The Antihypertensive Effects and Mechanisms of Huotan Jiedu Tongluo Decoction in Rats with H-Type Hypertension.

H-type hypertension, which is a specific form of hypertension characterized by elevated plasma homocysteine (Hcy) levels, has become a major public health challenge worldwide. This study investigated the hypotensive effects and underlying mechanisms of Huotan Jiedu Tongluo decoction (HTJDTLD), a highly effective traditional Chinese medicine formula commonly used to treat vascular stenosis. Methionine was used to induce H-type hypertension in rats, and HTJDTLD was administered intragastrically. Then, the systolic and diastolic blood pressures of the caudal artery of rats were measured by noninvasive rat caudal manometry. Histological assessment of the aorta was performed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to measure Hcy levels, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting were used to determine the mRNA and protein levels of Glucose regulatory protein 78 (GRP78), Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), c-Jun N-terminal kinases (JNK), and caspase-3. The results showed that HTJDTLD significantly lowered blood pressure, alleviated histopathological lesions, and decreased Hcy levels after methionine treatment. Moreover, HTJDTLD significantly inhibited the gene and protein expression of GRP78, JNK, TRAF2, and caspase 3, which are involved mainly in the endoplasmic reticulum (ER) stress-induced apoptosis pathway. Overall, the results indicated that HTJDTLD had effective antihypertensive effects in rats with H-type hypertension and revealed the antihypertensive mechanisms associated with inhibition of ER stress-induced apoptosis pathway activation.

Tribological properties of MAO ceramic coatings with annulus array texture on disposable surgical gloves.

Introduction: In recent research, the expansion in the use of Mg alloys for biomedical applications has been approached by modifying their surfaces in conjunction with micro-arc oxidation (MAO) techniques which enhance their abrasion and corrosion resistance. Methods: In this study, combining laser texturing and MAO techniques to produce the dense ceramic coatings with microstructures. On the surface of the AZ31 Mg alloy, a micro-raised annulus array texture has been designed in order to increase the surface friction under liquid lubrication and to improve the operator's grip when holding the tool. For this work, the micro-morphology of the coatings was characterised, and the friction properties of the commonly used scalpel shank material 316 L, the untextured surface and the textured surface were comparatively analysed against disposable surgical gloves. Results and discussion: The results show that the Laser-MAO ceramic coating grows homogenous, the porosity decreases from 14.3% to 7.8%, and the morphology after friction indicates that the coating has good wear resistance. More specifically, the average coefficient of friction (COF) of the three types of gloves coated with Laser-MAO ceramic was higher than that of the 316 L and MAO ceramic coatings under the action of the annulus-integrated texture under the lubrication conditions of physiological saline and defatted sheep blood, which achieved the goal of increasing friction for the purpose of helping to prevent the problem of tool slippage from the hand.

Another piece of the puzzle for the human microbiome: the gut virome under dietary modulation.

The virome is the most abundant and highly variable microbial consortium in the gut. Because of difficulties in isolating and culturing gut viruses and consequently shorting of reference genomes, the virome has remained a relatively elusive aspect of the human microbiome. In recent years, studies on the virome have accumulated growing evidence showing that the virome is diet-modulated and widely involved in regulating health. Here, we review the responses of the gut virome to dietary intake and the potential health implications, presenting changes in the gut viral community, preferences of viral members to particular diets. We further discuss how viral-bacterial interactions and phage lifestyle shifts shape the gut microbiota. We also discuss the specific functions conferred by diet on the gut virome and bacterial community in the context of horizontal gene transfer, as well as the import of new viral members along with the diet. Collating these studies will expand our understanding of the dietary regulation of the gut virome and inspire dietary interventions and health maintenance strategies targeting the gut microbiota.

Investigating the Impact of Gut Microbiota on Gout Through Mendelian Randomization.

