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1.
Article in English | MEDLINE | ID: mdl-38572646

ABSTRACT

BACKGROUND: Glycoursodeoxycholic acid (GUDCA) has been acknowledged for its ability to regulate lipid homeostasis and provide benefits for various metabolic disorders. However, the impact of GUDCA on arterial thrombotic events remains unexplored. The objective of this study is to examine the effects of GUDCA on thrombogenesis and elucidate its underlying mechanisms. METHODS: Plasma samples from patients with arterial thrombotic events and diet-induced obese mice were collected to determine the GUDCA concentrations using mass spectrometry. Multiple in vivo murine thrombosis models and in vitro platelet functional assays were conducted to comprehensively evaluate the antithrombotic effects of GUDCA. Moreover, lipidomic analysis was performed to identify the alterations of intraplatelet lipid components following GUDCA treatment. RESULTS: Plasma GUDCA level was significantly decreased in patients with arterial thrombotic events and negatively correlated with thrombotic propensity in diet-induced obese mice. GUDCA exhibited prominent suppressing effects on platelet reactivity as evidenced by the attenuation of platelet activation, secretion, aggregation, spreading, and retraction (P<0.05). In vivo, GUDCA administration robustly alleviated thrombogenesis (P<0.05) without affecting hemostasis. Mechanistically, GUDCA inhibited DGK (diacylglycerol kinase) activity, leading to the downregulation of the phosphatidic acid-mediated signaling pathway. Conversely, phosphatidic acid supplementation was sufficient to abolish the antithrombotic effects of GUDCA. More importantly, long-term oral administration of GUDCA normalized the enhanced DGK activity, thereby remarkably alleviating the platelet hyperreactivity as well as the heightened thrombotic tendency in diet-induced obese mice (P<0.05). CONCLUSIONS: Our study implicated that GUDCA reduces platelet hyperreactivity and improves thrombotic propensity by inhibiting DGKs activity, which is a potentially effective prophylactic approach and promising therapeutic agent for arterial thrombotic events.

2.
Org Lett ; 26(10): 2119-2123, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38436251

ABSTRACT

A green and highly efficient visible-light-induced radical cascade difluoroalkylation/cyclization reaction of N-cyanamide alkenes has been developed. A variety of CF2COR-containing quinazolinones have been obtained in high yields with cheap non-metallic 4CzIPN as the photocatalyst. This photocatalytic reaction provides rapid, facile, and practical access to valuable polycyclic quinazolinone, and it is amenable to the gram scale.

3.
Int J Biol Macromol ; 263(Pt 2): 130467, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38423433

ABSTRACT

In order to solve the problem of uneven microporous structure of Poly(L-lactic acid) (PLLA) bulk orientation by using biological safety multi-functional plant oil as chain extenders (CE), multi-armed flexible chains were introduced into PLLA through reactive processing to prepare long chain branched PLLA (LCB-PLLA). When the total content of the CE was 6.15 wt%, PLLA and the CE reacted most fully, while maintaining the tensile strength of PLLA and improving toughness. After introducing the LCB structure, the presence of multi-armed flexible chains increased the mobility of the molecular chains, resulting in a significantly lower degree of crystallinity. When the draw ratio up to 900 %, the crystallinity of LCB-PLLA-F-900 % was only 45.15 %, lower than that of PLLA-F-900 %. Thanks to the mobility of polymer chains can be enhanced, which reduces the degree of crystallinity while promoting the uniform growth of oriented microporous structures. Finally, an oriented micro-porous biomimetic LCB-PLLA material with an average cell diameter of 540 nm was prepared, and the results of in vitro cell culture showed that the oriented micro-porous LCB-PLLA biomimetic material was more conducive to cell proliferation.


