Isolation, Identification, and Biological Characterization of Phage vB_KpnM_KpVB3 Targeting Carbapenem-Resistant Klebsiella pneumoniae ST11.

OBJECTIVES: This study aimed to isolate a phage capable of lysing carbapenem-resistant Klebsiella pneumoniae (CRKP) and to analyze its biological characteristics and whole genome sequence. METHODS: The phage was isolated and purified from the sewage. Transmission electron microscopy (TEM) was employed to observe the bacteriophage's morphology. Phenotypic characterization of the bacteriophages were determined. The genomic information was analyzed. Evolutionary relationships were established through comparative genomics, proteomics, and phylogenetic analysis. RESULTS: The isolation of a virulent phage, named Klebsiella phage vB_KpnM_KpVB3, was notable for forming 6-7 mm transparent circular zones, each surrounded by a distinct halo. The phage had a head diameter of approximately 30 nm and a tail length of about 20 nm, being identified as a member of the Myoviridae family and the Caudovirales order. The optimal multiplicity of infection (MOI) was 0.00001, with an incubation period of 20 minutes and a lysis period of 60 minutes, and the number of released phages after lysis was 133±35 PFU/cell. The phage was relatively stable at temperatures ranging from 10 to 40°C and at pH values ranging from 3 to 11. Its lytic efficiency against CRKP was 30.30%. It has been shown to be able to destroy the biofilm of host bacteria. The bacteriophage genome consists of double-stranded DNA (dsDNA) with a total length of 48,394 base pairs, a GC content of 48.99%, and 78 open reading frames (ORFs). CONCLUSION: The study resulted in the isolation vB_KpnM_KpVB3, a phage demonstrating potential therapeutic efficacy against infections caused by CRKP.

Slimmable transformer with hybrid axial-attention for medical image segmentation.

The transformer architecture has achieved remarkable success in medical image analysis owing to its powerful capability for capturing long-range dependencies. However, due to the lack of intrinsic inductive bias in modeling visual structural information, the transformer generally requires a large-scale pre-training schedule, limiting the clinical applications over expensive small-scale medical data. To this end, we propose a slimmable transformer to explore intrinsic inductive bias via position information for medical image segmentation. Specifically, we empirically investigate how different position encoding strategies affect the prediction quality of the region of interest (ROI) and observe that ROIs are sensitive to different position encoding strategies. Motivated by this, we present a novel Hybrid Axial-Attention (HAA) that can be equipped with pixel-level spatial structure and relative position information as inductive bias. Moreover, we introduce a gating mechanism to achieve efficient feature selection and further improve the representation quality over small-scale datasets. Experiments on LGG and COVID-19 datasets prove the superiority of our method over the baseline and previous works. Internal workflow visualization with interpretability is conducted to validate our success better; the proposed slimmable transformer has the potential to be further developed into a visual software tool for improving computer-aided lesion diagnosis and treatment planning.

MiR-2110 induced by chemically synthesized cinobufagin functions as a tumor-metastatic suppressor via targeting FGFR1 to reduce PTEN ubiquitination degradation in nasopharyngeal carcinoma.

