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1.
Anal Chim Acta ; 1325: 343121, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39244307

ABSTRACT

BACKGROUND: Despite significant advancements in detecting Cd(II) using nanomaterials-modified sensitive interfaces, most detection methods rely solely on a single electrochemical stripping current to indicate concentration. This approach often overlooks potential inaccuracies caused by interference from coexisting ions. Therefore, establishing multi-dimensional signals that accurately reflect Cd(II) concentration in solution is crucial. RESULTS: In this study, we developed a system integrating concentration, electrochemical stripping current, and laser-induced breakdown spectroscopy (LIBS) characteristic peak intensity through in-situ laser-induced breakdown spectroscopy and electrochemical integrated devices. By simultaneously acquiring multi-dimensional signals to dynamically track the electrochemical deposition and stripping processes, we observed that replacement reactions occur between Cu(II) and Cd(II) on the surface of Ru-doped MoS2 modified carbon paper electrodes (Ru-MoS2/CP). These reactions facilitate the oxidation of Cd(0) to Cd(II) during the stripping process, significantly increasing the currents of Cd(II). Remarkably, the ingenious design of the Ru-MoS2 sensitive interface allowed for the undisturbed deposition of Cu(II) and Cd(II) during the electrochemical deposition process. Consequently, our in-situ integrated device achieved accurate detection of Cd(II) in complex environments, boasting a detection sensitivity of 8606.5 counts µM⁻1. SIGNIFICANCE: By coupling multi-dimensional signals from stripping current and LIBS spectra, we revealed the interference process between Cu(II) and Cd(II), providing valuable insights for accurate electrochemical analysis of heavy metal ions in complex water environments.

2.
Biol Direct ; 19(1): 78, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39242533

ABSTRACT

Choriocarcinoma is a malignant cancer that belongs to gestational trophoblastic neoplasia (GTN). Herein, serum metabolomic analysis was performed on 29 GTN patients and 30 healthy individuals to characterize the metabolic variations during GTN progression. Ultimately 24 differential metabolites (DMs) were identified, of which, Equol was down-regulated in GTN patients, whose VIP score is the 3rd highest among the 24 DMs. As an intestinal metabolite of daidzein, the anticancer potential of Equol has been demonstrated in multiple cancers, but not choriocarcinoma. Hence, human choriocarcinoma cell lines JEG-3 and Bewo were used and JEG-3-derived subcutaneous xenograft models were developed to assess the effect of Equol on choriocarcinoma. The results suggested that Equol treatment effectively suppressed choriocarcinoma cell proliferation, induced cell apoptosis, and reduced tumorigenesis. Label-free quantitative proteomics showed that 136 proteins were significantly affected by Equol and 20 proteins were enriched in Gene Ontology terms linked to protein degradation. Tripartite motif containing 21 (TRIM21), a E3 ubiquitin ligase, was up-regulated by Equol. Equol-induced effects on choriocarcinoma cells could be reversed by TRIM21 inhibition. Annexin A2 (ANXA2) interacted with TRIM21 and its ubiquitination was modulated by TRIM21. We found that TRIM21 was responsible for proteasome-mediated degradation of ANXA2 induced by Equol, and the inhibitory effects of Equol on the malignant behaviors of choriocarcinoma cells were realized by TRIM21-mediated down-regulation of ANXA2. Moreover, ß-catenin activation was inhibited by Equol, which also depended on TRIM21-mediated down-regulation of ANXA2. Taken together, Equol may be a novel candidate for the treatment for choriocarcinoma.


Subject(s)
Annexin A2 , Choriocarcinoma , Equol , Ubiquitination , Humans , Female , Annexin A2/metabolism , Annexin A2/genetics , Choriocarcinoma/metabolism , Choriocarcinoma/genetics , Equol/pharmacology , Cell Line, Tumor , Ubiquitination/drug effects , Animals , Mice , Cell Proliferation/drug effects , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Pregnancy , Mice, Nude , Uterine Neoplasms/metabolism , Uterine Neoplasms/drug therapy , Uterine Neoplasms/genetics , Mice, Inbred BALB C
3.
J Ethnopharmacol ; 337(Pt 1): 118784, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39244176

