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1.
Curr Opin Genet Dev ; 87: 102212, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38823337

ABSTRACT

The epitranscriptome encompasses a diverse array of dynamic and reversible RNA modifications, affecting both coding and noncoding RNAs. Over 170 types of RNA chemical modifications have been identified, underscoring the need for innovative detection methods to deepen our understanding of RNA modification roles and mechanisms. In particular, the base resolution and quantitative information on RNA modifications are critical for understanding the regulation and functions of RNA modifications. Based on detection throughput and principles, existing quantitative RNA modification detection methods can be categorized into two groups, including next-generation sequencing and nanopore direct RNA sequencing. In this review, we focus on methodologies for elucidating the base resolution and stoichiometric information of RNA modifications. In addition, we further discuss the challenges and the potential prospects of the quantitative RNA modification detection methods.

2.
RSC Chem Biol ; 5(6): 500-507, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38846078

ABSTRACT

DNA cytosine methylation, a crucial epigenetic modification, involves the dynamic interplay of 5-methylcytosine (5mC) and its oxidized form, 5-hydroxymethylcytosine (5hmC), generated by ten-eleven translocation (TET) DNA dioxygenases. This process is central to regulating gene expression, influencing critical biological processes such as development, disease progression, and aging. Recognizing the distinct functions of 5mC and 5hmC, researchers often employ restriction enzyme-based or chemical treatment methods for their simultaneous measurement from the same genomic sample. This enables a detailed understanding of the relationship between these modifications and their collective impact on cellular function. This review focuses on summarizing the technologies for detecting 5mC and 5hmC together but also discusses the limitations and potential future directions in this evolving field.

3.
Indian J Orthop ; 58(5): 587-597, 2024 May.
Article in English | MEDLINE | ID: mdl-38694692

ABSTRACT

Background: Lumbar disc herniation is a common degenerative lumbar disease with an increasing incidence. Percutaneous endoscopic lumbar discectomy can treat lumbar disc herniation safely and effectively with a minimally invasive procedure. However, the learning curve of this technology is steep, which means that initial learners are often not sufficiently proficient in endoscopic operations, which can easily lead to iatrogenic damage. At present, the application of computer deep learning technology to clinical diagnosis, treatment, and surgical navigation has achieved satisfactory results. Purpose: The objective of our team is to develop a multi-element identification system for the visual field of endoscopic spine surgery using deep learning algorithms and to evaluate the feasibility of this system. Method: We established an image database by collecting surgical videos of 48 patients diagnosed with lumbar disc herniation, which was labeled by two spinal surgeons. We selected 6000 images of the visual field of percutaneous endoscopic spine surgery (including various tissue structures and surgical instruments), divided into the training data, validation data, and test data according to 2:1:2. We developed convolutional neural network models based on instance segmentation-Solov2, CondInst, Mask R-CNN and Yolact, and set the four network model backbone as ResNet101 and ResNet50 respectively. Mean average precision (mAP) and frames per second (FPS) were used to measure the performance of each model for classification, localization and recognition in real time, and AP (average) is used to evaluate how easily an element is detected by neural networks based on computer deep learning. Result: Comprehensively comparing mAP and FSP of each model for bounding box test and segmentation task for the test set of images, we found that Solov2 (ResNet101) (mAP = 73.5%, FPS = 28.9), Mask R-CNN (ResNet101) (mAP = 72.8%, FPS = 28.5) models are the most stable, with higher precision and faster image processing speed. Combining the average precision of the elements in the bounding box test and segmentation tasks in each network, the AP(average) was highest for tool 3 (bbox-0.85, segm-0.89) and lowest for tool 5 (bbox-0.63, segm-0.72) in the instrumentation, whereas in the anatomical tissue elements, the fibrosus annulus (bbox-0.68, segm-0.69) and ligamentum flavum (bbox-0.65, segm-0.62) had higher AP(average),while extra-dural fat (bbox-0.42, segm-0.44) was lowest. Conclusion: Our team has developed a multi-element identification system for the visual field of percutaneous endoscopic spine surgery adapted to the interlaminar and foraminal approaches, which can identify and track anatomical tissue (nerve, ligamentum flavum, nucleus pulposus, etc.) and surgical instruments (endoscopic forceps, an high-speed diamond burr, etc.), which can be used in the future as a virtual educational tool or applied to the intraoperative real-time assistance system for spinal endoscopic operation.

