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1.
Int J Surg ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39248298

RESUMEN

OBJECTIVE: The present study aims to explore the roles of infusion time, administration sequence and interval of immunochemotherapy (IO) in predicting overall survival (OS) in patients with locally advanced ESCC. METHODS: This multi-center retrospective study enrolled advanced ESCC who received IO between Nov 2019 and Nov 2021. Patients were divided into groups according to the three classifiers (IO infusion time, administration sequence, and infusion interval), and were further analyzed for the roles of these classifiers in predicting the prognosis of the ESCC patients. RESULTS: A total of 183 eligible patients with locally advanced ESCC were included in this study. Patients who received ≥ 75% of immunotherapy drug infusions after 12:00 h had better OS compared to those who received < 75% of immunotherapy drug infusions after 12:00 h in the 1:1 propensity score matching analysis (HRadjusted: 0.38, 95% CI: 0.17-0.82; P = 0.013). Cox proportional hazards regression revealed that ESCC patients with shorter infusion interval (< 3.3 h) had better OS (HRadjusted: 0.34, 95% CI: 0.15-0.76; P = 0.008). CONCLUSION: For patients with ESCC, the OS is significantly better when immunotherapy was administered after 12:00 h. A shorter infusion interval (< 3.3 hours) on the same-day immunochemotherapy could lead to a better prognosis.

2.
Front Vet Sci ; 11: 1427690, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268515

RESUMEN

Introduction: Enterocytozoon bieneusi is one of the most important zoonotic pathogens, responsible for nearly 90% of human infections. Its host spectrum is broad in China, encompassing humans, non-human primates, domestic animals, wildlife, and wastewater. Wild rodents have the potential to act as carriers of E. bieneusi, facilitating the parasite's transmission to humans and domestic animals. Methods: The present study involved the collection of 344 wild rodents, representing nine species, from three provinces in China. The prevalence and genotypes of E. bieneusi were determined through amplification of the ITS gene. Evolutionary analysis was conducted using Mega 5.0 with the neighbor-joining method (Kimura 2-parameter model, 1,000 replicates). Results: Among the sampled wild rodents, 41 (11.92%) were tested positive for E. bieneusi. Rattus flavipectus exhibited the highest prevalence (11/39), while Bandicota indica and Rattus rattus sladeni showed no infections (0/39 and 0/5, respectively), highlighting significant differences. Environmental factors strongly influenced E. bieneusi infection; rodents residing in lake beaches (10.27%, 15/146) and fields (19.95%, 18/95) were more susceptible compared to those in mountainous areas (7.77%, 8/103). The study identified four known genotypes (D, Type IV, SDD5, PigEBITS7) and five novel genotypes (HNRV-1 to HNRV-3, GXRL-1, GXRL-2) in the investigated wild rodents, with Genotype D exhibiting the highest prevalence. Discussion: Remarkably, this study reports the presence of E. bieneusi, R. flavipectus, M. fortis, A. agrarius, R. losea, and N. lotipes for the first time. These findings underscore the common occurrence of E. bieneusi infection in wild rodents in China, highlighting its diverse nature and significant potential for zoonotic transmission. Hence, it is imperative to conduct a comprehensive epidemiological investigation of rodent infection with E. bieneusi, particularly focusing on wild rodents that are closely associated with humans. Additionally, developing appropriate measures and monitoring strategies to minimize the risk of infection is essential.

