Explore the vast range of titles available.

Development of photothermal materials which are able to harness sunlight and convert it to thermal energy seems attractive. Besides carbon-based nanomaterials, conjugated polymers are emerging promising photothermal materials but their facile syntheses remain challenging. In this work, by modification of a CBT-Cys click condensation reaction and rational design of the starting materials, we facilely synthesize conjugated polymers poly-2-phenyl-benzobisthiazole (PPBBT) and its dihexyl derivative with good photothermal properties. Under the irradiation of either sunlight-mimicking Xe light or near-infrared laser, we verify that PPBBT has comparable photothermal heating-up speed to that of star material single-wall carbon nanotube. Moreover, PPBBT is used to fabricate water-soluble NP PPBBT nanoparticles which maintain excellent photothermal properties in vitro and photothermal therapy effect on the tumours exposed to laser irradiation. We envision that our synthetic method provides a facile approach to fabricate conjugated polymers for more promising applications in biomedicine or photovoltaics in the near future. Conjugated polymers are of interest for photothermal applications; however, synthesis of these polymers can be complex. Here, the authors report on a facile synthesis method that uses a modified CBT-Cys click reaction to make conjugated polymers and test these polymers for photothermal therapy applications.

Oridonin (Ori) is the major active ingredient of the traditional Chinese medicinal herb Rabdosia rubescens and has anti-inflammatory activity, but the target of Ori remains unknown. NLRP3 is a central component of NLRP3 inflammasome and has been involved in a wide variety of chronic inflammation-driven human diseases. Here, we show that Ori is a specific and covalent inhibitor for NLRP3 inflammasome. Ori forms a covalent bond with the cysteine 279 of NLRP3 in NACHT domain to block the interaction between NLRP3 and NEK7, thereby inhibiting NLRP3 inflammasome assembly and activation. Importantly, Ori has both preventive or therapeutic effects on mouse models of peritonitis, gouty arthritis and type 2 diabetes, via inhibition of NLRP3 activation. Our results thus identify NLRP3 as the direct target of Ori for mediating Ori’s anti-inflammatory activity. Ori could serve as a lead for developing new therapeutics against NLRP3-driven diseases. The small molecule oridonin (Ori) from the traditional Chinese herb Rabdosia rubescens has anti-inflammatory activity. Here the authors show that Ori can be covalently linked to NLRP3 to prevent assembly of the NLRP3 inflammasome, and to ameliorate inflammation in several mouse disease models.

Through controlled synthesis and molecular assembly, biological systems are able to organize molecules into supramolecular structures that carry out sophisticated processes. Although chemists have reported a few examples of supramolecular assembly in water, the controlled covalent synthesis of large molecules and structures in vivo has remained challenging. Here we report a condensation reaction between 1,2-aminothiol and 2-cyanobenzothiazole that occurs in vitro and in living cells under the control of either pH, disulfide reduction or enzymatic cleavage. In vitro , the size and shape of the condensation products, and the nanostructures subsequently assembled, were different in each case and could thus be controlled by tuning the structure of the monomers. Direct imaging of the products obtained in the cells revealed their locations—near the Golgi bodies under enzymatic cleavage control—demonstrating the feasibility of a controlled and localized reaction in living cells. This intracellular condensation process enabled the imaging of the proteolytic activity of furin. Chemists have very few tools at their disposal for controlling synthetic processes under physiological conditions. Now, a monomer has been prepared that oligomerizes in living cells under the control of various triggers (pH change, disulfide reduction and enzymatic cleavage), showing promise for imaging or therapeutic applications.

