A hybrid topological quantum state in an elemental solid.

Topology1-3 and interactions are foundational concepts in the modern understanding of quantum matter. Their nexus yields three important research directions: (1) the competition between distinct interactions, as in several intertwined phases, (2) the interplay between interactions and topology that drives the phenomena in twisted layered materials and topological magnets, and (3) the coalescence of several topological orders to generate distinct novel phases. The first two examples have grown into major areas of research, although the last example remains mostly unexplored, mainly because of the lack of a material platform for experimental studies. Here, using tunnelling microscopy, photoemission spectroscopy and a theoretical analysis, we unveil a 'hybrid' topological phase of matter in the simple elemental-solid arsenic. Through a unique bulk-surface-edge correspondence, we uncover that arsenic features a conjoined strong and higher-order topology that stabilizes a hybrid topological phase. Although momentum-space spectroscopy measurements show signs of topological surface states, real-space microscopy measurements unravel a unique geometry of topologically induced step-edge conduction channels revealed on various natural nanostructures on the surface. Using theoretical models, we show that the existence of gapless step-edge states in arsenic relies on the simultaneous presence of both a non-trivial strong Z2 invariant and a non-trivial higher-order topological invariant, which provide experimental evidence for hybrid topology. Our study highlights pathways for exploring the interplay of different band topologies and harnessing the associated topological conduction channels in engineered quantum or nano-devices.

Integrated metabolome and transcriptome analyses reveal the role of BoGSTF12 in anthocyanin accumulation in Chinese kale (Brassica oleracea var. alboglabra).

BACKGROUND: The vivid red, purple, and blue hues that are observed in a variety of plant fruits, flowers, and leaves are produced by anthocyanins, which are naturally occurring pigments produced by a series of biochemical processes occurring inside the plant cells. The purple-stalked Chinese kale, a popular vegetable that contains anthocyanins, has many health benefits but needs to be investigated further to identify the genes involved in the anthocyanin biosynthesis and translocation in this vegetable. RESULTS: In this study, the purple- and green-stalked Chinese kale were examined using integrative transcriptome and metabolome analyses. The content of anthocyanins such as cyanidin-3-O-(6″-O-feruloyl) sophoroside-5-O-glucoside, cyanidin-3,5-O-diglucoside (cyanin), and cyanidin-3-O-(6″-O-p-hydroxybenzoyl) sophoroside-5-O-glucoside were considerably higher in purple-stalked Chinese kale than in its green-stalked relative. RNA-seq analysis indicated that 23 important anthocyanin biosynthesis genes, including 3 PAL, 2 C4H, 3 4CL, 3 CHS, 1 CHI, 1 F3H, 2 FLS, 2 F3'H, 1 DFR, 3 ANS, and 2 UFGT, along with the transcription factor BoMYB114, were significantly differentially expressed between the purple- and green-stalked varieties. Results of analyzing the expression levels of 11 genes involved in anthocyanin production using qRT-PCR further supported our findings. Association analysis between genes and metabolites revealed a strong correlation between BoGSTF12 and anthocyanin. We overexpressed BoGSTF12 in Arabidopsis thaliana tt19, an anthocyanin transport mutant, and this rescued the anthocyanin-loss phenotype in the stem and rosette leaves, indicating BoGSTF12 encodes an anthocyanin transporter that affects the accumulation of anthocyanins. CONCLUSION: This work represents a key step forward in our understanding of the molecular processes underlying anthocyanin production in Chinese kale. Our comprehensive metabolomic and transcriptome analyses provide important insights into the regulatory system that controls anthocyanin production and transport, while providing a foundation for further research to elucidate the physiological importance of the metabolites found in this nutritionally significant vegetable.

Lead Optimization of Butyrolactone I as an Orally Bioavailable Antiallergic Agent Targeting FcγRIIB.

Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, 1), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats. Therefore, a series of structural optimizations toward the metabolic pathways of BTL-I were conducted to provide 18 derives (2-19). Among them, BTL-MK (19) showed superior antiallergic activity and favorable pharmacokinetics compared to BTL-I, being twice as potent with a clearance (CL) rate of only 0.5% that of BTL-I. By oral administration, Cmax and area under the concentration-time curve (AUC0-∞) were 565 and 204 times higher than those of BTL-I, respectively. These findings suggest that butyrolactone methyl ketone (BTL-BK) could serve as a drug candidate for the treatment of FAs and offer valuable insights into optimizing the druggability of lead compounds.

EPA and DHA Differentially Improve Insulin Resistance by Reducing Adipose Tissue Inflammation - Targeting GPR120/PPARγ Pathway.

Insulin resistance (IR) is a global health challenge, often initiated by dysfunctional adipose tissue. Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) may have different effects on IR, but the mechanisms are unknown. This study aims to evaluate the protective effect of EPA and DHA against IR in a high-fat diet (HFD) mice model and investigate whether EPA and DHA alter IR modulate the G-protein-poupled receptor 120/peroxisome proliferator-activated receptor γ (GPR120/PPARγ) pathway in macrophages and adipocytes, which may affect IR in adipocytes. The findings of this study show that 4% DHA had a better effect in improving IR and reducing inflammatory cytokines in adipose tissue of mice. Additionally, in the cell experiment, the use of AH7614 (a GPR120 antagonist) inhibited the glucose consumption increase and the increasable expression of PPARγ and insulin signaling molecules mediated by DHA in adipocytes. Furthermore, GW9662 (a PPARγ antagonist) hindered the upregulation of glucose consumption and insulin signaling molecule expression induced by EPA and DHA in adipocytes. DHA exhibited significant effects in reducing the number of migrated cells and inflammation. The compounds AH7614 and GW9662 hindered the suppressive effects of EPA and DHA on macrophage-induced IR in adipocytes. These findings suggest that DHA has a stronger potential in improving IR in adipocytes through the GPR120/PPARγ pathway in macrophages, when compared to EPA.

CD3ε of a pan T cell marker involved in mouse Aspergillus fumigatus keratitis.

AIM: To explore whether CD3ε is involved in the adaptive immunity of Aspergillus fumigatus (A. fumigatus) keratitis in mice and the role of innate and adaptive immunity in it. METHODS: Mice models of A. fumigatus keratitis were established by intra-stromal injection and corneal epithelial scratching. Subconjunctival injections of natamycin, wedelolactone, LOX-1 inhibitor (poly I) or Dectin-1 inhibitor (laminarin) were used to treat mice with A. fumigatus keratitis. Mice were pretreated by intraperitoneal injection of anti-mouse CD3ε. We observed the corneal infection of mice under the slit lamp microscope and made a clinical score. The protein expression of CD3ε and interleukin-10 (IL-10) was determined by Western blotting. RESULTS: With the disease progresses, the degree of corneal opacity and edema augmented. In the intra-stromal injection models, CD3ε protein expression began to increase significantly on the 2nd day. However, in the scraping epithelial method models, CD3ε only began to increase on the 3rd day. After natamycin treatment, the degree of corneal inflammation in mice was significantly attenuated on the 3rd day. After wedelolactone treatment, the severity of keratitis worsened. And the amount of CD3ε protein was also reduced, compared with the control group. By inhibiting LOX-1 and Dectin-1, there was no significant difference in CD3ε production compared with the control group. After inhibiting CD3ε, corneal ulcer area and clinical score increased, and IL-10 expression was downregulated. CONCLUSION: As a pan T cell marker, CD3ε participate in the adaptive immunity of A. fumigatus keratitis in mice. In our mice models, the corneas will enter the adaptive immune stage faster. By regulating IL-10, CD3ε exerts anti-inflammatory and repairs effects in the adaptive immune stage.

Chemical Constituents from the deep-sea-derived Fungus Aureobasidium melanogenum LUO5.