3.
Int J Mol Sci ; 25(17)2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39273450

RESUMEN

Colletotrichum boninense is the main pathogenic fungus causing leaf spot disease in Sorghum sudangrass hybrids, which seriously impairs its quality and yield. In order to find an efficient and green means of control, this study used the agar disk diffusion method to screen for a fungicide with the strongest inhibitory effect on C. boninense from among several bacteria, fungi, and chemicals. Then, the changes in the plant's antioxidant system and metabolic levels after treatment were used to compare the three means of control. The lowest inhibitory concentration of Zalfexam was 10 mg/mL, at which point C. boninense did not grow, and the inhibition rates of Bacillus velezensis (X7) and Trichoderma harzianum were 33.87-51.85% and 77.86-80.56%, respectively. Superoxide dismutase (SOD) and chitinase were up-regulated 2.43 and 1.24 folds in the Trichoderma harzianum group (M group) and SOD activity was up-regulated 2.2 folds in the Bacillus velezensis group (X7 group) compared to the control group (CK group). SOD, peroxidase (POD), and chitinase activities were elevated in the Zalfexam group (HX group). The differential metabolites in different treatment groups were mainly enriched in amino acid metabolism and production, flavonoid production, and lipid metabolism pathways. Compared with the diseased plants (ZB group), the M, X7, HX, and CK groups were co-enriched in the tryptophan metabolic pathway and glutamate-arginine metabolic pathway, and only the CK group showed a down-regulation of the metabolites in the two common pathways, while the metabolites of the common pathways were up-regulated in the M, X7, and HX groups. In addition, the salicylic acid-jasmonic acid pathway and ascorbic acid-glutathione, which were unique to the M group, played an important role in helping Sorghum sudangrass hybrids to acquire systemic resistance against stress. This study fills the gap in the control of Colletotrichum boninene, which causes leaf spot disease in Sorghum sudangrass hybrids. This paper represents the first reported case of biological control for leaf spot disease in Sorghum sudangrass hybrids and provides a reference for the control of leaf spot disease in Sorghum sudangrass hybrids as well as other crops infected with Colletotrichum boninense.


Asunto(s)
Antioxidantes , Bacillus , Colletotrichum , Enfermedades de las Plantas , Sorghum , Sorghum/microbiología , Sorghum/metabolismo , Antioxidantes/metabolismo , Enfermedades de las Plantas/microbiología , Bacillus/metabolismo , Hypocreales/metabolismo , Superóxido Dismutasa/metabolismo , Quitinasas/metabolismo , Fungicidas Industriales/farmacología
4.
Heliyon ; 10(16): e36336, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39253238

RESUMEN

Tantalum is not only one of the critical metals applied in various advanced industries such as electronics, aerospace, military, and medical applications, but also is considered a conflict mineral, posing a threat to its global supply security. China plays a significant role in the tantalum industrial chain; however, the complete picture of its anthropogenic tantalum cycle remains unknown. This study investigates the tantalum cycles in China from 2000 to 2021 by conducting a dynamic material flow analysis. The results reveal that China's domestic tantalum consumption surged from 91 tons in 2000 to 580 tons in 2021. China heavily relied on importing tantalum minerals to support its domestic production, with a trade dependence rate of 90 %. Moreover, the trade volume of tantalum-related commodities experienced substantial growth from 2000 to 2014 and then fluctuated, with tantalum concentrates as the primary imported goods and electronic products as the primary exported goods. Approximately 24.9 % of the overall tantalum demand was met with secondary tantalum, in which 80 % of such secondary material being recovered during the refining and production stages. Policy recommendations are proposed accordingly, including diversifying tantalum mineral resources and increasing the recovery rates from end-of-life products. These policies can significantly contribute to achieving sufficient tantalum supply and maintaining sustainable tantalum supply chain in China.

5.
J Int Med Res ; 52(8): 3000605241271891, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39192603

RESUMEN

Median arcuate ligament (MAL) syndrome, otherwise known as celiac artery compression syndrome, is rare and is characterized by celiac artery compression by the median arcuate ligament. We report a unique case of MAL syndrome with recurrent myocardial infarction as the primary manifestation, and offer new pathophysiological insights. A man in his early 50s experienced recurrent upper abdominal pain, electrocardiographic changes, and elevated troponin concentrations, which suggested myocardial infarction. Contrast-enhanced computed tomography showed considerable celiac artery stenosis due to MAL syndrome. The patient was diagnosed with MAL syndrome and acute myocardial infarction. He declined revascularization owing to economic constraints, and opted to have conservative treatment with Chinese herbal extracts and medications. He succumbed to sudden cardiac death during a subsequent abdominal pain episode. The findings from this case show that MAL syndrome can present with recurrent myocardial infarction rather than typical intestinal angina symptoms. The pathophysiological link may involve intestinal and cardiac ischemia. An accurate diagnosis and appropriate management of MAL syndrome require careful evaluation and investigation.


