Ribosome ADP-ribosylation inhibits translation and maintains proteostasis in cancers.

Defects in translation lead to changes in the expression of proteins that can serve as drivers of cancer formation. Here, we show that cytosolic NAD+ synthesis plays an essential role in ovarian cancer by regulating translation and maintaining protein homeostasis. Expression of NMNAT-2, a cytosolic NAD+ synthase, is highly upregulated in ovarian cancers. NMNAT-2 supports the catalytic activity of the mono(ADP-ribosyl) transferase (MART) PARP-16, which mono(ADP-ribosyl)ates (MARylates) ribosomal proteins. Depletion of NMNAT-2 or PARP-16 leads to inhibition of MARylation, increased polysome association and enhanced translation of specific mRNAs, aggregation of their translated protein products, and reduced growth of ovarian cancer cells. Furthermore, MARylation of the ribosomal proteins, such as RPL24 and RPS6, inhibits polysome assembly by stabilizing eIF6 binding to ribosomes. Collectively, our results demonstrate that ribosome MARylation promotes protein homeostasis in cancers by fine-tuning the levels of protein synthesis and preventing toxic protein aggregation.

Single-cell discovery of m6A RNA modifications in the hippocampus.

N 6-Methyladenosine (m6A) is a prevalent and highly regulated RNA modification essential for RNA metabolism and normal brain function. It is particularly important in the hippocampus, where m6A is implicated in neurogenesis and learning. Although extensively studied, its presence in specific cell types remains poorly understood. We investigated m6A in the hippocampus at a single-cell resolution, revealing a comprehensive landscape of m6A modifications within individual cells. Through our analysis, we uncovered transcripts exhibiting a dense m6A profile, notably linked to neurological disorders such as Alzheimer's disease. Our findings suggest a pivotal role of m6A-containing transcripts, particularly in the context of CAMK2A neurons. Overall, this work provides new insights into the molecular mechanisms underlying hippocampal physiology and lays the foundation for future studies investigating the dynamic nature of m6A RNA methylation in the healthy and diseased brain.

Downregulation of a transcription factor associated with resistance to Bt toxin Vip3Aa in the invasive fall armyworm.

Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) have revolutionized control of some major pests. However, more than 25 cases of field-evolved practical resistance have reduced the efficacy of transgenic crops producing crystalline (Cry) Bt proteins, spurring adoption of alternatives including crops producing the Bt vegetative insecticidal protein Vip3Aa. Although practical resistance to Vip3Aa has not been reported yet, better understanding of the genetic basis of resistance to Vip3Aa is urgently needed to proactively monitor, delay, and counter pest resistance. This is especially important for fall armyworm (Spodoptera frugiperda), which has evolved practical resistance to Cry proteins and is one of the world's most damaging pests. Here, we report the identification of an association between downregulation of the transcription factor gene SfMyb and resistance to Vip3Aa in S. frugiperda. Results from a genome-wide association study, fine-scale mapping, and RNA-Seq identified this gene as a compelling candidate for contributing to the 206-fold resistance to Vip3Aa in a laboratory-selected strain. Experimental reduction of SfMyb expression in a susceptible strain using RNA interference (RNAi) or CRISPR/Cas9 gene editing decreased susceptibility to Vip3Aa, confirming that reduced expression of this gene can cause resistance to Vip3Aa. Relative to the wild-type promoter for SfMyb, the promoter in the resistant strain has deletions and lower activity. Data from yeast one-hybrid assays, genomics, RNA-Seq, RNAi, and proteomics identified genes that are strong candidates for mediating the effects of SfMyb on Vip3Aa resistance. The results reported here may facilitate progress in understanding and managing pest resistance to Vip3Aa.

Echoes of ancient introgression punctuate stable genomic lineages in the evolution of figs.

