Construction of CXCR4 Receptor-Targeted CuFeSe2 Nano Theranostic Platform and Its Application in MR/CT Dual Model Imaging and Photothermal Therapy.

Introduction: Targeting, imaging, and treating tumors represent major clinical challenges. Developing effective theranostic agents to address these issues is an urgent need. Methods: We introduce an "all-in-one" tumor-targeted theranostic platform using CuFeSe2-based composite nanoparticles (CuFeSe2@PA) for magnetic resonance (MR) and computed tomography (CT) dual model imaging-guided hyperthermia tumor ablation. Plerixafor (AMD3100) is bonded to the surface of CuFeSe2 as a targeting unit. Due to the robust interaction between AMD3100 and the overexpressed Chemokine CXC type receptor 4 (CXCR4) on the membrane of 4T1 cancer cells, CuFeSe2@PA specifically recognizes 4T1 cancer cells, enriching the tumor region. Results: CuFeSe2@PA serves as a contrast agent for T2-weighted MR imaging (relaxivity value of 1.61 mM-1 s-1) and CT imaging. Moreover, it effectively suppresses tumor growth through photothermal therapy (PTT) owing to its high photothermal conversion capability and stability, with minimized side effects demonstrated both in vitro and in vivo. Discussion: CuFeSe2@PA nanoparticles show potential as dual-mode imaging contrast agents for MR and CT and provide an effective means of tumor treatment through photothermal therapy. The surface modification with Plerixafor enhances the targeting ability of the nanoparticles, performing more significant efficacy and biocompatibility in the 4T1 cancer cell model. The study demonstrates that CuFeSe2@PA is a promising multifunctional theranostic platform with clinical application potential.

[Construction effect of fertile cultivated layer in albic soil â Effects of inversion tillage with organic mate-rials on the redistribution of organic matter in surface layer of albic soil]. / 白浆土肥沃耕层构建效应â .不同有机物料深混对白浆土有机质在表层土壤中再分布的影响.

Soil organic matter serves as a crucial indicator for soil quality. Albic soil, characterized by a barrier layer, exhibits limitations in organic matter content, which can adversely affect crop growth and development. To elucidate the impact of deep mixing of various organic materials on the redistribution of organic matter in the surface soil of albic soil could provide theoretical and technical insights for establishing suitable plough layers for albic soil in Northeast China. We conducted a two-year positioning experiment in Shuangyashan, Heilongjiang Province with five treatments, conventional shallow tillage (0-15 cm, CK), inversion tillage (0-35 cm) without or with straw return (T35 and T35+S), inversion tillage with cattle manure (T35+M) and cattle manure plus maize straw (T35+S+M). The results showed that soil fertilization via deep mixing of organic materials to a depth of 35 cm significantly increased maize yield in albic soil, with the T35+S+M treatment demonstrating the most pronounced effect, yielding an average production of 2934.76 kg·hm-2. Compared to CK, the T35 treatment resulted in a significant 8.4% decrease in organic matter content in the tillage layer, a significant 7.6% increase in organic matter in the sub-tillage layer, and a relative richness degree of soil organic matter in the sub-tillage layer increased by 17.5%. Deep mixed return of organic materials following deep ploughing markedly increased organic matter content of the plough layer, with organic matter conversion ranging from 16.3% to 31.0%. In comparison to the T35 treatment, there was no significant increase in soil organic matter content in the T35+S tillage layer and sub-tillage layer. Conversely, soil organic matter content increased by 4.6% and 6.9% in the T35+M and T35+S+M treatments, with corresponding increase of 11.2% and 15.4% in sub-tillage layer, respectively. Additionally, the soil organic matter richness index in sub-tillage layer increased by 2.5% and 5.1%, respectively. There was a significant positive correlation between organic matter content in the entire plough layer and maize yield, with a contribution rate of 17.5%. Therefore, the utilization of organic fertilizer or a combination of organic fertilizer and straw deep mixing can quickly fertilize albic soil by increasing soil organic matter content in both the whole tillage layer (0-35 cm) and the sub-tillage layer (15-35 cm).

