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1.
World J Gastrointest Oncol ; 16(6): 2271-2283, 2024 Jun 15.
Article de Anglais | MEDLINE | ID: mdl-38994170

RÉSUMÉ

The morbidity and mortality of gastrointestinal (GI) malignancies are among the highest in the world, posing a serious threat to human health. Because of the insidious onset of the cancer, it is difficult for patients to be diagnosed at an early stage, and it rapidly progresses to an advanced stage, resulting in poor treatment and prognosis. Fusobacterium nucleatum (F. nucleatum) is a gram-negative, spore-free anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal, esophageal, gastric, and pancreatic cancers via various intricate mechanisms. Recent development in novel research suggests that F. nucleatum may function as a biomarker in GI malignancies. Detecting the abundance of F. nucleatum in stool, saliva, and serum samples of patients may aid in the diagnosis, risk assessment, and prognosis monitoring of GI malignancies. This editorial systematically describes the biological roles and mechanisms of F. nucleatum in GI malignancies focusing on the application of F. nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F. nucleatum and GI tumors-related research.

2.
Res Sq ; 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38978583

RÉSUMÉ

The rapid onset of innate immune defenses is critical for early control of viral replication in an infected host, yet it can also lead to irreversible tissue damage, especially in the respiratory tract. Intricate regulatory mechanisms must exist that modulate inflammation, while controlling the infection. Here, B cells expressing choline acetyl transferase (ChAT), an enzyme required for production of the metabolite and neurotransmitter acetylcholine (ACh) are identified as such regulators of the immediate early response to influenza A virus. Lung tissue ChAT + B cells are shown to interact with a7 nicotinic Ach receptor-expressing lung interstitial macrophages in mice within 24h of infection to control their production of TNFa, shifting the balance towards reduced inflammation at the cost of enhanced viral replication. Thus, innate-stimulated B cells are key participants of an immediate-early regulatory cascade that controls lung tissue damage after viral infection.

3.
Sci Rep ; 14(1): 16745, 2024 Jul 20.
Article de Anglais | MEDLINE | ID: mdl-39033185

RÉSUMÉ

Patchouli alcohol (PA) is a widely used pharmaceutical ingredient in various Chinese traditional herbal medicine (THM) formulations, known for its modulatory effects on the gut microbiota. The present study investigated PA's anti-inflammatory and regulatory effects on gut microbiota and its mode of action (MOA). Based on the assessments of ulcerative colitis (UC) symptoms, PA exhibited promising preventions against inflammatory response. In accordance, the expressions of pro-inflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and chemokine ligand 5 were significantly attenuated under PA treatment. Furthermore, PA enhanced the intestinal barrier damage caused by dextran sodium sulfate (DSS). Interestingly, PA exhibited negligible inventions on DSS-induced gut microbiota dysbiosis. PA did not affect the diversity of the DSS gut microbiota, it did alter the composition, as evidenced by a significant increase in the Firmicutes-Bacteroidetes (F/B) ratio. Finally, the MOA of PA against inflammation in DSS-treated mice was addressed by suppressing the expressions of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS). In conclusion, PA prevented inflammatory response in the DSS-induced UC mice model via directly suppressing HO-1 and iNOS-associated antioxidant signal pathways, independent of its effects on gut microbiota composition.


Sujet(s)
Rectocolite hémorragique , Sulfate dextran , Modèles animaux de maladie humaine , Microbiome gastro-intestinal , Sesquiterpènes , Animaux , Rectocolite hémorragique/induit chimiquement , Rectocolite hémorragique/traitement médicamenteux , Rectocolite hémorragique/microbiologie , Rectocolite hémorragique/métabolisme , Souris , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Sesquiterpènes/pharmacologie , Heme oxygenase-1/métabolisme , Nitric oxide synthase type II/métabolisme , Mâle , Anti-inflammatoires/pharmacologie , Dysbiose/induit chimiquement , Dysbiose/microbiologie , Souris de lignée C57BL , Médicaments issus de plantes chinoises/pharmacologie , Médicaments issus de plantes chinoises/usage thérapeutique
4.
Front Plant Sci ; 15: 1431097, 2024.
Article de Anglais | MEDLINE | ID: mdl-38947949

