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Pyroptosis is an inflammatory cell death form triggered by protease-mediated truncation and release of the N-terminal pore-forming domain of the gasdermin (GSDM) family proteins in various cell types. We report a Bioorthogonally ACtivatable Base editor (BaseBAC) for

Purpose Mitotic spindle tissue protein 2A(MZT2A) has the properties of the core subunit of the γ-tubulin ring complex ( γ-TuRC ) and is involved in mediating the formation of bipolar spindles in mitosis. The lack of MZT2A will weaken the nucleation activity of microtubule ( MT ) and slow down the rate of cell proliferation. Although there is evidence that the expression of MZT2A plays a crucial role in the development of some tumors, there is still no research on MZT2A in pan-cancer. Therefore, we aim to explore the prognostic value of MZT2A in a variety of cancer types and to study its potential immune function. Methods This study was conducted with datasets from The Cancer Genome Atlas, the Cancer Cell Lineage Encyclopedia, Genotype Tissue Expression and the Human Protein Atlas. Bioinformatic methods were used to analyse the correlation between MZT2A expression levels in different tumours and survival prognosis, immune infiltration, immune checkpoint genes, immune regulatory genes, tumour mutational load (TMB), tumour neoantigens, homologous recombination defects (HRD), microsatellite instability (MSI), tumour stemness score and enrichment analysis regarding MZT2A. Results MZT2A was highly expressed in most tumours and was positively or negatively correlated with the prognosis of patients with different tumours. MZT2A was also found to be negatively correlated with the immune microenvironment, immune infiltrating cells, and immune-related genes in most tumours, and was strongly correlated with TMB in 11 tumours, MSI in 10 tumours, tumour neoantigens in 5 tumours, and HRD in 12 tumours, and MZT2A expression was significantly correlated with RNA stemness score (RNAss) in 24 tumours and DNA stemness score (DNAss) in 12 tumours. The results suggest that MZT2A can be used as a target or predictor of tumour therapy. the immunosuppressive effect of MZT2A in TME suggests that anti-MZT2A immunotherapy may be a new direction in cancer treatment. Conclusion MZT2A is involved in tumour development and can be used as a prognostic marker for a variety of tumours and as a target or predictor for tumour immunotherapy.

Bioorthogonal cleavage chemistry has been rapidly emerging as a powerful tool for manipulation and gain-of-function studies of biomolecules in living systems. While the initial bond formation-centered bioorthogonal reactions have been widely adopted for labeling, tracing, and capturing biomolecules, the newly developed bond cleavage-enabled bioorthogonal reactions have opened new possibilities for rescuing small molecules as well as biomacromolecules in living systems, allowing multidimensional controls over biological processes in vitro and in vivo. In this Outlook, we first summarized the development and applications of bioorthogonal cleavage reactions (BCRs) that restore the functions of chemical structures as well as more complex networks, including the liberation of prodrugs, release of bioconjugates, and in situ reactivation of intracellular proteins. As we embarked on this fruitful progress, we outlined the unmet scientific needs and future directions along this exciting avenue. We believe that the potential of BCRs will be further unleashed when combined with other frontier technologies, such as genetic code expansion and proximity-enabled chemical labeling., Bioorthogonal cleavage chemistry has been rapidly emerging as a powerful tool for manipulation and gain-of-function studies of biomolecules under living conditions.

The perfect absorption of electromagnetic waves has promoted many applications, including photovoltaics, radar cloaking, and molecular detection. Unlike conventional methods of critical coupling that require asymmetric boundaries or coherent perfect absorption that require multiple coherent incident beams, here we demonstrate single-beam perfect absorption in an on-chip cavity magnonic device without breaking its boundary symmetry. By exploiting magnon-mediated interference between two internal channels, both reflection and transmission of our device can be suppressed to zero, resulting in magnon-induced nearly perfect absorption (MIPA). Such interference can be tuned by the strength and direction of an external magnetic field, thus showing versatile controllability. Furthermore, the same multi-channel interference responsible for MIPA also produces level attraction (LA)-like hybridization between a cavity magnon polariton mode and a cavity photon mode, demonstrating that LA-like hybridization can be surprisingly realized in a coherently coupled system., Perfect absorption can be obtained for a single port device, or a device with multiple incident beams, but for multiport devices, the absorption is limited to around 50%. In this work, Rao et al. overcome this limitation, demonstrating near perfect absorption in a two port cavity magnon system.

