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1.
Environ Pollut ; 360: 124649, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39095004

RESUMEN

Dimethyl sulfide (DMS) is a prevalent volatile organic sulfur compound relevant to the global climate. Ecotoxicological effects of nano- and microplastics (NPs and MPs) on phytoplankton, zooplankton, and bacteria have been investigated by numerous studies. Yet, the influences of NPs/MPs on dimethylated sulfur compounds remains understudied. Herein, we investigated the impacts of polystyrene (PS) NPs/MPs (80 nm, 1 µm, and 10 µm) on zooplankton grazing, chlorophyll a (Chl a) concentration, bacterial community, dimethylsulfoniopropionate (DMSP), and DMS production in the microcosms. Our findings revealed that rotifer grazing increased the production of DMS in the absence of NPs/MPs but did not promote DMS production when exposed to NPs/MPs. The ingestion rates of the rotifer and copepod exposed to NPs/MPs at high concentrations were significantly reduced. NPs/MPs exposure significantly decreased DMS levels in the treatments with rotifers compared to the animal controls. In the bacterial microcosms, smaller NPs/MPs sizes were more detrimental to Chl a concentrations compared to larger sizes. The study revealed a stimulatory effect on Chl a concentrations, DMSPd concentrations, and bacterial abundances when exposed to 10 µm MP with low concentrations. The effects of NPs/MPs on DMS concentrations were both dose- and size-dependent, with NPs showing greater toxicity compared to larger MPs. NPs/MPs led to changes in bacterial community compositions, dependent on both dosage and size. NPs caused a notable decrease in the alpha diversities and richness of bacteria compared to MPs. These results provide insights into the influences of NPs/MPs on food webs, and subsequently organic sulfur compounds cycles.

2.
Clin Case Rep ; 12(8): e9234, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39109307

RESUMEN

Key Clinical Message: This case highlights the importance of carefully weighing the benefits and risks of beta-adrenergic blockade therapy based on symptoms, echocardiography, and BNP values in thyroid storm patients. Abstract: Thyroid storm is a rare but life-threatening condition in thyrotoxic patients. The keys to successful management of thyroid storm are early diagnosis, immediate anti-thyroid medications, and preventing multiorgan failure. We present a case of thyroid storm, acute decompensated heart failure, and atrial fibrillation with rapid ventricular response. We initiated propranolol to control thyroid storm. Soon after, the patient developed more severe heart failure with decreased ejection fraction (EF). We switched to diltiazem to control tachycardia, but the therapeutic effect was unsatisfactory. Finally, we used an ultra-short-acting beta-adrenergic blockade with strict monitoring of heart rate and echocardiography, and the patient survived. Beta-adrenergic blockades should be used cautiously in thyroid storm, especially patients with severe heart failure. Echocardiography can be used to aid in selection and monitoring of therapeutic drugs and prognostic outcomes in patients with thyroid storm and heart failure.

3.
J Colloid Interface Sci ; 677(Pt A): 502-511, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39106775

RESUMEN

Metal-organic framework (MOF) derivatives with tunable pore structure and improved conductivity are intensively designed as electroactive materials. Incorporating structure directing agents (SDA) is beneficial for designing MOF derivatives with excellent electrochemical performances. Ammonium fluoroborate has been reported as an effective SDA, coupled with cobalt salt and 2-methylimidazole, to synthesize zeolitic imidazolate framework-67 (ZIF-67) derivatives for charge storage. However, the synthetic environment for growing cobalt-based active materials is relatively complex. In this study, cobalt tetrafluoroborate (Co(BF4)2) is proposed as a novel cobalt precursor, supplementing cobalt ions and acting as the SDA in a single chemical, to synthesize the cobalt-based electroactive material of energy storage electrodes. Interactions between solvent molecules and solutes play significant roles on the morphology, composition, and electrochemical performance of active materials. Deionized water, methanol and ethanol are used as precursor solvents to understand their effects on material and electrochemical properties. The optimal electrode presents a specific capacitance of 608.3 F/g at 20 mV/s, attributed to the highest electrochemical surface area and evident compositions of cobalt fluoride and hydroxide. A battery supercapacitor hybrid achieves the maximum energy density of 45 Wh/kg at 429 W/kg. The CF retention of 100% and Coulombic efficiency of 99% are achieved after 10,000 cycles.