Asunto(s)
Arteria Celíaca , Síndrome del Ligamento Arcuato Medio , Infarto del Miocardio , Humanos , Masculino , Síndrome del Ligamento Arcuato Medio/complicaciones , Síndrome del Ligamento Arcuato Medio/diagnóstico , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/complicaciones , Infarto del Miocardio/etiología , Persona de Mediana Edad , Arteria Celíaca/diagnóstico por imagen , Arteria Celíaca/anomalías , Arteria Celíaca/patología , Recurrencia , Tomografía Computarizada por Rayos X , Electrocardiografía , Dolor Abdominal/etiología , Dolor Abdominal/diagnóstico
6.
J Agric Food Chem ; 72(36): 19966-19976, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39189841

RESUMEN

Phenylethanoid glycosides (PhGs) are naturally occurring glycosides derived from plants with various biological activities. Glycosyltransferases catalyze the production of PhGs from phenylethanols via a transglycosylation reaction. The low activity and stability of glycosyltransferase limit its industrial application. An ancestral glycosyltransferase, UGTAn85, with heat resistance, alkali resistance, and high stability was resurrected using ancestral sequence reconstruction technology. This enzyme can efficiently convert phenylethanols to PhGs. The optimal reaction temperature and pH for UGTAn85 were found to be 70 °C and pH 10.0, respectively. This study employed a combination of structure-guided rational design and co-evolution analysis to enhance its catalytic activity. Potential mutation sites were identified through computer-aided design, including homology modeling, molecular docking, Rosetta dock design, molecular dynamics simulation, and co-evolution analysis. By targeted mutagenesis, the UGTAn85 mutant Q23E/N65D exhibited a 2.2-fold increase in enzyme activity (11.85 U/mg) and elevated affinity (Km = 0.11 mM) for 2-phenylethanol compared to UGTAn85. Following a fed-batch reaction, 36.16 g/L 2-phenylethyl-ß-d-glucopyranoside and 51.49 g/L salidroside could be produced within 24 h, respectively. The findings in this study provide a new perspective on enhancing the stability and activity of glycosyltransferases, as well as a potential biocatalyst for the industrial production of PhGs.


Asunto(s)
Glucósidos , Glicosiltransferasas , Fenoles , Glucósidos/química , Glucósidos/metabolismo , Glucósidos/biosíntesis , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Glicosiltransferasas/química , Fenoles/metabolismo , Fenoles/química , Simulación del Acoplamiento Molecular , Estabilidad de Enzimas , Cinética , Alcohol Feniletílico/metabolismo , Alcohol Feniletílico/química , Alcohol Feniletílico/análogos & derivados , Ingeniería de Proteínas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Rhodiola/química , Rhodiola/genética , Rhodiola/enzimología , Rhodiola/metabolismo
7.
Nano Lett ; 24(35): 10964-10971, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39171642

RESUMEN

Two-dimensional (2D) antiferromagnetic (AFM) materials boasting a high Néel temperature (TN), high carrier mobility, and fast spin response under an external field are in great demand for efficient spintronics. Herein, we theoretically present the MoB3 monolayer as an ideal 2D platform for AFM spintronics. The AFM MoB3 monolayer features a symmetry-protected, 4-fold degenerate Dirac nodal line (DNL) at the Fermi level. It demonstrates a high magnetic anisotropy energy of 865 µeV/Mo and an ultrahigh TN of 1050 K, one of the highest recorded for 2D AFMs. Importantly, we reveal the ultrafast demagnetization of AFM MoB3 under laser irradiation, which induces a rapid transition from a DNL semimetallic state to a metallic state on the time scale of hundreds of femtoseconds. This work presents an effective method for designing advanced spintronics using 2D high-temperature DNL semimetals and opens up a new idea for ultrafast modulation of magnetization in topological semimetals.

8.
IEEE Trans Cybern ; PP2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39186434

RESUMEN

Quantized signal-driven control for nonlinear systems is of special interest in practice. However, it is nontrivial in the presence of mismatched uncertainties and intermittent denial of service (DoS) attacks. The underlying problem becomes even more complicated when both the input and output signals are attacked, rendering the state variables and the input signal inaccessible or unavailable for the control design. Only the quantized (and thus nondifferentiable) output signal is available in the absence of attack, making regular backstepping design inapplicable. This article introduces a novel adaptive output feedback control method to tackle the aforementioned challenges. First, we design a gain-switched quantized observer to estimate the unmeasurable state variables. Second, by employing a first-order dynamic filtering technique, we circumvent the nondifferentiability issue of virtual controller arising from the signal quantization. Third, we establish design conditions for the controller parameters. Fourth, we utilize a more comprehensive sector quantizer and develop adaptive estimators to deal with the unknown quantization parameters. Finally, we demonstrate that with the proposed control method, all the closed-loop signals are semiglobally uniformly ultimately bounded (SUUB), and the regulation error can be made small enough by appropriately tuning the design parameters. Numerical simulations confirm the efficacy of the proposed approach.