4.
Cell Death Differ ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698061

ABSTRACT

Uterine luminal epithelia (LE), the first layer contacting with the blastocyst, acquire receptivity for normal embryo implantation. Besides the well-accepted transcriptional regulation dominated by ovarian estrogen and progesterone for receptivity establishment, the involvement of epigenetic mechanisms remains elusive. This study systematically profiles the transcriptome and genome-wide H3K27me3 distribution in the LE throughout the preimplantation. Combining genetic and pharmacological approaches targeting the PRC2 core enzyme Ezh1/2, we demonstrate that the defective remodeling of H3K27me3 in the preimplantation stage disrupts the differentiation of LE, and derails uterine receptivity, resulting in implantation failure. Specifically, crucial epithelial genes, Pgr, Gata2, and Sgk1, are transcriptionally silenced through de novo deposition of H3K27me3 for LE transformation, and their sustained expression in the absence of H3K27me3 synergistically confines the nuclear translocation of FOXO1. Further functional studies identify several actin-associated genes, including Arpin, Tmod1, and Pdlim2, as novel direct targets of H3K27me3. Their aberrantly elevated expression impedes the morphological remodeling of LE, a hindrance alleviated by treatment with cytochalasin D which depolymerizes F-actin. Collectively, this study uncovers a previously unappreciated epigenetic regulatory mechanism for the transcriptional silencing of key LE genes via H3K27me3, essential for LE differentiation and thus embryo implantation.

5.
J Agric Food Chem ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807027

ABSTRACT

Plant pathogenic fungi pose a significant threat to agricultural production, necessitating the development of new and more effective fungicides. The ring replacement strategy has emerged as a highly successful approach in molecular design. In this study, we employed the ring replacement strategy to successfully design and synthesize 32 novel hydrazide derivatives containing diverse heterocycles, such as thiazole, isoxazole, pyrazole, thiadiazole, 1,3,4-oxadiazole, 1,2,4-oxadiazole, thiophene, pyridine, and pyrazine. Their antifungal activities were evaluated in vitro and in vivo. Bioassay results revealed that most of the title compounds displayed remarkable antifungal activities in vitro against four tested phytopathogenic fungi, including Fusarium graminearum, Botrytis cinerea, Sclerotinia sclerotiorum, and Rhizoctonia solani. Especially, compound 5aa displayed a broad spectrum of antifungal activity against F. graminearum, B. cinerea, S. sclerotiorum, and R. solani, with the corresponding EC50 values of 0.12, 4.48, 0.33, and 0.15 µg/mL, respectively. In the antifungal growth assay, compound 5aa displayed a protection efficacy of 75.5% against Fusarium head blight (FHB) at a concentration of 200 µg/mL. In another in vivo antifungal activity evaluation, compound 5aa exhibited a noteworthy protective efficacy of 92.0% against rape Sclerotinia rot (RSR) at a concentration of 100 µg/mL, which was comparable to the positive control tebuconazole (97.5%). The existing results suggest that compound 5aa has a broad-spectrum antifungal activity. Electron microscopy observations showed that compound 5aa might cause mycelial abnormalities and organelle damage in F. graminearum. Moreover, in the in vitro enzyme assay, we found that the target compounds 5aa, 5ab, and 5ca displayed significant inhibitory effects toward succinate dehydrogenase, with the corresponding IC50 values of 1.62, 1.74, and 1.96 µM, respectively, which were superior to that of boscalid (IC50 = 2.38 µM). Additionally, molecular docking and molecular dynamics simulation results revealed that compounds 5aa, 5ab, and 5ca have the capacity to bind in the active pocket of succinate dehydrogenase (SDH), establishing hydrogen-bonding interactions with neighboring amino acid residues.

