Light modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis.

Public health studies indicate that artificial light is a high-risk factor for metabolic disorders. However, the neural mechanism underlying metabolic modulation by light remains elusive. Here, we found that light can acutely decrease glucose tolerance (GT) in mice by activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) innervating the hypothalamic supraoptic nucleus (SON). Vasopressin neurons in the SON project to the paraventricular nucleus, then to the GABAergic neurons in the solitary tract nucleus, and eventually to brown adipose tissue (BAT). Light activation of this neural circuit directly blocks adaptive thermogenesis in BAT, thereby decreasing GT. In humans, light also modulates GT at the temperature where BAT is active. Thus, our work unveils a retina-SON-BAT axis that mediates the effect of light on glucose metabolism, which may explain the connection between artificial light and metabolic dysregulation, suggesting a potential prevention and treatment strategy for managing glucose metabolic disorders.

Foxm1 regulates cardiomyocyte proliferation in adult zebrafish after cardiac injury.

The regenerative capacity of the mammalian heart is poor, with one potential reason being that adult cardiomyocytes cannot proliferate at sufficient levels to replace lost tissue. During development and neonatal stages, cardiomyocytes can successfully divide under injury conditions; however, as these cells mature their ability to proliferate is lost. Therefore, understanding the regulatory programs that can induce post-mitotic cardiomyocytes into a proliferative state is essential to enhance cardiac regeneration. Here, we report that the forkhead transcription factor Foxm1 is required for cardiomyocyte proliferation after injury through transcriptional regulation of cell cycle genes. Transcriptomic analysis of injured zebrafish hearts revealed that foxm1 expression is increased in border zone cardiomyocytes. Decreased cardiomyocyte proliferation and expression of cell cycle genes in foxm1 mutant hearts was observed, suggesting it is required for cell cycle checkpoints. Subsequent analysis of a candidate Foxm1 target gene, cenpf, revealed that this microtubule and kinetochore binding protein is also required for cardiac regeneration. Moreover, cenpf mutants show increased cardiomyocyte binucleation. Thus, foxm1 and cenpf are required for cardiomyocytes to complete mitosis during zebrafish cardiac regeneration.

Unusual phototransduction via cross-motif signaling from Gq to adenylyl cyclase in intrinsically photosensitive retinalganglion cells.

Nonimage-forming vision in mammals is mediated primarily by melanopsin (OPN4)-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). In mouse M1-ipRGCs, melanopsin predominantly activates, via Gαq,11,14, phospholipase C-ß4 to open transient receptor 6 (TRPC6) and TRPC7 channels. In M2- and M4-ipRGCs, however, a prominent phototransduction mechanism involves the opening of hyperpolarization- and cyclic nucleotide-gated channels via cyclic nucleotide, although the upstream steps remain uncertain. We report here experiments, primarily on M4-ipRGCs, with photo-uncaging of cyclic nucleotides and virally expressed CNGA2 channels to conclude that the second messenger is cyclic adenosine monophosphate (cAMP) - very surprising considering that cyclic guanosine monophosphate (cGMP) is used in almost all cyclic nucleotide-mediated phototransduction mechanisms across the animal kingdom. We further found that the upstream G protein is likewise Gq, which via its Gßγ subunits directly activates adenylyl cyclase (AC). Our findings are a demonstration in a native cell of a cross-motif GPCR signaling pathway from Gq directly to AC with a specific function.

Coexistence within one cell of microvillous and ciliary phototransductions across M1- through M6-IpRGCs.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) serve as primary photoceptors by expressing the photopigment, melanopsin, and also as retinal relay neurons for rod and cone signals en route to the brain, in both cases for the purpose of non-image vision as well as aspects of image vision. So far, six subtypes of ipRGCs (M1 through M6) have been characterized. Regarding their phototransduction mechanisms, we have previously found that, unconventionally, rhabdomeric (microvillous) and ciliary signaling motifs co-exist within a given M1-, M2-, and M4-ipRGC, with the first mechanism involving PLCß4 and TRPC6,7 channels and the second involving cAMP and HCN channels. We have now examined M3-, M5-, and M6-cells and found that each cell likewise uses both signaling pathways for phototransduction, despite differences in the percentage representation by each pathway in a given ipRGC subtype for bright-flash responses (and saturated except for M6-cells). Generally, M3- and M5-cells show responses quite similar in kinetics to M2-responses, and M6-cell responses resemble broadly those of M1-cells although much lower in absolute sensitivity and amplitude. Therefore, similar to rod and cone subtypes in image vision, ipRGC subtypes possess the same phototransduction mechanism(s) even though they do not show microvilli or cilia morphologically.

