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Photocages enable the precise activation of molecular function with light in many research fields, such as anticancer treatment, where remote spatiotemporal control over the release of an active drug is needed. However, the poor physiological stability and tumor accumulation of conventional small molecular photocages are significant obstacles to developing efficient therapy in vivo. In this study, a new concept of "polyphotocage" is proposed through photocage–polymer hybrid macromolecular engineering. Photoresponsive Ru complex photocage is designed and fused with PEGylated polycarbonates, resulting in the polyphotocage. Various anticancer drugs can be readily conjugated to the polyphotocage via coordination linkage, which can be cut off to release drugs by red light. The polyphotocages can self‐assemble into nanoparticles, which enhances the stability of the Ru photocage and demonstrates the efficient accumulation in different‐sized tumorswith a high signal‐to‐background ratio. Furthermore, rapid cellular internalization and mitochondrial anchoring capability allowed the polyphotocages to deliver drugs into the mitochondria, which induces mitochondrial dysfunction and cell death. These properties ensure the effective delivery of anticancer drugs to solid tumors and multiple tiny tumors, ultimately inhibiting tumor proliferation. This strategy of polyphotocages provides a new platform for the future design of drug‐delivery systems for cancer photochemotherapy. [ABSTRACT FROM AUTHOR]

Conventional photocages only respond to short wavelength light, which is a significant obstacle to developing efficient phototherapy in vivo. The development of photocages activated by near‐infrared (NIR) light at wavelengths from 700 to 950 nm is important for in vivo studies but remains challenging. Herein, we describe the synthesis of a photocage based on a ruthenium (Ru) complex with NIR light‐triggered photocleavage reaction. The commercial anticancer drug, tetrahydrocurcumin (THC), was coordinated to the RuII center to create the Ru‐based photocage that is readily responsive to NIR light at 760 nm. The photocage inherited the anticancer properties of THC. As a proof‐of‐concept, we further engineered a self‐assembled photocage‐based nanoparticle system with amphiphilic block copolymers. Upon exposure to NIR light at 760 nm, the Ru complex‐based photocages were released from the polymeric nanoparticles and efficiently inhibited tumor proliferation in vivo. [ABSTRACT FROM AUTHOR]

Conventional photocages only respond to short wavelength light, which is a significant obstacle to developing efficient phototherapy in vivo. The development of photocages activated by near‐infrared (NIR) light at wavelengths from 700 to 950 nm is important for in vivo studies but remains challenging. Herein, we describe the synthesis of a photocage based on a ruthenium (Ru) complex with NIR light‐triggered photocleavage reaction. The commercial anticancer drug, tetrahydrocurcumin (THC), was coordinated to the RuII center to create the Ru‐based photocage that is readily responsive to NIR light at 760 nm. The photocage inherited the anticancer properties of THC. As a proof‐of‐concept, we further engineered a self‐assembled photocage‐based nanoparticle system with amphiphilic block copolymers. Upon exposure to NIR light at 760 nm, the Ru complex‐based photocages were released from the polymeric nanoparticles and efficiently inhibited tumor proliferation in vivo. [ABSTRACT FROM AUTHOR]

The synergistic combination of chemotherapy and photodynamic therapy has attracted considerable attention for its enhanced antitumoral effects; however, it remains challenging to successfully delivery photosensitizers and anticancer drugs while minimizing drug leakage at off‐target sites. A red‐light‐activatable metallopolymer, Poly(Ru/PTX), is synthesized for combined chemo‐photodynamic therapy. The polymer has a biodegradable backbone that contains a photosensitizer Ru complex and the anticancer drug paclitaxel (PTX) via a singlet oxygen (1O2) cleavable linker. The polymer self‐assembles into nanoparticles, which can efficiently accumulate at the tumor sites during blood circulation. The distribution of the therapeutic agents is synchronized because the Ru complex and PTX are covalently conjugate to the polymer, and off‐target toxicity during circulation is also mostly avoided. Red light irradiation at the tumor directly cleaves the Ru complex and produces 1O2 for photodynamic therapy. Sequentially, the generated 1O2 triggers the breakage of the linker to release the PTX for chemotherapy. Therefore, this novel sequential dual‐model release strategy creates a synergistic chemo‐photodynamic therapy while minimizing drug leakage. This study offers a new platform to develop smart delivery systems for the on‐demand release of therapeutic agents in vivo. [ABSTRACT FROM AUTHOR]

