Search

Tumor‐associated macrophages (TAMs) play a role in both pro‐ and anti‐tumor functions; and the targeted polarization from M2 to M1 TAMs has become an effective therapy option. Although detection of M1 TAMs is imperative to assess cancer immunotherapeutic efficacy, existing optical probes suffer from shallow tissue penetration depth and poor specificity toward M1 TAMs. Herein, we report a tandem‐locked NIR chemiluminescent (CL) probe for specific detection of M1 TAMs. Through a combined molecular engineering approach via both atomic alternation and introduction of electron‐withdrawing groups, near‐infrared (NIR) chemiluminophores are screened out to possess record‐long emission (over 800 nm), record‐high CL quantum yield (2.7 % einstein/mol), and prolonged half‐life (7.7 h). Based on an ideal chemiluminophore, the tandem‐locked probe (DPDGN) is developed to only activate CL signal in the presence of both tumour (γ‐glutamyl transpeptidase) and M1 macrophage biomarkers (nitric oxide). Such a tandem‐lock design ensures its high specificity towards M1 macrophages in the tumor microenvironment over those in normal tissues or peripheral blood. Thus, DPDGN permits noninvasive imaging and tracking of M1 TAM in the tumor of living mice during R837 treatment, showing a good correlation with ex vivo methods. This study not only reports a new molecular approach towards highly efficient chemiluminophores but also reveals the first tandem‐locked CL probes for enhanced imaging specificity. [ABSTRACT FROM AUTHOR]

Tumor‐associated macrophages (TAMs) play a role in both pro‐ and anti‐tumor functions; and the targeted polarization from M2 to M1 TAMs has become an effective therapy option. Although detection of M1 TAMs is imperative to assess cancer immunotherapeutic efficacy, existing optical probes suffer from shallow tissue penetration depth and poor specificity toward M1 TAMs. Herein, we report a tandem‐locked NIR chemiluminescent (CL) probe for specific detection of M1 TAMs. Through a combined molecular engineering approach via both atomic alternation and introduction of electron‐withdrawing groups, near‐infrared (NIR) chemiluminophores are screened out to possess record‐long emission (over 800 nm), record‐high CL quantum yield (2.7 % einstein/mol), and prolonged half‐life (7.7 h). Based on an ideal chemiluminophore, the tandem‐locked probe (DPDGN) is developed to only activate CL signal in the presence of both tumour (γ‐glutamyl transpeptidase) and M1 macrophage biomarkers (nitric oxide). Such a tandem‐lock design ensures its high specificity towards M1 macrophages in the tumor microenvironment over those in normal tissues or peripheral blood. Thus, DPDGN permits noninvasive imaging and tracking of M1 TAM in the tumor of living mice during R837 treatment, showing a good correlation with ex vivo methods. This study not only reports a new molecular approach towards highly efficient chemiluminophores but also reveals the first tandem‐locked CL probes for enhanced imaging specificity. [ABSTRACT FROM AUTHOR]

As a major carbon emitter, the power sector plays a crucial role in realizing the goal of carbon peaking and carbon neutrality. This study constructed a low-carbon power system based on the LEAP model (LEAP-GBA) with 2020 as a statistic base aiming of exploring the low-carbon transformation pathway of the power sector in the Guangdong–Hong Kong, and Macao Greater Bay Area (GBA). Five scenarios are set up to simulate the demand, power generation structure, carbon emissions, and power generation costs in the power sector under different scenarios. The results indicate that total electricity demand will peak after 2050, with 80% of it coming from industry, buildings and residential use. To achieve net-zero emissions from the power sector in the GBA, a future power generation mix dominated by nuclear and renewable energy generation and supplemented by fossil energy generation equipped with CCUS technologies. BECCS technology and nuclear power are the key to realize zero carbon emissions from the power sector in the GBA, so it should be the first to promote BECCS technology testing and commercial application, improve the deployment of nuclear power sites, and push forward the construction of nuclear power and technology improvement in the next 40 years. [ABSTRACT FROM AUTHOR]