The dysregulation of NLRP3 inflammasome can cause uncontrolled inflammation and drive the development of a wide variety of human diseases, but the medications targeting NLRP3 inflammasome are not available in clinic. Here, we show that tranilast (TR), an old anti‐allergic clinical drug, is a direct NLRP3 inhibitor. TR inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation. Mechanismly, TR directly binds to the NACHT domain of NLRP3 and suppresses the assembly of NLRP3 inflammasome by blocking NLRP3 oligomerization. In vivo experiments show that TR has remarkable preventive or therapeutic effects on the mouse models of NLRP3 inflammasome‐related human diseases, including gouty arthritis, cryopyrin‐associated autoinflammatory syndromes, and type 2 diabetes. Furthermore, TR is active ex vivo for synovial fluid mononuclear cells from patients with gout. Thus, our study identifies the old drug TR as a direct NLRP3 inhibitor and provides a potentially practical pharmacological approach for treating NLRP3‐driven diseases. Synopsis Tranilast (TR), an anti‐allergic clinical drug, is here reported as a NLRP3 inflammasome inhibitor with beneficial effects for NLRP3‐driven diseases. By direct binding to NLRP3, it inhibits its oligomerization and subsequent inflammasome assembly, caspase‐1 activation and IL‐1β production. TR specifically inhibits NLRP3 inflammasome activation in both human and mouse cells. TR binds to NLRP3 and inhibits its oligomerization and inflammasome complex formation. TR has remarkable preventive or therapeutic effects on the mouse models of NLRP3‐driven diseases. Graphical Abstract Tranilast (TR), an anti‐allergic clinical drug, is here reported as a NLRP3 inflammasome inhibitor with beneficial effects for NLRP3‐driven diseases. By direct binding to NLRP3, it inhibits its oligomerization and subsequent inflammasome assembly, caspase‐1 activation and IL‐1β production.

Azide-alkyne cycloaddition reaction is a very common organic reaction to synthesize nitrogen-containing heterocycles. Once catalyzed by Cu(I) or Ru(II), it turns out to be a click reaction and thus is widely applied in chemical biology for labeling. However, besides their poor regioselectivity towards this reaction, these metal ions are not biologically friendly. Hence, it is an urgent need to develop a metal-free azide–alkyne cycloaddition reaction for biomedical applications. In this work, we found that, in the absence of metal ions, supramolecular self-assembly in an aqueous solution could realize this reaction with excellent regioselectivity. Nap-Phe-Phe-Lys(azido)-OH firstly self-assembled into nanofibers. Then, Nap-Phe-Phe-Gly(alkynyl)-OH at equivalent concentration approached to react with the assembly to yield the cycloaddition product Nap-Phe-Phe-Lys(triazole)-Gly-Phe-Phe-Nap to form nanoribbons. Due to space confinement effect, the product was obtained with excellent regioselectivity. Employing the excellent properties of supramolecular self-assembly, we are applying this strategy to realize more reactions without metal ion catalysis. Metal-free versions of azide–alkyne cycloadditions could find widespread applications in biomedical contexts. Here, the authors report an assembly-driven, regioselective azide–alkyne cycloaddition.

Derived from the D‐luciferin regeneration pathway in firefly body, the click condensation reaction between 2‐cyanobenzothiazole (CBT) and D‐cysteine (Cys) (CBT‐Cys click reaction) possesses unique advantages, including superior biocompatibility, high second order reaction rate, and metal‐free mild conditions, emerging as a powerful bioorthogonal tool for a variety of chemical biological applications. Moreover, owing to its programmable controllability (e.g., pH, reduction, or enzyme), CBT‐Cys click reaction is exploited to fabricate stimuli‐activatable imaging probes with self‐assembling behaviors in physiological context. At stimuli‐rich pathological lesions of interest, these probes undergo CBT‐Cys click reaction to form cyclic dimers/oligomers or linear polymers, and further self‐assemble into nanostructures. The in situ formed nanostructures promote the selective accumulation and retention of imaging agent cargos at pathological lesions, thus enabling precise and enhanced in vivo imaging of diseases (especially tumors). To address the significance and recent breakthroughs of smart CBT‐Cys probes for enhanced optical imaging of tumors/other diseases, we herein propose this mini‐review, in which advances (particularly in recent 5 years) and potential challenges (or chances) in this field are emphasized. To address the significance and recent breakthroughs of smart CBT‐Cys probes for enhanced optical imaging of tumors/other diseases, the authors herein propose this mini‐review, in which advances (particularly in recent 5 years) and potential challenges (or chances) in this field are emphasized.