Introduction: To investigate risk factors associated with urinary tract infection (UTI), following ureteral stenting, for patients with renal colic during pregnancy. Patients and Methods: Patients with renal colic during pregnancy who underwent ureteral stenting in The First Affiliated Hospital of Guangzhou Medical University between 2009 and 2019 were examined retrospectively. Ureteral stenting patients who had UTIs after hospital discharge and before delivery were classified as the infected group. Multivariate logistic regression analysis was used to assess the risk factors associated with UTI after ureteral stenting. Results: A total of 102 patients were enrolled into the study. Mean age was 30 years (interquartile range [IQR]: 26–33 years) and mean gestation age was 22 weeks (IQR: 18–28 weeks). UTI occurred in 21 patients (20.6%). Compared with noninfected patients, infected patients had a higher rate of positive urine culture (52.4% vs 13.6%, p = 0.000), kidney stones ≥10 mm (81% vs 35.8%, p = 0.000), residual stones after ureteral stenting (71.4% vs 43.2%, p = 0.021), and different surgical indications and gestational ages (18 vs 23 weeks, p = 0.00). Multifactor analysis showed that gestational age, positive urine culture (odds ratio [OR] = 6.233, 95% confidence interval [CI]: 1.830–21.227), and stones ≥10 mm (OR = 0.124, 95% CI: 0.031–0.495) were independent risk factors for UTI after ureteral stenting in patients with renal colic. In the infection group, Escherichia coli was the most commonly found organism (47.4%). Conclusions: Gestational age, positive urine culture before surgery, and stone ≥10 mm were risk factors for UTI after ureteral stenting in pregnant patients with renal colic. E. coli was the main pathogen of UTI after this procedure. Preoperative anti-infection treatment needs to be based on drugs that are sensitive to E. coli. [ABSTRACT FROM AUTHOR]

Keywords: drug delivery; photoactivated chemotherapy; photolysis; polyphotocages; Ru complexes EN drug delivery photoactivated chemotherapy photolysis polyphotocages Ru complexes 1 1 1 06/30/23 20230626 NES 230626 B Polyphotocages b In article number 2300780, Wen Sun, Peiyuan Wang, and co-workers report a drug delivery platform based on Ru complex containing polyphotocage which is prepared through photocage-polymer hybrid macromolecular engineering. Red light irradiation of the polyphotocage triggers the breakage of the coordination bond between the complexes and anticancer drugs, which releases the drugs for photochemotherapy precisely. Drug delivery, photoactivated chemotherapy, photolysis, polyphotocages, Ru complexes. [Extracted from the article]

Inside Back Cover: A Near-Infrared Light-Activated Photocage Based on a Ruthenium Complex for Cancer Phototherapy (Angew. The photocage was engineered into amphiphilic block copolymers, forming nanoparticles via self-assembly, which release the ruthenium complex-based photocages to inhibit tumor proliferation in vivo upon exposure to NIR light. Photocages, Ruthenium complex, NIR light, Polymer nanoparticles, Photocleavage reaction. [Extracted from the article]

Photocages, Ruthenium complex, NIR light, Polymer nanoparticles, Photocleavage reaction Keywords: Photocages; Ruthenium complex; NIR light; Polymer nanoparticles; Photocleavage reaction EN Photocages Ruthenium complex NIR light Polymer nanoparticles Photocleavage reaction 1 1 1 06/06/23 20230612 NES 230612 B A ruthenium-based photocage b that can be activated by 760 nm NIR light via single-photon pathway is reported by Xuezhao Li, Wen Sun et al. in their Research Article (e202218768). The photocage was engineered into amphiphilic block copolymers, forming nanoparticles via self-assembly, which release the ruthenium complex-based photocages to inhibit tumor proliferation in vivo upon exposure to NIR light. [Extracted from the article]