Subject(s)
Bionics , Polyesters , Polyesters/chemistry , Polymers/chemistry , Tensile Strength , Porosity , Lactic Acid/chemistry
4.
Cell Metab ; 36(3): 598-616.e9, 2024 03 05.
Article in English | MEDLINE | ID: mdl-38401546

ABSTRACT

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Thrombosis , Humans , Mice , Animals , Integrin alpha2beta1/genetics , Integrin alpha2beta1/metabolism , Collagen/metabolism , Blood Platelets/metabolism , COVID-19/metabolism
5.
J Ethnopharmacol ; 323: 117615, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38163560

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Essential hypertension (EH) is one of the important risk factors of cardio-cerebrovascular diseases, and it can significantly increase the incidence and mortality of acute myocardial infarction, cerebral infarction and hemorrhage. Danhong Formula (DHF) was consisting of Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese) (Plant names have been checked with http://www.the plant list.org on June 28th, 2023) was approved by State Food and Drug Administration of China, that has been used for thousands of years in the treatment of cardiovascular diseases in China with proven safety and efficacy. Though our previous studies have found that DHF improved endothelial dysfunction (ED) and decreased high blood pressure (BP), the underlying mechanisms of its antihypertensive effect still remain unclear. AIM OF THE STUDY: This study investigated whether DHF regulated MicroRNA 24- Phosphatidylinositol 3-Kinase-Serine/Threonine Kinase- Endothelial Nitric Oxide Synthase (miR-24 - PI3K/AKT/eNOS) axis to produce antihypertensive effect and improve endothelial dysfunction. MATERIALS AND METHODS: Firstly, the chemical components of DHF were analyzed by UHPLC-MS. After that, BP was continuously monitored within the 1st, 3rd, and 4th week in SHR to evaluate the antihypertensive effect of DHF intraperitoneal injection. In addition, not only the contents of serum nitric oxide (NO), prostacyclin (PGI2), and angiotensin II (Ang II) were detected, but also the isolated aorta ring experiment was conducted to evaluate the vasomotoricity to evaluate of DHF on improving endothelial dysfunction. Key proteins or mRNA expression associated with miR-24 - PI3K/AKT/eNOS axis in aorta were detected by capillary Western blot, immunohistochemistry or RT-PCR to explore the underlying mechanisms. Index of NO, Ang II PGI2 and key proteins or mRNA expression were also conducted in miR-24-3p over-expression HUVECs model. RESULTS: Compared with SHR control group, DHF (4 mL/kg/day, 2 mL/kg/day, 1 mL/kg/day) treatment significantly reduced high BP in SHR and selectively increased acetylcholine (Ach) induced vasodilation, but not sodium nitroprusside (SNP) in a manner of concentration dependency in isolated aorta ring. DHF (4 mL/kg/day, 1 mL/kg/day) treatment was accompanying an increment of NO and PGI2, and lowering AngII in SHR. Moreover, DHF treatment significantly up-regulated expression of p-PI3K, p-AKT, mTOR, eNOS and p-eNOS, but down-regulated miR-24-3p expression in aorta. Compared with miR-24-3p over-expression HUVECs model group, DHF treatment inhibited miR- 24-3p expression and up-regulated p-PI3K, p-AKT, mTOR and eNOS mRNA expression. Similarly, DHF treatment increased PI3K, AKT, mTOR and eNOS protein expression in HUVECs by Western blot. CONCLUSIONS: These findings suggest that DHF alleviates endothelial dysfunction and reduces high BP in SHR mediated by down-regulating miR-24 via ultimately facilitating up-regulation of PI3K/AKT/eNOS axis. This current study firstly demonstrates a potential direction for antihypertensive mechanism of DHF from microRNA aspect and will promote its clinical applications.


