LRG1 promotes the apoptosis of pulmonary microvascular endothelial cells through KLK10 in chronic obstructive pulmonary disease.

INTRODUCTION: Cigarette smoking is one of the most important causes of COPD and could induce the apoptosis of pulmonary microvascular endothelial cells (PMVECs). The conditional knockout of LRG1 from endothelial cells reduced emphysema in mice. However, the mechanism of the deletion of LRG1 from endothelial cells rescued by cigarette smoke (CS) induced emphysema remains unclear. This research aimed to demonstrate whether LRG1 promotes the apoptosis of PMVECs through KLK10 in COPD. METHODS: Nineteen patients were divided into three groups: control non-COPD (n=7), smoker non-COPD (n=7), and COPD (n=5). The emphysema mouse model defined as the CS exposure group was induced by CS exposure plus cigarette smoke extract (CSE) intraperitoneal injection for 28 days. Primary PMVECs were isolated from the mouse by magnetic bead sorting method via CD31-Dynabeads. Apoptosis was detected by western blot and flow cytometry. RESULTS: LRG1 was increased in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. KLK10 was over-expressed in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. LRG1 promoted apoptosis in PMVECs. LRG1 knockdown reversed CSE-induced apoptosis in PMVECs. The mRNA and protein expression of KLK10 were increased after over-expressed LRG1 in PMVECs isolated from mice. Similarly, both the mRNA and protein levels of KLK10 were decreased after LRG1 knockdown in PMVECs. The result of co-immunoprecipitation revealed a protein-protein interaction between LRG1 and KLK10 in PMVECs. KLK10 promoted apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. KLK10 knockdown could reverse CSE-induced apoptosis in PMVECs. CONCLUSIONS: LRG1 promotes apoptosis via up-regulation of KLK10 in PMVECs isolated from mice. KLK10 promotes apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. There was a direct protein-protein interaction between LRG1 and KLK10 in PMVECs. Our novel findings provide insights into the understanding of LRG1/KLK10 function as a potential molecule in COPD.

Engineering injectable hyaluronic acid-based adhesive hydrogels with anchored PRP to pattern the micro-environment to accelerate diabetic wound healing.

Diabetic wounds remain a global challenge due to disordered wound healing led by inflammation, infection, oxidative stress, and delayed proliferation. Therefore, an ideal wound dressing for diabetic wounds not only needs tissue adhesiveness, injectability, and self-healing properties but also needs a full regulation of the microenvironment. In this work, adhesive wound dressings (HA-DA/PRP) with injectability were fabricated by combining platelet rich plasma (PRP) and dopamine-modified-hyaluronic acid (HA-DA). The engineered wound dressings exhibited tissue adhesiveness, rapid self-healing, and shape adaptability, thereby enhancing stability and adaptability to irregular wounds. The in vitro experiments demonstrated that HA-DA/PRP adhesives significantly promoted fibroblast proliferation and migration, attributed to the loaded PRP. The adhesives showed antibacterial properties against both gram-positive and negative bacteria. Moreover, in vitro experiments confirmed that HA-DA/PRP adhesives effectively mitigated oxidative stress and inflammation. Finally, HA-DA/PRP accelerated the healing of diabetic wounds by inhibiting bacterial growth, promoting granulation tissue regeneration, accelerating neovascularization, facilitating collagen deposition, and modulating inflammation through inducing M1 to M2 polarization, in an in vivo model of infected diabetic wounds. Overall, HA-DA/PRP adhesives with the ability to comprehensively regulate the microenvironment in diabetic wounds may provide a novel approach to expedite the diabetic wounds healing in clinic.

Molecular characterization and zoonotic potential of Cryptosporidium spp. and Giardia duodenalis in humans and domestic animals in Heilongjiang Province, China.