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR), the dried root and rhizome of Sophora tonkinensis Gagnep., is commonly used in the treatment of tonsillitis and pharyngitis, throat soreness and throat obstruction, swelling and aching of gum, etc. in China or other Asian countries. STR is usually used as the core herb in traditional Chinese medicine preparations, such as "Biyanling Tablets", "Fufang Muji Granules" and "Ganyanling Injections", etc. AIM OF THE REVIEW: This review aimed to provide a comprehensive analysis of STR in terms of botany, traditional use, phytochemistry, ethnopharmacology, pharmacology, pharmacokinetics, toxicology and detoxification strategy, to provide a rational application in future research. MATERIALS AND METHODS: The information involved in the study was gathered from a variety of electronic resources, including China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations. RESULTS: Till now, a total of 333 chemical components have been identified in STR, including 85 alkaloids, 124 flavonoids, 24 triterpenes, 27 triterpene saponins, 34 organic acids, 8 polysaccharides, etc. STR and its main active constituents have cardiovascular protection, anti-tumor activity, anti-inflammatory activity, antipyretic activity, analgesic activity, antibacterial activity, antifungal activity, antiviral activity, and hepatoprotective activity, etc. However, toxic effects of STR on the liver, nerves, heart, and gastrointestinal tract have also been observed. To mitigate these risks, STR needs attenuation before use, with the most common detoxification methods being processing and combined use with other drugs. The pharmacokinetics of STR in vivo and traditional and clinical prescriptions containing STR have been sorted out. Despite the potential therapeutic benefits of STR, further research is warranted to elucidate its hepatotoxicity, particularly in vivo, exploring aspects such as in vivo metabolism, distribution, and mechanisms. CONCLUSION: This review serves to emphasize the therapeutic potential of STR and highlights the crucial need to address its toxicity concerns before considering clinical application. Further research is required to comprehensively investigate the toxicological properties of STR, with particular emphasis on its hepatotoxicity and neurotoxicity. Such research endeavors have the potential to standardize the rational application of STR for optimal therapeutic outcomes.

4.
Microbiol Spectr ; : e0340623, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39240085

ABSTRACT

Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens. IMPORTANCE: Our study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

5.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1653-1660, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39235024

ABSTRACT

The construction of road infrastructure has resulted in the degradation of wildlife habitat and the decrease of ecological network connectivity and stability. Studying the impacts of road infrastructure on wildlife life and migration is significant for regional wildlife conservation and ecological network optimization. We assessed the impacts of road infrastructure on habitat suitability using the MaxEnt model based on wildlife occurrence point data in the Guangdong-Hong Kong-Macao Greater Bay Area. We constructed the ecological networks and identified ecological breakpoints using the minimum cumulative resistance model, and compared the ecological network connectivity of different scenarios with the landscape connectivity index and graph theory index. The results showed that railway and motorway significantly affected habitat suitability, causing a decrease in wildlife habitat suitability. Affected by road infrastructure, the fragmentation of ecological sources intensified, the resistance of ecological corridors increased, and the ecological network connectivity and stability significantly decreased. A total of 536 ecological breakpoints were identified, which were concentrated in the area adjacent to ecological sources. The results would provide important scientific references for wildlife habitat conservation and ecological restoration in the Guangdong-Hong Kong-Macao Greater Bay Area.


Subject(s)
Conservation of Natural Resources , Ecosystem , China , Animals , Animals, Wild/growth & development , Bays , Ecology , Hong Kong , Models, Theoretical , Transportation , Railroads
6.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1645-1652, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39235023