4.
J Innate Immun ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134014

RESUMEN

INTRODUCTION: MDM2 is known as the primary negative regulator of p53, MDM2 promotes lung cancer fibrosis and lung injury through p53-dependent and p53-independent pathways. However, the mechanism by which MDM2 influences the pathogenesis of asthma is unknown. In this study, we investigated the function of MDM2 in lung epithelial cells in type 2 lung inflammation. METHODS: We used type II alveolar epithelial cell-specific heterozygous knockout of Mdm2 mice to validate its function. Then papain-induced asthma model was established, and changes in inflammation were observed by measuring immunohistochemistry and flow cytometry analysis. RESULTS: In this study, we knockdown the mouse Mdm2 gene in type 2 alveolar epithelial cells. We demonstrated that heterozygous Mdm2 gene-deleted mice were highly susceptible to protease allergen papain-induced pulmonary inflammation characterized by increased ILC2 numbers, IL-5 and IL-13 cytokine levels, and lung pathology. A mechanistic study showed that following the decreased expression of Mdm2 in lung epithelial cells and A549 cell line, p53 was overactivated, and the expression of its downstream genes p21, Puma, and Noxa was elevated, which resulted in apoptosis. After Mdm2 knockdown, the mRNA expression of inflammation-related gene IL-25, HMGB1 and TNF-α were increased, which further amplified the downstream ILC2 response and lung inflammation. CONCLUSION: These results indicate that Mdm2 maintains the homeostasis of lung epithelial cells by targeting P53, and regulate the function of lung epithelial cells under type 2 lung inflammation.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39171447

RESUMEN

Insects have evolved a spectrum of strategies that facilitate survival in the face of adverse environmental conditions and bottom-up or top-down pressures. The egg is the first stage in the life cycle of most insects. It is not only immobile but in many insects is the stage that survives unfavourable seasons when food resources are unavailable. Eggs are targeted by oophagous natural enemies and also are subject to abiotic stresses. In response to these diverse stresses, insects have developed various egg protection strategies. Females of many insects lay eggs in clusters and then use their own body resources to cover them to provide protection from harsh environments and biotic attack. Such egg protection strategies have allowed some herbivorous insects to thrive in new environments and become serious invasive pests. Females of many insects protect their eggs in other ways (e.g. laying eggs in concealed places, direct parental care) while others do not provide protection at all. Here, we review various egg protective strategies in insects. Our focus is on adaptive ecological mechanisms and temporal variation as well as the benefits and costs of egg coverings. We highlight several case studies on how these egg protective traits might impede biological control of globally important agricultural and forest pests and propose a framework for incorporating egg protective traits into biological control programs especially for invasive insect pests.

6.
Angew Chem Int Ed Engl ; : e202414392, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39180230

RESUMEN

The thermodynamically and kinetically sluggish electrocatalytic C-N coupling from CO2 and NO3- is inert to initially take place while typically occurring after CO2 protonation, which severely dwindles urea efficiency and carbon atom economy. Herein, we report a single O-philic adsorption strategy to facilitate initial C-N coupling of *OCO and subsequent protonation over dual-metal hetero-single-atoms in N2-Fe-(N-B)2-Cu-N2 coordination mode (FeN4/B2CuN2@NC), which greatly inhibits the formation of C-containing byproducts and facilitates urea electrosynthesis in an unprecedented C-selectivity of 97.1% with urea yield of 2072.5 µg h-1 mgcat.-1 and 71.9% faradaic efficiency, outperforming state-of-the-art electrodes. The carbon-directed antibonding interaction with Cu-B is elaborated to benefit single O-philic adsorption of CO2 rather than conventional C-end or bridging O,O-end adsorption modes, which can accelerate the kinetics of initiated C-N coupling and protonation. Theoretical results indicate that the O- monodentate adsorption pathway benefits the thermodynamics of the C-N coupling of *OCO with *NO2 and the protonation rate-determining step, which markedly inhibits CO2 direct protonation. This oriented strategy of manipulating reactant adsorption patterns to initiate a specific step is universal to moderate oxophilic transition metals and offers a kinetic-enhanced path for multiple conversion processes.

