Advances in preclinical surgical therapy of cardiovascular diseases.

Cardiovascular disease is the most common cause of death worldwide, resulting in millions of deaths annually. Currently, there are still some deficiencies in the treatment of cardiovascular diseases. Innovative surgical treatments are currently being developed and tested in response to this situation. Large animal models, which are similar to humans in terms of anatomy, physiology, and genetics, play a crucial role in connecting basic research and clinical applications. This article reviews recent preclinical studies and the latest clinical advancements in cardiovascular disease based on large animal models, with a focus on targeted delivery, neural regulation, cardiac remodeling, and hemodynamic regulation. It provides new perspectives and ideas for clinical translation and offers new methods for clinical treatment.

The potential of urban irrigation for counteracting carbon-climate feedback.

Global climate changes, especially the rise of global mean temperature due to the increased carbon dioxide (CO2) concentration, can, in turn, result in higher anthropogenic and biogenic greenhouse gas emissions. This potentially leads to a positive loop of climate-carbon feedback in the Earth's climate system, which calls for sustainable environmental strategies that can mitigate both heat and carbon emissions, such as urban greening. In this study, we investigate the impact of urban irrigation over green spaces on ambient temperatures and CO2 exchange across major cities in the contiguous United States. Our modeling results indicate that the carbon release from urban ecosystem respiration is reduced by evaporative cooling in humid climate, but promoted in arid/semi-arid regions due to increased soil moisture. The irrigation-induced environmental co-benefit in heat and carbon mitigation is, in general, positively correlated with urban greening fraction and has the potential to help counteract climate-carbon feedback in the built environment.

Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.

Posttranslational modifications increase the complexity and functional diversity of proteins in response to complex external stimuli and internal changes. Among these, protein lipidations which refer to lipid attachment to proteins are prominent, which primarily encompassing five types including S-palmitoylation, N-myristoylation, S-prenylation, glycosylphosphatidylinositol (GPI) anchor and cholesterylation. Lipid attachment to proteins plays an essential role in the regulation of protein trafficking, localisation, stability, conformation, interactions and signal transduction by enhancing hydrophobicity. Accumulating evidence from genetic, structural, and biomedical studies has consistently shown that protein lipidation is pivotal in the regulation of broad physiological functions and is inextricably linked to a variety of diseases. Decades of dedicated research have driven the development of a wide range of drugs targeting protein lipidation, and several agents have been developed and tested in preclinical and clinical studies, some of which, such as asciminib and lonafarnib are FDA-approved for therapeutic use, indicating that targeting protein lipidations represents a promising therapeutic strategy. Here, we comprehensively review the known regulatory enzymes and catalytic mechanisms of various protein lipidation types, outline the impact of protein lipidations on physiology and disease, and highlight potential therapeutic targets and clinical research progress, aiming to provide a comprehensive reference for future protein lipidation research.

Optimization of the selection of suitable harvesting periods for medicinal plants: taking Dendrobium officinale as an example.

BACKGROUND: Dendrobium officinale is a medicinal plant with high commercial value. The Dendrobium officinale market in Yunnan is affected by the standardization of medicinal material quality control and the increase in market demand, mainly due to the inappropriate harvest time, which puts it under increasing resource pressure. In this study, considering the high polysaccharide content of Dendrobium leaves and its contribution to today's medical industry, (Fourier Transform Infrared Spectrometer) FTIR combined with chemometrics was used to combine the yields of both stem and leaf parts of Dendrobium officinale to identify the different harvesting periods and to predict the dry matter content for the selection of the optimal harvesting period. RESULTS: The Three-dimensional correlation spectroscopy (3DCOS) images of Dendrobium stems to build a (Split-Attention Networks) ResNet model can identify different harvesting periods 100%, which is 90% faster than (Support Vector Machine) SVM, and provides a scientific basis for modeling a large number of samples. The (Partial Least Squares Regression) PLSR model based on MSC preprocessing can predict the dry matter content of Dendrobium stems with Factor = 7, RMSE = 0.47, R2 = 0.99, RPD = 8.79; the PLSR model based on SG preprocessing can predict the dry matter content of Dendrobium leaves with Factor = 9, RMSE = 0.2, R2 = 0.99, RPD = 9.55. CONCLUSIONS: These results show that the ResNet model possesses a fast and accurate recognition ability, and at the same time can provide a scientific basis for the processing of a large number of sample data; the PLSR model with MSC and SG preprocessing can predict the dry matter content of Dendrobium stems and leaves, respectively; The suitable harvesting period for D. officinale is from November to April of the following year, with the best harvesting period being December. During this period, it is necessary to ensure sufficient water supply between 7:00 and 10:00 every day and to provide a certain degree of light blocking between 14:00 and 17:00.

