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Bacterial adaptive immunity uses CRISPR (clustered regularly interspaced short palindromic repeats)–associated (Cas) proteins together with CRISPR transcripts for foreign DNA degradation. In type II CRISPR-Cas systems, activation of Cas9 endonuclease for DNA recognition upon guide RNA binding occurs by an unknown mechanism. Crystal structures of Cas9 bound to single-guide RNA reveal a conformation distinct from both the apo and DNA-bound states, in which the 10-nucleotide RNA \"seed\" sequence required for initial DNA interrogation is preordered in an A-form conformation. This segment of the guide RNA is essential for Cas9 to form a DNA recognition–competent structure that is poised to engage double-stranded DNA target sequences. We construe this as convergent evolution of a \"seed\" mechanism reminiscent of that used by Argonaute proteins during RNA interference in eukaryotes.

Mycotoxins are toxic secondary metabolites produced by various types of fungi that are known to contaminate various food products; their presence in the food chain poses significant risks to human and animal health and leads to enormous economic losses in the food and feed industry worldwide. Ensuring food safety and quality by detoxifying mycotoxin is therefore of paramount importance. Several procedures to control fungal toxins have been extensively investigated, such as preventive measures, physical and chemical methods, and biological strategies. In recent years, microbial degradation of mycotoxins has attracted much attention due to its reliability, efficiency, and cost-effectiveness. Notably, bacterial species from the Bacillus genus have emerged as promising candidates for mycotoxin decontamination owing to their diverse metabolic capabilities and resilience in harsh environmental conditions. This review manuscript aims to provide a summary of recent studies on the biodegradation of fungal toxins by Bacillus bacteria, thereby illustrating their potential applications in the development of mycotoxin-degrading products.

Cardiac hypertrophy (CH) is an important characteristic in heart failure development. Chlorogenic acid (CGA), a crucial bioactive compound from honeysuckle, is reported to protect against CH. However, its underlying mechanism of action remains incompletely elucidated. Therefore, this study aimed to explore the mechanism underlying the protective effect of CGA on CH. This study established a CH model by stimulating AC16 cells with isoproterenol (Iso). The observed significant decrease in cell surface area, evaluated through fluorescence staining, along with the downregulation of CH-related markers, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC) at both mRNA and protein levels, provide compelling evidence of the protective effect of CGA against isoproterenol-induced CH. Mechanistically, CGA induced the expression of glycogen synthase kinase 3β (GSK-3β) while concurrently attenuating the expression of the core protein β-catenin in the Wnt/β-catenin signaling pathway. Furthermore, the experiment utilized the Wnt signaling activator IM-12 to observe its ability to modulate the impact of CGA pretreatment on the development of CH. Using the Gene Expression Omnibus (GEO) database combined with online platforms and tools, this study identified Wnt-related genes influenced by CGA in hypertrophic cardiomyopathy (HCM) and further validated the correlation between CGA and the Wnt/β-catenin signaling pathway in CH. This result provides new insights into the molecular mechanisms underlying the protective effect of CGA against CH, indicating CGA as a promising candidate for the prevention and treatment of heart diseases.

The two‐phase reaction of Na3V2(PO4)3 – Na1V2(PO4)3 in Na3V2(PO4)3 (NVP) is hindered by low electronic and ionic conductivity. To address this problem, a surface‐N‐doped NVP encapsulating by N‐doped carbon nanocage (N‐NVP/N‐CN) is rationally constructed, wherein the nitrogen is doped in both the surface crystal structure of NVP and carbon layer. The surface crystal modification decreases the energy barrier of Na+ diffusion from bulk to electrolyte, enhances intrinsic electronic conductivity, and releases lattice stress. Meanwhile, the porous architecture provides more active sites for redox reactions and shortens the diffusion path of ion. Furthermore, the new interphase of Na2V2(PO4)3 is detected by in situ XRD and clarified by density functional theory (DFT) calculation with a lower energy barrier during the fast reversible electrochemical three‐phase reaction of Na3V2(PO4)3 – Na2V2(PO4)3 – Na1V2(PO4)3. Therefore, as cathode of sodium‐ion battery, the N‐NVP/N‐CN exhibited specific capacities of 119.7 and 75.3 mAh g−1 at 1 C and even 200 C. Amazingly, high capacities of 89.0, 86.2, and 84.6 mAh g−1 are achieved after overlong 10000 cycles at 20, 40, and 50 C, respectively. This approach provides a new idea for surface crystal modification to cast intermediate Na2V2(PO4)3 phase for achieving excellent cycling stability and rate capability. A surface‐N‐doped Na3V2(PO4)3 (NVP) encapsulating by N‐doped carbon nanocage (N‐NVP/N‐CN) is constructed, which decreases the energy barrier of Na+ diffusion from bulk to electrolyte, enhances intrinsic electronic conductivity, and releases the lattice stress. Furthermore, this structure enables a fast reversible electrochemical three‐phase reaction of Na3V2(PO4)3 – Na2V2(PO4)3 – Na1V2(PO4)3 for excellent cycling stability and rate capability as cathode of sodium‐ion battery.

