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1.
Angew Chem Int Ed Engl ; : e202409019, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38785222

RESUMEN

Urea electrosynthesis from carbon dioxide (CO2) and nitrate (NO3-) is an alternative approach to traditional energy-intensive urea synthesis technology. Herein, we report a CuAu single-atom alloy (SAA) with electronic metal support interaction (EMSI), achieving a high urea yield rate of 813.6 µg h-1 mgcat-1 at -0.94 V versus reversible hydrogen electrode (vs. RHE) and a Faradaic efficiency (FE) of 45.2% at -0.74 V vs. RHE. In-situ experiments and theoretical calculations demonstrated that single-atom Cu sites modulate the adsorption behavior of intermediate species. Bimetallic sites synergistically accelerate C-N bond formation through spontaneous coupling of *CO and *NO to form *ONCO as key intermediates. More importantly, electronic metal support interaction between CuAu SAA and CeO2 carrier further modulates electron structure and interfacial microenvironment, endowing electrocatalysts with superior activity and durability. This work constructs SAA electrocatalysts with EMSI effect to tailor C-N coupling at the atomic level, which can provide guidance for the development of C-N coupling systems.

2.
Phytomedicine ; 129: 155663, 2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38759345

RESUMEN

BACKGROUNDS: Allergic rhinitis (AR) is a non-infectious chronic inflammation of the nasal mucosa mainly mediated by immunoglobulin E (IgE) in atopic individuals after exposure to allergens. The application of AR guideline-recommended pharmacotherapies can rapidly relieve symptoms of AR but with poor long-term efficacy, and many of these therapies have side effects. Many natural products and their derivatives have shown potential therapeutic effects on AR with fewer side effects. OBJECTIVES: This review aims to expand understanding of the roles and mechanisms of natural compounds in the treatment of AR and to highlight the importance of utilizing natural products in the treatment of AR. MATERIAL AND METHOD: We conducted a systematic literature search using PubMed, Web of Science, Google Scholar, and Clinical Trials. The search was performed using keywords including natural products, natural compounds, bioproducts, plant extracts, naturally derived products, natural resources, allergic rhinitis, hay fever, pollinosis, nasal allergy. Comprehensive research and compilation of existing literature were conducted. RESULTS: This article provided a comprehensive review of the potential therapeutic effects and mechanisms of natural compounds in the treatment of AR. We emphasized that natural products primarily exert their effects by modulating signalling pathways such as NF-κB, MAPKs, STAT3/ROR-γt/Foxp3, and GATA3/T-bet, thereby inhibiting the activation and expansion of allergic inflammation. We also discussed their toxicity and clinical applications in AR therapy. CONCLUSION: Taken together, natural products exhibit great potential in the treatment of AR. This review is also expected to facilitate the application of natural products as candidates for treating AR. Furthermore, drug discovery based on natural products has a promising prospect in AR treatment.

3.
Nat Commun ; 15(1): 3970, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730227

RESUMEN

High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identify TAD-constrained cis-regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.


Asunto(s)
Mal de Altura , Altitud , Regulación de la Expresión Génica , Hipoxia , Animales , Mal de Altura/genética , Mal de Altura/metabolismo , Ovinos , Hipoxia/genética , Hipoxia/metabolismo , Humanos , Aclimatación/genética , Transcripción Genética , Análisis de la Célula Individual , Femenino , Multiómica
4.
Yi Chuan ; 46(4): 266-278, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38632090

RESUMEN

RNA silencing (or RNA interference, RNAi) is a conserved mechanism for regulating gene expression in eukaryotes, which plays vital roles in plant development and response to biotic and abiotic stresses. The discovery of trans-kingdom RNAi and interspecies RNAi provides a theoretical basis for exploiting RNAi-based crop protection strategies. Here, we summarize the canonical RNAi mechanisms in plants and review representative studies associated with plant-pathogen interactions. Meanwhile, we also elaborate upon the principles of host-induced gene silencing, spray-induced gene silencing and microbe-induced gene silencing, and discuss their applications in crop protection, thereby providing help to establish novel RNAi-based crop protection strategies.


