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1.
Front Immunol ; 15: 1381802, 2024.
Article in English | MEDLINE | ID: mdl-38966637

ABSTRACT

Background: Yishen-Tongbi Decoction (YSTB), a traditional Chinese prescription, has been used to improve syndromes of rheumatoid arthritis (RA) for many years. Previous research has shown that YSTB has anti-inflammatory and analgesic properties. However, the underlying molecular mechanism of the anti-RA effects of YSTB remains unclear. Purpose and study design: The purpose of this research was to investigate how YSTB affected mice with collagen-induced arthritis (CIA) and RAW264.7 cells induced with lipopolysaccharide (LPS). Results: The findings show that YSTB could significantly improve the clinical arthritic symptoms of CIA mice (mitigate paw swelling, arthritis score, thymus and spleen indices, augment body weight), downregulated expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6 and IL-17, while upregulated the level of anti-inflammatory like IL-10 and transforming growth factor-ß (TGF-ß). Meanwhile, YSTB inhibits bone erosion and reduces inflammatory cell infiltration, synovial proliferation, and joint destruction in CIA mice. In addition, we found that YSTB was able to suppress the LPS-induced inflammation of RAW264.7 cells, which was ascribed to the suppression of nitric oxide (NO) production and reactive oxygen species formation (ROS). YSTB also inhibited the production of inducible nitric oxide synthase and reduced the releases of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 in LPS-induced RAW264.7 cells. Furthermore, the phosphorylation expression of JAK2, JAK3, STAT3, p38, ERK and p65 protein could be suppressed by YSTB, while the expression of SOCS3 could be activated. Conclusion: Taken together, YSTB possesses anti-inflammatory and prevention bone destruction effects in RA disease by regulating the JAK/STAT3/SOCS3 signaling pathway.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Drugs, Chinese Herbal , Janus Kinases , STAT3 Transcription Factor , Signal Transduction , Suppressor of Cytokine Signaling 3 Protein , Animals , Mice , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , RAW 264.7 Cells , STAT3 Transcription Factor/metabolism , Suppressor of Cytokine Signaling 3 Protein/metabolism , Suppressor of Cytokine Signaling 3 Protein/genetics , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Arthritis, Experimental/metabolism , Signal Transduction/drug effects , Janus Kinases/metabolism , Male , Cytokines/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Inflammation/drug therapy , Mice, Inbred DBA , Disease Models, Animal
2.
Free Radic Biol Med ; 222: 456-466, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38950659

ABSTRACT

Hepatocellular carcinoma (HCC), the primary form of liver cancer, is the third leading cause of cancer-related death globally. Hernandonine is a natural alkaloid derived from Hernandia nymphaeifolia that has been shown to exert various biological functions. In a previous study, hernandonine was shown to suppress the proliferation of several solid tumor cell lines without affecting normal human cell lines. However, little is known about the effect of hernandonine on HCC. Therefore, this study aimed to investigate the effect and mechanism of hernandonine on HCC in relation to autophagy. We found that hernandonine inhibited HCC cell growth in vitro and in vivo. In addition, hernandonine elicited autophagic cell death and DNA damage in HCC cells. RNA-seq analysis revealed that hernandonine upregulated p53 and Hippo signaling pathway-related genes in HCC cells. Small RNA interference of p53 resulted in hernandonine-induced autophagic cell death attenuation. However, inhibition of YAP sensitized HCC cells to hernandonine by increasing the autophagy induction. This is the first study to illustrate the complex involvement of p53 and YAP in the hernandonine-induced autophagic cell death in human HCC cells. Our findings provide novel evidence for the potential of hernandonine as a therapeutic agent for HCC treatment.

3.
J Asian Nat Prod Res ; : 1-7, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949198

ABSTRACT

One new canthinone glycoside (1), together with six known compounds (2-7) including three lignans (2-4), two coumarins (5-6) and one phenol (7) was isolated from the root barks of Ailanthus altissima. The structure of new compound 1 was established by the interpretation of UV, IR, MS and NMR data, while its absolute configuration was determined by acid hydrolysis and GIAO NMR calculations with DP4+ probability analysis. The inhibitory effects of all compounds on Nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that compounds 2 and 5 displayed NO production inhibitory activity with IC50 values of 30.1 and 15.3 µM, respectively.