9.
World J Gastrointest Oncol ; 16(8): 3436-3444, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39171182

RESUMEN

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in the world, and its prognosis is closely related to many factors. In recent years, the incidence of vascular thrombosis in patients with GC has gradually attracted increasing attention, and studies have shown that it may have a significant impact on the survival rate and prognosis of patients. However, the specific mechanism underlying the association between vascular thrombosis and the prognosis of patients with GC remains unclear. AIM: To analyze the relationships between vascular cancer support and other clinicopathological factors and their influence on the prognosis of patients with GC. METHODS: This study retrospectively analyzed the clinicopathological data of 621 patients with GC and divided them into a positive group and a negative group according to the presence or absence of a vascular thrombus. The difference in the 5-year cumulative survival rate between the two groups was compared, and the relationships between vascular cancer thrombus and other clinicopathological factors and their influence on the prognosis of patients with GC were analyzed. RESULTS: Among 621 patients with GC, the incidence of vascular thrombi was 31.7% (197 patients). Binary logistic regression analysis revealed that the degree of tumor differentiation, depth of invasion, and extent of lymph node metastasis were independent influencing factors for the occurrence of vascular thrombi in GC patients (P < 0.01). The trend of the χ 2 test showed that the degree of differentiation, depth of invasion, and extent of lymph node metastasis were linearly correlated with the percentage of vascular thrombi in GC patients (P < 0.01), and the correlation between lymph node metastasis and vascular thrombi was more significant (r = 0.387). Univariate analysis revealed that the 5-year cumulative survival rate of the positive group was significantly lower than that of the negative group (46.7% vs 73.3%, P < 0.01). Multivariate analysis revealed that age, tumor diameter, TNM stage, and vascular thrombus were independent risk factors for the prognosis of GC patients (all P < 0.05). Further stratified analysis revealed that the 5-year cumulative survival rate of stage III GC patients in the thrombolase-positive group was significantly lower than that in the thrombolase-negative group (36.1% vs 51.4%; P < 0.05). CONCLUSION: Vascular cancer status is an independent risk factor affecting the prognosis of patients with GC. The combination of vascular cancer suppositories and TNM staging can better judge the prognosis of patients with GC and guide more reasonable treatment.

10.
Comput Biol Med ; 179: 108835, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38996550

RESUMEN

Gene regulatory networks (GRNs) are crucial for understanding organismal molecular mechanisms and processes. Construction of GRN in the epithelioma papulosum cyprini (EPC) cells of cyprinid fish by spring viremia of carp virus (SVCV) infection helps understand the immune regulatory mechanisms that enhance the survival capabilities of cyprinid fish. Although many computational methods have been used to infer GRNs, specialized approaches for predicting the GRN of EPC cells following SVCV infection are lacking. In addition, most existing methods focus primarily on gene expression features, neglecting the valuable network structural information in known GRNs. In this study, we propose a novel supervised deep neural network, named MEFFGRN (Matrix Enhancement- and Feature Fusion-based method for Gene Regulatory Network inference), to accurately predict the GRN of EPC cells following SVCV infection. MEFFGRN considers both gene expression data and network structure information of known GRN and introduces a matrix enhancement method to address the sparsity issue of known GRN, extracting richer network structure information. To optimize the benefits of CNN (Convolutional Neural Network) in image processing, gene expression and enhanced GRN data were transformed into histogram images for each gene pair respectively. Subsequently, these histograms were separately fed into CNNs for training to obtain the corresponding gene expression and network structural features. Furthermore, a feature fusion mechanism was introduced to comprehensively integrate the gene expression and network structural features. This integration considers the specificity of each feature and their interactive information, resulting in a more comprehensive and precise feature representation during the fusion process. Experimental results from both real-world and benchmark datasets demonstrate that MEFFGRN achieves competitive performance compared with state-of-the-art computational methods. Furthermore, study findings from SVCV-infected EPC cells suggest that MEFFGRN can predict novel gene regulatory relationships.


