scNanoHi-C: a single-cell long-read concatemer sequencing method to reveal high-order chromatin structures within individual cells.

The high-order three-dimensional (3D) organization of regulatory genomic elements provides a topological basis for gene regulation, but it remains unclear how multiple regulatory elements across the mammalian genome interact within an individual cell. To address this, herein, we developed scNanoHi-C, which applies Nanopore long-read sequencing to explore genome-wide proximal high-order chromatin contacts within individual cells. We show that scNanoHi-C can reliably and effectively profile 3D chromatin structures and distinguish structure subtypes among individual cells. This method could also be used to detect genomic variations, including copy-number variations and structural variations, as well as to scaffold the de novo assembly of single-cell genomes. Notably, our results suggest that extensive high-order chromatin structures exist in active chromatin regions across the genome, and multiway interactions between enhancers and their target promoters were systematically identified within individual cells. Altogether, scNanoHi-C offers new opportunities to investigate high-order 3D genome structures at the single-cell level.

Constructing Symmetry-Mismatched RuxFe3-xO4 Heterointerface-Supported Ru Clusters for Efficient Hydrogen Evolution and Oxidation Reactions.

Ru-related catalysts have shown excellent performance for the hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR); however, a deep understanding of Ru-active sites on a nanoscale heterogeneous support for hydrogen catalysis is still lacking. Herein, a click chemistry strategy is proposed to design Ru cluster-decorated nanometer RuxFe3-xO4 heterointerfaces (Ru/RuxFe3-xO4) as highly effective bifunctional hydrogen catalysts. It is found that introducing Ru into nanometric Fe3O4 species breaks the symmetry configuration and optimizes the active site in Ru/RuxFe3-xO4 for HER and HOR. As expected, the catalyst displays prominent alkaline HER and HOR performance with mass activity much higher than that of commercial Pt/C as well as robust stability during catalysis because of the strong interaction between the Ru cluster and the RuxFe3-xO4 support, and the optimized adsorption intermediate (Had and OHad). This work sheds light on a promsing approach to improving the electrocatalysis performance of catalysts by the breaking of atomic dimension symmetry.

Long non-coding RNA NRAV in the 12q24.31 risk locus drives gastric cancer development through glucose metabolism reprogramming.

Long non-coding RNAs (lncRNAs) serve as vital candidates to mediate cancer risk. Here, we aimed to identify the risk single-nucleotide polymorphisms (SNPs)-induced lncRNAs and to investigate their roles in gastric cancer (GC) development. Through integrating the differential expression analysis of lncRNAs in GC tissues and expression quantitative trait loci analysis in normal stomach tissues and GC tissues, as well as genetic association analysis based on GC genome-wide association studies and an independent validation study, we identified four lncRNA-related SNPs consistently associated with GC risk, including SNHG7 [odds ratio (OR) = 1.16, 95% confidence interval (CI): 1.09-1.23], NRAV (OR = 1.11, 95% CI: 1.05-1.17), LINC01082 (OR = 1.16, 95% CI: 1.08-1.22) and FENDRR (OR = 1.16, 95% CI: 1.07-1.25). We further found that a functional SNP rs6489786 at 12q24.31 increases binding of MEOX1 or MEOX2 at a distal enhancer and results in up-regulation of NRAV. The functional assays revealed that NRAV accelerates GC cell proliferation while inhibits GC cell apoptosis. Mechanistically, NRAV decreases the expression of key subunit genes through the electron transport chain, thereby driving the glucose metabolism reprogramming from aerobic respiration to glycolysis. These findings suggest that regulating lncRNA expression is a crucial mechanism for risk-associated variants in promoting GC development.

Fast Nano-IR Hyperspectral Imaging Empowered by Large-Dataset-Free Miniaturized Spatial-Spectral Network.