4.
Nat Prod Res ; : 1-7, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949631

ABSTRACT

Seven polyketides, including an undescribed depsidone (1) and six previously reported 3,6,8-trihydroxy-1-methylxanthone (2), 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (3), methyl3-chloro-6-hydroxy-2-(4-hy-droxy-2-methoxy-6-methylphenoxy)-4- methoxybenzoate (4), xylarianin A (5), 4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydro-xymethyl-2-cyclohexen-1-one (6) and alternariol (7), have been isolated from cultures of the mangrove-derived fungus Penicillium robsamsonii HNNU0006. The structure of compound 1 was elucidated by extensive spectroscopic analysis and X-ray crystallography. Furthermore, all the compounds were evaluated their cytotoxic activities, and compounds 1 and 7 showed weak cytotoxicity against two cell lines Vero and A549 with IC50 values ranging from 95.6 and 296.5 µM, relative to the positive control Etoposide phosphate with IC50 values of 24.5 and 18.7 µM, respectively.

5.
Poult Sci ; 103(9): 104019, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38991384

ABSTRACT

Meat qualities of free-range chicken (Xuan-Zhou) (XZ-FRC) are closely associated with slaughter age and directly influence the economic benefits of supplier and consumer's preference. Understanding of the relationship between meat qualities and ages will be of prime important to explore a better slaughter age of XZ-FRC. In this study, the quality traits of breast and thigh muscles from XZ-FRCs at 9 to 14 wk were analyzed to establish a relatively reliable method for selecting a better slaughter age. The results showed that the effects of slaughter ages on color (CIE L*, a* and b* values), shear force, centrifugal loss, and flavor of XZ-FRCs were significant (P < 0.05). There were greater differences in meat qualities, whatever breast or thigh muscles, between same or different ages. Eleven feature indexes used for colligation evaluation of slaughter age were selected by combining the quality characteristics and data analysis. The score of colligation evaluation for XZ-FRCs at 12 wk was higher than that at 9 and 14 wk, suggesting that the 12 wk was an optimal slaughter age. This work would provide a reference method that helps the producers of livestock and poultry to select a better slaughter age.

6.
Mol Neurobiol ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38977622

ABSTRACT

Patients with hemorrhagic stroke have high rates of morbidity and mortality, and drugs for prevention are very limited. Mendelian randomization (MR) analysis can increase the success rate of drug development by providing genetic evidence. Previous MR analyses only analyzed the role of individual drug target genes in hemorrhagic stroke; therefore, we used MR analysis to systematically explore the druggable genes for hemorrhagic stroke. We sequentially performed summary-data-based MR analysis and two-sample MR analysis to assess the associations of all genes within the database with intracranial aneurysm, intracerebral hemorrhage, and their subtypes. Validated genes were further analyzed by colocalization. Only genes that were positive in all three analyses and were druggable were considered desirable genes. We also explored the mediators of genes affecting hemorrhagic stroke incidence. Finally, the associations of druggable genes with other cardiovascular diseases were analyzed to assess potential side effects. We identified 56 genes that significantly affected hemorrhagic stroke incidence. Moreover, TNFSF12, SLC22A4, SPARC, KL, RELT, and ADORA3 were found to be druggable. The inhibition of TNFSF12, SLC22A4, and SPARC can reduce the risk of intracranial aneurysm, subarachnoid hemorrhage, and intracerebral hemorrhage. Gene-induced hypertension may be a potential mechanism by which these genes cause hemorrhagic stroke. We also found that blocking these genes may cause side effects, such as ischemic stroke and its subtypes. Our study revealed that six druggable genes were associated with hemorrhagic stroke, and the inhibition of TNFSF12, SLC22A4, and SPARC had preventive effects against hemorrhagic strokes.

7.
World J Gastrointest Oncol ; 16(6): 2742-2756, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994144

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Platelets (PLTs) are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases. Aspirin is the most classic antiplatelet agent. However, the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study. AIM: To explore the impact of the antiplatelet effect of aspirin on the development of HCC. METHODS: Platelet-rich plasma, platelet plasma, pure platelet, and platelet lysate were prepared, and a coculture model of PLTs and HCC cells was established. CCK-8 analysis, apoptosis analysis, Transwell analysis, and real-time polymerase chain reaction (RT-PCR) were used to analyze the effects of PLTs on the growth, metastasis, and inflammatory microenvironment of HCC. RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways. Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo, and the effect of PLTs on the progression of HCC was detected. RESULTS: PLTs significantly promoted the growth, invasion, epithelial-mesenchymal transition, and formation of an inflammatory microenvironment in HCC cells. Activated PLTs promoted HCC progression by activating the mitogen-activated protein kinase/protein kinase B/signal transducer and activator of transcription three (MAPK/ AKT/STAT3) signaling axis. Additionally, aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation. CONCLUSION: PLTs play an important role in the pathogenesis of HCC, and aspirin can affect HCC progression by inhibiting platelet activity. These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