7.
Front Public Health ; 12: 1419305, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39185128

RESUMEN

There is intense competition among pharmaceutical companies with the rapid growth of the global pharmaceutical industry. In recent years, China has continuously increased the reform of the medical system. Technology mergers and acquisitions (M&A) in China's pharmaceutical industry have emerged in this complex policy and economic background. This paper conducts an empirical study from the dual perspectives of financial performance and innovation performance, based on unbalanced panel data of Chinese listed pharmaceutical firms from 2012 to 2022. The impact of technology M&A on firm performance is analyzed in terms of the heterogeneity of firm characteristics. Meanwhile, the relationship between R&D investment in technology M&A and firm performance is examined. The results show that technology M&A can promote the performance of pharmaceutical companies, and R&D investment has a mediating effect on the impact of technology M&A on corporate performance. Based on the above findings, this study enriches the relevant literature on technology M&A in the pharmaceutical industry, provides warnings and suggestions for pharmaceutical companies to improve corporate performance through technology M&A, and provides reference materials for future policy formulation.


Asunto(s)
Industria Farmacéutica , China , Humanos , Investigación Empírica , Inversiones en Salud
8.
J Chromatogr A ; 1733: 465278, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39163702

RESUMEN

Reversed-phase liquid chromatography (RPLC) represents an effective separation method, and is widely employed as the second dimension in most 2D-LC systems. Nevertheless, the solvent effect of the eluent from the first dimension on RPLC presents a challenge to the online coupling of RPLC with other separation modes, particularly normal phase liquid chromatography (NPLC). To address this issue, a comprehensive understanding of the solvent effect is essential. Following a comprehensive investigation into the influence of diverse solvents on RPLC separations, it was observed that alkane solvents, such as n-hexane, exhibited a pronounced tendency to be retained during RPLC separations. Such solvents do not affect the analysis of samples with weaker retention abilities than themselves, even when a large injection volume is used. The solvent effect was thus reduced by employing n-hexane-based solvent dilution. Leveraging the markedly enhanced solvent tolerance and extensive injection volume in RPLC, a versatile integration of the NPLC and RPLC was devised, necessitating merely a purge pump and a 10 port 2 position valve in conjunction with two sample loops. The novel 2D-LC system was then deployed for the analysis of propolis, a naturally occurring complex sample, and demonstrated remarkable separation efficiency.

10.
Int J Mol Sci ; 25(16)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39201534

RESUMEN

The purpose of this study was to investigate whether and how albiflorin, a natural monoterpene glycoside, affects the release of glutamate, one of the most important neurotransmitters involved in neurotoxicity, from cerebrocortical nerve terminals (synaptosomes) in rats. The results showed that albiflorin reduced 4-aminopyridine (4-AP)-elicited glutamate release from synaptosomes, which was abrogated in the absence of extracellular Ca2+ or in the presence of the vesicular glutamate transporter inhibitor or a P/Q-type Ca2+ channel inhibitor, indicating a mechanism of action involving Ca2+-dependent depression of vesicular exocytotic glutamate release. Albiflorin failed to alter the increase in the fluorescence intensity of 3,3-diethylthiacarbocyanine iodide (DiSC3(5)), a membrane-potential-sensitive dye. In addition, the suppression of protein kinase A (PKA) abolished the effect of albiflorin on glutamate release. Albiflorin also reduced the phosphorylation of PKA and synaptosomal-associated protein of 25 kDa (SNAP-25) and synapsin I at PKA-specific residues, which correlated with decreased available synaptic vesicles. The results of transmission electron microscopy (TEM) also observed that albiflorin reduces the release competence of synaptic vesicles evoked by 4-AP in synaptosomes. In conclusion, by studying synaptosomally released glutamate, we suggested that albiflorin reduces vesicular exocytotic glutamate release by decreasing extracellular Ca2+ entry via P/Q-type Ca2+ channels and reducing PKA-mediated synapsin I and SNAP-25 phosphorylation.


Asunto(s)
Corteza Cerebral , Proteínas Quinasas Dependientes de AMP Cíclico , Ácido Glutámico , Sinaptosomas , Animales , Ácido Glutámico/metabolismo , Sinaptosomas/metabolismo , Sinaptosomas/efectos de los fármacos , Ratas , Corteza Cerebral/metabolismo , Corteza Cerebral/efectos de los fármacos , Masculino , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Canales de Calcio Tipo Q/metabolismo , Ratas Sprague-Dawley , Canales de Calcio Tipo P/metabolismo , Hidrocarburos Aromáticos con Puentes/farmacología , Calcio/metabolismo , Fosforilación/efectos de los fármacos , Sinapsinas/metabolismo
11.
Int Immunopharmacol ; 140: 112842, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39094361