Gelatin/carboxymethylcellulose composite film combined with photodynamic antibacterial: New prospect for fruit preservation.

Plastic packaging causes environmental pollution, and the development of simple and effective biodegradable active packaging remains a challenge. In this study, gelatin (G) and sodium carboxymethylcellulose (CMC) were used as film materials, with the addition of curcumin (Cur), a photosensitive substance, to investigate the changes in the physical and chemical properties of the film and its application in fruit preservation. The results demonstrated that Cur was compatible with the film. With the addition of Cur, the thickness of the film increased up to 1.3 times, while the moisture content was reduced to 12.10 %. The tensile strength (TS) and elongation at break (EAB) of the film can reach 8.84 MPa and 19.33 %, respectively. The photodynamic antibacterial experiment revealed that the film containing 0.5 % Cur exhibited the highest antibacterial rate, reaching 99.99 % against Staphylococcus aureus (S. aureus) and 95 % against Escherichia coli (E. coli). During storage, the grapes remained unspoiled for up to 9 days after being phototreated with the film and the microbial content of the skin was much lower than that of the control group. In addition, Cur provided antioxidant activity for the film, with a scavenging activity of 39.54 % against the 2,2-diphenyl-1-picrind radical (DPPH). Bananas exposed to the film-forming solution for a short period of time remained fresh for up to 6 days. During preservation, the weight of the treated bananas decreased more slowly than that of the control group. In addition, the activity of SOD on the 7th day was approximately 20 U/g higher than that of the control group, which helped to reduce oxidative stress during banana preservation. In summary, G-CMC/Cur film is an optional fruit-cling film that can be used in food packaging.

Photodynamic antibacterial application of TiO2/curcumin/hydroxypropyl-cyclodextrin and its konjac glucomannan composite films.

Although photodynamic therapy (PDT) has great advantages for the treatment of bacterial infections, photosensitizers (PSs) often have many disadvantages that limit their application. Improving the shortcomings of PSs and developing efficient PDT antimicrobial materials remain serious challenges. In this study, a nanocomposite drug (TiO2/curcumin/hydroxypropyl-cyclodextrin, TiO2/Cur/HPCD) was constructed and combined with konjac glucomannan to form composite films (TiO2/Cur/HPCD films, KTCHD films). The stabilities of TiO2 and Cur were improved in the presence of HPCD. The particle size of TiO2/Cur/HPCD was approximately 33.9 nm, and the addition of TiO2/Cur/HPCD enhanced the mechanical properties of the films. Furthermore, TiO2/Cur/HPCD and KTCHD films exhibited good biocompatibility and PDT antibacterial effects. The antibacterial rate of TiO2/Cur/HPCD was 74.46 % against MRSA at 500 µg/mL and 99.998 % against E. coli at 400 µg/mL, while it was adsorbed on the surface of bacteria to improve the effectiveness of the treatment. In addition, studies in mice confirmed that TiO2/Cur/HPCD and KTCHD films can treat bacterial infections and promote wound healing, with a highest wound healing rate of 84.6 % in the KTCHD-10 films + Light group on day 12. Overall, TiO2/Cur/HPCD is a promising nano-antibacterial agent and KTCHD films have the potential to be employed as antibacterial and environment-friendly trauma dressings.

Efficient removal of tetracycline hydrochloride through novel Fe/BiOBr/Bi2WO6 photocatalyst prepared by dual-strategy under visible-light irradiation.