Asunto(s)
Enfermedades de los Peces , Redes Reguladoras de Genes , Infecciones por Rhabdoviridae , Rhabdoviridae , Animales , Rhabdoviridae/genética , Enfermedades de los Peces/genética , Enfermedades de los Peces/virología , Infecciones por Rhabdoviridae/genética , Infecciones por Rhabdoviridae/virología , Carpas/genética , Carpas/virología , Biología Computacional/métodos , Redes Neurales de la Computación , Cyprinidae/genética
11.
Dev Cell ; 59(16): 2254-2269.e6, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39053471

RESUMEN

Symbiotic nodules comprise two classes, indeterminate and determinate, defined by the presence/absence of apical meristem and developmental zonation. Why meristem and zonation are absent from determinate nodules remains unclear. Here, we define cell types in developing soybean nodules, highlighting the undifferentiated infection zones and differentiated nitrogen-fixation zones. Auxin governs infection zone maintenance. GRETCHEN HAGEN 3 (GH3) enzymes deactivate auxin by conjugation and promote cell differentiation. gh3 mutants increased undifferentiated cells and enlarged infection zones. The central symbiosis-transcription factor NIN2a activates GH3.1 to reduce auxin levels and facilitates cell differentiation. High auxin promotes NIN2a protein accumulation and enhances signaling, further deactivating auxin and depleting infection zones. Our findings shed light on the NIN2a-GH3-auxin module that drives soybean nodule cell differentiation. This study challenges our understanding of determinate nodule development and proposes that the regulation of nodule zonation offers valuable insights into broader mechanisms of cell differentiation across plant species.


Asunto(s)
Diferenciación Celular , Regulación de la Expresión Génica de las Plantas , Glycine max , Homeostasis , Ácidos Indolacéticos , Proteínas de Plantas , Nódulos de las Raíces de las Plantas , Transducción de Señal , Simbiosis , Glycine max/metabolismo , Glycine max/genética , Glycine max/crecimiento & desarrollo , Ácidos Indolacéticos/metabolismo , Nódulos de las Raíces de las Plantas/metabolismo , Nódulos de las Raíces de las Plantas/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Fijación del Nitrógeno
12.
J Gene Med ; 26(7): e3718, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38979822

RESUMEN

BACKGROUND: Icariin (ICA) inhibits inflammatory response in various diseases, but the mechanism underlying ICA treating airway inflammation in asthma needs further understood. We aimed to predict and validate the potential targets of ICA against asthma-associated airway inflammation using network pharmacology and experiments. METHODS: The ovalbumin-induced asthma-associated airway inflammation mice model was established. The effects of ICA were evaluated by behavioral, airway hyperresponsiveness, lung pathological changes, inflammatory cell and cytokines counts. Next, the corresponding targets of ICA were mined via the SEA, CTD, HERB, PharmMapper, Symmap database and the literature. Pubmed-Gene and GeneCards databases were used to screen asthma and airway inflammation-related targets. The overlapping targets were used to build an interaction network, analyze gene ontology and enrich pathways. Subsequently, flow cytometry, quantitative real-time PCR and western blotting were employed for validation. RESULTS: ICA alleviated the airway inflammation of asthma; 402 targets of ICA, 5136 targets of asthma and 4531 targets of airway inflammation were screened; 216 overlapping targets were matched and predicted ICA possesses the potential to modulate asthmatic airway inflammation by macrophage activation/polarization. Additionally, ICA decreased M1 but elevated M2. Potential targets that were disrupted by asthma inflammation were restored by ICA treatment. CONCLUSIONS: ICA alleviates airway inflammation in asthma by inhibiting the M1 polarization of alveolar macrophages, which is related to metabolic reprogramming. Jun, Jak2, Syk, Tnf, Aldh2, Aldh9a1, Nos1, Nos2 and Nos3 represent potential targets of therapeutic intervention. The present study enhances understanding of the anti-airway inflammation effects of ICA, especially in asthma.