The emerging field of nanoscale infrared (nano-IR) offers label-free molecular contrast, yet its imaging speed is limited by point-by-point traverse acquisition of a three-dimensional (3D) data cube. Here, we develop a spatial-spectral network (SS-Net), a miniaturized deep-learning model, together with compressive sampling to accelerate the nano-IR imaging. The compressive sampling is performed in both the spatial and spectral domains to accelerate the imaging process. The SS-Net is trained to learn the mapping from small nano-IR image patches to the corresponding spectra. With this elaborated mapping strategy, the training can be finished quickly within several minutes using the subsampled data, eliminating the need for a large-labeled dataset of common deep learning methods. We also designed an efficient loss function, which incorporates the image and spectral similarity to enhance the training. We first validate the SS-Net on an open stimulated Raman-scattering dataset; the results exhibit the potential of 10-fold imaging speed improvement with state-of-the-art performance. We then demonstrate the versatility of this approach on atomic force microscopy infrared (AFM-IR) microscopy with 7-fold imaging speed improvement, even on nanoscale Fourier transform infrared (nano-FTIR) microscopy with up to 261.6 folds faster imaging speed. We further showcase the generalization of this method on AFM-force volume-based multiparametric nanoimaging. This method establishes a paradigm for rapid nano-IR imaging, opening new possibilities for cutting-edge research in materials, photonics, and beyond.

Long-term Risks of Cirrhosis and Hepatocellular Carcinoma Across Steatotic Liver Disease Subtypes.

INTRODUCTION: The prospective study aimed to investigate the long-term associated risks of cirrhosis and hepatocellular carcinoma (HCC) across various subtypes of steatotic liver disease (SLD). METHODS: We enrolled 332,175 adults who participated in a health screening program between 1997 and 2013. Participants were categorized into various subtypes, including metabolic dysfunction-associated SLD (MASLD), MASLD with excessive alcohol consumption (MetALD), and alcohol-related liver disease (ALD), based on ultrasonography findings, alcohol consumption patterns, and cardiometabolic risk factors. We used computerized data linkage with nationwide registries from 1997 to 2019 to ascertain the incidence of cirrhosis and HCC. RESULTS: After a median follow-up of 16 years, 4,458 cases of cirrhosis and 1,392 cases of HCC occurred in the entire cohort, resulting in an incidence rate of 86.1 and 26.8 per 100,000 person-years, respectively. The ALD group exhibited the highest incidence rate for cirrhosis and HCC, followed by MetALD, MASLD, and non-SLD groups. The multivariate adjusted hazard ratios for HCC were 1.92 (95% confidence interval [CI] 1.51-2.44), 2.91 (95% CI 2.11-4.03), and 2.59 (95% CI 1.93-3.48) for MASLD, MetALD, and ALD, respectively, when compared with non-SLD without cardiometabolic risk factors. The pattern of the associated risk of cirrhosis was similar to that of HCC (all P value <0.001). The associated risk of cirrhosis for ALD increased to 4.74 (95% CI 4.08-5.52) when using non-SLD without cardiometabolic risk factors as a reference. DISCUSSION: This study highlights elevated risks of cirrhosis and HCC across various subtypes of SLD compared with non-SLD, emphasizing the importance of behavioral modifications for early prevention.

Midgut membrane protein BmSUH facilitates Bombyx mori nucleopolyhedrovirus oral infection.

Baculoviruses are virulent pathogens that infect a wide range of insects. They initiate infections via specific interactions between the structural proteins on the envelopes of occlusion-derived virions (ODVs) and the midgut cell surface receptors in hosts. However, host factors that are hijacked by baculoviruses for efficient infection remain largely unknown. In this study, we identified a membrane-associated protein sucrose hydrolase (BmSUH) as an ODV binding factor during Bombyx mori nucleopolyhedrovirus (BmNPV) primary infection. BmSUH was specifically expressed in the midgut microvilli where the ODV-midgut fusion happened. Knockout of BmSUH by CRISPR/Cas9 resulted in a significantly higher survival rate after BmNPV orally infection. Liquid chromatography-tandem mass spectrometry analysis and co-immunoprecipitation analysis demonstrated that PIF protein complex required for ODV binding could interact with BmSUH. Furthermore, fluorescence dequenching assay showed that the amount of ODV binding and fusion to the midgut decreased in BmSUH mutants compared to wild-type silkworm, suggesting the role of BmSUH as an ODV binding factor that mediates the ODV entry process. Based on a multilevel survey, the data showed that BmSUH acted as a host factor that facilitates BmNPV oral infection. More generally, this study indicated that disrupting essential protein-protein interactions required for baculovirus efficient entry may be broadly applicable to against viral infection.

Prognostic significance of platelet­to­albumin ratio in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: a retrospective study of 858 cases.