Subject(s)
Drugs, Chinese Herbal , Hypertension , MicroRNAs , Humans , Phosphatidylinositol 3-Kinase/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Blood Pressure , Proto-Oncogene Proteins c-akt/metabolism , Protein Serine-Threonine Kinases , Phosphatidylinositol 3-Kinases/metabolism , Antihypertensive Agents , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Hypertension/drug therapy , Angiotensin II/pharmacology , TOR Serine-Threonine Kinases , Serine , RNA, Messenger , Nitric Oxide/metabolism
6.
ACS Nano ; 18(4): 3497-3508, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38215492

ABSTRACT

Two-dimensional (2D) materials have attracted intense interest due to their potential for applications in fields ranging from chemical sensing to catalysis, energy storage, and biomedicine. Recently, peptoids, a class of biomimetic sequence-defined polymers, have been found to self-assemble into 2D crystalline sheets that exhibit unusual properties, such as high chemical stability and the ability to self-repair. The structure of a peptoid is close to that of a peptide except that the side chains are appended to the amide nitrogen rather than the α carbon. In this study, we investigated the effect of peptoid sequence on the mechanism and kinetics of 2D assembly on mica surfaces using in situ AFM and time-resolved X-ray scattering. We explored three distinct peptoid sequences that are amphiphilic in nature with hydrophobic and hydrophilic blocks and are known to self-assemble into 2D sheets. The results show that their assembly on mica starts with deposition of aggregates that spread to establish 2D islands, which then grow by attachment of peptoids, either monomers or unresolvable small oligomers, following well-known laws of crystal step advancement. Extraction of the solubility and kinetic coefficient from the dependence of the growth rate on peptoid concentration reveals striking differences between the sequences. The sequence with the slowest growth rate in bulk and with the highest solubility shows almost no detachment; i.e., once a growth unit attaches to the island edge, there is almost no probability of detaching. Furthermore, a peptoid sequence with a hydrophobic tail conjugated to the final carboxyl residue in the hydrophilic block has enhanced hydrophobic interactions and exhibits rapid assembly both in the bulk and on mica. These assembly outcomes suggest that, while the π-π interactions between adjacent hydrophobic blocks play a major role in peptoid assembly, sequence details, particularly the location of charged groups, as well as interaction with the underlying substrate can significantly alter the thermodynamic stability and assembly kinetics.


Subject(s)
Peptoids , Peptoids/chemistry , Peptides/chemistry , Aluminum Silicates , Amides/chemistry
7.
Opt Lett ; 49(1): 1-4, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38134137

ABSTRACT

Low spatial resolution is an urgent problem in integral imaging light-field displays (LFDs). This study proposes a computational method to enhance the spatial resolution without losing angular resolution. How rays reconstruct voxels through lenslets is changed so that every ray through a lenslet merely provides a subpixel. The three subpixels of a pixel no longer form one voxel but three independent voxels. We further demonstrate imperfect integration of subpixels, called the sampling error, can be eliminated on specific image depths, including the central depth plane. By realigning subpixels in the above manner under no sampling error, the sampling rate of voxels is three times the conventional pixel-based LFDs. Moreover, the ray number of every voxel is preserved for an unaffected angular resolution. With unavoidable component alignment errors, resolution gains of 2.52 and 2.0 are verified in simulation and experiment by computationally updating the elemental image array. The proposed computational method further reveals that LFDs intrinsically have a higher space-bandwidth product than presumed.

8.
Int J Mol Sci ; 24(23)2023 Nov 25.
Article in English | MEDLINE | ID: mdl-38069077

ABSTRACT

Propolis is a gelatinous substance processed by western worker bees from the resin of plant buds and mixed with the secretions of the maxillary glands and beeswax. Propolis has extensive biological activities and antitumor effects. There have been few reports about the antitumor effect of propolis against human cutaneous squamous cell carcinoma (CSCC) A431 cells and its potential mechanism. CCK-8 assays, label-free proteomics, RT-PCR, and a xenograft tumor model were employed to explore this possibility. The results showed that the inhibition rate of A431 cell proliferation by the ethanol extract of propolis (EEP) was dose-dependent, with an IC50 of 39.17 µg/mL. There were 193 differentially expressed proteins in the EEP group compared with the control group (p < 0.05), of which 103 proteins (53.37%) were upregulated, and 90 proteins (46.63%) were downregulated. The main three activated and suppressed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were extracellular matrix (ECM)-receptor interaction, amoebiasis, cell adhesion molecules (CAMs), nonalcoholic fatty liver disease (NAFLD), retrograde endocannabinoid signaling, and Alzheimer's disease. The tumor volume of the 100 mg/kg EEP group was significantly different from that of the control group (p < 0.05). These results provide a theoretical basis for the potential treatment of human CSCC A431 cell tumors using propolis.


