A LDH-Derived Metal Sulfide Nanosheet-Functionalized Bioactive Glass Scaffold for Vascularized Osteogenesis and Periprosthetic Infection Prevention/Treatment.

Periprosthetic infection and prosthetic loosing stand out as prevalent yet formidable complications following orthopedic implant surgeries. Synchronously addressing the two complications is long-time challenging. Herein, a bioactive glass scaffold (BGS) functionalized with MgCuFe-layered double hydroxide (LDH)-derived sulfide nanosheets (BGS/MCFS) is developed for vascularized osteogenesis and periprosthetic infection prevention/treatment. Apart from the antibacterial cations inhibiting bacterial energy and material metabolism, the exceptional near-infrared-II (NIR-II) photothermal performance empowers BGS/MCFS to eliminate periprosthetic infections, outperforming previously reported functionalized BGS. The rough surface topography and the presence of multi-bioactive metal ions bestow BGS/MCFS with exceptional osteogenic and angiogenic properties, with 8.5-fold and 2.3-fold enhancement in bone mass and neovascularization compared with BGS. Transcriptome sequencing highlights the involvement of the TGF-ß signaling pathway in these processes, while single-cell sequencing reveals a significant increase in osteoblasts and endothelial cells around BGS/MCFS compared to BGS.

Endogenous RBM4 prevents Ang II-induced cardiomyocyte hypertrophy via downregulating the expression of PTBP1.

Aberrant gene expression in cardiomyocyte has been revealed to be the fundamental essence of pathological cardiac hypertrophy. However, the detailed mechanisms are not fully understood. The underlying regulators of gene expression involved in cardiac hypertrophy remain to be further identified. Here, we report that the RNA-binding protein RNA-binding motif protein 4 (RBM4) functions as an endogenic protector that is able to fight against cardiomyocyte hypertrophy in vitro. Under pro-hypertrophic stimulation of angiotensin II (Ang II), the protein level of RBM4 in cardiomyocyte and myocardium is elevated. Knockdown of RBM4 can further aggravate cardiomyocyte hypertrophy, while over-expression of RBM4 represses cardiomyocyte hypertrophy. Mechanistically, RBM4 is localized in the nucleus and down-regulates the expression of polypyrimidine tract-binding protein 1 (PTBP1), which has been shown to aggravate cardiomyocyte hypertrophy. In addition, we suggest that the up-regulation of RBM4 in cardiomyocyte hypertrophy is caused by N6-methyladenosine (m6A). Ang II induces m6A methylation of RBM4 mRNA, which further enhances the YTH domain-containing family protein 1 (YTHDF1)-mediated translation of RBM4. Thus, our results reveal a novel pathway consisting of m6A, RBM4 and PTBP1, which is involved in cardiomyocyte hypertrophy.

A Redox-Active Iron-Organic Framework Cathodes for Sustainable Magnesium Metal Batteries.

Rechargeable magnesium metal batteries (RMBs) have shown promising prospects in sustainable energy storage due to the high crustal abundance, safety, and potentially large specific capacity of magnesium. However, their development is constrained by the lack of effective cathode materials that can achieve high capacity and stable magnesium storage at a practically reasonable rate. Herein, we construct a three-dimensional (3D) iron(III)-dihydroxy-benzoquinone (Fe2(DHBQ)3) metal-organic framework (MOF) material with dual redox centers of Fe3+ cations and DHBQ2- anions for reversible storage of Mg2+ in RMBs. Spectroscopic analysis and density functional theory (DFT) calculations reveal the redox chemistry of both Fe3+ ions and carbonyls from DHBQ ligands during electrochemical processes. Benefiting from the rational structure, the Fe2(DHBQ)3∥Mg cells exhibit a high reversible capacity of 395.3 mAh/g, large energy density of 463.5 Wh/kg, and high power density of 2456.0 W/kg. Moreover, the high electronic conductivity (8.35 × 10-5 S/cm) and favorable diffusion path of Mg2+ in Fe2(DHBQ)3 endow the cells with exceptional cycling stability and rate capability with a long life of 5000 cycles at 2000 mA/g. The dual redox-active MOF demonstrates a category of advanced cathode materials for high-performance RMBs.

Dose rate correction for the novel 2D diode array MapCHECK 3.