Lysine acetylation plays vital roles in the regulation of fundamental cellular processes, which is mediated by lysine acetyltransferases (KATs). Developing chemical biology probes for KAT activity detection is of important value in providing improved understanding of their biological functions. We reported a panel of “turn-on” fluorescent probes for sensitive and selective detection of KAT enzymatic activity through a simple mix-and-read format. Combined with bioorthogonal substrate labelling and click chemistry, these probes produced strong “turn-on” fluorescent signals in response to KAT-mediated acylation process. This chemical biology strategy diversifies the assay toolboxes to investigate functions and mechanisms of acetyltransferase enzymes. [ABSTRACT FROM AUTHOR]

Abstract: The side‐chain acetylation of lysine residues in histones and non‐histone proteins catalyzed by lysine acetyltransferases (KATs) represents a widespread posttranslational modification (PTM) in the eukaryotic cells. Lysine acetylation plays regulatory roles in major cellular pathways inside and outside the nucleus. In particular, KAT‐mediated histone acetylation has an effect on all DNA‐templated epigenetic processes. Aberrant expression and activation of KATs are commonly observed in human diseases, especially cancer. In recent years, the study of KAT functions in biology and disease has greatly benefited from chemical biology tools and strategies. In this Review, we present the past and current accomplishments in the design of chemical biology approaches for the interrogation of KAT activity and function. These methods and probes are classified according to their mechanisms of action and respective applications, with both strengths and limitations discussed. [ABSTRACT FROM AUTHOR]

Abstract: Die Seitenkettenacetylierung von Lysinresten in Histonen und Nicht‐Histon‐Proteinen durch Katalyse mit Lysin‐Acetyltransferasen (KATs) ist eine häufige posttranslationale Modifikation (PTM) in eukaryotischen Zellen. Die Lysin‐Acetylierung spielt eine regulatorische Rolle in wichtigen zellulären Prozessen. Einen besonderen Einfluss hat die KAT‐vermittelte Histon‐Acetylierung für alle durch DNA‐Template vermittelten epigenetischen Vorgänge. In den vergangenen Jahren hat sich gezeigt, dass das Studium von KAT‐Funktionen in biologischen und krankheitsbezogenen Prozessen in großem Maße von exakt konzipierten Strategien der chemischen Biologie profitiert. Hier werden Ansätze der chemischen Biologie zur Untersuchung der KAT‐Aktivität und ‐Funktion erläutert. Diese Methoden und Sonden werden entsprechend ihrem Wirkmechanismus und den jeweiligen Anwendungen eingeteilt, und ihre Stärken und Grenzen werden diskutiert. [ABSTRACT FROM AUTHOR]

Total syntheses of the erythrina alkaloids (±)-8-oxo-erythrinine and (±)-8-oxo-erythraline have been developed, based on a substrate-controlled intramolecular 6- exo- trig selective radical spirocyclization that establishes the quaternary center of the B-rings. An improved total synthesis of (±)-clivonine has also been reported, based on an intramolecular 6- endo-trig free-radical cyclization of a highly functionalized enamide, and a biomimetic ring-switch of a lycorine-type intermediate. These endo/ exo-selective sequences enabled us to rapidly assemble two different complex alkaloids from a common building block in an economical fashion. [ABSTRACT FROM AUTHOR]

Red light irradiation of polymer nanoparticles directly cleaves the Ru complex and produces SP 1 sp O SB 2 sb for photodynamic therapy, and sequentially, the generated SP 1 sp O SB 2 sb triggers the release of drugs for chemotherapy. This novel sequential dual-model release strategy creates a synergistic chemo-photodynamic therapy while minimizing the drug leakage. A Sequential Dual-Model Strategy Based on Photoactivatable Metallopolymer for On-Demand Release of Photosensitizers and Anticancer Drugs (Adv. Sci. 23/2021). [Extracted from the article]