Predictive value of serum alanine aminotransferase for fatty liver associated with metabolic dysfunction.

In this editorial, we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology (2024; 30: 1346-1357). The study highlights a noteworthy association between persistently elevated, yet high-normal levels of alanine transaminase (ALT) and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD has emerged as a globally prevalent chronic liver condition, whose incidence is steadily rising in parallel with improvements in living standards. Left unchecked, MAFLD can progress from hepatic steatosis to liver fibrosis, cirrhosis, and even hepatocellular carcinoma, underscoring the importance of early screening and diagnosis. ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage. While ALT levels demonstrate a significant correlation with the severity of fatty liver disease, they lack specificity. The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels. Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD, emphasizing the need for closer monitoring and potential intervention in such cases.

Rapid and accurate quantification of trypsin activity using integrated infrared and ultraviolet spectroscopy with data fusion techniques.

Proteases play a crucial role in industrial enzyme formulations, with activity fluctuations significantly impacting product quality and yield. Therefore, developing a method for precise and rapid detection of protease activity is paramount. This study aimed to develop a rapid and accurate method for quantifying trypsin activity using integrated infrared (IR) and ultraviolet (UV) spectroscopy combined with data fusion techniques. The developed method evaluates the enzymatic activity of trypsin under varying conditions, including temperature, pH, and ionic strength. By comparing different data fusion methods, the study identifies the optimal model for accurate enzyme activity prediction. The results demonstrated significant improvements in predictive performance using the feature-level data fusion approach. Additionally, substituting the spectral data of the samples in the validation sets into the best prediction model resulted in a minimal residual difference between predicted and true values, further verifying the model's accuracy and reliability. This innovative approach offers a practical solution for the efficient and precise quantification of enzyme activity, with broad applications in industrial processes.

Adaptability to the environment of protease by secondary structure changes and application to enzyme-selective hydrolysis.

The reactions involving enzymes are significantly influenced by various environmental factors. Clarity of how the activity and structure of proteases impact their function is crucial for more efficient application of enzymes as a tool. The impact of temperature, pH, and ionic strength on changes in protease activity, secondary structure, and protein conformation during enzymatic hydrolysis were investigated in this study. The enzymatic activity and secondary structure of acid-base protease were found to undergo significant modifications under different physical conditions, as demonstrated by UV spectrophotometry and FTIR spectroscopy analysis. Specifically, variations in α-helix and ß-fold content were observed to correlate with changes in enzyme activity. Molecular simulation analysis revealed that physical conditions have varying effects on the protease, particularly influencing enzyme activity and secondary structure. Evaluation of the proteases indicated alterations in both enzyme activity and structure. This treatment selectively hydrolyzed ß-lactoglobulin and reduced sensitization. These findings offer novel perspectives on the functionalities and regulatory mechanisms of proteases, as well as potential industrial applications.

The mechanism and promising therapeutic strategy of diabetic cardiomyopathy dysfunctions: Focus on pyroptosis.

Diabetes is a major risk factor for cardiovascular diseases, and myocardial damage caused by hyperglycemia is the main cause of heart failure. However, there is still a lack of systematic understanding of myocardial damage caused by diabetes. At present, we believe that the cellular inflammatory damage caused by hyperglycemia is one of the causes of diabetic cardiomyopathy. Pyroptosis, as a proinflammatory form of cell death, is closely related to the occurrence and development of diabetic cardiomyopathy. Therefore, this paper focuses on the important role of inflammation in the occurrence and development of diabetic cardiomyopathy. From the perspective of pyroptosis, we summarize the pyroptosis of different types of cells in diabetic cardiomyopathy and its related signaling pathways. It also summarizes the treatment of diabetic cardiomyopathy, hoping to provide methods for the prevention and treatment of diabetic cardiomyopathy by inhibiting pyroptosis.