PURPOSE: To investigate the dose rate dependence of MapCHECK3 and its influence on measurement accuracy, as well as the effect of dose rate correction. MATERIALS AND METHODS: The average and instantaneous dose rate dependence of MapCHECK2 and MapCHECK3 were studied. The accuracy of measurements was investigated where the dose rate differed significantly between dose calibration of the MapCHECK and the measurement. Measurements investigated include: the central axis dose for different fields at different depths, off-axis doses outside the field, and off-axis doses along the wedge direction. Measurements using an ion chamber were taken as the reference. Exponential functions were fit to account for average and instantaneous dose rate dependence for MapCHECK3 and used for dose rate correction. The effect of the dose rate correction was studied by comparing the differences between the measurements for MapCHECK (with and without the correction) and the reference. RESULTS: The maximum dose rate dependence of MapCHECK3 is greater than 2.5%. If the dose calibration factor derived from a 10 × 10 cm2 open field at 10 cm depth was used for measurements, the average differences in central diode dose were 0.8% ± 1.0% and 1.0% ± 0.8% for the studied field sizes and measurement depths, respectively. The introduction of wedge would not only induce -1.8% ± 1.3% difference in central diode dose, but also overestimate the effective wedge angle. After the instantaneous dose rate correction, above differences can be changed to 1.9% ± 8.1%, 0.2% ± 0.1%, and 0.0% ± 0.9%. The pass rate can be improved from 98.4% to 98.8%, 98.3%-100.0%, and 96.3%-100.0%, respectively. CONCLUSION: Compared with MapCHECK2 (SunPoint1 diodes), the more pronounced dose rate dependence of MapCHECK3 (SunPoint2 diodes) should be carefully considered. To ensure highly accurate measurement, it is suggested to perform the dose calibration at the same condition where measurement will be performed. Otherwise, the dose rate correction should be applied.

Degradation-Risk-Inspired Optimization of the Antifungal Oxazolinyl Aniline Lead by a Fusion of Triazole with Nicotinamide.

The discovery of readily available and easily modifiable new models is a crucial and practical solution for agrochemical innovation. Antifungal function-oriented fusion of triazole with the prevalidated lead (R)-LE001 affords a novel framework with a broad and enhanced antifungal spectrum. Characterized by the easy accessibility and adjustability of [1,2,4]triazolo[4,3-a]pyridine, modular fine-tuning provided a set of unprecedented leads (e.g., Z23, Z25, Z26, etc.) with superior antifungal potentials than the positive control boscalid. Candidate Z23 exhibited a more promising antifungal activity against Sclerotinia sclerotiorum, Botrytis cinerea, and Phytophthora capsici with EC50 values of 0.7, 0.6, and 0.5 µM, respectively. This candidate could effectively control boscalid-resistant B. cinerea strains and also exhibit good vivo efficacy in controlling gray mold. Noteworthily, both the SDH-inhibition and the efficiency against Oomycete P. capsici are quite distinct from that of the positive control boscalid. A molecular docking simulation also differentiates Z23 from boscalid. These findings highlight the potential of [1,2,4]triazolo[4,3-a]pyridine amide as a novel antifungal model.

Currency risk analysis of belt and road initiative countries.

The UN's Sustainable Development Goals (SDGs) highlight the role of debt sustainability in achieving sustainable development. China's Belt and Road Initiative (BRI) is an international cooperation effort that is endorsed by over 150 countries and organizations. Given the alignment between BRI development goals and the SDGs, the issue of debt sustainability in BRI countries warrants attention. While existing studies focus on sovereign risk in debt sustainability, there is a lack of emphasis on currency risk, indicating a need for further investigation to mitigate risks and comprehensively evaluate debt stability. Using data from 142 countries, this study examines currency risk reduction in BRI countries by assessing currency competitiveness. We find that the US dollar (USD) is the most competitive currency among BRI countries, followed by the Euro (EUR), Chinese yuan (CNY), sterling pound (GBP), and Japanese yen (JPY). The USD maintains its competitive edge over time, making it the preferred choice, with the EUR as a less optimal option and the CNY showing potential. Geographically, the EUR's close ties with BRI countries lend it prominence, followed by the USD, with the CNY gaining traction. GBP and JPY are considered conservative choices. Recommendations for currency selection vary based on countries' competitiveness, bilateral relationships, and development status.

[Clinical and genetic characteristics of a case of primary ciliary dyskinesia caused by new frameshift mutation of the DNAH5 gene].

