Stochastic growth and selective stabilization generate stereotyped dendritic arbors.

Stereotyped dendritic arbors are shaped by dynamic and stochastic growth during neuronal development. It remains unclear how guidance receptors and ligands coordinate branch dynamic growth, retraction, and stabilization to specify dendritic arbors. We previously showed that extracellular ligand SAX-7/LICAM dictates the shape of the PVD sensory neuron via binding to the dendritic guidance receptor DMA-1, a single transmembrane adhesion molecule. Here, we perform structure-function analyses of DMA-1 and unexpectedly find that robust, stochastic dendritic growth does not require ligand-binding. Instead, ligand-binding inhibits growth, prevents retraction, and specifies arbor shape. Furthermore, we demonstrate that dendritic growth requires a pool of ligand-free DMA-1, which is maintained by receptor endocytosis and reinsertion to the plasma membrane via recycling endosomes. Mutants defective of DMA-1 endocytosis show severely truncated dendritic arbors. We present a model in which ligand-free guidance receptor mediates intrinsic, stochastic dendritic growth, while extracellular ligands instruct dendrite shape by inhibiting growth.

Theoretical Study of the Decomposition Reactions of 2-Vinylfuran.

With the development of new synthetic methods, 2-vinylfuran (V2F) has become a potential renewable biofuel. In this work, the potential energy surfaces for the V2F unimolecular dissociation reaction, the H-addition reaction, and the H-abstraction reaction were constructed at the G4 level. The temperature- and pressure-dependent rate constants for the relevant reactions on the potential energy surfaces were calculated by solving the master equation based on the transition state theory and Rice-Ramsperger-Kassel-Marcus theory. The results show that the rate constant for the intramolecular H-transfer reaction of V2F with H atoms from the C(5) site to the C(4) site to form 2-vinylfuran-3(2H)-carbene, followed by the decomposition to form h145te3o, is the highest. The rate constants for the H-abstraction reaction of V2F with H atoms were the largest at C(6) on the branched chain, followed by C(7), and the rate constants for the H-abstraction reaction at C(3), C(4), and C(5) on the furan ring were not competitive. Negative temperature coefficient effects are observed for the rate constants of the addition reactions of V2F with H atoms at low pressures, with the H-addition rate constant at the C(5) site being the largest. This work not only provides the necessary rate constants for the reaction mechanism of V2F combustion but also provides theoretical guidance for the practical application of furan-based fuels.

Cell cycle perturbation uncouples mitotic progression and invasive behavior in a post-mitotic cell.

The acquisition of the post-mitotic state is crucial for the execution of many terminally differentiated cell behaviors during organismal development. However, the mechanisms that maintain the post-mitotic state in this context remain poorly understood. To gain insight into these mechanisms, we used the genetically and visually accessible model of C. elegans anchor cell (AC) invasion into the vulval epithelium. The AC is a terminally differentiated uterine cell that normally exits the cell cycle and enters a post-mitotic state before initiating contact between the uterus and vulva through a cell invasion event. Here, we set out to identify the set of negative cell cycle regulators that maintain the AC in this post-mitotic, invasive state. Our findings revealed a critical role for CKI-1 (p21CIP1/p27KIP1) in redundantly maintaining the post-mitotic state of the AC, as loss of CKI-1 in combination with other negative cell cycle regulators-including CKI-2 (p21CIP1/p27KIP1), LIN-35 (pRb/p107/p130), FZR-1 (Cdh1/Hct1), and LIN-23 (ß-TrCP)-resulted in proliferating ACs. Remarkably, time-lapse imaging revealed that these ACs retain their ability to invade. Upon examination of a node in the gene regulatory network controlling AC invasion, we determined that proliferating, invasive ACs do so by maintaining aspects of pro-invasive gene expression. We therefore report that the requirement for a post-mitotic state for invasive cell behavior can be bypassed following direct cell cycle perturbation.

Phenylboronic acid modification-based novel dumbbell-shaped Au-Ag nanorod SERS substrates for ultrasensitive detection of SO42.