Asunto(s)
Protección de Cultivos , Plantas , Interferencia de ARN , Plantas/genética , Eucariontes/genética , ARN Interferente Pequeño/genética
5.
World J Stem Cells ; 16(2): 207-227, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38455101

RESUMEN

BACKGROUND: Colorectal cancer stem cells (CCSCs) are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer (CRC) patients. CCSCs are generally accepted to be important sources of CRC and are responsible for the progression, metastasis, and therapeutic resistance of CRC. Therefore, targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC. AIM: To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism. METHODS: CCSCs were enriched from CRC cell lines by in conditioned serum-free medium. Western blot, Aldefluor, transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs. The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis, colony formation, sphere formation, flow cytometry, and western blotting assessments in vitro and tumor growth, immunohistochemistry and immunofluorescence assessments in vivo. RESULTS: Compared with parental cells, sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumorigenesis, demonstrating that the CRC sphere cells displayed CSC features. VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells, as indicated by their proliferation, migration and clonality in vitro, and suppressed the tumor of CCSC-derived xenograft tumors in vivo. Besides, VX-509 suppressed the CSC characteristics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition (EMT) signaling in vitro. Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differentially expressed genes and CSC-related database information. VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression. Moreover, VX-509 reversed the dedifferentiation of CCSCs and inhibited the progression of EMT induced by Nodal overexpression. CONCLUSION: VX-509 prevents the EMT process in CCSCs by inhibiting the transcription and protein expression of Nodal, and inhibits the dedifferentiated self-renewal of CCSCs.

6.
Pathol Res Pract ; 256: 155251, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38490097

RESUMEN

Aberrant adrenal function has been frequently reported in COVID-19 patients, but histopathological evidence remains limited. This retrospective autopsy study aims to scrutinize the impact of COVID-19 duration on adrenocortical zonational architecture and peripheral corticosteroid reactivity. The adrenal glands procured from 15 long intensive care unit (ICU)-stay COVID-19 patients, 9 short ICU-stay COVID-19 patients, and 20 matched controls. Subjects who had received glucocorticoid treatment prior to sampling were excluded. Applying hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, we disclosed that the adrenocortical zonational structure was substantially disorganized in COVID-19 patients, which long ICU-stay patients manifested a higher prevalence of severe disorganization (67%) than short ICU-stay patients (11%; P = 0.0058). The adrenal cortex of COVID-19 patients exhibited a 40% decrease in the zona glomerulosa (ZG) area and a 74% increase in the zona fasciculata (ZF) area (both P < 0.0001) relative to controls. Furthermore, among long ICU-stay COVID-19 patients, the ZG area diminished by 31% (P = 0.0004), and the ZF area expanded by 27% (P = 0.0004) in comparison to short ICU-stay patients. The zona reticularis (ZR) area remained unaltered. Nuclear translocation of corticosteroid receptors in the liver and kidney of long ICU-stay COVID-19 patients was at least 43% lower than in short ICU-stay patients (both P < 0.05). These findings underscore the necessity for clinicians to monitor adrenal function in long-stay COVID-19 patients.


Asunto(s)
Corteza Suprarrenal , COVID-19 , Humanos , Enfermedad Crítica , Estudios Retrospectivos , Glándulas Suprarrenales , Corticoesteroides
7.
Int J Cancer ; 154(12): 2075-2089, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38367273

RESUMEN

Females with existing high-risk HPV (HR-HPV) infections remain at risk of subsequent multiple or recurrent infections, on which benefit from HPV vaccines was under-reported. We pooled individual-level data from four large-scale, RCTs of AS04-HPV-16/18 vaccine to evaluate efficacy and immunogenicity in females DNA-positive to any HR-HPV types at first vaccination. Females receiving the AS04-HPV-16/18 vaccine in the original RCTs constituted the vaccine group in the present study, while those unvaccinated served as the control group. Vaccine efficacy (VE) against new infections and associated cervical intraepithelial neoplasia (CIN) 2+ in females DNA-negative to the considered HR-HPV type but positive to any other HR-HPV types, VE against reinfections in females DNA-positive to the considered HR-HPV type but cleared naturally during later follow-up, and levels of anti-HPV-16/18 IgG were assessed. Our final analyses included 5137 females (vaccine group = 2532, control group = 2605). The median follow-up time was 47.88 months (IQR: 45.72-50.04). For the prevention of precancerous lesions related to the non-infected HR-HPV types at baseline, VE against HPV-16/18 related CIN 2+ was 82.70% (95% CI: 63.70-93.00%). For the prevention of reinfections related to the infected HR-HPV types following natural clearance, VE against HPV-16/18 12MPI was non-significant (p > .05), albeit robust immunity persisted for at least 48 months. Females with existing HR-HPV infections at first vaccination still benefit from vaccination in preventing precancers related to the non-infected types at baseline. VE against reinfections related to the infected types following natural clearance remains to be further investigated.


Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Papillomavirus Humano 16 , Vacunas contra Papillomavirus/uso terapéutico , Reinfección/complicaciones , Papillomavirus Humano 18 , Vacunación , ADN
8.
Small ; : e2308781, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38308349

RESUMEN

A Lanthanum ion (La3+ ) incorporation strategy is implemented to modify Ba2 Bi2 O6 -based double perovskite photoelectrodes. X-ray diffraction (XRD) characterization shows that highly crystalline Ba2 La0.4 Bi1.6 O6 double perovskites with the space group I2/m are successfully prepared. UV-vis absorption spectra and the Tauc-plot reveal an optical band gap Eg ≈1.57 ± 0.01 eV. A thickness dependence of the photoelectrodes photoelectrochemical (PEC) performance shows that the submicron (≈1 µm) 4-times spin-coated thin film photoelectrode displays strong p-type conductivity, which delivers an encouraging photocurrent density of 0.88 mA cm-2 at 0.25 VRHE under AM 1.5G illumination. 10-times coated and 20-times coated medium thick (125.8-197 µm) photoelectrodes that exhibit moderate p-type conductivity, show further enhanced photocurrent densities of 1.5 mA cm-2 at 0 VRHE . In contrast, charge recombination centers existing in a standard thick pellet (≈500 µm) Ba2 La0.4 Bi1.6 O6 photoelectrode can quench photo-generated charge carriers and greatly undermine PEC activities. The approach to doping at the Bi(III) sites contrasts with earlier efforts that focus on doping at the Bi(V) sites and thus paves the way for further tailoring a family of novel promising photocathode materials for efficient solar-water conversion devices.

9.
Cell Res ; 34(2): 140-150, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38182887

RESUMEN

Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-born zoonotic bunyavirus that causes severe hemorrhagic fever and death in humans. CCHFV enters the cell via clathrin-mediated endocytosis which is dependent on its surface glycoproteins. However, the cellular receptors that are required for CCHFV entry are unknown. Here we show that the low density lipoprotein receptor (LDLR) is an entry receptor for CCHFV. Genetic knockout of LDLR impairs viral infection in various CCHFV-susceptible human, monkey and mouse cells, which is restored upon reconstitution with ectopically-expressed LDLR. Mutagenesis studies indicate that the ligand binding domain (LBD) of LDLR is necessary for CCHFV infection. LDLR binds directly to CCHFV glycoprotein Gc with high affinity, which supports virus attachment and internalization into host cells. Consistently, a soluble sLDLR-Fc fusion protein or anti-LDLR blocking antibodies impair CCHFV infection into various susceptible cells. Furthermore, genetic knockout of LDLR or administration of an LDLR blocking antibody significantly reduces viral loads, pathological effects and death following CCHFV infection in mice. Our findings suggest that LDLR is an entry receptor for CCHFV and pharmacological targeting of LDLR may provide a strategy to prevent and treat Crimean-Congo hemorrhagic fever.


Asunto(s)
Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea , Receptores de LDL , Animales , Humanos , Ratones , Endocitosis , Glicoproteínas/metabolismo , Virus de la Fiebre Hemorrágica de Crimea-Congo/genética , Virus de la Fiebre Hemorrágica de Crimea-Congo/metabolismo , Fiebre Hemorrágica de Crimea/prevención & control , Receptores de LDL/metabolismo , Internalización del Virus
10.
Phytomedicine ; 124: 155263, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38181532