OBJECTIVE: To investigate the clinical and genetic characteristics of a case of primary ciliary dyskinesia (PCD). METHODS: We collected the clinical data on a case of PCD treated in the Department of Reproductive Medicine of Linyi People's Hospital in July 2020, detected the genes of the patient by whole-exome sequencing (WES), verified the candidate mutations by Sanger sequencing, and predicted the protein structure of the mutant gene by SWISS-MODEL. RESULTS: The proband was found with the clinical phenotypes of chronic rhinitis, bronchiectasis, visceral transposition and male infertility. WES revealed a homozygous frameshift variation of c.12890dup (p.N4297Kfs*13) in exon 74 of the DNAH5 gene, which led to the premature termination of polypeptide chain synthesis and affected the gene function. SWISS-MODEL prediction showed that some of the amino acid residues were deleted after mutation, resulting in a 3D conformational change of the protein. This variation was not recorded in the ClinVar, gnomAD and OMIM databases and, according to the relevant guidelines of the American College of Genetics and Genomics, was classified as a pathogenic variation (PVS1+PM2_P+PM3_P). CONCLUSION: The homozygous variation of the DNAH5 gene c.12890dup (p.N4297Kfs*13) may be the cause of the clinical phenotype of this case of PCD, and the above findings have enriched the variation spectrum of the DNAH5 gene.

Evaluation of the mechanical properties of porcine kidney.

With the development of medical diagnosis and treatment, knowing the mechanical properties of living tissues becomes critical. The aim of this study was to investigation material properties of the fresh porcine kidney and the parametric characterization of its viscoelastic material behavior. The material investigation included uniaxial tension tests in different strain rates, relaxation tests, as well as hydrostatic compression tests on the samples extracted from the fresh porcine kidney cortex. Tension tests and relaxation tests were performed by a planar dog-bone specimen with a micron loading testing machine. Hydrostatic compression tests were performed on the kidney cylinder sample which was placed in a compression chamber. Furthermore, a nonlinear viscoelastic model recently proposed by us was employed to characterize the tension data at different strain rates and relaxation test data. The the experimental and numerical results show that the stress-strain relations of the porcine kidney cortex at different strain rates in tension are presented for the first time and a higher strain rate results in higher ultimate strength and initial Young modulus but a lower rupture strain. A damage-dependent visco-elastic model is employed to model the tension data at different strain rates and relaxation data and exhibits a good agreement with the experimental data, which also demonstrates that the damage has an obvious influence on the stress-strain relation. Through comparison with the existing reference covering the uniaxial compression data, it seems that the mechanical behavior of the porcine kidney cortex manifests a stress state-dependent mechanical behavior. The ultimate strength and rupture strain are larger in compression than that in tension.

Exosomes derived from mouse vibrissa dermal papilla cells promote hair follicle regeneration during wound healing by activating Wnt/ß-catenin signaling pathway.

Hair follicle (HF) regeneration during wound healing continues to present a significant clinical challenge. Dermal papilla cell-derived exosomes (DPC-Exos) hold immense potential for inducing HF neogenesis. However, the accurate role and underlying mechanisms of DPC-Exos in HF regeneration in wound healing remain to be fully explained. This study, represents the first analysis into the effects of DPC-Exos on fibroblasts during wound healing. Our findings demonstrated that DPC-Exos could stimulate the proliferation and migration of fibroblasts, more importantly, enhance the hair-inducing capacity of fibroblasts. Fibroblasts treated with DPC-Exos were capable of inducing HF neogenesis in nude mice when combined with neonatal mice epidermal cells. In addition, DPC-Exos accelerated wound re-epithelialization and promoted HF regeneration during the healing process. Treatment with DPC-Exos led to increased expression levels of the Wnt pathway transcription factors ß-catenin and Lef1 in both fibroblasts and the dermis of skin wounds. Specifically, the application of a Wnt pathway inhibitor reduced the effects of DPC-Exos on fibroblasts and wound healing. Accordingly, these results offer evidence that DPC-Exos promote HF regeneration during wound healing by enhancing the hair-inducing capacity of fibroblasts and activating the Wnt/ß-catenin signaling pathway. This suggests that DPC-Exos may represent a promising therapeutic strategy for achieving regenerative wound healing.

A wide-bandgap graphene-like structure C6BN with ultra-low dielectric constant.