Based on the coordination principle of Lewis acids, a 4-mercaptophenylboronic acid (4-MPBA)-modified novel dumbbell-shaped Au-Ag nanorod (4-MPBA@DS Au-AgNR) substrate was developed, which could be combined with the surface-enhanced Raman scattering (SERS) technique to detect SO42- with high sensitivity and specificity. DS Au-AgNRs synthesized in this study with a dumbbell-shaped structure were verified by finite-difference time domain (FDTD) simulation to be capable of stimulating strong localized electromagnetic enhancement (EM) at nano-edge and gap, generating a large number of "hot spots" exhibiting excellent SERS performance. The 4-MPBA modified on its surface could specifically recognize SO42-, producing a change in the spectral peak at 1382 cm-1, thus realizing highly sensitive and specific sensing of SO42-. Under optimized conditions, this SERS sensor responded rapidly to SO42- within 2 minutes and demonstrated outstanding specificity. Calculation of the ratio of the characteristic peaks at 1382 and 1070 cm-1 (I1382/I1070) enabled the quantitative detection of SO42- in the range of 1 × 10-8-1 × 10-3 M, and the detection threshold was as low as 1 nM, which was superior to those of similar detection methods. Importantly, the utility and reliability of this SERS substrate for the determination of SO42- in actual samples were evaluated using ion chromatography as the gold standard, and there was no significant difference between the two protocols (P > 0.05), and the RSD was less than 6% with a satisfactory recovery rate (97.6-102.3%). Therefore, the present protocol has the advantages of simplicity and rapidity, high sensitivity, specificity, stability, and practicability in the determination of SO42- in aqueous solution, providing a reliable solution for tracing SO42- in the fields of food safety and environmental testing.

LPD-3 as a megaprotein brake for aging and insulin-mTOR signaling in C. elegans.

Insulin-mechanistic target of rapamycin (mTOR) signaling drives anabolic growth during organismal development; its late-life dysregulation contributes to aging and limits lifespans. Age-related regulatory mechanisms and functional consequences of insulin-mTOR remain incompletely understood. Here, we identify LPD-3 as a megaprotein that orchestrates the tempo of insulin-mTOR signaling during C. elegans aging. We find that an agonist insulin, INS-7, is drastically overproduced from early life and shortens lifespan in lpd-3 mutants. LPD-3 forms a bridge-like tunnel megaprotein to facilitate non-vesicular cellular lipid trafficking. Lipidomic profiling reveals increased hexaceramide species in lpd-3 mutants, accompanied by up-regulation of hexaceramide biosynthetic enzymes, including HYL-1. Reducing the abundance of HYL-1, insulin receptor/DAF-2 or mTOR/LET-363, normalizes INS-7 levels and rescues the lifespan of lpd-3 mutants. LPD-3 antagonizes SINH-1, a key mTORC2 component, and decreases expression with age. We propose that LPD-3 acts as a megaprotein brake for organismal aging and that its age-dependent decline restricts lifespan through the sphingolipid-hexaceramide and insulin-mTOR pathways.

Cell cycle perturbation uncouples mitotic progression and invasive behavior in a post-mitotic cell.

The acquisition of the post-mitotic state is crucial for the execution of many terminally differentiated cell behaviors during organismal development. However, the mechanisms that maintain the post-mitotic state in this context remain poorly understood. To gain insight into these mechanisms, we used the genetically and visually accessible model of C. elegans anchor cell (AC) invasion into the vulval epithelium. The AC is a terminally differentiated uterine cell that normally exits the cell cycle and enters a post-mitotic state, initiating contact between the uterus and vulva through a cell invasion event. Here, we set out to identify the set of negative cell cycle regulators that maintain the AC in this post-mitotic, invasive state. Our findings revealed a critical role for CKI-1 (p21CIP1/p27KIP1) in redundantly maintaining the post-mitotic state of the AC, as loss of CKI-1 in combination with other negative cell cycle regulators-including CKI-2 (p21CIP1/p27KIP1), LIN-35 (pRb/p107/p130), FZR-1 (Cdh1/Hct1), and LIN-23 (ß-TrCP)-resulted in proliferating ACs. Remarkably, time-lapse imaging revealed that these ACs retain their ability to invade. Upon examination of a node in the gene regulatory network controlling AC invasion, we determined that proliferating, invasive ACs do so by maintaining aspects of pro-invasive gene expression. We therefore report that the requirement for a post-mitotic state for invasive cell behavior can be bypassed following direct cell cycle perturbation.