BACKGROUND: Cryptosporidiosis and giardiasis are significant parasitic diseases shared between humans and domestic animals. Due to the close contact between humans and domestic animals in rural areas, it is important to consider the potential transmission of zoonotic parasites from infected domestic animals to humans. This investigation aimed to determine the prevalence and molecular characteristics of Cryptosporidium spp. and Giardia duodenalis in domestic animals and villagers. METHODS: A total of 116 fecal samples from villagers and 686 fecal samples from domestic animals in Heilongjiang Province, China, were analyzed for two parasites using nested polymerase chain reaction (PCR) targeting various genetic loci and DNA sequence analysis of the PCR products. RESULTS: By sequence analysis of the SSU rRNA gene, the prevalence of Cryptosporidium in humans was 0.9% (1/116), with one species of C. parvum (n = 1) detected; among domestic animals, the prevalence was 2.6% (18/686), with five species identified: C. suis (n = 7) and C. scrofarum (n = 7) in pigs, C. meleagridis (n = 1) in chickens, C. andersoni (n = 1) in cattle, and C. canis (n = 2) in foxes. C. parvum and C. canis were further subtyped as IIdA19G1 and XXa4 on the basis of gp60 gene. Regarding G. duodenalis, based on the SSU rRNA, bg, gdh, and tpi genes, the prevalence in domestic animals was 5.1% (31/608), with three assemblages identified: A (n = 1) in pigs, D (n = 1) in foxes, and E (n = 27) in geese, cattle, pigs, ducks, and sheep, along with mixed infection of A + E (n = 1) in one pig and B + E (n = 1) in one sheep. No G. duodenalis was detected in humans (0/116). CONCLUSIONS: The present results show that no overlap of subtypes between animals and villagers was found in Cryptosporidium spp. and G. duodenalis, indicating a minor role of domestic animals in infecting humans in this population. However, the presence of zoonotic protozoa in domestic animals highlights the need for special attention to high-risk individuals during close contact with domestic animals.

Evaluation of the Risk Prediction Models in Predicting Kidney Outcomes in Antiglomerular Basement Membrane Disease.

Introduction: A previous study showed that the renal risk score (RRS) was transferrable to antiglomerular basement membrane (anti-GBM) disease and proposed a risk stratification according to the need of renal replacement therapy (RRT) and the percentage of normal glomeruli (N). Herein, we analyzed the risk factors associated with kidney outcomes in patients with biopsy-proven anti-GBM disease and evaluated these 2 prognosis systems. Methods: A total of 120 patients with biopsy-proven anti-GBM disease with complete clinicopathologic and outcome data were analyzed. Results: The median time to kidney biopsy was 41 days (interquartile range [IQR]: 22-63 days). RRT and N were the only independent predictors of end-stage kidney disease (ESKD). Patients with N ≥10% were more likely to achieve ESKD-free outcomes, even in the subcohort of patients who underwent posttreatment biopsies (P < 0.001). N and serum creatinine at presentation (cut-off values 750 µmol/l and 1300 µmol/l) were 2 independent factors for predicting kidney recovery. The RRS and the risk stratification tool exhibited predictive value for ESKD and could be transferred to patients with kidney biopsy following treatment (Harrell's C statistic [C] = 0.738 and C = 0.817, respectively). However, a cross-over of outcomes among groups was observed in the risk stratification tool in long-term follow-up, when patients with RRT and N ≥10% achieved better kidney outcomes than those without RRT but N <10%. Conclusion: Normal glomeruli percentage, even posttreatment, was a strong indicator for kidney outcomes, especially on long-term prognosis. Serum creatinine is a predictor for kidney recovery, independent of biopsy findings. The risk stratification tool for kidney survival was transferrable to patients with anti-GBM disease with biopsy following treatment in our cohort; however, this needs further validations for long-term outcomes.

Boundary attention with multi-task consistency constraints for semi-supervised 2D echocardiography segmentation.

The 2D echocardiography semantic automatic segmentation technique is important in clinical applications for cardiac function assessment and diagnosis of cardiac diseases. However, automatic segmentation of 2D echocardiograms also faces the problems of loss of image boundary information, loss of image localization information, and limitations in data acquisition and annotation. To address these issues, this paper proposes a semi-supervised echocardiography segmentation method. It consists of two models: (1) a boundary attention transformer net (BATNet) and (2) a multi-task level semi-supervised model with consistency constraints on boundary features (semi-BATNet). BATNet is able to capture the location and spatial information of the input feature maps by using the self-attention mechanism. The multi-task level semi-supervised model with boundary feature consistency constraints (semi-BATNet) encourages consistent predictions of boundary features at different scales from the student and teacher networks to calculate the multi-scale consistency loss for unlabeled data. The proposed semi-BATNet was extensively evaluated on the dataset of cardiac acquisitions for multi-structure ultrasound segmentation (CAMUS) and self-collected echocardiography dataset from the First Affiliated Hospital of Chongqing Medical University. Experimental results on the CAMUS dataset showed that when only 25% of the images are labeled, the proposed method greatly improved the segmentation performance by utilizing unlabeled images, and it also outperformed five state-of-the-art semi-supervised segmentation methods. Moreover, when only 50% of the images labeled, semi-BATNet achieved the Dice coefficient values of 0.936, the Jaccard similarity of 0.881 on self-collected echocardiography dataset. Semi-BATNet can complete a more accurate segmentation of cardiac structures in 2D echocardiograms, indicating that it has the potential to accurately and efficiently assist cardiologists.