6.
Environ Pollut ; 351: 124059, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38703979

ABSTRACT

The hazards of man-made chiral compounds are of great public concern, with reports of worrying stereoselective compounds and an urgent need to assess their transport. This study evaluated the transport of 2-arylpropionic acid derivatives enantiomers (2-APA) in porous media under a variety of solution chemistry conditions via column packing assays. The results revealed the introduction of Malic acid (MA) enantiomers enhanced the mobility of 2-APA enantiomers, but the enhancement effect was different for different 2-APA enantiomers. Batch sorption experiments confirmed that the MA enantiomers occupied the sorption site of the quartz sand, thus reducing the deposition of the 2-APA enantiomer. Homo- or heterochirality between 2-APA and MA dominates the transport of 2-APA enantiomers, with homochirality between them triggering stronger retention and vice versa. Further evaluating the effect of solution chemistry conditions on the transport of 2-APA enantiomers, increased ionic strength attenuated the mobility of 2-APA enantiomers, whereas introduced coexisting cations enhanced the retention of 2-APA enantiomers in the column. The redundancy analyses corroborated these solution chemistry conditions were negatively correlated with the transport of 2-APA enantiomers. The coupling of pH and these conditions reveals electrostatic forces dominate the transport behavior and stereoselective interactions of 2-APA enantiomers. Distinguishing the transport of enantiomeric pair helps to understand the difference in stereoselectivity of enantiomers and promises to remove the more hazardous one.


Subject(s)
Propionates , Stereoisomerism , Propionates/chemistry , Porosity , Adsorption , Malates/chemistry , Hydrogen-Ion Concentration
7.
Int J Biol Macromol ; 270(Pt 1): 132278, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38750856

ABSTRACT

Leeches secrete various biologically active substances which have important medical and pharmaceutical values in antithrombotic treatments. Here, we provide a high quality genome of two Asian medicinal leeches Hirudo nipponia and Hirudo tianjinensis, based on which, we identified 22 antithrombotic gene families, including fourteen coagulation inhibitors, four platelet aggregation inhibitors, three fibrinolysis enhancers, and one tissue penetration enhancer. The total numbers of antithrombotic genes were similar between H. nipponia (N = 86) and H. tianjinensis (N = 83). Molecular evolution analysis showed that no significant differences were detected between the two species in any of the three selection indices (dN, dS, and dN/dS), nor in the number of sites under positive/purifying selection. RNA-Seq based gene expression analysis showed that the overall expression patterns of the antithrombotic gene families were not significantly deviated between the two species. Our results indicated that there were rather close similarities between the two leeches on genomic characteristics, especially for the molecular evolution and expression of antithrombotic genes. Our study provides the most comprehensive collection of antithrombotic biomacromolecules from the two Asian medicinal leeches to date. These results will greatly facilitate the research and application of leech derivatives for medical and pharmaceutical purposes of thrombosis.


Subject(s)
Fibrinolytic Agents , Genomics , Leeches , Animals , Leeches/genetics , Genomics/methods , Fibrinolytic Agents/pharmacology , Phylogeny , Evolution, Molecular , Genome
8.
Indian J Dermatol ; 69(1): 57-62, 2024.
Article in English | MEDLINE | ID: mdl-38572045

ABSTRACT

Warts are caused by human papillomavirus (HPV) infection and can involve multiple parts of skin and mucosa, of which periungual and subungual warts are the most difficult to treat. Periungual or subungual wart is verruca vulgaris growing around or under the fingernail, destroying and deforming the nail and nail bed. Currently, liquid nitrogen cryotherapy and CO2 laser are often used for the treatment. Clinically, few doctors routinely use photodynamic therapy (PDT) to treat viral warts. We used PDT combined with liquid nitrogen cryotherapy and curettage to successfully treat a case of intractable periungual and subungual warts.

