Network and Experimental Pharmacology on Mechanism of Yixintai Regulates the TMAO/PKC/NF-κB Signaling Pathway in Treating Heart Failure.

Objective: This study aims to explore the mechanism of action of Yixintai in treating chronic ischemic heart failure by combining bioinformatics and experimental validation. Materials and Methods: Five potential drugs for treating heart failure were obtained from Yixintai (YXT) through early mass spectrometry detection. The targets of YXT for treating heart failure were obtained by a search of online databases. Gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted on the common targets using the DAVID database. A rat heart failure model was established by ligating the anterior descending branch of the left coronary artery. A small animal color Doppler ultrasound imaging system detected cardiac function indicators. Hematoxylin-eosin (HE), Masson's, and electron microscopy were used to observe the pathological morphology of the myocardium in rats with heart failure. The network pharmacology analysis results were validated by ELISA, qPCR, and Western blotting. Results: A total of 107 effective targets were obtained by combining compound targets and eliminating duplicate values. PPI analysis showed that inflammation-related proteins (TNF and IL1B) were key targets for treating heart failure, and KEGG enrichment suggested that NF-κB signaling pathway was a key pathway for YXT treatment of heart failure. Animal model validation results indicated the following: YXT can significantly reduce the content of intestinal microbiota metabolites such as trimethylamine oxide (TMAO) and improve heart failure by improving the EF and FS values of heart ultrasound in rats and reducing the levels of serum NT-proBNP, ANP, and BNP to improve heart failure. Together, YXT can inhibit cardiac muscle hypertrophy and fibrosis in rats and improve myocardial ultrastructure and serum IL-1ß, IL-6, and TNF-α levels. These effects are achieved by inhibiting the expressions of NF-κB and PKC. Conclusion: YXT regulates the TMAO/PKC/NF-κB signaling pathway in heart failure.

Characterization of sexual maturity-associated N6-methyladenosine in boar testes.

BACKGROUND: The health and size of the testes are crucial for boar fertility. Testicular development is tightly regulated by epigenetics. N6-methyladenosine (m6A) modification is a prevalent internal modification on mRNA and plays an important role in development. The mRNA m6A methylation in boar testicular development still needs to be investigated. RESULTS: Using the MeRIP-seq technique, we identify and profile m6A modification in boar testes between piglets and adults. The results showed 7783 distinct m6A peaks in piglets and 6590 distinct m6A peaks in adults, with 2,471 peaks shared between the two groups. Enrichment of GO and KEGG analysis reveal dynamic m6A methylation in various biological processes and signalling pathways. Meanwhile, we conjointly analyzed differentially methylated and expressed genes in boar testes before and after sexual maturity, and reproductive related genes (TLE4, TSSK3, TSSK6, C11ORF94, PATZ1, PHLPP1 and PAQR7) were identified. Functional enrichment analysis showed that differential genes are associated with important biological functions, including regulation of growth and development, regulation of metabolic processes and protein catabolic processes. CONCLUSION: The results demonstrate that m6A methylation, differential expression and the related signalling pathways are crucial for boar testicular development. These results suggest a role for m6A modification in boar testicular development and provided a resource for future studies on m6A function in boar testicular development.

Clinical outcomes and risk factors for mortality in recipients with carbapenem-resistant gram-negative bacilli infections after kidney transplantation treated with ceftazidime-avibactam: a retrospective study.

Background: Ceftazidime-avibactam is a treatment option for carbapenem-resistant gram-negative bacilli (CR-GNB) infections. However, the risk factors associated with ceftazidime-avibactam (CAZ-AVI) treatment failure in kidney transplant (KT) recipients and the need for CAZ-AVI-based combination therapy remain unclear. Methods: From June 2019 to December 2023, a retrospective observational study of KT recipients with CR-GNB infection treated with CAZ-AVI was conducted, with the primary outcome being 30-day mortality and secondary outcomes being clinical cure, microbiological cure, and safety. Risk factors for 30-day mortality and clinical failure were also investigated. Results: A total of 81 KT recipients treated with CAZ-AVI were included in this study. Forty recipients (49.4%) received CAZ-AVI monotherapy, with a 30-day mortality of 22.2%. The clinical cure and microbiological cure rates of CAZ/AVI therapy were 72.8% and 66.7%, respectively. CAZ-AVI alone or in combination with other medications had no effect on clinical cure or 30-day mortality. Multivariate logistic regression analysis revealed that a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR]: 4.517; 95% confidence interval [CI]: 1.397-14.607; P = 0.012) was an independent risk factor for 30-day mortality. Clinical cure was positively associated with the administration of CAZ-AVI within 48 hours of infection onset (OR: 11.009; 95% CI: 1.344-90.197; P=0.025) and negatively associated with higher APACHE II scores (OR: 0.700; 95% CI: 0.555-0.882; P=0.002). Four (4.9%) recipients experienced recurrence within 90 days after the initial infection, 3 (3.7%) recipients experienced CAZ-AVI-related adverse events, and no CAZ-AVI resistance was identified. Conclusion: CAZ-AVI is an effective medication for treating CR-GNB infections following kidney transplantation, even as monotherapy. Optimization of CAZ/AVI therapy (used within 48 hours of infection onset) is positively associated with potential clinical benefit. Further larger-scale studies are needed to validate these findings.