RESUMEN

Taiwan Chingguan Yihau (NRICM101) is a Traditional Chinese medicine (TCM) formula used to treat coronavirus disease 2019; however, its impact on epilepsy has not been revealed. Therefore, the present study evaluated the anti-epileptogenic effect of orally administered NRICM101 on kainic acid (KA)-induced seizures in rats and investigated its possible mechanisms of action. Sprague-Dawley rats were administered NRICM101 (300 mg/kg) by oral gavage for 7 consecutive days before receiving an intraperitoneal injection of KA (15 mg/kg). NRICM101 considerably reduced the seizure behavior and electroencephalographic seizures induced by KA in rats. NRICM101 also significantly decreased the neuronal loss and glutamate increase and increased GLAST, GLT-1, GAD67, GDH and GS levels in the cortex and hippocampus of KA-treated rats. In addition, NRICM101 significantly suppressed astrogliosis (as determined by decreased GFAP expression); neuroinflammatory signaling (as determined by reduced HMGB1, TLR-4, IL-1ß, IL-1R, IL-6, p-JAK2, p-STAT3, TNF-α, TNFR1 and p-IκB levels, and increased cytosolic p65-NFκB levels); and necroptosis (as determined by decreased p-RIPK3 and p-MLKL levels) in the cortex and hippocampus of KA-treated rats. The effects of NRICM101 were similar to those of carbamazepine, a well-recognized antiseizure drug. Furthermore, no toxic effects of NRICM101 on the liver and kidney were observed in NRICM101-treated rats. The results indicate that NRICM101 has antiepileptogenic and neuroprotective effects through the suppression of the inflammatory cues (HMGB1/TLR4, Il-1ß/IL-1R1, IL-6/p-JAK2/p-STAT3, and TNF-α/TNFR1/NF-κB) and necroptosis signaling pathways (TNF-α/TNFR1/RIP3/MLKL) associated with glutamate level regulation in the brain and is innocuous. Our findings highlight the promising role of NRICM101 in the management of epilepsy.


Asunto(s)
Medicamentos Herbarios Chinos , Ácido Glutámico , Ácido Kaínico , Ratas Sprague-Dawley , Convulsiones , Animales , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Masculino , Ratas , Ácido Glutámico/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/inmunología , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Transducción de Señal/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología
12.
Pest Manag Sci ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39189553

RESUMEN

BACKGROUND: Epicoccum sorghinum is a pathogenic fungus that causes leaf spot in a wide range of plants, including maize, and synthesizes the mycotoxin tenuazonic acid (TEA), which is carcinogenic. Despite the relevant economic and yield losses caused by E. sorghinum worldwide, methods for the control of this pathogen are lacking. RESULTS: In this work, the efficacy of Bacillus-produced dipicolinic acid (DPA) for control of E. sorghinum was evaluated using in vitro and in vivo assays, and compared with the efficacy of three commercial fungicides, including carbendazim, prochloraz, and thiram. DPA inhibited E. sorghinum mycelial growth, and conidia germination, and produced important alterations in E. sorghinum hyphae. Interestingly, 10 mM DPA reduced TEA biosynthesis by 86.6%. Although DPA rapidly degraded on maize leaves, 10 mM DPA showed higher preventive (67.4% lesion length inhibition) and inhibitory (89.5% lesion length inhibition) efficacies for the control of E. sorghinum on maize leaves compared to the commercial fungicides. CONCLUSIONS: Collectively, this study presents the first method for the control of E. sorghinum on maize and demonstrates that DPA application is a suitable approach to inhibit E. sorghinum symptoms in plants and TEA biosynthesis. © 2024 Society of Chemical Industry.

13.
Inorg Chem ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39197012

RESUMEN

Exploiting a photocatalyst with high stability and excellent activity for Cr(VI) reduction under mild conditions is crucial yet challenging. Herein, the rigid aromatic multicarboxylate ligand with chromophore anthracene was selected to coordinate with multivalent metal ion manganese and to obtain a stable two-dimensional (2D) Mn-based metal-organic framework (MOF), LCUH-120, which can efficiently and quickly convert Cr(VI) into Cr(III) under light without the need for any additional photosensitizer. The efficient photosensitive anthracene group serves as a photosensitizer center and multivalent Mn(II) ion as a photocatalyst center in LCUH-120, and the conversion of Cr(VI) to Cr(III) can be realized completely in just 40 min. Specifically, the rate constant (k) and reduction rate of the Cr(VI) photocatalytic reaction can be high up to 0.134 min-1 and 2.50 mgCr(VI) g-1cata min-1 in an acidic environment (pH = 2), respectively. Compared to our previously reported three-dimensional (3D) Sm-MOF, LCUH-120 exhibits a significantly higher catalytic reaction rate, which might be ascribed to the fact that the photocatalyst center Mn node can improve the rate of electron transfer and promote the separation of holes and photogenerated electrons. In an acidic environment, the reaction mechanism can be verified through various contrast experiments and theoretical simulations.