RESUMEN

BACKGROUND: Anomalous activation of NF-κB signaling is associated with many inflammatory disorders, such as ulcerative colitis (UC) and acute lung injury (ALI). NF-κB activation requires the ubiquitination of receptor-interacting protein 1 (RIP1) and NF-κB essential modulator (NEMO). Therefore, inhibition of ubiquitation of RIP1 and NEMO may serve as a potential approach for inhibiting NF-κB activation and alleviating inflammatory disorders. PURPOSE: Here, we identified arteannuin B (ATB), a sesquiterpene lactone found in the traditional Chinese medicine Artemisia annua that is used to treat malaria and inflammatory diseases, as a potent anti-inflammatory compound, and then characterized the putative mechanisms of its anti-inflammatory action. METHODS: Detections of inflammatory mediators and cytokines in LPS- or TNF-α-stimulated murine macrophages using RT-qPCR, ELISA, and western blotting, respectively. Western blotting, CETSA, DARTS, MST, gene knockdown, LC-MS/MS, and molecular docking were used to determine the potential target and molecular mechanism of ATB. The pharmacological effects of ATB were further evaluated in DSS-induced colitis and LPS-induced ALI in vivo. RESULTS: ATB effectively diminished the generation of NO and PGE2 by down-regulating iNOS and COX2 expression, and decreased the mRNA expression and release of IL-1ß, IL-6, and TNF-α in LPS-exposed RAW264.7 macrophages. The anti-inflammatory effect of ATB was further demonstrated in LPS-treated BMDMs and TNF-α-activated RAW264.7 cells. We further found that ATB obviously inhibited NF-κB activation induced by LPS or TNF-α in vitro. Moreover, compared with ATB, dihydroarteannuin B (DATB) which lost the unsaturated double bond, completely failed to repress LPS-induced NO release and NF-κB activation in vitro. Furthermore, UBE2D3, a ubiquitin-conjugating enzyme, was identified as the functional target of ATB, but not DATB. UBE2D3 knockdown significantly abolished ATB-mediated inhibition on LPS-induced NO production. Mechanistically, ATB could covalently bind to the catalytic cysteine 85 of UBE2D3, thereby inhibiting the function of UBE2D3 and preventing ubiquitination of RIP1 and NEMO. In vivo, ATB treatment exhibited robust protective effects against DSS-induced UC and LPS-induced ALI. CONCLUSION: Our findings first demonstrated that ATB exerted anti-inflammatory functions by repression of NF-κB pathway via covalently binding to UBE2D3, and raised the possibility that ATB could be effective in the treatment of inflammatory diseases and other diseases associated with abnormal NF-κB activation.


Asunto(s)
Artemisia annua , Artemisininas , Colitis Ulcerosa , Animales , Ratones , FN-kappa B/metabolismo , Enzimas Ubiquitina-Conjugadoras , Factor de Necrosis Tumoral alfa/metabolismo , Lipopolisacáridos/farmacología , Cromatografía Liquida , Simulación del Acoplamiento Molecular , Espectrometría de Masas en Tándem , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Lactonas , Inflamación/metabolismo
11.
Toxins (Basel) ; 15(12)2023 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-38133198

RESUMEN

Aflatoxin B1 (AFB1) is a hazardous mycotoxin that often contaminates animal feed and may potentially induce severe liver damage if ingested. The liver is the primary organ responsible for AFB1 detoxification through enzyme-catalyzed xenobiotic metabolism and bile acid (BA)-associated excretion. In this study, we sought to investigate whether exogenous BA improves hepatic AFB1 detoxification to alleviate AFB1-induced liver injury in broiler chickens. Five-day-old broiler chicks were randomly assigned to three groups. CON and AFB1 received a basal diet; AFB1 + BA received a basal diet with 250 mg/kg BA for 20 days. After a 3-day pre-feed, AFB1 and AFB1 + BA were daily gavaged with 250 µg/kg BW AFB1, while CON received gavage solvent for AFB1 treatment. Dietary BA supplementation protected chickens from AFB1-induced hepatic inflammation and oxidative stress. The hepatic biotransformation of AFB1 to its metabolite AFBO was improved, with accelerated excretion to the gallbladder and cecum. Accordantly, AFB1-induced down-regulation of detoxification genes, including cytochrome P450 enzymes, glutathione S-transferases, and the bile salt export pump, was rescued by BA supplementation. Moreover, liver X receptor α, suppressed by AFB1, was enhanced in BA-treated broiler chickens. These results indicate that dietary BA supplementation improves hepatic AFB1 detoxification and excretion through LXRα-involved regulation of xenobiotic enzymes.