[Ferroptosis in the testis: Progress in research].

Ferroptosis is a form of cell death resulting from the disruption of iron metabolism within cells and excessive accumulation of lipid peroxides. Research indicates that, under the influence of various pathogenic factors, ferroptosis impacts the male reproductive system and fertility by affecting the synthesis of testicular hormones and regulation of cellular functions through different pathways and numerators. This paper provides an overview of the action mechanisms of ferroptosis in the testis and its correlation with pathogenicity, offering some new insights into the treatment of male reproductive system diseases.

Hyperreactio luteinalis and follicle-stimulating hormone receptor gene activation mutations: A case report.

INTRODUCTION AND IMPORTANCE: Spontaneous ovarian luteal hyperfunction after pregnancy is associated with activating mutations in the follicle-stimulating hormone receptor gene, and clarification of the etiology can help with subsequent treatment. PRESENTATION OF CASE: A 32-year-old woman presented with enlarged ovaries and bilateral ovarian polycystic echoes at 12 weeks of both pregnancies. The first pregnancy underwent transabdominal bilateral ovarian aspiration at 17 weeks and was spontaneously aborted 4 days after the procedure. After the discovery of bilateral ovarian polycystic echoes in the second pregnancy, genetic testing suggested the presence of activating mutations in the follicle-stimulating hormone receptor (FSHR) gene, resulting in ovarian luteinization, and the patient's condition was stabilized after conservative treatment. CLINICAL DISCUSSION: Ovarian luteal hyperfunction may be associated with hyperandrogenemia, thyroid-stimulating hormone abnormalities, abnormal testosterone levels, and genetic mutations. When ovarian luteal hyperfunction occurs, it is recommended to search for the etiology and treat the symptoms. CONCLUSION: Patients presenting with spontaneous ovarian hyperlutealization should be operated on cautiously, treated conservatively, closely observed, and managed for complications, and genetic testing should be performed to clarify the etiology if necessary.

Enhanced Cardiomyocyte NLRP3 Inflammasome-Mediated Pyroptosis Promotes d-Galactose-Induced Cardiac Aging.

BACKGROUND: Cardiac aging represents an independent risk factor for aging-associated cardiovascular diseases. Although evidence suggests an association between NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome formation and numerous cardiovascular diseases, its role in cardiac aging remains largely unclear. METHODS AND RESULTS: The longevity of mice with wild-type and NLRP3 knockout (NLRP3-/-) genotypes was assessed, with or without d-galactose treatment. Cardiac function was evaluated using echocardiography, and cardiac histopathology was examined through hematoxylin and eosin and Masson's trichrome staining. Senescence-associated ß-galactosidase (SA-ß-gal) staining was employed to detect cardiac aging. Western blotting was used to assess aging-related proteins (p53, p21) and pyroptosis-related proteins. Additionally, dihydroethidium staining, lactate dehydrogenase release, and interleukin-1ß ELISA assays were performed, along with measurements of total superoxide dismutase and malondialdehyde levels. In vitro, H9c2 cells were exposed to d-galactose for 24 hours in the absence or presence of N-acetyl-l-cysteine (reactive oxygen species inhibitor), BAY-117082 (nuclear factor κ-light-chain enhancer of activated B cells inhibitor), MCC950 (NLRP3 inhibitor), and VX-765 (Caspase-1 inhibitor). Immunofluorescence staining was employed to detect p53, gasdermin D, and apoptosis-associated speck-like protein proteins. Intracellular reactive oxygen species levels were assessed using fluorescence microscopy and flow cytometry. Senescence-associated ß-galactosidase staining and Western blotting were also employed in vitro for the same purpose. The results showed that NLRP3 upregulation was implicated in aging and cardiovascular diseases. Inhibition of NLRP3 extended life span, mitigated the aging phenotype, improved cardiac function and blood pressure, ameliorated lipid metabolism abnormalities, inhibited pyroptosis in cardiomyocytes, and ultimately alleviated cardiac aging. In vitro, the inhibition of reactive oxygen species, nuclear factor κ-light-chain enhancer of activated B cells, NLRP3, or caspase-1 attenuated NLRP3 inflammasome-mediated pyroptosis. CONCLUSIONS: The reactive oxygen species/nuclear factor κ-light-chain enhancer of activated B cells/NLRP3 signaling pathway loop contributes to d-galactose-treated cardiomyocyte senescence and cardiac aging.