Two organo‐bimetallic complexes of ferrocene and organotin were synthesized and evaluated as potential anticancer drugs. MTT results indicated that the two complexes showed excellent antitumor activity against a variety of cancer cell lines compared with cisplatin and ferrocene alone. Different from the previous similar metal drugs available, the complexes synthesized in this work have a concentration‐dependent effect on immunogenic cell death (ICD) related proteins and the level of adenosine triphosphate(ATP) intracellular. The up‐regulation of related proteins leads to the imbalance of mitochondrial homeostasis, and the destruction of the electron transport chain which causes the accumulation of reactive oxygen species(ROS)in the mitochondria and induces cell death. In the wound healing assay, the complex can effectively inhibit the growth and reproduction of cells. The promising results displayed by the organo‐bimetallic complexes open avenues for new anticancer drugs. [ABSTRACT FROM AUTHOR]

Cytokine therapy mediates the interaction between immune cells and non‐immune cells in the tumor microenvironment (TME), forming a promising approach in cancer therapy. However, the dose‐dependent adverse effects and non‐selective stimulation of cytokines limit their clinical use. We herein report a sonodynamic cytokine nano‐immunocomplex (SPNAI) that specifically activates effector T cells (Teffs) for antitumor immunotherapy. By conjugating anti‐interleukin‐2 (anti‐IL‐2) antibodies S4B6 on the semiconducting polymer nanoparticles to afford SPNA, this nanoantibody SPNA can bind with IL‐2 to form SPNAI which can block the interaction between IL‐2 and regulatory T cells (Tregs), selectively activating Teffs in TME. Moreover, SPNAI generates 1O2 to trigger immunogenic cell death of cancer cells upon sono‐irradiation, which promotes the maturation of dendritic cells and the proliferation of Teffs. This SPNAI‐mediated combination sonodynamic immunotherapy thus elevates the ratio of Teffs/Tregs in TME, resulting in inhibition of tumor growth, suppression of lung metastasis and prevention of tumor relapse. [ABSTRACT FROM AUTHOR]

Cytokine therapy mediates the interaction between immune cells and non‐immune cells in the tumor microenvironment (TME), forming a promising approach in cancer therapy. However, the dose‐dependent adverse effects and non‐selective stimulation of cytokines limit their clinical use. We herein report a sonodynamic cytokine nano‐immunocomplex (SPNAI) that specifically activates effector T cells (Teffs) for antitumor immunotherapy. By conjugating anti‐interleukin‐2 (anti‐IL‐2) antibodies S4B6 on the semiconducting polymer nanoparticles to afford SPNA, this nanoantibody SPNA can bind with IL‐2 to form SPNAI which can block the interaction between IL‐2 and regulatory T cells (Tregs), selectively activating Teffs in TME. Moreover, SPNAI generates 1O2 to trigger immunogenic cell death of cancer cells upon sono‐irradiation, which promotes the maturation of dendritic cells and the proliferation of Teffs. This SPNAI‐mediated combination sonodynamic immunotherapy thus elevates the ratio of Teffs/Tregs in TME, resulting in inhibition of tumor growth, suppression of lung metastasis and prevention of tumor relapse. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has shown tremendous potential to train the intrinsic immune system against malignancy in the clinic. However, the extracellular matrix (ECM) in tumor microenvironment is a formidable barrier that not only restricts the penetration of therapeutic drugs but also prevents the infiltration of antitumor immune cells. We herein report a semiconducting polymer‐based ECM nanoremodeler (SPNcb) to combine photodynamic antitumor activity with cancer‐specific inhibition of collagen‐crosslinking enzymes (lysyl oxidase (LOX) family) for activatable cancer photo‐immunotherapy. SPNcb is self‐assembled from an amphiphilic semiconducting polymer conjugated with a LOX inhibitor (β‐aminopropionitrile, BAPN) via a cancer biomarker (cathepsin B, CatB)‐cleavable segment. BAPN can be exclusively activated to inhibit LOX activity in the presence of the tumor‐overexpressed CatB, thus blocking collagen crosslinking and decreasing ECM stiffness. Such an ECM nanoremodeler synergizes immunogenic phototherapy and checkpoint blockade immunotherapy to improve the tumor infiltration of cytotoxic T cells, inhibiting tumor growth and metastasis. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has shown tremendous potential to train the intrinsic immune system against malignancy in the clinic. However, the extracellular matrix (ECM) in tumor microenvironment is a formidable barrier that not only restricts the penetration of therapeutic drugs but also prevents the infiltration of antitumor immune cells. We herein report a semiconducting polymer‐based ECM nanoremodeler (SPNcb) to combine photodynamic antitumor activity with cancer‐specific inhibition of collagen‐crosslinking enzymes (lysyl oxidase (LOX) family) for activatable cancer photo‐immunotherapy. SPNcb is self‐assembled from an amphiphilic semiconducting polymer conjugated with a LOX inhibitor (β‐aminopropionitrile, BAPN) via a cancer biomarker (cathepsin B, CatB)‐cleavable segment. BAPN can be exclusively activated to inhibit LOX activity in the presence of the tumor‐overexpressed CatB, thus blocking collagen crosslinking and decreasing ECM stiffness. Such an ECM nanoremodeler synergizes immunogenic phototherapy and checkpoint blockade immunotherapy to improve the tumor infiltration of cytotoxic T cells, inhibiting tumor growth and metastasis. [ABSTRACT FROM AUTHOR]

