Obrienhaas5414

We believe this work provides a general method for developing high-performance, cost-effective, and durable thermocells and also expands the applicability of thermocells in wearable systems.Serotonin is a key neurotransmitter involved in numerous physiological processes and serves as an important precursor for manufacturing bioactive indoleamines and alkaloids used in the treatment of human pathologies. In humans, serotonin sensing and signaling can occur by 12 G protein-coupled receptors (GPCRs) coupled to Gα proteins. In yeast, human serotonin GPCRs coupled to Gα proteins have previously been shown to function as whole-cell biosensors of serotonin. However, systematic characterization of serotonin biosensing modalities between variant serotonin GPCRs and application thereof for high-resolution serotonin quantification is still awaiting. To systematically assess GPCR signaling in response to serotonin, we characterized reporter gene expression at two different pHs of a 144-sized library encoding all 12 human serotonin GPCRs in combination with 12 different Gα proteins engineered in yeast. From this screen, we observed changes in the biosensor sensitivities of >4 orders of magnitude. Furthermore, adopting optimal biosensing designs and pH conditions enabled high-resolution high-performance liquid chromatography-validated sensing of serotonin produced in yeast. Lastly, we used the yeast platform to characterize 19 serotonin GPCR polymorphisms found in human populations. While major differences in signaling were observed among the individual polymorphisms when studied in yeast, a cross-comparison of selected variants in mammalian cells showed both similar and disparate results. Taken together, our study highlights serotonin biosensing modalities of relevance to both biotechnological and potential human health applications.The protein-ligand scoring function plays an important role in computer-aided drug discovery and is heavily used in virtual screening and lead optimization. In this study, we developed a new empirical protein-ligand scoring function with amino acid-specific interaction components for hydrogen bond, van der Waals, and electrostatic interactions. In addition, hydrophobic, π-stacking, π-cation, and metal-ligand interactions are also included in the new scoring function. To better evaluate the performance of the AA-Score, we generated several new test sets for evaluation of scoring, ranking, and docking performances, respectively. Extensive tests show that AA-Score performs well on scoring, docking, and ranking as compared to other widely used traditional scoring functions. The performance improvement of AA-Score benefits from the decomposition of individual interaction into amino acid-specific types. To facilitate applications, we developed an easy-to-use tool to analyze protein-ligand interaction fingerprint and predict binding affinity using the AA-Score. The source code and associated running examples can be found at https//github.com/xundrug/AA-Score-Tool.Target-enabled bioorthogonal reaction and self-assembly of a small-molecule probe into supramolecules have shown promise for molecular imaging. In this paper, we report a new stimuli-responsive bioorthogonal reaction scaffold (SF) for controlling in situ self-assembly by engineering the condensation reaction between 2-cyanobenzothiazole and cysteine. For probes with the SF scaffold, intramolecular cyclization took place soon after activation, which could efficiently outcompete free cysteine even at a low concentration and result in efficient aggregation in the target. Through integration with different enzyme-responsive substrates and an ammoniomethyl-trifluoroborate moiety (AmBF3), two radioactive positron emission tomography (PET) tracers, [18F]SF-DEVD and [18F]SF-Glu, were designed, which showed high stability under physiological conditions and could produce clear PET signal in tumors to detect enzyme activity (e.g., caspase-3, γ-glutamyltranspeptidase) timely and accurately. Our results demonstrated that the scaffold SF could serve as a general molecular scaffold in the development of smart PET tracers for noninvasive imaging of enzyme activity, which could contribute to tumor detection and treatment efficacy evaluation.This study examines the atomic confinement of commercial Pt/C electrocatalysts. While a high electrocatalytic activity for the oxygen reduction reaction is important for proton-exchange membrane fuel cell (PEMFC) performance, the high stability of the electrocatalyst is essential for real applications under harsh operating conditions. The demands necessitate the development of advanced electrocatalysts that are resistant to corrosion. A combination of diazonium chemistry with Cu electrodeposition permits the selective protection of the carbon surface of the commercial Pt/C to prevent corrosion while improving wettability and ionic transfer. The resulting electrocatalysts exhibit an exceptional ORR stability after accelerated stress testing (AST) with a 250% improvement in comparison with unprotected commercial Pt/C. This novel electrochemical pathway provides a much-needed boost to carbon-based catalytic supports, which still face several stability challenges in energy applications in a harsh environment.Multiple antibiotics and mycotoxins usually simultaneously exist in foods, which poses a serious threat to human health. How to detect them in one test with high sensitivity and fidelity is challenging. In this study, we develop a dual readout lateral flow immunodetection platform that can quantitatively detect five kinds of antibiotics and five kinds of mycotoxins within one sample. The platform is composed of a chip and a portable readout instrument where gold nanoparticle (AuNP)-based and chemiluminescence immunoassays could be performed to reach a maximum throughput of 220 analytes in one setting. For a rapid screen, qualitative analysis by detecting the color change