It is important to investigate whether combining two modification strategies has a synergistic effect on the activity of photocatalysts. In this manuscript, Fe-doped BiOBr/Bi2WO6 heterojunctions were synthesized by a one-pot solvothermal method, and excellent photocatalytic performance was obtained for the degradation of tetracycline hydrochloride (TCH) in water without the addition of surfactant. Combining experiments and characterization, the synergistic effect between Fe ion doping and the BiOBr/Bi2WO6 heterojunction was elucidated. The Fe/BiOBr/Bi2WO6 composite photocatalyst had a beneficial void structure, enhanced visible light response, and could inhibit the recombination of photogenerated support well, which improved the photocatalytic activity. The presented experiments demonstrate that Fe/BiOBr/Bi2WO6 removes 97% of TCH from aqueous solution, while pure BiOBr and Bi2WO6 only remove 56% and 65% of TCH, respectively. Finally, the separation and transfer mechanisms of photoexcited carriers were determined in conjunction with the experimental results. This study provides a new direction for the design of efficient photocatalysts through the use of a dual co-modification strategy.

The Population Divergence and Genetic Basis of Local Adaptation of Wild Soybean (Glycine soja) in China.

Glycine soja is the wild relative species of cultivated soybean. In this study, we investigated the population divergence and genetic basis of the local adaptation of wild soybean in China using genome-wide single-nucleotide polymorphisms (SNPs) of a population of 72 G. soja accessions. Using phylogenetic analysis, we observed that G. soja accessions clustered into three distinct groups, each corresponding to a specific geographic region, the northeastern region (NER), central region (CR), and southern region (SR), consistent with previous studies. Notably, we found a significant positive correlation between genetic and geographic distances. Further population structure analysis revealed each group was associated with an ancestral population and a specific geographic area. By utilizing the genome sequencing data of accessions from 16 different locations, we inferred the population history of these wild soybean groups. Our results indicate that the three groups diverged ~25,000 years ago, coinciding with the time of the last glacial maximum. The effective population size of the SR group expanded first, and subsequently, the NER and CR groups expanded approximately 5000 and 2500 years ago, respectively. Moreover, 83, 104, and 101 significant associated loci (SALs) were identified using genome-wide association analysis for annual mean temperature, annual precipitation, and latitude, respectively. Functional analysis of genes located in SALs highlighted candidate genes related to local adaptation. This study highlights the significant role of geographic isolation and environmental factors in shaping the genetic structure and adaptability of wild soybean populations. Furthermore, it emphasizes the value of wild soybean as a crucial genetic resource for enhancing the adaptability of cultivated soybeans, which have experienced a loss of genetic diversity due to domestication and intensive breeding practices. The insights gained from our research provide valuable information for the protection, conservation, and utilization of this important genetic resource.

Single-Cell RNA-Sequencing Analysis of Colonic Lamina Propria Immune Cells Reveals the Key Immune Cell-Related Genes of Ulcerative Colitis.

Background: Ulcerative colitis (UC) is a severe threat to humans worldwide. Single-cell RNA sequencing (scRNA-seq) can be used to screen gene expression patterns of each cell in the intestine, provide new insights into the potential mechanism of UC, and analyze the development of immune cell changes. These findings can provide new ideas for the diagnosis and treatment of intestinal diseases. In this study, bioinformatics analysis combined with experiments applied in dextran sulfate sodium (DSS)-induced colitis mice was used to explore new diagnostic genes for UC and their potential relationship with immune cells. Methods: We downloaded microarray datasets (GSE75214, GSE87473, GSE92415) from the Gene Expression Omnibus and used these datasets to screen differentially expressed genes (DEGs) and conduct Weighted Gene Co-expression Network Analysis (WGCNA) after quality control. The hub genes were screened, and ROC curves were drawn to verify the reliability of the results in both training set (GSE75214, GSE87473, GSE92415) and validation cohort (GSE87466). Also, we explored the relation of diagnostic genes and immune cells by CIBERSORT algorithm and single-cell analysis. Finally, the expression of hub genes and their relation with immune cells were verified in DSS-induced colitis mice. Results: Diagnostic genes (ANXA5, MMP7, NR1H4, CYP3A4, ABCG2) were identified. In addition, we found these five genes firmly related to immune infiltration. The DSS-induced colitis mice confirm that the expression of ANXA5 mainly increased in the intestinal macrophages and had a strong negative correlation with M2 macrophages, which indicated its possible influence on the polarization of macrophages in UC patients. Conclusion: We identified ANXA5, MMP7, NR1H4, CYP3A4, and ABCG2 as diagnostic genes of UC that are closely related to immune infiltration and ANXA5 maintains a negative correlation with M2 macrophages which indicated its possible influence on the polarization of macrophage in UC patients.