Background: The relationship between gout and gut microbiota has attracted significant attention in current research. However, due to the diverse range of gut microbiota, the specific causal effect on gout remains unclear. This study utilizes Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and gout, aiming to elucidate the underlying mechanism of microbiome-mediated gout and provide valuable guidance for clinical prevention and treatment. Materials and Methods: The largest genome-wide association study meta-analysis conducted by the MiBioGen Consortium (n=18,340) was utilized to perform a two-sample Mendelian randomization investigation on aggregate statistics of intestinal microbiota. Summary statistics for gout were utilized from the data released by EBI. Various methods, including inverse variance weighted, weighted median, weighted model, MR-Egger, and Simple-mode, were employed to assess the causal relationship between gut microbiota and gout. Reverse Mendelian randomization analysis revealed a causal association between bacteria and gout in forward Mendelian randomization analysis. Cochran's Q statistic was used to quantify instrumental variable heterogeneity. Results: The inverse variance weighted estimation revealed that Rikenellaceae exhibited a slight protective effect on gout, while the presence of Ruminococcaceae UCG_011 is associated with a marginal increase in the risk of gout. According to the reverse Mendelian Randomization results, no significant causal relationship between gout and gut microbiota was observed. No significant heterogeneity of instrumental variables or level pleiotropy was detected. Conclusion: Our MR analysis revealed a potential causal relationship between the development of gout and specific gut microbiota; however, the causal effect was not robust, and further research is warranted to elucidate its underlying mechanism in gout development. Considering the significant association between diet, gut microbiota, and gout, these findings undoubtedly shed light on the mechanisms of microbiota-mediated gout and provide new insights for translational research on managing and standardizing treatment for this condition.

Addressing Challenges in Ion-Selectivity Characterization in Nanopores.

Ion selectivity is the basis for designing smart nanopore/channel-based devices, e.g., ion separators and biosensors. Quantitative characterization of ion selectivities in nanopores often employs the Nernst or Goldman-Hodgkin-Katz (GHK) equation to interpret transmembrane potentials. However, the direction of the measured transmembrane potential drop is not specified in these equations, and selectivity values calculated using absolute values of transmembrane potentials do not directly reveal the ion for which the membrane is selective. Moreover, researchers arbitrarily choose whether to use the Nernst or GHK equation and overlook the significant differences between them, leading to ineffective quantitative comparisons between studies. This work addresses these challenges through (a) specifying the transmembrane potential (sign) and salt concentrations in terms of working and reference electrodes and the solutions in which they reside when using the Nernst and GHK equations, (b) reporting of both Nernst-selectivity and GHK-selectivity along with solution compositions and transmembrane potentials when comparing different nanopores/channels, and (c) performing simulations to define an ideal selectivity for nanochannels. Experimental and modeling studies provide significant insight into these fundamental equations and guidelines for the development of nanopore/channel-based devices.

HGCLAMIR: Hypergraph contrastive learning with attention mechanism and integrated multi-view representation for predicting miRNA-disease associations.

Existing studies have shown that the abnormal expression of microRNAs (miRNAs) usually leads to the occurrence and development of human diseases. Identifying disease-related miRNAs contributes to studying the pathogenesis of diseases at the molecular level. As traditional biological experiments are time-consuming and expensive, computational methods have been used as an effective complement to infer the potential associations between miRNAs and diseases. However, most of the existing computational methods still face three main challenges: (i) learning of high-order relations; (ii) insufficient representation learning ability; (iii) importance learning and integration of multi-view embedding representation. To this end, we developed a HyperGraph Contrastive Learning with view-aware Attention Mechanism and Integrated multi-view Representation (HGCLAMIR) model to discover potential miRNA-disease associations. First, hypergraph convolutional network (HGCN) was utilized to capture high-order complex relations from hypergraphs related to miRNAs and diseases. Then, we combined HGCN with contrastive learning to improve and enhance the embedded representation learning ability of HGCN. Moreover, we introduced view-aware attention mechanism to adaptively weight the embedded representations of different views, thereby obtaining the importance of multi-view latent representations. Next, we innovatively proposed integrated representation learning to integrate the embedded representation information of multiple views for obtaining more reasonable embedding information. Finally, the integrated representation information was fed into a neural network-based matrix completion method to perform miRNA-disease association prediction. Experimental results on the cross-validation set and independent test set indicated that HGCLAMIR can achieve better prediction performance than other baseline models. Furthermore, the results of case studies and enrichment analysis further demonstrated the accuracy of HGCLAMIR and unconfirmed potential associations had biological significance.

