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Homologous recombination (HR), catalyzed in an evolutionarily conserved manner by active RecA/Rad51 nucleofilaments, maintains genomic integrity and promotes biological evolution and diversity. The structures of RecA/Rad51 nucleofilaments provide information critical for the entire HR process. By exploiting a unique capillary electrophoresis-laser-induced fluorescence polarization assay, we have discovered an active form of RecA nucleofilament, stimulated by ATP hydrolysis, that contains mainly unbound nucleotide sites. This finding was confirmed by a nuclease protection assay and electron microscopy (EM) imaging. We further found that these RecA-unsaturated filaments promote strand exchange in vitro and HR in vivo . RecA mutants (P67D and P67E), which only form RecA-unsaturated nucleofilaments, were able to mediate HR in vitro and in vivo , but mutants favoring the formation of the saturated nucleofilaments failed to support HR. We thus present a new model for RecA-mediated HR in which RecA utilizes its intrinsic DNA binding-dependent ATPase activity to remodel the nucleofilaments to a less saturated form and thereby promote HR.

The aim of this work was to investigate the correlation between scanning laser polarimetry with variable corneal compensation (GDx VCC) parameters and blue-on-yellow perimetry (B/YP) indices in ocular hypertension (OHT). One eye each of 52 patients with OHT (with a normal visual field, a normal optic nerve, and an untreated IOP > 21 mmHg) was chosen. All patients were examined with the Octopus 101 automated perimetry dG2 program using the dynamic/normal strategy (white-on-white perimetry, W/WP), with the dG2 program using the dynamic strategy/BY method (blue-on-yellow perimetry, B/YP), and with GDx VCC. Seven of the 52 OHT patients had both B/YP visual field loss and retinal nerve fiber layer (RNFL) defects with the GDx VCC measurements, and four patients demonstrated regions of B/YP visual field defects with corresponding RNFL defects on GDx VCC examination. A mild significant correlation was found between B/YP mean sensitivity (MS) and the superior average ( R 2 =0.138, p  = 0.049). No significant correlation was found between the W/WP indices and GDx VCC parameters. B/YP MS correlated with the superior average of GDx VCC in OHT patients. The findings brought up the possibility of using both techniques for clinical examination to yield converging data.

In this paper, we consider a continuous-time model with discrete and dis-tributed delays to describe how two pieces of information interact in online social networks. Sufficient conditions are carried out to illustrate the stability of each e-quilibrium. Taking time delay as a bifurcation parameter, the system undergoes a sequence of Hopf bifurcation when this parameter passes through a critical value. By methods of multiple scales, we prove that the direction of Hopf bifurcation is depending on the condition which is related to delay.

The development of enantiodivergent catalysis for the preparation of both enantiomers of a chiral compound is of importance in pharmaceutical and bioorganic chemistry. With the design of a class of reactive and stereoselective organocatalysts, acyclic chiral secondary amines, a method for achieving the enantiodivergence is developed simply by changing the secondary N - i -Bu- to N -Me-group within the catalyst architecture while maintaining the same absolute configuration of the catalysts, which modulates the catalyst conformation. This catalyst-controlled enantiodivergent method not only enables challenging asymmetric transformations to occur in an enantiodivergent manner but also features a high level of stereocontrol and broad scope that is demonstrated in eight different reactions (90 examples), all delivering both enantiomers of a range of structurally diverse products including hitherto less accessible, yet important, compounds in good yields with high stereoselectivities. Enantiodivergent methods, which to access both enantiomers of the same compound, are of importance in drug synthesis. Here, the authors show that by simply changing a N i Bu- to a NMe-group in readily available amine organocatalysts, high stereocontrol and broad scope are achieved in eight asymmetric reactions.

HighlightsResponsive photonic nanorobots (RPNRs) simultaneously exhibit energetic magnetically-propelled swarming motions, bright stimuli-responsive structural colors, and photothermal conversion.The swarming RPNRs can actively navigate in complex environments and collectively map out local physicochemical conditions (e.g., pH, temperature, or glucose concentration) on the fly via their bright responsive structural colors.The swarming RPNRs can visualize an unknown target (e.g., tumor lesion) via motile-targeting mapping and then guide the external NIR light to initiate localized photothermal treatment.Micro/nanorobots can propel and navigate in many hard-to-reach biological environments, and thus may bring revolutionary changes to biomedical research and applications. However, current MNRs lack the capability to collectively perceive and report physicochemical changes in unknown microenvironments. Here we propose to develop swarming responsive photonic nanorobots that can map local physicochemical conditions on the fly and further guide localized photothermal treatment. The RPNRs consist of a photonic nanochain of periodically-assembled magnetic Fe3O4 nanoparticles encapsulated in a responsive hydrogel shell, and show multiple integrated functions, including energetic magnetically-driven swarming motions, bright stimuli-responsive structural colors, and photothermal conversion. Thus, they can actively navigate in complex environments utilizing their controllable swarming motions, then visualize unknown targets (e.g., tumor lesion) by collectively mapping out local abnormal physicochemical conditions (e.g., pH, temperature, or glucose concentration) via their responsive structural colors, and further guide external light irradiation to initiate localized photothermal treatment. This work facilitates the development of intelligent motile nanosensors and versatile multifunctional nanotheranostics for cancer and inflammatory diseases.