Three amphioxus reference genomes reveal gene and chromosome evolution of chordates.

The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding of the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention, or rearrangements between descendants of whole-genome duplications, which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its three-dimensional chromatin architecture at the onset of zygotic activation and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.

TransIntegrator: capture nearly full protein-coding transcript variants via integrating Illumina and PacBio transcriptomes.

Genes have the ability to produce transcript variants that perform specific cellular functions. However, accurately detecting all transcript variants remains a long-standing challenge, especially when working with poorly annotated genomes or without a known genome. To address this issue, we have developed a new computational method, TransIntegrator, which enables transcriptome-wide detection of novel transcript variants. For this, we determined 10 Illumina sequencing transcriptomes and a PacBio full-length transcriptome for consecutive embryo development stages of amphioxus, a species of great evolutionary importance. Based on the transcriptomes, we employed TransIntegrator to create a comprehensive transcript variant library, namely iTranscriptome. The resulting iTrancriptome contained 91 915 distinct transcript variants, with an average of 2.4 variants per gene. This substantially improved current amphioxus genome annotation by expanding the number of genes from 21 954 to 38 777. Further analysis manifested that the gene expansion was largely ascribed to integration of multiple Illumina datasets instead of involving the PacBio data. Moreover, we demonstrated an example application of TransIntegrator, via generating iTrancriptome, in aiding accurate transcriptome assembly, which significantly outperformed other hybrid methods such as IDP-denovo and Trinity. For user convenience, we have deposited the source codes of TransIntegrator on GitHub as well as a conda package in Anaconda. In summary, this study proposes an affordable but efficient method for reliable transcriptomic research in most species.

Dynamic and static interactions between p120 catenin and E-cadherin regulate the stability of cell-cell adhesion.

The association of p120 catenin (p120) with the juxtamembrane domain (JMD) of the cadherin cytoplasmic tail is critical for the surface stability of cadherin-catenin cell-cell adhesion complexes. Here, we present the crystal structure of p120 isoform 4A in complex with the JMD core region (JMD(core)) of E-cadherin. The p120 armadillo repeat domain contains modular binding pockets that are complementary to electrostatic and hydrophobic properties of the JMD(core). Single-residue mutations within the JMD(core)-binding site of p120 abolished its interaction with E- and N-cadherins in vitro and in cultured cells. These mutations of p120 enabled us to clearly differentiate between N-cadherin-dependent and -independent steps of neuronal dendritic spine morphogenesis crucial for synapse development. NMR studies revealed that p120 regulates the stability of cadherin-mediated cell-cell adhesion by associating with the majority of the JMD, including residues implicated in clathrin-mediated endocytosis and Hakai-dependent ubiquitination of E-cadherin, through its discrete "dynamic" and "static" binding sites.

The role of acid-sensing ion channels in monosodium urate-induced gouty pain in mice.

Acid-sensing ion channels (ASICs) in dorsal root ganglion (DRG) neurons play an important role in inflammatory pain. The objective of this study is to observe the regulatory role of ASICs in monosodium urate (MSU) crystal-induced gout pain and explore the basis for ASICs in DRG neurons as a target for gout pain treatment. The gout arthritis model was induced by injecting MSU crystals into the ankle joint of mice. The circumference of the ankle joint was used to evaluate the degree of swelling; the von Frey filaments were used to determine the withdrawal threshold of the paw. ASIC currents and action potentials (APs) were recorded by patch clamp technique in DRG neurons. The results displayed that injecting MSU crystals caused ankle edema and mechanical hyperalgesia of the paw, which was relieved after amiloride treatment. The ASIC currents in DRG neurons were increased to a peak on the second day after injecting MSU crystals, which were decreased after amiloride treatment. MSU treatment increased the current density of ASICs in different diameter DRG cells. MSU treatment does not change the characteristics of AP. The results suggest that ASICs in DRG neurons participate in MSU crystal-induced gout pain.

Visible Light-Gating Responsive Nanochannel for Controlled Release of the Fungicide.