RÉSUMÉ

Tender bamboo shoots undergo rapid senescence that influences their quality and commercial value after harvest. In this study, the tender sweet bamboo shoots ('Wensun') were packed by a passive modified atmosphere packaging (PMAP) to inhibit the senescence process, taking polyethylene package as control. The increase in CO2 and the decrease in O2 gas concentrations in the headspace atmosphere of the packages were remarkably modified by PMAP treatments. The modified gas atmosphere packaging inhibited the changes in firmness, as well as the content of cellulose, total pectin, and lignin in the cell walls of bamboo shoots. The enzymatic activities of cellulase, pectinase, and polygalacturonase that act on cell wall polysaccharides, and phenylalanine ammonia lyase, cinnamyl alcohol dehydrogenase, peroxidase, and laccase regulating the lignin biosynthesis were modified by PMAP treatment different from control during storage. The expression levels of the lignin biosynthesis genes PePAL3/4, PeCAD, Pe4CL5, PeC4H, PeCCOAOMT, PeCOMT, cellulose synthase PeCESA1, and related transcription factors PeSND2, PeKNAT7, PeMYB20, PeMYB63, and PeMYB85 were clearly regulated. These results suggest that PMAP efficiently retards the changes in lignin and cell wall polysaccharides, thus delaying the senescence of tender sweet bamboo shoots during storage.

5.
Cell Host Microbe ; 32(7): 1103-1113.e6, 2024 Jul 10.
Article de Anglais | MEDLINE | ID: mdl-38838675

RÉSUMÉ

Antibiotic treatment promotes the outgrowth of intestinal Candida albicans, but the mechanisms driving this fungal bloom remain incompletely understood. We identify oxygen as a resource required for post-antibiotic C. albicans expansion. C. albicans depleted simple sugars in the ceca of gnotobiotic mice but required oxygen to grow on these resources in vitro, pointing to anaerobiosis as a potential factor limiting growth in the gut. Clostridia species limit oxygen availability in the large intestine by producing butyrate, which activates peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling to maintain epithelial hypoxia. Streptomycin treatment depleted Clostridia-derived butyrate to increase epithelial oxygenation, but the PPAR-γ agonist 5-aminosalicylic acid (5-ASA) functionally replaced Clostridia species to restore epithelial hypoxia and colonization resistance against C. albicans. Additionally, probiotic Escherichia coli required oxygen respiration to prevent a post-antibiotic bloom of C. albicans, further supporting the role of oxygen in colonization resistance. We conclude that limited access to oxygen maintains colonization resistance against C. albicans.


Sujet(s)
Candida albicans , Oxygène , Candida albicans/effets des médicaments et des substances chimiques , Animaux , Souris , Oxygène/métabolisme , Récepteur PPAR gamma/métabolisme , Antibactériens/pharmacologie , Escherichia coli/effets des médicaments et des substances chimiques , Candidose/microbiologie , Anaérobiose , Hypoxie/métabolisme , Souris de lignée C57BL , Streptomycine/pharmacologie , Humains , Caecum/microbiologie , Muqueuse intestinale/microbiologie , Muqueuse intestinale/métabolisme , Axénie
6.
Theranostics ; 14(8): 3282-3299, 2024.
Article de Anglais | MEDLINE | ID: mdl-38855179

RÉSUMÉ

Rationale: Pharmacological targeting of mitochondrial ion channels is developing as a new direction in cancer therapy. The opening or closing of these channels can impact mitochondrial function and structure by interfering with intracellular ion homeostasis, thereby regulating cell fate. Nevertheless, their abnormal expression or regulation poses challenges in eliminating cancer cells, and further contributes to metastasis, recurrence, and drug resistance. Methods: We developed an engineered mitochondrial targeted delivery system with self-reinforcing potassium ion (K+) influx via amphiphilic mitochondrial targeting polymer (TMP) as carriers to co-deliver natural K+ channel agonists (Dinitrogen oxide, DZX) and artificial K+ channel molecules (5F8). Results: Using this method, DZX specifically activated natural K+ channels, whereas 5F8 assembled artificial K+ channels on the mitochondrial membrane, leading to mitochondrial K+ influx, as well as oxidative stress and activation of the mitochondrial apoptotic pathway. Conclusion: The synergistic effect of 5F8 and DZX presents greater effectiveness in killing cancer cells than DZX alone, and effectively inhibited tumor recurrence and lung metastasis following surgical resection of breast cancer tumors in animal models. This strategy innovatively integrates antihypertensive drugs with artificial ion channel molecules for the first time to effectively inhibit tumor recurrence and metastasis by disrupting intracellular ion homeostasis, which will provide a novel perspective for postoperative tumor therapy.