This study introduces a new wide-bandgap graphene-like structure, denoted as C6BN, achieved by incorporating an eight-electron BN pair, substantially modifying its electronic properties. Utilizing extensive density functional calculations, we comprehensively analyzed the stability, electronic structure, mechanical properties, and optical-electrical characteristics of C6BN. Our investigations reveal the material's exceptional thermodynamic, mechanical, and dynamic stability. Notably, the calculated wide bandgap of 2.81 eV in C6BN, supported by analyses of energy levels, band structures, and density of states, positions it as a promising two-dimensional wide-bandgap semiconductor. Additionally, C6BN exhibits isotropic mechanical features, highlighting its inherent flexibility. Remarkably, our calculations indicate an ultra-low dielectric constant (k = 1.67) for C6BN, surpassing that of well-established third-generation semiconductors. Further exploration into the thermoelectric properties of C6BN demonstrates its promising performance, as evidenced by calculations of thermal conductivity (κ), power factor (P), and Seebeck coefficient (S). In summary, our findings underscore the significant potential of the proposed C6BN structure as a flexible two-dimensional material poised to drive future advancements in electronic and energy-related technologies.

Sialic acid metabolism of oral bacteria and its potential role in colorectal cancer and Alzheimer's disease.

Sialic acid metabolism in oral bacteria is a complex process involving nutrient acquisition, immune evasion, cell surface modification, and the production of metabolites that contribute to bacterial persistence and virulence in the oral cavity. In addition to causing various periodontal diseases, certain oral pathogenic bacteria, such as Porphyromonas gingivalis, Tannerella forsythia, and Fusobacterium nucleatum, can induce inflammatory reactions and influence the immunity of host cells. These associations with host cells are linked to various diseases, particularly colorectal cancer and Alzheimer's disease. Sialic acid can be found in the host oral mucosa, saliva, or food residues in the oral cavity, and it may promote the colonization of oral bacteria and contribute to disease development. This review aims to summarize the role of sialic acid metabolism in oral bacteria and discuss its effect on the pathogenesis of colorectal cancer and Alzheimer's disease.

CD248 interacts with ECM to promote hypertrophic scar formation and development.

Hypertrophic scar (HS) presents a significant clinical challenge, frequently arising as a fibrotic sequela of burn injuries and trauma. Characterized by the aberrant activation and proliferation of myofibroblasts, HS lacks a targeted therapeutic approach to effectively reduce this dysregulation. This study offers novel evidence of upregulated expression of CD248 in HS tissues compared to normal skin (NS) tissues. Specifically, the expression of CD248 was predominantly localized to α-SMA+-myofibroblasts in the dermis. To explain the functional role of CD248 in dermal myofibroblast activity, we employed a targeted anti-CD248 antibody, IgG78. Both CD248 intervention and IgG78 treatment effectively suppressed the proliferative, migratory, and ECM-synthesizing activities of myofibroblasts isolated from HS dermis. In addition, IgG78 administration significantly attenuated HS formation in an in vivo rabbit ear model. The LC/MS analysis coupled with co-immunoprecipitation of HS tissues indicated a direct interaction between CD248 and the ECM components Fibronectin (FN) and Collagen I (COL I). These findings collectively suggest that CD248 may function as a pro-fibrotic factor in HS development through its interaction with ECM constituents. The utilization of an anti-CD248 antibody, such as IgG78, represents a promising novel therapeutic strategy for the treatment of HS.

miR-125b-5p delivered by adipose-derived stem cell exosomes alleviates hypertrophic scarring by suppressing Smad2.