[Display omitted] • The dehydrogenation reaction of 18H-DBT over Pt/Al 2 O 3 was performed in fixed-bed reactor. • Low pressure and high temperature can increase dehydrogenation degree but produce by-products. • The continuous reaction has a positive significance in the scalable application with the high hydrogen production capacity of 14.8 mol H2 /(g Pt ‧h). The dehydrogenation of perhydro-dibenzyltoluene (18H-DBT) is the key reaction in cyclic hydrogen storage, but it is usually investigated in batch reactors. In this work, the dehydrogenation reaction of 18H-DBT over Pt/Al 2 O 3 was performed in a fixed-bed, and the effects of Pt loading and reaction conditions on dehydrogenation activity were investigated. The results show that increasing the Pt loading could increase the dehydrogenation rate; however, the average electron density of Pt will increase accordingly, resulting in more byproducts. Low pressure and high temperature can increase the dehydrogenation degree but produce undesired byproducts. Therefore, 0.5 MPa and 330 °C are the optimal reaction conditions. When the LHSV was increased to 10 mL/(g cat ‧h), the hydrogen production capacity reached 14.8 mol H2 /(g Pt ‧h), which is much higher than the processing capacity of the reaction kettle in the literature. This result indicates that continuous reactions have positive significance in the large-scale application of 18H-DBT hydrogen production. [ABSTRACT FROM AUTHOR]