Sujet(s)
Homéostasie , Mitochondries , Animaux , Mitochondries/métabolisme , Mitochondries/effets des médicaments et des substances chimiques , Humains , Homéostasie/effets des médicaments et des substances chimiques , Souris , Lignée cellulaire tumorale , Femelle , Récidive tumorale locale/prévention et contrôle , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Apoptose/effets des médicaments et des substances chimiques , Potassium/métabolisme , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/secondaire , Tumeurs du poumon/anatomopathologie , Tumeurs du poumon/métabolisme , Souris de lignée BALB C , Canaux ioniques/métabolisme , Canaux potassiques/métabolisme , Souris nude , Métastase tumorale
7.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2178-2187, 2024 Apr.
Article de Chinois | MEDLINE | ID: mdl-38812233

RÉSUMÉ

This paper aims to explore the effect of Xuming Decoction in the Records of Proved Prescriptions, Ancient and Modern on cerebral ischemic injury and angiogenesis in the rat model of acute cerebral infarction. SD rats were randomized into 6 groups: sham group, model group, low-, medium-, and high-dose(5.13, 10.26, and 20.52 g·kg~(-1), respectively) Xuming Decoction groups, and butylphthalide(0.06 g·kg~(-1)) group. After the successful establishment of the rat model by middle cerebral artery occlusion(MCAO), rats in the sham and model groups were administrated with distilled water and those in other groups with corresponding drugs for 7 consecutive days. After the neurological function was scored, all the rats were sacrificed, and the brain tissue samples were collected. The degree of cerebral ischemic injury was assessed by the neurological deficit score and staining with 2,3,5-triphenyltetrazolium chloride. Hematoxylin-eosin staining was performed to observe the pathological changes in the brain. Transmission electron microscopy was employed to observe the ultrastructures of neurons and microvascular endothelial cells(ECs) on the ischemic side of the brain tissue. Immunofluorescence assay was employed to detect the expression of von Willebrand factor(vWF) and hematopoietic progenitor cell antigen CD34(CD34) in the ischemic brain tissue. Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of Runt-related transcription factor 1(RUNX1), vascular endothelial growth factor(VEGF), angiopoietin-1(Ang-1), angiopoietin-2(Ang-2), and VEGF receptor 2(VEGFR2) in the ischemic brain tissue. The results showed that compared with the sham group, the model group showed increased neurological deficit score and cerebral infarction area(P<0.01), pathological changes, and damaged ultrastructure of neurons and microvascular ECs in the ischemic brain tissue. Furthermore, the modeling up-regulated the mRNA levels of RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01) and the protein levels of vWF, CD34, RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.05 or P<0.01). Compared with the model group, high-dose Xuming Decoction and butylphthalide decreased the neurological deficit score and cerebral infarction area(P<0.01) and alleviated the pathological changes and damage of the ultrastructure of neurons and microvascular ECs in the ischemic brain tissue. Moreover, they up-regulated the mRNA levels of RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01) and the protein levels of vWF, CD34, RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01). The results suggest that Xuming Decoction in the Records of Proved Prescriptions, Ancient and Modern can promote the angiogenesis and collateral circulation establishment to alleviate neurological dysfunction of the ischemic brain tissue in MCAO rats by regulating the RUNX1/VEGF pathway.


Sujet(s)
Encéphalopathie ischémique , Infarctus cérébral , Modèles animaux de maladie humaine , Médicaments issus de plantes chinoises , Rat Sprague-Dawley , Animaux , Rats , Mâle , Médicaments issus de plantes chinoises/pharmacologie , Infarctus cérébral/traitement médicamenteux , Infarctus cérébral/métabolisme , Infarctus cérébral/génétique , Encéphalopathie ischémique/traitement médicamenteux , Encéphalopathie ischémique/métabolisme , Encéphalopathie ischémique/génétique , Humains , Facteur de croissance endothéliale vasculaire de type A/génétique , Facteur de croissance endothéliale vasculaire de type A/métabolisme , Néovascularisation physiologique/effets des médicaments et des substances chimiques , Angiopoïétine-2/génétique , Angiopoïétine-2/métabolisme ,
8.
J Steroid Biochem Mol Biol ; 242: 106547, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38754522

