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Over the past century, the field of antibody discovery has undergone significant evolution, excluding the current exploration stage of artificial intelligence‐based antibody generation and the often overlooked non‐animal sourced antibody discovery, which typically requires mature in vitro affinity and the selection of high‐quality antigen formulations. This journey has traversed various stages, from methods involving serum‐based antibody acquisition, the isolation of B cells capable of perpetual antibody production through hybridoma technology, to the in‐depth exploration of genetic material using the phage display system, and the current stage involving diverse single B cell screening techniques. Additionally, the emergence of machine learning has brought impressive scientific and technological breakthroughs across research domains, proving to be a powerful application in the field of antibody discovery. However, each technique comes with its limitations, such as variability and control challenges in serum‐based acquisition, lengthy and difficult hybridoma‐derived antibody development, potential limitations in sequence and epitope diversity due to immunization biases in phage display techniques, and costly single B cell screening. Protein mass spectrometry sequencing, with shorter acquisition time and lower costs, is seen as a shortcut by diagnostic companies, impacting traditional antibody development. In diagnostic antibody development, methodological differences in downstream assays and the impact of constant regions outside the Fv core are often neglected. This paper deeply analyzes challenges, proposing innovative strategies for the next generation of diagnostic antibody development. Aimed at moving closer to the gold standard of antibody discovery, these strategies enhance the competitiveness of diagnostic reagent products. This study has systematically organized the discovery of antibodies into three stages and analyzed the advantages and disadvantages of each stage. Meanwhile, This study deeply analyzes challenges, proposing innovative strategies for the next generation of diagnostic antibody development. Aimed at moving closer to the gold standard of antibody discovery, these strategies enhance the competitiveness of diagnostic reagent products.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivoimaging, and behavioral measurements to show that the loss of Fmr1impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KOmice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAAreceptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KOmice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.

This paper proposes a complex PI current controller design method of three-phase inverter based on multiple equations construction. The mathematical model of three-phase inverter system plays an important role in the controller design process. In the synchronous reference frame, the inverter model introduces coupling elements, which is different from the model in the stationary reference frame and brings difficulty for current controller design. Complex vector model (CVM) is introduced in the current loop, which is established in the synchronous reference frame and takes part in the current controller design. Multiple equations construction is established to solve the parameters of the complex PI current controller. Because the controller satisfies the restrictions of the multiple equations, it can realize good dynamic performance and the coupling characteristic of the three-phase system. In this paper, the CVM is established. The process of construct and solve the multiple equations is analyzed in detail. The accuracy of the inverter system is validated. Finally the simulation and experimental results are given to verify the theoretical analysis.

Based on Global Coupled Ionosphere‐Thermosphere‐Electrodynamics Model, the solution of the 3‐dimensional current in the ionospheric region, the equivalent sheet current and filed‐aligned current are examined. The simulation study enables a comprehensive analysis of the effect of the geomagnetic field configuration, especially the non‐dipole component and tilt angle, on the ionospheric electrodynamics phenomena. Different geomagnetic field configurations are specified in the present work, including realistic geomagnetic field (RGF), tilted dipole geomagnetic field (TDGF) and zero‐declination dipole geomagnetic field (ZDGF). Our simulation focuses on the seasonal variation of Sq current, primarily governed by annual and semi‐annual variation. The modulation of the tilt angle of the geomagnetic field is globally distributed, whereas the modulation of the geomagnetic anomaly is localized. At mid‐latitudes, the annual mean and semi‐annual amplitudes of the Sq current are negatively correlated with the magnetic field strength, especially shown in geomagnetic anomaly area, while there is the opposite effect in the geomagnetic conjugate regions of the opposite hemispheres. The annual variation of Sq current system is more affected by the offset of the geomagnetic latitudes and geographical latitudes. The seasonal variation of the total Sq current is also modulated by the geomagnetic field. The annual mean, the annual and semi‐annual components of the total Sq current are negatively correlated with the magnetic field strength, while the annual variation is also controlled by the tilt angle of the geomagnetic field. The solar radiation affects the semi‐annual variation of the current more strongly than the annual variation. Ionospheric currents and magnetic fields exert significant influences on energy and material transport within the ionosphere, playing a pivotal role in Earth's electromagnetic environment, which is the primary focus of ionospheric research. To investigate the impact of the geomagnetic field on the ionospheric current system, we employ a theoretical model (GCITEM) for simulation work. In this simulation, we consider both the realistic geomagnetic field configuration and two hypothetical idealized configurations of the geomagnetic field: one excluding non‐dipole terms and the other further aligning the geomagnetic axis with Earth's spin axis. The analysis of the longitude and the seasonal variation of the simulated currents under realistic magnetic field conditions has been validated through previous observation results. In comparison to simulation results obtained under hypothetical configurations, we discern and analyze the modulation and mechanism of non‐dipole terms and the tilt angle of geomagnetic field on the variability of the ionospheric current system, which are discussed in detail within this paper. This study facilitates the analysis and prediction of long‐term changes in the geomagnetic field's effects on ionospheric current generation and the impact on space's electromagnetic environment. The geomagnetic field intensity exerts a significant influence on the Sq currents and exhibits a negative correlation with Sq currentThe annual mean and annual variation amplitude of Sq current are positively correlated with the geomagnetic anomaly at conjugate pointsThe tilt angle of the geomagnetic field affects the annual variation of Sq current globally, but hardly effects the semiannual variation The geomagnetic field intensity exerts a significant influence on the Sq currents and exhibits a negative correlation with Sq current The annual mean and annual variation amplitude of Sq current are positively correlated with the geomagnetic anomaly at conjugate points The tilt angle of the geomagnetic field affects the annual variation of Sq current globally, but hardly effects the semiannual variation