8.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3548-3551, 2024 Jul.
Article in Chinese | MEDLINE | ID: mdl-39041126

ABSTRACT

An OSMAC strategy was used to study secondary metabolites and anti-inflammatory activities of the endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal. The PDB ferment of fungus P. herquei JX4 was isolated, purified, and identified by using silica gel column chromatography, gel column chromatography, octadecylsilyl(ODS) column chromatography, and semi-preparative high-performance liquid chromatography. Two new pinophol derivatives, pinophol H(1) and pinophol I(2) were isolated and identified, and they were evaluated in terms of the inhibitory activities against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse macrophage RAW264.7 cells. The results showed that compound 1 had significant inhibitory activity on NO production, with an IC_(50) value of 8.12 µmol·L~(-1).


Subject(s)
Nitric Oxide , Penicillium , Penicillium/chemistry , Mice , Animals , RAW 264.7 Cells , Macrophages/drug effects , Endophytes/chemistry , Molecular Structure , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry
9.
Zhongguo Zhong Yao Za Zhi ; 49(11): 2940-2946, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39041153

ABSTRACT

The chemical constituents from Leucas ciliata belonging to Leucas genus in Lamiaceae were systematically explored by silica gel column chromatography, ODS column chromatography, Sephadex LH-20 gel column chromatography, and preparative high performance liquid chromatography, and seventeen phenolic acids were isolated. The chemical structures of the compounds were identified by their physicochemical properties, spectroscopic data, and literature. They were 4-hydroxyphenethyl ethyl succinate(1), 4-hydroxyphenethyl methyl succinate(2), 2-(4-hydroxyphenyl) ethyl acetate(3), p-hydroxyphenylethyl anisate(4), cassia cis-trans diphenylpropanoid(5), p-coumaric acid(6), 3,4-dihydroxybenzenepropionic acid methyl ester(7), caffeic acid(8), trans-p-hydroxyl ethyl cinnamate(9), methyl p-hydroxybenzeneacetate(10), 4-hydroxyphenethyl alcohol(11), syringic acid(12), vanillin(13), protocatechuic acid(14), salicylic acid(15), p-hydroxybenzaldehyde(16), and diorcinol(17). Among them, compound 1 was new, and compounds 2-10, 12, 14, and 16-17 were isolated from the plants belonging to Leucas genus for the first time. All compounds were obtained from L. ciliata for the first time. The anti-inflammatory activity of compounds 1-17 on NO production in lipopolysaccharide(LPS)-induced mouse leukemia cells of monocyte macrophage(RAW264. 7) cells was evaluated. The results showed that compounds 5, 7, and 9 exhibited significant anti-inflammatory activity, with IC50values of(10. 14±0. 36)-(21. 17±0. 11) µmol·L~(-1).


Subject(s)
Anti-Inflammatory Agents , Hydroxybenzoates , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Hydroxybenzoates/chemistry , Hydroxybenzoates/pharmacology , Animals , Mice , RAW 264.7 Cells , Lamiaceae/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Molecular Structure , Nitric Oxide , Macrophages/drug effects
10.
Zhongguo Zhong Yao Za Zhi ; 49(11): 3081-3094, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39041168