Studies investigating the evolution of flowering plants have long focused on isolating mechanisms such as pollinator specificity. Some recent studies have proposed a role for introgressive hybridization between species, recognizing that isolating processes such as pollinator specialization may not be complete barriers to hybridization. Occasional hybridization may therefore lead to distinct yet reproductively connected lineages. We investigate the balance between introgression and reproductive isolation in a diverse clade using a densely sampled phylogenomic study of fig trees (Ficus, Moraceae). Codiversification with specialized pollinating wasps (Agaonidae) is recognized as a major engine of fig diversity, leading to about 850 species. Nevertheless, some studies have focused on the importance of hybridization in Ficus, highlighting the consequences of pollinator sharing. Here, we employ dense taxon sampling (520 species) throughout Moraceae and 1,751 loci to investigate phylogenetic relationships and the prevalence of introgression among species throughout the history of Ficus. We present a well-resolved phylogenomic backbone for Ficus, providing a solid foundation for an updated classification. Our results paint a picture of phylogenetically stable evolution within lineages punctuated by occasional local introgression events likely mediated by local pollinator sharing, illustrated by clear cases of cytoplasmic introgression that have been nearly drowned out of the nuclear genome through subsequent lineage fidelity. The phylogenetic history of figs thus highlights that while hybridization is an important process in plant evolution, the mere ability of species to hybridize locally does not necessarily translate into ongoing introgression between distant lineages, particularly in the presence of obligate plant-pollinator relationships.

Transcription factor OsMYB30 increases trehalose content to inhibit α-amylase and seed germination at low temperature.

Low-temperature germination (LTG) is an important agronomic trait for direct-seeding cultivation of rice (Oryza sativa). Both OsMYB30 and OsTPP1 regulate the cold stress response in rice, but the function of OsMYB30 and OsTPP1 in regulating LTG and the underlying molecular mechanism remains unknown. Employing transcriptomics and functional studies revealed a sugar signaling pathway that regulates seed germination in response to low temperature (LT). Expression of OsMYB30 and OsTPP1 was induced by LT during seed germination, and overexpressing either OsMYB30 or OsTPP1 delayed seed germination and increased sensitivity to LT during seed germination. Transcriptomics and qPCR revealed that expression of OsTPP1 was upregulated in OsMYB30-overexpressing lines but downregulated in OsMYB30-knockout lines. In vitro and in vivo experiments revealed that OsMYB30 bound to the promoter of OsTPP1 and regulated the abundance of OsTPP1 transcripts. Overaccumulation of trehalose (Tre) was found in both OsMYB30- and OsTPP1-overexpressing lines, resulting in inhibition of α-amylase 1a (OsAMY1a) gene during seed germination. Both LT and exogenous Tre treatments suppressed the expression of OsAMY1a, and the osamy1a mutant was not sensitive to exogenous Tre during seed germination. Overall, we concluded that OsMYB30 expression was induced by LT to activate the expression of OsTPP1 and increase Tre content, which thus inhibited α-amylase activity and seed germination. This study identified a phytohormone-independent pathway that integrates environmental cues with internal factors to control seed germination.

Evaluating the depression state during perinatal period by non-invasive scalp EEG.

Perinatal depression, with a prevalence of 10 to 20% in United States, is usually missed as multiple symptoms of perinatal depression are common in pregnant women. Worse, the diagnosis of perinatal depression still largely relies on questionnaires, leaving the objective biomarker being unveiled yet. This study suggested a safe and non-invasive technique to diagnose perinatal depression and further explore its underlying mechanism. Considering the non-invasiveness and clinical convenience of electroencephalogram for mothers-to-be and fetuses, we collected the resting-state electroencephalogram of pregnant women at the 38th week of gestation. Subsequently, the difference in network topology between perinatal depression patients and healthy mothers-to-be was explored, with related spatial patterns being adopted to achieve the classification of pregnant women with perinatal depression from those healthy ones. We found that the perinatal depression patients had decreased brain network connectivity, which indexed impaired efficiency of information processing. By adopting the spatial patterns, the perinatal depression could be accurately recognized with an accuracy of 87.88%; meanwhile, the depression severity at the individual level was effectively predicted, as well. These findings consistently illustrated that the resting-state electroencephalogram network could be a reliable tool for investigating the depression state across pregnant women, and will further facilitate the clinical diagnosis of perinatal depression.