Three new C10 and C12 aliphatic δ-lactones (1-3), three new fatty acid methyl esters (4-6), and eight known compounds (7-14) were isolated from the marine Aureobasidium sp. LUO5. Their structures were established by detailed analyses of the NMR, HRESIMS, optical rotation, and ECD data. All isolates were tested for their inhibitory effects on nitric oxide production in LPS-induced BV-2 cells. Notably, compound 4 displayed the strongest inhibitory effect with the IC50 value of 120.3 nM.

Genome Mining of a Deep-Sea-Derived Penicillium allii-sativi Revealed Polyketide-Terpenoid Hybrids with Antiosteoporosis Activity.

Two novel meroterpenoids, alliisativins A and B (1, 2) were discovered through a genome-based exploration of the biosynthetic gene clusters of the deep-sea-derived fungus Penicillium allii-sativi MCCC entry 3A00580. Extensive spectroscopic analysis, quantum calculations, chemical derivatization, and biogenetic considerations were utilized to establish their structures. Alliisativins A and B (1, 2) possess a unique carbon skeleton featuring a drimane sesquiterpene with a highly oxidized polyketide. Noteworthily, alliisativin A (1) showed dual activity in promoting osteogenesis and inhibiting osteoclast, indicating an antiosteoporosis potential.

CH-VAD left ventricular assist implantation combined with the Bentall procedure and coronary artery bypass grafting.

Left ventricular assist device (LVAD) implantation is an effective alternative treatment to heart transplantation, especially for end-stage heart failure patients who are ineligible for or unable to await a heart transplant. This report describes a complex and innovative surgery where LVAD implantation was performed alongside multiple concomitant cardiac and aortic procedures. A 62-year-old male patient with complicated comorbidities developed acute myocardial infarction and subsequent refractory advanced heart failure. Given his critically ill condition and intractable anatomical malformations, the CH-VAD left ventricular assist system implantation was performed concomitantly with the Bentall procedure, coronary artery bypass grafting, tricuspid valvuloplasty, and foramen ovale closure. The patient was successfully discharged. This case details the medical decision-making process and surgical strategy and demonstrates the feasibility of LVAD implantation combined with multiple additional cardiac and aortic procedures in expert cardiac centres. Success relies on experienced cardiac surgeons and a multidisciplinary LVAD Heart Team, ensuring excellence in surgical techniques, preoperative evaluation, post-operative care, and rehabilitation.

CircITGA7 regulates malignant phenotypes in bladder cancer cells via targeting miR-330-3p/KLF10 axis.

Bladder cancer (BCa) is one of the common malignancies. Circular RNAs (circRNAs) play regulatory roles in cancer progression. CircITGA7 is a circRNA generated from several exons of ITGA7. The potential role of circITGA7 in BCa remains unknown and needs to be explored. Quantitative real time polymerase chain reaction (qRT-PCR) was used to assess circITGA7 and miR-330-3p expression in BCa tissues and cell lines. Kaplan-Meier analysis was used to evaluate the overall survival of these BCa patients. The biological function of circITGA7 was examined by overexpression of circITGA7 using CCK-8, EdU, wound-healing, and Transwell assays. Xenograft assay was performed to further validate the in vitro results. To explore the mechanism of circITGA7, luciferase reporter, RNA pull-down, fluorescence in situ hybridization (FISH) assays were employed to examine the binding interaction among circITGA7, miR-330-3p and kruppel-like factor 10 (KLF10). Western blot was used to study the protein levels of KLF10.CircITGA7 was downregulated in BCa tissues and cell lines and indicated longer overall survival. Moreover, circITGA7 restricted cell proliferation, migration and invasion of BCa through negatively regulating miR-330-3p. The in vivo model showed that circITGA7 influenced the tumor growth. Besides, the overexpression of miR-330-3p promoted cell progression by directly targeting KLF10. Mechanistically, circITGA7 inhibited BCa progression by activating KLF10 via targeting miR-330-3p.CircITGA7 alleviates BCa cell progression via circITGA7/hsa-miR-330-3p/KLF10 axis, which may provide novel therapeutic targets for BCa.