The transcriptional landscape of Populus pattern/effector-triggered immunity and how PagWRKY18 involved in it.

Plants trigger a robust immune response by activating massive transcriptome reprogramming through crosstalk between PTI and ETI. However, how PTI and ETI contribute to the quantitative or/and qualitative output of immunity and how they work together when both are being activated were unclear. In this study, we performed a comprehensive overview of pathogen-triggered transcriptomic reprogramming by analyzing temporal changes in the transcriptome up to 144 h after Colletotrichum gloeosporioides inoculated in Populus. Moreover, we constructed a hierarchical gene regulatory network of PagWRKY18 and its potential target genes to explore the underlying regulatory mechanisms of PagWRKY18 that are not yet clear. Interestingly, we confirmed that PagWRKY18 protein can directly bind the W-box elements in the promoter of a transmembrane leucine-rich repeat receptor-like kinase, PagSOBIR1 gene, to trigger PTI. At the same time, PagWRKY18 functions in disease tolerance by modulation of ROS homeostasis and induction of cell death via directly targeting PagGSTU7 and PagPR4 respectively. Furthermore, PagPR4 can interact with PagWRKY18 to inhibit the expression of PagPR4 genes, forming a negative feedback loop. Taken together, these results suggest that PagWRKY18 may be involved in regulating crosstalk between PTI and ETI to activate a robust immune response and maintain intracellular homeostasis.

Effect of physical exercise on the emotional and cognitive levels of patients with substance use disorder: a meta-analysis.

Introduction: This study investigated the impact of different modes of physical exercise on the emotional and cognitive levels of patients with Substance Use Disorder (SUD). By exploring the most effective intervention types, cycle, frequency, and duration, we aimed to provide evidence-based recommendations for the adjunctive treatment of SUD. Methods: We conducted a systematic search in five databases, including PubMed, Web of Science, The Cochrane Library, ScienceDirect, and EBSCO, from database inception up to May 2023, and identified 4,255 randomized controlled trials addressing the influence of physical exercise on the emotional and cognitive levels of SUD patients. Data extraction and analysis were performed using Review Manager 5.4 software, focusing on 11 studies that met the inclusion criteria and included 895 participants. Subsequently, a meta-analysis was conducted using Stata 16.0 software, presenting the results in the form of standardized mean differences (SMD) and 95% confidence intervals (CI). Results: Our findings indicate that physical exercise significantly alleviates anxiety and depression in SUD patients while improving their cognitive function. Specifically, physical exercise was found to reduce anxiety (SMD = -0.726 [-1.349, -0.103], p < 0.05) and depression (SMD = -0.666 [-1.077, -0.255], p < 0.05) and enhance cognitive levels (SMD = -0.523 [-0.887, -0.159], p < 0.05) among patients. Subgroup analysis further revealed that SUD patients benefitted most from physical exercise when engaging in aerobic exercises lasting over 12 weeks, with a frequency exceeding 40 sessions and each session lasting more than 60 min. Discussion: In conclusion, our study affirms that physical exercise mitigates anxiety and depression while enhancing cognitive function in SUD patients, making it an effective measure for adjunctive clinical treatment.

Impact of aerosol-boundary layer interactions on PM2.5 pollution during cold air pool events in a semi-arid urban basin.

