Coaxial fiber organic electrochemical transistor with high transconductance

Fiber organic electrochemical transistors(OECTs)have received extensive attention in wearable and implantable biosensors because of their high flexibility and low working voltage.However,the transconductance of fiber OECTs is much lower compared with the planar counterparts,leading to low sensitivity.Here,we developed fiber OECTs in a coaxial configuration with microscale channel length to achieve the highest transconductance of 135 mS,which is one to two orders of magnitude higher than that of the state-of-the-art fiber OECTs.Coaxial fiber OECT based sensors showed high sensitivities of 12.78,20.53 and 3.78 mA/decade to ascorbic acid,hydrogen peroxide and glucose,respectively.These fiber OECTs were woven into a fabric to monitor the glucose in sweat during exercise and implanted in mouse brain to detect ascorbic acid.This coaxial architectural design offers an effective way to promote the performance of fiber OECTs and realize highly sensitive detection of biochemicals.

Alternative splicing of a carboxyl/choline esterase gene enhances the fenpropathrin tolerance of Tetranychus cinnabarinus

Detoxification plays a crucial role in agricultural pests to withstand pesticides,and cytochrome P450s,carboxyl/choline esterases(CCEs),and glutathione-S-transferases are the main proteins responsible for their detoxification ability.The activity of CCEs can be upregulated,downregulated,or modified by mutation.However,few studies have examined the role of alternative splicing in altering the properties of CCEs.We identified 2 variants of TcCCE23 in Tetranychus cinnabarinus:a long version(CCE23-V1)and a short version that is 18 nucleotides shorter than CCE23-V1(CCE23-V2).Whether splicing affects the activity of TcCCE23 remains unclear.Overexpression of CCE23-V2 in fenpropathrin-resistant T.cinnabarinus revealed that splicing affected the detoxification of fenpropathrin by CCE23-V2.The mortality of mites was significantly higher when the expression of CCE23-V2 was knocked down(43.2%±3.3%)via injection of CCE23-dsRNA(double-stranded RNA)compared with the control group injected with green fluorescent protein-dsRNA under fenpropathrin exposure;however,the downregulation of CCE23-V1(61.3%±6.3%)by CCE23-small interfering RNA had no such effect,indicating CCE23-V2 plays a greater role in xenobiotic metabolism than CCE23-V1.The tolerance of flies overexpressing CCE23-V2 to fenpropathrin(50%lethal dose[LD_(50)]=19.47μg/g)was significantly higher than that of Gal4/UAS-CCE23-V1 transgenic flies(LD_(50)=13.11μg/g).Molecular docking analysis showed that splicing opened a“gate”that enlarges the substrate binding cavity of CCE23-V2,might enhance the ability of CCE23-V2 to harbor fenpropathrin molecules.These findings suggest that splicing might enhance the detoxifying capability of TcCCE23.Generally,our data improve the understanding of the diversity and complexity of the mechanisms underlying the regulation of CCEs.

PROTACs: great opportunities for academia and industry

Although many kinds of therapies are applied in the clinic,drug-resistance is a major and unavoidable problem.Another disturbing statistic is the limited number of drug targets,which are presently only 20–25%of all protein targets that are currently being studied.Moreover,the focus of current explorations of targets are their enzymatic functions,which ignores the functions from their scaffold moiety.As a promising and appealing technology,PROteolysis TArgeting Chimeras(PROTACs)have attracted great attention both from academia and industry for finding available approaches to solve the above problems.PROTACs regulate protein function by degrading target proteins instead of inhibiting them,providing more sensitivity to drug-resistant targets and a greater chance to affect the nonenzymatic functions.PROTACs have been proven to show better selectivity compared to classic inhibitors.PROTACs can be described as a chemical knockdown approach with rapidity and reversibility,which presents new and different biology compared to other gene editing tools by avoiding misinterpretations that arise from potential genetic compensation and/or spontaneous mutations.PRTOACs have been widely explored throughout the world and have outperformed not only in cancer diseases,but also in immune disorders,viral infections and neurodegenerative diseases.Although PROTACs present a very promising and powerful approach for crossing the hurdles of present drug discovery and tool development in biology,more efforts are needed to gain to get deeper insight into the efficacy and safety of PROTACs in the clinic.More target binders and more E3 ligases applicable for developing PROTACs are waiting for exploration.