Asunto(s)
Asma , Modelos Animales de Enfermedad , Flavonoides , Activación de Macrófagos , Macrófagos Alveolares , Farmacología en Red , Animales , Asma/tratamiento farmacológico , Asma/metabolismo , Ratones , Flavonoides/farmacología , Flavonoides/uso terapéutico , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/inmunología , Activación de Macrófagos/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Citocinas/metabolismo , Ovalbúmina , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Femenino
13.
Artículo en Inglés | MEDLINE | ID: mdl-38980654

RESUMEN

To investigate the impacts of circ_0069094 on acute coronary syndrome. Real-time polymerase chain reaction was used to detect the expression levels of circ_0069094, and its diagnostic performance was evaluated using ROC curve. Spearman's method was performed for correlation analysis. The levels of SOD, MDA, vWF in ACS rat models were assessed by commercial kits. The activities of H/R cell models were detected by CCK-8, Transwell, flow cytometry. The GO and KEGG were performed to analyze the function of targeted genes of miR-484. The concentration of circ_0069094 was decreased in patients with ACS, ACS rat models and H/R HUVEC models. The dysfunction of SOD, MDA, vWF, LVIDs, LVDD, and LVEF in the ACS models was regulated by the increase of circ_0069094. The viability, migration, apoptosis of the H/R models were regulated by circ_0069094. MiR-484 was a ceRNA of circ_0069094 and mediated the function of circ_0069094.

14.
Molecules ; 29(13)2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38999069

RESUMEN

The prevalence of major bacterial infections has emerged as a significant menace to human health and life. Conventional treatment methods primarily rely on antibiotic therapy, but the overuse of these drugs has led to a decline in their efficacy. Moreover, bacteria have developed resistance towards antibiotics, giving rise to the emergence of superbugs. Consequently, there is an urgent need for novel antibacterial agents or alternative strategies to combat bacterial infections. Nanoantibiotics encompass a class of nano-antibacterial materials that possess inherent antimicrobial activity or can serve as carriers to enhance drug delivery efficiency and safety. In recent years, metal nanoclusters (M NCs) have gained prominence in the field of nanoantibiotics due to their ultra-small size (less than 3 nm) and distinctive electronic and optical properties, as well as their biosafety features. In this review, we discuss the recent progress of M NCs as a new generation of antibacterial agents. First, the main synthesis methods and characteristics of M NCs are presented. Then, we focus on reviewing various strategies for detecting and treating pathogenic bacterial infections using M NCs, summarizing the antibacterial effects of these nanoantibiotics on wound infections, biofilms, and oral infections. Finally, we propose a perspective on the remaining challenges and future developments of M NCs for bacterial infectious therapy.


Asunto(s)
Antibacterianos , Infecciones Bacterianas , Nanopartículas del Metal , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Humanos , Bacterias/efectos de los fármacos , Biopelículas/efectos de los fármacos , Animales
15.
J Med Virol ; 96(8): e29830, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39072764

RESUMEN

In the current antiretroviral landscape, continuous efforts are still needed to search for novel chemotypes of human immunodeficiency virus type 1 (HIV-1) inhibitors with improved drug resistance profiles and favorable drug-like properties. Herein, we report the design, synthesis, biological characterization, and druggability evaluation of a class of non-nucleoside reverse transcriptase inhibitors. Guided by the available crystallographic information, a series of novel indolylarylsulfone derivatives were rationally discovered via the substituent decorating strategy to fully explore the chemical space of the entrance channel. Among them, compound 11h bearing the cyano-substituted benzyl moiety proved to be the most effective inhibitor against HIV-1 wild-type and mutant strains (EC50 = 0.0039-0.338 µM), being far more potent than or comparable to etravirine and doravirine. Besides, 11h did not exhibit cytotoxicity at the maximum test concentration. Meanwhile, the binding target of 11h was further confirmed to be reverse transcriptase (IC50 = 0.055 µM). Preliminary structure-activity relationship were discussed to guide further optimization work. Molecular docking and dynamics simulation studies were investigated in detail to rationalize the biological evaluation results. Further drug-likeness assessment indicated that 11h possessed excellent physicochemical properties. Moreover, no apparent hERG blockade liability and cytochrome P450 inhibition were observed for 11h. Notably, 11h was characterized by favorable in vitro metabolic stability with moderate clearance rates and long half-lives in human plasma and liver microsomes. Overall, 11h holds great promise as an ideal Anti-HIV-1 lead compound due to its potent antiviral efficacy, low toxicity, and favorable drug-like profiles.