Global emission reductions still must address winter fine particulate matter (PM2.5) pollution in urban basins with enclosed terrains and frequent cold air pool (CAP) events when the temperatures within the basin are colder than above it. The effects of urban basin aerosol-boundary layer interactions on PM2.5 pollution during CAP events remain unclear. Intensive boundary layer observations in January 2021 and numerical models were used to investigate this issue in the semi-arid urban Lanzhou Basin of China. The results showed that CAPs formed because of the synoptic weather system that exacerbated the warming over the basin. The CAPs in this experiment were characterized by stronger temperature inversion (TI) layers in the vertical direction and lower relative humidity, lower wind speed, and weaker turbulence at the bottom of the basin compared to other conditions. The strong TI layers below the top of the basin inhibited the vertical dispersion of pollutants in the basin and concentrated the PM2.5 within a height of 0.3 km from the bottom of the basin. During CAP events, the proportion of elemental carbon in PM2.5 increased, whereas that of secondary inorganic species decreased. Aerosol absorption increased faster than scattering during CAP events. Therefore, the mean single scattering albedo decreased from 0.85 during non-CAP periods to 0.81 during CAP events. Radiosonde-sounding observations and numerical simulations indicated that aerosols accumulating in the lower basin heated the atmosphere during the daytime and facilitated boundary layer development via the "stove effect" (absorption aerosol heats lower atmosphere to promote boundary layer development). No significant "dome effect" (absorption aerosol heats the upper boundary layer to suppress boundary layer development) occurred during the two CAP events. These findings provide a theoretical basis for scientifically-guided PM2.5 pollution control in winter in isolated urban basins.

The Role of Zuo Jin Wan in Modulating the Tumor Microenvironment of Colorectal Cancer.

INTRODUCTION: Traditional Chinese medicine (TCM) can modulate the immune function of tumor patients in various ways. Zuojin Wan (ZJW, a 6:1 ratio of Huanglian and Wuzhuyu) can modulate the microenvironment of ulcerative colitis, but its role in regulating the CRC microenvironment remains unclear. Exploring the role of ZJW in CRC immunomodulation may improve the antitumor effect of existing immunotherapeutic strategies. MATERIAL AND METHODS: The active compounds of each herb in ZJW were obtained from the HIT2.0 database with literature evidence. Single-cell RNA sequencing data of CRC were obtained from published studies (PMID: 32451460, 32103181, and 32561858). Pathway enrichment was analyzed using the reactome database, and intergenic correlation analysis was performed using the corrplot R software package. ZJW-regulated gene expression was verified by RT-qPCR. RESULTS: Huanglian and Wuzhu contain 19 and 4 compounds, respectively. Huang Lian targets 146 proteins, and Wu Zhu Yu targets 28 proteins based on evidence from the literature. ZJW regulates a range of biological processes associated with immune function, including cytokine signaling and Toll-Like Receptor 4 (TLR4) cascade. ZJW regulates malignant CRC cells, immune cells (including T-cells, B-cells, mast cells, NK/NKT cells, and myeloid cells), and other non-immune cells (including endothelial cells, enteric glial cells, and pericytes). We confirmed that ZJW significantly downregulated the expression of TIMP1 and MTDH. CONCLUSIONS: ZJW regulates a range of cells in the CRC microenvironment, including malignant CRC, immune cells, and stromal cells. In CRC cell lines, downregulation of TIMP1 and MTDH by ZJW may play an important role in the immunomodulation in CRC.

Single-cell RNA sequencing reveals that the immunosuppression landscape induced by chronic stress promotes colorectal cancer metastasis.

The high prevalence of depressive disorders in individuals with cancer and their contribution to tumour progression is a topic that is gradually gaining attention. Recent evidence has shown that there are prominent connections between immune gene variants and mood disorders. The homeostasis of the tumour immune microenvironment (TIME) and the infiltration and activation of immune cells play a very important role in the antitumour effect. In this study, we established a compound mouse model with chronic unpredictable mild stress (CUMS) and orthotopic colorectal cancer to simulate colorectal cancer (CRC) patients with depression. Using 10✕Genomics single-cell transcriptome sequencing technology, we profiled nearly 30,000 cells from tumour samples of 8 mice from the control and CUMS groups, revealed that immune cells in tumours under a chronic stress state trend toward a more immunosuppressive and exhaustive status, and described the crosstalk between the overall inflammatory environment and immunosuppressive landscape to provide mechanistic information or efficacious strategies for immune-oncology treatments in CRC with depressive disorders.

DTAN: Diffusion-based Text Attention Network for medical image segmentation.

