Functionally Distinct Neuronal Ensembles within the Memory Engram.

Memories are believed to be encoded by sparse ensembles of neurons in the brain. However, it remains unclear whether there is functional heterogeneity within individual memory engrams, i.e., if separate neuronal subpopulations encode distinct aspects of the memory and drive memory expression differently. Here, we show that contextual fear memory engrams in the mouse dentate gyrus contain functionally distinct neuronal ensembles, genetically defined by the Fos- or Npas4-dependent transcriptional pathways. The Fos-dependent ensemble promotes memory generalization and receives enhanced excitatory synaptic inputs from the medial entorhinal cortex, which we find itself also mediates generalization. The Npas4-dependent ensemble promotes memory discrimination and receives enhanced inhibitory drive from local cholecystokinin-expressing interneurons, the activity of which is required for discrimination. Our study provides causal evidence for functional heterogeneity within the memory engram and reveals synaptic and circuit mechanisms used by each ensemble to regulate the memory discrimination-generalization balance.

Identification and characterization of two O-methyltransferases involved in biosynthesis of methylated 2-(2-phenethyl)chromones in agarwood.

The 2-(2-phenethyl)chromones (PECs) are the signature constituents responsible for the fragrance and pharmacological properties of agarwood. O-Methyltransferases (OMTs) are necessary for the biosynthesis of methylated PECs, but there is little known about OMTs in Aquilaria sinensis. In this study, we identified 29 OMT genes from the A. sinensis genome. Expression analysis showed they were differentially expressed in different tissues and responded to drill wounding. Comprehensive analysis of the gene expression and methylated PEC content revealed that AsOMT2, AsOMT8, AsOMT11, AsOMT16, and AsOMT28 could potentially be involved in methylated PECs biosynthesis. In vitro enzyme assays and functional analysis in Nicotiana benthamiana demonstrated that AsOMT11 and AsOMT16 could methylate 6-hydroxy-2-(2-phenylethyl)chromone to form 6-methoxy-2-(2-phenylethyl)chromone. A transient overexpression experiment in the variety 'Qi-Nan' revealed that AsOMT11 and AsOMT16 could significantly promote the accumulation of three major methylated PECs. Our results provide candidate genes for the mass production of methylated PECs using synthetic biology.

Non-Abelian Topological Phases and Their Quotient Relations in Acoustic Systems.

Non-Abelian topological phases (NATPs) exhibit enigmatic intrinsic physics distinct from well-established Abelian topological phases, while lacking straightforward configuration and manipulation, especially for classical waves. In this Letter, we exploit novel braiding-type couplings among a pair of triple-component acoustic dipoles, which act as functional elements with effective imaginary couplings. Sequencing them in one dimension allows us to generate acoustic NATPs in a compact yet time-reversal invariant Hermitian system. We further provide the whole phase diagram that encompasses all i, j, and k non-Abelian phases, and directly demonstrate their unique quotient relations via different end point states. Our NATPs based on real-space braiding may inspire the exploration of acoustic devices with non-commutative characters.

Mitigation of reverse osmosis membrane fouling by coagulation pretreatment to remove silica and transparent exopolymer particles.

The dissolution of silica and transparent exopolymer particles (TEP) can deposit on the membrane surface and cause serious membrane fouling in reverse osmosis (RO) technology. Coagulation, as a common pretreatment process for RO, can effectively intercept pollutants and alleviate membrane fouling. In this study, FeCl3 and AlCl3 coagulants and polyacrylamide (PAM) flocculants were used to explore the optimal coagulation conditions to reduce the concentration of silica and TEP in the RO process. The results showed that the two coagulants had the best removal effect on pollutants when the pH was 7 and the dosage was 50 mg/L. Considering the proportion of reversible fouling after coagulation, the removal rate of pollutants, and the residual amount of coagulation metal ions, the best PAM dosage was 5 mg/L for FeCl3 and 1 mg/L for AlCl3. After coagulation pretreatment, the Zeta potential decreased, and the particle size distribution increased, making pollutants tend to aggregate, thus effectively removing foulants. The removal mechanisms of pollutants by coagulation pretreatment were determined to be adsorption, electric neutralization and co-precipitation. This study determined the best removal conditions of silica and TEP by coagulation and explored the removal mechanism.

The LATS2 tumor suppressor inhibits SREBP and suppresses hepatic cholesterol accumulation.