Fluidic phase-change materials with continuous latent heat from theoretically tunable ternary metals for efficient thermal management.

Phase-change materials (PCMs), as important energy storage materials (ESMs), have been widely used in heat dissipation for electronics. However, PCMs are encountering huge challenges since the extremely limited space in microelectronics largely suppresses the applied volume of PCMs, which demands excellent PCMs that can fully utilize the valuable latent heat. This work successfully found a universal strategy toward powerful ESMs from fluidic ternary metals (TMs, GaInSn as a representative TM in this work). TMs exhibit high thermal conductivity (20.3 W m-1 K-1) and significantly effective latent heat (115 J/cm3) and, more important, show continuous phase transition and full utilization of the valuable latent heat. Interestingly, theoretical prediction through ternary phase diagram is carried out to easily tune the melting range, latent heat, and fluidity (viscosity) of TMs to adapt with different service conditions. As a result, thermally conductive silicone grease can be conveniently fabricated via simple shear mixing of TM and polymers. Such thermally conductive TM grease inherits the merits of TM, exhibiting continuous thermal control over daily electronics according to thermal shock performance.

Robots as models of evolving systems.

Experimental robobiological physics can bring insights into biological evolution. We present a development of hybrid analog/digital autonomous robots with mutable diploid dominant/recessive 6-byte genomes. The robots are capable of death, rebirth, and breeding. We map the quasi-steady-state surviving local density of the robots onto a multidimensional abstract "survival landscape." We show that robot death in complex, self-adaptive stress landscapes proceeds by a general lowering of the robotic genetic diversity, and that stochastically changing landscapes are the most difficult to survive.

Population genomics of Agrotis segetum provide insights into the local adaptive evolution of agricultural pests.

BACKGROUND: The adaptive mechanisms of agricultural pests are the key to understanding the evolution of the pests and to developing new control strategies. However, there are few studies on the genetic basis of adaptations of agricultural pests. The turnip moth, Agrotis segetum (Lepidoptera: Noctuidae) is an important underground pest that affects a wide range of host plants and has a strong capacity to adapt to new environments. It is thus a good model for studying the adaptive evolution of pest species. RESULTS: We assembled a high-quality reference genome of A. segetum using PacBio reads. Then, we constructed a variation map of A. segetum by resequencing 98 individuals collected from six natural populations in China. The analysis of the population structure showed that all individuals were divided into four well-differentiated populations, corresponding to their geographical distribution. Selective sweep analysis and environmental association studies showed that candidate genes associated with local adaptation were functionally correlated with detoxification metabolism and glucose metabolism. CONCLUSIONS: Our study of A. segetum has provided insights into the genetic mechanisms of local adaptation and evolution; it has also produced genetic resources for developing new pest management strategies.

Terahertz s-SNOM Imaging of a Single Cell with Nanoscale Resolution.

Terahertz scattering scanning near-field optical microscopy is a robust spectral detection technique with a nanoscale resolution. However, there are still major challenges in investigating the heterogeneity of cell membrane components in individual cells. Here, we present a novel and comprehensive analytical approach for detecting and investigating heterogeneity in cell membrane components at the single-cell level. In comparison to the resolution of the topographical atomic force microscopy image, the spatial resolution of the terahertz near-field amplitude image is 3 times that of the former. This ultrafine resolution enables the compositional distribution in the cell membrane, such as the distribution of extracellular vesicles, to be finely characterized. Furthermore, via extraction of the near-field absorption images at specific frequencies, the visualization and compositional difference analysis of cell membrane components can be presented in detail. These findings have significant implications for the intuitive and visual analysis of cell development and disease evolutionary pathways.

A Trifolium repens flavodoxin-like quinone reductase 1 (TrFQR1) improves plant adaptability to high temperature associated with oxidative homeostasis and lipids remodeling.