Metal-free direct amidation of peptidyl thiol esters with α-amino acid esters in the presence of bis(trimethylsilyl) acetamide (BSA) has been developed. This general method provides convenient access to N-protected peptides in good yields under mild conditions and demonstrates a high tolerance to functionality. [ABSTRACT FROM AUTHOR]

Over the past decades, transition metal complexes have been successfully used in anticancer phototherapies. They have shown promising properties in many different areas including photo-induced ligand exchange or release, rich excited state behavior, and versatile biochemical properties. When encorporated into polymeric frameworks and become part of nanostructures, photoresponsive metallopolymer nanoparticles (MPNs) show enhanced water solubility, extended blood circulation and increased tumor-specific accumulation, which greatly improves the tumor therapeutic effects compared to low-molecule-weight metal complexes. In this review, we aim to present the recent development of photoresponsive MPNs as therapeutic nanomedicines. This review will summarize four major areas separately, namely platinum-containing polymers, zinc-containing polymers, iridium-containing polymers and ruthenium-containing polymers. Representative MPNs of each type are discussed in terms of their design strategies, fabrication methods, and working mechanisms. Current challenges and future perspectives in this field are also highlighted. [ABSTRACT FROM AUTHOR]

This article reports the synthesis and characterization of a novel self-immolative linker, based on thiocarbonates, which releases a free thiol upon activation via enzymes. We demonstrate that thiocarbonate self-immolative linkers can be used to detect the enzymes penicillin G amidase (PGA) and nitroreductase (NTR) with high sensitivity using absorption spectroscopy. Paired with modern thiol amplification technology, the detection of PGA and NTR were achieved at concentrations of 160 nM and 52 nM respectively. In addition, the PGA probe was shown to be compatible with both biological thiols and enzymes present in cell lysates. [ABSTRACT FROM AUTHOR]

Metal‐based drugs currently dominate the field of chemotherapeutic agents; however, achieving the controlled activation of metal prodrugs remains a substantial challenge. Here, we propose a universal strategy for the radiation‐triggered activation of metal prodrugs via nanosurface energy transfer (NSET). The core–shell nanoplatform (Ru‐GNC) is composed of gold nanoclusters (GNC) and ruthenium (Ru)‐containing organic–inorganic hybrid coatings. Upon X‐ray irradiation, chemotherapeutic Ru (II) complexes were released in a controlled manner through a unique NSET process involving the transfer of photoelectron energy from the radiation‐excited Ru‐GNCs to the Ru‐containing hybrid layer. In contrast to the traditional radiation‐triggered activation of prodrugs, such an NSET‐based system ensures that the reactive species in the tumor microenvironment are present in sufficient quantity and are not easily quenched. Additionally, ultrasmall Ru‐GNCs preferably target mitochondria and profoundly disrupt the respiratory chain upon irradiation, leading to radiosensitization by generating abundant reactive oxygen species. Consequently, Ru‐GNC‐directed radiochemotherapy induces immunogenic cell death, resulting in significant therapeutic outcomes when combined with the programmed cell death‐ligand 1 (PD−L1) checkpoint blockade. This NSET strategy represents a breakthrough in designing radiation‐triggered nanoplatforms for metal‐prodrug‐mediated cancer treatment in an efficient and controllable manner. [ABSTRACT FROM AUTHOR]

Metal‐based drugs currently dominate the field of chemotherapeutic agents; however, achieving the controlled activation of metal prodrugs remains a substantial challenge. Here, we propose a universal strategy for the radiation‐triggered activation of metal prodrugs via nanosurface energy transfer (NSET). The core–shell nanoplatform (Ru‐GNC) is composed of gold nanoclusters (GNC) and ruthenium (Ru)‐containing organic–inorganic hybrid coatings. Upon X‐ray irradiation, chemotherapeutic Ru (II) complexes were released in a controlled manner through a unique NSET process involving the transfer of photoelectron energy from the radiation‐excited Ru‐GNCs to the Ru‐containing hybrid layer. In contrast to the traditional radiation‐triggered activation of prodrugs, such an NSET‐based system ensures that the reactive species in the tumor microenvironment are present in sufficient quantity and are not easily quenched. Additionally, ultrasmall Ru‐GNCs preferably target mitochondria and profoundly disrupt the respiratory chain upon irradiation, leading to radiosensitization by generating abundant reactive oxygen species. Consequently, Ru‐GNC‐directed radiochemotherapy induces immunogenic cell death, resulting in significant therapeutic outcomes when combined with the programmed cell death‐ligand 1 (PD−L1) checkpoint blockade. This NSET strategy represents a breakthrough in designing radiation‐triggered nanoplatforms for metal‐prodrug‐mediated cancer treatment in an efficient and controllable manner. [ABSTRACT FROM AUTHOR]