14.
Eur J Surg Oncol ; 50(10): 108580, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39116516

RESUMEN

BACKGROUND: The newly released Asian Working Group for Cachexia (AWGC) criteria share similar diagnostic items with the Global Leadership Initiative on Malnutrition (GLIM) criteria. This study aims to compare the AWGC cachexia and GLIM malnutrition in patients with gastric cancer and investigate whether one diagnosis continues to be a prognostic factor in individuals diagnosed with the other condition. METHODS: Data of patients who underwent radical gastrectomy for gastric adenocarcinoma were prospectively collected from 2013 to 2019. The AWGC and GLIM criteria were applied to diagnosis cachexia and malnutrition, respectively. Univariate and multivariate logistic and Cox regression were used to verify the effect of relevant factors on postoperative complications and overall survival. RESULTS: A total of 1420 patients were included, among whom 174 (12.3 %) were diagnosed with AWGC-cachexia alone, 85 (6.0 %) were diagnosed with GLIM-malnutrition alone, and 324 (22.8 %) had both AWGC-cachexia and GLIM-malnutrition. Both AWGC-cachexia and GLIM-malnutrition were independent risk factors for complications and overall survival. When they coexisted, the odds ratios (OR) and hazard ratios (HR) tended to be higher. In the AWGC-cachexia subset, GLIM-malnutrition remained an independent risk factor (HR = 1.544, 95 % CI = 1.098-2.171, P = 0.012) for overall survival after the adjustment of confounding factors. Similarly, in the GLIM-malnutrition subset, AWGC-cachexia remained an independent risk factor for overall survival (HR = 1.697, 95 % CI = 1.087-2.650, P = 0.020). Patients with both cachexia and malnutrition had the worst overall survival. CONCLUSION: AWGC-cachexia and GLIM-malnutrition criteria were two non-redundancy tools in reflecting mortality risk in preoperative nutritional assessment.

15.
Ecotoxicology ; 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39066991

RESUMEN

Cadmium (Cd), a widely distributed environmental pollutant in agroecosystems, causes negative effects on crops and herbivores through bottom-up processes. The gut microbial community of an insect can play a critical role in response to metal stress. To understand how microbiota affect the stress responses of organisms to heavy metals in agroecosystems, we initially used 16S rRNA sequencing to characterize the larval gut microbiota of Chilo suppressalis, an important agricultural pest, exposed to a diet containing Cd. The species richness, diversity, and composition of the gut microbial community was then analyzed. Results revealed that while the richness (Chao1 and ACE) of gut microbiota in larvae exposed to Cd was not significantly affected, diversity (Shannon and Simpson) was reduced due to changes in species distribution and relative abundance. Overall, the most abundant genus was Enterococcus, while the abundance of the genera Micrococcaceae and Faecalibaculum in the control significantly superior to that in Cd-exposed pests. Phylogenetic investigation of microbial communities by the reconstruction of unobserved states (PICRUSt) showed that the intestinal microorganisms appear to participate in 34 pathways, especially those used in environmental information processing and the metabolism of the organism. This study suggests that the gut microbiota of C. suppressalis are significantly impacted by Cd exposure and highlights the importance of the gut microbiome in host stress responses and negative effects of Cd pollution in agroecosystems.