Maintenance of stable mitochondrial respiratory chains could enhance adaptability to high temperature, but the potential mechanism was not elucidated clearly in plants. In this study, we identified and isolated a TrFQR1 gene encoding the flavodoxin-like quinone reductase 1 (TrFQR1) located in mitochondria of leguminous white clover (Trifolium repens). Phylogenetic analysis indicated that amino acid sequences of FQR1 in various plant species showed a high degree of similarities. Ectopic expression of TrFQR1 protected yeast (Saccharomyces cerevisiae) from heat damage and toxic levels of benzoquinone, phenanthraquinone and hydroquinone. Transgenic Arabidopsis thaliana and white clover overexpressing TrFQR1 exhibited significantly lower oxidative damage and better photosynthetic capacity and growth than wild-type in response to high-temperature stress, whereas AtFQR1-RNAi A. thaliana showed more severe oxidative damage and growth retardation under heat stress. TrFQR1-transgenic white clover also maintained better respiratory electron transport chain than wild-type plants, as manifested by significantly higher mitochondrial complex II and III activities, alternative oxidase activity, NAD(P)H content, and coenzyme Q10 content in response to heat stress. In addition, overexpression of TrFQR1 enhanced the accumulation of lipids including phosphatidylglycerol, monogalactosyl diacylglycerol, sulfoquinovosyl diacylglycerol and cardiolipin as important compositions of bilayers involved in dynamic membrane assembly in mitochondria or chloroplasts positively associated with heat tolerance. TrFQR1-transgenic white clover also exhibited higher lipids saturation level and phosphatidylcholine:phosphatidylethanolamine ratio, which could be beneficial to membrane stability and integrity during a prolonged period of heat stress. The current study proves that TrFQR1 is essential for heat tolerance associated with mitochondrial respiratory chain, cellular reactive oxygen species homeostasis, and lipids remodeling in plants. TrFQR1 could be selected as a key candidate marker gene to screen heat-tolerant genotypes or develop heat-tolerant crops via molecular-based breeding.

Population Genomics Provide Insights into the Evolution and Adaptation of the Asia Corn Borer.

Understanding the genetic basis of pest adaptive evolution and the risk of adaptation in response to climate change is essential for the development of sustainable agricultural practices. However, the genetic basis of climatic adaptation for the Asian corn borer (ACB), Ostrinia furnacalis, the main pest of corn in Asia and Oceania, is poorly understood. Here, we revealed the genomic loci underlying the climatic adaptation and evolution in ACB by integrating population genomic and environmental factors. We assembled a 471-Mb chromosome-scale reference genome of ACB and resequenced 423 individuals covering 27 representative geographic areas. We inferred that the ACB effective population size changes tracked with the global temperature and followed by a recent decline. Based on an integrated analysis of whole-genome selection scans and genome-wide genotype-environment association studies, we revealed the genetic basis of ACB adaption to diverse climates. For diapause traits, we identified a major effect association locus containing a circadian clock gene (period) by analyzing a diapause-segregating population. Moreover, our predictions indicated that the northern populations were more ecologically resilient to climate change than the southern populations. Together, our results revealed the genomic basis for ACB environmental adaptation and provided potential candidate genes for future evolutionary studies and genetic adaptation to climate change, intending to maintain the efficacy and sustainability of novel control techniques.

Genome-wide identification of Aux/IAA gene family in white clover (Trifolium repens L.) and functional verification of TrIAA18 under different abiotic stress.

BACKGROUND: White clover (Trifolium repens L.) is an excellent leguminous cool-season forage with a high protein content and strong nitrogen-fixing ability. Despite these advantages, its growth and development are markedly sensitive to environmental factors. Indole-3-acetic acid (IAA) is the major growth hormone in plants, regulating plant growth, development, and response to adversity. Nevertheless, the specific regulatory functions of Aux/IAA genes in response to abiotic stresses in white clover remain largely unexplored. RESULTS: In this study, we identified 47 Aux/IAA genes in the white clover genome, which were categorized into five groups based on phylogenetic analysis. The TrIAAs promoter region co-existed with different cis-regulatory elements involved in developmental and hormonal regulation, and stress responses, which may be closely related to their diverse regulatory roles. Collinearity analysis showed that the amplification of the TrIAA gene family was mainly carried out by segmental duplication. White clover Aux/IAA genes showed different expression patterns in different tissues and under different stress treatments. In addition, we performed a yeast two-hybrid analysis to investigate the interaction between white clover Aux/IAA and ARF proteins. Heterologous expression indicated that TrIAA18 could enhance stress tolerance in both yeast and transgenic Arabidopsis thaliana. CONCLUSION: These findings provide new scientific insights into the molecular mechanisms of growth hormone signaling in white clover and its functional characteristics in response to environmental stress.