In the current era, diffusion models have emerged as a groundbreaking force in the realm of medical image segmentation. Against this backdrop, we introduce the Diffusion Text-Attention Network (DTAN), a pioneering segmentation framework that amalgamates the principles of text attention with diffusion models to enhance the precision and integrity of medical image segmentation. Our proposed DTAN architecture is designed to steer the segmentation process towards areas of interest by leveraging a text attention mechanism. This mechanism is adept at identifying and zeroing in on the regions of significance, thus improving the accuracy and robustness of the segmentation. In parallel, the integration of a diffusion model serves to diminish the influence of noise and irrelevant background data in medical images, thereby improving the quality of the segmentation results. The diffusion model is instrumental in filtering out extraneous factors, allowing the network to more effectively capture the nuances and characteristics of the target regions, which in turn enhances segmentation precision. We have subjected DTAN to rigorous evaluation across three datasets: Kvasir-Sessile, Kvasir-SEG, and GlaS. Our focus was particularly drawn to the Kvasir-Sessile dataset due to its relevance to clinical applications. When benchmarked against other state-of-the-art methods, our approach demonstrated significant improvements on the Kvasir-Sessile dataset, with a 2.77% increase in mean Intersection over Union (mIoU) and a 3.06% increase in mean Dice Similarity Coefficient (mDSC). These results provide strong evidence of the DTAN's generalizability and robustness, and its distinct advantages in the task of medical image segmentation.

A 3D Multilevel Heterostructure Containing 2D Vertically Aligned MoS2 Nanosheets and 1D Sandwich C-MoS2-C Nanotubes to Enhance the Storage of Li+ Ions.

To overcome the disadvantages of the MoS2 anode for LIBs in terms of low intrinsic conductivity, poor mechanical stability, and adverse reaction with electrolytes, a 3D multilevel heterostructure (VANS-MoS2-CNTs) has been successfully prepared by a simple hydrothermal method followed by thermal treatment. VANS-MoS2-CNTs are made up of 2D vertically aligned MoS2 nanosheets (VANS) and 1D sandwich C-MoS2-C nanotubes (CNTs). The sandwich-like nanotube is the core part, which is made up of the MoS2 nanotube covered by carbon layers on both side surfaces. Due to the special heterostructure, VANS-MoS2-CNTs have good conductivity, high structured stability, and excellent Li+/electron transport, resulting in high discharge capacity (1587 mAh/g at a current density of 0.1 A/g), excellent rate capacity (1330 and 730 mAh/g at current densities of 0.1 and 2 A/g, respectively), and good cyclic stability (1270 mAh/g at 0.1 A/g after 100 cycles).

A Study on Site Selection for Regional Air Rescue Centers Based on Multi-Objective Jellyfish Search Algorithm.

In recent years, air emergency rescue capabilities have become increasingly important as an indicator of national comprehensive strength and development status. Air emergency rescue performs an indispensable role in addressing social emergencies by virtue of its fast response capabilities and extensive coverage. This vital aspect of emergency response ensures the timely deployment of rescue personnel and resources, enabling efficient operations in diverse and often challenging environments. To enhance regional emergency response capabilities, this paper presents a novel siting model that overcomes the limitation of single-objective approaches by integrating multiple objectives and considering the synergistic effects of network nodes, and the corresponding efficient solving algorithm is designed for this model. First, a multi-objective optimization function is established that fully incorporates the construction cost of the rescue station, response time, and radiation range. A radiation function is developed to evaluate the degree of radiation for each candidate airport. Second, the multi-objective jellyfish search algorithm (MOJS) is employed to search for Pareto optimal solutions of the model using MATLAB tools. Finally, the proposed algorithm is applied to analyze and verify the site selection for a regional air emergency rescue center in a certain region of China, and ArcGIS tools are used to draw the site selection results separately by prioritizing the construction cost under different numbers of site selection points. The results demonstrate that the proposed model can achieve the desired site selection goals, thus providing a feasible and accurate method for future air emergency rescue station selection problems.

Clinical and pathological characteristics of DKD patients with early-onset type 2 diabetes.