Structural insights into the formation of repulsive netrin guidance complexes.

Netrins dictate attractive and repulsive responses during axon growth and cell migration, where the presence of the receptor Uncoordinated-5 (UNC-5) on target cells results in repulsion. Here, we showed that UNC-5 is a heparin-binding protein, determined its structure bound to a heparin fragment, and could modulate UNC-5-heparin affinity using a directed evolution platform or structure-based rational design. We demonstrated that UNC-5 and UNC-6/netrin form a large, stable, and rigid complex in the presence of heparin, and heparin and UNC-5 exclude the attractive UNC-40/DCC receptor from binding to UNC-6/netrin to a large extent. Caenorhabditis elegans with a heparin-binding-deficient UNC-5 fail to establish proper gonad morphology due to abrogated cell migration, which relies on repulsive UNC-5 signaling in response to UNC-6. Combining UNC-5 mutations targeting heparin and UNC-6/netrin contacts results in complete cell migration and axon guidance defects. Our findings establish repulsive netrin responses to be mediated through a glycosaminoglycan-regulated macromolecular complex.

Achieving High-Temperature Phosphorescence by Organic Cocrystal Engineering.

Organic phosphors offer a promising alternative in optoelectronics, but their temperature-sensitive feature has restricted their applications in high-temperature scenarios, and the attainment of high-temperature phosphorescence (HTP) is still challenging. Herein, a series of organic cocrystal phosphors are constructed by supramolecular assembly with an ultralong emission lifetime of up to 2.16 s. Intriguingly, remarkable stabilization of triplet excitons can also be realized at elevated temperature, and green phosphorescence is still exhibited in solid state even up to 150 °C. From special molecular packing within the crystal lattice, it has been observed that the orientation of isolated water cluster and well-controlled molecular organization via multiple interactions can favor the structural rigidity of cocrystals more effectively to suppress the nonradiative transition, thus resulting in efficient room-temperature phosphorescence and unprecedented survival of HTP.

Simultaneous detection of urea and lactate in sweat based on a wearable sweat biosensor.

Urea and lactate are biomarkers in sweat that is closely associated with human health. This study introduces portable, rapid, sensitive, stable, and high-throughput wearable sweat biosensors utilizing Au-Ag nanoshuttles (Au-Ag NSs) for the simultaneous detection of sweat urea and lactate. The Au-Ag NSs arrays within the biosensor's microfluidic cavity provide a substantial surface-enhanced Raman scattering (SERS) enhancement effect. The limit of detection (LOD) for urea and lactate are 2.35 × 10-6 and 8.66 × 10-7 mol/L, respectively. This wearable sweat biosensor demonstrates high resistance to compression bending, repeatability, and stability and can be securely attached to various body parts. Real-time sweat analysis of volunteers wearing the biosensors during exercise demonstrated the method's practicality. This wearable sweat biosensor holds significant potential for monitoring sweat dynamics and serves as a valuable tool for assessing bioinformation in sweat.

'It's a lonely journey': caregiving experiences and psychosocial distress among Chinese American dementia family caregivers.

OBJECTIVES: Chinese American family caregivers of persons with Alzheimer's disease and related dementia (ADRD) are a vulnerable but understudied population. The goal of this qualitative study was to examine their caregiving experiences and psychosocial distress process and explore intervention strategies. METHODS: In-depth individual interviews were conducted with 18 Chinese American dementia caregivers. All interviews were transcribed verbatim; thematic content analysis was conducted to construct a conceptual framework. RESULTS: All participants reported high levels of caregiving stress associated with care-recipients' advanced symptoms and required assistance in activities in daily living. The relationship of caregiver and care-recipient was strained in their roles transition. The complex healthcare system, insurance policies, and a lack of linguistically appropriate services aggravated their psychosocial distress. Chinese cultural norms on 'family harmony' hindered their seeking of social support. Prolonged caregiving stress led to physical and mental impairment, including poor sleep, depression, and chronic conditions. Participants described their caregiving experience as 'a lonely journey' with a pervasive sense of hopelessness and withdrawal; their distress process was positively or negatively influenced by their coping strategies. All participants were eager for any kind of support; especially culturally appropriate programs that could improve their caregiving skills, self-care, and access to services. CONCLUSION: Our data suggest that Chinese American dementia caregivers, especially those with limited English proficiency, experience elevated psychosocial distress, which was aggravated by the barriers to social support and health services due to their immigrant and minority status. Culturally appropriate targeted intervention is urgently needed for this underserved and vulnerable population.

MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement.

Microtubule doublets (MTDs) comprise an incomplete microtubule (B-tubule) attached to the side of a complete cylindrical microtubule. These compound microtubules are conserved in cilia across the tree of life; however, the mechanisms by which MTDs form and are maintained in vivo remain poorly understood. Here, we identify microtubule-associated protein 9 (MAP9) as an MTD-associated protein. We demonstrate that C. elegans MAPH-9, a MAP9 homolog, is present during MTD assembly and localizes exclusively to MTDs, a preference that is in part mediated by tubulin polyglutamylation. We find that loss of MAPH-9 causes ultrastructural MTD defects, including shortened and/or squashed B-tubules with reduced numbers of protofilaments, dysregulated axonemal motor velocity, and perturbed cilia function. Because we find that the mammalian ortholog MAP9 localizes to axonemes in cultured mammalian cells and mouse tissues, we propose that MAP9/MAPH-9 plays a conserved role in regulating ciliary motors and supporting the structure of axonemal MTDs.

SAD-1 kinase controls presynaptic phase separation by relieving SYD-2/Liprin-α autoinhibition.

Neuronal development orchestrates the formation of an enormous number of synapses that connect the nervous system. In developing presynapses, the core active zone structure has been found to assemble through liquid-liquid phase separation. Here, we find that the phase separation of Caenorhabditis elegans SYD-2/Liprin-α, a key active zone scaffold, is controlled by phosphorylation. We identify the SAD-1 kinase as a regulator of SYD-2 phase separation and determine presynaptic assembly is impaired in sad-1 mutants and increased by overactivation of SAD-1. Using phosphoproteomics, we find SAD-1 phosphorylates SYD-2 on 3 sites that are critical to activate phase separation. Mechanistically, SAD-1 phosphorylation relieves a binding interaction between 2 folded domains in SYD-2 that inhibits phase separation by an intrinsically disordered region (IDR). We find synaptic cell adhesion molecules localize SAD-1 to nascent synapses upstream of active zone formation. We conclude that SAD-1 phosphorylates SYD-2 at developing synapses, activating its phase separation and active zone assembly.

Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans.

A growing body of evidence suggests that cell division and basement membrane invasion are mutually exclusive cellular behaviors. How cells switch between proliferative and invasive states is not well understood. Here, we investigated this dichotomy in vivo by examining two cell types in the developing Caenorhabditis elegans somatic gonad that derive from equipotent progenitors, but exhibit distinct cell behaviors: the post-mitotic, invasive anchor cell and the neighboring proliferative, non-invasive ventral uterine (VU) cells. We show that the fates of these cells post-specification are more plastic than previously appreciated and that levels of NHR-67 are important for discriminating between invasive and proliferative behavior. Transcription of NHR-67 is downregulated following post-translational degradation of its direct upstream regulator, HLH-2 (E/Daughterless) in VU cells. In the nuclei of VU cells, residual NHR-67 protein is compartmentalized into discrete punctae that are dynamic over the cell cycle and exhibit liquid-like properties. By screening for proteins that colocalize with NHR-67 punctae, we identified new regulators of uterine cell fate maintenance: homologs of the transcriptional co-repressor Groucho (UNC-37 and LSY-22), as well as the TCF/LEF homolog POP-1. We propose a model in which the association of NHR-67 with the Groucho/TCF complex suppresses the default invasive state in non-invasive cells, which complements transcriptional regulation to add robustness to the proliferative-invasive cellular switch in vivo.