9.
Insects ; 15(4)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38667360

ABSTRACT

Mountain ecosystems harbor evolutionarily unique and exceptionally rich biodiversity, particularly in insects. In this study, we characterized the diversity, community stability, and assembly mechanisms of butterflies on a subtropical mountain in the Chebaling National Nature Reserve, Guangdong Province, China, using grid-based monitoring across the entire region for two years. The results showed that species richness, abundance, and Faith's phylogenetic diversity decreased with increasing elevation; taxonomic diversity played a considerable role in mediating the effects of environmental changes on stability. Moreover, our results showed that stochastic processes are dominant in governing the assembly of butterfly communities across all elevational gradients, with habitats at an elevation of 416-580 m subjected to the strongest stochastic processes, whereas heterogeneous selection processes displayed stronger effects on the assembly of butterfly communities at 744-908 m, 580-744 m, and 908-1072 m, with abiotic factors inferred as the main driving forces. In addition, significant differences were detected between the barcode tree and the placement tree for the calculated ß-NTI values at 416-580 m. Overall, this study provides new insights into the effects of environmental change on the stability and assembly of butterflies in Chebaling, which will be beneficial for biodiversity conservation and policy development.

10.
Ecol Evol ; 14(4): e11218, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38606343

ABSTRACT

Insects harbor a remarkable diversity of gut microbiomes critical for host survival, health, and fitness, but the mechanism of this structured symbiotic community remains poorly known, especially for the insect group consisting of many closely related species that inhabit the Qinghai-Tibet Plateau. Here, we firstly analyzed population-level 16S rRNA microbial dataset, comprising 11 Parnassius species covering 5 subgenera, from 14 populations mostly sampled in mountainous regions across northwestern-to-southeastern China, and meanwhile clarified the relative importance of multiple factors on gut microbial community structure and evolution. Our findings indicated that both host genetics and larval host plant modulated gut microbial diversity and community structure. Moreover, the effect analysis of host genetics and larval diet on gut microbiomes showed that host genetics played a critical role in governing the gut microbial beta diversity and the symbiotic community structure, while larval host plant remarkably influenced the functional evolution of gut microbiomes. These findings of the intimate insect-microbe-plant interactions jointly provide some new insights into the correlation among the host genetic background, larval host plant, the structure and evolution of gut microbiome, as well as the mechanisms of high-altitude adaptation in closely related species of this alpine butterfly group.

11.
BMC Cardiovasc Disord ; 24(1): 223, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658849

ABSTRACT

BACKGROUND: Long-term exposure to a high altitude environment with low pressure and low oxygen could cause abnormalities in the structure and function of the heart. Myocardial strain is a sensitive indicator for assessing myocardial dysfunction, monitoring myocardial strain is of great significance for the early diagnosis and treatment of high altitude heart-related diseases. This study applies cardiac magnetic resonance tissue tracking technology (CMR-TT) to evaluate the changes in left ventricular myocardial function and structure in rats in high altitude environment. METHODS: 6-week-old male rats were randomized into plateau hypoxia rats (plateau group, n = 21) as the experimental group and plain rats (plain group, n = 10) as the control group. plateau group rats were transported from Chengdu (altitude: 360 m), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (altitude: 3850 m), Yushu, China, and then fed for 12 weeks there, while plain group rats were fed in Chengdu(altitude: 360 m), China. Using 7.0 T cardiac magnetic resonance (CMR) to evaluate the left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), as well as myocardial strain parameters including the peak global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). The rats were euthanized and a myocardial biopsy was obtained after the magnetic resonance imaging scan. RESULTS: The plateau rats showed more lower left ventricular GLS and GRS (P < 0.05) than the plain rats. However, there was no statistically significant difference in left ventricular EDV, ESV, SV, EF and GCS compared to the plain rats (P > 0.05). CONCLUSIONS: After 12 weeks of exposure to high altitude low-pressure hypoxia environment, the left ventricular global strain was partially decreased and myocardium is damaged, while the whole heart ejection fraction was still preserved, the myocardial strain was more sensitive than the ejection fraction in monitoring cardiac function.


Subject(s)
Altitude , Stroke Volume , Ventricular Function, Left , Animals , Male , Rats, Sprague-Dawley , Altitude Sickness/physiopathology , Altitude Sickness/diagnostic imaging , Predictive Value of Tests , Magnetic Resonance Imaging, Cine , Magnetic Resonance Imaging , Time Factors , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology , Rats , Hypoxia/physiopathology
12.
Polymers (Basel) ; 16(6)2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38543453