Seismic noise in South China Sea: High-quality time-frequency analysis from 0.01 to 125 Hz.

An efficient and precise time-frequency analysis method for real-time ocean bottom seismometer (RTOBS) data in the South China Sea (SCS) is presented. Overcoming the limitations of conventional methods, the method involves temporal segmentation, unique frequency octaves, and Fourier transforms to generate power spectral density (PSD) and probability density function profiles. The method demonstrates superior precision, computational efficiency, and full-bandwidth (0 to Nyquist) capability compared to traditional techniques, as validated through theoretical and empirical evaluations. Applied to SCS RTOBS data, it unveils temporal PSD variations, shedding light on underwater noise sources like earthquakes, offshore blasting, ship-induced disturbances, and tidal effects. Establishing background noise levels in the SCS supports noise source categorization and ocean environment monitoring. Furthermore, comparing onshore and offshore seismic stations advances interdisciplinary research, fostering a comprehensive understanding of acoustics and seismology in the region.

Interplay between mesenchymal stem cells and macrophages: Promoting bone tissue repair.

The repair of bone tissue damage is a complex process that is well-orchestrated in time and space, a focus and difficulty in orthopedic treatment. In recent years, the success of mesenchymal stem cells (MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine. MSCs are closely related to macrophages. On one hand, MSCs regulate the immune regulatory function by influencing macrophages proliferation, infiltration, and phenotype polarization, while also affecting the osteoclasts differentiation of macrophages. On the other hand, macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment. The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration. Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair, and will also provide a reference for further application of MSCs in other diseases.

PITPNA-AS1 Inhibits Cell Proliferation and Migration in Ovarian Cancer by Regulating the MIR-223-3p/RHOB Axis.

Background: Ovarian cancer is a fatal gynecologic malignancy. Long non-coding RNA (lncRNA) has been verified to serve as key regulator in ovarian cancer tumorigenesis. Objective: The aim of the study was to study the functions and mechanism of lncRNA PITPNA-AS1 in ovarian cancer cellular process. Methods: Clinical ovarian cancer samples were collected and stored at an academic medical center. Cellular fractionation assays and fluorescence in situ hybridization were conducted to locate PITPNA-AS1 in OC cells. TUNEL staining, colony-forming assays, and Transwell assays were performed for evaluating cell apoptosis as well as proliferative and migratory abilities. Western blot was conducted for quantifying protein levels of epithelialmesenchymal transition markers. The binding relation between genes was verified by RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays. Gene expression levels in ovarian cancer tissues and cells were subjected to RT-qPCR. Results: PITPNA-AS1 level was downregulated in ovarian cancer samples and cells. PITPNA-AS1 overexpression contributed to the accelerated ovarian cancer cell apoptosis and inhibited cell migration, proliferation, and epithelial-mesenchymal transition process. In addition, PITPNA-AS1 interacted with miR-223-3p to regulate RHOB. RHOB knockdown partially counteracted the repressive impact of PITPNA-AS1 on ovarian cancer cell activities. Conclusion: PITPNA-AS1 inhibited ovarian cancer cellular behaviors by targeting miR-223-3p and regulating RHOB.

METTL3 inhibits BMSC apoptosis and facilitates osteonecrosis repair via an m6A-IGF2BP2-dependent mechanism.