Significant correlation between leaf vein length per unit area and stomatal density: evidence from Red Tip and Chinese photinias.

The vascular veins in photosynthetic leaves play an important role in transporting water and sugars throughout the plant body, and their venation pattern and vein density determine the hydraulic efficiency of the leaf. Likewise, stomatal density (SD) can influence photosynthetic gas exchange. However, the correlation between leaf vein density and SD is seldom reported. Herein, we examined 16 leaves from the hybrid Photinia × fraseri and 16 leaves from one of its parents, P. serratifolia, to explore the correlation between leaf vein density and SD. For each leaf, equidistant lamina quadrats were excised along two longitudinal transects (one along the midrib and another along the leaf margin). For each quadrat, micrographs of 1.2 mm × 0.9 mm stomatal imprints, and 2.51 mm × 1.88 mm micrographs of leaf veins were used to measure total vein area per leaf unit area (VAA) and total vein length per unit area (VLA), as indicators of leaf vein density, to determine the correlation between SD and leaf vein density. For each taxon, there was no significant correlation between SD and VAA, but there was a significant correlation between SD and VLA. The data indicate that SD is not positively correlated with VAA but positively correlated with VLA for both the hybrid and the parent species. This study indicates that future work should focus on the relationships between SD and total vein length per unit area rather than on total leaf vein area per unit area within and across species.

Precise Regulation in Chain-Edge Structural Microenvironments of 1D Covalent Organic Frameworks for Photocatalysis.

Covalent organic frameworks (COFs) constitute a promising research topic for photocatalytic reactions, but the rules and conformational relationships of 1D COFs are poorly defined. Herein, the chain edge structure is designed by precise modulation at the atomic level, and the 1D COFs bonded by C, O, and S elements is directionally prepared for oxygen-tolerant photoinduced electron transfer-atom transfer radical polymerization (PET-ATRP) reactions. It is demonstrated that heteroatom-type chain edge structures (─O─, ─S─) lead to a decrease in intra-plane conjugation, which restricts the effective transport of photogenerated electrons along the direction of the 1D strip. In contrast, the all-carbon type chain edge structure (─C─) with higher intra-plane conjugation not only reduces the energy loss of photoexcited electrons but also enhances the carrier density, which exhibits the optimal photopolymerization performance. This work offers valuable guidance in the exploitation of 1D COFs for high photocatalytic performance. This work offers valuable guidance in the exploitation of 1D COFs for high photocatalytic performance.

Manipulating Crystal Growth and Secondary Phase PbI2 to Enable Efficient and Stable Perovskite Solar Cells with Natural Additives.

In perovskite solar cells (PSCs), the inherent defects of perovskite film and the random distribution of excess lead iodide (PbI2) prevent the improvement of efficiency and stability. Herein, natural cellulose is used as the raw material to design a series of cellulose derivatives for perovskite crystallization engineering. The cationic cellulose derivative C-Im-CN with cyano-imidazolium (Im-CN) cation and chloride anion prominently promotes the crystallization process, grain growth, and directional orientation of perovskite. Meanwhile, excess PbI2 is transferred to the surface of perovskite grains or formed plate-like crystallites in local domains. These effects result in suppressing defect formation, decreasing grain boundaries, enhancing carrier extraction, inhibiting non-radiative recombination, and dramatically prolonging carrier lifetimes. Thus, the PSCs exhibit a high power conversion efficiency of 24.71%. Moreover, C-Im-CN has multiple interaction sites and polymer skeleton, so the unencapsulated PSCs maintain above 91.3% of their initial efficiencies after 3000 h of continuous operation in a conventional air atmosphere and have good stability under high humidity conditions. The utilization of biopolymers with excellent structure-designability to manage the perovskite opens a state-of-the-art avenue for manufacturing and improving PSCs.

Pore-Size-Dependent Role of Functional Elements at the Outer Surface and Inner Wall in Single-Nanochannel Biosensors.