The Hippo signaling pathway is a major regulator of organ size. In the liver, Hippo pathway deregulation promotes hyperplasia and hepatocellular carcinoma primarily through hyperactivation of its downstream effector, YAP. The LATS2 tumor suppressor is a core member of the Hippo pathway. A screen for LATS2-interacting proteins in liver-derived cells identified the transcription factor SREBP2, master regulator of cholesterol homeostasis. LATS2 down-regulation caused SREBP activation and accumulation of excessive cholesterol. Likewise, mice harboring liver-specific Lats2 conditional knockout (Lats2-CKO) displayed constitutive SREBP activation and overexpressed SREBP target genes and developed spontaneous fatty liver disease. Interestingly, the impact of LATS2 depletion on SREBP-mediated transcription was clearly distinct from that of YAP overexpression. When challenged with excess dietary cholesterol, Lats2-CKO mice manifested more severe liver damage than wild-type mice. Surprisingly, apoptosis, inflammation, and fibrosis were actually attenuated relative to wild-type mice, in association with impaired p53 activation. Subsequently, Lats2-CKO mice failed to recover effectively from cholesterol-induced damage upon return to a normal diet. Additionally, decreased LATS2 mRNA in association with increased SREBP target gene expression was observed in a subset of human nonalcoholic fatty liver disease cases. Together, these findings further highlight the tight links between tumor suppressors and metabolic homeostasis.

Microneedling Therapy for Striae Distensae: Systematic Review and Meta-Analysis.

INTRODUCTION: Striae distensae (SD), linear scars of derma, caused by disproportionate skin stretching, which indicates a cosmetic problem and even endangers individuals' psychosocial health. Microneedling, representing a relatively new procedural therapy, has shown brightening but diverse results in the remedy of SD. Our study systematically investigates and further evaluates the efficacy of microneedling for SD. METHOD: This study was conducted following the PRISMA guidelines. According to the preplanned search strategy, four electronic databases were comprehensively searched for eligible clinical controlled studies. Standardized mean difference (SMD) and odd ratio (OR) with 95% confidence intervals were calculated for continuous data and dichotomous data, respectively. RESULTS: According to the predetermined criteria, eleven eligible articles of six RCTs and five non-RCTs were included. Concerning clinical improvement, a significant difference was observed in the microneedle radiofrequency treatment subgroup (SMD: 0.57, 95% CI 0.20-0.94, P = 0.003). The pooled result of the second subgroup revealed that microneedling and lasers producing almost comparable effectiveness for treating SD with no significant difference (P = 0.35). The analysis result of the third subgroup of microneedling versus non-laser therapy indicated significant difference at the 5% significance level (SMD:1.01, 95% CI 0.51-1.51, P < 0.0001). With regard to patient satisfaction, the pooled estimate concluded that participants' satisfaction with therapeutic effect between MRF and laser group was comparable (P = 0.26), whereas microneedling exhibited significant superiority than both laser (P = 0.04) and non-laser treatments (SMD: 0.95, 95% CI 0.52-1.38, P < 0.0001). Occurrence of post-inflammatory hyperpigmentation (PIH) was not obvious in microneedling therapy compared to other treatments, and a statistically difference was observed (P = 0.0003). Microneedling treatment caused significant pain compared with laser therapy (P < 0.00001). CONCLUSION: This systematic review and meta-analysis has provided initial evidence of the efficacy and safety of microneedling technology for SD. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Constructing Metal(II)-Sulfate Site Catalysts toward Low Overpotential Carbon Dioxide Electroreduction to Fuel Chemicals.

Precise regulation of the active site structure is an important means to enhance the activity and selectivity of catalysts in CO2 electroreduction. Here, we creatively introduce anionic groups, which can not only stabilize metal sites with strong coordination ability but also have rich interactions with protons at active sites to modify the electronic structure and proton transfer process of catalysts. This strategy helps to convert CO2 into fuel chemicals at low overpotentials. As a typical example, a composite catalyst, CuO/Cu-NSO4/CN, with highly dispersed Cu(II)-SO4 sites has been reported, in which CO2 electroreduction to formate occurs at a low overpotential with a high Faradaic efficiency (-0.5 V vs. RHE, FEformate=87.4 %). Pure HCOOH is produced with an energy conversion efficiency of 44.3 % at a cell voltage of 2.8 V. Theoretical modeling demonstrates that sulfate promotes CO2 transformation into a carboxyl intermediate followed by HCOOH generation, whose mechanism is significantly different from that of the traditional process via a formate intermediate for HCOOH production.

Stress-induced changes of the cholinergic circuitry promote retrieval-based generalization of aversive memories.