ABSTRACT

Herein, wheat straw residue and pulping waste liquid were collected from pulping mill and mixed to prepare bio-based granular fuels by using compression molding technology, and to explore the comprehensive utilization of the industrial waste of pulping and papermaking. The effects of pulping waste liquid on granular fuel properties were analyzed systemically. Further study of the function of pulping waste liquid, cellulose and hemicellulose was used to replace wheat straw residue and avoid the interference factors. Therefore, the prediction models of granular fuels were established with influencing factors that included cellulose, hemicellulose and pulping waste liquid. The granular fuels had the best performance with 18.30% solid content of pulping waste liquid. The highest transverse compressive strength of granular fuel was 102.61 MPa, and the activation energy was 81.71 KJ·mol-1. A series of curve fitting prediction models were established to clarify the forming process of granular fuel, and it turned out that the pulping waste liquid could improve the adhesion between solid particles and increase their compression resistance.

13.
Postgrad Med J ; 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38497290

ABSTRACT

PURPOSE: (i) To analyze age-adjusted incidence rates of synchronous bone metastases diagnosed alongside primary malignancy from 2010 to 2018 in the US population, (ii) determine the incidence proportions (IPs) and characteristics of synchronous bone metastases among newly diagnosed cancer patients in the USA especially pediatric cases, and (iii) assess the implications of synchronous bone metastases on cancer patient's survival, and identify the survival risk factors for these cancer patients. METHODS: Utilizing data from the Surveillance, Epidemiology, and End Results (SEER) program (2010-2018), we calculated age-adjusted IPs and annual percentage change (APC), and employed logistic regression and Cox regression models for our analysis. RESULTS: 3 300 736 cancer patients were identified. The age-adjusted incidence rates of synchronous bone metastases increased from 2010 (18.04/100 000) to 2018 (20.89/100 000; APC: 2.3, 95% confidence interval [CI], 1.4-3.1), but decreased in lung cancer (average APC: -1.0, 95% CI, -1.8 to -0.3). The highest IPs were observed in pediatric neuroblastoma (43.2%; 95% CI, 39.8%-46.7%) and adult small cell carcinoma (23.1%; 95% CI, 22.7%-23.4%). Multivariate logistic analyses revealed that primary tumor characteristics were correlated with higher bone metastases risk. Survival analyses also showed varied prognostic outcomes based on metastasis sites and demographics among cancer patients. Landmark analyses further indicated among long-term cancer survivors (≥3 and ≥5 years), patients with de novo bone metastases had the poorest survival rates compared with those with other synchronous metastases (P < 0.001). CONCLUSION: This study provides a population-based estimation of the incidence and prognosis for synchronous bone metastases. Our findings highlight the need for early identification of high-risk groups and multidisciplinary approaches to improve prognosis of cancer patients with de novo bone metastases.

14.
J Nat Med ; 78(3): 664-676, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38427210

ABSTRACT

This study investigates the cardioprotective effects of Paeoniflorin (PF) on left ventricular remodeling following acute myocardial infarction (AMI) under conditions of hypobaric hypoxia. Left ventricular remodeling post-AMI plays a pivotal role in exacerbating heart failure, especially at high altitudes. Using a rat model of AMI, the study aimed to evaluate the cardioprotective potential of PF under hypobaric hypoxia. Ninety male rats were divided into four groups: sham-operated controls under normoxia/hypobaria, an AMI model group, and a PF treatment group. PF was administered for 4 weeks after AMI induction. Left ventricular function was assessed using cardiac magnetic resonance imaging. Biochemical assays of cuproptosis, oxidative stress, apoptosis, inflammation, and fibrosis were performed. Results demonstrated PF significantly improved left ventricular function and remodeling after AMI under hypobaric hypoxia. Mechanistically, PF decreased FDX1/DLAT expression and serum copper while increasing pyruvate. It also attenuated apoptosis, inflammation, and fibrosis by modulating Bcl-2, Bax, NLRP3, and oxidative stress markers. Thus, PF exhibits therapeutic potential for left ventricular remodeling post-AMI at high altitude by inhibiting cuproptosis, inflammation, apoptosis and fibrosis. Further studies are warranted to optimize dosage and duration and elucidate PF's mechanisms of action.