Taxonomic and functional variations in the microbial community during the upgrade process of a full-scale landfill leachate treatment plant-from conventional to partial nitrification-denitrification

Because of the low access to biodegradable organic substances used for denitrification,the partial nitrification-denitrification process has been considered as a low-cost,sustainable alternative for landfill leachate treatment.In this study,the process upgrade from conventional to partial nitrificationdenitrification was comprehensively investigated in a full-scale landfill leachate treatment plant(LLTP).The partial nitrification-denitrification system was successfully achieved through the optimizing dissolved oxygen and the external carbon source,with effluent nitrogen concentrations lower than 150 mg/L.Moreover,the upgrading process facilitated the enrichment of Nitrosomonas(abundance increased from 0.4%to 3.3%),which was also evidenced by increased abundance of amoA/B/C genes carried by Nitrosomonas.Although Nitrospira(accounting for 0.1%-0.6%)was found to stably exist in the reactor tank,considerable nitrite accumulation occurred in the reactor(reaching 98.8 mg/L),indicating high-efficiency of the partial nitrification process.Moreover,the abundance of Thauera,the dominant denitrifying bacteria responsible for nitrite reduction,gradually increased from 0.60%to 5.52%during the upgrade process.This process caused great changes in the microbial community,inducing continuous succession of heterotrophic bacteria accompanied by enhanced metabolic potentials toward organic substances.The results obtained in this study advanced our understanding of the operation of a partial nitrification-denitrification system and provided a technical case for the upgrade of currently existing full-scale LLTPs.

Whole-brain patterns of the presynaptic inputs and axonal projections of BDNF neurons in the paraventricular nucleus

Brain-derived neurotrophic factor (BDNF) plays a crucial role in human obesity. Yet, the neural circuitry supporting the BDNF-mediated control of energy homeostasis remains largely undefined. To map key regions that might provide inputs to or receive inputs from the paraventricular nucleus (PVN) BDNF neurons, a key type of cells in regulating feeding and thermogenesis, we used rabies virus-based transsynaptic labeling and adeno-associated virus based anterograde tracing techniques to reveal their whole-brain distributions. We found that dozens of brain regions provide dense inputs to or receive dense inputs from PVN BDNF neurons, including several known weight control regions and several novel regions that might be functionally important for the BDNF-mediated regulation of energy homeostasis.Interestingly, several regions show very dense reciprocal connections with PVN BDNF neurons, including the lateral septum, the preoptic area, the ventromedial hypothalamic nucleus, the paraventricular thalamic nucleus, the zona incerta, the lateral parabrachial nucleus, the subiculum, the raphe magnus nucleus, and the raphe pallidus nucleus. These strong anatomical connections might be indicative of important functional connections. Therefore, we provide an outline of potential neural circuitry mediated by PVN BDNF neurons, which might be helpful to resolve the complex obesity network.

GPR54 deficiency reduces the Treg population and aggravates experimental autoimmune encephalomyelitis in mice

GPR54 is highly expressed in the central nervous system and plays a crucial role in pubertal development. However, GRP54 is also expressed in the immune system, implying possible immunoregulatory functions. Here we investigated the role of GPR54 in T cell and immune tolerance. GPR54 deficiency led to an enlarged thymus, an increased number of thymocytes, and altered thymic micro-architecture starting around puberty, indicating GPR54 function in T-cell development through its regulatory effect on the gonadal system. However, flow cytometry revealed a significant reduction in the peripheral regulatory T cell population and a moderate decrease in CD4 single-positive thymocytes in prepubertal Gpr54^(-/-) mice. These phenotypes were confirmed in chimeric mice with GPR54 deficient bone marrow-derived cells. In addition, we found elevated T cell activation in peripheral and thymic T cells in Gpr54^(-/-) mice. When intact mice were immunized with myelin oligodendrocyte glycoprotein, a more severe experimental autoimmune encephalomyelitis(EAE) developed in the Gpr54^(-/-) mice. Interestingly, aggravated EAE disease was also manifested in castrated and bone marrow chimeric Gpr54^(-/-) mice compared to the respective wild-type control,suggesting a defect in self-tolerance resulting from GPR54 deletion through a mechanism that bypassed sex hormones. These findings demonstrate a novel role for GPR54 in regulating self-tolerant immunity in a sex hormone independent manner.