Subject(s)
Carcinoma, Squamous Cell , Propolis , Skin Neoplasms , Humans , Cell Line, Tumor , Propolis/pharmacology , Carcinoma, Squamous Cell/drug therapy , Skin Neoplasms/drug therapy , Plant Extracts/pharmacology , Ethanol/pharmacology , Cell Proliferation
9.
J Phys Chem B ; 127(50): 10723-10729, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38063500

ABSTRACT

A combined computational and experimental study has been carried out to explore and test a quantitative correlation relationship between the relative catalytic efficiency (RCE) of human butyrylcholinesrase (BChE) mutant-catalyzed hydrolysis of substrate (-)-cocaine and the total hydrogen bonding energy (tHBE) of the carbonyl oxygen of the substrate with the oxyanion hole of the enzyme in the modeled transition-state structure (TS1), demonstrating a satisfactory linear correlation relationship between ln(RCE) and tHBE. The satisfactory correlation relationship has led us to computationally predict and experimentally confirm new human BChE mutants that have a further improved catalytic activity against (-)-cocaine, including the most active one (the A199S/F227S/S287G/A328W/Y332G mutant) with a 2790-fold improved catalytic efficiency (kcat/KM = 2.5 × 109 min-1 M-1) compared to the wild-type human BChE. Compared to the reference mutant (the A199S/S287G/A328W/Y332G mutant) tested in the reported clinical development of an enzyme therapy for cocaine dependence treatment, this new mutant (with a newly predicted additional F227S mutation) has an improved catalytic efficiency against (-)-cocaine by ∼2.6-fold. The good agreement between the computational and experimental ln(RCE) values suggests that the obtained correlation relationship is robust for computational prediction. A similar correlation relationship could also be explored in studying BChE or other serine hydrolases/esterases with an oxyanion hole stabilizing the carbonyl oxygen in the rate-determining reaction step of the enzymatic hydrolysis of other substrates.


Subject(s)
Butyrylcholinesterase , Cocaine , Humans , Butyrylcholinesterase/genetics , Butyrylcholinesterase/chemistry , Catalysis , Cocaine/chemistry , Hydrogen Bonding , Hydrolysis , Models, Molecular , Oxygen
10.
Micromachines (Basel) ; 14(12)2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38138354

ABSTRACT

All-inorganic lead halide perovskite has emerged as an attractive semiconducting material due to its unique optoelectronic properties. However, its poor environmental stability restricts its broad application. Here, a simple method for the fabrication of CsPb2Br5/TiO2 is investigated. The introduction of p-aminobenzoic acid, which has two functional groups, is critical for the capping of amorphous TiO2 on CsPb2Br5. After calcination at 300 °C, amorphous TiO2 crystallizes into the anatase phase. The CsPb2Br5/TiO2 NCs show high long-term stability in water and enhanced stability against ultraviolet radiation and heat treatment, owing to the chemical stability of TiO2. More importantly, photo-electrochemical characterizations indicate that the formation of TiO2 shells can increase the charge separation efficiency. Hence, CsPb2Br5/TiO2 exhibits improved photoelectric activity owing to the electrical conductivity of the TiO2 in water. This study provides a new route for the fabrication of optoelectronic devices and photocatalysts based on perovskite NCs in the aqueous phase. Furthermore, the present results demonstrate that CsPb2Br5/TiO2 NCs has considerable potential to be used as a photoelectric material in optical sensing and monitoring.