Construction of a gene model related to the prognosis of patients with gastric cancer receiving immunotherapy and exploration of COX7A1 gene function.

BACKGROUND: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. METHODS: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. RESULTS: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). CONCLUSIONS: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.

Maresin 1 Activates LGR6 to Alleviate Neuroinflammation via the CREB/JMJD3/IRF4 Pathway in a Rat Model of Subarachnoid Hemorrhage.

Neuroinflammation is an early event of brain injury after subarachnoid hemorrhage (SAH). Whether the macrophage mediators in resolving inflammation 1 (MaR1) is involved in SAH pathogenesis is unknown. In this study, 205 male Sprague-Dawley rats were subjected to SAH via endovascular perforation in the experimental and control groups. MaR1 was dosed intranasally at 1 h after SAH, with LGR6 siRNA and KG-501, GSK-J4 administered to determine the signaling pathway. Neurobehavioral, histological and biochemical data were obtained from the animal groups with designated treatments. The results showed: (i) The leucine-rich repeat containing G protein-coupled receptor 6 (LGR6) was decreased after SAH and reached to the lowest level at 24 h after SAH. Jumonji d3 (JMJD3) protein levels tended to increase and peaked at 24 h after SAH. LGR6 and JMJD3 expression were co-localized with microglia. (ii) MaR1 administration mitigated short-term neurological deficits, brain edema and long-term neurobehavioral performance after SAH, and attenuated microglial activation and neutrophil infiltration. (iii) Knockdown of LGR6, inhibition of CREB phosphorylation or JMJD3 activity abolished the anti-neuroinflammatory effect of MaR1 on the expression of CREB, CBP, JMJD3, IRF4, IRF5, IL-1ß, IL-6 and IL-10, thus prevented microglial activation and neutrophil infiltration. Together, the results show that MaR1 can activate LGR6 and affect CREB/JMJD3/IRF4 signaling to attenuate neuroinflammation after SAH, pointing to a potential pharmacological utility in this disorder.

miR-196b-5p regulates inflammatory process and migration via targeting Nras in trabecular meshwork cells.

Glaucoma, an insidious ophthalmic pathology, is typified by an aberrant surge in intraocular pressure (IOP) which culminates in the degeneration of retinal ganglion cells and optical neuropathy. The mitigation of IOP stands as the principal therapeutic strategy to forestall vision loss. The trabecular meshwork's (TM) integrity and functionality are pivotal in modulating aqueous humor egress. Despite their potential significance in glaucomatous pathophysiology, the implications of microRNAs (miRNAs) on TM functionality remain largely enigmatic. Transcriptomic sequencing was employed to delineate the miRNA expression paradigm within the limbal region of rodent glaucoma models, aiming to elucidate miRNA-mediated mechanisms within the glaucomatous milieu. Analytical scrutiny of the sequencing data disclosed 174 miRNAs with altered expression profiles, partitioned into 86 miRNAs with augmented expression and 88 with diminished expression. Notably, miRNAs such as hsa-miR-196b-5p were identified as having substantial expression discrepancies with concomitant statistical robustness, suggesting a potential contributory role in glaucomatous progression. Subsequent in vitro assays affirmed that miR-196b-5p augments the inflammatory cascade within immortalized human TM (iHTM) and glaucoma-induced human TM (GTM3) cells, concurrently attenuating cellular proliferation, motility, and cytoskeletal architecture. Additionally, miR-196b-5p implicates itself in the regulation of IOP and inflammatory processes in rodent models. At a mechanistic level, miR-196b-5p modulates its effects via the targeted repression of Nras (neuroblastoma RAS viral oncogene homolog). Collectively, these transcriptomic investigations furnish a comprehensive vista into the regulatory roles of miRNAs within the glaucomatous framework, and the identification of differentially expressed miRNAs alongside their targets could potentially illuminate novel molecular pathways implicated in glaucoma, thereby aiding in the development of innovative therapeutic avenues.