Tumor cell metastasis is the key cause of death in patients with nasopharyngeal carcinoma (NPC). MiR-2110 was cloned and identified in Epstein-Barr virus (EBV)-positive NPC, but its role is unclear in NPC. In this study, we investigated the effect of miR-2110 on NPC metastasis and its related molecular basis. In addition, we also explored whether miR-2110 can be regulated by cinobufotalin (CB) and participate in the inhibition of CB on NPC metastasis. Bioinformatics, RT-PCR, and in situ hybridization were used to observe the expression of miR-2110 in NPC tissues and cells. Scratch, Boyden, and tail vein metastasis model of nude mouse were used to detect the effect of miR-2110 on NPC metastasis. Western blot, Co-IP, luciferase activity, colocalization of micro confocal and ubiquitination assays were used to identify the molecular mechanism of miR-2110 affecting NPC metastasis. Finally, miR-2110 induced by CB participates in CB-stimulated inhibition of NPC metastasis was explored. The data showed that increased miR-2110 significantly suppresses NPC cell migration, invasion, and metastasis. Suppressing miR-2110 markedly restored NPC cell migration and invasion. Mechanistically, miR-2110 directly targeted FGFR1 and reduced its protein expression. Decreased FGFR1 attenuated its recruitment of NEDD4, which downregulated NEDD4-induced phosphatase and tensin homolog (PTEN) ubiquitination and degradation and further increased PTEN protein stability, thereby inactivating PI3K/AKT-stimulated epithelial-mesenchymal transition signaling and ultimately suppressing NPC metastasis. Interestingly, CB, a potential new inhibitory drug for NPC metastasis, significantly induced miR-2110 expression by suppressing PI3K/AKT/c-Jun-mediated transcription inhibition. Suppression of miR-2110 significantly restored cell migration and invasion in CB-treated NPC cells. Finally, a clinical sample assay indicated that reduced miR-2110 was negatively correlated with NPC lymph node metastasis and positively related to NPC patient survival prognosis. In summary, miR-2110 is a metastatic suppressor involving in CB-induced suppression of NPC metastasis.

Analysis of Key Genes and miRNA-mRNA Networks Associated with Glucocorticoids Treatment in Chronic Obstructive Pulmonary Disease.

Background: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear. Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained. Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated. Results: ① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated. Conclusion: In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.

Whole-genome sequencing of allotetraploid bermudagrass reveals the origin of Cynodon and candidate genes for salt tolerance.

Bermudagrass (Cynodon dactylon) is a globally distributed, extensively used warm-season turf and forage grass with high tolerance to salinity and drought stress in alkaline environments. However, the origin of the species and genetic mechanisms for salinity tolerance in the species are basically unknown. Accordingly, we set out to study evolution divergence events in the Cynodon genome and to identify genes for salinity tolerance. We developed a 604.0 Mb chromosome-level polyploid genome sequence for bermudagrass 'A12359' (n = 18). The C. dactylon genome comprises 2 complete sets of homoeologous chromosomes, each with approximately 30 000 genes, and most genes are conserved as syntenic pairs. Phylogenetic study showed that the initial Cynodon species diverged from Oropetium thomaeum approximately 19.7-25.4 million years ago (Mya), the A and B subgenomes of C. dactylon diverged approximately 6.3-9.1 Mya, and the bermudagrass polyploidization event occurred 1.5 Mya on the African continent. Moreover, we identified 82 candidate genes associated with seven agronomic traits using a genome-wide association study, and three single-nucleotide polymorphisms were strongly associated with three salt resistance genes: RAP2-2, CNG channels, and F14D7.1. These genes may be associated with enhanced bermudagrass salt tolerance. These bermudagrass genomic resources, when integrated, may provide fundamental insights into evolution of diploid and tetraploid genomes and enhance the efficacy of comparative genomics in studying salt tolerance in Cynodon.

Identification of two key genes involved in flavonoid catabolism and their different roles in apple resistance to biotic stresses.

Biosynthesis of flavonoid aglycones and glycosides is well established. However, key genes involved in their catabolism are poorly understood, even though the products of hydrolysis and oxidation play important roles in plant resistance to biotic stress. Here, we report on catabolism of dihydrochalcones (DHCs), the most abundant flavonoids in domesticated apple and wild Malus. Two key genes, BGLU13.1 and PPO05, were identified by activity-directed protein purification. BGLU13.1-A hydrolyzed phlorizin, (the most abundant DHC in domesticated apple) to produce phloretin which was then oxidized by PPO05. The process differed in some wild Malus, where trilobatin (a positional isomer of phlorizin) was mainly oxidized by PPO05. The effects of DHC catabolism on apple resistance to biotic stresses was investigated using transgenic plants. Either directly or indirectly, phlorizin hydrolysis affected resistance to the phytophagous pest two-spotted spider mite, while oxidation of trilobatin was involved in resistance to the biotrophic fungus Podosphaera leucotricha. DHC catabolism did not affect apple resistance to necrotrophic pathogens Valsa mali and Erwinia amylovara. These results suggest that different DHC catabolism pathways play different roles in apple resistance to biotic stresses. The role of DHC catabolism on apple resistance appeared closely related to the mode of invasion/damage used by pathogen/pest.