11.
Opt Express ; 31(22): 35835-35849, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-38017747

ABSTRACT

Integral imaging light field displays (InIm-LFDs) can provide realistic 3D images by showing an elemental image array (EIA) under a lens array. However, it is always challenging to computationally generate an EIA in real-time with entry-level computing hardware because the current practice that projects many viewpoints to the EIA induces heavy computations. This study discards the viewpoint-based strategy, revisits the early point retracing rendering method, and proposes that InIm-LFDs and regular 2D displays share two similar signal processing phases: sampling and reconstructing. An InIm-LFD is demonstrated to create a finite number of static voxels for signal sampling. Each voxel is invariantly formed by homogeneous pixels for signal reconstructing. We obtain the static voxel-pixel mapping through arbitrarily accurate raytracing in advance and store it as a lookup table (LUT). Our EIA rendering method first resamples input 3D data with the pre-defined voxels and then assigns every voxel's value to its homogeneous pixels through the LUT. As a result, the proposed method reduces the computational complexity by several orders of magnitude. The experimental rendering speed is as fast as 7 to 10 ms for a full-HD EIA frame on an entry-level laptop. Finally, considering a voxel may not be perfectly integrated by its homogeneous pixels, called the sampling error, the proposed and conventional viewpoint-based methods are analyzed in the Fourier domain. We prove that even with severe sampling errors, the two methods negligibly differ in the output signal's frequency spectrum. We expect the proposed method to break the long-standing tradeoff between rendering speed, accuracy, and system complexity for computer-generated integral imaging.

12.
J Agric Food Chem ; 71(46): 17752-17762, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37943715

ABSTRACT

Natural products are a crucial source in the development of new eco-friendly antiviral agents to control plant viral diseases. In our previous studies, some ferulic acid derivatives with good antiviral activity were obtained as an immune activator. To continue the discovery of eco-friendly antiviral agents, different monosaccharides were introduced into cinnamic acid skeletons by an activity-based strategy to obtain a series of cinnamic acid derivatives containing glycoside scaffolds, and their antiviral activities against tobacco mosaic virus (TMV) and tomato spotted wilt virus (TSWV) were evaluated. Among them, compound 8d showed the greatest protective activities against TMV and TSWV, with the EC50 values of 128.5 and 236.8 µg mL-1, respectively, which were superior to those of ningnanmycin (238.5 and 315.7 µg mL-1, respectively). Moreover, compound 8d could significantly improve the defense enzyme activities of peroxidase, chitinase, and ß-1,3-glucanase. Proteomic and transcriptome analyses indicated that compound 8d regulated gene transcription and protein expression levels involved in the defense response to resist virus infection. The present study revealed that compound 8d is a potential lead candidate for the development of novel, eco-friendly, and natural-product-based antiviral agents.


Subject(s)
Glycosides , Tobacco Mosaic Virus , Structure-Activity Relationship , Glycosides/pharmacology , Proteomics , Antiviral Agents/pharmacology , Drug Design
13.
Structure ; 31(12): 1604-1615.e8, 2023 12 07.
Article in English | MEDLINE | ID: mdl-37794595

ABSTRACT

4-Hydroxyphenylpyruvate dioxygenase (HPPD) has attracted increasing attention as a target for treating type I tyrosinemia and other diseases with defects in tyrosine catabolism. Only one commercial drug, 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC), clinically treat type I tyrosinemia, but show some severe side effects in clinical application. Here, we determined the structure of human HPPD-NTBC complex, and developed new pyrazole-benzothiadiazole 2,2-dioxide hybrids from the binding of NTBC. These compounds showed improved inhibition against human HPPD, among which compound a10 was the most active candidate. The Absorption Distribution Metabolism Excretion Toxicity (ADMET) predicted properties suggested that a10 had good druggability, and was with lower toxicity than NTBC. The structure comparison between inhibitor-bound and ligand-free form human HPPD showed a large conformational change of the C-terminal helix. Furthermore, the loop 1 and α7 helix were found adopting different conformations to assist the gating of the cavity, which explains the gating mechanism of human HPPD.