With the development of battery technology, large-scale battery applications are increasing. In order to obtain a higher current and voltage level and improve the overall energy efficiency, batteries are connected in series and parallel. Bulk model is the most used model to simulate battery packs, and the simulation results of single cell are enlarged several times to represent a battery pack. But bulk model ignores inconsistency between the batteries, and when the current magnification is large, such as in the extreme fast charge scenario, this neglect cannot reflect the current distribution inside the battery pack. Our paper proposes a simplify algorithm based on equivalent circuit model, which applied for non-uniform series and parallel-connected batteries. This simplification can greatly improve simulation speed while maintaining accuracy under the consideration of inconsistency. More importantly, this algorithm applies to any complex circuit, regardless of how many series-parallel structure layers. With the proposed algorithm, Monte Carlo simulations were evaluated to obtain the influence of battery series and parallel number and normal distribution parameters on current distribution. Simulation results show that an increase in the number of series will reduce the inconsistency of the current distribution, and an increase in the number of parallel and an increase in the relative standard deviation of the normal distribution of the battery parameters will increase the inconsistency of the current distribution.

A catalytic system to synthesize α-amino amides from isocyanates and ketimines has been developed using visible light iridium photoredox catalysis via umpolung reactivity of ketimines. Cross-couplings between diverse ketimine and isocyanate substrates have been evaluated, affording the desired α-amino amide products in good yields. In addition, a metal-free catalytic system using perylene and N,N-diisopropylethylamine has been developed. Finally, single-step synthesis of the psychoactive drug benzodiazepine-2-one analogue from one of the coupling products has been achieved, indicating the great application potential of the synthetic method developed herein.

With the development of extreme fast charging technology, charging stations need to use energy storage stations to reduce the rising peak to average power ratio (PAPR). Lithium-ion capacitor (LIC) is a chemical power source that uses both Faraday process and non-Faraday process to store energy. Because of its attractive performance in terms of rate characteristics and chemical stability, it is suitable for some energy storage stations that consider both power density and energy density. It is important to describe the current-voltage characteristics of LIC to predict the charge and discharge efficiency in the early design of energy storage power stations. During the test, however, a full discharge or charge results in a high temperature rise, and the electrical model parameters near a specific temperature point cannot be accurately obtained. The short current pulses cannot stabilize the polarization. In this paper, a high-accuracy parameters identification method based on an improved Butler-Volmer-Equation-Based electrical model is used to summarize the phenomena caused by the rate of change of high-energy LIC. The accuracy of the method is tested under the dynamic stress condition test. The maximum voltage error is less than 2%. Energy efficiency calculation based on the used model is simulated by the design condition from the energy storage station of the Haizhu line in Guangzhou. The maximum error is less than 0.2%.

The controlled synthesis of calcium carbonate particles surface-functionalized with azido groups and its subsequent copper-catalyzed alkyne-azide cycloaddition (CuAAC) reactions with organocatalysts bearing alkyne anchors allowed the preparation of novel catalytic materials. A calcium carbonate-supported α,α-diarylprolinol silyl ether prepared in this manner catalyzes Michael addition of aldehydes to trans-β-nitrostyrenes with very high diastereo- and enantioselectivity. The immobilized catalyst can be recovered by simple decantation and reused. In addition, this heterogeneous catalytic system can also be adapted to continuous-flow operation, affording a five-fold productivity increase in comparison with the batch process.

The dynamic interactions between RNAs and proteins play crucial roles in regulating diverse cellular processes. Proteome-wide characterization of these interactions in their native cellular context remains desirable but challenging. Herein, we developed a photocatalytic crosslinking (PhotoCAX) strategy coupled with mass spectrometry (PhotoCAX-MS) and RNA sequencing (PhotoCAX-seq) for the study of the composition and dynamics of protein-RNA interactions. By integrating the blue light-triggered photocatalyst with a dual-functional RNA-protein crosslinker (RP-linker) and the phase separation-based enrichment strategy, PhotoCAX-MS revealed a total of 2044 RBPs in human HEK293 cells. We further employed PhotoCAX to investigate the dynamic change of RBPome in macrophage cells upon LPS-stimulation, as well as the identification of RBPs interacting directly with the 5' untranslated regions of SARS-CoV-2 RNA.