Fungicides have been widely used to protect crops from the disease of pythium aphanidermatum (PA). However, excessive use of synthetic fungicides can lead to fungal pathogens developing microbicide resistance. Recently, biomimetic nano-delivery systems have been used for controlled release, reducing the overuse of fungicides, and thereby protecting the environment. In this paper, inspired by chloroplast membranes, visible light biomimetic channels are constructed by using retinal, the main component of green pigment on chloroplasts in plants, which can achieve the precise controlled release of the model fungicide methylene blue (MB). The experimental results show that the biomimetic channels have good circularity after and before light conditions. In addition, it is also found that the release of MB in visible light by the retinal-modified channels is 8.78 µmol·m-2·h-1, which is four times higher than that in the before light conditions. Furthermore, MB, a bactericide drug model released under visible light, can effectively inhibit the growth of PA, reaching a 97% inhibition effect. The biomimetic nanochannels can realize the controlled release of the fungicide MB, which provides a new way for the treatment of PA on the leaves surface of cucumber, further expanding the application field of biomimetic nanomembrane carrier materials.

Constructing Asymmetric Charge Polarized NiCo Prussian Blue Analogue for Promoted Electrocatalytic Methanol to Formate Conversion.

The highly selective electrochemical conversion of methanol to formate is of great significance for various clean energy devices, but understanding the structure-to-property relationship remains unclear. Here, the asymmetric charge polarized NiCo prussian blue analogue (NiCo PBA-100) is reported to exhibit remarkable catalytic performance with high current density (210 mA cm-2 @1.65 V vs RHE) and Faraday efficiency (over 90%). Meanwhile, the hybrid water splitting and Zinc-methanol-battery assembled by NiCo PBA-100 display the promoted performance with decent stability. X-ray absorption spectroscopy (XAS) and operando Raman spectroscopy indicate that the asymmetric charge polarization in NiCo PBA leads to more unoccupied states of Ni and occupied states of Co, thereby facilitating the rapid transformation of the high-active catalytic centers. Density functional theory calculations combining operando Fourier transform infrared spectroscopy demonstrate that the final reconstructed catalyst derived by NiCo PBA-100 exhibits rearranged d band properties along with a lowered energy barrier of the rate-determining step and favors the desired formate production.

Enhancement and suppression of nonsequential double ionization by spatially inhomogeneous fields.

Using the three-dimensional classical ensemble approach, we theoretically investigate the nonsequential double ionization of argon atoms in an intense laser field enhanced by bowtie-nanotip. We observe an anomalous decrease in the double ionization yield as the laser intensity increases, along with a significant gap in the low momentum of photoelectrons. According to our theoretical analysis, the finite range of the induced field by the nanostructure is the fundamental cause of the decline in double ionization yield. Driven by the enhanced inhomogeneous field, energetic electrons can escape from the finite range of nanotips without returning. This reduces the possibility of re-scattering on the nucleus and imprints the finite size effect into the double ionization yield and momentum distribution of photoelectrons in the form of yield decline and a gap in the photoelectron-momentum distribution.

Association between the triglyceride-glucose index and subclinical left ventricular systolic dysfunction in obese patients.

BACKGROUND: The association between the triglyceride-glucose (TyG) index and subclinical left ventricular (LV) systolic dysfunction in obese patients remains unclear. This study aimed to investigate the relationship between the TyG index and LV global longitudinal strain (GLS) in obese patients. METHODS: A total of 1028 obese patients from January 2019 to January 2024 were included in the present study. Clinical parameters and biochemical and echocardiographic data were obtained from the participants. LV GLS was obtained from the GE EchoPAC workstation for evaluating subclinical LV function. The TyG index was calculated as Ln (fasting TG [mg/dL] × fasting glucose [mg/dL]/2). LV GLS was compared between obese patients with a high TyG index and those with a low TyG index. RESULTS: Obese patients with a high TyG index had greater incidences of hypertension, diabetes mellitus and hyperlipidaemia. The LV GLS was significantly lower in the high TyG index group than in the low TyG index group (P = 0.01). After adjusting for sex, age, body mass index, heart rate, hypertension, diabetes mellitus, dyslipidaemia, blood urea nitrogen, serum creatinine, LV mass and LV hypertrophy, the TyG index remained an independent risk indicator related to an LV GLS < 20% (OR: 1.520, 95% CI: 1.040 to 2.221; P = 0.031). CONCLUSIONS: We concluded that an increase in the TyG index is independently associated with subclinical LV systolic dysfunction in obese patients.

Recombinant human IL-37 attenuates acute cardiac allograft rejection in mice.

BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed in vitro. Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4+ cell inhibition was also elucidated. RESULTS: Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4+ and CD11c+ cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4+ cells of splenocytes. In vitro, similar to the in vivo experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4+ cells. CONCLUSIONS: We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.

Staphylococcal enterotoxin B exposed to pregnant rats inhibits the hedgehog signaling pathway in thymic T lymphocytes of the offspring.

The Hedgehog (Hh) signaling pathway is involved in T cell differentiation and development and plays a major regulatory part in different stages of T cell development. A previous study by us suggested that prenatal exposure to staphylococcal enterotoxin B (SEB) changed the percentages of T cell subpopulation in the offspring thymus. However, it is unclear whether prenatal SEB exposure impacts the Hh signaling pathway in thymic T cells. In the present study, pregnant rats at gestational day 16 were intravenously injected once with 15 µg SEB, and the thymi of both neonatal and adult offspring rats were aseptically acquired to scrutinize the effects of SEB on the Hh signaling pathway. It firstly found that prenatal SEB exposure clearly caused the increased expression of Shh and Dhh ligands of the Hh signaling pathway in thymus tissue of both neonatal and adult offspring rats, but significantly decreased the expression levels of membrane receptors of Ptch1 and Smo, transcription factor Gli1, as well as target genes of CyclinD1, C-myc, and N-myc in Hh signaling pathway of thymic T cells. These data suggest that prenatal SEB exposure inhibits the Hh signaling pathway in thymic T lymphocytes of the neonatal offspring, and this effect can be maintained in adult offspring via the imprinting effect.

Efficient Adsorption and Elimination of Tm3+ For Enhanced Seed Germination Using Pillar[5]Arene Polymer.

While rare earth elements (REEs) are essential for modern technology, their production methods raise concerns for agriculture. Researchers are now exploring ways to control and recycle REEs pollution, aiming to minimize agricultural impacts and potentially even develop methods to utilize these elements for improved crop yields. Regarding this issue, a new type of pillar[5]arene polymer (Pol-P[5]-BTZP) has been designed and synthesized by click reaction to enhance the efficiency of adsorption and recovery of rare earth metals. This polymer incorporates the unique structure of 2,6-di-1,2,3-triazolyl-pyridine. The results of various analyses revealed that Pol-P[5]-BTZP exhibits excellent thermal stability, a high specific surface area, and well-distributed networks of micropores and mesoporous structures. The adsorption capacity of Pol-P[5]-BTZP for Tm3+, a representative REE, was evaluated using the Langmuir and Freundlich isothermal adsorption models with a maximum adsorption capacity (Qmax) of 127.71 mg/g. Furthermore, the versatility of Pol-P[5]-BTZP in adsorption and recovering various REEs was tested. In addition to its adsorption capabilities, the potential of Pol-P[5]-BTZP for rare earth recovery and reuse was assessed through experiments on the impact of Tm3+ and La3+ on seed germination. These experiments demonstrated the wide-ranging applicability of Pol-P[5]-BTZP in recovering and reusing REEs for green agriculture.

Selectively Transport and Removal of Fluoride Ion by Pillar[5]Arene Polymer-Filled Nanochannel Membrane.

Excess fluoride ions in groundwater accumulate through the roots of crops, affecting photosynthesis and inhibiting their growth. Long-term bioaccumulation also threatens human health because it is poorly degradable and toxic. Currently, one of the biggest challenges is developing a unique material that can efficiently remove fluoride ions from the environment. The excellent properties of functionalized pillar[5]arene polymer-filled nanochannel membranes were explored to address this challenge. Constructing a multistage porous nanochannel membrane, consisting of microscale etched nanochannels and nanoscale pillar[5]arene cross-linked polymer voids. A fluoride removal rate of 0.0088 mmol ⋅ L-1 ⋅ min-1 was achieved. Notably, this rate surpassed the rates observed with other control ions by a factor of 6 to 8.8. Our research provides a new direction for developing water fluoride ion removal materials.

Differences between long- and short-wavelength light-induced retinal damage and the role of PARP-1 in retinal injury induced by blue light.