Ligand-controlled regiodivergent Ni-catalyzed trans-hydroboration/carboboration of internal alkynes with B2pin2.

Unprecedented regioselective trans-hydroboration and carboboration of unbiased electronically internal alkynes were realized via a nickel catalysis system with the aid of the directing group strategy. Furthermore, the excellent α- and ß-regioselectivity could be accurately switched by the nitrogen ligand (terpy) and phosphine ligand (Xantphos). Mechanistic studies provided an insight into the rational reaction process, that underwent the cis-to-trans isomerization of alkenyl nickel species. This transformation not only expands the scope of transition-metal-catalyzed boration of internal alkynes but also, more particularly, portrays the vast prospects of the directing group strategy in the selective functionalization of unactivated alkynes.

Effect of electroacupuncture of "Jiaji" (EX-B2) on NOD-like receptor protein 3 mediated pyroptosis in spinal cord tissue of rats with acute spinal cord injury. / å¤¹è„Šç”µé’ˆå¯¹æ€¥æ€§è„Šé«“æŸä¼¤å¤§é¼ è„Šé«“ç»„ç»‡NODæ ·å—ä½“çƒ­è›‹ç™½ç»“æž„åŸŸç›¸å ³è›‹ç™½3介导的细胞焦亡的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) stimulation of "Jiaji"(EX-B2) on motor function, histomorphology, and expression of NOD-like receptor protein 3 (NLRP3) and N-terminal domain of gasdermin D (GSDMD-N) in the spinal cord tissue of rats with spinal cord injury (SCI), so as to explore its mechanism underlying improvement of SCI. METHODS: Forty eight female SD rats were randomly divided into sham surgery (sham), SCI model (model), EA, and NLRP3 agonist (monosodium urate, MSU) combined with Jiaji EA (MSU+EA) groups, with 12 rats in each group which were further divided into 3 d and 7 d subgroups, with 6 rats at each time point. Two EA groups received EA stimulation of EX-B2 with a frequency of 100 Hz, electrical current of 1-2 mA for 30 min, once a day for 3 or 7 days. After 5 min, 6 h, and 24 h of modeling, rats of the MSU+EA group received intraperitoneal injection of MSU (200 µg/kg, 200 µg/mL) . The motor function was evaluated using Basso-Beattie-Bresnahan (BBB) scale, the morphological structure of rat spinal cord tissue was observed by H.E. staining. The expression of pyroptosis related factors NLRP3, cleaved Caspase-1 and GSDMD-N of the spinal cord was observed by using immunohistochemistry and Western blot separately, the expression and localization of Iba-1 and GSDMD-N in the spinal cord tissue were observed using immunofluorescence double staining method. RESULTS: Compared with the sham group, the BBB scores after modeling and on day 3 and 7 were decreased (P<0.05), while the average OD values (immunoactivity) and expression levels of NLRP3, cleaved Caspase-1 and GSDMD-N proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N (co-expression) of the spinal cord tissues on day 3 and 7 were significantly increased in the model group (P<0.05). In comparison with the model group, the BBB scores on day 3 and 7 were obviously increased (P<0.05), while the immunoactivity and expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N on day 3 and 7 significantly down-regulated in the EA group (P<0.05) but not in the MSU+EA group (P>0.05), suggesting an elimination of the effects of EA after administration of NLRP3 agonist (MSU). H.E. staining showed obvious bleeding area in the spinal cord tissue, loose tissue and inflammatory cell infiltration on day 3 after modeling, and basic absorption of the bleeding, loose tissue, obvious vacuolar changes of the white matter area, loss and contraction of neurons with infiltration of a large number of inflammatory cells, which was milder in the EA group but not in the MSU+EA group. CONCLUSIONS: EA of EX-B2 can improve the motor function of SCI rats, which may be related to its functions in inhibiting pyroptosis of microglia mediated by NLRP3/Caspase-1 signaling pathway.