Inverse-electron-demand Diels-Alder (IEDDA) reaction has become the most attractive bioorthogonal reaction due to its advantages of good biocompatibility, high reaction specificity and fast reaction kinetics. Therefore, extensive studies have been conducted in terms of reaction mechanism, reactants synthesis, chemistry optimization, biological applications, etc ., for IEDDA ligation and cleavage reactions respectively. In this review, first of all, we introduce the development and optimizations of the IEDDA reaction, followed by its biological applications including biomolecules labeling, protein manipulation, activation, drug delivery, pharmacokinetics study, prodrug releasing, siRNA activation and solid phase RNA purification. At last, we envision that further studies and applications of the IEDDA reaction are in demand, and expect that by exploring more optimized reaction pairs and wider biological applications, the research area of bioorthogonal chemistry would rush into a new era.

Heterogeneous and self-distributed massive data has always been the core issue of knowledge openness and knowledge sharing. Because the library has a wide range of data sources, various types of resources, and many operating platforms, a large amount of heterogeneous data is stored in it, which greatly affects the sharing of resources in the library. Linked Data, as one of the implementation methods of Semantic Web technology, can promote the interconnection and interoperability of data in different fields and promote the opening and sharing of knowledge. Therefore, this paper proposes the construction of library resources based on Linked Data, aiming to study how to optimize the association rules of Linked Data in the context of the Semantic Web and promote the continuous realization of open sharing of information resources. Experiments show that, under the action of the optimized association rules, the support degree between data can reach 79%, and the data association degree can be increased to 84%.

With the deepening of the reform and development of higher education, many colleges and universities have taken the merger as an opportunity to promote the leap-forward development of their schools. Some colleges and universities that have not merged have also taken the newly-built campus as a new growth point to promote the rapid development of their schools. The library’s collection structure reflects a library’s document support ability, and the formation of the collection structure depends on the accumulation of document resources. Based on semantic web technology, this paper studies the construction of library literature resources. Among the institutions that choose to give priority to the development of library literature resources in the development strategy of main literature resources, the proportion of long-term preservation practice has reached 65.23%, compared with 57.42% of all other institutions. Due to the small number of samples, we cannot make a simple statistical inference, but it may reflect from the other side that the institutions that pay attention to digital resources are slightly more active in implementing preservation activities than other institutions. Based on the semantic web technology, the integrity and continuity of important documents and characteristic resources were kept and we paid attention to the collection of publications and academic documents related to our school. Under the double restriction of document resources guarantee, the acquisition behavior of guarantee systems at all levels will gradually strengthen self-control, actively establish the concept of coordination and sharing, and gradually move from randomness to standardization.

Spatiotemporally resolved dissection of subcellular proteome is crucial to our understanding of cellular functions in health and disease. We herein report a bioorthogonal and photocatalytic decaging-enabled proximity labeling strategy (CAT-Prox) for spatiotemporally resolved mitochondrial proteome profiling in living cells. Our systematic survey of the photocatalysts has led to the identification of Ir(ppy)2bpy as a bioorthogonal and mitochondria-targeting catalyst that allowed photocontrolled, rapid rescue of azidobenzyl-caged quinone methide as a highly reactive Michael acceptor for proximity-based protein labeling in mitochondria of live cells. Upon careful validation through in vitro labeling, mitochondria-targeting specificity, in situ catalytic activity as well as protein tagging, we applied CAT-Prox for mitochondria proteome profiling in living Hela cells as well as hard-to-transfect macrophage RAW264.7 cells with approximately 70% mitochondria specificity observed from up to 300 proteins enriched. Finally, CAT-Prox was further applied to the dynamic dissection of mitochondria proteome of macrophage cells upon lipopolysaccharide stimulation. By integrating photocatalytic decaging chemistry with proximity-based protein labeling, CAT-Prox offers a general, catalytic, and nongenetic alternative to the enzyme-based proximity labeling strategies for diverse live cell settings.