RÉSUMÉ

Premature ovarian insufficiency (POI) presents a substantial challenge to women's physiological and psychological well-being. Hormone replacement therapy, as the preferred therapeutic approach, involves solely exogenous supplementation of estrogen. Moxibustion, a traditional Chinese external treatment, has been investigated in our previous studies. It not only improves hormone levels and clinical symptoms in POI patients but also safeguards ovarian reserve. This study aims to explore the regulatory mechanisms by which moxibustion modulates hormone levels and restores ovarian function in POI. A POI rat model was established using cyclophosphamide, and moxibustion treatment was applied at acupoints "CV4" and "SP6" for a total of four courses. Subsequently, ovaries from each group were subjected to transcriptome sequencing (Bulk RNA-seq). Target pathways and key genes were selected through enrichment analysis and GSVA scoring, with validation using various techniques including electron microscopy, ELISA, Western blot, and immunohistochemistry. The results demonstrated that moxibustion restored the estrous cycle in POI rats, improved sex hormone levels, reduced the number of atretic follicles, and increased the count of dominant follicles (P<0.05). Bulk RNA-seq analysis revealed that moxibustion downregulated pathways associated with ovarian dysfunction, infertility, and immune responses, upregulated pathways related to follicular development and ovarian steroidogenesis. Furthermore, our data confirmed that moxibustion significantly increased the number of ovarian granulosa cells (GCs) and upregulated the expression of proteins related to steroidogenesis in GCs, including FSHR, P450 arom, cAMP, PKA, and CREB (P<0.05), with no significant effect observed on proteins related to steroidogenesis in theca cells. These outcomes aligned with the RNA-seq results. In conclusion, these findings propose that moxibustion enhances steroidogenesis in GCs through the activation of the cAMP/PKA/CREB pathway, consequently improving impaired ovarian function in POI rats. This study provides robust evidence supporting moxibustion as a targeted intervention for treating POI by specifically regulating steroidogenesis in GCs.


Sujet(s)
Protéine de liaison à l'élément de réponse à l'AMP cyclique , Cyclic AMP-Dependent Protein Kinases , AMP cyclique , Cellules de la granulosa , Moxibustion , Insuffisance ovarienne primitive , Animaux , Femelle , Rats , AMP cyclique/métabolisme , Protéine de liaison à l'élément de réponse à l'AMP cyclique/métabolisme , Protéine de liaison à l'élément de réponse à l'AMP cyclique/génétique , Cyclic AMP-Dependent Protein Kinases/métabolisme , Cyclic AMP-Dependent Protein Kinases/génétique , Cellules de la granulosa/métabolisme , Ovaire/métabolisme , Insuffisance ovarienne primitive/thérapie , Insuffisance ovarienne primitive/métabolisme , Insuffisance ovarienne primitive/génétique , Rat Sprague-Dawley , Transduction du signal
9.
Mycopathologia ; 189(3): 32, 2024 Apr 15.
Article de Anglais | MEDLINE | ID: mdl-38622365

RÉSUMÉ

The rare fungus Candida saopaulonensis has never been reported to be associated with human infection. We report the draft genome sequence of the first clinical isolate of C. saopaulonensis, which was isolated from a very premature infant with sepsis. This is the first genome assembly reaching the near-complete chromosomal level with structural annotation for this species, opening up avenues for exploring evolutionary patterns and genetic mechanisms of pathogenesis.