AIMS: In diabetic kidney disease (DKD) patients, early-onset T2DM effects on renal disease severity and outcomes remain uncertain. Herein, we aim to investigate the clinicopathological characteristics and renal outcomes in DKD patients with early-onset T2DM. METHODS: 489 patients with T2DM and DKD were retrospectively recruited and classified as having early (age at onset of T2DM < 40 years) and late (age at onset of T2DM ≥ 40 years) T2DM onset, analyzing the clinical and histopathological data. The predictive value of early-onset T2DM to renal outcomes in DKD patients was analyzed by Cox's regression. RESULTS: Among 489 DKD patients, 142 and 347 were classified as early and late T2DM onset, respectively. Early-onset T2DM patients exhibited worse glycaemic control (7.36 % ± 1.80 % vs. 6.86 % ± 1.57 %, P = 0.007) and more severe proteinuria (3.69 [1.55 to 7.03] vs. 1.81 [0.50 to 4.33] g/24 h, P < 0.001). Those with early-onset T2DM presented more severe glomerular lesions. In univariable Cox regression, early-onset T2DM showed a significant correlation with renal composite endpoint (HR [95%CI]: 0.56 [0.43 to 0.73], P < 0.001). However, after adjusting for potential confounders, early-onset T2DM was not independently correlated with renal composite endpoint (HR [95%CI]: 0.74 [0.46 to 1.21], P = 0.232). CONCLUSIONS: In DKD patients with early-onset T2DM, renal clinicopathological manifestations were severe. Age at onset in T2DM was significantly correlated with eGFR slope (r = 0.211, P < 0.001).

Chronic stress promotes colorectal cancer progression by enhancing glycolysis through ß2-AR/CREB1 signal pathway.

Colorectal cancer (CRC) is a common malignancy worldwide, and chronic stress has been considered as a significant risk factor for CRC. However, the role of chronic stress in CRC progression is unclear. The present study showed that pre-exposure to chronic stress facilitated CRC tumor growth in mice, and epinephrine promoted CRC cell proliferation in vitro. Metabolomics analysis revealed that chronic stress reshaped metabolic pathways to enhance glycolysis. Additional studies have shown that stress enhanced the expression levels of glycolytic-associated enzymes, including GLUT1, HK2 and PFKP. Mechanistically, chronic stress activated the ß2-AR/PKA/CREB1 pathway, as a result, phosphorylated CREB1 transcriptional induced glycolytic enzymes expression. Furthermore, stress-induced cell proliferation and tumor growth could be reversed by administration of glycolysis inhibitor 2-deoxyglucose (2-DG) and ß2-AR antagonist ICI118,551, respectively. Altogether, these findings define novel insights into the stress-induced epinephrine-mediated CRC progression from the point of view of tumor energy metabolism reprogramming and provide a perspective on targeting glycolysis as a potential approach in stress-associated CRC treatment.

The Facile Synthesis of Hollow CuS Microspheres Assembled from Nanosheets for Li-Ion Storage and Photocatalytic Applications.

Herein, well-defined hollow CuS microspheres assembled from nanosheets were successfully synthesized through a facile solvothermal method. Hollow CuS microspheres have an average diameter of 1.5 µm; moreover, the primary CuS nanosheets have an ultrathin thickness of about 10 nm and are bound by {0001} polar facets. When used as anodes for lithium-ion batteries (LIBs), hollow CuS microspheres exhibit excellent electrochemical properties, including a large discharge capacity (610.1 mAh g-1 at 0.5 C), an excellent rate capability (207.6 and 143.4 mAh g-1 at 1 and 5 C), and a superior cyclic stability (196.3 mAh g-1 at 1 C after 500 cycles). When used as photocatalysts for Rhodamine B (RhB), hollow CuS microspheres can degrade more than 99% of the initial RhB within 21 min. These excellent Li-ion storage properties and photocatalytical performances are attributed to their unique hierarchical hollow structure.

Adhesive hydrogels in osteoarthritis: from design to application.

Osteoarthritis (OA) is the most common type of degenerative joint disease which affects 7% of the global population and more than 500 million people worldwide. One research frontier is the development of hydrogels for OA treatment, which operate either as functional scaffolds of tissue engineering or as delivery vehicles of functional additives. Both approaches address the big challenge: establishing stable integration of such delivery systems or implants. Adhesive hydrogels provide possible solutions to this challenge. However, few studies have described the current advances in using adhesive hydrogel for OA treatment. This review summarizes the commonly used hydrogels with their adhesion mechanisms and components. Additionally, recognizing that OA is a complex disease involving different biological mechanisms, the bioactive therapeutic strategies are also presented. By presenting the adhesive hydrogels in an interdisciplinary way, including both the fields of chemistry and biology, this review will attempt to provide a comprehensive insight for designing novel bioadhesive systems for OA therapy.