Generalization, the process of applying knowledge acquired in one context to other contexts, often drives the expression of similar behaviors in related situations. At the cellular level, generalization is thought to depend on the activity of overlapping neurons that represent shared features between contexts (general representations). Using contextual fear conditioning in mice, we demonstrate that generalization can also occur in response to stress and result from reactivation of specific, rather than general context representations. We found that generalization emerges during memory retrieval, along with stress-induced abnormalities of septohippocampal oscillatory activity and acetylcholine release, which are typically found in negative affective states. In hippocampal neurons that represent aversive memories and drive generalization, cholinergic septohippocampal afferents contributed to a unique reactivation pattern of cFos, Npas4, and repressor element-1 silencing transcription factor (REST). Together, these findings suggest that generalization can be triggered by perceptually dissimilar but valence-congruent memories of specific aversive experiences. Through promoting the reactivation of such memories and their interference with ongoing behavior, abnormal cholinergic signaling could underlie maladaptive cognitive and behavioral generalization linked to negative affective states.

Progressive Stabilization of Brain Network Dynamics during Childhood and Adolescence.

Functional brain networks require dynamic reconfiguration to support flexible cognitive function. However, the developmental principles shaping brain network dynamics remain poorly understood. Here, we report the longitudinal development of large-scale brain network dynamics during childhood and adolescence, and its connection with gene expression profiles. Using a multilayer network model, we show the temporally varying modular architecture of child brain networks, with higher network switching primarily in the association cortex and lower switching in the primary regions. This topographical profile exhibits progressive maturation, which manifests as reduced modular dynamics, particularly in the transmodal (e.g., default-mode and frontoparietal) and sensorimotor regions. These developmental refinements mediate age-related enhancements of global network segregation and are linked with the expression profiles of genes associated with the enrichment of ion transport and nucleobase-containing compound transport. These results highlight a progressive stabilization of brain dynamics, which expand our understanding of the neural mechanisms that underlie cognitive development.

Suppressing grating lobes of large-aperture optical phased array with circular array design.

An optical phased array (OPA), especially a two-dimensional (2D) OPA, suffers from the trade-off among steering range, beam width, and the number of antennas. Aperiodic 2D array designs currently aimed to reduce the number of antennas and reduce grating lobes within a wide range fall short when an aperture approaches millimeter size. A circular OPA design is proposed to address this issue. The circular design substantially reduces the number of antennas while achieving the same wide steering range and narrow beam width of optimized aperiodic 2D OPA designs. Its efficient suppression of grating lobes, the key to a wide steering range with minimal number of antennas and large antenna spacing, is theoretically studied and validated by simulation. The novel, to the best of our knowledge, design allows less than 100 antennas, orders of magnitude reduction, for millimeter size aperture OPA designs. It paves the way for commercialization by significantly reducing control complexity and power consumption.

Experimental Demonstration of Bulk-Hinge Correspondence in a Three-Dimensional Topological Dirac Acoustic Crystal.

Three-dimensional topological Dirac semimetal (DSM) is a vital state to explore topological phases and phase transitions. However, its bulk-boundary correspondence is elusive. Here, we experimentally investigate the higher-order hinge states in an acoustic DSM. Not only removable trivial surface states but also robust nontrivial hinge arcs are observed, attributed to the direct correspondence between bulk polarization and hinge charge. We further reveal that a pair of zigzag and bearded hinges possess arcs located in complementary momentum regions. Our work provides solid proof of the bulk-hinge correspondence in DSM and sheds light on the study of topological hierarchy across dimensions.

Two-dimensional single-lobe Si photonic optical phased array with minimal antennas using a non-uniform large spacing array design.

We report a two-dimensional Si photonic optical phased array (OPA) optimized for a large optical aperture with a minimal number of antennas while maintaining single-lobe far field. The OPA chip has an optical aperture of ∼200µm by 150 µm comprising a 9×9 antenna array. The two-dimensional spacings between these antennas are much larger than the wavelength and are highly non-uniform optimized by the genetic deep learning algorithm. The phase of each antenna is independently tunable by a thermo-optical phase shifter. The experimental results validate the design and exhibit a 0.39∘×0.41∘ beamwidth within the 3 dB steering range of 14∘×11∘ limited by the numerical aperture of the far-field camera system. The method can be easily extended to a larger aperture for narrower beamwidth and wider steering range.

Effective half-wavelength pitch optical phased array design for aliasing-free 2D beam steering.