Hypoxia-induced apoptosis of bone marrow mesenchymal stem cells (BMSCs) limits the efficacy of their transplantation for steroid-induced osteonecrosis of the femoral head (SONFH). As apoptosis and RNA methylation are closely related, exploring the role and mechanism of RNA methylation in hypoxic apoptosis of BMSCs is expected to identify new targets for transplantation of BMSCs for SONFH and enhance transplantation efficacy. We performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA-seq on a hypoxia-induced apoptosis BMSC model and found that the RNA methyltransferase-like 3 (METTL3) is involved in hypoxia-induced BMSC apoptosis. The expression of METTL3 was downregulated in BMSCs after hypoxia and in BMSCs implanted in osteonecrosis areas. Knockdown of METLL3 under normoxic conditions promoted apoptosis of BMSCs. In contrast, overexpression of METTL3 promoted the survival of BMSCs under hypoxic conditions, and overexpression of METTL3 promoted the survival of BMSCs in the osteonecrosis area and the repair of the osteonecrosis area. Regarding the mechanism, the m6A levels of the mRNAs of anti-apoptotic genes Bcl-2, Mcl-1, and BIRC5 were significantly increased upon the overexpression of METTL3 under hypoxic conditions, which promoted the binding of Bcl-2, Mcl-1, and BIRC5 mRNAs to IGF2BP2, enhanced the mRNA stability, and increased the protein expression of the three anti-apoptotic genes. In conclusion, overexpression of METTL3 promoted m6A modification of mRNAs of Bcl-2, Mcl-1, and BIRC5, promoted the binding of IGF2BP2 to the above-mentioned mRNAs, enhanced mRNA stability, inhibited hypoxia-induced BMSC apoptosis, and promoted repair of SONFH, thereby providing novel targets for transplantation of BMSCs for SONFH.

Integrating single-cell and multi-omic approaches reveals Euphorbiae Humifusae Herba-dependent mitochondrial dysfunction in non-small-cell lung cancer.

Euphorbiae Humifusae Herba (EHH) is a pivotal therapeutic agent with diverse pharmacological effects. However, a substantial gap exists in understanding its pharmacological properties and anti-tumour mechanisms. This study aimed to address this gap by exploring EHH's pharmacological properties, identifying NSCLC therapy-associated protein targets, and elucidating how EHH induces mitochondrial disruption in NSCLC cells, offering insights into novel NSCLC treatment strategies. String database was utilized to explore protein-protein interactions. Subsequently, single-cell analysis and multi-omics further unveiled the impact of EHH-targeted genes on the immune microenvironment of NSCLC, as well as their influence on immunotherapeutic responses. Finally, both in vivo and in vitro experiments elucidated the anti-tumour mechanisms of EHH, specifically through the assessment of mitochondrial ROS levels and alterations in mitochondrial membrane potential. EHH exerts its influence through engagement with a cluster of 10 genes, including the apoptotic gene CASP3. This regulatory impact on the immune milieu within NSCLC holds promise as an indicator for predicting responses to immunotherapy. Besides, EHH demonstrated the capability to induce mitochondrial ROS generation and perturbations in mitochondrial membrane potential in NSCLC cells, ultimately leading to mitochondrial dysfunction and consequent apoptosis of tumour cells. EHH induces mitochondrial disruption in NSCLC cells, leading to cell apoptosis to inhibit the progress of NSCLC.

Can energy saving and emission reduction policies promote green transformation of industrial enterprises--The Case of China.

In the context of the continued advancement of the green economy transition, the proactive pursuit of carbon emissions reduction and the early attainment of carbon neutrality goals have emerged as essential components in promoting high-quality economic development. Not only does it contribute to the creation of a community of human destiny, but it is also vital to the realization of sustainable development for human civilization. A dynamic evolutionary game model, which encompasses the interactions among government, enterprises, and the public, was constructed to examine the inherent impact mechanisms of the behavior of three players on the development of a green economy under the context of energy saving and emission reduction subsidies. The results showed that the incentive and punishment mechanisms served as effective tools for harmonizing the interests of system members. Within the mechanisms, the public demonstrated a higher sensitivity to rewards, while enterprises exhibited greater responsiveness to fines. Consequently, the government could influence the behavior of enterprises by incentivizing the public to serve as a third-party inquiry and oversight body. Simultaneously, the government could encourage enterprises to expedite green technology innovation by employing a combination of incentive and punishment mechanisms.

What Matters for the Charge Transport of Two-Dimensional Perovskites?

Compared to three-dimensional (3D) perovskites, two-dimensional (2D) perovskites exhibit excellent stability, structural diversity, and tunable bandgaps, making them highly promising for applications in solar cells, light-emitting diodes and photodetectors. However, the trade-off for worse charge transport is a critical issue that needs to be addressed. This comprehensive review first discusses the structure of 3D and 2D metal halide perovskites, then summarizes the significant factors influencing charge transport in detail and provides a brief overview of the testing methods. Subsequently, various strategies to improve the charge transport are presented, including tuning A'-site organic spacer cations, A-site cations, B-site metal cations, and X-site halide ions. Finally, an outlook on the future development of improving the 2D perovskites' charge transport is discussed. This article is protected by copyright. All rights reserved.