Eosinophils are important immune effector cells that affect T cell‐mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted the outcome of cancer immunotherapies. We herein report an eosinophil‐activating semiconducting polymer nanoparticle (SPNe) to improve photodynamic tumor immunogenicity, modulate eosinophil chemotaxis, and reinvigorate T‐cell immunity for activated cancer photo‐immunotherapy. SPNe comprises an amphiphilic semiconducting polymer and a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via a 1O2‐cleavable thioketal linker. Upon localized NIR photoirradiation, SPNe generates 1O2 to elicit immunogenic cell death of tumors and induce specific activation of sitagliptin. The subsequent inhibition of DPP4 increases intratumoral CCL11 levels to promote eosinophil chemotaxis and activation. SPNe‐mediated photo‐immunotherapy synergized with immune checkpoint blockade greatly promotes tumor infiltration and activation of both eosinophils and T cells, effectively inhibiting tumor growth and metastasis. Thus, this study presents a generic polymeric nanoplatform to modulate specific immune cells for precision cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Adipose dysfunction in lipodystrophic SEIPIN deficiency is associated with multiple metabolic disorders and increased risks of developing cardiovascular diseases, such as atherosclerosis, cardiac hypertrophy, and heart failure. Recently, adipose transplantation has been found to correct adipose dysfunction and metabolic disorders in lipodystrophic Seipin knockout mice; however, whether adipose transplantation could improve lipodystrophy-associated cardiovascular consequences is still unclear. Here, we aimed to explore the effects of adipose transplantation on lipodystrophy-associated metabolic cardiovascular diseases in Seipin knockout mice crossed into atherosclerosis-prone apolipoprotein E (Apoe) knockout background. At 2 months of age, lipodystrophic Seipin/Apoe double knockout mice and nonlipodystrophic Apoe knockout controls were subjected to adipose transplantation or sham operation. Seven months later, mice were euthanized. Our data showed that although adipose transplantation had no significant impact on endogenous adipose atrophy or gene expression, it remarkably increased plasma leptin but not adiponectin concentration in Seipin/Apoe double knockout mice. This led to significantly reduced hyperlipidemia, hepatic steatosis, and insulin resistance in Seipin/Apoe double knockout mice. Consequently, atherosclerosis burden, intraplaque macrophage infiltration, and aortic inflammatory gene expression were all attenuated in Seipin/Apoe double knockout mice with adipose transplantation. However, adipocyte morphology, macrophage infiltration, or fibrosis of the perivascular adipose tissue was not altered in Seipin/Apoe double knockout mice with adipose transplantation, followed by no significant improvement of vasoconstriction or relaxation. In conclusion, we demonstrate that adipose transplantation could alleviate lipodystrophy-associated metabolic disorders and atherosclerosis but has an almost null impact on perivascular adipose abnormality or vascular dysfunction in lipodystrophic Seipin/Apoe double knockout mice. NEW & NOTEWORTHY: Adipose transplantation (AT) reverses multiply metabolic derangements in lipodystrophy, but whether it could improve lipodystrophy-related cardiovascular consequences is unknown. Here, using Seipin/Apoe double knockout mice as a lipodystrophy disease model, we showed that AT partially restored adipose functionality, which translated into significantly reduced atherosclerosis. However, AT was incapable of reversing perivascular adipose abnormality or vascular dysfunction. The current study provides preliminary experimental evidence on the therapeutic potential of AT on lipodystrophy-related metabolic cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The Szegedy's quantum walk can give rise to a quadratic speed-up when the Markov chain is ergodic and symmetric. However, the quantum search on a one-dimensional (1D) cycle graph does not achieve a speed-up. In this paper, we study the effects of self-loops on the 1D cycle by Szegedy's quantum search. First, with the help of self-loops, Szegedy's quantum search can increase the success probability of finding a marked vertex on the 1D cycle. Second, the general expressions for the evolving states and the success probability on the 1D cycle with self-loops are explicitly presented by the symmetric tridiagonal matrix. The evolution of success probability is slower and smaller with the increase in the weight of the self-loops. Third, an approximate entanglement formula of the success probability is derived by a concave function, where the entanglement is measured by the reduced von Neumann entropy. The existence of a turning point is confirmed, and it was found to depend on the maximum eigenvalue of the initial superposition state and the number of marked vertices. Before the turning point, the entanglement first increased and then decreased. [ABSTRACT FROM AUTHOR]

Separative extended-gate AlGaAs/GaAs high electron mobility transistor (HEMT) biosensors based on the capacitance change strategy are proposed and fabricated. The working mechanism underlying this strategy is clearly clarified via examining the capacitance evolution on biorecognition and the capacitance matching issue between the HEMT and the sensing pad. The fabricated biosensors demonstrate a good linear current/voltage response to a label-free prostate-specific antigen (PSA) target over a broad concentration range of 100 fg/ml to 10 ng/ml in both 0.1× and 1× phosphate buffered saline solutions. Specifically, the sensitivity variation approaches 8.7% dec−1 at the critical concentration level of 2–8 ng/ml that enters the normal PSA region in the human body. The advantages of high sensitivity, low-cost, and convenience of usage make the proposed HEMT biosensors potential candidates for prostate cancer diagnosis. [ABSTRACT FROM AUTHOR]