We present a method to design an optical phased array (OPA) simultaneously realizing both narrow beam width and aliasing-free 2D beam steering without the need to arrange the antennas at actual half-wavelength pitch. The method realizes an effective half-wavelength pitch in one direction formed by location projection of the antennas. The distances between the antennas in the other direction can be sufficiently large to form an effective large aperture realizing narrow beam width without needing a long grating. The presented method is proven by both theory and numerical simulations to achieve an equivalent grating-lobe-free far field of an ordinary half-wavelength pitch design. One design example exhibits 180° steering with a minimal beam width of 0.4° * 0.032° and a sidelobe suppression ratio of >13d B.

Compact 2D serpentine optical phased array.

We present a two-dimensional (2D) Si photonics optical phased array (OPA) using a serpentine design which eliminates the long directional couplers used in many 2D OPA designs. It significantly reduces the distance between the antenna benefitting far-field sidelobe reduction while maintaining high optical power use efficiency.

Pharmacokinetic comparisons of six steroid saponins in rat plasma following oral administration of crude and stir-fried Fructus Tribuli extracts by UHPLC-MS/MS.

Modern pharmacological studies have shown that Fructus Tribuli can improve sexual function and treat cardiovascular diseases. In this study, we focused on comparing the pharmacokinetics of crude Fructus Tribuli (CFT) and stir-fried Fructus Tribuli (SFT) to further clarify the changes in chemical composition in vivo. The quantitation of six analytes was performed in a triple quadrupole mass spectrometer using the multiple reaction monitoring mode. Separation was performed on a Halo® C18 column using 0.05% formic acid and 5 µmol/L sodium formate in water, and 0.05% formic acid and 5 µmol/L sodium formate in acetonitrile as the mobile phase. The selectivity, precision, accuracy, extraction recovery, matrix effect and stability of the method were fully validated. Compared with the crude group, the parameters Cmax and AUC0-t of terrestroside B and terrestrosin K increased significantly (P < 0.05), but the Cmax and AUC0-t of polianthoside D, terrestrinin D, tribuluside A and terrestrosin D were decreased, terrestrosin D being especially decreased (P < 0.05), after oral administration of SFT extract. These results showed that the developed method was suitable for pharmacokinetic analysis of the six steroid saponins of CFT and SFT in rat plasma, and can be used to facilitate future clinical studies.

Metal-Organic Framework Nanoparticles for Ameliorating Breast Cancer-Associated Osteolysis.

Breast cancer metastases to bone poses a significant challenge for the administration of treatment strategies. The bone microenvironment, metastatic tumor cells, osteoclasts, and tumor-associated macrophages (TAMs) all play crucial and synergistic roles in creating a favorable environment for the proliferation, progression, and survival of the metastatic tumor, which in turn induces osteoclast-mediated bone destruction. In this study, we functionalized immunostimulatory cytosine-phosphate-guanosine (CpG)-loaded metal-organic framework (MOF) nanoparticles with bone targeting capabilities by surface modification with FDA approved antiresorptive bisphosphonate, zoledronic acid (ZOL). The functionalized bone targeting immunostimulatory MOF (BT-isMOF) nanoparticles demonstrates strong binding to calcium phosphate in vitro and exhibits specific targeting and accumulation in bone tissues in vivo. In vitro cellular and biochemical analyses demonstrated that the BT-isMOF nanoparticles could potently inhibit osteoclast formation and concomitantly induce macrophages polarization toward the M1 pro-inflammatory phenotype. Finally, using the intratibial murine model of breast cancer bone metastasis, we showed that the administration of BT-isMOF nanoparticles significantly suppressed osteoclast-mediated bone destruction and enhanced polarization of tumor-resident macrophages to M1 phenotype. Together, our data provides promising evidence for the potential therapeutic application of the BT-isMOF nanoparticles in the treatment of breast cancer bone metastases.

Loss of DNA methylation in zebrafish embryos activates retrotransposons to trigger antiviral signaling.

Complex cytoplasmic nucleotide-sensing mechanisms can recognize foreign DNA based on a lack of methylation and initiate an immune response to clear the infection. Zebrafish embryos with global DNA hypomethylation caused by mutations in the ubiquitin-like with PHD and ring finger domains 1 (uhrf1) or DNA methyltransferase 1 (dnmt1) genes exhibit a robust interferon induction characteristic of the first line of defense against viral infection. We found that this interferon induction occurred in non-immune cells and examined whether intracellular viral sensing pathways in these cells were the trigger. RNA-seq analysis of uhrf1 and dnmt1 mutants revealed widespread induction of Class I retrotransposons and activation of cytoplasmic DNA viral sensors. Attenuating Sting, phosphorylated Tbk1 and, importantly, blocking reverse transcriptase activity suppressed the expression of interferon genes in uhrf1 mutants. Thus, activation of transposons in cells with global DNA hypomethylation mimics a viral infection by activating cytoplasmic DNA sensors. This suggests that antiviral pathways serve as surveillance of cells that have derepressed intragenomic parasites due to DNA hypomethylation.