Design,synthesis,and biological evaluation of multiple targeting antimalarials

Malaria still threatens global health seriously today.While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors,multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance.Here,we performed a structure-based drug design on mitochondrial respiratory chain of Plasmodium falciparum and identified an extremely potent molecule,RYL-581,which binds to multiple protein binding sites of P.falciparum simultaneously(allosteric site of type Ⅱ NADH dehydrogenase,Q_(o) and Q_(i) sites of cytochrome bc_(1)).Antimalarials with such multiple targeting mechanism of action have never been reported before.RYL-581 kills various drug-resistant strains in vitro and shows good solubility as well as in vivo activity.This structurebased strategy for designing RYL-581 from starting compound may be helpful for other medicinal chemistry projects in the future,especially for drug discovery on membrane-associated targets.

Chitosan based antibacterial composite materials for leather industry: a review

Chitosan is an amorphous translucent substance with a structural unit similar to the polysaccharide structure of the extracellular matrix,It has good antibacterial,biocompatible,and degradable properties.It has important application value in leather,water treatment,medicine,food and other fields,so chitosan and its modified products have received widespread attention.This article reviewed the preparation methods of chitosan-based antibacterial composites in recent years,including chitosan/collagen,chitosan/graphene,chitosan/tannic acid,and chitosan/polyethylene glycol composite materials,elaborates their modification methods and antibacterial mechanism were reviewed in detail,and its applications in the leather industry as antibacterial auxiliaries and water treatment antibacterial adsorption materials were discussed.Finally,the future development and challenges of chitosan-based composite materials in the leather industry were forecasted.

外源基因表达造成的群体感应细菌生存压力的建模分析（英文）

外源基因的表达及其对细菌种群的影响对于群体感应系统和合成生物学产业的研究具有重要意义。然而,人们对于表达外源蛋白的细菌本身的行为模式仍然知之甚少。为了研究菌落生长和外源基因表达的过程究竟受到哪些因素的影响,文中测量了受Lux类受体调控的外源基因在N-酰基高丝氨酸内酯(N-acyl homoserine lactone,N-AHL)信号分子诱导下的表达,并模拟了其对细菌种群动态的影响。文中建立了一个假设性的数学模型,对信号分子诱导表达下细菌种群生长受影响的现象进行了分析。先前的研究通常将细菌种群生长受群体感应系统影响的现象归咎于合成群体感应信号分子的消耗与N-AHL信号分子的毒性,文中提供了对于这种生存压力的另一种可能的解释。

Synthesis of Quaternary Carbon-Centered Benzoindolizidinones via Novel Photoredox-Catalyzed Alkene Aminoarylation: Facile Access to Tylophorine and Analogues

Photoredox-catalyzed aminoarylation and thioami-nation of unactivated alkenes have been developed,providing novel synthetic routes to access synthe-tically challenging quaternary carbon-centered benzoindolizidinones and trifluoromethylthiolated piperidines using readily available starting materials.Notably,these transformations were enabled by merging amidyl radical generation from N-alkyl benzamides with oxidant incorporation.Density functional theory calculations were performed to understand the reaction mechanism and to rationa-lize the regioselectivities.Moreover,the newly deve-loped catalytic aminoarylation provided a convenient synthetic route for natural product tylophorine and its gem-dimethyl analogues with greatly improved drug-like properties such as enhanced solubility and stability.