Sono‐immunotherapy holds great potential for deep tumor inhibition; however, smart sono‐therapeutic agents to simultaneously eliminate 'domestic' tumor cells and regulate the 'community' tumor immune microenvironment have rarely been developed. Herein, we report a spatiotemporally controllable semiconducting iron‐chelated nano‐metallomodulator (SINM) for hypersensitive sono‐metallo‐immunotherapy of cancer. SINM consists of a semiconducting polymer (SP) backbone chelating iron ions (Fe3+) with thiophene‐based Schiff base structure, and a hydrophilic side chain. Upon accumulation in tumors after systemic administration, SINM specifically arouses ferroptosis and M1 macrophage polarization due to its response toward the tumor redox environment; meanwhile, the chelation of Fe3+ enhances the sono‐sensitizing effect of SPs, leading to enhanced generation of reactive oxygen species for immunogenic cell death. Such combined sonodynamic metallo‐immunotherapy of SINM efficiently ablates deep tumor and spatiotemporally regulates immunophenotypes. [ABSTRACT FROM AUTHOR]

Sono‐immunotherapy holds great potential for deep tumor inhibition; however, smart sono‐therapeutic agents to simultaneously eliminate 'domestic' tumor cells and regulate the 'community' tumor immune microenvironment have rarely been developed. Herein, we report a spatiotemporally controllable semiconducting iron‐chelated nano‐metallomodulator (SINM) for hypersensitive sono‐metallo‐immunotherapy of cancer. SINM consists of a semiconducting polymer (SP) backbone chelating iron ions (Fe3+) with thiophene‐based Schiff base structure, and a hydrophilic side chain. Upon accumulation in tumors after systemic administration, SINM specifically arouses ferroptosis and M1 macrophage polarization due to its response toward the tumor redox environment; meanwhile, the chelation of Fe3+ enhances the sono‐sensitizing effect of SPs, leading to enhanced generation of reactive oxygen species for immunogenic cell death. Such combined sonodynamic metallo‐immunotherapy of SINM efficiently ablates deep tumor and spatiotemporally regulates immunophenotypes. [ABSTRACT FROM AUTHOR]

Background: Gastrodin is an effective polyphenol extracted from Chinese natural herbal Gastrodiae elata Blume, which exhibits antioxidant and anti-inflammatory effects. It has been reported to benefit neurodegenerative diseases, but the effect of Gastrodin on atherosclerosis and the underlying mechanisms remain elusive. The aim of this study is to investigate the function and mechanism of Gastrodin in atherosclerosis. Methods: Atherosclerosis mouse model was established by fed low density lipoprotein receptor-deficient (Ldlr−/−) mice with a high fat diet (HFD, 20% fat and 0.5 cholesterol) for 8 weeks and Gastrodin was administered daily via oral gavage. Plasma lipid levels were measured using commercial kits. En face and aortic sinus lipid accumulation were analyzed with Oil Red O staining. In vitro cell models using foam cell formation model and classical atherosclerosis inflammation model, macrophages were incubated with oxygenized low-density lipoproteins (ox-LDL) or lipopolysaccharide (LPS) in the presence of different concentration of Gastrodin or vehicle solution. Foam cell formation and cellular lipid content were evaluated by Oil Red O staining and intracellular lipids extraction analysis. Gene expression and proteins related to cholesterol influx and efflux were examined by quantitative reverse transcription PCR (RT-qPCR) and western blotting analysis. Furthermore, the effect of Gastrodin on LPS induced macrophage inflammatory responses and NF-κB pathway were evaluated by RT-qPCR and western blotting analysis. Results: Gastrodin administration reduced the body weight, plasma lipid levels in Ldlr−/− mice after fed a high fat diet. Oil Red O staining showed Gastrodin-treated mice displayed less atherosclerosis lesion area. Furthermore, Gastrodin treatment significantly ameliorated ox-LDL-induced macrophage-derived foam cells formation through suppressing genes expression related to cholesterol efflux including scavenger receptor class B and ATP-binding cassette transporter A1. Moreover, Gastrodin markedly suppressed pro-inflammatory cytokines secretion and LPS induced inflammatory response in macrophage through downregulating NF-κB pathway. Conclusions: Our study demonstrated that Gastrodin attenuates atherosclerosis by suppressing foam cells formation and LPS-induced inflammatory response and represents a novel therapeutic target for the treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Psoriasis is one of the common chronic inflammatory skin diseases worldwide. The skin microbiota plays a role in psoriasis through regulating skin homeostasis. However, the studies on the interactions between symbiotic microbial strains and psoriasis are limited. In this study, Staphylococcus strain XSB102 was isolated from the skin of human, which was identified as Staphylococcus warneri using VITEK2 Compact. To reveal the roles of Staphylococcus warneri on psoriasis, XSB102 were applied on the back of imiquimod-induced psoriasis-like dermatitis mice. The results indicated that it exacerbated the psoriasis and significantly increased the thickening of the epidermis. Furthermore, in vitro experiments confirmed that inactivated strain XSB102 could promote the proliferation of human epidermal keratinocytes (HaCaT) cell. However, real-time quantitative PCR and immunofluorescence results suggested that the expression of inflammatory factors such as IL-17a, IL-6, and so on were not significantly increased, while extracellular matrix related factors such as Col6a3 and TGIF2 were significantly increased after XSB102 administration. This study indicates that Staphylococcus warneri XSB102 can exacerbate psoriasis and promote keratinocyte proliferation independently of inflammatory factors, which paves the way for further exploration of the relationship between skin microbiota and psoriasis. [ABSTRACT FROM AUTHOR]