Sujet(s)
Candida , Sepsie , Humains , Nouveau-né , Candida/génétique , Génome fongique , Prématuré
10.
World J Gastrointest Oncol ; 16(3): 979-990, 2024 Mar 15.
Article de Anglais | MEDLINE | ID: mdl-38577474

RÉSUMÉ

BACKGROUND: Helicobacter pylori (H. pylori) is the primary risk factor for gastric cancer (GC), the Wnt/ß-Catenin signaling pathway is closely linked to tumourigenesis. GC has a high mortality rate and treatment cost, and there are no drugs to prevent the progression of gastric precancerous lesions to GC. Therefore, it is necessary to find a novel drug that is inexpensive and preventive to against GC. AIM: To explore the effects of H. pylori and Moluodan on the Wnt/ß-Catenin signaling pathway and precancerous lesions of GC (PLGC). METHODS: Mice were divided into the control, N-methyl-N-nitrosourea (MNU), H. pylori + MNU, and Moluodan groups. We first created an H. pylori infection model in the H. pylori + MNU and Moluodan groups. A PLGC model was created in the remaining three groups except for the control group. Moluodan was fed to mice in the Moloudan group ad libitum. The general condition of mice were observed during the whole experiment period. Gastric tissues of mice were grossly and microscopically examined. Through quantitative real-time PCR (qRT-PCR) and Western blotting analysis, the expression of relevant genes were detected. RESULTS: Mice in the H. pylori + MNU group showed the worst performance in general condition, gastric tissue visual and microscopic observation, followed by the MNU group, Moluodan group and the control group. QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes, the results showed that the H. pylori + MNU group had the highest expression, followed by the MNU group, Moluodan group and the control group. CONCLUSION: H. pylori can activate the Wnt/ß-catenin signaling pathway, thereby facilitating the development and progression of PLGC. Moluodan suppressed the activation of the Wnt/ß-catenin signaling pathway, thereby decreasing the progression of PLGC.

11.
Ecotoxicol Environ Saf ; 276: 116334, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38626607

RÉSUMÉ

Thioacetamide (TAA) within the liver generates hepatotoxic metabolites that can be induce hepatic fibrosis, similar to the clinical pathological features of chronic human liver disease. The potential protective effect of Albiflorin (ALB), a monoterpenoid glycoside found in Paeonia lactiflora Pall, against hepatic fibrosis was investigated. The mouse hepatic fibrosis model was induced with an intraperitoneal injection of TAA. Hepatic stellate cells (HSCs) were subjected to treatment with transforming growth factor-beta (TGF-ß), while lipopolysaccharide/adenosine triphosphate (LPS/ATP) was added to stimulate mouse peritoneal macrophages (MPMs), leading to the acquisition of conditioned medium. For TAA-treated mice, ALB reduced ALT, AST, HYP levels in serum or liver. The administration of ALB reduced histopathological abnormalities, and significantly regulated the expressions of nuclear receptor-related 1 protein (NURR1) and the P2X purinoceptor 7 receptor (P2×7r) in liver. ALB could suppress HSCs epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, and pro-inflammatory factor level. ALB also remarkably up-regulated NURR1, inhibited P2×7r signaling pathway, and worked as working as C-DIM12, a NURR1 agonist. Moreover, deficiency of NURR1 in activated HSCs and Kupffer cells weakened the regulatory effect of ALB on P2×7r inhibition. NURR1-mediated inhibition of inflammatory contributed to the regulation of ALB ameliorates TAA-induced hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. Therefore, ALB plays a significant part in the mitigation of TAA-induced hepatotoxicity this highlights the potential of ALB as a protective intervention for hepatic fibrosis.


Sujet(s)
Cellules étoilées du foie , Cirrhose du foie , Membre-2 du groupe A de la sous-famille-4 de récepteurs nucléaires , Transduction du signal , Thioacétamide , Animaux , Thioacétamide/toxicité , Cellules étoilées du foie/effets des médicaments et des substances chimiques , Souris , Cirrhose du foie/induit chimiquement , Cirrhose du foie/traitement médicamenteux , Transduction du signal/effets des médicaments et des substances chimiques , Mâle , Membre-2 du groupe A de la sous-famille-4 de récepteurs nucléaires/métabolisme , Membre-2 du groupe A de la sous-famille-4 de récepteurs nucléaires/génétique , Composés pontés/pharmacologie , Souris de lignée C57BL , Inflammation/induit chimiquement , Inflammation/traitement médicamenteux , Transition épithélio-mésenchymateuse/effets des médicaments et des substances chimiques
12.
Int J Pharm ; 657: 124126, 2024 May 25.
Article de Anglais | MEDLINE | ID: mdl-38626845

