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To develop low-power, non-volatile computing-in-memory device using ferroelectric transistor technologies, ferroelectric channel materials with scaled thicknesses are required. Two-dimensional semiconductors, such as molybdenum disulfide (MoS 2 ), equipped with sliding ferroelectricity could provide an answer. However, achieving switchable electric polarization in epitaxial MoS 2 remains challenging due to the absence of mobile domain boundaries. Here we show that polarity-switchable epitaxial rhombohedral-stacked (3R) MoS 2 can be used as a ferroelectric channel in ferroelectric memory transistors. We show that a shear transformation can spontaneously occur in 3R MoS 2 epilayers, producing heterostructures with stable ferroelectric domains embedded in a highly dislocated and unstable non-ferroelectric matrix. This diffusionless phase transformation process produces mobile screw dislocations that enable collective polarity control of 3R MoS 2 via an electric field. Polarization–electric-field measurements reveal a switching field of 0.036 V nm −1 for shear-transformed 3R MoS 2 . Our sliding ferroelectric transistors are non-volatile memory units with thicknesses of only two atomic layers and exhibit an average memory window of 7 V with an applied voltage of 10 V, retention times greater than 10 4  seconds and endurance greater than 10 4 cycles. Rhombohedral-stacked molybdenum disulfide with sliding ferroelectric behaviour can be used to create atomically thin ferroelectric transistors for computing-in-memory device applications.

RecQ is a highly conserved helicase necessary for maintaining genome stability in all organisms. Genome comparison showed that a homologue of RecQ in Deinococcus radiodurans designated as DR1289 is a member of RecQ family with unusual domain arrangement： a helicase domain, an RecQ C-terminal domain, and surprisingly three HRDC domain repeats, whose function, however, remains obscure currently. Using an insertion deletion, we discovered that the DRRecQ mutation causes an increase in gamma radiation, hydroxyurea and mitomycine C and UV sensitivity. Using the shuttle plasmid pRADK, we complemented various domains of the D. radiodurans RecQ （DRRecQ） to the mutant in vivo. Results suggested that both the helicase and helicase-and-RNase-D-C-terminal （HRDC） domains are essential for complementing several phenotypes. The complementation and biochemical function of DRRecQ variants with different domains truncated in vitro suggested that both the helicase and three HRDC domains are necessary for RecQ functions in D. radiodurans, while three HRDC domains have a synergistic effect on the whole function. Our finding leads to the hypothesis that the RecF recombination pathway is likely a primary path of double strand break repair in this well-known radioresistant organism.

In semiconducting monolayer transition metal dichalcogenides (ML-TMDs), broken inversion symmetry and strong spin-orbit coupling result in spin-valley lock-in effects so that the valley degeneracy may be lifted by external magnetic fields, potentially leading to real-space structural transformation. Here, we report magnetic field (B)-induced giant electric hysteretic responses to back-gate voltages in ML-MoS2 field-effect transistors (FETs) on SiO2/Si at temperatures < 20 K. The observed hysteresis increases with |B| up to 12 T and is tunable by varying the temperature. Raman spectroscopic and scanning tunneling microscopic studies reveal significant lattice expansion with increasing |B| at 4.2 K, and this lattice expansion becomes asymmetric in ML-MoS2 FETs on rigid SiO2/Si substrates, leading to out-of-plane mirror symmetry breaking and the emergence of a tunable out-of-plane ferroelectric-like polar order. This broken symmetry-induced polarization in ML-MoS2 shows typical ferroelectric butterfly hysteresis in piezo-response force microscopy, adding ML-MoS2 to the single-layer material family that exhibit out-of-plane polar order-induced ferroelectricity, which is promising for such technological applications as cryo-temperature ultracompact non-volatile memories, memtransistors, and ultrasensitive magnetic field sensors. Moreover, the polar effect induced by asymmetric lattice expansion may be further generalized to other ML-TMDs and achieved by nanoscale strain engineering of the substrate without magnetic fields.