MRPS23 is a novel prognostic biomarker and promotes glioma progression.

Mitochondrial ribosomal protein S23 (MRPS23), a component of the ribosome small subunit, has been reported to be overexpressed in various cancers and has been predicted to be involved in increased cell proliferation. It has been confirmed that MRPS23 was involved in the regulation of breast cancer and hepatocellular carcinoma cell proliferation. However, little is known about the function of MRPS23 in glioma. In this study, we found that MRPS23 expression was higher in gliomas than in adjacent normal tissues. Higher expression of MRPS23 in gliomas correlated with poorer prognosis, unfavorable histological features, absence of mutations in the isocitrate dehydrogenase gene (IDH), absence of chromosome 1p and 19q deletions, and responses to chemoradiotherapy. Univariate and multivariate Cox analysis demonstrated MRPS23 expression was independently prognostic of overall survival, disease-free survival, and progression-free survival in patients with glioma. KEGG enrichment analysis results indicated that high MRPS23 expression was associated with cell proliferation and immune response-related signaling pathways. We also confirmed that MRPS23 was highly expressed in glioma cells lines, and MRPS23 knockdown significantly reduced cell survival, proliferation, and migration of glioma cells lines. Collectively, these findings offer mechanistic insights into how MRPS23 during glioma progression, and identify MRPS23 as a potential therapeutic target in the future.

Spindle apparatus coiled-coil protein 1 (SPDL1) serves as a novel prognostic biomarker in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) has a poor prognosis, an ineffective diagnosis, and a high degree of aggressiveness. Therefore, novel therapeutic targets for TNBC urgently need to be identified. METHODS: Through a series of bioinformatics analyses, including analysis of differential gene expression, protein-protein interaction (PPI) network, univariate cox regression, immune infiltration, pathway enrichment, etc, as well as auxiliary immunohistochemistry (IHC) and protein quantitativae analysis, to explore prognostic marker for TNBC. RESULTS: In TNBC tissues, we found that SPDL1 (CCDC99) was considerably overexpressed at both the mRNA and protein levels compared to that in normal and non-TNBC tissues. Additionally, we found that SPDL1-high expression was strongly linked to poor prognosis in TNBC patients. Excessive SPDL1 expression was positively correlated with tumor growth and strongly linked to the cell cycle, DNA replication, and the p53 signaling pathway. In addition, CIBERSORT analysis revealed that SPDL1 can affect the tumor immune microenvironment (TME) in TNBC, encourage the development of TNBC and act as a potential prognostic biomarker for TNBC. Patients with SPDL1-high expression were more sensitive to AZD8055. Notably, we discovered that SPDL1 is highly expressed in the majority of malignancies and may have an impact on the pancancer prognosis. CONCLUSIONS: SPDL1 can serve as a novel prognostic marker for TNBC and pancancer patients.

Anti-necroptosis and anti-ferroptosis compounds from the Deep-Sea-Derived fungus Aspergillus sp. MCCC 3A00392.

Eight undescribed (1-8) and 46 known compounds (9-54) were isolated from the deep-sea-derived Aspergillus sp. MCCC 3A00392. Compounds 1-3 were three novel oxoindolo diterpenoids, 4-6 were three bisabolane sesquiterpenoids, while 7 and 8 were two monocyclic cyclopropanes. Their structures were established by exhaustive analyses of the HRESIMS, NMR, and theoretical calculations of the NMR data and ECD spectra. Compounds 10, 33, 38, and 39 were able to inhibit tumor necrosis factor (TNF)-induced necroptosis in murine L929 cell lines. Functional experiments verified that compounds 10 and 39 inhibited necroptosis by downregulating the phosphorylation of RIPK3 and MLKL. Moreover, compound 39 also reduced the phosphorylation of RIPK1. Compounds 10, 33, and 34 displayed potent inhibitory activities against RSL-3 induced ferroptosis with the EC50 value of 3.0 µM, 0.4 µM, and 0.1 µM, respectively. Compound 10 inhibited ferroptosis by the downregulation of HMOX1, while compounds 33 and 34 inhibited ferroptosis through regulation of NRF2/SLC7A11/GCLM axis. However, these compounds only showed weak effect in either the necroptosis or ferroptosis relative mouse disease models. Further studies of pharmacokinetics and pharmacodynamics might improve their in vivo bioactivities.