Autophagy plays a crucial role in tumorigenesis and progression, but current approaches to visualize it in vivo show limited precision due to their single-analyte-responsive mode. Hence, by simultaneously employing dual autophagy enzymes Atg4B and cathepsin B to trigger the in situ formation of luciferin, we herein propose a strategy for precise autophagy bioluminescence imaging. An Atg4B-responsive peptide Ac-Thr-Phe-Gly-d-Cys (TFGC) and a cathepsin B-activatable compound Ac-Lys-Gly-Arg-Arg-CBT (KGRR-CBT) were rationally designed. During tumor autophagy, these two compounds were uptaken by cancer cells and cleaved by their corresponding enzymes to yield d-cysteine and 2-cyano-6-aminobenzothiazole, respectively, which underwent a CBT-Cys click reaction to yield d-aminoluciferin, turning the bioluminescence “on”. The responsiveness of these two compounds toward the two enzymes was tested in vitro, and the ability to turn bioluminescence “on” was validated in living cancer cells and in vivo. We anticipate that our precise autophagy imaging strategy could be further applied for the diagnosis of autophagy-related diseases in the near future.

Even though great advances have been achieved in the synthesis of luminescent metal nanoclusters, it is still challenging to develop metal nanoclusters with high quantum efficiency as well as multiple sensing functionalities. Here, we demonstrate the rapid preparation of glutathione-capped Au/Ag nanoclusters （GS-Au/Ag NCs） using microwave irradiation and their unique sensing capacities. Compared to bare GS-Au NCs, the doped Au/Ag NCs possess an enhanced quantum yield （7.8% compared to 2.2% for GS-Au NCs）. Several characterization techniques were used to elucidate the atomic composition, particulate character, and electronic structure of the fabricated NCs. According to the X-ray photoelectron spectroscopy （XPS） and X-ray absorption near-edge structure （XANES） spectra, a significant amount of Au exists in the oxidized state as Au（I）, and the Ag atoms are positively charged. In contrast to those nanoclusters that detect only one analyte, the GS-Au/Ag NCs can be used as a versatile sensor for metal ions, anions, and small molecules. In this manner, the NCs can be regarded as a unique sensor-on-a-nanoparticle.

Preeclampsia is a serious complication of pregnancy, which affects 2-8% of all pregnancies and is one of the leading causes of maternal and perinatal mortality and morbidity worldwide. To better understand the molecular mechanisms involved in pathological development of placenta in preeclampsia, we used high-resolution LC-MS/MS technologies to construct a comparative N-glycoproteomic and phosphoproteomic profiling of human placental plasma membrane in normal and preeclamptic pregnancies. A total of 1027 N-glyco- and 2094 phospho- sites were detected in human placental plasma membrane, and 5 N-glyco- and 38 phospho- proteins, respectively, with differentially expression were definitively identified between control and preeclamptic placental plasma membrane. Further bioinformatics analysis indicated that these differentially expressed proteins correlate with several specific cellular processes occurring during pathological changes of preeclamptic placental plasma membrane.

To better understand the molecular mechanisms involved in pathological development of placenta in preeclampsia, we used LC-MS/MS to construct a large-scale comparative proteome profile of human placentas from normal and preeclamptic pregnancies. A total of 2636 proteins were detected in human placentas, and 171 different proteins were definitively identified between control and preeclamptic placentas. Further bioinformatics analysis indicated that these differentially expressed proteins correlate with several specific cellular processes which occur during pathological changes of preeclamptic placenta. 6 proteins were randomly selected to verify their expression patterns with Western blotting. Of which, 3 proteins' cellular localizations were validated with immunohistochemistry. Elucidation of how protein-expression changes coordinate the pathological development would provide researchers with a better understanding of the critical biological processes of preeclampsia and potential targets for therapeutic agents to regulate placenta function, and eventually benefit the treatment of preeclampsia.