Adeno‐associated virus (AAV) has emerged as a leading vector for gene therapy due to its broad host range, low pathogenicity, and ability to facilitate long‐term gene expression. However, AAV vectors face limitations, including immunogenicity and insufficient targeting specificity. To enhance the efficacy of gene therapy, researchers have been modifying the AAV vector using various methods. Traditional experimental approaches for optimizing AAV vector are often time‐consuming, resource‐intensive, and difficult to replicate. The advancement of artificial intelligence (AI), particularly machine learning, offers significant potential to accelerate capsid optimization while reducing development time and manufacturing costs. This review compares traditional and AI‐based methods of AAV vector engineering and highlights recent research in AAV engineering using AI algorithms. Adeno‐associated virus (AAV) has emerged as a leading vector for gene therapy. However, AAV vectors face limitations, including immunogenicity and insufficient targeting specificity. Various methods have been used to engineer the AAV vector. This review compares traditional and AI‐based methods of AAV vector engineering and highlights recent research in AAV engineering using AI algorithms.

Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno‐associated virus (AAV)‐mediated OTOF gene replacement therapy is extensively validated in Otof‐deficient mice. However, the clinical safety and efficacy of AAV‐OTOF is not reported. Here, AAV‐OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non‐human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV‐OTOF is delivered into one cochlea of a 5‐year‐old deaf patient and into the bilateral cochleae of an 8‐year‐old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure‐tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5‐year‐old patient can be restored to the normal range at 1 month after AAV‐OTOF injection, while the 8‐year‐old patient can hear the conversational sounds. Most importantly, the 5‐year‐old patient can hear and recognize speech only through the AAV‐OTOF‐injected ear. This study is the first to demonstrate the safety and efficacy of AAV‐OTOF in patients, expands and optimizes current OTOF‐related gene therapy and provides valuable information for further application of gene therapies for deafness. This study evaluates the efficacy and safety of an adeno‐associated virus (AAV) based gene therapy AAV‐OTOF in patients with DFNB9 deafness. AAV‐OTOF injection can restore the hearing function of the previous deaf ear to a normal level with safety. This proof of concept study provides clinical gene therapy data for DFNB9 deafness and also supplies support for other inner ear gene therapies.

Swarming magnetic micro/nanorobots hold great promise for biomedical applications, but at present suffer from inferior capabilities to perceive and respond to chemical signals in local microenvironments. Here we demonstrate swarming magnetic photonic‐crystal microrobots (PC‐bots) capable of spontaneously performing on‐the‐fly visual pH detection and self‐regulated drug delivery by perceiving local pH changes. The magnetic PC‐bots consist of pH‐responsive hydrogel microspheres with encapsulated one‐dimensional periodic assemblies of Fe 3 O 4 nanoparticles. By programming external rotating magnetic fields, they can self‐organize into large swarms with much‐enhanced collective velocity to actively find targets while shining bright “blinking” structural colors. When approaching the target with abnormal pH conditions (e.g., an ulcerated superficial tumor lesion), the PC‐bots can visualize local pH changes on the fly via pH‐responsive structural colors, and realize self‐regulated release of the loaded drugs by recognizing local pH. This work facilitates the development of intelligent micro/nanorobots for active “motile‐targeting” tumor diagnosis and treatment. image

The investigation of seepage situation of a reservoir under complex geological conditions is greatly significant and is necessary to be determined by geologic survey or numerical analysis. Based on previous geological survey data, a 3-dimensional seepage back analysis was conducted. In this study, two hydraulic conditions of unsteady and steady seepage were considered, and the corresponding back analysis came down to a multi-objective decision-making problem. The GRNN model was trained by PSO algorithm for obtaining the relationship between permeability coefficients and monitoring data, and by combining the NSGA-II algorithm, the best unbiased solution of permeability coefficients for the multi-objective function established by monitoring data of seepage discharge and pressure head was searched via iteration calculation. On this basis, the seepage safety of the reservoir was evaluated. Through taking the seepage discharge of the whole reservoir into account, the problem in the traditional seepage field back analysis that the foundation strata seepage parameters are insensitive to the pressure head inside the dam was solved. And the inversion results can provide a supplement for the geological survey under complex geological conditions. The method adopted in this paper may provide significant references for the anti-seepage design and reinforcement of hydraulic structures with complex geological conditions.

Bismuth (Bi) has been prompted many investigations into the development of next-generation energy storage systems on account of its unique physicochemical properties. Although there are still some challenges, the application of metallic Bi-based materials in the field of energy storage still has good prospects. Herein, we systematically review the application and development of metallic Bi-based anode in lithium ion batteries and beyond-lithium ion batteries. The reaction mechanism, modification methodologies and their relationship with electrochemical performance are discussed in detail. Additionally, owing to the unique physicochemical properties of Bi and Bi-based alloys, some innovative investigations of metallic Bi-based materials in alkali metal anode modification and sulfur cathodes are systematically summarized for the first time. Following the obtained insights, the main unsolved challenges and research directions are pointed out on the research trend and potential applications of the Bi-based materials in various energy storage fields in the future.