sFgl2 gene-modified MSCs regulate the differentiation of CD4+ T cells in the treatment of autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is a T-cell-mediated autoimmune liver disease that can lead to liver injury and has a poor long-term prognosis. Mesenchymal stromal cells (MSCs) have immunosuppressive effects and can treat AIH. CD4+ T cells express the unique inhibitory Fcγ receptor (FcγRIIB), which is the only receptor for the immunosuppressive factor soluble fibrinogen-like protein 2 (sFgl2). This study aimed to examine the therapeutic effect of sFgl2 gene-modified MSCs (sFgl2-MSCs) on AIH. METHODS: MSCs were obtained from the inguinal fat of mice and cocultured with CD4+ T cells sorted from mouse spleens. FcγRIIB expression on CD4+ T cells was determined by flow cytometry. sFgl2 expression in MSCs transfected with lentiviral vectors carrying the Fgl2 gene and a green fluorescent protein-encoding sequence was determined by enzyme-linked immunosorbent assay. The percentages of Th1 cells Th17 cells and regulatory T cells (Tregs) were determined by flow cytometry And the levels of p-SHP2 and p-SMAD2/3 were detected by Western blotting after the cells were cocultured with MSCs for 72 h. After locating MSCs by in vivo imaging Con A-induced experimental AIH mice were randomly divided into 4 groups and administered different treatments. After 24 h histopathological scores liver function and cytokine levels were examined and the proportions of CD4+ T cells CD8+ T cells Tregs Th17 cells and Th1 cells in the spleen and liver were determined by flow cytometry. In addition immunohistochemical staining was used to detect the liver infiltration of T-bet-, Foxp3- and RORγ-positive cells. RESULTS: FcγRIIB expression on CD4+ T cells was upregulated after coculture with MSCs. After coculture with sFgl2-MSCs, the proportion of Tregs among CD4+ T cells increased, the proportion of Th17 and Th1 cells decreased, and the levels of p-SHP2 and p-SMAD2/3 increased. In vivo, sFgl2-MSCs significantly improved liver function, decreased liver necrosis area, decreased tumor necrosis factor-α, interleukin (IL)-1ß and IL-6 expression, increased IL-10 expression, reduced liver infiltration of CD4+ T and CD8+ T cells, increased the proportion of Tregs and reduced the proportions of Th17 and Th1 cells in mice. CONCLUSION: By promoting Tregs differentiation and inhibiting Th17 and Th1 cell differentiation, sFgl2 gene-modified MSCs have a more powerful therapeutic effect on Con A-induced experimental AIH and may represent a strategy for the clinical treatment of AIH.

Comparison of vonoprazan-based with rabeprazole-based dual therapy for treatment-naive patients of Helicobacter pylori infection: a prospective, multi-center, randomized controlled study.

BACKGROUND: The application of vonoprazan significantly improved the eradication rate of Helicobacter pylori (H. pylori). This study aimed to compare efficacy and safety of the 10-day vonoprazan-amoxicillin (VA) and 14-day rabeprazole-amoxicillin (RA) dual therapy, and to provide a more efficient, safer, and convenient dual regimen for H. pylori infection. METHODS: This was a prospective, open-label, multi-center, randomized controlled study of treatment-naive patients with H. pylori infection. The participants were randomly assigned to the 10-day VA group with vonoprazan 20 mg Bid plus amoxicillin 1 g Tid or the 14-day RA group with rabeprazole 10 mg Tid plus amoxicillin 1 g Tid. The effectiveness, the adverse events, and the patient compliance of the two groups were compared. RESULTS: A total of 690 patients were enrolled. The eradication rates of 10-day VA and 14-day RA dual therapy were 89.3% and 84.9% in intention-to-treat (ITT) analysis (P = 0.088); 90.6% and 85.9% by modified intention-to-treat (mITT) analysis (P = 0.059); 91.4% and 86.6% by per-protocol (PP) analysis (P = 0.047). Non-inferiority was confirmed between the two groups (all P < 0.001). No discernible differences were observed in adverse effects and compliance between groups. Poor compliance reduced the eradication efficacy (P < 0.05). CONCLUSIONS: The 10-day VA dual therapy was non-inferior to the 14-day RA dual therapy for H. pylori treatment-naive patients, which should be given priority in the first-line treatment. The application of vonoprazan reduced treatment course and antibiotic use. Patients' adherence was crucial for the success of eradication.