Asunto(s)
Aflatoxina B1 , Pollos , Animales , Aflatoxina B1/toxicidad , Aflatoxina B1/metabolismo , Pollos/metabolismo , Xenobióticos/metabolismo , Hígado/metabolismo , Biotransformación , Alimentación Animal/análisis
12.
Pathol Res Pract ; 252: 154920, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37948998

RESUMEN

Clinical data indicates that SARS-CoV-2 infection-induced respiratory failure is a fatal condition for severe COVID-19 patients. However, the pathological alterations of different types of respiratory failure remained unknown for severe COVID-19 patients. This study aims to evaluate whether there are differences in the performance of various types of respiratory failure in severe COVID-19 patients and investigate the pathological basis for these differences. The lung tissue sections of severe COVID-19 patients were assessed for the degree of injury and immune responses. Transcriptome data were used to analyze the molecular basis in severe COVID-19 patients. Severe COVID-19 patients with combined oxygenation and ventilatory failure presented more severe pulmonary fibrosis, airway obstruction, and prolonged disease course. The number of M2 macrophages increased with the degree of fibrosis in patients, suggesting that it may be closely related to the development of pulmonary fibrosis. The co-existence of pro-inflammatory and anti-inflammatory cytokines in the pulmonary environment could also participate in the progression of pulmonary fibrosis. Furthermore, the increased apoptosis in the lungs of COVID-19 patients with severe pulmonary fibrosis may represent a critical factor linking sustained inflammatory responses to fibrosis. Our findings indicate that during the extended phase of COVID-19, antifibrotic and antiapoptotic treatments should be considered in conjunction with the progression of the disease.


Asunto(s)
COVID-19 , Fibrosis Pulmonar , Insuficiencia Respiratoria , Humanos , COVID-19/complicaciones , COVID-19/patología , Fibrosis Pulmonar/patología , Autopsia , SARS-CoV-2 , Pulmón/patología , Macrófagos/patología , Insuficiencia Respiratoria/patología , Apoptosis
13.
Ying Yong Sheng Tai Xue Bao ; 34(11): 2978-2984, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37997408

RESUMEN

We measured winter and summer soil organic carbon (SOC) contents in two typical coastal wetlands, the Spartina alterniflora salt marsh and the non-vegetation mudflat, on the south side of the Chuandong River Estuary in Yancheng, Jiangsu Province. We investigated the spatiotemporal variations of soil organic carbon contents and its driving factors. The results showed that SOC content ranged from 0.75 to 2.38 g·kg-1 in the mudflat area and from 2.07 to 18.59 g·kg-1 in the S. alterniflora salt marsh area, showing a decreasing trend towards the sea. The SOC content in the S. alterniflora salt marsh area was approximately 2.5 to 3.5 times of that in the mudflat area. Within a depth range of 1 m, there was no vertical variation in SOC content in the mudflat area, but an increasing and then decreasing pattern in the S. alterniflora marsh area with the peak occurring in the depth range of 20 to 30 cm. Soil organic carbon content exhibited significant seasonal difference, with higher value in summer than in winter. The summer SOC content was 5% to 10% higher than that in winter in the S. alterniflora marsh area, while it was 43% higher in summer than in winter in the mudflat area. In the S. alterniflora marsh area, soil organic carbon content was positively correlated with soil moisture and salinity, but negatively correlated with sediment particle size. In contrast, there was no significant correlation between soil organic carbon content and soil physicochemi-cal factors in the mudflat area. Those results indicated that the correlation between various soil physicochemical factors and SOC is established on the basis of vegetation cover in coastal wetlands. Our findings could provide valuable insights for the conservation of blue carbon ecosystems in coastal wetlands in China.


Asunto(s)
Ecosistema , Humedales , Carbono/análisis , Suelo/química , China , Poaceae , Especies Introducidas
14.
J Dig Dis ; 24(11): 584-593, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37847845

RESUMEN

OBJECTIVES: Currently, most colorectal neoplasia (CRN) screening strategies target asymptomatic individuals. However, studies on patients with non-specific gastrointestinal symptoms (NSGS) are limited. We aimed to develop a CRN risk score specifically for patients with NSGS. METHODS: We prospectively enrolled patients who underwent initial colonoscopy between June 2020 and June 2021. A new risk scoring system was constructed and its applicability was evaluated. RESULTS: A total of 1522 consecutive patients were enrolled, among whom 1016 symptomatic patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. The constructed Symptomatic Patients Colorectal Screening (SPCS) score showed higher diagnostic efficacy and sensitivity than several previous scoring systems. Using the SPCS score, the patients were divided into a low-risk group (-2 to 3 points) and a high-risk group (4-10 points) for CRN. Additionally, the detection rate of CRN in the training and validation cohorts of the high-risk group were 41.7% and 37.0%, respectively. The SPCS score detected 79.3% (188/237) of CRN and 87.5% (42/48) of advanced CRN in the high-risk group, which reduced the workload of colonoscopy to 45.9% (466/1016). CONCLUSION: An effective CRN risk scoring system was established and validated for symptomatic patients, which accurately classified individuals into low-risk and high-risk groups for CRN and might be used to optimize colonoscopic resource allocation.