Monolayer Vacancy-Induced MXene Memory for Write-Verify-Free Programming.

The fundamental logic states of 1 and 0 in Complementary Metal-Oxide-Semiconductor (CMOS) are essential for modern high-speed non-volatile solid-state memories. However, the accumulated storage signal in conventional physical components often leads to data distortion after multiple write operations. This necessitates a write-verify operation to ensure proper values within the 0/1 threshold ranges. In this work, a non-gradual switching memory with two distinct stable resistance levels is introduced, enabled by the asymmetric vertical structure of monolayer vacancy-induced oxidized Ti3C2Tx MXene for efficient carrier trapping and releasing. This non-cumulative resistance effect allows non-volatile memories to attain valid 0/1 logic levels through direct reprogramming, eliminating the need for a write-verify operation. The device exhibits superior performance characteristics, including short write/erase times (100 ns), a large switching ratio (≈3 × 104), long cyclic endurance (>104 cycles), extended retention (>4 × 106 s), and highly resistive stability (>104 continuous write operations). These findings present promising avenues for next-generation resistive memories, offering faster programming speed, exceptional write performance, and streamlined algorithms.

3D Fast Sodium Transport Network of MoS2 Endowed by Coupling of Sulfur Vacancies and Sn Doping for Outstanding Sodium Storage.

A sulfur vacancy-rich, Sn-doped as well as carbon-coated MoS2 composite (Vs-SMS@C) is rationally synthesized via a simple hydrothermal method combined with ball-milling reduction, which enhances the sodium storage performance. Benefiting from the 3D fast Na+ transport network composed of the defective carbon coating, Mo─S─C bonds, enlarged interlayer spacing, S-vacancies, and lattice distortion in the composite, the Na+ storage kinetics is significantly accelerated. As expected, Vs-SMS@C releases an ultrahigh reversible capacity of 1089 mAh g-1 at 0.1 A g-1, higher than the theoretical capacity. It delivers a satisfactory capacity of 463 mAh g-1 at a high current density of 10 A g-1, which is the state-of-the-art rate capability compared to other MoS2 based sodium ion battery anodes to the knowledge. Moreover, a super long-term cycle stability is achieved by Vs-SMS@C, which keeps 91.6% of the initial capacity after 3000 cycles under the current density of 5 A g-1 in the voltage of 0.3-3.0 V. The sodium storage mechanism of Vs-SMS@C is investigated by employing electrochemical methods and ex situ techniques. The synergistic effect between S-vacancies and doped-Sn is evidenced by DFT calculations. This work opens new ideas for seeking excellent metal sulfide anodes.

Menarche-a journey into womanhood: age at menarche and health-related outcomes in East Asians.

STUDY QUESTION: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION: Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Unified framework for terahertz radiation from a single- or two-color plasma filament.

The plasma filament induced by photo-ionization in transparent media (e.g., air) is a competitive terahertz (THz) source, whose mechanism has been widely studied in two separate schemes, i.e., the one- or two-color femtosecond laser filamentation. However, the physical commonality of these two schemes is less explored currently, and a common theory is in urgent need. Here, we proposed the traveling-wave antenna (TWA) model applicable to both single- and dual-color laser fields, which successfully reproduced the reported far-field THz angular distribution/dispersion from different filament lengths with either a constant or a varied plasma density. This work paves the way toward a deeper understanding of the important laser-filament-based THz sources within the same theoretical framework.

Glycometabolic reprogramming in cementoblasts: A vital target for enhancing cell mineralization.