Infectious endocarditis is a life-threatening disease, and diagnostics are urgently needed to accurately diagnose this disease especially in the case of prosthetic valve endocarditis. We show here that maltohexaose conjugated to indocyanine green (MH-ICG) can detect Staphylococcus aureus (S. aureus) infection in a rat model of infective endocarditis. The affinity of MH-ICG to S. aureus was determined and had a Km and Vmax of 5.4 μM and 3.0 X 10−6 μmol/minutes/108 CFU, respectively. MH-ICG had no detectable toxicity to mammalian cells at concentrations as high as 100 μM. The in vivo efficiency of MH-ICG in rats was evaluated using a right heart endocarditis model, and the accumulation of MH-ICG in the bacterial vegetations was 2.5 ± 0.2 times higher than that in the control left ventricular wall. The biological half-life of MH-ICG in healthy rats was 14.0 ± 1.3 minutes, and approximately 50% of injected MH-ICG was excreted into the feces after 24 hours. These data demonstrate that MH-ICG was internalized by bacteria with high specificity and that MH-ICG specifically accumulated in bacterial vegetations in a rat model of endocarditis. These results demonstrate the potential efficacy of this agent in the detection of infective endocarditis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel structures of bio-based monomer and network. • Green route based on CO 2 and bio-based resources. • Rapid self-healing and highly effective remolding. • Closed-loop recyclability of NIPU. • NIPU-based phase transition materials with latent heat reaching 128 J/g. Developing bio-based non-isocyanate polyurethanes (NIPUs) to replace petroleum-based conventional polyurethanes (PUs) plays an essential role in green production and relieving energy pressure. However, the synthesis of NIPUs using renewable resources, and recycling after reaching service time remain to be solved. Herein, a novel structural cross-linked NIPU network with closed-loop recyclability was prepared, which is derived from abundant lignin-derived and carbon dioxide (CO 2) resources. The obtained NIPUs with dual dynamic covalent bonds exhibit relatively low activation energy (70.34 kJ/mol) and remarkable remolding efficiency (∼100 %). Importantly, spiro bi-acetal structures in polymer chains impart closed-loop recyclability to the obtained NIPUs. The results showed that they can be degraded at room temperature followed by regeneration with nearly full recovery of properties. Moreover, bio-based NIPUs are used as supporting materials to produce phase change materials (PCMs) for the first time, and the latent heat reaches 128.2 J/g. The material has favorable form stability and is leakage-proof owing to ZnⅡ-carboxylates coordination interactions and stable cross-linked networks. This study demonstrates a method for the synthesis of closed-loop recyclable NIPUs from renewable resources, enriching synthetic diversity while providing an initial exploration of its potential as PCMs. [ABSTRACT FROM AUTHOR]

Genome-editing tools such as Cre recombinase (Cre), zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and most recently the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein system have revolutionized biomedical research, agriculture, microbial engineering, and therapeutic development. Direct delivery of genome editing enzymes, as opposed to their corresponding DNA and mRNA precursors, is advantageous since they do not require transcription and/or translation. In addition, prolonged overexpression is a problem when delivering viral vector or plasmid DNA which is bypassed when delivering whole proteins. This lowers the risk of insertional mutagenesis and makes for relatively easier manufacturing. However, a major limitation of utilizing genome editing proteins in vivo is their low delivery efficiency, and currently the most successful strategy involves using potentially immunogenic viral vectors. This lack of safe and effective non-viral delivery systems is still a big hurdle for the clinical translation of such enzymes. This review discusses the challenges of non-viral delivery strategies of widely used genome editing enzymes, including Cre recombinase, ZFNs and TALENs, CRISPR/Cas9, and Cas12a (Cpf1) in their protein format and highlights recent innovations of non-viral delivery strategies which have the potential to overcome current delivery limitations and advance the clinical translation of genome editing. Unlabelled Image [ABSTRACT FROM AUTHOR]