Subject(s)
Glucosides , Hypoxia , Monoterpenes , Myocardial Infarction , Oxidative Stress , Rats, Sprague-Dawley , Ventricular Remodeling , Animals , Glucosides/pharmacology , Glucosides/therapeutic use , Ventricular Remodeling/drug effects , Male , Rats , Monoterpenes/pharmacology , Monoterpenes/therapeutic use , Myocardial Infarction/drug therapy , Oxidative Stress/drug effects , Hypoxia/drug therapy , Apoptosis/drug effects , Disease Models, Animal , Ventricular Function, Left/drug effects
15.
Materials (Basel) ; 17(5)2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38473590

ABSTRACT

Transition metals and their oxide compounds exhibit excellent chemical reactivity; however, their easy agglomeration and high cost limit their catalysis applications. In this study, an interpolation structure of a Myriophyllum verticillatum L. biochar-supported Mn/Mg composite (Mn/Mg@MV) was prepared to degrade triphenyl phosphate (TPhP) from wastewater through the activating periodate (PI) process. Interestingly, the Mn/Mg@MV composite showed strong radical self-producing capacities. The Mn/Mg@MV system degraded 93.34% TPhP (pH 5, 10 µM) within 150 min. The experimental results confirmed that the predominant role of IO3· and the auxiliary ·OH jointly contributed to the TPhP degradation. In addition, the TPhP pollutants were degraded to various intermediates and subsequent Mg mineral phase mineralization via mechanisms like interfacial processes and radical oxidation. DFT theoretical calculations further indicated that the synergy between Mn and Mg induced the charge transfer of the carbon-based surface, leading to the formation of an ·OH radical-enriched surface and enhancing the multivariate interface process of ·OH, IO3, and Mn(VII) to TPhP degradation, resulting in the further formation of Mg PO4 mineralization.

16.
Hepatology ; 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38377452

ABSTRACT

BACKGROUND AND AIMS: Protein tyrosine sulfation (PTS) is a common posttranslational modification that regulates a variety of physiological and pathological processes. However, the role of PTS in cancer remains poorly understood. The goal of this study was to determine whether and how PTS plays a role in HCC progression. APPROACH AND RESULTS: By mass spectrometry and bioinformatics analysis, we identified SAV1 as a novel substrate of PTS in HCC. Oxidative stress upregulates the transcription of SLC35B2, a Golgi-resident transporter of sulfate donor 3'-phosphoadenosine 5'-phosphosulfate, leading to increased sulfation of SAV1. Sulfation of SAV1 disrupts the formation of the SAV1-MST1 complex, resulting in a decrease of MST1 phosphorylation and subsequent inactivation of Hippo signaling. These molecular events ultimately foster the growth of HCC cells both in vivo and in vitro. Moreover, SLC35B2 is a novel transcription target gene of the Hippo pathway, constituting a positive feedback loop that facilitates HCC progression under oxidative stress. CONCLUSIONS: Our findings reveal a regulatory mechanism of the SLC35B2/SAV1 sulfation axis in response to oxidative stress, highlighting its potential as a promising therapeutic target for HCC.

17.
Phytochemistry ; 220: 114037, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38387725

ABSTRACT

Five undescribed bisabosqual-type meroterpenoids, bisabosquals E (1) and F (2), stachybisbins J-L (4-6), together with two known ones, were isolated from a novel endophytic fungus KMU22001 within the Stachybotryaceae family. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, single-crystal X-ray diffraction and electronic circular dichroism calculations. Compounds 2, 4 and 6 exhibited significant cytotoxicities against five human cancer cell lines with IC50 values ranging from 1.80 ± 0.08 to 17.76 ± 0.97 µM.


Subject(s)
Antineoplastic Agents , Delphinium , Humans , Molecular Structure , Antineoplastic Agents/pharmacology , Crystallography, X-Ray , Circular Dichroism
18.
Adv Healthc Mater ; 13(14): e2400047, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38364079