Adeno-associated virus (AAV) is a promising vector for in vivo gene therapy because of its excellent safety profile and ability to mediate stable gene expression in human subjects. However, there are still numerous challenges that need to be resolved before this gene delivery vehicle is used in clinical applications, such as the inability of AAV to effectively target specific tissues, preexisting neutralizing antibodies in human populations, and a limited AAV packaging capacity. Over the past two decades, much genetic modification work has been performed with the AAV capsid gene, resulting in a large number of variants with modified characteristics, rendering AAV a versatile vector for more efficient gene therapy applications for different genetic diseases.

In this paper, an adaptive radical basis function neural network (RBFNN) is proposed to deal with dynamic tracking error problems which are the mathematic model uncertain or complex for the three-phase active power filter (APF). The adaptive RBFNN systems are employed to approximate the system function term f^(x) in the sliding mode controller. Different from back propagation neural network (BPNN), RBFNN is local uniformly convergence so that it enhances the convergence speed of weights. According to Lyapunov stability analysis guarantee the control algorithm stable implementing that is working out the adaptive law and dragging the states onto the sliding surface and sliding along it. This approach is almost model-free requiring a minimal amount of a priori knowledge and is robust in the face of parameter changes. The simulation results of APF demonstrate the outstanding compensation performance and strong robustness.

The prevalence of adeno-associated virus (AAV) has been investigated in bat populations, but little is known about the biological properties of this virus. In this study, four full-length bat AAV capsid genes were isolated in China, with their amino acid sequences sharing 61% identity with those of AAV2 on average. These capsid genes could package AAV particles in combination with AAV2 repand ITRs, albeit at a lower efficiency. Bat AAVs could only slightly infect mouse liver but could transduce mouse muscle to some extent after systemic administration with a higher muscle/liver ratio than that of primate AAVs. Bat AAV 10HB showed moderate muscle transduction, similar to that of AAV2, during direct intramuscular injection and, compared with other AAV serotypes, was also relatively efficient in resisting human antibody neutralization after intramuscular injection. Evolutionary analysis revealed a number of codons in bat AAV capsid genes subject to positive selection, with sites corresponding to V259 and N691 in 10HB capsids being localized on the surface of the AAV2 capsid. Mutagenesis studies indicated that the positive selection in bat AAV capsids is driven by their tropism evolution in host species. Taken together, the results of this study indicate that bat AAV 10HB vector has the possible applications for muscular gene therapy, especially in the presence of human AAV neutralizing antibodies.

Short-term memory (STM) is crucial for animals to hold information for a small period of time. Persistent or recurrent neural activity, together with neural oscillations, is known to encode the STM at the cellular level. However, the coding mechanisms at the microcircuitry level remain a mystery. Here, we performed two-photon imaging on behaving mice to monitor the activity of neuronal microcircuitry. We discovered a neuronal subpopulation in the medial prefrontal cortex (mPFC) that exhibited emergent properties in a context-dependent manner underlying a STM-like behavior paradigm. These neuronal subpopulations exclusively comprise excitatory neurons and mainly represent a group of neurons with stronger functional connections. Microcircuitry plasticity was maintained for minutes and was absent in an animal model of Alzheimer’s disease (AD). Thus, these results point to a functional coding mechanism that relies on the emergent behavior of a functionally defined neuronal assembly to encode STM.