Enzymatische Reaktionen können endogene Nährstoffe eines Tumors verbrauchen und zytotoxische Spezies erzeugen und sind daher vielversprechende Werkzeuge für die Behandlung bösartiger Tumore. Inspiriert von der Natur, in der Enzyme in Membranen kompartimentiert sind, um eine hohe Reaktionseffizienz zu erreichen und biologische Prozesse von der Umwelt zu trennen, entwickelten wir liposomale Nanoreaktoren, die enzymatische Kaskadenreaktionen im wässrigen Nanoconfinement des Liposoms durchführen können. Die Nanoreaktoren hemmten das Tumorwachstum in vivo effektiv, indem sie Tumornährstoffe (Glukose und Sauerstoff) verbrauchten und hochgradig zytotoxische Hydroxylradikale (⋅OH) produzierten. Die Ko‐Kompartimentierung von Glukoseoxidase (GOx) und Meerrettichperoxidase (HRP) in Liposomen konnte die lokale Konzentration des Zwischenprodukts Wasserstoffperoxid (H2O2) sowie den Säuregrad aufgrund der Bildung von Gluconsäure durch GOx erhöhen. Sowohl H2O2 als auch der Säuregehalt beschleunigten die zweite Stufe der Reaktion durch HRP und verbesserten so die Gesamteffizienz der Kaskadenreaktion. Die biomimetische Kompartimentierung enzymatischer Tandemreaktionen in biokompatiblen Liposomen ist ein vielversprechender Weg für die Entwicklung katalytischer Nanomedikamente für die Antitumortherapie. [ABSTRACT FROM AUTHOR]

Enzymatic reactions can consume endogenous nutrients of tumors and produce cytotoxic species and are therefore promising tools for treating malignant tumors. Inspired by nature where enzymes are compartmentalized in membranes to achieve high reaction efficiency and separate biological processes with the environment, we develop liposomal nanoreactors that can perform enzymatic cascade reactions in the aqueous nanoconfinement of liposomes. The nanoreactors effectively inhibited tumor growth in vivo by consuming tumor nutrients (glucose and oxygen) and producing highly cytotoxic hydroxyl radicals (⋅OH). Co‐compartmentalization of glucose oxidase (GOx) and horseradish peroxidase (HRP) in liposomes could increase local concentration of the intermediate product hydrogen peroxide (H2O2) as well as the acidity due to the generation of gluconic acid by GOx. Both H2O2 and acidity accelerate the second‐step reaction by HRP, hence improving the overall efficiency of the cascade reaction. The biomimetic compartmentalization of enzymatic tandem reactions in biocompatible liposomes provides a promising direction for developing catalytic nanomedicines in antitumor therapy. [ABSTRACT FROM AUTHOR]

Review: data since 2005; 81 refs. [ABSTRACT FROM AUTHOR]

Objective: Intrahepatic cholestasis of pregnancy (ICP) may lead to sudden onset of stillbirth, which most likely is related to uteroplacental insufficiency and dysregulation of the fetal blood supply. The relaxing effect of corticotropin-releasing hormone (CRH) on blood vessels was measured to examine the role of CRH in the pathogenesis of ICP. Methods: Eighty normal pregnant women and 80 ICP patients were divided into four groups of 20 cases, respectively, each based on gestational age from week 34 to 37. Radioimmunoassay was used to measure CRH in plasma samples collected from all of the subjects. Results: Plasma CRH increased markedly from week 34 to 37 in both ICP and healthy patients, but the increase was lower in the ICP group. Plasma CRH was 322 ± 61 pg/ml in mild ICP cases at 37 weeks' compared to 1,066 ± 173 pg/ml in controls (p < 0.05), but only 218 ± 128 pg/ml in severe ICP (p < 0.05). Plasma CRH was significantly lower at all other measured time points in patients with severe ICP. In ICP patients, there was a negative correlation between plasma CRH and total bile acid (TBA). Conclusion: A limited increasing CRH level and negative correlation of CRH with TBA were unveiled in ICP patients. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A recent article in Angewandte Chemie discusses a new approach to cancer chemotherapy using radiation-triggered metal prodrug activation. The researchers, including Fangman Chen, Wen Sun, and Dan Shao, developed a strategy called nanosurface energy transfer to overcome the limitations of current methods. This technique showed promising results in combined cancer treatment. The article provides valuable insights for library patrons researching cancer treatment options. [Extracted from the article]