BACKGROUND: Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. METHODS: We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram's predictive accuracy to rigorous independent validation. RESULTS: The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28-0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64-0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65-0.74). CONCLUSIONS: In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.

Integrated transcriptomics and epigenomics reveal chamber-specific and species-specific characteristics of human and mouse hearts.

DNA methylation, chromatin accessibility, and gene expression represent different levels information in biological process, but a comprehensive multiomics analysis of the mammalian heart is lacking. Here, we applied nucleosome occupancy and methylome sequencing, which detected DNA methylation and chromatin accessibility simultaneously, as well as RNA-seq, for multiomics analysis of the 4 chambers of adult and fetal human hearts, and adult mouse hearts. Our results showed conserved region-specific patterns in the mammalian heart at transcriptome and DNA methylation level. Adult and fetal human hearts showed distinct features in DNA methylome, chromatin accessibility, and transcriptome. Novel long noncoding RNAs were identified in the human heart, and the gene expression profiles of major cardiovascular diseases associated genes were displayed. Furthermore, cross-species comparisons revealed human-specific and mouse-specific differentially expressed genes between the atria and ventricles. We also reported the relationship among multiomics and found there was a bell-shaped relationship between gene-body methylation and expression in the human heart. In general, our study provided comprehensive spatiotemporal and evolutionary insights into the regulation of gene expression in the heart.

Chemical synthesis of a 28 kDa full-length PET degrading enzyme ICCG by the removable backbone modification strategy.

Chemical protein synthesis offers a powerful way to access otherwise-difficult-to-obtain proteins such as mirror-image proteins. Although a large number of proteins have been chemically synthesized to date, the acquisition to proteins containing hydrophobic peptide fragments has proven challenging. Here, we describe an approach that combines the removable backbone modification strategy and the peptide hydrazide-based native chemical ligation for the chemical synthesis of a 28 kDa full-length PET degrading enzyme IGGC (a higher depolymerization efficiency of variant leaf-branch compost cutinase (LCC)) containing hydrophobic peptide segments. The synthetic ICCG exhibits the enzymatic activity and will be useful in establishing the corresponding mirror-image version of ICCG.

Rational design and synthesis of triazene-amonafide derivatives as novel potential antitumor agents causing oxidative damage towards DNA through intercalation mode.

In this work, we rationally designed and synthesized two novel triazene-amonafide derivatives 2-(2-(diisopropylamino)ethyl)-5-(3,3-dimethyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-11) and 5-(3,3-diethyltriaz-1-en-1-yl)-2-(2-(diisopropylamino)ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-12) as potential antitumor agents. The DNA damage induced by the intercalation mode of D-11 (D-12) towards DNA was electrochemically detected through the construction of efficient biosensors. The consecutive processes of reversible redox of naphthylimide ring and irreversible oxidation of triazene moiety were elucidated on the surface of glassy carbon electrode (GCE) by CV, SWV, and DPV methods. Electrochemical biosensors were obtained through the immobilization of ctDNA, G-quadruplexes, poly(dG), and poly(dA), respectively, on the clean surface of GCE. After the incubation of biosensors with D-11 or D-12, the peaks of dGuo and dAdo decreased prominently, and the peak of 8-oxoGua appeared at +0.50 V, suggesting that the interaction between D-11 (D-12) and DNA could result in the oxidative damage of guanine. Unexpected, the as-prepared DNA biosensor possessed satisfactory anti-interference property and good practicability in real samples. UV-vis and fluorescence spectra, and gel electrophoresis assays were employed to further confirm the intercalation mode of D-11 (D-12) towards DNA base pairs. Moreover, D-11 was proved to exhibit stronger anti-proliferation activity than mitionafide and amonafide against both A549 and HeLa cell lines.

Yield stress Measurement of municipal sludge: A comprehensive evaluation of testing methods and concentration effects using a rotational rheometer.