Polydopamine-curcumin coating of titanium for remarkable antibacterial activity via synergistic photodynamic and photothermal properties.

Combined photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a novel and effective antibacterial strategy. In order to endow titanium (Ti) with antibacterial properties, the Ti-PDA-Cur composite was prepared using the excellent adhesion properties of polydopamine (PDA) to load curcumin (Cur) on the surface of Ti. The Ti-PDA-Cur coating can produce singlet oxygen (1 O2 ) and heat under 405 + 808 nm light irradiation, which can effectively kill Staphylococcus aureus and Escherichia coli. Moreover, the cytotoxicity and hemolysis rate of Ti-PDA-Cur were low, indicating its good biocompatibility. Therefore, this study provided a new strategy for the development of new Ti implants.

Global research trends and hotspots of Helicobacter pylori eradication based on clinical trial registration platforms: A cross-sectional analysis.

BACKGROUND: This study aimed to obtain an overview of clinical trials on Helicobacter pylori (H. pylori) eradication and analyze the global trends and hotspots in this field. METHODS: We collected the data from clinical trials focused on H. pylori eradication in the primary clinical trial registries from 2000 to 2022 in the world. Then we analyzed the research trends and hotspots in H. pylori eradication regimens in different regions at different periods. RESULTS: A total of 780 clinical trials were included, which were mainly conducted in Asia (682), followed by Europe (59), Africa (20), North America (16), South America (7), Oceania (2). The most active countries were China (343), Iran (140), South Korea (63), and Japan (73). "Bismuth-containing quadruple therapy (BQT)" was the most studied regimen (159, 20.38 %). Additionally, clinical trials focused on potassium-competitive acid blockers (P-CABs)-based therapy, probiotics, and high-dose dual therapy (HDDT) were constantly increasing. BQT received the most attention in China (26.53 %) and Iran (22.14 %), while it was tailored therapy in South Korea (23.29 %). P-CABs-based therapy was the main reseach hotspot in Japan (61.90 %). CONCLUSION: How to eradicate H. pylori infection has been a heated research topic. BQT, P-CABs-based therapy, probiotics, and HDDT attracted the most attention in recent years.

Self-powered dual-mode sensing strategy based on graphdiyne and DNA nanoring for sensitive detection of tumor biomarker.

MicroRNA-21 (miRNA-21) is currently the only known oncogenic miRNA that is upregulated in almost all malignant tumors and exhibits a broad spectrum of tumor recognition characteristics. It holds significant value in the early diagnosis, malignant degree assessment, and prognostic evaluation of tumors. In this study, a novel dual-mode self-powered sensing platform is developed using Au nanoparticles/graphdiyne as the electrode substrate and combined with DNA nanoring for highly sensitive and specific detection of miRNA-21. The DNA nanoring structure, which is easy to prepare and contains multiple recognition sites, induces significant electrochemical/colorimetric signal responses of the signaling molecule methylene blue. Under optimal conditions, the linear ranges of the electrochemical and colorimetric detection modes of this self-powered sensor are 0.1 fM-100 pM and 0.1 fM-10 nM, respectively, with the detection limits of 35.1 aM and 61.6 aM (S/N=3). This strategy provides a new reference for the sensitive detection of microRNA and has immense potential for application in the screening and detection of clinical nucleic acid diseases.

Tomato Maturity Detection and Counting Model Based on MHSA-YOLOv8.

The online automated maturity grading and counting of tomato fruits has a certain promoting effect on digital supervision of fruit growth status and unmanned precision operations during the planting process. The traditional grading and counting of tomato fruit maturity is mostly done manually, which is time-consuming and laborious work, and its precision depends on the accuracy of human eye observation. The combination of artificial intelligence and machine vision has to some extent solved this problem. In this work, firstly, a digital camera is used to obtain tomato fruit image datasets, taking into account factors such as occlusion and external light interference. Secondly, based on the tomato maturity grading task requirements, the MHSA attention mechanism is adopted to improve YOLOv8's backbone to enhance the network's ability to extract diverse features. The Precision, Recall, F1-score, and mAP50 of the tomato fruit maturity grading model constructed based on MHSA-YOLOv8 were 0.806, 0.807, 0.806, and 0.864, respectively, which improved the performance of the model with a slight increase in model size. Finally, thanks to the excellent performance of MHSA-YOLOv8, the Precision, Recall, F1-score, and mAP50 of the constructed counting models were 0.990, 0.960, 0.975, and 0.916, respectively. The tomato maturity grading and counting model constructed in this study is not only suitable for online detection but also for offline detection, which greatly helps to improve the harvesting and grading efficiency of tomato growers. The main innovations of this study are summarized as follows: (1) a tomato maturity grading and counting dataset collected from actual production scenarios was constructed; (2) considering the complexity of the environment, this study proposes a new object detection method, MHSA-YOLOv8, and constructs tomato maturity grading models and counting models, respectively; (3) the models constructed in this study are not only suitable for online grading and counting but also for offline grading and counting.