ABSTRACT

The effect and mechanism of Huangqin Qingre Chubi Capsules(HQC) on rheumatoid arthritis(RA) were studied.Seventy male SPF rats were randomly divided into normal group, model group, low-(0. 18 g·kg~(-1)), middle-(0. 36 g·kg~(-1)), and high-(0. 72 g·kg~(-1)) dose groups of HQC, methotrexate group(MTX, 0. 75 mg·kg~(-1)), and negative control group(NC group, model +saline). Adjuvant arthritis fibroblast-like synoviocytes(AA-FLS) were divided into normal group, model group, low-, middle-, and high-dose groups of HQC, and negative control group. RT-qPCR and Western blot were used to detect the m RNA and protein expressions of METTL3, SFRP4, ß-catenin, CCND1, c-Myc, MMP3, and fibronectin. The protein expression of MMP3 and ß-catenin was detected by immunofluorescence. The gene expression level of METTL3 on AA-FLS was knocked down to further examine the expression of each gene. ELISA measured the levels of IL-1ß, IL-6, and IL-8. The results showed that compared with the normal group, rats in the model group found redness and swelling in their limbs and significantly increased joint swelling. Compared with the model group, the joint swelling degree of each treatment group significantly decreased(P<0. 05). The paw retraction threshold and body weight mass index both significantly increased(P<0. 05). METTL3 was highly expressed on AA and negatively correlated with the expression of SFRP4. After treatment, the m RNA and protein expression of METTL3, ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 were significantly decreased on AA-FLS(P< 0. 05). Compared with the model group, knocking down METTL3 resulted in reduced m RNA and protein expression of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3(P< 0. 05). At the same time, the m RNA and protein expressions of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 in the HQC+METTL3 knockdown group were significantly lower than those in the METTL3 knockdown group(P<0. 05). HQC could reduce the levels of IL-1ß, IL-6, and IL-8 to varying degrees(P<0. 05). The results indicate that HQC has a significant improvement effect on arthritis in AA rats. The expression of METTL3 is significantly increased in synovial tissue and AA-FLS of AA rats, which may be a potential target for the diagnosis and treatment of RA. HQC improves RA through the METTL3-SFRP4/Wnt/ß-catenin signaling pathway and has significant antiinflammatory and anti-rheumatic effects.


Subject(s)
Arthritis, Rheumatoid , Capsules , Drugs, Chinese Herbal , Wnt Signaling Pathway , beta Catenin , Animals , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/genetics , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Rats , Male , Wnt Signaling Pathway/drug effects , beta Catenin/metabolism , beta Catenin/genetics , Methyltransferases/genetics , Methyltransferases/metabolism , Humans , Rats, Sprague-Dawley , Synoviocytes/drug effects , Synoviocytes/metabolism , Proto-Oncogene Proteins
11.
J Neuroeng Rehabil ; 21(1): 116, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997727

ABSTRACT

OBJECTIVE: This study explored the impact of one session of low-pressure leg blood flow restriction (BFR) during treadmill walking on dual-task performance in older adults using the neurovisceral integration model framework. METHODS: Twenty-seven older adults participated in 20-min treadmill sessions, either with BFR (100 mmHg cuff pressure on both thighs) or without it (NBFR). Dual-task performance, measured through light-pod tapping while standing on foam, and heart rate variability during treadmill walking were compared. RESULTS: Following BFR treadmill walking, the reaction time (p = 0.002) and sway area (p = 0.012) of the posture dual-task were significantly reduced. Participants exhibited a lower mean heart rate (p < 0.001) and higher heart rate variability (p = 0.038) during BFR treadmill walking. Notably, BFR also led to band-specific reductions in regional brain activities (theta, alpha, and beta bands, p < 0.05). The topology of the EEG network in the theta and alpha bands became more star-like in the post-test after BFR treadmill walking (p < 0.005). CONCLUSION: BFR treadmill walking improves dual-task performance in older adults via vagally-mediated network integration with superior neural economy. This approach has the potential to prevent age-related falls by promoting cognitive reserves.


Subject(s)
Heart Rate , Walking , Humans , Aged , Male , Female , Walking/physiology , Heart Rate/physiology , Exercise Test , Brain/physiology , Brain/diagnostic imaging , Brain/blood supply , Regional Blood Flow/physiology , Psychomotor Performance/physiology , Leg/physiology
12.
Genes Dis ; 11(5): 101021, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39006182

ABSTRACT

Malformations of cortical development (MCD) are a group of developmental disorders characterized by abnormal cortical structures caused by genetic or harmful environmental factors. Many kinds of MCD are caused by genetic variation. MCD is the common cause of intellectual disability and intractable epilepsy. With rapid advances in imaging and sequencing technologies, the diagnostic rate of MCD has been increasing, and many potential genes causing MCD have been successively identified. However, the high genetic heterogeneity of MCD makes it challenging to understand the molecular pathogenesis of MCD and to identify effective targeted drugs. Thus, in this review, we outline important events of cortical development. Then we illustrate the progress of molecular genetic studies about MCD focusing on the PI3K/PTEN/AKT/mTOR pathway. Finally, we briefly discuss the diagnostic methods, disease models, and therapeutic strategies for MCD. The information will facilitate further research on MCD. Understanding the role of the PI3K/PTEN/AKT/mTOR pathway in MCD could lead to a novel strategy for treating MCD-related diseases.