RÉSUMÉ

As the monotherapy of available analgesics is usually accompanied by serious side effects or limited efficacy in the management of chronic pain, multimodal analgesia is widely used to achieve improved benefit-to-risk ratios in clinic. Drug-drug salts are extensively researched to optimize the physicochemical properties of active pharmaceutical ingredients (APIs) and achieve clinical benefits compared with individual APIs or their combination. New drug-drug salt crystals metformin-ibuprofen (MET-IBU) and metformin-naproxen (MET-NAP) were prepared from metformin (MET) and two poorly water-soluble anti-inflammatory drugs (IBU and NAP) by the solvent evaporation method. The structures of these crystals were confirmed by single crystal and powder X-ray diffraction, Hirshfeld surface, Fourier transform infrared spectroscopy and thermal analysis. Both MET-IBU and MET-NAP showed significantly improved solubility and intrinsic dissolution rate than the pure IBU or NAP. The stability test indicated that MET-IBU and MET-NAP have excellent physical stability under stressing test (10 days) and accelerated conditions (3 months). Moreover, isobolographic analysis suggested that MET-IBU and MET-NAP exerted potent and synergistic antinociceptive effects in λ-Carrageenan-induced inflammatory pain in mice, and both of them had an advantage in rapid pain relief. These results demonstrated the potential of MET-IBU and MET-NAP to achieve synergistic antinociceptive effects by developing drug-drug salt crystals.


Sujet(s)
Analgésiques , Cristallisation , Synergie des médicaments , Ibuprofène , Metformine , Naproxène , Solubilité , Metformine/composition chimique , Metformine/administration et posologie , Metformine/pharmacologie , Animaux , Naproxène/composition chimique , Naproxène/administration et posologie , Ibuprofène/composition chimique , Ibuprofène/administration et posologie , Ibuprofène/pharmacologie , Analgésiques/composition chimique , Analgésiques/administration et posologie , Analgésiques/pharmacologie , Souris , Mâle , Anti-inflammatoires non stéroïdiens/composition chimique , Anti-inflammatoires non stéroïdiens/administration et posologie , Anti-inflammatoires non stéroïdiens/pharmacologie , Douleur/traitement médicamenteux , Stabilité de médicament , Carragénane , Libération de médicament , Sels/composition chimique
13.
Chem Commun (Camb) ; 60(39): 5201-5204, 2024 May 09.
Article de Anglais | MEDLINE | ID: mdl-38651837

RÉSUMÉ

The defluoroborylation of fluoroarenes by chromium-catalyzed cleavage of unactivated C-F bonds is described. The reaction uses HBpin as the boron source, low-cost and commercially available chromium salt as the precatalyst, and terpyridine as a crucial ligand, providing a protocol with atom-efficient benefits and a wide range of applicable substrates for the functionalization of aryl C-F bonds. Preliminary mechanistic studies indicate that an unprecedented Cr-catalyzed magnesiation of the unactivated C-F bond occurred. The generated arylmagnesium intermediates then participated in the subsequent borylation reaction. The application of the strategy in the preparation of valuable derivatives is demonstrated by the late-stage functionalization of boronate ester groups.

14.
Heliyon ; 10(6): e27935, 2024 Mar 30.
Article de Anglais | MEDLINE | ID: mdl-38515688

RÉSUMÉ

Objectives: This study was aimed at analyzing the burden and trend of Alzheimer's disease and other dementias attributed to smoking (SADD) in the Belt and Road Initiative (BRI) countries during 1990-2019. Methods: Data from The 2019 Global Burden of Disease Study was used to extract information on the burden of SADD in terms of the numbers and age-standardized rate of mortality (ASMR) and disability-adjusted life years (ASDALR) in the BRI countries for 1990-2019. The average annual percent change (AAPC) was used to analyze the temporal trends of ASDALR from 1990 to 2019 and in the final decade by Joinpoint regression analysis. Results: The DALYs of SADD were the highest in China, India, and the Russian Federation in 1990 and in Lebanon, Montenegro and Bosnia, and Herzegovina in 2019. From 1990 to 2019, the ASDALR in China had increased from 55.50/105 to 66.18/105, but decreased from 2010 to 2019, while that of India had declined from 32.84/105 to 29.35/105, but increased from 2010 to 2019. The ASDALR showed the fastest increase in the Russian Federation, with AAPC of 1.97% (95% confidence interval [CI]: 1.77%, 2.16%), and the fastest decline in Sri Lanka, with AAPC of -2.69% (95% CI: 2.79%, -2.59%). ASMR and ASDALR from SADD showed a substantial decline during 1990-2019 both globally and in the different socio-demographic index (SDI) regions (all P < 0.05, except for the high-middle-SDI region). Compared to the rates in males, the AAPC in ASDALR of females was significantly greater in 20 countries(all P < 0.05). In the age group of 20-54 years, the DALYs rate showed a decreasing trend only in 13 members in the low-SDI region (all P < 0.05). Conclusion: Under the premise of eliminating the differences, mobilizing resources in the country itself, the BRI organization, and globally will help reduce the global SADD burden and achieve healthy and sustainable development.