[Traditional Chinese medicine used as anti-aging agent by targeting nuclear factor erythroid 2-related factor 2 signaling pathway].

The imbalance of redox homeostasis is a major characteristic of aging and contributes to the pathogenesis of various aging-related diseases. As a regulatory hub of redox homeostasis, nuclear factor erythroid 2-related factor 2 (NRF2) can attenuate oxidative stress by activating the transcription of many antioxidant enzymes. China is the birthplace of traditional Chinese medicine (TCM) which has been wildly used as medicine for thousands of years. Recently, TCM as anti-aging medicine has attracted enormous attention. Focusing on the NRF2 signaling pathway, this paper summarizes the correlation between various anti-aging TCM and the NRF2 signaling, and discusses the common key mechanisms by which TCM slows the aging process by targeting the NRF2 signaling network.

Wnt signaling and contact-mediated repulsion shape sensory dendritic fields.

The complete and non-redundant coverage of sensory tissues by neighboring neurons enables effective detection of stimuli in the environment. How the neurites of adjacent neurons establish their boundaries to achieve this completeness in coverage remains incompletely understood. Here, we use distinct fluorescent reporters to study two neighboring sensory neurons with complex dendritic arbors, FLP and PVD, in C. elegans . We quantify the sizes of their dendritic fields, and identify CWN-2/Wnt and LIN-17/Frizzled as a ligand and receptor that regulate the relative dendritic field sizes of these two neurons. Loss of either cwn-2 or lin-17 results in complementary changes in the size of the dendritic fields of both neurons; the FLP arbor expands, while that of PVD shrinks. Using an endogenous knock-in mNeonGreen-CWN-2/Wnt, we find that CWN-2/Wnt is localized along the path of growing FLP dendrites. Dynamic imaging shows a significant braking of FLP dendrite growth upon CWN-2/Wnt contact. We find that LIN-17/Frizzled functions cell-autonomously in FLP to limit dendritic field size and propose that PVD fills the space left by FLP through contact-induced retraction. Our results reveal that interactions of dendrites with adjacent dendrites and with environmental cues both shape the boundaries of neighboring dendritic fields. Highlights: ▫ Secreted Wnt CWN-2 and cell-autonomous activity of neuronal LIN-17/Frizzled receptors restrict FLP dendritic field sizes▫ Endogenously tagged CWN-2/Wnt is punctate and visible in the same plane of growing FLP dendrites▫ Growth of developing FLP dendrites is inhibited upon contact with extracellular CWN-2/Wnt and with PVD dendrites.

Theoretical and Modeling Study about the Low-Temperature Reaction Mechanism Between Oxymethylene Ether-2 (OME2) Radicals and O2.

Oxymethylene ether-2 (CH3-O-CH2-O-CH2-O-CH3, OME2), a carbon-neutral fuel, was hydrogenated from CO2 captured in air or exhaust gases and reused for synthesis with renewable electricity. In the current work, two different potential energy surfaces (PESs) for the reaction of OME2 radicals with O2 were constructed at the CCSD(T)/CBS//M062X/6-311++G(d,p) level. Based on the Rice-Ramsperger-Kassel-Marcus (RRKM) theory and transition state theory, the temperature- and pressure-dependent rate constants for the relevant reactions on the PES were calculated by solving the master equation. The Arrhenius equation has been used to fit the temperature- and pressure-dependent reaction rate constants. The main reaction channels on the PES are discussed, showing that initial adduct generation and intramolecular H-transfer reactions are the key reaction channels for low-temperature combustion. Among them, the HO2 concerted elimination reaction channel needs to overcome higher energy barriers leading to uncompetitive HO2 concerted elimination reactions. The calculated rate constants were updated to the OME2 combustion model, and the updated model is in considerable agreement with experimentally measured data on the ignition delay time in the shock tube. The present work provides support for further studies on the oxidation reaction of long-chain OME..

Controlling magnon-magnon entanglement and steering by atomic coherence.