Management of triplet excitons transition: fine regulation of Förster and dexter energy transfer simultaneously.

Understanding and management of triplet excitons transition in the same molecule remain a great challenge. Hence, for the first time, by host engineering, manageable transitions of triplet excitons in a naphthalimide derivative NDOH were achieved, and monitored through the intensity ratio (ITADF/IRTP) between thermally activated delayed fluorescence (TADF) and room-temperature phosphorescence (RTP). Energy differences between lowest triplet excited states of host and guest were changed from 0.03 to 0.17 eV, and ITADF/IRTP of NDOH decreased by 200 times, thus red shifting the afterglow color. It was proposed that shorter conjugation length led to larger band gaps of host materials, thus contributing to efficient Dexter and inefficient Förster energy transfer. Interestingly, no transition to singlet state and only strongest RTP with quantum yield of 13.9% could be observed, when PBNC with loosest stacking and largest band gap acted as host. This work provides novel insight for the management and prediction of triplet exciton transitions and the development of smart afterglow materials.

A dynamic nomogram for predicting intraoperative brain bulge during decompressive craniectomy in patients with traumatic brain injury: a retrospective study.

OBJECTIVE: The aim of this paper is to investigate the risk factors associated with intraoperative brain bulge (IOBB), especially the computed tomography (CT) value of the diseased lateral transverse sinus, and to develop a reliable predictive model to alert neurosurgeons to the possibility of IOBB. METHODS: A retrospective analysis was performed on 937 patients undergoing traumatic decompressive craniectomy. A total of 644 patients from Fuzong Clinical Medical College of Fujian Medical University were included in the development cohort, and 293 patients from the First Affiliated Hospital of Shantou University Medical College were included in the external validation cohort. Univariate and multifactorial logistic regression analyses identified independent risk factors associated with IOBB. The logistic regression models consisted of independent risk factors, and receiver operating characteristic curves, calibration, and decision curve analyses were used to assess the performance of the models. Various machine learning models were used to compare with the logistic regression model and analyze the importance of the factors, which were eventually jointly developed into a dynamic nomogram for predicting IOBB and published online in the form of a simple calculator. RESULTS: IOBB occurred in 93/644 (14.4%) patients in the developmental cohort and 47/293 (16.0%) in the validation cohort. Univariate and multifactorial regression analyses showed that age, subdural hematoma, contralateral fracture, brain contusion, and CT value of the diseased lateral transverse sinus were associated with IOBB. A logistic regression model (full model) consisting of the above risk factors had excellent predictive power in both the development cohort [area under the curve (AUC)=0.930] and the validation cohort (AUC=0.913). Among the four machine learning models, the AdaBoost model showed the best predictive value (AUC=0.998). Factors in the AdaBoost model were ranked by importance and combined with the full model to create a dynamic nomogram for clinical application, which was published online as a practical and easy-to-use calculator. CONCLUSIONS: The CT value of the diseased lateral transverse is an independent risk factor and a reliable predictor of IOBB. The online dynamic nomogram formed by combining logistic regression analysis models and machine learning models can more accurately predict the possibility of IOBBs in patients undergoing traumatic decompressive craniectomy.

Enhancing Photocatalytic CO2 Conversion through Oxygen-Vacancy-Mediated Topological Phase Transition.