13.
Sci Total Environ ; 948: 174736, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39029762

ABSTRACT

Excessive accumulation of chromium (Cr) causes severe damage to both physiological and biochemical processes and consequently growth repression in plants. Hexavalent chromium [Cr(VI)]-elicited alterations in plants have been widely elucidated at either physiological or molecular level, whereas little is known about trivalent chromium [Cr(III)]. Here, we found that both Cr(III) and Cr(VI) significantly inhibited root growth in rice plants. However, rice plants under Cr(VI) showed significantly less inhibition in root growth than those under Cr(III) at low levels, which might be attributed to the different hormetic effects of Cr(III) and Cr(VI) on rice plants. It was unexpected that Cr(III) could be actively taken up by rice roots similarly to Cr(VI); whereas they exhibited different kinetic uptake patterns. Furthermore, root-to-shoot Cr translocation under Cr(VI) was much lower than that under Cr(III). These results indicate that the uptake, translocation, and toxicity of Cr(III) differed greatly from those of Cr(VI). Transcriptome profiling of rice roots revealed that a series of gene families involved in detoxification, including ATP-binding cassette (ABC) transporters, multidrug and toxic compound extrusion proteins (MATEs), and Tau class glutathione S-transferases (GSTUs), were significantly associated with Cr accumulation and detoxification in rice roots. In addition, much more members of these gene families were upregulated by Cr(VI) compared to Cr(III), suggesting their vital roles in Cr uptake, translocation, and detoxification, especially under Cr(VI) stress. Further comparison of gstu9 and gstu10/50 mutants with their wild type confirmed that GSTUs play complex roles in the intracellular Cr transport and redox homeostasis during Cr(III) or Cr(VI) stress. Taken together, our findings provides new insights into the differential behaviors of Cr(III) and Cr(VI) in rice roots, as well as new candidate genes such as OsABCs and OsGSTUs, to further elucidate the mechanisms of the uptake, translocation, and detoxification of Cr(III) and Cr(VI).

14.
Plant Cell Environ ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946254

ABSTRACT

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

15.
Nat Commun ; 15(1): 6208, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043681

ABSTRACT

It is vital to explore effective ways for prolonging electrode lifespans under harsh electrolysis conditions, such as high current densities, acid environment, and impure water source. Here we report alternating electrolysis approaches that realize promptly and regularly repair/maintenance and concurrent bubble evolution. Electrode lifespans are improved by co-action of Fe group elemental ions and alkali metal cations, especially a unique Co2+-Na+ combo. A commercial Ni foam sustains ampere-level current densities alternatingly during continuous electrolysis for 93.8 h in an acidic solution, whereas such a Ni foam is completely dissolved in ~2 h for conventional electrolysis conditions. The work not only explores an alternating electrolysis-based system, alkali metal cation-based catalytic systems, and alkali metal cation-based electrodeposition techniques, and beyond, but demonstrates the possibility of prolonged electrolysis by repeated deposition-dissolution processes. With enough adjustable experimental variables, the upper improvement limit in the electrode lifespan would be high.

16.
Glycoconj J ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39046578

ABSTRACT

Pertussis vaccines have been very effective in controlling whooping-cough epidemics but are ineffective in controlling circulation in older children and adults, thus facilitating the onset of future outbreaks. Antibodies against the lipopolysaccharide could reduce the carriage of the bacteria, its circulation, and transmission. The oligosaccharide fragments from the lipopolysaccharide may become a potential complement to existing vaccines in the form of protein glycoconjugates. An important step in the development of this type of vaccine is defining the minimal oligosaccharide epitope recognized by B. pertussis anti-lipopolysaccharide antibodies. This paper describes the complete synthesis of oligosaccharides containing two to five monosaccharide units corresponding to the pentasaccharide at the nonreducing end of the lipooligosaccharide and their recognition by mice and rabbit antibodies elicited against whole-cell B. pertussis. For the first time, we report that the terminal disaccharide, α-D-GlcNAcp-(1 → 4)-(2,3-di-NAc)-D-ManAp acid is the minimal structure recognized by antibodies induced by B. pertussis.