W-Shaped π-Extended Double Undecabenzo[7]helicene.

A chiral W-shaped fully π-extended double [7]helicene (ED7H) has been synthesized and fully characterized. It displays fluorescence emission (λem = 636 nm) with a quantum yield (Φf) of 0.10. In comparison to its X-shaped and monomict π-extended [7]helicene analogues, enantiopure W-shaped ED7H exhibited superior chiral optical characteristics, including distinct circular dichroism signals from 400 to 650 nm, a good dissymmetric emission factor |glum| of 4 × 10-3, and a circularly polarized luminescence brightness value BCPL of 42 M-1 cm-1.

Generation of an induced pluripotent stem cell line (CSBZZUi001-A) from a female Alzheimer's patient carrying the PSEN1 709 T > C heterozygous mutation.

Pluripotent stem cells were generated through the electroporation of episomal plasmids, containing crucial reprogramming factors, into skin fibroblasts extracted from a female Alzheimer's patient harboring the PSEN1 709 T > C (p.Phe237Leu) heterozygous mutation. The pluripotent stem cells exhibit a normal karyotype and express pivotal stem cell markers including TRA-1-60, Nanog, SOX2, and OCT4. Furthermore, their capacity to differentiate into the three germ layers in in vivo teratoma experiments has been substantiated. The pluripotent stem cell line can serve as a cellular model for Alzheimer's disease, offering significant value in elucidating the pathogenesis and therapeutic strategies of the disease.

Genetic evidence for the causal impact of insomnia on gastrointestinal diseases and the mediating effects of adiposity traits.

BACKGROUND AND AIM: Insomnia has been implicated in gastrointestinal diseases (GIs), but the causal effect between insomnia and GIs and underlying mechanisms remain unknown. METHODS: By using the released summary-level data, we conducted a two-step Mendelian randomization (MR) analysis to examine the relationship between insomnia and four GIs and estimate the mediating role of candidate mediators. The first step was to investigate the causal association between insomnia and GIs using univariable MR analysis. The second step was to estimate the mediation proportion of selected mediators in these associations using multivariable MR analysis. Subsequently, results from different datasets were combined using the fixed-effect meta-analysis. RESULTS: Univariable MR analysis provided strong evidence for the causal effects of insomnia on four GIs after Bonferroni correction for multiple comparisons, including peptic ulcer disease (PUD) (odds ratio [OR] = 1.15, 95% interval confidence [CI] = 1.10-1.20, P = 1.83 × 10-9), gastroesophageal reflux (GORD) (OR = 1.19, 95% CI = 1.16-1.22, P = 5.95 × 10-42), irritable bowel syndrome (IBS) (OR = 1.18, 95% CI = 1.15-1.22, P = 8.69 × 10-25), and inflammatory bowel disease (IBD) (OR = 1.09, 95% CI = 1.03-1.05, P = 3.46 × 10-3). In the mediation analysis, body mass index (BMI) and waist-to-hip ratio (WHR) were selected as mediators in the association between insomnia and PUD (BMI: mediation proportion [95% CI]: 13.61% [7.64%-20.70%]; WHR: 8.74% [5.50%-12.44%]) and GORD (BMI: 11.82% [5.94%-18.74%]; WHR: 7.68% [4.73%-11.12%]). CONCLUSIONS: Our findings suggest that genetically instrumented insomnia has causal effects on PUD, GORD, IBS, and IBD, respectively. Adiposity traits partially mediated the associations between insomnia and GIs. Further clinical studies are warranted to evaluate the protective effect of insomnia treatment on GIs.