Biological nanopores feature functional elements on the outer surfaces (FEOS) and inner walls (FEIW), enabling precise control over ions and molecules with exceptional sensitivity and specificity. This provides valuable inspiration to scientists for the development of intelligent artificial nanochannel-based platforms, with a wide range of potential applications, including biosensors. Much effort has been dedicated to investigating the distinct contribution of FEOS and FEIW of multichannel membrane biosensors. However, the intricate interactions among neighboring pores in multichannel biosensors have presented challenges. This underscores the untapped potential of single nanochannels as ideal candidates in this field. Here, we employed single nanochannel membranes with different pore sizes to investigate the distinct contributions of FEIW and FEOS to single-nanochannel biosensors, combined with numerical simulations. Our findings revealed that alterations in the negative charges of FEIW and FEOS, induced by target binding, have differential effects on ion transport, contingent upon the degree of nanoconfinement. In the case of smaller pores, such as 20 nm, the ion concentration polarization driven by FEIW can independently control ion transport through the surface's electric double layer. However, as the pore size increases to 40-60 nm, both FEIW and FEOS become essential for effective ion concentration polarization. When the pore size reaches 100 nm, both FEIW and FEOS are ineffective and thus unsuitable for biosensors. Simulations demonstrate that the observed phenomena can be attributed to the interactions between the charges of FEIW and FEOS within the overlapping electric double layer under confinement. These results underscore the critical role of pore size as a key parameter in governing the functionality of probes within or on nanopore-based biosensors as well as in the design of nanopore-based devices.

Quorum sensing bacteria improve microbial networks stability and complexity in wastewater treatment plants.

Quorum-sensing bacteria (QSB) are crucial factors for microbial communication, yet their ecological role in wastewater treatment plants (WWTPs) remains unclear. Here, we developed a method to identify QSB by comparing 16S rRNA gene sequences. QSB in 388 activated sludge samples collected from 130 WWTPs across China primarily were identified as rare taxa and conditionally rare taxa. A co-occurrence network shared by all sludge communities revealed that QSB exhibited higher average clustering coefficient (0.46) than non-QSB (0.15). Individual sludge networks demonstrated that quorum sensing microbiomes were positively correlated with network robustness and network complexity, including average clustering coefficient and link density. We confirmed that QSB keystones and QSB nodes have a positive impact on network complexity by influencing network modularity through a structural equation model. Meanwhile, QSB communities directly contributed to maintaining network robustness (r = 0.29, P < 0.05). Hence, QSB play an important role in promoting network complexity and stability. Furthermore, QSB communities were positively associated with the functional composition of activated sludge communities (r = 0.33, P < 0.01), especially the denitrification capacity (r = 0.45, P < 0.001). Overall, we elucidated the ecological significance of QSB and provided support for QS-based regulation of activated sludge microbial communities.

Environmental-friendly, flexible silk fibroin-based film as dual-responsive shape memory material.

Bio-based shape memory materials have attracted wide attention due to their biocompatibility, degradability and safety. However, designing and manufacturing wearable bio-based shape memory films with excellent flexibility and toughness is still a challenge. In this work, silk fibroin substrate with a ß-sheet structure was combined with a tri-block shape memory copolymer to prepare a transparent composited shape memory film. The silk fibroin-based film showed a dual-responsive shape memory function, which can respond to both temperature and water stimuli. This film has a sensitive water-responsive shape memory, which starts deforming after exposure to water for 3 s and fully recovers in 30 s. In addition, the composite film shows highly stretchable (>300 %) and could maintain its high tensile properties after 5 cycles of regeneration. The films also exhibited rapid degradation ability. This study provides new insights for the design of dual-responsive shape memory materials by combining biocompatible matrix and multi-block SMP to simultaneously enhance the mechanical properties, which can be used for intelligent packaging, medical supplies, soft actuators and wearable devices.

Mertk Reduces Blood-Spinal Cord Barrier Permeability Through the Rhoa/Rock1/P-MLC Pathway After Spinal Cord Injury.