15.
Mol Plant Microbe Interact ; 37(6): 488-497, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38427716

RÉSUMÉ

Gti1/Pac2 is a fungal-specific transcription factor family with a stable and conserved N-terminal domain. Generally, there are two members in this family, named Gti1/Wor1/Rpy1/Mit1/Reg1/Ros1/Sge1 and Pac2, which are involved in fungal growth, development, stress response, spore production, pathogenicity, and so on. The Gti1/Pac2 family proteins share some conserved and distinct functions. For example, in Schizosaccharomyces pombe, Gti1 promotes the initiation of gluconate uptake during glucose starvation, while Pac2 controls the onset of sexual development in a pathway independent of the cAMP cascade. In the last two decades, more attention was focused on the Gti1 and its orthologs because of their significant effect on morphological switching and fungal virulence. By contrast, limited work was published on the functions of Pac2, which is required for stress responses and conidiation, but plays a minor role in fungal virulence. In this review, we present an overview of our current understanding of the Gti1/Pac2 proteins that contribute to fungal development and/or pathogenicity and of the regulation mechanisms during infection related development. Understanding the working networks of the conserved Gti1/Pac2 transcription factors in fungal pathogenicity not only advances our knowledge of the highly elaborate infection process but may also lead to the development of novel strategies for the control of plant disease. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Sujet(s)
Protéines fongiques , Stress physiologique , Protéines fongiques/métabolisme , Protéines fongiques/génétique , Virulence , Champignons/pathogénicité , Champignons/métabolisme , Champignons/physiologie , Régulation de l'expression des gènes fongiques , Facteurs de transcription/métabolisme , Facteurs de transcription/génétique , Maladies des plantes/microbiologie , Morphogenèse
16.
Nat Commun ; 15(1): 1138, 2024 Feb 07.
Article de Anglais | MEDLINE | ID: mdl-38326391

RÉSUMÉ

Two-dimensional (2D) semiconductor-based vertical-transport field-effect transistors (VTFETs) - in which the current flows perpendicularly to the substrate surface direction - are in the drive to surmount the stringent downscaling constraints faced by the conventional planar FETs. However, low-power device operation with a sub-60 mV/dec subthreshold swing (SS) at room temperature along with an ultra-scaled channel length remains challenging for 2D semiconductor-based VTFETs. Here, we report steep-slope VTFETs that combine a gate-controllable van der Waals heterojunction and a metal-filamentary threshold switch (TS), featuring a vertical transport channel thinner than 5 nm and sub-thermionic turn-on characteristics. The integrated TS-VTFETs were realised with efficient current switching behaviours, exhibiting a current modulation ratio exceeding 1 × 108 and an average sub-60 mV/dec SS over 6 decades of drain current. The proposed TS-VTFETs with excellent area- and energy-efficiency could help to tackle the performance degradation-device downscaling dilemma faced by logic transistor technologies.