Artificial intelligence in dentistry: A bibliometric analysis from 2000 to 2023.

Background/purpose: Artificial intelligence (AI) is reshaping clinical practice in dentistry. This study aims to provide a comprehensive overview of global trends and research hotspots on the application of AI to dentistry. Materials and methods: Studies on AI in dentistry published between 2000 and 2023 were retrieved from the Web of Science Core Collection. Bibliometric parameters were extracted and bibliometric analysis was conducted using VOSviewer, Pajek, and CiteSpace software. Results: A total of 651 publications were identified, 88.7 % of which were published after 2019. Publications originating from the United States and China accounted for 34.5 % of the total. The Charité Medical University of Berlin was the institution with the highest number of publications, and Schwendicke and Krois were the most active authors in the field. The Journal of Dentistry had the highest citation count. The focus of AI in dentistry primarily centered on the analysis of imaging data and the dental diseases most frequently associated with AI were periodontitis, bone fractures, and dental caries. The dental AI applications most frequently discussed since 2019 included neural networks, medical devices, clinical decision support systems, head and neck cancer, support vector machine, geometric deep learning, and precision medicine. Conclusion: Research on AI in dentistry is experiencing explosive growth. The prevailing research emphasis and anticipated future development involve the establishment of medical devices and clinical decision support systems based on innovative AI algorithms to advance precision dentistry. This study provides dentists with valuable insights into this field.

Supplier selection in green supply chain management using correlation-based TOPSIS in a q-rung orthopair fuzzy soft environment.

Fuzzy hybrid models are efficient mathematical tools for managing unclear and vague data in real-world scenarios. This research explores the q-rung orthopair fuzzy soft set (q-ROFSS), which presents incomplete and ambiguous details in decision-making problems. The main intention of this study is to describe and evaluate the characteristics of the correlation coefficient (CC) and weighted correlation coefficient (WCC) for q-ROFSS. Also, the technique for order preference should be enhanced by similarity to the ideal solution (TOPSIS) with extended measures in q-ROFSS settings. Furthermore, we integrated mathematical formulations of correlation obstructions to confirm the consistency of the planned technique. It helps handle difficulties involving multi-attribute group decision-making (MAGDM). Moreover, a numerical illustration is presented to clarify how the advocated decision-making methodology can be implemented in evaluating suppliers in green supply chain management (GSCM). As a result, each alternative is assessed using multiple criteria, such as quality and reliability, capacity and scalability, compliance and certifications, and sustainability practices. The technique proposed in this study retains the selected research's specific structure more effectively than current techniques. A comparative analysis further substantiates the feasibility and effectiveness of the proposed approach over other decision-making techniques.

Iridium(III) carbene complexes as potent girdin inhibitors against metastatic cancers.

Many cancer-driving protein targets remain undruggable due to a lack of binding molecular scaffolds. In this regard, octahedral metal complexes with unique and versatile three-dimensional structures have rarely been explored as inhibitors of undruggable protein targets. Here, we describe antitumor iridium(III) pyridinium-N-heterocyclic carbene complex 1a, which profoundly reduces the viability of lung and breast cancer cells as well as cancer patient-derived organoids at low micromolar concentrations. Compound 1a effectively inhibits the growth of non-small-cell lung cancer and triple-negative breast cancer xenograft tumors, impedes the metastatic spread of breast cancer cells, and can be modified into an antibody-drug conjugate payload to achieve precise tumor delivery in mice. Identified by thermal proteome profiling, an important molecular target of 1a in cellulo is Girdin, a multifunctional adaptor protein that is overexpressed in cancer cells and unequivocally serves as a signaling hub for multiple pivotal oncogenic pathways. However, specific small-molecule inhibitors of Girdin have not yet been developed. Notably, 1a exhibits high binding affinity to Girdin with a Kd of 1.3 µM and targets the Girdin-linked EGFR/AKT/mTOR/STAT3 cancer-driving pathway, inhibiting cancer cell proliferation and metastatic activity. Our study reveals a potent Girdin-targeting anticancer compound and demonstrates that octahedral metal complexes constitute an untapped library of small-molecule inhibitors that can fit into the ligand-binding pockets of key oncoproteins.