Weak adsorption of gas reactants and strong binding of intermediates present a significant challenge for most transition metal oxides, particularly in the realm of CO2 photoreduction. Herein, we demonstrate that the adsorption can be fine-tuned by phase engineering of oxide catalysts. An oxygen vacancy mediated topological phase transition in Ni-Co oxide nanowires, supported on a hierarchical graphene aerogel (GA), is observed from a spinel phase to a rock-salt phase. Such in situ phase transition empowers the Ni-Co oxide catalyst with a strong internal electric field and the attainment of abundant oxygen vacancies. Among a series of catalysts, the in situ transformed spinel/rock-salt heterojunction supported on GA stands out for an exceptional photocatalytic CO2 reduction activity and selectivity, yielding an impressive CO production rate of 12.5 mmol g-1 h-1 and high selectivity of 96.5 %. This remarkable performance is a result of the robust interfacial coupling between two topological phases that optimizes the electronic structures through directional charge transfer across interfaces. The phase transition process induces more Co2+ in octahedral site, which can effectively enhance the Co-O covalency. This synergistic effect balances the surface activation of CO2 molecules and desorption of reaction intermediates, thereby lowering the energetic barrier of the rate-limiting step.

Correlation Between Intracoronary Vascular Ultrasound Indexes in Patients with Coronary Heart Disease.

Background: Coronary atherosclerosis is a serious and progressive condition characterized by the accumulation of plaques, consisting of fat, cholesterol, and other substances, within the arteries that supply blood to the heart. These plaques can harden and narrow the arteries, leading to reduced blood flow to the heart muscle. Objective: The primary objective of this study is to investigate the correlation between specific cardiovascular parameters and intracoronary vascular ultrasound indexes in patients diagnosed with coronary heart disease. This investigation aims to explore the relationships between intracoronary vascular ultrasound measurements and three key cardiovascular parameters: epicardial fat pad thickness, mono-platelet polymer levels, and small dense low-density lipoprotein cholesterol (sdLDL-C) levels. Methods: In this investigation, we applied a comprehensive method to evaluate atherosclerotic plaque characteristics in patients with diverse stages of coronary heart disease (CHD), contrasting these profiles with those of healthy individuals. Our study included 80 acute myocardial infarction (AMI) patients, 145 with unstable angina pectoris (UAP), 175 with stable angina pectoris (SAP), and 100 controls. We utilized intravascular ultrasound (IVUS), an advanced imaging technique that surpasses traditional angiography by providing detailed, high-resolution images of both the coronary artery lumen and wall, including plaque composition. This approach is pivotal for assessing plaque stability, a key factor in the risk of rupture and subsequent cardiovascular events, indicated by features like lipid-rich cores and thin fibrous caps. During IVUS, we quantified parameters such as plaque area, load, and the remodeling index, the latter offering insights into vascular adaptation to plaque buildup. Additionally, we conducted a correlation analysis between IVUS indices and three cardiovascular markers: epicardial fat pad thickness, monocyte-platelet aggregates, and sdLDL-C levels. The goal was to ascertain the predictive value of these markers in tandem with IVUS for determining the stability of coronary artery atherosclerotic plaques. This integrative approach enhances understanding of plaque formation and destabilization, potentially informing more effective CHD prevention and management strategies. Results: Our study revealed distinct variations in key parameters across patient groups with different forms of CHD and healthy controls. Notably, we observed significant differences in gender distribution, hypertension, and diabetes mellitus prevalence among these groups. In terms of IVUS indexes and cardiovascular parameters, the SAP group exhibited markedly different results compared to the AMI and UAP groups. Specifically, the SAP patients showed the lowest values for EMMA, plaque area, plaque burden, reconstruction index, and positive remodeling. Additionally, they exhibited the thickest fibrous caps. In contrast, the AMI and UAP groups presented similar outcomes in these aspects. Regarding the epicardial fat pad thickness, the positive rate of monocyte-platelet aggregates, and the levels of sdLDL-C, there were no significant differences between the AMI and UAP groups. However, these parameters were notably higher in the AMI and UAP groups compared to the SAP group. Crucially, we established a significant correlation between the thickness of the epicardial fat pad, the positive rate of monocyte-platelet aggregates, and the sdLDL-C levels with plaque loading rate and remodeling index. These correlations underscore the potential utility of these parameters as indicators of plaque stability and cardiovascular risk in patients with CHD. This highlights the complexity of atherosclerotic disease progression and underscores the importance of a multifaceted approach to assessing and managing CHD. Conclusion: Our research delineates the critical role of the remodeling index, epicardial fat pad thickness, monocyte-platelet aggregates, and sdLDL-C levels as key prognostic tools for assessing coronary plaque stability in coronary artery disease (CAD). These biomarkers collectively provide an enhanced perspective on plaque vulnerability, an essential aspect in the genesis of acute coronary events. Clinically, these findings are pivotal. They offer a refined approach to CAD management and risk evaluation, allowing for the precise identification of patients at increased risk of plaque rupture, a precursor to acute coronary syndromes. This precision facilitates the adoption of more individualized treatment strategies, focusing on aggressive interventions for high-risk patients and more conservative management for those with stable plaques.