Cementum, a constituent part of periodontal tissues, has important adaptive and reparative functions. It serves to attach the tooth to alveolar bone and acts as a barrier delimit epithelial growth and bacteria evasion. A dynamic and highly responsive cementum is essential for maintaining occlusal relationships and the integrity of the root surface. It is a thin layer of mineralized tissue mainly produced by cementoblasts. Cementoblasts are osteoblast-like cells essential for the restoration of periodontal tissues. In recent years, glucose metabolism has been found to be critical in bone remodeling and osteoblast differentiation. However, the glucose metabolism of cementoblasts remains incompletely understood. First, immunohistochemistry staining and in vivo tracing with 18 F-fluorodeoxyglucose (18 F-FDG) revealed significantly higher glucose metabolism in cementum formation. To test the bioenergetic pathways of cementoblast differentiation, we compared the bioenergetic profiles of mineralized and unmineralized cementoblasts. As a result, we observed a significant increase in the consumption of glucose and production of lactate, coupled with the higher expression of glycolysis-related genes. However, the expression of oxidative phosphorylation-related genes was downregulated. The verified results were consistent with the RNA sequencing results. Likewise, targeted energy metabolomics shows that the levels of glycolytic metabolites were significantly higher in the mineralized cementoblasts. Seahorse assays identified an increase in glycolytic flux and reduced oxygen consumption during cementoblast mineralization. Apart from that, we also found that lactate dehydrogenase A (LDHA), a key glycolysis enzyme, positively regulates the mineralization of cementoblasts. In summary, cementoblasts mainly utilized glycolysis rather than oxidative phosphorylation during the mineralization process.

Anxiolytic effect of antidiabetic metformin is mediated by AMPK activation in mPFC inhibitory neurons.

Diabetic patients receiving the antidiabetic drug metformin have been observed to exhibit a lower prevalence of anxiety disorders, yet the precise mechanism behind this phenomenon is unclear. In our study, we found that anxiety induces a region-specific reduction in AMPK activity in the medial prefrontal cortex (mPFC). Concurrently, transgenic mice with brain-specific AMPK knockout displayed abnormal anxiety-like behaviors. Treatment with metformin or the overexpression of AMPK restored normal AMPK activity in the mPFC and mitigated social stress-induced anxiety-like behaviors. Furthermore, the specific genetic deletion of AMPK in the mPFC not only instigated anxiety in mice but also nullified the anxiolytic effects of metformin. Brain slice recordings revealed that GABAergic excitation and the resulting inhibitory inputs to mPFC pyramidal neurons were selectively diminished in stressed mice. This reduction led to an excitation-inhibition imbalance, which was effectively reversed by metformin treatment or AMPK overexpression. Moreover, the genetic deletion of AMPK in the mPFC resulted in a similar defect in GABAergic inhibitory transmission and a consequent hypo-inhibition of mPFC pyramidal neurons. We also generated a mouse model with AMPK knockout specific to GABAergic neurons. The anxiety-like behaviors in this transgenic mouse demonstrated the unique role of AMPK in the GABAergic system in relation to anxiety. Therefore, our findings suggest that the activation of AMPK in mPFC inhibitory neurons underlies the anxiolytic effects of metformin, highlighting the potential of this primary antidiabetic drug as a therapeutic option for treating anxiety disorders.

Synergetic Responses of Multiple Functions Induced by Phase Transition in Molecular Materials.

Materials that integrate magnetism, electricity and luminescence can not only improve the operational efficiency of devices, but also potentially generate new functions through their coupling. Therefore, multifunctional synergistic effects have broad application prospects in fields such as optoelectronic devices, information storage and processing, and quantum computing. However, in the research field of molecular materials, there are few reports on the synergistic multifunctional properties. The main reason is that there is insufficient awareness of how to obtain such material. In this brief review, we summarized the molecular materials with this characteristic. The structural phase transition of substances will cause changes in their physical properties, as the electronic configurations of the active unit in different structural phases are different. Therefore, we will classify and describe the multifunctional synergistic complexes based on the structural factors that cause the first-order phase transition of the complexes. This enables us to quickly screen complexes with synergistic responses to these properties through structural phase transitions, providing ideas for studying the synergistic response of physical properties in molecular materials.