of the deposited AuNPs on the chip could be realized. For quantitative results, chemiluminescence imaging and analysis can be completed within 15 min. Apart from the high throughput and high efficiency, this platform has a high detection sensitivity. For instance, the limit of detection (LOD) for thiamphenicol (a representative antibiotic) and fumonisins B1 (a representative mycotoxin) is 8 times and 40 times lower than those of the previously reported methods, respectively. Thus, this dual readout immunodetection platform is promising as a universal device for rapid and quantitative detection of multiple analytes with high throughput, high sensitivity, and high fidelity.De novo molecule design algorithms often result in chemically unfeasible or synthetically inaccessible molecules. A natural idea to mitigate this problem is to bias these algorithms toward more easily synthesizable molecules using a proxy score for synthetic accessibility. However, using currently available proxies can still result in highly unrealistic compounds. Here, we propose a novel approach, RetroGNN, to estimate synthesizability. First, we search for routes using synthesis planning software for a large number of random molecules. This information is then used to train a graph neural network to predict the outcome of the synthesis planner given the target molecule, in which the regression task can be used as a synthesizability scorer. We highlight how RetroGNN can be used in generative molecule-discovery pipelines together with other scoring functions. We evaluate our approach on several QSAR-based molecule design benchmarks, for which we find synthesizable molecules with state-of-the-art scores. Compared to the virtual screening of 5 million existing molecules from the ZINC database, using RetroGNNScore with a simple fragment-based de novo design algorithm finds molecules predicted to be more likely to possess the desired activity exponentially faster, while maintaining good druglike properties and being easier to synthesize. Importantly, our deep neural network can successfully filter out hard to synthesize molecules while achieving a 105 times speedup over using retrosynthesis planning software.Owing to the instability of organic materials, an inorganic perovskite solar cell (PSC) attracts much attention in recent years. However, the instability of phase and overmuch traps lead to the inferior performance of inorganic perovskite solar cell, a high performance inorganic PSC is desirable. The element of cerium possesses a suitable chemical and physcial properties to substitute lead. We utilize cerium to partially substitute lead, a lead-cerium (Pb-Ce) bimetal based inorganic PSC is successfully achieved to modify the stability of PSC, the CsPb0.85Ce0.1I3 based PSC exhibits a champion PCE (power conversion efficiency) of 17.57%, and the tolerance of thermal, illumination, and environmental are enhanced among 10-20%. The enhanced PCE is ascribed to the structure of lead-cerium (Pb-Ce) bimetal perovskite absorbing layers and high quality of perovskite film.N-l-Lactoyl phenylalanine (N-l-lactoyl-Phe) has been identified as a taste-active contributor in many fermented foods. However, its preparation, taste property, and content in foodstuffs are little known to date. In the current study, two preparation technologies of N-l-lactoyl-Phe including heating and enzymatic methods were investigated. Other investigations include its taste property and quantification in several fermented foods. The results indicated that the heating preparation and enzymatic preparation only produced N-l-lactoyl-Phe instead of N-d-lactoyl-Phe in the presence of l-lactate/d-lactate and l-phenylalanine (Phe). A high yield (58.0% ± 0.7%) of N-l-lactoyl-Phe was achieved under the following conditions Phe, lactate, CaO, and water at molar ratios of 180.39 kept at 100 °C for 3 h. With nine enzymes, a maximum yield of 21.2% ± 0.3% was achieved in the aqueous solution under mild operating conditions 0.18 M Phe, 0.90 M lactate, 5 g/L Debitrase HYW 20, pH 8, and 55 °C for 24 h. The sensory evaluation revealed that N-l-lactoyl-Phe in water enhanced the salty and umami intensity. It also enhanced the thickness, mouthfulness, and continuity of salt solution, model broth, and chicken broth, revealing that N-l-lactoyl-Phe was a kokumi-active compound. The kokumi thresholds of N-l-lactoyl-Phe in these solutions were 50, 50, and 25 mg/L, respectively. N-l-Lactoyl-Phe was quantified in traditional Chinese fermented foods as 30.12 ± 0.28 mg/kg in preserved pickles, 14.11 ± 0.14 mg/kg in soybean paste, 4.87 ± 0.16 mg/kg in fermented bean, 0.71 ± 0.11 mg/kg in rice vinegar, and 20.34 ± 0.18 mg/kg in soy sauce. These results revealed the potential of N-l-lactoyl-Phe as a taste enhancer, presenting a new opportunity for the food industry.The activation of the cyclic GMP-AMP synthase-stimulator of interferon gene (STING) pathway has been associated with the pathogenesis of many autoimmune and inflammatory disorders, and small molecules targeting STING have emerged as a new therapeutic strategy for the treatment of these diseases. While several STING inhibitors have been identified with potent anti-inflammatory effects, we would like to explore STING degraders based on the proteolysis-targeting chimera (PROTAC) technology as an alternative strategy to target the STING pathway. Thus, we designed and synthesized a series of STING protein degraders based on a small-molecule STING inhibitor (C-170) and pomalidomide (a CRBN ligand). These compounds demonstrated moderate STING-degrading activities. Among them, SP23 achieved the highest degradation potency with a DC50 of 3.2 μM. Importantly, SP23 exerted high anti-inflammatory efficacy in a cisplatin-induced acute kidney injury mouse model by modulating the STING signaling pathway. Taken together, SP23 represents the first PROTAC degrader of STING deserving further investigation as a new anti-inflammatory agent.