ABSTRACT

In the hilly region of Chinese Loess Plateau, rainwater harvesting is a common ecological engineering measure utilized to reduce soil erosion and amplify the efficiency of water resource utilization. However, the effects on rainwater harvesting and the chief influencing factors of biocrusts as a potential material are unclear. In this study, we conducted a field simulation experiment with intensities of 40, 60, 80, and 100 mm·h-1 between bare soil and biocrusts developed in aeolian soils, with bare soil as a control to explore the differences of the initial abstraction time, cumulative rainfall amount, and rainfall harvesting efficiency. We further analyzed the influencing factors of the rainwater harvesting effect. The results showed that the biocrusted soil-surfaces significantly decreased the initial abstraction time. When compared with the cyano biocrusts and bare soil, the reduction of the initial abstraction time of moss biocrusts was decreased by 49.7%-77.5% and 89.7%-110.0% when the rainfall intensities ranged from 40 to 100 mm·h-1 and the slope was 40°. In addition, biocrusted soil surfaces significantly increased the cumulative rainfall amount and rainfall harvesting efficiency. These differences were considerable amongst the dissimilar surface cover types. In comparison to bare soil, when the rainfall intensity was 100 mm·h-1 and the slope was 40°, the cumulative rainfall harvesting efficiency of moss and cyano biocrusts was increased by 29.6% and 7.8%, respectively. Both moss and cyano biocrusts increased rainfall harvesting efficiency of 25.7% and 6.8%, respectively. Variance analysis demonstrated that the rainfall harvesting efficiency was appreciably affected by surface cover type, slope, and rainfall intensity. The interaction between these factors was considerable except for slope and rainfall intensity. Additionally, important considerations for the actual construction included slope length, slope, and biocrust cultivation. In conclusion, biocrusted soil-surfaces have a high rainfall harvesting efficiency, but moss biocrusts have a much greater rain-collecting effect that improves even more as the slope and intensity of the rain increases.


Subject(s)
Rain , Soil , China , Soil/chemistry , Conservation of Natural Resources , Altitude , Soil Erosion/prevention & control , Ecosystem , Bryophyta/growth & development
7.
J Ethnopharmacol ; 337(Pt 1): 118783, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39244175

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxyli Radix (ZR), the dry root of Zanthoxylum nitidum (Roxb.) DC (ZN) is known as Liang Mian Zhen in China and has been the preferred Chinese medicine for the treatment of inflammation and cancer disease at home and abroad. ZR has been used as the core ingredient in anti-inflammatory traditional medicines, such as Sanjiuweitai granules and Jinji tablets, etc. AIM OF THE WORK: This review aimed to provide a comprehensive overview of ZR in terms of traditional uses, quality control, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics. Meanwhile, the anti-inflammatory substances and mechanism of ZR were emphasized, to offer new perspectives and broad scopes for future studies. MATERIALS AND METHODS: The information was retrieved from Web of Science, Researchgate, Google Scholar, SciFinder, X-MOL, PubMed, China National Knowledge Infrastructure (CNKI), Chinese Masters and Doctoral Dissertations, and Elsevier between 1984 and 2024. RESULTS: Till now, a total of 184 chemical components have been identified in ZR, including 91 alkaloids, 22 lignans, 4 flavonoids, 19 coumarins, 17 terpenoids, and 31 other types. Pharmacological studies have proved that ZR had a variety of biological activities, such as anti-tumour, antibacterial, antioxidant and other activities, particularly in anti-inflammation. ZR exerts anti-inflammatory disease effects by modulating various signaling pathways, including MAPK, NF-κB, P13/AKT and JAK/STAT. Pharmacokinetic studies have shown that ZR exhibits low absorption rates, broad distribution, and rapid metabolism. Additionally, this review also revealed the shortcomings of current research on ZR and possible future research directions. CONCLUSION: Extensive literature analysis indicates that ZR and its bioactive constituents possess diverse pharmacological activities, especially anti-inflammation. Moreover, in order to promote the safety and adaptability of ZR in clinical application, it is also strongly recommended that further research should focus on toxicity studies, pharmacokinetic studies of herb-drug interactions, and quality control.

8.
Neurol Sci ; 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39266808

ABSTRACT

BACKGROUND: Primary Meige syndrome (PMS) is a rare form of dystonia, and comparative analysis of globus pallidus internal deep brain stimulation (GPi-DBS), subthalamic nucleus deep brain stimulation (STN-DBS), and pallidotomy has been lacking. This study aims to compare the efficacy, safety, and psychiatric features of GPi-DBS, STN-DBS, and pallidotomy in patients with PMS. METHODS: This prospective cohort study was divided into three groups: GPi-DBS, STN-DBS, and pallidotomy. Clinical assessments, including motor and non-motor domains, were evaluated at baseline and at 1 year and 3 years after neurostimulation/surgery. RESULTS: Ninety-eight patients were recruited: 46 patients received GPi-DBS, 34 received STN-DBS, and 18 underwent pallidotomy. In the GPi-DBS group, the movement score of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) improved from a mean (SE) of 13.8 (1.0) before surgery to 5.0 (0.7) (95% CI, -10.5 to -7.1; P < 0.001) at 3 years. Similarly, in the STN-DBS group, the mean (SE) score improved from 13.2 (0.8) to 3.5 (0.5) (95% CI, -10.3 to -8.1; P < 0.001) at 3 years, and in the pallidotomy group, it improved from 14.9 (1.3) to 6.0 (1.1) (95% CI, -11.3 to -6.5; P < 0.001) at 3 years. They were comparable therapeutic approaches for PMS that can improve motor function and quality of life without non-motor side effects. CONCLUSIONS: DBS and pallidotomy are safe and effective treatments for PMS, and an in-depth exploration of non-motor symptoms may be a new entry point for gaining a comprehensive understanding of the pathophysiology.