Asunto(s)
Fármacos Anti-VIH , Diseño de Fármacos , VIH-1 , Simulación del Acoplamiento Molecular , Inhibidores de la Transcriptasa Inversa , Sulfonas , VIH-1/efectos de los fármacos , Humanos , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/química , Relación Estructura-Actividad , Sulfonas/farmacología , Sulfonas/síntesis química , Sulfonas/química , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/síntesis química , Inhibidores de la Transcriptasa Inversa/química , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Transcriptasa Inversa del VIH/metabolismo
16.
Front Vet Sci ; 11: 1432741, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39071781

RESUMEN

Introduction: Blastocystis is one of the most critical intestinal protozoans in various hosts, including humans and mice. To determine the status of Blastocystis infection in wild rodents in China. Methods: A total of 344 faecal samples were collected from seven wild rodent species from three provinces, and the small subunit ribosomal RNA (SSU rRNA) genes of Blastocystis were amplified to determine their prevalence and subtypes. Results: Of the 344 samples, 54 (15.70%) were detected as Blastocystis-positive. The prevalence of Blastocystis was 26.14% (40/153), 7.95% (7/88), and 6.80% (7/103) in wild rodents from Hunan Province, Yunnan Province, and Guangxi Province, respectively. The prevalence of Blastocystis in different wild rodent species varied from 0.00% (0/13) in Mus musculus to 40.00% (2/5) in Rattus rattus sladeni. The prevalence of Blastocystis in samples from the lake beach area (27.40%, 40/146) was significantly higher than in those from the mountain (6.80%, 7/103) and field regions (7.37%, 7/95). The prevalence in different seasons was 26.14% in summer (40/153), 7.95% in autumn (7/88), and 6.80% in winter (7/103). Moreover, a total of two Blastocystis subtypes were identified in the investigated wild rodents, including ST4 and ST5. Discussion: The present study discovered the existence of Blastocystis infection in Rattus favipectus, Microtus fortis, Apodemus agrarius, Bandicota indica, Rattus rattus sladeni, and Rattus losea, expanding the host range of this parasite. The findings also demonstrate that wild rodents may be an important potential infection source for Blastocystis infection in humans and other animals.

17.
J Transl Med ; 22(1): 678, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049031

RESUMEN

BACKGROUND: Patients with lung adenocarcinoma (LUAD) have a low response rate to immune checkpoint blockade. It is highly important to explore the tumor immune escape mechanism of LUAD patients and expand the population of patients who may benefit from immunotherapy. METHODS: Based on 954 bulk RNA-seq data of LUAD patients and 15 single-cell RNA-seq data, the relationships between tumor immune dysfunction and exclusion (TIDE) scores and survival prognosis in each patient were calculated and evaluated, and the immune escape mechanism affecting the independent prognosis of LUAD patients was identified. Functional enrichment analysis explored the antitumour immune response and biological behavior of tumor cells among different LUAD groups. Single-cell annotation and pseudotemporal analysis were used to explore the target molecules and immune escape mechanisms of LUAD. RESULTS: Myeloid-derived suppressor cells (MDSCs) and IRF8 were identified as risk and protective factors for the independent prognosis of LUAD patients, respectively. In the tumor microenvironment of patients with high infiltration of MDSCs, the antitumor immune response is significantly suppressed, while tumor cell division, proliferation, and distant metastasis are significantly enhanced. Single-cell RNA-seq analysis revealed that IRF8 is an important regulator of MDSC differentiation in LUAD myeloid cells. In addition, IRF8 may regulate the differentiation of MDSCs through the IL6-JAK-STAT3 signalling pathway. CONCLUSIONS: IRF8 deficiency impairs the normal development of LUAD myeloid cells and induces their differentiation into MDSCs, thereby accelerating the immune escape of LUAD cells. IRF8-targeted activation to inhibit the formation of MDSCs may be a new target for immunotherapy in LUAD.