Here we show that it is possible to control magnon-magnon entanglement in a hybrid magnon-atom-cavity system based on atomic coherence. In a four-level V-type atomic system, two strong fields are applied to drive two dipole-allowed transitions and two microwave cavity modes are coupled with two dipole forbidden transitions as well as two magnon modes simultaneously. It is found that the stable magnon-magnon entanglement, one-way steering and two-way EPR steering can be generated and controlled by atomic coherence according to the following two points: (i) the coherent coupling between magnon and atoms is established via exchange of virtual photons; (ii) the dissipation of magnon mode is dominant over amplification since one of the atomic states mediated one-channel interaction always keeps empty. The coherent control of magnon-magnon correlations provides an effective approach to modify macroscopic quantum effects using the laser-driven atomic systems.

Phase regulation enabling dense polymer-based composite electrolytes for solid-state lithium metal batteries.

Solid polymer electrolytes with large-scale processability and interfacial compatibility are promising candidates for solid-state lithium metal batteries. Among various systems, poly(vinylidene fluoride)-based polymer electrolytes with residual solvent are appealing for room-temperature battery operations. However, their porous structure and limited ionic conductivity hinder practical application. Herein, we propose a phase regulation strategy to disrupt the symmetry of poly(vinylidene fluoride) chains and obtain the dense composite electrolyte through the incorporation of MoSe2 sheets. The electrolyte with high dielectric constant can optimize the solvation structures to achieve high ionic conductivity and low activation energy. The in-situ reactions between MoSe2 and Li metal generate Li2Se fast conductor in solid electrolyte interphase, which improves the Coulombic efficiency and interfacial kinetics. The solid-state Li||Li cells achieve robust cycling at 1 mA cm-2, and the Li||LiNi0.8Co0.1Mn0.1O2 full cells show practical performance at high rate (3C), high loading (2.6 mAh cm-2) and in pouch cell.

DNA barcoding of marine teleost fishes (Teleostei) in Cebu, the Philippines, a biodiversity hotspot of the coral triangle.

A morphology-based barcoding library of market teleost fishes (Teleostei) in Cebu is built based on cytochrome c oxidase subunit I (COI) sequences and voucher specimens which aimed to establish a reliable reference of frequently traded fishes in the province, a biodiversity hotspot at the center of the Philippine archipelago. A total of 1721 specimens were collected from 18 fish markets and landing sites around the province, in which 538 specimens were sequenced belonging to 393 species from 229 genera, 86 families, and 37 orders. Most speciose families are coral reef or reef-related shallow-water species. Twelve species from 11 families are newly recorded in the Philippine waters, among which 7 species are deep-sea inhabitants, while 3 species have expanded their distribution range. Only 20 taxa could not be identified to the species level due to the difficulty in morphological examinations, absence of matched reference sequences in online databases, and/or problematic species awaiting further studies. This first comprehensive DNA barcoding survey of Cebu fishes can facilitate further taxonomic research as well as the conservation and management of fisheries in the Philippines.

MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity.

Transcription factors (TFs) play critical roles in specifying many aspects of neuronal cell fate including dendritic morphology. How TFs are accurately regulated during neuronal morphogenesis is not fully understood. Here, we show that LIM homeodomain protein MEC-3, the key TF for C. elegans PVD dendrite morphogenesis, is regulated by both alternative splicing and an E3 ubiquitin ligase. The mec-3 gene generates several transcripts by alternative splicing. We find that mbl-1, the orthologue of the muscular dystrophy disease gene muscleblind-like (MBNL), is required for PVD dendrite arbor formation. Our data suggest mbl-1 regulates the alternative splicing of mec-3 to produce its long isoform. Deleting the long isoform of mec-3(deExon2) causes reduction of dendrite complexity. Through a genetic modifier screen, we find that mutation in the E3 ubiquitin ligase EEL-1 suppresses mbl-1 phenotype. eel-1 mutants also suppress mec-3(deExon2) mutant but not the mec-3 null phenotype. Loss of EEL-1 alone leads to excessive dendrite branches. Together, these results indicate that MEC-3 is fine-tuned by alternative splicing and the ubiquitin system to produce the optimal level of dendrite branches.