Exploring the importance of m5c in the diagnosis and subtype classification of COPD using the GEO database.

BACKGROUND: 5-Methylcytosine (m5C) is an mRNA modifier that is associated with the occurrence and development of viral infection, pulmonary fibrosis, lung cancer, and other diseases. However, the role of m5C regulators in chronic obstructive pulmonary disease (COPD) remains unknown. METHODS: In this study, by analysing the GSE42057 dataset, the differential expression of m5c regulators in the COPD group and control group was obtained, and a correlation analysis was conducted. The random forest model and support vector machine model were used to predict the occurrence of COPD. A nomogram model was also constructed to predict the prevalence of COPD. The COPD patients were divided into subtypes by consistent cluster analysis based on m5c methylation regulators. Immune cell infiltration was performed on the m5c methylation subtypes. Differentially expressed genes (DEGs) between m5c methylation subtypes were screened, and the DEGs were analysed by Gene Ontology (GO) Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, we verified the expression of several m5C regulators and related pathways using a COPD cell model. RESULTS: Seven m5c methylation regulators were differentially expressed. The random forest model based on the above genes was the most accurate for predicting the occurrence of COPD. A nomogram model based on the above genes could also accurately predict the prevalence of COPD, and the implementation of these models could benefit COPD patients. The consistent cluster analysis divided the COPD patients into two subtypes (Cluster A and Cluster B). The main component analysis algorithm determined the m5c methylation subtypes and found that patients in Cluster A had a higher m5c score than those in Cluster B. GO analysis of the DEGs between the m5c methylation COPD patient subtypes revealed that DEGS were mainly enriched in leukocyte-mediated immunity and regulation of T-cell activation. KEGG analysis revealed that DEGS were mainly enriched in Th1 and Th2 cell differentiation, neutrophil extracellular trap formation, and the NF-κB signalling pathway. Immunocyte correlation analysis revealed that Cluster B was associated with neutrophil- and macrophage-mediated immunity, while Cluster A was associated with CD4 + T-cell- and CD8 + T-cell-mediated immunity. Cell experiments have also verified some of the above research results. CONCLUSION: The diagnosis and subtype classification of COPD patients based on m5c regulators may provide a new strategy for the diagnosis and treatment of COPD.

Ultra-High-Density Ferroelectric Array Formed by Sliding Ferroelectric Moiré Superlattices.