ABSTRACT

The presence of multidrug-resistant bacteria has challenged the clinical treatment of bacterial infection. There is a real need for the development of novel biocompatible materials with broad-spectrum antimicrobial activities. Antimicrobial hydrogels show great potential in infected wound healing but are still being challenged. Herein, broad-spectrum antibacterial and mechanically tunable amyloid-based hydrogels based on self-assembly and local mineralization of silver nanoparticles are reported. The mineralized hydrogels are biocompatible and have the advantages of sustained release of silver, prolonged antimicrobial effect, and improved adhesion capacity. Moreover, the mineralized hydrogels display a significant antimicrobial effect against both Gram-positive and Gram-negative bacteria in cells and mice by inducing membrane damage and reactive oxygen species toxicity in bacteria. In addition, the mineralized hydrogels can rapidly accelerate wound healing by the synergy between their antibacterial activity and intrinsic improvement for cell proliferation and migration. This study provides a modular approach to developing a multifunctional protein hydrogel platform based on biomolecule-coordinated self-assembly for a wide range of biomedical applications.


Subject(s)
Anti-Bacterial Agents , Cell Proliferation , Hydrogels , Silver , Wound Healing , Silver/chemistry , Silver/pharmacology , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Wound Healing/drug effects , Cell Proliferation/drug effects , Mice , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Metal Nanoparticles/chemistry , Humans , Reactive Oxygen Species/metabolism , Microbial Sensitivity Tests , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
19.
Nat Plants ; 10(4): 618-632, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38409290

ABSTRACT

Effector proteins secreted by plant pathogenic fungi are important artilleries against host immunity, but there is no precedent of such effectors being explored as antifungal targets. Here we demonstrate that MoErs1, a species-specific effector protein secreted by the rice blast fungus Magnaporthe oryzae, inhibits the function of rice papain-like cysteine protease OsRD21 involved in rice immunity. Disrupting MoErs1-OsRD21 interaction effectively controls rice blast. In addition, we show that FY21001, a structure-function-based designer compound, specifically binds to and inhibits MoErs1 function. FY21001 significantly and effectively controls rice blast in field tests. Our study revealed a novel concept of targeting pathogen-specific effector proteins to prevent and manage crop diseases.


Subject(s)
Fungal Proteins , Oryza , Plant Diseases , Oryza/microbiology , Plant Diseases/microbiology , Fungal Proteins/metabolism , Fungal Proteins/genetics , Plant Proteins/metabolism , Plant Proteins/genetics , Host-Pathogen Interactions , Papain/metabolism , Ascomycota , Magnaporthe
20.
J Pain Res ; 17: 381-392, 2024.
Article in English | MEDLINE | ID: mdl-38312505

ABSTRACT

Objective: To validate whether a residual mass demonstrated on early postoperative MR after percutaneous endoscopic lumbar discectomy (PELD) is indeed an intraoperatively retained annulus fibrosus, and explore the correlation between imaging changes in the residual mass and clinical prognosis of patients. Methods: A prospective study of 118 patients were included. During surgery, a contrast medium, Gadopentetate Dimeglumine, was injected around the ruptured annulus fibrosus. The intensity of the T2 signal, the size of the remaining mass (SR), and the cross-sectional area of the spinal canal (SCSA), VAS, and ODI were assessed at preoperative, 1-h (7-day), 6-month, and 12-month postoperative intervals. Based on VAS at 7 days post-surgery, patients were classified into either a non-remission group (Group A, VAS > 3) or a remission group (Group B, VAS ≤ 3). Results: Six patients who developed recurrent LDH were excluded. A residual mass was detected on MRI 1 h after surgery in 94.6% (106/112). During one year of follow-up, 90.1% (101/112) of the patients displayed fibrous annulus remodeling, although 68.7% (77/112) still exhibited herniation. Significant differences were found in the ODI between Groups A and B one week after surgery (p < 0.001). However, no significant differences were observed in T2 signal intensity, SR, and SCSA at 1-h, 6-month and 12-month post-surgery (p > 0.05) between the two groups. In a multiple linear regression analysis, early postoperative ODI changes were associated with T2 signal (B = -10.22, sig < 0.05), long-term changes were associated with alterations in SR (B = 5.63, sig < 0.05) and SCSA (B = -0.13, sig < 0.05). Conclusion: The residual mass observed in early postoperative MR images after PELD was the retained annulus fibrosus intraoperatively. Short-term changes in clinical symptoms after PELD were linked to T2 signal intensity, while long-term changes were associated with changes in SR and SCSA.

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