miR-29a-3p Regulates Autophagy by Targeting Akt3-Mediated mTOR in SiO2-Induced Lung Fibrosis.

Silicosis is a refractory pneumoconiosis of unknown etiology that is characterized by diffuse lung fibrosis, and microRNA (miRNA) dysregulation is connected to silicosis. Emerging evidence suggests that miRNAs modulate pulmonary fibrosis through autophagy; however, its underlying molecular mechanism remains unclear. In agreement with miRNA microarray analysis, the qRT-PCR results showed that miR-29a-3p was significantly decreased in the pulmonary fibrosis model both in vitro and in vivo. Increased autophagosome was observed via transmission electron microscopy in lung epithelial cell models and lung tissue of silicosis mice. The expression of autophagy-related proteins LC3α/ß and Beclin1 were upregulated. The results from using 3-methyladenine, an autophagy inhibitor, or rapamycin, an autophagy inducer, together with TGF-ß1, indicated that autophagy attenuates fibrosis by protecting lung epithelial cells. In TGF-ß1-treated TC-1 cells, transfection with miR-29a-3p mimics activated protective autophagy and reduced alpha-smooth muscle actin and collagen I expression. miRNA TargetScan predicted, and dual-luciferase reporter experiments identified Akt3 as a direct target of miR-29a-3p. Furthermore, Akt3 expression was significantly elevated in the silicosis mouse model and TGF-ß1-treated TC-1 cells. The mammalian target of rapamycin (mTOR) is a central regulator of the autophagy process. Silencing Akt3 inhibited the transduction of the mTOR signaling pathway and activated autophagy in TGF-ß1-treated TC-1 cells. These results show that miR-29a-3p overexpression can partially reverse the fibrotic effects by activating autophagy of the pulmonary epithelial cells regulated by the Akt3/mTOR pathway. Therefore, targeting miR-29a-3p may provide a new therapeutic strategy for silica-induced pulmonary fibrosis.

Circ_0087862 promotes tumorigenesis and glycolysis in colorectal cancer by sponging miR-296-3p to regulate PGK1 expression.

BACKGROUND: Circular RNAs (circRNAs) exert crucial roles in tumor progression of multiple cancers, including colorectal cancer (CRC). However, the functions of most circRNAs are not been fully elucidated. In this study, the role and mechanism of circ_0087862 in CRC were investigated. METHODS: The expression of circ_0087862, microRNA-296-3p (miR-296-3p) and phosphoglycerate kinase 1 (PGK1) was detected by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to assess cell proliferation. Flow cytometry was employed to analyze cell apoptosis. Transwell assay was employed to evaluate cell invasion. Western blot assay was employed to detect the level of related protein markers and PGK1. The glucose consumption, lactate production were tested by corresponding kits. The relationship between miR-296-3p and circ_0087862 or PGK1 was verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP) assay. The in vivo function of circ_0087862 was examined by xenograft mice model. RESULTS: The expression levels of circ_0087862 and PGK1 were up-regulated in CRC tissues and cells, while miR-296-3p was down-regulated. Circ_0087862 silencing suppressed cell proliferation, invasion and glycolysis and promoted cell apoptosis in CRC cells. Circ_0087862 targeted miR-296-3p in CRC cells. MiR-296-3p inhibition reversed circ_0087862 silencing-mediated inhibition effect on cell proliferation, invasion and glycolysis, as well as the promotion effect on cell apoptosis. PGK1 was a target of miR-296-3p, and the overexpression of PGK1 attenuated miR-296-3p-mediated tumor suppression effect on CRC progression. Moreover, knockdown of circ_0087862 inhibited tumorigenesis in vivo. CONCLUSION: Circ_0087862 promoted CRC progression via miR-296-3p/PGK1 axis and might act as a potential target for CRC therapy.