2D van der Waals (vdW) materials offer infinite possibilities for constructing unique ferroelectrics through simple layer stacking and rotation. In this work, we stack nonferroelectric GeS2 and ferroelectric CuInP2S6 to form heterostructures by combining sliding ferroelectric polarization with displacement ferroelectric polarization to achieve multiple polarization states. First-principles calculations reveal that the polarization reversal of the CuInP2S6 component in the GeS2/CuInP2S6/GeS2 heterostructure can simultaneously drive the switching of sliding ferroelectric polarization, displaying a robust coupling of the two polarizations and leading to the overall polarization switching. Based on this, ferroelectric arrays with a density of 6.55 × 1012 cm-2 (equivalent to a storage density of 0.7 TB cm-2) were constructed in a moiré superlattice, and the polarization strength of array elements was 11.77 pC/m, higher than that of all reported 2D vdW out-of-plane ferroelectrics. High density, large polarization, and electrically switchable array elements in ferroelectric arrays provide unprecedented opportunities to design 2D high-density nonvolatile ferroelectric memories.

Targeting B4GALT7 suppresses the proliferation, migration and invasion of hepatocellular carcinoma through the Cdc2/CyclinB1 and miR-338-3p/MMP2 pathway.

Background: As a three-dimensional network involving glycosaminoglycans (GAGs), proteoglycans (PGs) and other glycoproteins, the role of extracellular matrix (ECM) in tumorigenesis is well revealed. Abnormal glycosylation in liver cancer is correlated with tumorigenesis and chemoresistance. However, the role of galactosyltransferase in HCC (hepatocellular carcinoma) is largely unknown. Methods: Here, the oncogenic functions of B4GALT7 (beta-1,4-galactosyltransferase 7) were identified in HCC by a panel of in vitro experiments, including MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, transwell and flow cytometry assay. The expression of B4GALT7 in HCC cell lines and tissues were examined by qPCR (real-time quantitative polymerase chain reaction) and western blot assay. The binding between B4GALT7 and miR-338-3p was examined by dual-luciferase reporter assay. Results: B4GALT7 encodes galactosyltransferase I and it is highly expressed in HCC cells and human HCC tissues compared with para-tumor specimens. MiR-338-3p was identified to bind the 3' UTR (untranslated region) of B4GALT7. Highly expressed miR-338-3p suppressed HCC cell invasive abilities and rescued the tumor-promoting effect of B4GALT7 in HCC. ShRNA (short hairpin RNA) mediated B4GALT7 suppression reduced HCC cell invasive abilities, and inhibited the expression of MMP-2 and Erk signaling. Conclusion: These findings identified B4GALT7 as a potential prognostic biomarker and therapeutic target for HCC.

Transcriptomic analysis reveals that methyl jasmonate confers salt tolerance in alfalfa by regulating antioxidant activity and ion homeostasis.

Introduction: Alfalfa, a globally cultivated forage crop, faces significant challenges due to its vulnerability to salt stress. Jasmonates (JAs) play a pivotal role in modulating both plant growth and response to stressors. Methods: In this study, alfalfa plants were subjected to 150 mM NaCl with or without methyl jasmonate (MeJA). The physiological parameters were detected and a transcriptomic analysis was performed to elucidate the mechanisms underlying MeJA-mediated salt tolerance in alfalfa. Results: Results showed that exogenous MeJA regulated alfalfa seed germination and primary root growth in a dose-dependent manner, with 5µM MeJA exerting the most efficient in enhancing salt tolerance. MeJA at this concentration elavated the salt tolerance of young alfalfa seedlings by refining plant growth, enhancing antioxidant capacity and ameliorating Na+ overaccumulation. Subsequent transcriptomic analysis identified genes differentially regulated by MeJA+NaCl treatment and NaCl alone. PageMan analysis revealed several significantly enriched categories altered by MeJA+NaCl treatment, compared with NaCl treatment alone, including genes involved in secondary metabolism, glutathione-based redox regulation, cell cycle, transcription factors (TFs), and other signal transductions (such as calcium and ROS). Further weighted gene co-expression network analysis (WGCNA) uncovered that turquoise and yellow gene modules were tightly linked to antioxidant enzymes activity and ion content, respectively. Pyruvate decar-boxylase (PDC) and RNA demethylase (ALKBH10B) were identified as the most central hub genes in these two modules. Also, some TFs-hub genes were identified by WGCNA in these two modules highly positive-related to antioxidant enzymes activity and ion content. Discussion: MeJA triggered a large-scale transcriptomic remodeling, which might be mediated by transcriptional regulation through TFs or post-transcriptional regulation through demethylation. Our findings contributed new perspectives for understanding the underneath mechanisms by which JA-mediated salt tolerance in alfalfa.