Accurate prediction and measurement of yield stress are crucial for optimizing sludge treatment and disposal. However, the differences and applicability of various methods for measuring yield stress are subjects of ongoing debate. Meanwhile, literature on measuring sludge yield stress is limited to low solid concentrations (TS <10%), understanding and studying the yield stress of medium to high solid concentration sludge is crucial due to increasingly stringent standards for sludge treatment and disposal. So, this study employed a rotational rheometer to measure sludge yield stress across a wide range of TS (4-50%) using steady shear, dynamic oscillatory shear, and transient shear. The study derived significant conclusions by comparing and summarizing the applicability and limitations of each testing method: Dynamic oscillatory shear methods, including G'-σ curve method, γ-σ curve method, and G**γc method can measure sludge yield stress ranging from 4% to 40% TS, while other methods are restricted to low or limited solid concentrations; The G' = G″ method, utilizing the intersection of G' and G″ curves, consistently yields the highest value for yield stress when 4%≤ TS ≤ 12%; The rotational rheometer cannot measure sludge yield stress when the solid concentration exceeds 40% TS; The relationship between sludge yield stress and solid concentration is stronger as a power-law for TS ≤ 25%, transitioning to linear for higher concentrations (28%≤ TS <40%). This study systematically explores the applicability and limitations of various measurement methods for characterizing sludge yield stress across a wide range of solid concentrations, providing valuable guidance for scientific measurement and highlighting challenging research issues.

Aflatoxin B1-exposed hepatocyte-derived extracellular vesicles: Initiating hepatic stellate cell-mediated liver fibrosis through a p53-Parkin-dependent mitophagy pathway.

Environmental aflatoxin B1 (AFB1) exposure has been proposed to contribute to hepatocellular carcinoma by promoting liver fibrosis, but the potential mechanisms remain to be further elucidated. Extracellular vesicles (EVs) were recognized as crucial traffickers for hepatic intercellular communication and play a vital role in the pathological process of liver fibrosis. The AFB1-exposed hepatocyte-derived EVs (AFB1-EVs) were extracted, and the functional effects of AFB1-EVs on the activation of hepatic stellate cells (HSCs) were explored to investigate the molecular mechanism of AFB1 exposure-induced liver fibrogenesis. Our results revealed that an environment-level AFB1 exposure induced liver fibrosis via HSCs activation in mice, while the AFB1-EVs mediated hepatotoxicity and liver fibrogenesis in vitro and in vivo. AFB1 exposure in vitro increased PINK1/Parkin-dependent mitophagy in hepatocytes, where upregulated transcription of the PARK2 gene via p53 nuclear translocation and mitochondrial recruitment of Parkin, and promoted AFB1-EVs-mediated mitochondria-trafficking communication between hepatocytes and HSCs. The knockdown of Parkin in HepaRG cells reversed HSCs activation by blocking the mitophagy-related AFB1-EVs trafficking. This study further revealed that the hepatic fibrogenesis of AFB1 exposure was rescued by genetic intervention with siPARK2 or p53's Pifithrin-α (PFTα) inhibitors. Furthermore, AFB1-EVs-induced HSCs activation was relieved by GW4869 pharmaceutic inhibition of EVs secretion. These results revealed a novel mechanism that AFB1 exposure-induced p53-Parkin signal axis regulated mitophagy-dependent hepatocyte-derived EVs to mediate the mitochondria-trafficking intercellular communication between hepatocytes and HSCs in the local hepatotoxic microenvironment to promote the activated HSCs-associated liver fibrogenesis. Our study provided insight into p53-Parkin-dependent pathway regulation and promised an advanced strategy targeting intervention to EVs-mediated mitochondria trafficking for preventing xenobiotics-induced liver fibrosis.

Circ_UBAP2 exacerbates proliferation and metastasis of OS via targeting miR-665/miR-370-3p/HMGA1 axis.

Circ_UBAP2 is extensively engaged in regulating the development of various malignancies, containing osteosarcoma (OS). However, its biological significance and function are not fully understood. In this study, we found that circ_UBAP2 and HMGA1 levels were up-regulated, and miR-370-3p and miR-665 expressions were decreased in osteosarcoma tissues. Inhibition of circ_UBAP2 or HMGA1 expression in OS cells, cell viability, invasion and migration abilitities were notably hindered, and cell apoptosis abilities were increased. Bioinformatics analysis predicted that miR-665 and miR-370-3p were the downstream targets of circ_UBAP2, and the dual luciferase experiment demonstrated the correlation between them. In addition, inhibition of miR-665 and miR-370-3p expression could significantly reverse the impact of knocking down circ_UBAP2 on OS cells. HMGA1 was discovered to become the downstream target of both miR-665 and miR-370-3p. It was shown that over-expression of miR-665 or miR-370-3p notably stimulated the cell growth, invasion, and migration of osteosarcoma cells, while hindered cell apoptosis. Nevertheless, this effect could be reversed by concurrent over-expression of HMGA1. Our data strongly prove that circ_UBAP2 makes a vital impact on promoting the proliferation, invasion as well as migration of osteosarcoma cells via down-regulating the level of miR-665 and miR-370-3p, and later up-regulating the level of HMGA1. In conclusion, circ_UBAP2 is upregulated in osteosarcoma, and it competitively adsorbs miR-370-3p and miR-665, resulting in up-regulation of HMGA1, thus promoting OS development.