9.
Vet Parasitol ; 331: 110296, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39217762

ABSTRACT

Coccidiosis is an important parasitic disease that has serious adverse effects on the global poultry industry. The mechanism by which the pathogenic factors of Eimeria tenella damage host cells is unknown. Some kinases from the rhoptry compartment can regulate apoptosis of host cells. This study focused on revealing the role and critical nodes of E. tenella rhoptry protein (EtROP) 38 in controlling the apoptosis of host cells via the P38 mitogen-activated protein kinase (MAPK) signaling pathway. The cells were treated with EtROP38 protein, siRNA p38MAPK, or both. The rate of infection, apoptosis, and the dynamic changes in the expression and activation of key factor genes of the P38MAPK signaling pathway in host cells infected with E. tenella were measured. The results showed that the addition of EtROP38 and/or knockdown of the host cells p38 gene reduced the apoptosis rate of cecal epithelial cells (CECS), decreased the mRNA expressions of p38, p53, c-myc, c-fos, and c-jun and increased the expression of p65, decreased the protein expressions of c-myc, c-fos, and c-jun, decreased the p38 protein phosphorylation level, and increased the p65 protein phosphorylation level in CECS. When E. tenella was inoculated for 4-96 h, the addition of Et ROP38 and/or host cell p38 knockdown both increased the infection rate of host cells, and this effect was more pronounced with the addition of EtROP38 with the host cell p38 knockdown. These observations indicate that E. tenella can inhibits the activation of the p38MAPK signaling pathway in host cells via EtROP38, which suppresses apoptosis in host cells.


Subject(s)
Apoptosis , Chickens , Eimeria tenella , p38 Mitogen-Activated Protein Kinases , Eimeria tenella/physiology , Animals , p38 Mitogen-Activated Protein Kinases/metabolism , p38 Mitogen-Activated Protein Kinases/genetics , Poultry Diseases/parasitology , Protozoan Proteins/metabolism , Protozoan Proteins/genetics , Coccidiosis/parasitology , Coccidiosis/veterinary , MAP Kinase Signaling System , Epithelial Cells/parasitology , Cecum/parasitology , Signal Transduction
10.
Rapid Commun Mass Spectrom ; 38(19): e9880, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39159996

ABSTRACT

RATIONALE: Isopsoralen (ISO), a quality control marker (Q-marker) in Psoraleae Fructus, is proven to present an obvious anti-osteoporosis effect. Until now, the metabolism and anti-osteoporosis mechanisms of ISO have not been fully elucidated, greatly restricting its drug development. METHODS: The metabolites of ISO in rats were profiled by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential anti-osteoporosis mechanism of ISO in vivo was predicted by using network pharmacology. RESULTS: A total of 15 metabolites were characterized in rats after ingestion of ISO (20 mg/kg/day, by gavage), including 2 in plasma, 12 in urine, 6 in feces, 1 in heart, 3 in liver, 1 in spleen, 1 in lung, 3 in kidney, and 2 in brain. The pharmacology network results showed that ISO and its metabolites could regulate AKT1, SRC, NFKB1, EGFR, MAPK3, etc., involved in the prolactin signaling pathway, ErbB signaling pathway, thyroid hormone pathway, and PI3K-Akt signaling pathway. CONCLUSIONS: This is the first time for revealing the in vivo metabolism features and potential anti-osteoporosis mechanism of ISO by metabolite profiling and network pharmacology, providing data for further verification of pharmacological mechanism.