[Effect of Low-density Polyethylene Microplastics on Natural Attenuation of Oxygenated Polycyclic Aromatic Hydrocarbons in Soil].

The continuous accumulation of microplastics in agricultural soils may affect the natural attenuation of oxygen-containing polycyclic aromatic hydrocarbons (OPAHs). The effects of low-density polyethylene (LDPE) microplastics with the spiking proportion of 1 % and 0.01 % in soils on the natural attenuation of OPAHs were investigated via soil microcosm experiments. The relation between the response of bacterial communities and OPAHs dissipation was also explored. The initial content of OPAHs in the soil was 34.6 mg·kg-1. The dissipation of OPAHs in the soil on day 14 was inhibited by LDPE. The contents of OPAHs in LDPE groups were higher than that in the control by 0.9-1.6 mg·kg-1, and the inhibition degree increased with the proportion of LDPE. The contents of OPAHs were not significantly different among groups on day 28, indicating that the inhibitory effect of LDPE disappeared. LDPE did not change the composition of the dominant taxa in the OPAHs-contaminated soil community but influenced the relative abundances of some dominant taxa. LDPE increased the relative abundance of Proteobacteria and Actinobacteria at the phylum level and decreased that of Bacillus and increased those of Micromonospora, Sphingomonas, and Nitrospira (potential degrading bacteria of LDPE and endogenous substances) at the genus level, all four of which were the main genera dominating intergroup community differences. LDPE changed the α and ß diversity of bacterial communities, but the extents were not significant. LDPE affected the function of the bacterial community, reducing the total abundance of PAHs-degrading genes and some degrading enzymes, inhibiting the growth of PAHs-degrading bacteria and thus interfering with the natural decay of OPAHs.

Honokiol and magnolol: A review of structure-activity relationships of their derivatives.

Honokiol (HK) and magnolol (MAG) are typical representatives of neolignans possessing a wide range of biological activities and are employed as traditional medicines in Asia. In the past few decades, HK and MAG have been proven to be promising chemical scaffolds for the development of novel neolignan drugs. This review focuses on recent advances in the medicinal chemistry of HK and MAG derivatives, especially their structure-activity relationships. In addition, it also presents a comprehensive summary of the pharmacology, biosynthetic pathways, and metabolic characteristics of HK and MAG. This review can provide pharmaceutical chemists deeper insights into medicinal research on HK and MAG, and a reference for the rational design of HK and MAG derivatives.

Safety and hematological toxicities of PARP inhibitors in patients with cancer: a systematic review of randomized controlled trials and a pharmacovigilance analysis.

INTRODUCTION: This study aimed to estimate the toxicities of PARP inhibitors (PARPis), based on randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS) database. METHODS: Four electronic databases were searched from inception to 16 April 2024, for RCTs of approved PARPis. The primary and secondary outcomes were grade 3-5 adverse events (AEs) and grade 3-5 hematological AE, respectively. We conducted network meta-analyses to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of outcomes. A disproportionality analysis was conducted to estimate the signals of hematological AEs associated with PARPis from the FAERS database. RESULTS: Overall, 27 RCTs involving 11,067 patients with cancer were included. Olaparib had the best safety profile for any grade 3-5 AEs and hematological AEs among four approved PARPis. Olaparib did not increase the risk of thrombocytopenia (RR: 1.48; 95%CI: 0.64-3.39), but other PARPis did. Furthermore 14,780 hematological AE reports associated with PARPis were identified in the FAERS database, and all PARPis were associated with strong hematological AE signals. Hematological AEs mainly occurred within the first 3 months (80.84%) after PARPi initiation. CONCLUSION: Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months. REGISTRATION: PROSPERO (CRD42022385274).