A recent article in Angewandte Chemie International Edition discusses a new approach to cancer chemotherapy using radiation-triggered metal prodrug activation. The researchers, Fangman Chen, Wen Sun, Dan Shao, and their colleagues, developed a strategy called nanosurface energy transfer to overcome the limitations of current methods. This technique showed promising results in combined cancer treatment. The article provides valuable insights for library patrons researching cancer treatment options. [Extracted from the article]

The expression of beta-lactamases in bacteria is a central cause of drug resistance. In this report, we present a beta-lactamase chemiluminescent probe, termed CCP, which can for the first time detect beta-lactamase activity via chemiluminescence and can detect beta lactamase with a sensitivity that is 4-orders of magnitude higher than the commercially available fluorescent lactamase substrate fluorocillin. [ABSTRACT FROM AUTHOR]

• Zinc salts of amino acids were developed as a new class of biocompatible NAs for PLLA. • The nucleation mechanism was explained by epitaxial nucleation based on lattice matching. • The difference in nucleation ability was attributed to the size and uniformity of NA particles. • Zinc d -phenylalaninate is a promising NA as bioresource additive of PLLA. The slow crystallization speed of poly(l -lactide) (PLLA) during practical processing results in the low degree of crystallinity and thus poor heat resistance of the molded articles, which prevents the wider applications of PLLA. The additive of biocompatible nucleating agents is one of the most effective means to promote the crystallization of PLLA, which synchronously preserves the bio-advantages of PLLA materials for biomedical and food applications. In this work, a series of zinc salts of amino acids, including nine kinds of l -amino acids and six types of d - or dl -configuration amino acids, was prepared and evaluated as nucleating agents (NAs) for PLLA. The nucleation effect of NAs was compared in terms of the nonisothermal melt crystallization peak temperature of PLLA with 1 wt% loading of NAs under a cooling rate of 10 °C/min. It was found that the nucleation effect of the zinc salts of amino acids depends on the ligand and its configuration. The nucleation mechanism and the difference of nucleation ability were also discussed and explained. Among these tested NAs, zinc d -phenylalaninate (Zn(d -Phe) 2) is the most effective one, which is comparable to the current outstanding NAs, evidenced by the crystallization peak temperature at 130 °C accompanying with the crystallization enthalpy up to 48 J/g. It is expected that Zn(d -Phe) 2 is a promising nucleating agent providing high nucleation activity in injection molding and extrusion processing of PLLA articles. [ABSTRACT FROM AUTHOR]

The intrinsic drawback of slow crystallization rate of poly(l-lactide) (PLLA) inevitably deteriorates its final properties of the molded articles. In this work, we proposed a new strategy towards poly(l-lactide) with enhanced crystallization rate by ring opening polymerization (ROP) of l-lactide (l-LA) catalyzed by biocompatible zinc salts of amino acids. For the first time we developed a one-pot facile method of zinc salts of amino acids acting dual roles of catalysis of l-LA polymerization and in situ nucleation of the as-prepared PLLA. Nine zinc salts of different amino acids, including three kinds of amino acids ligands (alanine, phenylalanine, and proline) with l/d-enantiomers and their equimolar racemic mixtures, were first prepared and tested as catalysts of l-LA polymerization. A partial racemization was observed for zinc salts of amino acids whereas no racemization was detected for the reference stannous octoate. The polymerization mechanism study showed that the interaction of zinc salts of amino acids and benzyl alcohol forms the actual initiator for l-LA polymerization. Isothermal crystallization kinetics analysis showed that the residual zinc salts of amino acids exhibited a significant nucleation effect on PLLA, evidenced by the promotion of the crystallization rate, depending on the amino acid ligand and its configuration. Meanwhile, the residual zinc salts of amino acids did not compromise the thermal stability of the pristine PLLA. [ABSTRACT FROM AUTHOR]