Coagulation as an effective method for cyanobacterial bloom control: A review.

Eutrophication, the over-enrichment with nutrients, for example, nitrogen and phosphorus, of ponds, reservoirs and lakes, is an urgent water quality issue. The most notorious symptom of eutrophication is a massive proliferation of cyanobacteria, which cause aquatic organism death, impair ecosystem and harm human health. The method considered to be most effective to counteract eutrophication is to reduce external nutrient inputs. However, merely controlling external nutrient load is insufficient to mitigate eutrophication. Consequently, a rapid diminishing of cyanobacterial blooms is relied on in-lake intervention, which may encompass a great variety of different approaches. Coagulation/flocculation is the most used and important water purification unit. Since cyanobacterial cells generally carry negative charges, coagulants are added to water to neutralize the negative charges on the surface of cyanobacteria, causing them to destabilize and precipitate. Most of cyanobacteria and their metabolites can be removed simultaneously. However, when cyanobacterial density is high, sticky secretions distribute outside cells because of the small size of cyanobacteria. The sticky secretions are easily to form complex colloids with coagulants, making it difficult for cyanobacteria to destabilize and resulting in unsatisfactory treatment effects of coagulation on cyanobacteria. Therefore, various coagulants and coagulation methods were developed. In this paper, the focus is on the coagulation of cyanobacteria as a promising tool to manage eutrophication. Basic principles, applications, pros and cons of chemical, physical and biological coagulation are reviewed. In addition, the application of coagulation in water treatment is discussed. It is the aim of this review article to provide a significant reference for large-scale governance of cyanobacterial blooms. PRACTITIONER POINTS: Flocculation was a promising tool for controlling cyanobacteria blooms. Basic principles of four kinds of flocculation methods were elucidated. Flocculant was important in the flocculation process.

Marine-Derived Alternariol Monomethyl Ether Alleviates Ovalbumin-Induced Food Allergy by Suppressing MAPK and NF-κB Signaling Pathways of Mast Cells.

The prevalence of food allergies has grown dramatically over the past decade. Recently, studies have shown the potential of marine substances to alleviate food allergies. We utilized a rat basophilic leukemia (RBL)-2H3 model to evaluate the antiallergic effects of alternariol monomethyl ether (AME) extracted from marine fungi Alternaria sp. Our results showed that AME attenuated food allergy symptoms in mice and reduced histamine release in serum. The population of mast cells in the spleen and mesenteric lymph nodes was considerably reduced. Moreover, in vitro assays also revealed that AME inhibited the release of ß-hexosaminidase and histamine. Transcriptomic analysis uncovered that AME regulated gene expression associated with mast cells. Additionally, Western blotting demonstrated that AME suppressed mast cell activation by modulating MAPK and NF-κB signaling pathways. Taken together, these findings provide a theoretical basis for the potential antiallergic use of marine-derived compounds in the development of functional foods.

GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain.