The discovery of interfacial ferroelectricity in two-dimensional rhombohedral (3R)-stacked semiconductors opens up a new pathway for achieving ultrathin computing-in-memory devices. However, exploring ferroelectricity switching in natural 3R crystals is difficult due to lack of co-existing 3R stacking domains. Here, we present that MoS2 homoepitaxial patterns with 3R polytypic domains can manifest switchable ferroelectricity at room-temperature. Based on the diffusion limited aggregation theory, such MoS2 patterns are formed under the low Mo chemical potential and low temperature with respect to common chemical vapor deposition synthesis. The alternation of 3R polytypes in the MoS2 homoepitaxial patterns, observed by scanning transmission electron microscopy, accounts for ferroelectricity switching. The MoS2 field-effect transistors with 3R polytypic domains exhibit a repeatable counterclockwise hysteresis with gate voltage sweeping, an indication of ferroelectricity switching, and the memory window exceeds those measured for compact-shaped 3R bilayer devices. This work provides a direct growth concept for layered 3R-based ferroelectric memory.

In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression. Alzheimer’s disease: A new biomarker for disease progression? Molecular tests built around analyzing B cells, a specialized type of immune cell, could aid in the diagnosis of Alzheimer’s disease. Liu-Lin Xiong from the Affiliated Hospital of Zunyi Medical University, China, and coworkers used single-cell RNA sequencing to profile gene activity in individual peripheral blood mononuclear cells from people with and without Alzheimer’s disease. They discovered that people with Alzheimer’s, especially those with more advanced disease, had lower levels of circulating B cells than healthy subjects. Twenty-five specific genes in the B cells were expressed at significantly higher or lower levels as the disease progressed. The researchers found similar results regarding B cells and Alzheimer’s progression in mouse models, and showed that massive depletion of B cells in the early onset was associated with accelerated cognitive decline and increased accumulation of sticky brain plaques.

Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD). Accumulated damaged mitochondria, which are associated with impaired mitophagy, contribute to neurodegeneration in AD. We show levels of Disrupted‐in‐schizophrenia‐1 (DISC1), which is genetically associated with psychiatric disorders and AD, decrease in the brains of AD patients and transgenic model mice and in Aβ‐treated cultured cells. Disrupted‐in‐schizophrenia‐1 contains a canonical LC3‐interacting region (LIR) motif (210FSFI213), through which DISC1 directly binds to LC3‐I/II. Overexpression of DISC1 enhances mitophagy through its binding to LC3, whereas knocking‐down of DISC1 blocks Aβ‐induced mitophagy. We further observe overexpression of DISC1, but not its mutant (muFSFI) which abolishes the interaction of DISC1 with LC3, rescues Aβ‐induced mitochondrial dysfunction, loss of spines, suppressed long‐term potentiation (LTP). Overexpression of DISC1 via adeno‐associated virus (serotype 8, AAV8) in the hippocampus of 8‐month‐old APP/PS1 transgenic mice for 4 months rescues cognitive deficits, synaptic loss, and Aβ plaque accumulation, in a way dependent on the interaction of DISC1 with LC3. These results indicate that DISC1 is a novel mitophagy receptor, which protects synaptic plasticity from Aβ accumulation‐induced toxicity through promoting mitophagy.

Neonatal hypoxic–ischemic (HI) injury derived from asphyxia during perinatal period, is a serious complication of neonatal asphyxia and the main cause of neonatal acute death and chronic neurological injury. Aberrant autophagy occurs in many nervous system diseases, but its role and underlying mechanism in HI injury is largely unknown. Here, we successfully constructed a newborn rat model of HI brain injury, and the knockout-miR-127-3p (KO-miR-127-3p) rats were structured by using CRISPR/Cas9. Subsequently, the in vitro functional experiments, in vivo zea-longa scores, as well as bioinformatics analyses and biological experiments were applied. The expression of autophagy-related proteins, including ATG12, P62, Beclin-1, LC3II in HI cortex with miR-127-3p knockout was significantly decreased, and autophagic vacuoles were disappeared. Moreover, miR-127-3p has a specific regulatory effect on CISD1 expression, another crucial molecule in autophagy process. Accordingly, the overexpression of CISD1 effectively inhibited the autophagic cell death and physiological dysfunction in the brain of HI injury, whereas si-CISD1 reversed the neuroprotective effects of KO-miR-127-3p. Our findings explained the underlying mechanism for HI injury, and miR-127-3p targeting CISD1 signal could be supposed as a new treatment strategy to prevent and treat HI injury.