Effect of acupuncture on BDNF signaling pathways in several nervous system diseases.

In recent years, the understanding of the mechanisms of acupuncture in the treatment of neurological disorders has deepened, and considerable progress has been made in basic and clinical research on acupuncture, but the relationship between acupuncture treatment mechanisms and brain-derived neurotrophic factor (BDNF) has not yet been elucidated. A wealth of evidence has shown that acupuncture exhibits a dual regulatory function of activating or inhibiting different BDNF pathways. This review focuses on recent research advances on the effect of acupuncture on BDNF and downstream signaling pathways in several neurological disorders. Firstly, the signaling pathways of BDNF and its function in regulating plasticity are outlined. Furthermore, this review discusses explicitly the regulation of BDNF by acupuncture in several nervous system diseases, including neuropathic pain, Parkinson's disease, cerebral ischemia, depression, spinal cord injury, and other diseases. The underlying mechanisms of BDNF regulation by acupuncture are also discussed. This review aims to improve the theoretical system of the mechanism of acupuncture action through further elucidation of the mechanism of acupuncture modulation of BDNF in the treatment of neurological diseases and to provide evidence to support the wide application of acupuncture in clinical practice.

Influence of Molecular Structure and Material Properties on the Output Performance of Liquid-Solid Triboelectric Nanogenerators.

With the advantages of superior wear resistance, mechanical durability, and stability, the liquid-solid triboelectric nanogenerator (LS-TENG) has been attracting much attention in the field of energy harvesting and self-powered sensors. However, most of the studies on LS-TENG focused on device innovations, changes in solid materials, and the effect of solid properties on output performance, and there is a lack of studies on liquids, especially at the molecular level. A U-tube LS-TENG was assembled to conduct experiments, whereby the effects of molecular structures, including molecular composition, carbon chain length, functional groups and material properties on the output performance were investigated. The deuterium replacing hydrogen and the atomic compositions could not achieve the enhancement of the output performance. Whether the chemical functional groups improve the output performance of LS-TENG depends on the mating solid material. Hydroxyl and cyanogenic groups can improve the output performance for the FEP case, while amide and cyanogenic groups can improve the output performance for the PTFE case. The order of output performances for functional groups of four groups of liquids with both FEP and PTFE materials is also obtained. It was also found that the dielectric constant is not positively correlated with the output performance. The results of this study might provide a reference for the deeper study and application of LS-TENG.

[Phage antibody library technology in tumor therapy: a review].

Tumor is a serious threat to human health. At present, surgical resection, chemoradiotherapy, targeted therapy and immunotherapy are the main therapeutic strategies. Monoclonal antibody has gradually become an indispensable drug type in the clinical treatment of cancer due to its high efficiency and low toxicity. Phage antibody library technology (PALT) is a novel monoclonal antibody preparation technique. The recombinant immunoglobulin variable region of heavy chain (VH)/variable region of light chain (VL) gene is integrated into the phage vector, and the antibody is expressed on the phage surface in the form of fusion protein to obtain a diverse antibody library. Through the process of adsorption-elution-amplification, the antibody library can be screened to obtain the antibody molecule with specific binding antigen as well as its gene sequence. PALT has the advantages of short antibody production cycle, strong plasticity of antibody structure, large antibody yield, high diversity and direct production of humanized antibodies. It has been used in screening tumor markers and preparation of antibody drugs for breast cancer, gastric cancer, lung cancer and liver cancer. This article reviews the recent progress and the application of PALT in tumor therapy.