Asunto(s)
Colonoscopía , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer , Factores de Riesgo
15.
Genome Res ; 33(10): 1690-1707, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37884341

RESUMEN

The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.


Asunto(s)
Metagenoma , Microbiota , Ovinos/genética , Animales , Transcriptoma , Rumen , Rumiantes/genética
16.
Int Immunopharmacol ; 124(Pt B): 110965, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37741124

RESUMEN

Isolinderalactone is the main sesquiterpene lactone isolated from Lindera aggregata, a traditional Chinese medicine widely used to treat pain and inflammation. Although isolinderalactone has been demonstrated to possess anti-cancer effect, its anti-inflammatory activity and underlying mechanism has not been well characterized. Herein, isolinderalactone was able to significantly inhibit the production of NO and PGE2 by reducing the expressions of iNOS and COX2 in LPS-stimulated RAW264.7 macrophages and BMDMs, and decreased the mRNA levels of IL-1ß, IL-6, and TNF-α in LPS-induced RAW264.7 cells. In vivo, isolinderalactone effectively alleviated LPS-induced acute lung injury (ALI), which manifested as reduction in pulmonary inflammatory infiltration, myeloperoxidase activity, and production of PGE2, IL-1ß, IL-6, TNF-α, and malondialdehyde. Furthermore, isolinderalactone inhibited phosphorylation of IKKα/ß, phosphorylation and degradation of IκBα, and nuclear translocation of NF-κB p65, thereby blocking NF-κB pro-inflammatory pathway. Meanwhile, isolinderalactone reduced the intracellular ROS through promoting the activation of Nrf2-HMOX1 antioxidant axis. By using drug affinity responsive target stability assay and molecular docking, isolinderalactone was found to covalently interact with IKKα/ß and Keap1, which may contribute to its anti-inflammatory action. Additionally, a thiol donor ß-mercaptoethanol significantly abolished isolinderalactone-mediated anti-inflammatory action in vitro, indicating the crucial role of the unsaturated lactone of isolinderalactone on its anti-inflammatory effects. Taken together, isolinderalactone protected against LPS-induced ALI in mice, which may be associated with its inhibition of NF-κB pathway and activation of Nrf2 signaling in macrophages.


Asunto(s)
Lesión Pulmonar Aguda , Sesquiterpenos , Animales , Ratones , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Antiinflamatorios/farmacología , Quinasa I-kappa B/metabolismo , Interleucina-6/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Lactonas/farmacología , Lactonas/uso terapéutico , Lactonas/metabolismo , Lipopolisacáridos/farmacología , Macrófagos , Simulación del Acoplamiento Molecular , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Sesquiterpenos/farmacología , Sesquiterpenos/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismo
17.
World J Gastrointest Surg ; 15(8): 1641-1651, 2023 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-37701695

RESUMEN

BACKGROUND: Portal hypertension combined with esophagogastric variceal bleeding (EGVB) is a serious complication in patients with hepatitis B virus (HBV)-related cirrhosis in China. Splenectomy plus pericardial devascularization (SPD) and transjugular intrahepatic portosystemic shunt (TIPS) are effective treatments for EGVB. However, a comparison of the effectiveness and safety of those methods is lacking. AIM: To compare the prognosis after SPD vs TIPS for acute EGVB after failure of endoscopic therapy or secondary prophylaxis of variceal rebleeding (VRB) in patients with HBV-related cirrhosis combined with portal hypertension. METHODS: This retrospective cohort study included 318 patients with HBV-related cirrhosis and EGVB who underwent SPD or TIPS at West China Hospital of Sichuan University during 2009-2013. Propensity score-matched analysis (PSM), the Kaplan-Meier method, and multivariate Cox regression analysis were used to compare overall survival, VRB rate, liver function abnormality rate, and hepatocellular carcinoma (HCC) incidence between the two patient groups. RESULTS: The median age was 45.0 years (n = 318; 226 (71.1%) males). During a median follow-up duration of 43.0 mo, 18 (11.1%) and 33 (21.2%) patients died in the SPD and TIPS groups, respectively. After PSM, SPD was significantly associated with better overall survival (OS) (P = 0.01), lower rates of abnormal liver function (P < 0.001), and a lower incidence of HCC (P = 0.02) than TIPS. The VRB rate did not differ significantly between the two groups (P = 0.09). CONCLUSION: Compared with TIPS, SPD is associated with higher postoperative OS rates, lower rates of abnormal liver function and HCC, and better quality of survival as acute EGVB treatment after failed endoscopic therapy or as secondary prophylaxis of VRB in patients with HBV-related cirrhosis combined with portal hypertension. There is no significant between-group difference in VRB rates.