ERAAP is an intracellular amino-peptidase that plays a central role in determining the repertoire of peptides displayed by cells by MHC class I molecules, and dysfunctions in ERAAP are linked to a variety of diseases. There is therefore great interest in developing probes that can image ERAAP in cells. In this report we present a fluorescent probe, termed Ep, that can image ERAAP activity in live cells. Ep is composed of a 10 amino acid ERAAP substrate that has a donor quencher pair conjugated to it, composed of BODIPY and dinitro-toluene. Ep undergoes a 20-fold increase in fluorescence after ERAAP cleavage, and was able to image ERAAP activity in cell culture via fluorescence microscopy. In addition, we used Ep to develop a high throughput screen for ERAAP inhibitors, and screened an electrophile library containing 1460 compounds. From this Ep based screen we identified aromatic alkyne-ketone as a lead fragment that can irreversibly inhibit ERAAP activity. We anticipate numerous applications of Ep given its unique ability to image ERAAP within cells. [ABSTRACT FROM AUTHOR]

Acetylation of α-tubulin at Lys-40 is a potential biomarker for cognitive deficits in various neurological disorders. However, this key post-translational modification (PTM) has not been previously studied with mass spectrometry, due to the inadequate distribution of tryptic cleavage sites. Following peptic digestion, a surrogate sequence containing this key PTM site was identified and was found to be stable and quantitatively reproducible. A highly sensitive and specific SISCAPA-LC-MS method for quantitating rat brain tubulin acetylation was developed, validated, and applied, and only required a small amount of tissue (2.2 mg). This workflow includes peptic digestion, stable-isotope dilution, capture with antiacetylated peptide antibody bound on protein G beads, and quantitation using LC-MS. The method allowed a lower limit of quantitation at 2.50 pmol/mg and provided a linear range of 2.50-62.50 pmol/mg. Selectivity, intra and interday precision and accuracy were also validated. This method has been successfully applied in a preclinical study of organophosphate neurotoxicity, and we found that chronic exposure to chlorpyrifos led to a significant and persistent inhibition of brain tubulin acetylation. [ABSTRACT FROM AUTHOR]

[Display omitted] • GPCRs enable the body to perceive changes in the internal or external environment. • GPCRs are pharmacologically important targets for drug discovery. • Fluorescent probes can monitor the behavior of receptors in disease conditions. Scientists Robert J. Lefkowitz and Brian K. Kobilka won the Nobel Prize in 2012 for reporting a groundbreaking discovery that revealed a crucial member of the receptor family, the G-protein-coupled receptors (GPCRs). GPCRs are the collective names for over 1,000 seven-transmembrane receptors that are responsible for multiple types of cell signaling responses. When activated by various stimuli (e.g., photons and small molecules), GPCRs interact with intracellular proteins to mediate downstream signals. The role of GPCRs in physiological and pathological processes renders them candidate targets in the development of many drugs. Recent research on GPCR structural biology has considerably improved our knowledge of GPCR signaling. However, the precise binding mechanism of diverse ligands to GPCRs to generate unique signal transduction and the involvement of GPCRs in disease pathogenesis remain controversial. The designing of tools for studying the pharmacology of GPCRs is critical to identifying safer and more effective therapies. Various molecular probes for investigating receptor structure and function have proven essential in GPCR research. This review summarizes the physiological functions of some GPCRs and discusses the molecular design strategies, applications, and development status of small molecule organic fluorescence probes of various GPCRs in humans. [ABSTRACT FROM AUTHOR]