Photobiomodulation (PBM) therapy uses light of different wavelengths to treat various retinal degeneration diseases, but the potential damage to the retina caused by long-term light irradiation is still unclear. This study were designed to detect the difference between long- and short-wavelength light (650-nm red light and 450-nm blue light, 2.55 mW/cm2, reference intensity in PBM)-induced injury. In addition, a comparative study was conducted to investigate the differences in retinal light damage induced by different irradiation protocols (short periods of repeated irradiation and a long period of constant irradiation). Furthermore, the protective role of PARP-1 inhibition on the molecular mechanism of blue light-induced injury was confirmed by a gene knockdown technique or a specific inhibitor through in vitro and in vivo experiments. The results showed that the susceptibility to retinal damage caused by irradiation with long- and short-wavelength light is different. Shorter wavelength lights, such as blue light, induce more severe retinal damage, while the retina exhibits better resistance to longer wavelength lights, such as red light. In addition, repeated irradiation for short periods induces less retinal damage than constant exposure over a long period. PARP-1 plays a critical role in the molecular mechanism of blue light-induced damage in photoreceptors and retina, and inhibiting PARP-1 can significantly protect the retina against blue light damage. This study lays an experimental foundation for assessing the safety of phototherapy products and for developing target drugs to protect the retina from light damage.

Bimetallic Ag125Cu8 Nanocluster, Structure Determination, and Nonlinear Optical Properties.

The atomic precision of the subnanometer nanoclusters has provided sound proof on the structural correlation of metal complexes and larger-sized metal nanoparticles. Herein, we report the synthesis, crystallography, structural characterization, electrochemistry, and optical properties of a 133-atom intermetallic nanocluster protected by 57 thiolates (3-methylbenzenethiol, abbreviated as m-MBTH) and 3 chlorides, with the formula of Ag125Cu8(m-MBT)57Cl3. This is the largest Ag-Cu bimetallic cluster ever reported. Crystallographic analysis revealed that the nanocluster has a three-layer concentric core-shell structure, Ag7@Ag47@Ag71Cu8S57Cl3, and the Ag54 metal kernel adopts a D5h symmetry. The nuclei number is between that of the previously reported large silver cluster [Ag136(SR)64Cl3Ag0.45]- and the large silver-rich cluster Au130-xAgx(SR)55 (x = 98). All these three clusters bear a similar metallic core structure, while the main structural difference lies in the shell motif structures. Electron counting revealed an open electron shell with 73 delocalized electrons, which was verified by the electron paramagnetic resonance analysis. The DPV electrochemical measurement indicates a multielectron state quantization double-layer charging shape and single-electron sequential charging and discharging characteristic of the AgCu alloy cluster. In addition, the open-hole Z-scan test reveals the nonlinear optical absorption (2-3 optical absorption in the NIR-II/III region) of Ag125Cu8 nanoclusters.

Synthesis of sulfinamides via photocatalytic alkylation or arylation of sulfinylamine.

Sulfinamides are a versatile class of compounds that find applications in both organic synthesis and pharmaceuticals. Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. Commercially available potassium trifluoro(organo)borates and readily available sulfinyl amines are rationally used and converted to a series of alkyl or aryl sulfinamides in moderate to high yields. The reaction allows for the gram-scale preparation of sulfinamides. Moreover, sulfonimidamides, sulfonimidate esters and sulfonyl amides could be obtained in one pot.

MiR-339-5p inhibits replication of porcine reproductive and respiratory syndrome virus by targeting viral gene regions.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a variable virus, whose spread cannot be totally stopped by vaccination. PRRSV infection results in abortion and respiratory symptoms in pregnant pigs. One crucial component of the anti-viral infection strategy is microRNA (miRNA), a class of multifunctional small molecules. It is unknown whether miR-339-5p can specifically target the PRRSV gene and prevent the virus from replicating, despite the fact that miR-339-5p is markedly up-regulated during the PRRSV infection. In this pursuit, the present study revealed that the two PRRSV areas targeted by miR-339-5p were PRRSV nsp2-3378 to 3403 and PRRSV nsp2-3112 to 3133 using the miRanda program. Dual luciferase reporter assays showed that the miR-339-5p target region of the PRRSV gene sequence exhibited 100% homology and was highly conserved. Furthermore, the ability of miR-339-5p to target PRRSV gene areas was verified. It was found that the overexpression of miR-339-5p markedly reduced the PRRSV replication through PRRSV infection trials. The precursor sequence of ssc-miR-339-5p was amplified using the DNA of pig lung tissue as a template in order to create a fragment of 402 bp of porcine-derived miR-339-5p precursor sequence, which was then used to produce the eukaryotic expression plasmid of miR-339-5p. In conclusion, miR-339-5p can target the specific PRRSV gene areas and prevent PRRSV replication, offering fresh perspectives for the creation of medications that combat the PRRSV infection.