Determination and prediction of the appropriate depth of right internal jugular vein catheterization via the middle approach in adults using transesophageal echocardiography.

PURPOSE: The appropriate depth of right internal jugular venous (RIJV) catheterization is still under debated. In this study, transesophageal echocardiography (TEE) is used to develop a prediction formula for fixed RIJV catheter depth. METHODS: Eighty patients with indications for intraoperative TEE and central line placement were enrolled. After intubation, a RIJV catheter was inserted via the middle approach using the Seldinger technique. When the J-tip of the guide wire appeared at the junction of the superior vena cava and the right atrium under TEE guidance, the guide wire was pulled back by approximately 2-3 cm, until its tip was out of the pericardial fold. This depth was regarded as the insertion depth of the central venous catheter. Body landmark distance was measured, and the prediction formula was generated. RESULTS: The mean central line depth after TEE-guided placement was 15.1 ± 1.7 cm. The prediction formula developed is as follows: Insertion depth = (Height ÷ 20) + (D ÷ 2), where D equals the distance from the insertion point to the sternal angle via the right sternoclavicular joint (r = 0.595, r2  = 0.354, P < 0.01). CONCLUSIONS: TEE is an effective method for determining the appropriate insertion depth for an RIJV catheter. The prediction formula can be used as a reference for future RIJV catheterizations via the middle approach.

Photonic topological insulator with broken time-reversal symmetry.

A topological insulator is a material with an insulating interior but time-reversal symmetry-protected conducting edge states. Since its prediction and discovery almost a decade ago, such a symmetry-protected topological phase has been explored beyond electronic systems in the realm of photonics. Electrons are spin-1/2 particles, whereas photons are spin-1 particles. The distinct spin difference between these two kinds of particles means that their corresponding symmetry is fundamentally different. It is well understood that an electronic topological insulator is protected by the electron's spin-1/2 (fermionic) time-reversal symmetry [Formula: see text] However, the same protection does not exist under normal circumstances for a photonic topological insulator, due to photon's spin-1 (bosonic) time-reversal symmetry [Formula: see text] In this work, we report a design of photonic topological insulator using the Tellegen magnetoelectric coupling as the photonic pseudospin orbit interaction for left and right circularly polarized helical spin states. The Tellegen magnetoelectric coupling breaks bosonic time-reversal symmetry but instead gives rise to a conserved artificial fermionic-like-pseudo time-reversal symmetry, Tp ([Formula: see text]), due to the electromagnetic duality. Surprisingly, we find that, in this system, the helical edge states are, in fact, protected by this fermionic-like pseudo time-reversal symmetry Tp rather than by the bosonic time-reversal symmetry Tb This remarkable finding is expected to pave a new path to understanding the symmetry protection mechanism for topological phases of other fundamental particles and to searching for novel implementations for topological insulators.

A Simulation Study on the Interaction Between Pollutant Nanoparticles and the Pulmonary Surfactant Monolayer.

A good understanding of the mechanism of interaction between inhaled pollutant nanoparticles (NPs) and the pulmonary surfactant monolayer is useful to study the impact of fine particulate matter on human health. In this work, we established coarse-grained models of four representative NPs with different hydrophilicity properties in the air (i.e., CaSO4, C, SiO2, and C6H14O2 NPs) and the pulmonary surfactant monolayer. Molecular dynamic simulations of the interaction during exhalation and inhalation breathing states were performed. The effects of NP hydrophilicity levels, NP structural properties, and cholesterol content in the monolayer on the behaviors of NP embedment or the transmembrane were analyzed by calculating the changes in potential energy, NP displacement, monolayer orderliness, and surface tension. Results showed that NPs can inhibit the ability of the monolayer to adjust surface tension. For all breathing states, the hydrophobic C NP cannot translocate across the monolayer and had the greatest influence on the structural properties of the monolayer, whereas the strongly hydrophilic SiO2 and C6H14O2 NPs can cross the monolayer with little impact. The semi-hydrophilic CaSO4 NP can penetrate the monolayer only during the inhalation breathing state. The hydrophilic flaky NP shows the best penetration ability, followed by the rod-shaped NP and spherical NP in turn. An increase in cholesterol content of the monolayer led to improved orderliness and decreased fluidity of the membrane system due to enhanced intermolecular forces. Consequently, difficulty in crossing the monolayer increased for the NPs.