DLAT as a Cuproptosis Promoter and a Molecular Target of Elesclomol in Hepatocellular Carcinoma.

OBJECTIVE: Cuproptosis is a novel cell death pathway that was newly discovered in early 2022. However, cuproptosis is still in its infancy in many respects and warrants further research in hepatocellular carcinoma (HCC). This study aimed to analyze the mechanism of cuprptosis in HCC. METHODS: Herein, the tumor microenvironment infiltration landscape of molecular subtypes was illustrated using GSVA, ssGSEA, TIMER, CIBERSORT, and ESTIMATE algorithms based on the expression profile of cuproptosis-related genes (CRGs) from TCGA and GEO databases. Then, the least absolute shrinkage and selection operator regression method was applied to construct a cuproptosis signature to quantify the cuproptosis profile of HCC. Further, we explored the expression of three hub CRGs in cell lines and clinical patient tissues of HCC by Western blotting, qRT-PCR and immunohistochemistry. Finally, we examined the function of dihydrolipoamide S-acetyltransferase (DLAT) in cuproptosis in HCC by loss-of-function strategy, Western blotting and CCK8 assay. RESULTS: Three distinct molecular subtypes were identified. Cluster 2 had the greatest infiltration of immune cells with best prognosis. The cuproptosis signature was indicative of tumor subtype, immunity, and prognosis for HCC, and specifically, a low cuproptosis score foreshadowed good prognosis. DLAT was highly expressed in liver cancer cell lines and HCC tissues and positively correlated with clinical stage and grade. We also found that potent copper ionophore elesclomol could induce cuproptosis in a copper-dependent manner. Selective Cu++ chelator ammonium tetrathiomolybdate and downregulating DLAT expression by siRNA could effectively inhibit cuproptosis. CONCLUSION: Cuproptosis and DLAT as a promising biomarker could help to determine the prognosis of HCC and may offer novel insights for effective treatment.

The impact of urban irrigation on the temperature-carbon feedback in U.S. cities.

Urban areas experience numerous environmental challenges, among which the anthropogenic emissions of heat and carbon are two major contributors, the former is responsible for the notorious urban heat effect, the latter longterm climate changes. Moreover, the exchange of heat and carbon dioxide are closely interlinked in the built environment, and can form positive feedback loops that accelerate the degradation of urban environmental quality. Among a handful countermeasures for heat and carbon mitigation, urban irrigation is believed to be effective in cooling, yet the understanding of its impact on the co-evolution of heat and carbon emission remains obscure. In this study, we conducted multiphysics urban climate modeling for all urban areas in the contiguous United States, and evaluated the irrigation-induced cooling and carbon mitigation. Furthermore, we assessed the impact of urban irrigation on the potential heat-carbon feedback loop, with their strength of coupling quantified by an advanced causal inference method using the convergent cross mapping algorithms. It is found that the impact of urban irrigation varies vastly in geographically different cities, with its local and non-local effect unraveling distinct pathways of heat-carbon feedback mechanism.

Photothermal-driven disassembly of naphthalocyanine nano-photosensitizers for photothermal and photodynamic therapy.

The disassembly of nanomaterials is of particular interest for high-quality imaging and targeted therapies in the field of nanomedicine. In this study, we developed a novel strategy for fabricating self-assembled naphthalocyanine photosensitizers (SiNc@CEL) with intrinsically unique photochemical and photophysical properties. SiNc@CEL could be disassembled under the photothermal effect, and its photoactivity could be enhanced by 780 nm laser irradiation. Moreover, SiNc@CEL generates reactive oxygen species, including superoxide radicals (O2•-) and singlet oxygen (1O2), as well as good photothermal properties, facilitating the application of multifunctional phototherapy. In vitro evaluation indicated that SiNc@CEL possesses an excellent bactericidal effect under a combination of photodynamic (PDT) and photothermal therapy (PTT). The in vivo treatment of a full-layer skin defect model of Escherichia coli (E. coli) infection showed that SiNc@CEL had superior antibacterial and wound-healing abilities. These results provide the basis for a feasible strategy to enhance the phototherapeutic effect of photosensitizer (PS) systems.