Disruption of the blood-spinal cord barrier (BSCB) is a critical event in the secondary injury following spinal cord injury (SCI). Mertk has been reported to play an important role in regulating inflammation and cytoskeletal dynamics. However, the specific involvement of Mertk in BSCB remains elusive. Here, we demonstrated a distinct role of Mertk in the repair of BSCB. Mertk expression is decreased in endothelial cells following SCI. Overexpression of Mertk upregulated tight junction proteins (TJs), reducing BSCB permeability and subsequently inhibiting inflammation and apoptosis. Ultimately, this led to enhanced neural regeneration and functional recovery. Further experiments revealed that the RhoA/Rock1/P-MLC pathway plays a key role in the effects of Mertk. These findings highlight the role of Mertk in promoting SCI recovery through its ability to mitigate BSCB permeability and may provide potential targets for SCI repair.

Abnormal energy metabolism, oxidative stress, and polyunsaturated fatty acid metabolism in depressed adolescents associated with childhood maltreatment: A targeted metabolite analysis.

The purpose of this study was to explore the metabolomic differences between Major depressive disorder (MDD) and healthy individuals among adolescents and the association between childhood maltreatment (CM) and differentially abundant metabolites. The exploratory study included 40 first-episode drug-naïve adolescents with MDD and 20 healthy volunteers. We used the Beck Depression Inventory (BDI-13) to assess the severity of depression and the Childhood Trauma Questionnaire (CTQ) to assess the presence of childhood maltreatment. The plasma samples from all participants were collected for targeted metabolomics analysis using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC‒MS/MS) methods. Spearman correlation was applied to analyse the correlations between clinical variables and metabolites. We found 11 increased metabolites and 37 decreased metabolites that differed between adolescents with MDD and healthy individuals. Pathway enrichment analysis of differentially abundant metabolites showed abnormalities in energy metabolism and oxidative stress in MDD. Importantly, we found that creatine, valine, isoleucine, glutamic acid and pyroglutamic acid were negatively correlated with the BDI-13, while isocitric acid, fatty acid and acylcarnitine were negatively associated with CTQ, and 4-hydroxyproline was positively related to CTQ in adolescents with MDD. These studies provide new ideas for the pathogenesis and potential treatment of adolescents with MDD.

Circular RNA MKLN1 promotes epithelial-mesenchymal transition in pulmonary fibrosis by regulating the miR-26a/b-5p/CDK8 axis in human alveolar epithelial cells and mice models.

Pulmonary fibrosis involves destruction of the lung parenchyma and extracellular matrix deposition. Effective treatments for pulmonary fibrosis are lacking and its pathogenesis is still unclear. Studies have found that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AECs) plays an important role in progression of pulmonary fibrosis. Thus, an in-depth exploration of its mechanism might identify new therapeutic targets. In this study, we revealed that a novel circular RNA, MKLN1 (circMKLN1), was significantly elevated in two pulmonary fibrosis models (intraperitoneally with PQ, 50 mg/kg for 7 days, and intratracheally with BLM, 5 mg/kg for 28 days). Additionally, circMKLN1 was positively correlated with the severity of pulmonary fibrosis. Inhibition of circMKLN1 expression significantly reduced collagen deposition and inhibited EMT in AECs. EMT was aggravated after circMKLN1 overexpression in AECs. MiR-26a-5p/miR-26b-5p (miR-26a/b), the targets of circMKLN1, were confirmed by luciferase reporter assays. CircMKLN1 inhibition elevated miR-26a/b expression. Significantly decreased expression of CDK8 (one of the miR-26a/b targets) was observed after inhibition of circMKLN1. EMT was exacerbated again, and CDK8 expression was significantly increased after circMKLN1 inhibition and cotransfection of miR-26a/b inhibitors in AECs. Our research indicated that circMKLN1 promoted CDK8 expression through sponge adsorption of miR-26a/b, which regulates EMT and pulmonary fibrosis. This study provides a theoretical basis for finding new targets or biomarkers in pulmonary fibrosis.

Unveiling the role of YARS1 in bladder cancer: A prognostic biomarker and therapeutic target.