Double tract reconstruction improves the quality of life and better maintain the BMI of patients with proximal gastric cancer.

PURPOSE: The aim of this study is to investigate the effect of double-tract reconstruction on short-term clinical outcome, quality of life and nutritional status of patients after proximal gastrectomy by comparing with esophagogastrostomy and total gastrectomy with Roux-en-Y reconstruction. METHODS: The clinical data of patients who underwent double tract reconstruction (DTR), esophagogastrostomy (EG), total gastrectomy with Roux-en-Y reconstruction (TG-RY) were retrospectively collected from May 2020 to May 2022. The clinical characteristics, short-term surgical outcomes, postoperative quality of life and nutritional status were compared among the three groups. RESULTS: Compared with the DTR group, the operation time in the TG group was significantly shorter (200(180,240) minutes vs. 230(210,255) minutes, p < 0.01), and more lymph nodes were removed (28(22, 25) vs. 22(19.31), p < 0.01), there were no significant differences in intraoperative blood loss, first flatus time, postoperative hospital stay and postoperative complication rate among the three groups. Postoperative digestive tract angiography was completed in 36 patients in the DTR group, of which 21 (58.3%) showed double-tract type of food passing. The incidence of postoperative reflux symptoms was 9.2% in the DTR group, 43.8% in the EG group and 23.2% in the TG group, repectively (P < 0.01). EORTCQLQ-STO22 questionnaire survey showed that compared with EG group, DTR group had fewer reflux symptoms (P < 0.05), fewer anxiety symptoms (P < 0.05) and more swallowing symptoms (P < 0.05). Compared with TG group, DTR group had fewer reflux symptoms (P < 0.05). There were no other significant differences between the two groups. Compared with TG group and EG group, DTR can better maintain postoperative BMI, and there is no statistical difference between the three groups in terms of hemoglobin and albumin. CONCLUSIONS: Although partial double-tract reconstruction approach does not always ensure food to enter the distal jejunum along the two pathways as expected, it still shows satisfactory anti-reflux effect. Moreover, it might improve patients' quality of life and maintain better nutritional status comparing with gastroesophageal anastomosis and total gastrectomy with Roux-en-Y reconstruction.

An Ultrasensitive Room-Temperature H2 Sensor Based on a TiO2 Rutile-Anatase Homojunction.

Metal oxide semiconductor hetero- and homojunctions are commonly constructed to improve the performance of hydrogen sensors at room temperature. In this study, a simple two-step hydrothermal method was employed to prepare TiO2 films with homojunctions of rutile and anatase phases (denoted as TiO2-R/A). Then, the microstructure of anatase-phase TiO2 was altered by controlling the amount of hydrochloric acid to realize a more favorable porous structure for charge transport and a larger surface area for contact with H2. The sensor used a Pt interdigital electrode. At an optimal HCl dosage (25 mL), anatase-phase TiO2 uniformly covered rutile-phase TiO2 nanorods, resulting in a greater response to H2 at 2500 ppm compared with that of a rutile TiO2 nanorod sensor by a factor of 1153. The response time was 21 s, mainly because the homojunction formed by the TiO2 rutile and anatase phases increased the synergistic effect of the charge transfer and potential barrier between the two phases, resulting in the formation of more superoxide (O2-) free radicals on the surface. Furthermore, the porous structure increased the surface area for H2 adsorption. The TiO2-R/A-based sensor exhibited high selectivity, long-term stability, and a fast response. This study provides new insights into the design of commercially competitive hydrogen sensors.

Intranasal Pathway for Nanoparticles to Enter the Central Nervous System.