16.
ACS Appl Mater Interfaces ; 16(30): 39942-39951, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39023134

RESUMEN

There is an urgent need for lithium-ion batteries with high energy density to meet the increasing demand for advanced devices and ecofriendly electric vehicles. Spinel LiNi0.5Mn1.5O4 (LNMO) is the most promising cathode material for achieving high energy density due to its high operating voltage (4.75 V vs Li/Li+) and impressive capacity of 147 mAh g-1. However, the binders conventionally used are prone to high potential and oxidation at the cathode side, resulting in a loss of the ability to bond active material and conductive agent integrity. This can lead to severe capacity fading and irreversible battery failure. This study demonstrates that incorporating acrylic anhydride and methyl methacrylate into conventional acrylonitrile through solution polymerization improves the binding energy and voltage resistance. The results indicate that the triblock poly(acrylonitrile-methyl methacrylate-acrylic anhydride) (PAMA) binder has a much higher peeling strength (0.506 N cm-1) compared to its polyvinylidene fluoride (PVDF) counterpart (0.3 N cm-1), making it a more feasible strategy. When assembled with LiNi0.5Mn1.5O4, the PAMA based electrode maintains a capacity retention of 70.7% after 800 cycles at 0.1 C, which is significantly higher than the 33.9% retention of the PVDFbased electrode. This is due to the large number of polar groups, including ─C≡N and ─C═O, on PAMA, which are conducive to adsorbing lithium polysulfide. The S@PAMA electrode is tested and maintained a capacity value of 628.7 mAh g-1 after long-term cycling, confirming its ability to effectively suppress the shuttle effect.

18.
Int J Med Sci ; 21(9): 1661-1671, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006848

RESUMEN

Background and aim: Patients with chronic hepatitis B patients (CHB) with low-level viremia (LLV) are not necessarily at low risk of developing hepatocellular carcinoma (HCC). The question of whether CHB patients with LLV require immediate antiviral agent (AVT) or long-term AVT remains controversial. The study aims to investigate the risk of HCC development and the risk factors in CHB patients with LLV and construct a nomogram model predicting the risk of HCC. Methods: We conducted a retrospective cohort study that enrolled 16,895 CHB patients from January 2008 to December 2020. The patients were divided into three groups for comparison: the LLV group, maintained virological response (MVR) group and HBV-DNA>2000 group. The cumulative incidence of progression to HCC was assessed. Cox regression analysis was performed to determine the final risk factors, and a nomogram model was constructed. The 10-fold Cross-Validation method was utilized for internal validation. Results: A total of 408 new cases of HCC occurred during the average follow-up period of 5.78 years. The 3, 5, and 10-year cumulative HCC risks in the LLV group were 3.56%, 4.96%, and 9.51%, respectively. There was a significant difference in the cumulative risk of HCC between the HBV-DNA level > 2000 IU/mL and LLV groups (p = 0.049). Independent risk factors for HCC development in LLV group included male gender, age, presence of cirrhosis, and platelets count. The Area Under the Curve (AUC) values for the 3-year and 5-year prediction from our HCC risk prediction model were 0.75 and 0.76, respectively. Conclusion: Patients with LLV and MVR are still at risk for developing HCC. The nomogram established for CHB patient with LLV, incorporating identified significant risk factors, serves as an effective tool for predicting HCC-free outcomes. This nomogram model provides valuable information for determining appropriate surveillance strategies and prescribing AVT.


Asunto(s)
Carcinoma Hepatocelular , Virus de la Hepatitis B , Hepatitis B Crónica , Neoplasias Hepáticas , Nomogramas , Viremia , Humanos , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Masculino , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virología , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Viremia/complicaciones , Adulto , Virus de la Hepatitis B/aislamiento & purificación , Antivirales/uso terapéutico , Incidencia , ADN Viral/sangre
19.
Adv Sci (Weinh) ; : e2308890, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004913

RESUMEN

Interferons (IFNs) activate JAK-STAT pathways to induce downstream effector genes for host defense against invaded pathogens and tumors. Here both type I (ß) and II (γ) IFNs are shown that can activate the transcription factor IRF3 in parallel with STAT1. IRF3-deficiency impairs transcription of a subset of downstream effector genes induced by IFN-ß and IFN-γ. Mechanistically, IFN-induced activation of IRF3 is dependent on the cGAS-STING-TBK1 axis. Both IFN-ß and IFN-γ cause mitochondrial DNA release into the cytosol. In addition, IFNs induce JAK1-mediated tyrosine phosphorylation of cGAS at Y214/Y215, which is essential for its DNA binding activity and signaling. Furthermore, deficiency of cGAS, STING, or IRF3 impairs IFN-ß- or IFN-γ-mediated antiviral and antitumor activities. The findings reveal a novel IRF3 activation pathway parallel with the canonical STAT1/2 activation pathways triggered by IFNs and provide an explanation for the pleiotropic roles of the cGAS-STING-IRF3 axis in host defense.

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