Growth-regulating factor 15-mediated gene regulatory network enhances salt tolerance in poplar.

Soil salinity is an important determinant of crop productivity and triggers salt stress response pathways in plants. The salt stress response is controlled by transcriptional regulatory networks that maintain regulatory homeostasis through combinations of transcription factor (TF)-DNA and TF-TF interactions. We investigated the transcriptome of poplar 84 K (Populus alba × Populus glandulosa) under salt stress using samples collected at 4- or 6-h intervals within 2 days of salt stress treatment. We detected 24,973 differentially expressed genes, including 2,231 TFs that might be responsive to salt stress. To explore these interactions and targets of TFs in perennial woody plants, we combined gene regulatory networks, DNA affinity purification sequencing, yeast two-hybrid-sequencing, and multi-gene association approaches. Growth-regulating factor 15 (PagGRF15) and its target, high-affinity K+ transporter 6 (PagHAK6), were identified as an important regulatory module in the salt stress response. Overexpression of PagGRF15 and PagHAK6 in transgenic lines improved salt tolerance by enhancing Na+ transport and modulating H2O2 accumulation in poplar. Yeast two-hybrid assays identified more than 420 PagGRF15-interacting proteins, including ETHYLENE RESPONSE FACTOR TFs and a zinc finger protein (C2H2) that are produced in response to a variety of phytohormones and environmental signals and are likely involved in abiotic stress. Therefore, our findings demonstrate that PagGRF15 is a multifunctional TF involved in growth, development, and salt stress tolerance, highlighting the capability of a multifaceted approach in identifying regulatory nodes in plants.

The role of YAP1 in survival prediction, immune modulation, and drug response: A pan-cancer perspective.

Introduction: Dysregulation of the Hippo signaling pathway has been implicated in multiple pathologies, including cancer, and YAP1 is the major effector of the pathway. In this study, we assessed the role of YAP1 in prognostic value, immunomodulation, and drug response from a pan-cancer perspective. Methods: We compared YAP1 expression between normal and cancerous tissues and among different pathologic stages survival analysis and gene set enrichment analysis were performed. Additionally, we performed correlation analyses of YAP1 expression with RNA modification-related gene expression, tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint regulator expression, and infiltration of immune cells. Correlations between YAP1 expression and IC50s (half-maximal inhibitory concentrations) of drugs in the CellMiner database were calculated. Results: We found that YAP1 was aberrantly expressed in various cancer types and regulated by its DNA methylation and post-transcriptional modifications, particularly m6A methylation. High expression of YAP1 was associated with poor survival outcomes in ACC, BLCA, LGG, LUAD, and PAAD. YAP1 expression was negatively correlated with the infiltration of CD8+ T lymphocytes, CD4+ Th1 cells, T follicular helper cells, NKT cells, and activated NK cells, and positively correlated with the infiltration of myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) in pan-cancer. Higher YAP1 expression showed upregulation of TGF-ß signaling, Hedgehog signaling, and KRAS signaling. IC50s of FDA-approved chemotherapeutic drugs capable of inhibiting DNA synthesis, including teniposide, dacarbazine, and doxorubicin, as well as inhibitors of hypoxia-inducible factor, MCL-1, ribonucleotide reductase, and FASN in clinical trials were negatively correlated with YAP1 expression. Discussion: In conclusion, YAP1 is aberrantly expressed in various cancer types and regulated by its DNA methylation and post-transcriptional modifications. High expression of YAP1 is associated with poor survival outcomes in certain cancer types. YAP1 may promote tumor progression through immunosuppression, particularly by suppressing the infiltration of CD8+ T lymphocytes, CD4+ Th1 cells, T follicular helper cells, NKT cells, and activated NK cells, as well as recruiting MDSCs and CAFs in pan-cancer. The tumor-promoting activity of YAP1 is attributed to the activation of TGF-ß, Hedgehog, and KRAS signaling pathways. AZD2858 and varlitinib might be effective in cancer patients with high YAP1 expression.