Spatiotemporally resolved dissection of subcellular proteome is crucial to our understanding of cellular functions in health and disease. Although enzyme-based proximity labeling strategies have emerged as powerful methods to portray the compartmentalized proteome of diverse organelles, current approaches still suffer from limitations such as the genetic operation that is not compatible with hard-to-transfect cells as well as overexpression of the fusion protein that may cause altered intracellular localization. We herein report a non-genetic strategy termed bioorthogonal and photocatalytic decaging-mediated proximity labeling (CAT-Prox) for spatiotemporally resolved proteome profiling in living cells. Our systematic survey of the organometallic photocatalysts has led to the identification of Ir(ppy)2bpy as a bioorthogonal and mitochondria-targeting complex that allowed photo-controlled, rapid rescue of azidobenzyl-caged quinone methide as a highly reactive Michael acceptor for proximity-based protein labelings. By coupling with quantitative mass spectrometry, CAT-Prox revealed the dynamic mitochondria proteome of cancer cells and macrophage cells under normal and stressed conditions. Furthermore, by targeting the photocatalyst to cell membrane receptors, CAT-Prox allowed microdomain proteome profiling on live cell surface. Together, CAT-Prox integrated the advantages of both enzymatic and chemical-based proximity labeling approaches as a general spatiotemporal proteomics platform for diverse subcellular spaces and cell types.

The expression of microRNAs (miRNAs) in the serum of B-cell acute lymphoblastic leukemia (B-ALL) patients is abnormal. However, the mechanism is not clear. Recent studies have shown that the methylation state of circulating cell-free DNA (cfDNA) is different between tumor patients and normal people. Therefore, we speculate that abnormal expression of miRNA may be associated with methylation in cfDNA. The aim of this study was to establish a fluorescently labeled B-ALL transplantation animal model, so as to explore the relationship between the serum miRNA expression and the related gene of cfDNA methylation. The expression levels of miRNAs were detected with quantitative real-time PCR (qRT-PCR). The cfDNA methylation levels of related gene were tested by bisulfite sequencing polymerase chain reaction (BSP). The result showed that the expression levels of miR-196b, miR-203, miR-34a-5p, miR-335-3p, miR-34b-5p, miR-615, miR-375-3p and miR-193b-5p in the serum of the model mice were significantly lower than those of the control (P

The expression of microRNAs (miRNAs) in the serum of B-cell acute lymphoblastic leukemia (B-ALL) patients is abnormal. Nevertheless, the underlying mechanism remains unclear. Recent studies indicate that the methylation state of circulating cell-free DNA (cfDNA) is different between cancer patients and healthy individuals. Therefore, we speculate that abnormal expression of miRNA may be associated with cfDNA methylation.A green fluorescent protein (GFP) labeled B-ALL transplantation animal model was established to explore the relationship between the miRNA expression and cfDNA methylation of the related gene. Quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of miRNAs. Further, cfDNA methylation levels of the related genes were evaluated through bisulfite sequencing polymerase chain reaction (BSP).The expression levels of miR-196b, miR-203, miR-34a-5p, miR-335-3p, miR-34b-5p, miR-615, miR-375-3p and miR-193b-5p in the serum of the model mice were significantly lower than those of the control group (P 0.05). The methylation level of miR-196b promoter in cfDNA of the model group was significantly lower than that of the control group (P 0.05), whereas no significant difference was noted in miR-203 promoter. The methylation levels of miR-196b and miR-203 coding region in cfDNA of the model group were significantly higher than those of the control group (P 0.05).These results showed that CpG island hypermethylation in the miRNA coding region of cfDNA is related to the low expression of miR-196b and miR-203.