G protein-coupled receptor 39 (GPR39) senses the change of extracellular divalent zinc ion and signals through multiple G proteins to a broad spectrum of downstream effectors. Here, we found that GPR39 was prevalent at inhibitory synapses of spinal cord somatostatin-positive (SOM+) interneurons, a mechanosensitive subpopulation that is critical for the conveyance of mechanical pain. GPR39 complexed specifically with inhibitory glycine receptors (GlyRs) and helped maintain glycinergic transmission in a manner independent of G protein signalings. Targeted knockdown of GPR39 in SOM+ interneurons reduced the glycinergic inhibition and facilitated the excitatory output from SOM+ interneurons to spinoparabrachial neurons that engaged superspinal neural circuits encoding both the sensory discriminative and affective motivational domains of pain experience. Our data showed that pharmacological activation of GPR39 or augmenting GPR39 interaction with GlyRs at the spinal level effectively alleviated the sensory and affective pain induced by complete Freund's adjuvant and implicated GPR39 as a promising therapeutic target for the treatment of inflammatory mechanical pain.

Short-term antiplatelet versus anticoagulant therapy after left atrial appendage closure: a systematic review and meta-analysis.

This meta-analysis compared the efficacy and safety of different antithrombotic regimens after left atrial appendage closure (LAAC). PubMed, Embase, Medline, Cochrane Library databases were systematically searched from their inception to March 2023. Patients were divided into short-term oral anticoagulation (OAC) group and antiplatelet therapy (APT) group. The incidence of events were performed using RevMan 5.4. The events including device-related thrombus (DRT), ischemic stroke/systemic embolization (SE), major bleeding, any bleeding, any major adverse event and all-cause mortality. Subgroup analysis were based on OAC alone or OAC plus single antiplatelet therapy (SAPT) in OAC group. Oral anticoagulants include warfarin and direct oral anticoagulant (DOAC). Fourteen studies with 35,166 patients were included. We found that the incidence of DRT (OR = 0.49, 95% CI 0.36-0.66, P＜0.0001) and all-cause mortality (OR = 0.71, 95% CI 0.57-0.89, P = 0.002) were significantly lower in OAC group than APT group. However, there was no statistical differences in the incidence rates of ischemic stroke/SE (OR = 0.77, 95% CI 0.49-1.20, P = 0.25), major bleeding (OR = 0.84, 95% CI 0.55-1.27, P = 0.84), any bleeding (OR = 0.83, 95% CI 0.56-1.22, P = 0.34) and any major adverse event (OR = 0.56, 95% CI 0.30-1.03, P = 0.06) in the two groups. Subgroup analysis found that the incidence of DRT, all-cause mortality and any major adverse event in OAC monotherapy were lower than that in APT group (P＜0.05), but not statistically different from other outcome. The incidence of DRT, all-cause mortality, any major adverse event and any bleeding in DOAC were significantly better than APT group (P＜0.05). While warfarin only has better incidence of DRT than APT (P＜0.05), there was no statistical difference between the two groups in other outcome (P＞0.05). The incidence of DRT was significantly lower than APT group (P＜0.05), major bleeding were higher, and the rest of the outcome did not show any statistically significant differences(P＞0.05) when OAC plus SAPT. Based on the existing data, short-term OAC may be favored over APT for patients who undergo LAAC. DOAC monotherapy may be favored over warfarin monotherapy or OAC plus APT, when selecting anticoagulant therapies.

Enhancing Plasmonic Hot Electron Energy on Ag Surface by Amine Coordination.

Plasmonic catalysis has emerged as a promising approach to solar-chemical energy conversion. Notably, hot carriers play a decisive role in plasmonic catalysis since only when their energy matches with the LUMO or HOMO energy of the reactant molecule, can the reaction be activated. However, the hot carrier energy depends on the intrinsic physicochemical properties of the plasmonic metal substrate and the interaction with incident light. Tuning the hot carrier energy is of great significance for plasmonic catalysis but remains challenging. Here, we demonstrate that the energy of hot electrons can be significantly elevated to an unprecedented level through the coordination of amines on Ag surface. The bonding of amines and Ag reduces the work function of nanoparticles, leading to the increase of hot electron energy by 0.4 eV. This enhancement of energy promotes the cleavage of C-X (X=Cl, F) bonds upon excitation by visible light. This study provides new insights for promoting plasmonic charge transfer and enhancing the photocatalytic performance of plasmon-mediated systems.