Subject(s)
Herbicides , Thiadiazoles , Tyrosinemias , Humans , Tyrosinemias/drug therapy , Thiadiazoles/pharmacology , Thiadiazoles/therapeutic use , Pyrazoles/pharmacology , Enzyme Inhibitors/pharmacology
14.
J Phys Chem Lett ; 14(43): 9732-9739, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37882440

ABSTRACT

Achieving predictable biomimetic crystallization using sequence-defined synthetic molecules in mild conditions represents a long-standing challenge in materials synthesis. Herein we report a peptoid-based approach for biomimetic control over the formation of nanostructured ZnO materials in ambient aqueous conditions. A series of two-dimensional (2D) ZnO nanomaterials have been successfully obtained using amphiphilic peptoids with different numbers, ratios, and patterns of various hydrophilic and hydrophobic side chains. By investigating the relationship between peptoid hydrophobicity and the thickness of the resultant ZnO nanomaterials, we found the critical role of peptoid hydrophobicity in the peptoid-controlled ZnO formation. Our results suggest that tuning the hydrophobicity of peptoids can be used to moderate peptoid-ZnO surface interactions, thus controlling the formation of ultrathin (<2.5 nm) 2D ZnO nanomaterials. The peptoid-controlled formation of ZnO nanomaterials was further investigated using ultrasmall-angle X-ray scattering (USAXS). Our work suggests a new approach to synthesizing 2D metal oxide nanomaterials using sequence-defined synthetic molecules.

15.
Foods ; 12(17)2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37685123

ABSTRACT

Propolis is a well-known natural antibacterial substance with various biological activities, such as anti-inflammatory and antioxidant activity. However, applications of propolis are limited due to its low water solubility. In this study, propolis microcapsules were developed with a core material of ethanol extract of propolis and shell materials of gum arabic and ß-cyclodextrin using a spray-drying technique. The optional processing formula, particle size distribution, morphology, dissolution property, and antibacterial activity of propolis microcapsules were determined. The results showed that the optional processing obtained an embedding rate of 90.99% propolis microcapsules with an average particle size of 445.66 ± 16.96 nm. The infrared spectrogram and thermogravimetric analyses showed that propolis was embedded in the shell materials. The propolis microcapsules were continuously released in water and fully released on the eighth day, and compared to propolis, the microcapsules exhibited weaker antibacterial activity. The minimum inhibitory concentrations (MICs) of propolis microcapsules against Escherichia coli and Staphylococcus aureus were 0.15 and 1.25 mg/mL, and their minimum bactericidal concentrations (MBCs) were 0.3 and 1.25 mg/mL, respectively. This water-soluble propolis microcapsule shows the potential for use as a sustained-release food additive, preservative, or drug.

16.
Cent Eur J Immunol ; 48(2): 111-125, 2023.
Article in English | MEDLINE | ID: mdl-37692032

ABSTRACT

Introduction: At present, cancer remains a persistent public health challenge facing the whole world. Studies have found that PTPN21 is associated with the development of cancer. However, the prognostic potential of PTPN21 in pan-cancer remains unclear. In this work, we aimed to analyze the expression and prognostic value of PTPN21 in pan-cancer and to further study the relationship between PTPN21 and immune infiltration. Material and methods: TCGA and GEO data were used for expression and survival analysis. Genetic alterations in PTPN21 from TCGA cancer were studied in cBioPortal. TIMER2 was used to evaluate the correlation between PTPN21 expression and immune infiltration. The R packages "ggplot2" and "clusterProfiler" were used for GO and KEGG analysis. Results: PTPN21 was found to be a valuable diagnostic biomarker in multiple cancers, including bladder urothelial carcinoma (BLCA), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and lung squamous cell carcinoma (LUSC). In addition, we observed that PTPN21 expression was associated with a variety of tumor mutations. Our results indicated a correlation between PTPN21 expression and immune infiltration. Enrichment analysis showed that PTPN21 was mainly involved in the regulation of neuroactive ligand-receptor interaction. Conclusions: Our study showed that PTPN21 expression is associated with clinical prognosis, mutation, and immune infiltration of tumors. PTPN21 may be a potential biomarker for many cancers, especially in KIRC.