Introduction Self‐repair of spinal cord injury (SCI) has been found in humans and experimental animals with partial recovery of neurological functions. However, the regulatory mechanisms underlying the spontaneous locomotion recovery after SCI are elusive. Aims This study was aimed at evaluating the pathological changes in injured spinal cord and exploring the possible mechanism related to the spontaneous recovery. Results Immunofluorescence staining was performed to detect GAP43 expression in lesion site after spinal cord transection (SCT) in rats. Then RNA sequencing and gene ontology (GO) analysis were employed to predict lncRNA that correlates with GAP43. LncRNA smart‐silencing was applied to verify the function of lncRNA vof16 in vitro, and knockout rats were used to evaluate its role in neurobehavioral functions after SCT. MicroRNA sequencing, target scan, and RNA22 prediction were performed to further explore the underlying regulatory mechanisms, and miR‐185‐5p stands out. A miR‐185‐5p site‐regulated relationship with GAP43 and vof16 was determined by luciferase activity analysis. GAP43‐silencing, miR‐185‐5p‐mimic/inhibitor, and miR‐185‐5p knockout rats were also applied to elucidate their effects on spinal cord neurite growth and neurobehavioral function after SCT. We found that a time‐dependent increase of GAP43 corresponded with the limited neurological recovery in rats with SCT. CRNA chip and GO analysis revealed lncRNA vof16 was the most functional in targeting GAP43 in SCT rats. Additionally, silencing vof16 suppressed neurite growth and attenuated the motor dysfunction in SCT rats. Luciferase reporter assay showed that miR‐185‐5p competitively bound the same regulatory region of vof16 and GAP43. Conclusions Our data indicated miR‐185‐5p could be a detrimental factor in SCT, and vof16 may function as a ceRNA by competitively binding miR‐185‐5p to modulate GAP43 in the process of self‐recovery after SCT. Our study revealed a novel vof16‐miR‐185‐5p‐GAP43 regulatory network in neurological self‐repair after SCT and may underlie the potential treatment target for SCI. Here, we found that vof16‐miR185‐5p‐GAP43 network is closely related to SCT self‐repair, and simultaneously enhances motor and sensory function after SCT. Knocking out vof16 or GAP43 could inhibit the self‐repair of spinal cord and neurite growth, while miR‐185‐5p knockout promoted the axonal growth after SCT. Furthermore, miR‐185‐5p can competitively bind the same regulatory region of vof16 and GAP43. Our study provides a novel regulatory network that functions via a miRNA competitive mechanism mediated by vof16 in SCT self‐repair and axonal growth.

The cellular and molecular mechanisms underlying cortical alterations during early fetal development in Down syndrome (DS) remain largely unexplored. Here, we perform single-nucleus RNA sequencing (snRNA-seq) analysis on mid-gestational DS and control brain samples, including prefrontal cortex (PFC) and superior temporal plane cortex (STP). Through comparative spatiotemporal analyses, we decode cell-type- and region-specific transcriptional alterations associated with chr21 abnormalities, including a disrupted inhibitory-to-excitatory balance during mid-gestational development. RUNX1 and APP emerge as the most significantly dysregulated chromosome21 genes in the PFC and STP, respectively. Abnormal cortical distribution of excitatory neurons in both regions is potentially driven by dysregulated neuronal migration genes and impaired lactylation metabolism. Moreover, glial cells modulate the differentiation and migration of excitatory neurons through multiple intercellular signaling pathways. These findings provide critical insights into the pathogenesis of DS-related mid-gestational cortical abnormalities and offer valuable resources for disease modeling and development of spatiotemporally targeted therapeutic strategies. Here, Xiong et al investigate mid-gestational brain development from Down syndrome and control brain samples using single-nucleus RNA sequencing. They report cell-type- and region-specific transcriptional alterations associated with chr21 abnormalities.

Since the early 2000s, China has carried out extensive “grain-for-green” and grazing exclusion practices to combat desertification in the desertification-prone region (DPR). However, the environmental and socioeconomic impacts of these practices remain unclear. We quantify and compare the changes in fractional vegetation cover (FVC) with economic and population data in the DPR before and after the implementation of these environmental programmes. Here we show that climatic change and CO 2 fertilization are relatively strong drivers of vegetation rehabilitation from 2001-2020 in the DPR, and the declines in the direct incomes of farmers and herders caused by ecological practices exceed the subsidies provided by governments. To minimize economic hardship, enhance food security, and improve the returns on policy investments in the DPR, China needs to adapt its environmental programmes to address the potential impacts of future climate change and create positive synergies to combat desertification and improve the economy in this region. This paper shows that desertification combating practices decline incomes of farmers and herders, and China needs to adapt its ecological programmes to address the impacts of climate change and create positive synergies to combat desertification.