Residents' KABP and Social Support Statuses Under Normalized COVID-19 Pandemic Prevention and Control: A Cross-Sectional Study.

OBJECTIVES: To investigate the status quo of residents' knowledge, attitude, belief, and practice (KABP) and social support and the correlation of KABP with social support under normalized coronavirus disease (COVID-19) pandemic prevention and control. METHODS: A questionnaire was designed based on the KABP model, and an online survey was conducted among residents in September 2022. SPSS software (version 25.0) was used to analyze the data. Two independent sample t-tests, one-way analysis of variance (ANOVA), multivariate linear regression analysis, and Pearson's correlation analysis were conducted. RESULTS: In total, 326 valid questionnaires were obtained. The scoring rates of residents' KABP and social support were 68.1%, 92.2%, 89.3%, 75.3%, and 62.6%, respectively. Main factors influencing residents' knowledge included gender, nationality, education level, practice, and social support; those influencing attitude were belief and practice; those influencing belief were place of residence, attitude, and practice; those influencing practice were knowledge, attitude, belief, and social support; and those influencing social support were marital status, place of residence, knowledge, and practice. Social support was positively correlated with knowledge and practice. CONCLUSIONS: This study provides a scientific foundation for the current normalized prevention and control of COVID-19 and is conducive to health managers to better carry out prevention and control related health education for specific groups.

Design of a prodrug photocage for cancer cells detection and anticancer drug release.

Developing probes for simultaneous diagnosis and killing of cancer cells is crucial, yet challenging. This article presents the design and synthesis of a novel Rhodamine B fluorescence probe. The design strategy involves utilizing an anticancer drug (Melphalan) to bind with a fluorescent group (HRhod-OH), forming HRhod-MeL, which is non-fluorescent. However, when exposed to the high levels of reactive oxygen species (ROS) of cancer cells, HRhod-MeL transforms into a red-emitting Photocage (Rhod-MeL), and selectively accumulates in the mitochondria of cancer cells, where, when activated with green light (556 nm), anti-cancer drugs released. The Photocage improve the efficacy of anti-cancer drugs and enables the precise diagnosis and killing of cancer cells. Therefore, the prepared Photocage can detect cancer cells and release anticancer drugs in situ, which provides a new method for the development of prodrugs.

Genome-Wide Analysis Elucidates the Roles of GhTIR1/AFB Genes Reveals the Function of Gh_D08G0763 (GhTIR1) in Cold Stress in G. hirsutum.

This study identified 13 GhTIR1/AFB members in G. hirsutum through bioinformatics methods and divided them into three subgroups by phylogenetic tree analysis. Motif and gene structure analysis showed that the genes in this family were highly conserved. Promoter cis-acting element analysis found that the promoters of GhTIR1/AFBs contained a large number of cis-acting elements in response to growth and development and abiotic stress. Further RT-qPCR results showed that GhTIR1/AFB genes responded to various abiotic stresses such as IAA, ABA, cold, and heat, and the expression levels of each gene changed obviously, especially Gh_D08G0763 (GhTIR1), which responded significantly to cold injury. Using VIGS (virus-induced gene silencing) technology to silence Gh_D08G0763 in the cold-tolerant cotton variety ZM36, it was found that the resistance of ZM36 to cold damage was significantly reduced. The physiological response mechanism of the Gh_D08G0763 in resisting cold damage was further analyzed through trypan blue staining of leaves and determination of enzyme activity levels. This study provided effective genetic resources for cotton cold-tolerance breeding.

Comparative effectiveness of ehealth self-management interventions for patients with heart failure: A Bayesian network meta-analysis.