17.
J Org Chem ; 88(18): 13279-13290, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37650696

ABSTRACT

A strategy utilizing silver-catalyzed oxidative decarboxylation radical cascade cyclization of arylthiodifluoroacetic acids with alkenes for the simple and efficient preparation of difluoromethylated thiochromanes and 2,2-disubstituted-N-arylbutanamides derivatives has been developed. This approach includes good functional group tolerance, easily accessible starting materials, and operational simplicity.

18.
Org Lett ; 25(30): 5650-5655, 2023 08 04.
Article in English | MEDLINE | ID: mdl-37490590

ABSTRACT

Modification of organic molecules with fluorine functionalities offers a critical approach to develop new pharmaceuticals. Here, we report a multienzyme strategy for biocatalytic fluoroalkylation using S-adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) and fluorinated SAM cofactors prepared from ATP and fluorinated l-methionine analogues by an engineered human methionine adenosyltransferase hMAT2AI322A. This work introduces the first example of biocatalytic 3,3-difluoroallylation. Importantly, this strategy can be applied to late-stage site-selective fluoroalkylation of complex molecule vancomycin with conversions up to 99%.


Subject(s)
Methionine , S-Adenosylmethionine , Humans , Methionine/metabolism , S-Adenosylmethionine/metabolism , Methyltransferases/metabolism , Racemethionine , Biocatalysis
19.
Materials (Basel) ; 16(14)2023 Jul 10.
Article in English | MEDLINE | ID: mdl-37512199

ABSTRACT

2 at.% Cu + 2 at.% Ni were co-doped in ZnO nanoparticles by a simple hydrothermal method, and then the modified nanoparticles were compounded into Cu-Ni alloy coatings using an electroplating technique. The effects of the current density (15-45 mA/cm2) on the phase structure, surface morphology, thickness, microhardness, corrosion resistance, and photocatalytic properties of the coatings were investigated. The results show that the Cu-Ni-Zn0.96Ni0.02Cu0.02O nanocomposite coatings had the highest compactness and the best overall performance at a current density of 35 mA/cm2. At this point, the co-deposition rate reached its maximum, resulting in the deposition of more Zn0.96Ni0.02Cu0.02O nanoparticles in the coating. More nanoparticles were dispersed in the coating with a better particle strengthening effect, which resulted in a minimum crystallite size of 15.21 nm and a maximum microhardness of 558 HV. Moreover, the surface structure of the coatings became finer and denser. Therefore, the corrosion resistance was significantly improved with a corrosion current density of 2.21 × 10-3 mA/cm2, and the charge transfer resistance was up to 20.98 kΩ·cm2. The maximum decolorization rate of the rhodamine B solution was 24.08% under ultraviolet light irradiation for 5 h. The improvement in the comprehensive performance was mainly attributed to the greater concentration of Zn0.96Ni0.02Cu0.02O nanoparticles in the coating, which played the role of the particle-reinforced phase and reduced the microstructure defects.

20.
J Agric Food Chem ; 71(29): 10970-10981, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37439585

ABSTRACT

The use of herbicide combinations is a common practice in modern agriculture. However, unexpected results may be observed due to herbicide and weed diversity, therefore, highlighting the need for a predictive strategy. To this end, a data set was made based on recent studies. This data set included herbicide attributes, such as active ingredient, chemical family, and mode of action, and weed attributes, namely, species, clade, type of leaves, family, and lifespan. Globally, additive interactions (46.30%) were more frequent than antagonistic (29.09%) and synergistic (24.61%) ones. The occurrence of these herbicide interactions with regard to herbicide and weed features is also discussed. Moreover, mesotrione and glyphosate have been, respectively, identified as the most promising or inadequate herbicides in predicting beneficial mixtures. The resulting global trend could guide farmers in their choice of beneficial herbicide companions.


Subject(s)
Herbicides , Herbicides/pharmacology , Weed Control/methods , Herbicide Resistance , Agriculture , Plant Weeds
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