Intranasal administration was previously proposed for delivering drugs for central nervous system (CNS) diseases. However, the delivery and elimination pathways, which are very imperative to know for exploring the therapeutic applications of any given CNS drugs, remain far from clear. Because lipophilicity has a high priority in the design of CNS drugs, the as-prepared CNS drugs tend to form aggregates. Therefore, a PEGylated Fe3O4 nanoparticle labeled with a fluorescent dye was prepared as a model drug and studied to elucidate the delivery pathways of intranasally administered nanodrugs. Through magnetic resonance imaging, the distribution of the nanoparticles was investigated in vivo. Through ex vivo fluorescence imaging and microscopy studies, more precise distribution of the nanoparticles across the entire brain was disclosed. Moreover, the elimination of the nanoparticles from cerebrospinal fluid was carefully studied. The temporal dose levels of intranasally delivered nanodrugs in different parts of the brain were also investigated.

Exogenous Eugenol Alleviates Salt Stress in Tobacco Seedlings by Regulating the Antioxidant System and Hormone Signaling.

Salt stress seriously affects crop growth, leading to a decline in crop quality and yield. Application of exogenous substances to improve the salt tolerance of crops and promote their growth under salt stress has become a widespread and effective means. Eugenol is a small molecule of plant origin with medicinal properties such as antibacterial, antiviral, and antioxidant properties. In this study, tobacco seedlings were placed in Hoagland's solution containing NaCl in the presence or absence of eugenol, and physiological indices related to stress tolerance were measured along with transcriptome sequencing. The results showed that eugenol improved the growth of tobacco seedlings under salt stress. It promoted carbon and nitrogen metabolism, increased the activities of nitrate reductase (NR), sucrose synthase (SS), and glutamine synthetase (GS) by 31.03, 5.80, and 51.06%. It also activated the enzymatic and non-enzymatic antioxidant systems, reduced the accumulation of reactive oxygen species in the tobacco seedlings, and increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) by 24.38%, 18.22%, 21.60%, and 28.8%, respectively. The content of glutathione (GSH) was increased by 29.49%, and the content of superoxide anion (O2-) and malondialdehyde (MDA) were reduced by 29.83 and 33.86%, respectively. Promoted osmoregulation, the content of Na+ decreased by 34.34, K+ increased by 41.25%, and starch and soluble sugar increased by 7.72% and 25.42%, respectively. It coordinated hormone signaling in seedlings; the content of abscisic acid (ABA) and gibberellic acid 3 (GA3) increased by 51.93% and 266.28%, respectively. The transcriptome data indicated that the differentially expressed genes were mainly enriched in phenylpropanoid biosynthesis, the MAPK signaling pathway, and phytohormone signal transduction pathways. The results of this study revealed the novel role of eugenol in regulating plant resistance and provided a reference for the use of exogenous substances to alleviate salt stress.

Implication of lncRNA MSTRG.81401 in Hippocampal Pyroptosis Induced by P2X7 Receptor in Type 2 Diabetic Rats with Neuropathic Pain Combined with Depression.

Major depressive disorder (MDD) is a common complication of diabetes and is often observed alongside diabetic neuropathic pain (DNP) as a comorbidity in diabetic patients. Long non-coding RNA (lncRNA) plays an important role in various pathophysiological processes. The P2X7 receptor is responsible for triggering inflammatory responses, such as pyroptosis, linked to pain and depression. The aim of this study was to investigate the effect of lncRNA MSTRG.81401 on hippocampal pyroptosis induced by the P2X7 receptor in diabetic rats with DNP combined with MDD (DNP + MDD). Our results showed that the expression of lncRNA MSTRG.81401 was significantly elevated in the hippocampus of DNP + MDD rats compared with the control group. Following the administration of shRNA targeting lncRNA MSTRG.81401, a notable elevation in mechanical and thermal pain thresholds was observed in rats with comorbid DNP and MDD. Additionally, significant improvements in depression-like behaviors were evident in the open-field test (OFT), sucrose preference test (SPT), and forced swim test (FST). In the DNP + MDD rats, elevated levels in hippocampal P2X7 receptor mRNA and protein were observed, along with increased co-expression of P2X7 and the astrocytic marker glial fibrillary acidic protein (GFAP). Meanwhile, in DNP + MDD rats, the heightened mRNA expression of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), pyroptosis-related protein Gasdermin D (GSDMD), caspase-1, IL-1ß, IL-18, and TNF-α was detected, in addition to increased serum levels of IL-1ß, IL-18 and TNF-α. After shRNA treatment with lncRNA MSTRG.81401, the above abnormal changes in indicators for pyroptosis and inflammation were improved. Therefore, our study demonstrates that shRNA of lncRNA MSTRG.81401 can alleviate the pain and depression-like behaviors in diabetic rats associated with the comorbidity of DNP and MDD by inhibiting the hippocampal P2X7 receptor-mediated pyroptosis pathway and pro-inflammatory responses. This suggests that the P2X7R/NLRP3/caspase-1 implicated pyroptosis and inflammatory scenario may serve as a potential target for the management of comorbid DNP and MDD in diabetes.