Subject(s)
Furocoumarins , Network Pharmacology , Psoralea , Rats, Sprague-Dawley , Animals , Furocoumarins/pharmacology , Furocoumarins/chemistry , Psoralea/chemistry , Rats , Chromatography, High Pressure Liquid/methods , Male , Osteoporosis/drug therapy , Osteoporosis/metabolism , Quality Control , Biomarkers/analysis , Biomarkers/metabolism , Biomarkers/urine , Fruit/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Mass Spectrometry/methods , Bone Density Conservation Agents/pharmacology , Metabolome/drug effects , Metabolomics/methods
11.
Phytother Res ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39120474

ABSTRACT

Calycosin (Caly), a flavonoid compound, demonstrates a variety of beneficial properties. However, the specific mechanisms behind Caly's anticancer effects remain largely unexplored. Network pharmacology was used to explore the potential targets of Caly in renal cancer. Additionally, RNA-seq sequencing was used to detect changes in genes in renal cancer cells after Caly treatment. Validation was carried out through quantitative reverse transcription-PCR and Western blot analysis. The luciferase reporter assay was applied to pinpoint the interaction site between MAZ and HAS2. Furthermore, the immunoprecipitation assay was utilized to examine the ubiquitination and degradation of MAZ. In vivo experiments using cell line-derived xenograft mouse models were performed to assess Calycosin's impact on cancer growth. Network pharmacology research suggests Caly plays a role in promoting apoptosis and inhibiting cell adhesion in renal cancer. In vitro, Caly has been observed to suppress proliferation, colony formation, and metastasis of renal cancer cells while also triggering apoptosis. Additionally, it appears to diminish hyaluronic acid synthesis by downregulating HAS2 expression. MAZ is identified as a transcriptional regulator of HAS2 expression. Calycosin further facilitates the degradation of MAZ via the ubiquitin-proteasome pathway. Notably, Caly demonstrates efficacy in reducing the growth of renal cell carcinoma xenograft tumors in vivo. Our findings indicate that Caly suppresses the proliferation, metastasis, and progression of renal cell carcinoma through its action on the MAZ/HAS2 signaling pathway. Thus, Caly represents a promising therapeutic candidate for the treatment of renal cell carcinoma.

13.
PLoS Negl Trop Dis ; 18(8): e0012428, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39159234

ABSTRACT

BACKGROUND: Schistosomiasis is a relatively neglected parasitic disease that afflicts more than 250 million people worldwide, for which the control strategy relies mainly on mass treatment with the only available drug, praziquantel (PZQ). This approach is not sustainable and is a priority for developing novel drug candidates for the treatment and control of schistosomiasis. METHODOLOGYS/PRINCIPAL FINDINGS: In our previous study, we found that DW-3-15, a kind of PZQ derivative, could significantly downregulate the expression of the histone acetyltransferase of Schistosoma japonicum (SjHAT). In this study, several commercially available HAT inhibitors, A485, C646 and curcumin were screened in vitro to verify their antischistosomal activities against S. japonicum juveniles and adults. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of HAT inhibitors in vitro. Quantitative real-time PCR was employed to detect the mRNA level of SjHAT after treatment with different HAT inhibitors. Our results demonstrated that curcumin was the most effective inhibitor against both juveniles and adults of S. japonicum, and its schistosomicidal effects were time- and dose dependent. However, A485 and C646 had limited antischistosomal activity. Scanning electron microscopy demonstrated that in comparison with DW-3-15, curcumin caused similar tegumental changes in male adult worms. Furthermore, both curcumin and DW-3-15 significantly decreased the SjHAT mRNA level, and curcumin dose-dependently reduced the SjHAT expression level in female, male and juvenile worms. CONCLUSIONS: Among the three commercially available HATs, curcumin was the most potent against schistosomes. Both curcumin and our patent compound DW-3-15 markedly downregulated the expression of SjHAT, indicating that SjHAT may be a potential therapeutic target for developing novel antischistosomal drug candidates.


Subject(s)
Curcumin , Histone Acetyltransferases , Schistosoma japonicum , Animals , Schistosoma japonicum/drug effects , Curcumin/pharmacology , Histone Acetyltransferases/antagonists & inhibitors , Histone Acetyltransferases/metabolism , Histone Acetyltransferases/genetics , Female , Male , Enzyme Inhibitors/pharmacology , Microscopy, Electron, Scanning , Real-Time Polymerase Chain Reaction , Mice , Schistosomicides/pharmacology
14.
Org Lett ; 26(35): 7463-7467, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39190923

ABSTRACT

A bioinspired total synthesis of 3-epi-junipercedrol, which contains a strained tricyclo[5.2.2.03,7]undecane allo-cedrane framework and five stereocenters, was accomplished via an effective anionic semipinacol rearrangement of a tricyclic cedrane mesylate. The corresponding cedrane precursor was synthesized efficiently by employing the reductive oxy-Nazarov cyclization and an intramolecular aldol condensation as the key steps. This synthetic approach provided a further evidence for the biogenetic relationship between the typical cedrane and allo-cedrane sesquiterpenoids.

