also, single starvation therapy shows limited ability on resisting tumors. The “metal-oxidase” cascade catalytic system is to introduce intracellular metabolite oxidases into the metal-based nanoplatform, which perfectly solves the shortcomings of the above-mentioned monotherapiesIn this system, oxidases can not only consume tumor nutrients to produce a “starvation effect”, but also provide CDT with sufficient H 2 O 2 and a suitable acidic environment, which further promote synergy between CDT and starvation therapy, leading to enhanced antitumor effects. More importantly, the “metal-oxidase” system can be combined with other antitumor therapies (such as photothermal therapy, hypoxia-activated drug therapy, chemotherapy, and immunotherapy) to maximize their antitumor effects. In addition, both metal-based nanoparticles and oxidases can activate tumor immunity through multiple pathways, so the combination of the “metal-oxidase” system with immunotherapy has a powerful synergistic effect. This article firstly introduced the metals which induce CDT and the oxidases which induce starvation therapy and then described the “metal-oxidase” cascade catalytic system in detail. Moreover, we highlight the application of the “metal-oxidase” system in combination with numerous antitumor therapies, especially in combination with immunotherapy, expecting to provide new ideas for tumor treatment.

Gallic acid (GA) is a naturally occurring polyphenol compound present in fruits, vegetables, and herbal medicines. According to previous studies, GA has many biological properties, including antioxidant, anticancer, anti-inflammatory, and antimicrobial properties. GA and its derivatives have multiple industrial uses, such as food supplements or additives. Additionally, recent studies have shown that GA and its derivatives not only enhance gut microbiome (GM) activities, but also modulate immune responses. Thus, GA has great potential to facilitate natural defense against microbial infections and modulate the immune response. However, the exact mechanisms of GA acts on the GM and immune system remain unclear. In this review, first the physicochemical properties, bioavailability, absorption, and metabolism of GA are introduced, and then we summarize recent findings concerning its roles in gastrointestinal health. Furthermore, the present review attempts to explain how GA influences the GM and modulates the immune response to maintain intestinal health.

For effectively assessing blood, red blood cell (RBC) aggregation and blood viscosity have been measured in microfluidic environments. However, the previous methods still face several challenges (dead-volume loss, RBC sedimentation, hematocrit-sensitive blood velocity, and precise flow rate control). In this study, a novel method is suggested to resolve several issues. Air cavity (Vair = 250 μL) is secured above the blood column (at least 100 μL) loaded into a driving syringe. To probe RBC aggregation and blood viscosity, a microfluidic chip consists of a main channel (γ˙ > 1000 s−1) and an aggregation channel (γ˙ < 50 s−1). Blood is supplied into a microfluidic chip with two-step blood delivery (i.e., air compression for RBC aggregation, and syringe pump for blood viscosity). RBC aggregation index and blood viscosity are obtained from time-lapse image intensity and blood flow rate in both channels. As performance demonstrations, first, the measurement accuracy of fluid viscosity is validated with glycerin solution. Then, the present method is adopted to probe the difference in hematocrit and dextran concentration. At last, the proposed method is employed to detect heat-shocked RBCs (45~50 °C for 40 min). In conclusion, the proposed method has the ability to accurately measure substantial changes in RBCs or blood medium.

The biomechanical properties of blood are regarded as promising biomarkers for monitoring early-stage abnormalities and disease progression. To detect any changes in blood, it is necessary to measure as many rheological properties as possible. Herein, a novel method is proposed for measuring multiple rheological properties of blood using a microfluidic chip. The syringe pump turns off for 5 min to induce RBC (red blood cell) sedimentation in the driving syringe. RBC aggregation is determined by analyzing the time-lapse blood image intensity at stasis: I(t) = I1 exp (−k1t) + I2 exp (−k2t). RBC-rich blood and RBC-depleted blood are sequentially infused into the microfluidic chip. Based on blood pressure estimated with time-lapse blood velocity, blood viscosity is acquired with the Hagen–Poiseuille law. RBC sedimentation is quantified as RBC sedimentation distance (Xesr) and erythrocyte sedimentation rate (ESR). The proposed method provides a consistent viscosity compared with previous methods. Two of the four variables (I1, I2) exhibited a strong correlation with the conventional RBC aggregation index (AI). The indices Xesr and ESR showed consistent trends with respect to the blood medium and hematocrit. In conclusion, the proposed method is then regarded as effective for monitoring multiple rheological properties.