YARS is responsible for catalysing the binding of tyrosine to its cognate tRNA and plays a crucial role in basic biosynthesis. However, its biological functions in bladder cancer remains to be proven. We analysed variations in YARS1 expression and survival in bladder cancer using multiple data sets, including TCGA-BLCA, GSE13507 and bladder cancer-specific tissue microarrays. Furthermore, we explored the biological functions of YARS1 using transcriptome data. Our findings revealed a noteworthy correlation between YARS1 and immune infiltration in bladder cancer, as determined using the XCELL algorithm and single-cell analysis. In addition, we employed the TIDE algorithm to evaluate the responsiveness of different cohorts to immune checkpoint therapy. We investigated the regulatory associations between YARS1 and various aspects of bladder cancer, including senescence, ferroptosis and stemness. Finally, we established a ceRNA network that is directly linked to the overall prognosis, YARS1 can serve as a prognostic biomarker for bladder cancer; its interaction with MYC has implications for bladder cancer cell senescence, ferroptosis and stemness. Moreover, the identified ceRNA network has potential as a therapeutic target in bladder cancer.

Multidimensional pan-cancer analysis of HSPA5 and its validation in the prognostic value of bladder cancer.

Endoplasmic reticulum (ER) stress-related genes are closely related to the occurrence, development, and immunotherapy response of tumors. This study provides a comprehensive assessment of HSPA5 from a pan-cancer perspective using multi-omics data. We analyzed the function of HSPA5 in multiple tumor types using multiple databases. Finally, immunohistochemistry was used to examine the relationship between HSPA5 expression in tissue microarrays from 100 patients with bladder cancer and the prognosis of patients with bladder cancer. Using the TCGA database, we were able to determine that HSPA5 is significantly elevated in a number of common malignancies and is linked with a bad prognosis. Cox regression analysis showed that the high expression of HSPA5 was correlated with OS, progression free survival (PFS), disease free survival (DFS), and disease special survival (DSS) of adrenocortical carcinoma (ACC). In addition, we discovered significant disparities in HSPA5 methylation and phosphorylation levels between various malignancies and normal tissues. HSPA5 expression was significantly correlated with the levels of infiltrating cells and immune checkpoint genes. HSPA5 is highly expressed in bladder cancer and patients with high HSPA5 expression have a poor prognosis. Our study provides a basis for further understanding of the role of ER stress-related gene HSPA5 in different tumor genesis and development. HSPA5 has also been shown to be a prognostic biomarker for bladder cancer patients.

Constructions of quorum sensing signaling network for activated sludge microbial community.

In wastewater treatment systems, the interactions among various microbes based on chemical signals, namely quorum sensing (QS), play critical roles in influencing microbial structure and function. However, it is challenging to understand the QS-controlled behaviors and the underlying mechanisms in complex microbial communities. In this study, we constructed a QS signaling network, providing insights into the intra- and interspecies interactions of activated sludge microbial communities based on diverse QS signal molecules. Our research underscores the role of diffusible signal factors in both intra- and interspecies communication among activated sludge microorganisms, and signal molecules commonly considered to mediate intraspecies communication may also participate in interspecies communication. QS signaling molecules play an important role as communal resources among the entire microbial group. The communication network within the microbial community is highly redundant, significantly contributing to the stability of natural microbial systems. This work contributes to the establishment of QS signaling network for activated sludge microbial communities, which may complement metabolic exchanges in explaining activated sludge microbial community structure and may help with a variety of future applications, such as making the dynamics and resilience of highly complex ecosystems more predictable.

Controllable π-π coupling of intramolecular dimer models in aggregated states.

π-π coupling as a common interaction plays a key role in emissions, transport and mechanical properties of organic materials. However, the precise control of π-π coupling is still challenging owing to the possible interference from other intermolecular interactions in the aggregated state, usually resulting in uncontrollable emission properties. Herein, with the rational construction of intramolecular dimer models and crystal engineering, π-π coupling can be subtly modulated by conformation variation with balanced π-π and π-solvent interactions and visualized by green-to-blue emission switching. Moreover, it can rapidly respond to temperature, pressure and mechanical force, affording a facile way to modulate π-π coupling in situ. This work contributes to a deeper understanding of the internal mechanism of molecular motions in aggregated states.