Background CD47, the integrin-related protein, plays an important role in immune resistance and escape of tumor cells. Antibodies blocking the CD47/SIRPα signal pathway can effectively stimulate macrophage-mediated phagocytosis of tumor cells, which becomes a promising approach for tumor immunotherapy. Nanobodies (Nbs) derived from camelid animals are emerging as a new force in antibody therapy. Results HuNb1-IgG4, an innovative anti-CD47 nanobody, was developed with high affinity and specificity. It effectively enhanced macrophage-mediated phagocytosis of tumor cells in vitro and showed potent anti-ovarian and anti-lymphoma activity in vivo. Importantly, HuNb1-IgG4 did not induce the agglutination of human red blood cells (RBCs) in vitro and exhibited high safety for hematopoietic system in cynomolgus monkey. In addition, HuNb1-IgG4 could be produced on a large scale in CHO-S cells with high activity and good stability. Also, we established anti-CD47/CD20 bispecific antibody (BsAb) consisted of HuNb1 and Rituximab, showing more preference binding to tumor cells and more potent anti-lymphoma activity compared to HuNb1-IgG4. Conclusions Both of HuNb1-IgG4 and anti-CD47/CD20 BsAb are potent antagonists of CD47/SIRPα pathway and promising candidates for clinical trials.

Under physiological conditions, retinal pigment epithelium (RPE) is a cellular monolayer composed of mitotically quiescent cells. Tight junctions and adherens junctions maintain the polarity of RPE cells, and are required for cellular functions. In proliferative vitreoretinopathy (PVR), upon retinal tear, RPE cells lose cell-cell contact, undergo epithelial-mesenchymal transition (EMT), and ultimately transform into myofibroblasts, leading to the formation of fibrocellular membranes on both surfaces of the detached retina and on the posterior hyaloids, which causes tractional retinal detachment. In PVR, RPE cells are crucial contributors, and multiple signaling pathways, including the SMAD-dependent pathway, Rho pathway, MAPK pathways, Jagged/Notch pathway, and the Wnt/β-catenin pathway are activated. These pathways mediate the EMT of RPE cells, which play a key role in the pathogenesis of PVR. This review summarizes the current body of knowledge on the polarized phenotype of RPE, the role of cell-cell contact, and the molecular mechanisms underlying the RPE EMT in PVR, emphasizing key insights into potential approaches to prevent PVR.

Rechargeable sodium-chlorine (Na-Cl 2 ) batteries show great promise in grid energy storage applications due to their high electrochemical performance. However, the use of highly corrosive thionyl chloride (SOCl 2 )-based electrolytes has severely hindered their real-world applications. Here we show a non-corrosive ester (methyl dichloroacetate) as a promising alternative to SOCl 2 , which can form a non-corrosive electrolyte with aluminum chloride and sodium bis(fluorosulfonyl)imide for high-performance rechargeable Na-Cl 2 batteries. The resultant battery shows a reversible capacity of up to 1200 mAh g −1 at a current density of 100 mA g −1 calculated based on the mass of carbon with a discharge voltage of ~2.5 V, a wide temperature range from −40 to 80 °C, and long-term cycling stability of 700 cycles at −40 °C, which outperforms conventional rechargeable Na-Cl 2 batteries and state-of-the-art Na metal batteries. The electrochemical performance and safety have been further extended to fibre batteries, which realize wearable applications of rechargeable Na-Cl 2 batteries. Based on donor number and charge transfer as two key descriptors, we further propose the design principle of organic electrolytes for rechargeable Na-Cl 2 batteries, which can fully unlock the designability and sustainability of organic solvents towards practical Na-Cl 2 batteries. Rechargeable sodium-chlorine (Na-Cl 2 ) batteries hold promise for grid energy storage but face challenges of corrosive thionyl chloride (SOCl 2 ) electrolytes. Here, authors introduce a non-corrosive ester as an alternative, enabling Na-Cl 2 batteries with a wide temperature range from −40 to 80 °C.

We study compensation contracts of individual portfolio managers using handcollected data of over 4,500 U.S. mutual funds. Variations in the compensation structures are broadly consistent with an optimal contracting equilibrium. The likelihood of explicit performance-based incentives is positively correlated with the intensity of agency conflicts, as proxied by the advisor's clientele dispersion, its affiliations in the financial industry, and its ownership structure. Investor sophistication and the threat of dismissal in outsourced funds serve as substitutes for explicit performancebased incentives. Finally, we find little evidence of differences in future performance associated with any particular compensation arrangement.

Cancer immunotherapy, especially immune-checkpoint inhibitors (ICIs), has paved a new way for the treatment of many types of malignancies, particularly advanced-stage cancers. Accumulating evidence suggests that as a molecular imaging modality, positron emission tomography/computed tomography (PET/CT) can play a vital role in the management of ICIs therapy by using different molecular probes and metabolic parameters. In this review, we will provide a comprehensive overview of the clinical data to support the importance of 18 F-fluorodeoxyglucose PET/CT ( 18 F-FDG PET/CT) imaging in the treatment of ICIs, including the evaluation of the tumor microenvironment, discovery of immune-related adverse events, evaluation of therapeutic efficacy, and prediction of therapeutic prognosis. We also discuss perspectives on the development direction of 18 F-FDG PET/CT imaging, with a particular emphasis on possible challenges in the future. In addition, we summarize the researches on novel PET molecular probes that are expected to potentially promote the precise application of ICIs.

Sea anemone peptides represent a valuable class of biomolecules in the marine toxin library due to their various structures and functions. Among these, ShK domain peptides are particularly notable for their selective inhibition of the Kv1.3 channel, holding great potential for applications in immune regulation and the treatment of metabolic disorders. However, these peptides’ structural complexity and diversity have posed challenges for functional prediction. In this study, we compared 36 ShK domain peptides from four species of sea anemone in the South China Sea and explored their binding ability with Kv1.3 channels by combining molecular docking and dynamics simulation studies. Our findings highlight that variations in loop length, residue composition, and charge distribution among ShK domain peptides affect their binding stability and specificity. This work presents an efficient strategy for large-scale peptide structure prediction and activity screening, providing a valuable foundation for future pharmacological research.