15.
Bioorg Med Chem Lett ; 112: 129932, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39182737

ABSTRACT

Glycogen synthase kinase 3ß (GSK-3ß) is a potential therapeutic target for the treatment of a variety of human diseases. Here, we report the design and synthesis of a series of thieno[3,2-c]pyrazol-urea derivatives and evaluation of their GSK-3ß inhibitory activity. Among these analogues, the compound without substitution on terminal phenyl ring (3a) was found to be the most potent GSK-3ß inhibitor with an IC50 of 74.4 nM, while substitution on the terminal phenyl (3b-3p) led to decreased potency, independent of the position, size, or electronic properties of the substituents. Kinase selectivity assay revealed that 3a showed good selectivity over a panel of kinases, but was less selective over CDK1, CDK2 and CDK5. Additionally, the pharmacological properties of the synthesized compounds were investigated computationally by the SwissADME and the results showed that most of the compounds have good ADME profiles.


Subject(s)
Drug Design , Glycogen Synthase Kinase 3 beta , Protein Kinase Inhibitors , Pyrazoles , Urea , Pyrazoles/chemistry , Pyrazoles/pharmacology , Pyrazoles/chemical synthesis , Humans , Glycogen Synthase Kinase 3 beta/antagonists & inhibitors , Glycogen Synthase Kinase 3 beta/metabolism , Urea/pharmacology , Urea/analogs & derivatives , Urea/chemistry , Urea/chemical synthesis , Structure-Activity Relationship , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Molecular Structure , Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3/metabolism , Dose-Response Relationship, Drug
16.
Angew Chem Int Ed Engl ; : e202413782, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39193821

ABSTRACT

Cross conjugation, though prevalent in many organic compounds, is typically considered less effective for electron delocalization compared to linear conjugation. Consequently, it is rarely used as the backbone structure for semiconducting conjugated polymers. In this study, we designed and synthesized a novel building block, TIDP, which features a central cyclic dipeptide with cross conjugation characteristics. Strong intramolecular hydrogen bonding interactions confer TIDP with a highly rigid and coplanar conformation. Importantly, theoretical calculations reveal that π electrons are well delocalized across the entire structure, despite its low aromaticity. Conjugated polymers incorporating TIDP exhibit high charge carrier mobilities, demonstrating the effective π electron delocalization of this innovative building block. Our findings show that with rational design, cross conjugation can achieve effective π electron delocalization, providing a valuable approach for developing high-performance conjugated polymers for organic electronic materials.

17.
Bioprocess Biosyst Eng ; 47(9): 1453-1469, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38976006

ABSTRACT

Bio-cement is a green and energy-saving building material that has attracted much attention in the field of ecological environment and geotechnical engineering in recent years. The aim of this study is to investigate the use of bio-cement (enzyme-induced calcium carbonate precipitation-EICP) in combination with admixtures for the improvement of desert sands, which can effectively improve the mechanical properties of desert sands and is particularly suitable for sand-rich countries. In addition, the suitability of tap water in bio-cement was elucidated and the optimum ratio of each influencing factor when tap water is used as a solvent was derived. The results showed that peak values of unconfined compressive strength (maximum increase of about 130 times), shear strength (increase of 27.09%), calcium carbonate precipitation value (increase of about 4.39 times), and permeability (decrease of about 93.72 times) were obtained in the specimens modified by EICP combined with admixture as compared to the specimens modified by EICP only. The incorporation of skimmed milk powder, though significantly increasing the strength, is not conducive to cost control. The microscopic tests show that the incorporation of admixtures can provide nucleation sites for EICP, thus improving the properties of desert sand. This work can provide new research ideas for cross-fertilization between the disciplines of bio-engineering, ecology, and civil engineering.