17.
J Affect Disord ; 352: 342-348, 2024 May 01.
Article de Anglais | MEDLINE | ID: mdl-38364978

RÉSUMÉ

BACKGROUND: The incidence of adolescent depression has markedly risen in recent years, with a high recurrence rate into adulthood. Diagnosis in adolescents is challenging due to subjective factors, highlighting the crucial need for objective diagnostic markers. METHODS: Our study enrolled 204 participants, including healthy controls (n = 88) and first-episode adolescent depression patients (n = 116). Serum samples underwent gas chromatography-mass spectrometry (GC-MS) analysis to assess non-esterified fatty acids (NEFA) expression. Machine learning and ROC analysis were employed to identify potential biomarkers, followed by bioinformatics analysis to explore underlying mechanisms. RESULTS: Nearly all differentially expressed NEFA exhibited significant downregulation. Notably, nonanoic acid, cis-10-pentadecenoic acid, cis-10-carboenoic acid, and cis-11-eicosenoic acid demonstrated excellent performance in distinguishing adolescent depression patients. Metabolite-gene interaction analysis revealed these NEFAs interacted with multiple genes. KEGG pathway analysis on these genes suggested that differentially expressed NEFA may impact PPAR and cAMP signaling pathways. LIMITATIONS: Inclusion of diverse populations for evaluation is warranted. Biomarkers identified in this study require samples that are more in line with the experimental design for external validation, and further basic research is necessary to validate the potential depressive mechanisms of NEFA. CONCLUSIONS: The overall reduction in NEFA expression in first-episode adolescent depression patients suggests a potential mediation of depression symptoms through cAMP and PPAR signaling pathways. NEFA levels show promise as a diagnostic tool for identifying first-episode adolescent depression patients.


Sujet(s)
Dépression , Acide gras libre , Humains , Adolescent , Acide gras libre/métabolisme , Dépression/diagnostic , Récepteurs activés par les proliférateurs de peroxysomes , Marqueurs biologiques , Chromatographie gazeuse-spectrométrie de masse
18.
Nanoscale ; 16(7): 3226-3242, 2024 Feb 15.
Article de Anglais | MEDLINE | ID: mdl-38284230

RÉSUMÉ

Chimeric antigen receptor T (CAR-T) cells have shown promising outcomes in the treatment of hematologic malignancies. However, CAR-T cell therapy in solid tumor treatment has been significantly hindered, due to the complex manufacturing process, difficulties in proliferation and infiltration, lack of precision, or poor visualization ability. Fortunately, recent reports have shown that functional biomaterial designs such as nanoparticles, polymers, hydrogels, or implantable scaffolds might have potential to address the above challenges. In this review, we aim to summarize the recent advances in the designs of functional biomaterials for assisting CAR-T cell therapy for potential solid tumor treatments. Firstly, by enabling efficient CAR gene delivery in vivo and in vitro, functional biomaterials can streamline the difficult process of CAR-T cell therapy manufacturing. Secondly, they might also serve as carriers for drugs and bioactive molecules, promoting the proliferation and infiltration of CAR-T cells. Furthermore, a number of functional biomaterial designs with immunomodulatory properties might modulate the tumor microenvironment, which could provide a platform for combination therapies or improve the efficacy of CAR-T cell therapy through synergistic therapeutic effects. Last but not least, the current challenges with biomaterials-based CAR-T therapies will also be discussed, which might be helpful for the future design of CAR-T therapy in solid tumor treatment.


Sujet(s)
Tumeurs , Récepteurs chimériques pour l'antigène , Humains , Association thérapeutique , Tumeurs/thérapie , Matériaux biocompatibles/usage thérapeutique , Thérapie cellulaire et tissulaire , Microenvironnement tumoral
19.
Huan Jing Ke Xue ; 45(1): 1-7, 2024 Jan 08.
Article de Chinois | MEDLINE | ID: mdl-38216453

RÉSUMÉ

Based on the observation data of the daily maximum 8-hour ozone (O3) average concentration[MDA8-O3, ρ(O3-8h)] and meteorological reanalysis data in the Pearl River Delta Region from 2015 to 2022, four machine learning methods, i.e., support vector machine regression (SVR), random forest (RF), multi-layer perceptron (MLP), and lightweight gradient boosting machine (LG) were used to establish MDA8-O3 prediction models. The results showed that the SVR model had the best prediction performance on MDA8-O3 during the whole year, the coefficient of determination (R2) reached 0.86, and the root mean square error (RMSE) and mean absolute error (MAE) were 16.3 µg·m-3 and 12.3 µg·m-3, respectively. The prediction performance of the SVR model in autumn was still slightly better than that of LG and MLP, with R2,RMSE,and MAE values of 0.88, 19.8 µg·m-3,and 16.1 µg·m-3, respectively. The RF model performed the worst in the autumn prediction. In addition, the models trained by data from the whole year had better prediction ability on autumn MDA8-O3 than that of those only trained by autumn data, and the R2 differed 0.08-0.14.

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