OBJECTIVE: This study evaluated the effectiveness of electronic self-management support interventions in reducing all-cause mortality, cardiovascular mortality, readmission rates, and HF-related readmission in heart failure patients. METHODS: Following the PRISMA-P guidelines and PRISMS taxonomy, we searched Pubmed, Cochrane Library, and Embase for RCTs and trials of electronic health technologies for heart failure interventions. Develop support programs in advance for education, monitoring, reminders, or a combination of these to screen and categorize studies. The Cochrane ROB2 tool was used to assess the risk of bias. RESULTS: The monitoring interventions may improve all-cause mortality (OR 0.77, 95% CI 0.63 to 0.93) and cardiovascular mortality (OR 0.75, 95% CI 0.61 to 0.93) compared to usual care. Reminder interventions were associated with significantly reducing readmission rates (OR 0.07, 95% CI 0.00 to 0.94). Mixed interventions were most effective in reducing HF-related readmission rates (OR 0.75, 95% CI 0.56 to 0.99). CONCLUSION: Electronic self-management interventions, particularly monitoring and reminders, can potentially improve outcomes of heart failure patients, including reducing all-cause mortality, cardiovascular mortality, and readmission rates. PRACTICE IMPLICATIONS: The eHealth model and the combination of self-management are significant for long-term intervention in patients with HF to improve their quality of life and prognosis.

Ganonorsterone A, a norsteroid from the medicinal fungus Ganoderma lingzhi.

Phytochemical investigation on the fruiting bodies of the medicinal fungus Ganoderma lingzhi led to the isolation of a new norsteroid, namely ganonorsterone A (1), together with one known steroid, cyathisterol (2). The structure and absolute configuration of compound 1 were assigned by extensive analysis of MS, NMR data, and quantum-chemical calculations including electronic circular dichroism (ECD) and calculated 13C NMR-DP4+ analysis. Bioassay results showed that compound 1 displayed moderate inhibition on NO production in RAW 264.7 macrophages.

Photothermal-Responsive Lightweight Hydrogel Actuator Loaded with Polydopamine-Modified Hollow Glass Microspheres.

Aquatic actuators based on the light-to-work conversion are of paramount significance for the development of cutting-edge fields including robots, micromachines, and intelligent systems. Herein, we report the design and synthesis of near-infrared light-driven hydrogel actuators through loading with lightweight polydopamine-modified hollow glass microspheres (PDA-HGMPs) into responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogels. These PDA-HGMPs can not only function as an excellent photothermal agent but also accelerate the swelling/desewlling of hydrogels due to their reconstruction for polymer gel skeleton, which speeds up the response rate of hydrogel actuators. The resulting hydrogel actuator shows controlled movements under light illumination, including complex self-propellant and floating/sinking motions. As the proof-of-concept demonstrations, a self-sensing robot is conceptualized by integrating the PDA-HGMP-containing hydrogel actuator with an ultrathin and miniature pressure sensor. Hopefully, this work can offer some important insights into the research of smart aquatic soft actuators, paving the way to the potential applications in emerging fields including micromachines and intelligent systems.

Adsorption and desorption behavior of Zn2+ in a flow-through electrosorption reactor.

As heavy metal industrial wastewater increases in volume and complexity, we need more efficient, cheaper, and renewable technologies to curb its environmental impact. Compared to advection electrosorption, through-flow electrosorption is a hotspot technique that makes more efficient use of the adsorption capacity of activated carbon fiber mats. A cascade flow-through electrosorption assembly based on activated carbon fiber was used to obtain the best adsorption of Zn2+ in water at a voltage of 2 V, pH value of 8, plate spacing of 3 mm, and temperature of 15°C. The process is more closely fitted to the secondary adsorption kinetic equation and the Langmuir equation. The adsorption capacity of the module decreases at a progressively slower rate with the number of cycles and will eventually retain 75% of its peak value with significant regenerability. The study of this module can provide technical support for treating heavy metal wastewater.

A near-IR ratiometric fluorescent probe for the precise tracking of senescence: a multidimensional sensing assay of biomarkers in cell senescence pathways.

Senescence is a complex physiological process that can be induced by a range of factors, and cellular damage caused by reactive oxygen species (ROS) is one of the major triggers. In order to learn and solve age-related diseases, tracking strategies through biomarkers, including senescence-associated ß-galactosidase (SA-ß-gal), with high sensitivity and accuracy, have been considered as a promising solution. However, endogenous ß-gal accumulation is not only associated with senescence but also with other physiological processes. Therefore, additional assays are needed to define cellular senescence further. In this work, a fancy fluorescent probe SA-HCy-1 for accurately monitoring senescence is developed, with SA-ß-gal and HClO as targets under high lysosomal pH conditions (pH > 6.0) specifically, on account of the role ß-gal commonly played as an ovarian cancer biomarker. Therefore, precise tracking of cellular senescence could be achieved in view of these three dimensions, with response in dual fluorescence channels providing a ratiometric sensing pattern. This elaborate strategy has been verified to be suitable for biological applications by skin photo-aging evaluation and cellular passage tracing, displaying a significantly improved sensitivity compared with the commercial X-gal kit measurement.