Nucleophilic Reaction-Enabled Chloride Modification on CsPbI3 Quantum Dots for Pure Red Light-Emitting Diodes with Efficiency Exceeding 26 .

High-performance pure red perovskite light-emitting diodes (PeLEDs) with an emission wavelength shorter than 650 nm are ideal for wide-color-gamut displays, yet remain an unprecedented challenge to progress. Mixed-halide CsPb(Br/I)3 emitter-based PeLEDs suffer spectral stability induced by halide phase segregation and CsPbI3 quantum dots (QDs) suffer from a compromise between emission wavelength and electroluminescence efficiency. Here, we demonstrate efficient pure red PeLEDs with an emission centered at 638 nm based on PbClx -modified CsPbI3 QDs. A nucleophilic reaction that releases chloride ions and manipulates the ligand equilibrium of the colloidal system is developed to synthesize the pure red emission QDs. The comprehensive structural and spectroscopic characterizations evidence the formation of PbClx outside the CsPbI3 QDs, which regulates exciton recombination and prevents the exciton from dissociation induced by surface defects. In consequence, PeLEDs based on PbClx -modified CsPbI3 QDs with superior optoelectronic properties demonstrate stable electroluminescence spectra at high driving voltages, a record external quantum efficiency of 26.1 %, optimal efficiency roll-off of 16.0 % at 1000 cd m-2 , and a half lifetime of 7.5 hours at 100 cd m-2 , representing the state-of-the-art pure red PeLEDs. This work provides new insight into constructing the carrier-confined structure on perovskite QDs for high-performance PeLEDs.

Effects of carbamazepine on BDNF expression in trigeminal ganglia and serum in rats with trigeminal neuralgia. / å¡é©¬è¥¿å¹³å¯¹ä¸‰å‰ç¥žç»ç—›å¤§é¼ ä¸‰å‰ç¥žç»èŠ‚åŠè¡€æ¸ ä¸­BDNF表达变化的影响.

OBJECTIVES: Trigeminal neuralgia (TN) is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy. There are numerous treatments for TN, but currently the main clinical approach is to suppress pain by carbamazepine (CBZ). Brain-derived neurotrophic factor (BDNF) is closely related to chronic pain. This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion (TG) and serum of TN via a chronic constriction injury of the infraorbital nerve (ION-CCI) rat model. METHODS: The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group, a TN group, a TN+low-dose CBZ treatment group (TN+20 mg/kg CBZ group), a TN+medium-dose CBZ treatment group (TN+40 mg/kg CBZ group), and a TN+high-dose CBZ treatment group (TN+80 mg/kg CBZ group). The mechanical pain threshold in each group of rats was measured regularly before and after surgery. The expressions of BDNF and tyrosine kinase receptor B (TrkB) mRNA in TGs of rats in different groups were determined by real-time PCR, and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence. Western Blotting was used to detect the protein expression of BDNF, TrkB, extracellular regulated protein kinases (ERK), and phospho-extracellular regulated protein kinases (p-ERK) in TGs of rats in different groups. The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery (all P>0.05). From the 3rd day after operation, the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group (all P<0.01), and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 CBZ mg/kg group was higher than that in the TN group (all P<0.05). The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group (all P<0.05), and those in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than the TN group (all P<0.05). The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group (all P<0.05). The BDNF and neuron-specific nuclear protein (NeuN) were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group (all P<0.05). The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group (P<0.05). The levels of BDNF in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold (r=-0.650, P<0.01). CONCLUSIONS: CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats, reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway, so as to inhibit TN. The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.