The high electron mobility transistor (HEMT)-based biosensors are highly competitive in the ultimate application of portable and point-of-care testing. Herein, we have demonstrated highly sensitive and real-time detection of cardiac troponin I (cTnI), a biomarker for the diagnosis of acute myocardial infarction (AMI) using AlGaAs/GaAs HEMT-based biosensors. The device has achieved a lower detection limit of 1 pg/ml in the buffer solution and less than 30 s response time, which demonstrated significant promise in the early diagnosis and screening of AMI. In addition, our results are consistent with the enzyme-linked immunosorbent assay according to the AMI patient's blood test results. Furthermore, by comparing the two HEMT structures, we also calculated the equilibrium dissociation constant (KD) of the cTnI and cTnI antibody and analyzed the sensing mechanism. The results show that this method is very promising for early diagnosis of AMI. [ABSTRACT FROM AUTHOR]

The efficacy of combination immunotherapy has been limited by tumor specificity and immune‐related adverse events (irAEs). Herein, we report the development of polymeric STING pro‐agonists (PSPA), whose sono‐immunotherapeutic efficacy is activated by sono‐irradiation and elevated glutathione (GSH) within the tumor microenvironment (TME). PSPA is composed of sonosensitizers (semiconducting polymer) and STING agonists (MSA‐2) via the GSH‐activatable linkers. Under sono‐irradiation, PSPA serves as a sonosensitizer to generate 1O2 and induce immunogenic cell death (ICD) of malignant tumor cells. Furthermore, MSA‐2 is released specifically in tumor microenvironment with highly expressed GSH, minimizing off‐target side effects. The activation of the STING pathway elevates the interferon‐β level and synergizes with SDT to enhance the anti‐tumor response. Therefore, this work proposes a universal approach for spatiotemporal regulation of cancer sono‐immunotherapy. [ABSTRACT FROM AUTHOR]

The efficacy of combination immunotherapy has been limited by tumor specificity and immune‐related adverse events (irAEs). Herein, we report the development of polymeric STING pro‐agonists (PSPA), whose sono‐immunotherapeutic efficacy is activated by sono‐irradiation and elevated glutathione (GSH) within the tumor microenvironment (TME). PSPA is composed of sonosensitizers (semiconducting polymer) and STING agonists (MSA‐2) via the GSH‐activatable linkers. Under sono‐irradiation, PSPA serves as a sonosensitizer to generate 1O2 and induce immunogenic cell death (ICD) of malignant tumor cells. Furthermore, MSA‐2 is released specifically in tumor microenvironment with highly expressed GSH, minimizing off‐target side effects. The activation of the STING pathway elevates the interferon‐β level and synergizes with SDT to enhance the anti‐tumor response. Therefore, this work proposes a universal approach for spatiotemporal regulation of cancer sono‐immunotherapy. [ABSTRACT FROM AUTHOR]