Asunto(s)
Adenocarcinoma del Pulmón , Factores Reguladores del Interferón , Neoplasias Pulmonares , Células Supresoras de Origen Mieloide , Microambiente Tumoral , Humanos , Células Supresoras de Origen Mieloide/inmunología , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Factores Reguladores del Interferón/metabolismo , Factores Reguladores del Interferón/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Microambiente Tumoral/inmunología , Pronóstico , Femenino , Regulación Neoplásica de la Expresión Génica , Transducción de Señal , Masculino , Escape del Tumor , Evasión Inmune , Análisis de la Célula Individual , Diferenciación Celular
18.
Phys Chem Chem Phys ; 26(31): 21173-21185, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39072651

RESUMEN

As a derivative of the two-dimensional material family, two-dimensional Janus materials have garnered widespread attention in recent years. Consequently, in this work, we systematically investigated the stability, electronic properties, photocatalytic properties, optical properties, and carrier mobility of SPtAZ2 (A = Si and Ge; Z = N, P, and As) monolayers using first-principles calculations. In the equilibrium state, we identified four stable structures that exhibited the properties of indirect band gap semiconductors using the HSE06 hybrid functional. Through the exploration of the photocatalytic and optical properties of these four stable structures, we observed that SPtSiN2, SPtSiP2, and SPtGeAs2 monolayers possess favorable band edge positions, high solar-to-hydrogen efficiency (up to 30.74%), and light absorption efficiency, thus endowing these three structures with commendable photocatalytic and light absorption performance. We additionally calculated the carrier mobility of these three structures and identified significant differences in electron and hole mobilities in the same direction, facilitating the effective separation of electrons and holes. Finally, we explored the effects of biaxial strain on the electronic properties, photocatalysis, and light absorption of stable SPtAZ2 monolayers. Our research results not only expand the 2D Janus material family, but also successfully predict a type of photocatalyst capable of utilizing visible light for overall water splitting.

19.
Research (Wash D C) ; 7: 0411, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38974011

RESUMEN

Molecular materials possessing switchable magneto-optical properties are of great interest due to their potential applications in spintronics and molecular devices. However, switching their photoluminescence (PL) and single-molecule magnet (SMM) behavior via light-induced structural changes still constitutes a formidable challenge. Here, a series of cubane structures were synthesized via self-assembly of 9-anthracene carboxylic acid (HAC) and rare-earth ions. All complexes exhibited obvious photochromic phenomena and complete PL quenching upon Xe lamp irradiation, which were realized via the synergistic effect of photogenerated radicals and [4 + 4] photocycloaddition of the AC components. The quenched PL showed the largest fluorescence intensity change (99.72%) in electron-transfer photochromic materials. A reversible decoloration process was realized via mechanical grinding, which is unexpectedly in the electron-transfer photochromic materials. Importantly, an SMM behavior of the Dy analog was observed after room-temperature irradiation due to the photocycloaddition of AC ligands and the photogenerated stable radicals changed the electrostatic ligand field and magnetic coupling. Moreover, based on the remarkably photochromic and photoluminescent properties of these compounds, 2 demos were applied to support their application in information anti-counterfeiting and inkless printing. This work, for the first time utilizing the simultaneous modulation of photocycloaddition and photogenerated radicals in one system, realizes complete PL quenching and light-induced SMM behavior, providing a dynamical switch for the construction of multifunctional polymorphic materials with optical response and optical storage devices.

20.
Adv Mater ; : e2403413, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39011771

RESUMEN

The rapid development of the Internet of Things (IoT) has accelerated the advancement of indoor photovoltaics (IPVs) that directly power wireless IoT devices. The interest in lead-free perovskites for IPVs stems from their similar optoelectronic properties to high-performance lead halide perovskites, but without concerns about toxic lead leakage in indoor environments. However, currently prevalent lead-free perovskite IPVs, especially tin halide perovskites (THPs), still exhibit inferior performance, arising from their uncontrollable crystallization. Here, a novel adhesive bonding strategy is proposed for precisely regulating heterogeneous nucleation kinetics of THPs by introducing alkali metal fluorides. These ionic adhesives boost the work of adhesion at the buried interface between substrates and perovskite film, subsequently reducing the contact angle and energy barrier for heterogeneous nucleation, resulting in high-quality THP films. The resulting THP solar cells achieve an efficiency of 20.12% under indoor illumination at 1000 lux, exceeding all types of lead-free perovskite IPVs and successfully powering radio frequency identification-based sensors.

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