In working condition of battery packs, the battery pack consistency has a great impact on the overall performance of the battery pack. In order to build an accurate battery pack model, we need to build a battery pack consistency model. Firstly, we used a Gaussian mixture model to fit the statistical characteristics of a single parameter. This method can accurately fit the skewness in the parameter distribution and fit the multi-peak characteristics that may appear. Secondly, we constructed a nonparametric battery pack consistency model using a Generative Adversarial Networks (GAN). Our consistency model can accurately describe the statistical characteristics of a single parameter and fits the correlation coefficient between parameters. The battery pack model substituted into the GAN-generated battery parameters exhibits a very high similarity to the experimental data. The relative errors of the simulation results are less than 0.6 % for the terminal voltage and less than 0.3 % for the energy utilization efficiency (EUE), proving the advantages of the GAN consistency model in fitting the distribution of the battery parameters. Finally, we implemented the GAN consistency model in an embedded system with limited computing resources, which proves that our proposed model has the ability to run normally on existing BMS.

Under photoredox catalysis conditions, the conventional electrophilic reactivity of ketimines is inverted to generate nucleophilic species. As a result, chemoselective cross-electrophile couplings between aldehydes and ketimines are achieved via umpolung reactivity of ketimines to furnish amino alcohols (44 examples with good to excellent yields). To illustrate the utility of the amino alcohol products, 1,2-dihydroindol-3-one-based fluorophores are easily synthesized using the coupling products. Finally, a plausible reaction pathway is discussed.

Adverse drug reactions (ADRs) restrict the maximum doses applicable in chemotherapy, which leads to failure in cancer treatment. Various approaches, including nano-drug and prodrug strategies aimed at reducing ADRs, have been developed, but these strategies have their own pitfalls. A renovated strategy for ADR reduction is urgently needed. Here, we employ an enzymatic supramolecular self-assembly process to accumulate a bioorthogonal decaging reaction trigger inside targeted cancer cells, enabling spatiotemporally controlled, synergistic prodrug activation. The bioorthogonally activated prodrug exhibits significantly enhanced potency against cancer cells compared with normal cells. This prodrug activation strategy further demonstrates high tumour inhibition efficacy with satisfactory biocompatibility, pharmacokinetics, and safety in vivo. We envision that integration of enzymatic and bioorthogonal reactions will serve as a general small-molecule-based strategy for alleviation of ADRs in chemotherapy., The side effects of cancer drugs limit their utility. Here, the authors developed a method in which an inactive (prodrug) version of the cancer drug doxorubicin enters tumour cells and then gets activated inside the cells upon a trigger facilitated by enzyme-instructed supramolecular self-assembly.

Solid support-enabled site isolation has previously allowed to use paraldehyde as an acetaldehyde surrogate in aldol reactions. However, only electron-poor aldehydes were tolerated by the system. Herein, we show that the temporary conversion of benzaldehyde into η6-benzaldehyde Cr(CO)3 circumvents this limitation. Asymmetric synthesis of (R)-Phenoperidine, as well as formal syntheses of (R)-Fluoxetine and (R)-Atomoxetine, illustrate the benefits of this strategy.

A novel carbanionic reactivity of imines mediated by photoredox catalysis is demonstrated. The umpolung imine reactivity is exemplified by proton abstraction from water as a key step in the reduction of benzophenone ketimines to amines (up to 98% yield). Deuterium is introduced into amines efficiently using D2O as an inexpensive deuterium source (≥95% D ratio). The mechanism of this unusual transformation is probed.

The science and art of preventing and managing disease and prolonging life is dependent on advances in medicine, biology, and biochemistry. Many of these advances will involve interactions of small molecules with biological entities. As such, they will rely on the efficient synthesis of active compounds with very high stereochemical purity. Although enantioselective reactions are important in this regard, most stereocenters in complex molecule synthesis are installed in diastereoselective reactions. Perhaps the most well-known diastereoselective C-C bond-forming reaction is the addition of nucleophiles to carbonyl groups with α- or β-stereogenic centers. Diastereoselective additions of organometallic reagents to protected chiral α- and β-hydroxy aldehydes and ketones are described by either Cram chelation or Felkin-Anh models, which are protecting group (PG)-dependent. Small PGs (X = OMOM, OBn, etc.) favor Cram chelation, wherein both the carbonyl group and the O-PG bind to the Lewis acidic metal, providing syn diol motifs. In contrast, silyl PGs, with the OSiR