Background: Hypertrophic scarring is the most serious and unmet challenge following burn and trauma injury and often leads to pain, itching and even loss of function. However, the demand for ideal scar prevention and treatment is difficult to satisfy. We aimed to discover the effects and mechanisms of adipose-derived stem cell (ADSC) exosomes in hypertrophic scarring. Methods: ADSC exosomes were isolated from the culture supernatant of ADSCs and identified by nanoparticle tracking analysis, transmission electron microscopy and western blotting. The effect of ADSC exosomes on wound healing and scar formation was detected by the wound model of BALB/c mice. We isolated myofibroblasts from hypertrophic scar tissue and detected the cell viability, proliferation and migration of myofibroblasts. In addition, collagen formation and fibrosis-related molecules were also detected. To further disclose the mechanism of ADSC exosomes on fibrosis in myofibroblasts, we detected the expression of Smad2 in hypertrophic scar tissue and normal skin and the regulatory mechanism of ADSC exosomes on Smad2. Injection of bleomycin was performed in male BALB/c mice to establish an in vivo fibrosis model while ADSC exosomes were administered to observe their protective effect. The tissue injury of mice was observed via hematoxylin and eosin and Masson staining and related testing. Results: In this study, we found that ADSC exosomes could not only speed up wound healing and improve healing quality but also prevent scar formation. ADSC exosomes inhibited expression of fibrosis-related molecules such as α-smooth muscle actin, collagen I (COL1) and COL3 and inhibited the transdifferentiation of myofibroblasts. In addition, we verified that Smad2 is highly expressed in both hypertrophic scar tissue and hypertrophic fibroblasts, while ADSC exosomes downregulated the expression of Smad2 in hypertrophic fibroblasts. Further regulatory mechanism analysis revealed that microRNA-125b-5p (miR-125b-5p) is highly expressed in ADSC exosomes and binds to the 3' untranslated region of Smad2, thus inhibiting its expression. In vivo experiments also revealed that ADSC exosomes could alleviate bleomycin-induced skin fibrosis and downregulate the expression of Smad2. Conclusions: We found that ADSC exosomes could alleviate hypertrophic scars via the suppression of Smad2 by the specific delivery of miR-125b-5p.

Myocardial ischemia simulation based on a multi-scale heart electrophysiology model.

BACKGROUND: Myocardial ischemia, caused by insufficient myocardial blood supply, is a leading cause of human death worldwide. Therefore, it is crucial to prioritize the prevention and treatment of this condition. Mathematical modeling is a powerful technique for studying heart diseases. OBJECTIVE: The aim of this study was to discuss the quantitative relationship between extracellular potassium concentration and the degree of myocardial ischemia directly related to it. METHODS: A human cardiac electrophysiological multiscale model was developed to calculate action potentials of all cells simultaneously, enhancing efficiency over traditional reaction-diffusion models. RESULTS: Contrary to the commonly held view that myocardial ischemia is caused by an increase in extracellular potassium concentration, our simulation results indicate that level 1 ischemia is associated with a decrease in extracellular potassium concentration. CONCLUSION: This unusual finding provides a new perspective on the mechanisms underlying myocardial ischemia and has the potential to lead to the development of new diagnostic and treatment strategies.

Staphylococcus Aureus Membrane Vesicles Kill Tumor Cells Through a Caspase-1-Dependent Pyroptosis Pathway.

Introduction: Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated. Methods: MVs of Staphylococcus aureus USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2-MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor. Results: The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 µg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2-MVs (R2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10-3 µg. Antares2-MVs can directly target tumor tissues in vivo, and 20 µg/mL Antares2-MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo. Conclusion: S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment.

Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

Ultrasensitive label-free electrochemical aptasensor for Pb2+ detection exploiting Exo III amplification and AgPt/GO nanocomposite-enhanced transduction.

Lead ion pollution has become a serious public health concern worldwide. Therefore, sensitive detection of Pb2+ is critical to control lead pollution, assess risks, and safeguard the health of vulnerable populations. This study reports a highly sensitive labelling-free electrochemical aptasensor for Pb2+ detection. The aptasensor employs silver-platinum nanoparticles/graphene oxide (AgPt/GO) and Exonuclease III (Exo III) for signal amplification. GO provides high surface area and conductivity for immobilizing AgPt NPs, facilitating the immobilization of aptamer (Apt) probes on the electrode surface. Exo III enzymatically cleaves DNA strands on the electrode surface, releasing DNA segments to amplify the signal further. The synergistic amplification by AgPt/GO and ExoIII enables an extremely wide linear detection range of 0.05 pM-5 nM for Pb2+, with a low detection limit of 0.019 pM. Additionally, the G-quadruplex structure ensures excellent selectivity for Pb2+ detection, resulting in high reproducibility and stability of the aptasensor. The aptasensor was successfully applied to detect spiked Pb2+ in tap water samples, achieving recovery rates ranging from 96 to 108.4 %. By integrating nanomaterials, aptamers and enzymatic amplification, the aptasensor facilitates highly sensitive and selective detection of Pb2+, demonstrating potential for practical applications in environmental monitoring.

Eudistomins Y-Inspired Design and Divergent Optimization of Heteroaryl Ketones for New Antifungal Leads.