18.
Infect Dis Poverty ; 12(1): 86, 2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37735709

RESUMEN

The human papillomavirus (HPV) vaccine is the first vaccine developed specifically targeting the prevention of cervical cancer. For more than 15 years, China has expedited a series of efforts on research and development of the domestically manufactured HPV vaccines, producing local population-based evidence, promoting free HPV vaccination from pilots, and launching action plans to tackle barriers in the scale-up of HPV vaccination. To further roll out the HPV vaccination program in China, several challenges should be addressed to support the steps forward. The availability of more locally manufactured HPV vaccines, pricing negotiation and local evidence supporting the efficacy of one-dose schedule would greatly alleviate the continued supply and financial constraints in China. Meanwhile, more attention should be paid to girls living in low-resource areas and males to ensure equal access to the HPV vaccination. Furthermore, linkage to secondary prevention and further real-world monitoring and evaluation are warranted to inform effective cervical cancer prevention strategies in the post-vaccine era.


Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Masculino , Humanos , Virus del Papiloma Humano , Infecciones por Papillomavirus/prevención & control , Neoplasias del Cuello Uterino/prevención & control , Vacunación , China
19.
Inorg Chem ; 62(29): 11287-11290, 2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37429008

RESUMEN

In this work, a new alkaline-stable boron imidazolate framework (BIF-90) was rationally designed and successfully synthesized by solvothermal reaction. Due to its potential electrocatalytic active sites (Co, B, N, and S) and chemical stabilities, BIF-90 was explored as a bifunctional electrocatalyst toward electrochemical oxygen reactions, namely, oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). This work will open new avenues toward the design of stable, cheap, and more active BIFs as bifunctional catalysts.

20.
Acta Radiol ; 64(9): 2552-2560, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37331987

RESUMEN

BACKGROUND: Non-invasive detection of isocitrate dehydrogenase (IDH) mutational status in gliomas is clinically meaningful for molecular stratification of glioma; however, it remains challenging. PURPOSE: To investigate the usefulness of texture analysis (TA) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and histogram analysis of diffusion kurtosis imaging (DKI) maps for evaluating IDH mutational status in gliomas. MATERIAL AND METHODS: This retrospective study enrolled 84 patients with histologically confirmed gliomas, comprising IDH-mutant (n = 34) and IDH-wildtype (n = 50). TA was performed for the quantitative parameters derived by DCE-MRI. Histogram analysis was performed for the quantitative parameters derived by DKI. Unpaired Student's t-test was used to identify IDH-mutant and IDH-wildtype gliomas. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to compare the diagnostic performance of each parameter and their combination for predicting the IDH mutational status in gliomas. RESULTS: Significant statistical differences in the TA of DCE-MRI and histogram analysis of DKI were observed between IDH-mutant and IDH-wildtype gliomas (all P < 0.05). Using multivariable logistic regression, the entropy of Ktrans, skewness of Ve, and Kapp-90th had higher prediction potential for IDH mutations with areas under the ROC curve (AUC) of 0.915, 0.735, and 0.830, respectively. A combination of these analyses for the identification of IDH mutation improved the AUC to 0.978, with a sensitivity and specificity of 94.1% and 96.0%, respectively, which was higher than the single analysis (P < 0.05). CONCLUSION: Integrating the TA of DCE-MRI and histogram analysis of DKI may help to predict the IDH mutational status.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Isocitrato Deshidrogenasa/genética , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Imagen de Difusión por Resonancia Magnética/métodos , Estudios Retrospectivos , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/patología , Imagen por Resonancia Magnética/métodos , Mutación
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