A general and high-efficiency C-alkylation of oxindoles and barbituric acids has been developed by a Cp∗Ir complex [Cp∗Ir (2,2′-bpyO)(OH)]Na with a bipyridine-based functional ligand. In particular, H2O was selected as the solvent instead of the organic solvent in this catalytic system. Through mild reaction conditions gave a variety of corresponding alkylated heterocyclic compounds with good to excellent yields. More importantly, the gram-scale C-alkylation reaction was successfully carried out with good yield using a common route with only a single purification by column chromatography.

This paper describes an endoscopic-inspired imaging system employing a micro-electromechanical system (MEMS) micromirror scanner to achieve beam scanning for optical coherence tomography (OCT) imaging. Miniaturization of a scanning mirror using MEMS technology can allow a fully functional imaging probe to be contained in a package sufficiently small for utilization in a working channel of a standard gastroesophageal endoscope. This work employs advanced image processing techniques to enhance the images acquired using the MEMS scanner to correct non-idealities in mirror performance. The experimental results demonstrate the effectiveness of the proposed technique.

In this work, we examine the impact of increased anthropogenic emissions on equatorial plasma bubble (EPB) occurrence by modeling the growth rate of Rayleigh‐Taylor (R‐T) instability (γRT${\gamma }_{RT}$), which is closely related to EPB generation. Using the global coupled ionosphere‐thermosphere‐electrodynamics model‐institute of geology and geophysics, Chinese Academy of Sciences model, γRT${\gamma }_{RT}$is calculated under three different CO2emission levels. As CO2increases, γRT${\gamma }_{RT}$significantly increases at low altitudes (<∼260 km) and decreases at high altitudes (>∼320 km). In the altitudes in between, γRT${\gamma }_{RT}$increases (decreases) before (after) midnight. Longitudinal variability of the γRT${\gamma }_{RT}$change is manifested apparently above ∼280 km, while it is insignificant for low altitudes. Term analysis revealed that changes in the gravity term and the electric‐field term are the main causes and that the neutral‐wind term is insignificant. The investigation indicates that increased anthropogenic emissions can change EPB occurrence and, in turn, the radio‐communication system and therefore influence modern technological systems, which is expected to be more serious in the future. Equatorial plasma bubbles (EPBs) are ionospheric plasma irregularities that negatively influence radio propagation and even disrupt communication and navigation systems. In this work, we attempt to elucidate whether increased anthropogenic emissions impact EPB occurrence. To quantitatively characterize the EPB occurrence, the Rayleigh‐Taylor (R‐T) instability growth rate (γRT${\gamma }_{RT}$) defined by Sultan (1996), https://doi.org/10.1029/96ja00682is used. based on a thermosphere‐ionosphere coupled model, global coupled ionosphere‐thermosphere‐electrodynamics model‐institute of geology and geophysics, chinese academy of sciences, γRT${\gamma }_{RT}$is calculated for three different CO2emission levels. The results show that as CO2increases, γRT${\gamma }_{RT}$significantly increases at low altitudes (<∼260 km) and decreases at high altitudes (>∼320 km). In the altitudes in between, γRT${\gamma }_{RT}$increases before midnight but decreases after midnight. Longitudinal variability of the γRT${\gamma }_{RT}$change is manifested apparently above ∼280 km but is insignificant at low altitudes. As a first step, this work revealed a possible link between long‐term anthropogenic climate change and short‐term space weather events that impact modern communication. Global Coupled Ionosphere‐Thermosphere‐Electrodynamics Model‐Institute of Geology and Geophysics, Chinese Academy of Sciences simulation revealed that the equatorial plasma bubble (EPB) occurrence would increase below 260 km and decrease above 320 km as CO2 emissions increaseThe EPB occurrence change shows local‐time and longitudinal dependence that maximum generally occurred at American sector before midnightCO2 impacts on the electron density, conductivity, and electric fields cause the EPB occurrence change, while dynamic impacts are limited Global Coupled Ionosphere‐Thermosphere‐Electrodynamics Model‐Institute of Geology and Geophysics, Chinese Academy of Sciences simulation revealed that the equatorial plasma bubble (EPB) occurrence would increase below 260 km and decrease above 320 km as CO2 emissions increase The EPB occurrence change shows local‐time and longitudinal dependence that maximum generally occurred at American sector before midnight CO2 impacts on the electron density, conductivity, and electric fields cause the EPB occurrence change, while dynamic impacts are limited