The discovery of structurally distinct leads is imperative in modern agrochemical science. Inspired by eudistomins Y and the framework-related pharmaceuticals, aryl heteroaryl ketone was drawn as a common model intriguing the design and divergent synthesis of 14 kinds of heteroaryl ketones aligned with their oxime derivatives. Antifungal function-oriented phenotypical screen protruded benzothiazolyl-phenyl oxime 5a as a promising model, and the concomitant modification led to benzothiazolyl oxime 5am (EC50 = 5.17 µM) as a superior lead than fluoxastrobin (EC50 = 7.54 µM) against Sclerotinia sclerotiorum. Scaffold hopping of the phenyl subunit identified benzothiazolyl-pyridyl oxime as a novel antifungal scaffold accompanied by acquiring oxime 5bm with remarkable activity (EC50 = 3.57 µM) against Pyricularia oryzae. Molecular docking showed that candidate 5am could form more hydrogen bonds with the amino acid residues of actin than metrafenone. This compound also demonstrated better curative efficacy than that of fluoxastrobin and metrafenone in controlling the plant disease caused by S. sclerotiorum. These results rationalize the discovery of antifungal candidates based on aryl heteroaryl ketone.

Network pharmacology, bioinformatics, and experimental validation to identify the role of Hedyotis diffusa willd against gastric cancer through the activation of the endoplasmic reticulum stress.

Background: Globally, gastric cancer (GC) is recognized as the third leading cause of cancer-related deaths and the fifth most prevalent malignant disease. Multiple studies have indicated that Hedyotis diffusa Willd, in pinyin, called Bai Hua She Cao (BHSSC), a traditional Chinese medicine (TCM) is an herbal remedy for cancer treatment. However, the specific mechanisms underlying its anti-tumor properties and mode of action are still unclear. Methods: To determine the role of BHSSC in GC, candidate target genes were selected from The Encyclopedia of Traditional Chinese Medicine (ETCM) and analyzed using network pharmacology, bioinformatics, and experimental validation. Differentially expressed genes (DEGs) associated with gastric cancer were obtained from RNA sequencing (RNA-seq) data sourced from The Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD). The Reactome Pathway was examined using Analysis Tools, while KEGG pathways were analyzed using KOBAS. Gene Ontology (GO) evaluations were performed using WebGestalt and DAVID. The relationships between proteins were investigated using the STRING database. Furthermore, cell viability, colony formation, and cell migration ability were conducted in gastric cancer cells, BGC-823 and MGC-803. Results: Network pharmacology and bioinformatics analyses revealed a significant association between BHSSC and metabolic pathways. In vitro experiments demonstrated that BHSSC effectively suppressed gastric cancer cell proliferation and colony formation, inhibited cell migration, and activated the endoplasmic reticulum (ER) stress. Furthermore, it was found that enhancement of the expression of IRE1α and BIP is the mechanism by which BHSSC activates ER stress. Conclusions: The findings suggest that BHSSC exerts its effects through modulation of metabolic pathways, leading to the suppression of cell proliferation, inhibition of cell migration, and activation of the endoplasmic reticulum. These results provide valuable insights into the mechanisms underlying the therapeutic effects of BHSSC in GC and support its potential as a novel treatment option.

Rapid Plasma Electrolytic Oxidation Synthesis of Intermetallic PtBi/MgO/Mg Monolithic Catalyst for Efficient Removal of Organic Pollutants.

The intermetallic PtBi/MgO/Mg monolithic catalyst was first prepared using non-equilibrium plasma electrolytic oxidation (PEO) technology. Spherical aberration-corrected transmission electron microscope (ACTEM) observation confirms the successful synthesis of the PtBi intermetallic structure. The efficiency of PtBi/Mg/MgO catalysts in catalyzing the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of NaBH4 was demonstrated. The activity factor for the catalyst is 31.8 s-1 g-1, which is much higher than reported values. In addition, the resultant catalyst also exhibits excellent catalytic activity in the organic pollutant reaction of p-nitrobenzoic acid (p-NBA) and methyl orange (MO). Moreover, benefiting from ordered atomic structures and the half-embedded PtBi nanoparticles (NPs), the catalyst demonstrates excellent stability and reproducibility in the degradation of 4-NP. This study provides an example of a simple method for the preparation of intermetallic structures as catalysts for organic pollutant degradation.