17.
J Am Chem Soc ; 146(26): 18011-18018, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38905313

ABSTRACT

Bioisosterism is a valuable principle exploited in drug discovery to fine-tune physicochemical properties of bioactive compounds. Functionalized 3-aryl oxetanes, as an important class of bioisosteres for benzoyl groups (highly prevalent structures in approved drugs), have been rarely utilized in agrochemicals and pharmaceuticals due to significant synthetic challenges. Here, we present a modular synthetic strategy based on the unexplored yet readily available reagents, oxetanyl trichloroacetimidates, inspired by Schmidt glycosylation, enabling easy access to a library of functionalized oxetanes. This operationally simple protocol leverages the vast existing libraries of aryl halides and various nucleophiles. The power and generality of this approach is demonstrated by late-stage functionalization of complex molecules, as well as the rapid synthesis of oxetane analogues of bioactive molecules and marketed drugs. Preliminary mechanistic study suggests that the oxygen atom in the oxetane ring plays a crucial role in stabilizing the carbocation intermediates.

18.
Microorganisms ; 12(6)2024 May 24.
Article in English | MEDLINE | ID: mdl-38930441

ABSTRACT

The lack of efficient ways to dispose of lignocellulosic agricultural residues is a serious environmental issue. Low temperatures greatly impact the ability of organisms to degrade these wastes and convert them into nutrients. Here, we report the isolation and genomic characterization of a microbial consortium capable of degrading corn straw at low temperatures. The microorganisms isolated showed fast cellulose-degrading capabilities, as confirmed by scanning electron microscopy and the weight loss in corn straw. Bacteria in the consortium behaved as three diverse and functionally distinct populations, while fungi behaved as a single population in both diversity and functions overtime. The bacterial genus Pseudomonas and the fungal genus Thermoascus had prominent roles in the microbial consortium, showing significant lignocellulose waste-degrading functions. Bacteria and fungi present in the consortium contained high relative abundance of genes for membrane components, with amino acid breakdown and carbohydrate degradation being the most important metabolic pathways for bacteria, while fungi contained more genes involved in energy use, carbohydrate degradation, lipid and fatty acid decomposition, and biosynthesis.

19.
Medicine (Baltimore) ; 103(26): e38540, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38941410

ABSTRACT

RATIONALE: Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed through intraoperative rapid pathology, this condition generally has a favorable prognosis. Nevertheless, comprehensive treatment guidelines across all disease stages are lacking, the purpose of this study is to report 1 case of the disease and propose the treatment plan for each stage of the disease. PATIENT CONCERNS: A patient presented with thyroid swelling, classified as C-TIRADS 4A following a physical examination. Preoperative thyroid puncture identified papillary thyroid carcinoma, and genetic testing revealed a BRAF gene exon 15-point mutation. Ancillary tests showed a slightly decreased thyroid stimulating hormone (TSH) level (0.172) with no other significant abnormalities. DIAGNOSES: Preoperative fine-needle aspiration cytology (FNAC) confirmed right-side thyroid cancer. Intraoperative exploration uncovered a TGDC and intraoperative rapid pathology confirmed thyroglossal duct carcinoma. INTERVENTIONS: A Sistrunk operation and ipsilateral thyroidectomy were performed. OUTCOMES: Postoperative recovery was satisfactory. LESSONS: Thyroglossal duct carcinoma is a rare disease affecting the neck. Due to limited clinical cases and the favorable prognosis associated with this condition, there is currently no established set of diagnostic and treatment guidelines. According to tumor size, lymph node metastasis, thyroid status and other factors, the corresponding treatment methods were established for each stage of thyroglossal duct cancer, which laid the foundation for the subsequent treatment development of this disease.


Subject(s)
Thyroglossal Cyst , Thyroid Neoplasms , Humans , Thyroglossal Cyst/surgery , Thyroglossal Cyst/pathology , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/genetics , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/surgery , Thyroid Cancer, Papillary/diagnosis , Thyroid Cancer, Papillary/genetics , Female , Thyroidectomy/methods , Male , Proto-Oncogene Proteins B-raf/genetics , Adult , Biopsy, Fine-Needle
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