Subject(s)
Calcium Carbonate , Sand , Sand/chemistry , Calcium Carbonate/chemistry , Construction Materials , Desert Climate , Compressive Strength
18.
Eur J Pharmacol ; 979: 176806, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38986830

ABSTRACT

Chronic kidney disease (CKD) is a clinical syndrome characterized by persistent renal function decline. Renal fibrosis is the main pathological process in CKD, but an effective treatment does not exist. Stratifin (SFN) is a highly-conserved, multi-function soluble acidic protein. Therefore, this study explored the effects of SFN on renal fibrosis. First, we found that SFN was highly expressed in patients with CKD, as well as in renal fibrosis animal and cell models. Next, transforming growth factor-beta 1 (TGF-ß1) induced injury and fibrosis in human renal tubule epithelial cells, and SFN knockdown reversed these effects. Furthermore, SFN knockdown mitigated unilateral ureteral obstruction (UUO)-induced renal tubular dilatation and renal interstitial fibrosis in mice. Liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP), and immunofluorescence co-localization assays demonstrated that SFN bound the non-muscle myosin-encoding gene, myosin heavy chain 9 (MYH9), in the cytoplasm of renal tubular epithelial cells. MYH9 knockdown also reduced Col-1 and α-SMA expression, which are fibrosis markers. Finally, silencing SFN decreased MYH9 expression, alleviating renal fibrosis. These results suggest that SFN promotes renal fibrosis in CKD by interacting with MYH9. This study may provide potential strategies for the treatment of CKD.


Subject(s)
Kidney , Myosin Heavy Chains , Renal Insufficiency, Chronic , Animals , Humans , Male , Mice , Cell Line , Disease Models, Animal , Fibrosis , Kidney/pathology , Kidney/metabolism , Mice, Inbred C57BL , Molecular Motor Proteins/metabolism , Molecular Motor Proteins/genetics , Myosin Heavy Chains/metabolism , Myosin Heavy Chains/genetics , Protein Binding , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , Renal Insufficiency, Chronic/genetics , Transforming Growth Factor beta1/metabolism , Ureteral Obstruction/pathology , Ureteral Obstruction/metabolism , Ureteral Obstruction/complications
19.
J Am Chem Soc ; 146(28): 18841-18847, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38975938

ABSTRACT

An asymmetric intramolecular spiro-amination to high steric hindering α-C-H bond of 1,3-dicarbonyl via nitrene transfer using inactive aryl azides has been carried out by developing a novel Cp*Ir(III)-SPDO (spiro-pyrrolidine oxazoline) catalyst, thereby enabling the first successful construction of structurally rigid spiro-quaternary indolinone cores with moderate to high yields and excellent enantioselectivities. DFT computations support the presence of double bridging H-F bonds between [SbF6]- and both the ligand and substrate, which favors the plane-differentiation of the enol π-bond for nitrenoid attacking. These findings open up numerous opportunities for the development of new asymmetric nitrene transfer systems.

20.
Cell Rep ; 43(7): 114463, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38985675

ABSTRACT

Foliar pigmentation patterns vary among plant species and growth conditions. In this study, we utilize hyperspectral imaging to assess foliar pigmentation in the bryophyte Marchantia polymorpha under nutrient stress and identify associated genetic factors. Using singular value decomposition (SVD) for feature selection, we quantitate color variations induced by deficiencies in phosphate, nitrate, magnesium, calcium, and iron. Pseudo-colored thallus images show that disrupting MpWRKY10 causes irregular pigmentation with auronidin accumulation. Transcriptomic profiling shows that MpWRKY10 regulates phenylpropanoid pathway enzymes and R2R3-MYB transcription factors during phosphate deficiency, with MpMYB14 upregulation preceding pigment accumulation. MpWRKY10 is downregulated in older, pigmented thalli under phosphate deficiency but maintained in young thalli, where it suppresses pigmentation genes. This downregulation is absent in pigmented thalli due to aging. Comparative transcriptome analysis suggests similar WRKY and MYB roles in nutrient response and pigmentation in red-leaf lettuce, alluding to conserved genetic factors controlling foliar pigmentation patterns under nutrient deficiency.


Subject(s)
Gene Expression Regulation, Plant , Hyperspectral Imaging , Marchantia , Pigmentation , Plant Proteins , Pigmentation/genetics , Marchantia/genetics , Marchantia/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Hyperspectral Imaging/methods , Plant Leaves/metabolism , Plant Leaves/genetics , Transcription Factors/metabolism , Transcription Factors/genetics
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