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1.
J Environ Sci (China) ; 148: 502-514, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39095184

RESUMEN

Objective weather classification methods have been extensively applied to identify dominant ozone-favorable synoptic weather patterns (SWPs), however, the consistency of different classification methods is rarely examined. In this study, we apply two widely-used objective methods, the self-organizing map (SOM) and K-means clustering analysis, to derive ozone-favorable SWPs at four Chinese megacities in 2015-2022. We find that the two algorithms are largely consistent in recognizing dominant ozone-favorable SWPs for four Chinese megacities. In the case of classifying six SWPs, the derived circulation fields are highly similar with a spatial correlation of 0.99 between the two methods, and the difference in the mean frequency of each SWP is less than 7%. The six dominant ozone-favorable SWPs in Guangzhou are all characterized by anomaly higher radiation and temperature, lower cloud cover, relative humidity, and wind speed, and stronger subsidence compared to climatology mean. We find that during 2015-2022, the occurrence of ozone-favorable SWPs days increases significantly at a rate of 3.2 day/year, faster than the increases in the ozone exceedance days (3.0 day/year). The interannual variability between the occurrence of ozone-favorable SWPs and ozone exceedance days are generally consistent with a temporal correlation coefficient of 0.6. In particular, the significant increase in ozone-favorable SWPs in 2022, especially the Subtropical High type which typically occurs in September, is consistent with a long-lasting ozone pollution episode in Guangzhou during September 2022. Our results thus reveal that enhanced frequency of ozone-favorable SWPs plays an important role in the observed 2015-2022 ozone increase in Guangzhou.


Asunto(s)
Contaminantes Atmosféricos , Monitoreo del Ambiente , Ozono , Tiempo (Meteorología) , Ozono/análisis , China , Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos
2.
Mol Med Rep ; 30(5)2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39301641

RESUMEN

Copper, a vital trace element, is indispensable for the maintenance of physiological functioning, particularly in the cardiac system. Unlike other forms of cell death such as iron death and apoptosis, copper­induced cell death has gained increasing recognition as a significant process influencing the development of cardiovascular diseases. The present review highlights the significance of maintaining copper homeostasis in addressing cardiovascular diseases. This review delves into the crucial roles of copper in physiology, including the metabolic pathways and its absorption, transport and excretion. It provides detailed insights into the mechanisms underlying cardiovascular diseases resulting from both excess and deficient copper levels. Additionally, it summarizes strategies for treating copper imbalances through approaches such as copper chelators and ion carriers while discussing their limitations and future prospects.


Asunto(s)
Enfermedades Cardiovasculares , Cobre , Humanos , Enfermedades Cardiovasculares/metabolismo , Cobre/metabolismo , Animales , Homeostasis , Quelantes/uso terapéutico , Iones/metabolismo
3.
Lab Chip ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39315634

RESUMEN

Cell sorting holds broad applications in fields such as early cancer diagnosis, cell differentiation studies, drug screening, and single-cell sequencing. However, achieving high-throughput and high-purity in label-free single-cell sorting is challenging. To overcome this issue, we propose a label-free, high-throughput, and high-accuracy impedance-activated cell sorting system based on impedance detection and dual membrane pumps. Leveraging the low-latency characteristics of FPGA, the system facilitates real-time dual-frequency single-cell impedance detection with high-throughput (5 × 104 cells per s) for HeLa, MDA-MB-231, and Jurkat cells. Furthermore, the system accomplishes low-latency (less than 0.3 ms), label-free, high-throughput (1000 particles per s) and high-accuracy (almost 99%) single-particle sorting using FPGA-based high-precision sort-timing prediction. In experiments with Jurkat and MDA-MB-231 cells, the system achieved a throughput of up to 1000 cells per s, maintaining a pre-sorting purity of 28.57% and increasing post-sorting purity to 97.09%. These findings indicate that our system holds significant potential for applications in label-free, high-throughput cell sorting.

4.
Front Behav Neurosci ; 18: 1453161, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39301432

RESUMEN

Objective: Depression may be accompanied by cognitive impairment, but its pathogenesis remains unclear. This study aims to investigate the protective effects of fluoxetine on behavioral performance and prefrontal cortex neuronal damage in rats with depression-associated cognitive impairment, based on the observation of VGLUT2 protein expression. Methods: Forty-five SPF-grade male SD rats were randomly divided into three groups (n = 15): normal control group (CON), depression group (DD), and fluoxetine group (DD + F). The CON group was reared normally, while the DD and DD + F groups underwent chronic unpredictable mild stress (CUMS) combined with social isolation to induce a depression-related cognitive dysfunction model. After modeling, the DD + F group was treated with fluoxetine (10 mg/kg, ig) for 14 days. Behavioral tests were performed to assess changes in mood, cognition, learning, and social abilities. Histopathological observations were made to examine pathological changes, neuronal apoptosis, ultrastructure, and dendritic spine density in the prefrontal cortex. The concentration, relative expression level, and mRNA expression of VGLUT2 protein were also measured. Finally, a correlation analysis was performed between the relative expression level and mRNA expression of VGLUT2 protein and the pathological changes in neurons. Results: Compared to the CON group, the DD group exhibited decreased body weight, anhedonia, increased behavioral despair, reduced locomotor activity and spontaneous exploratory behavior, impaired spatial learning and memory, and decreased social interaction and social cognitive ability. Pathological damage was observed in the prefrontal cortex, with neuronal apoptosis, ultrastructural damage, and reduced neuroplasticity. The concentration, relative expression, and mRNA expression levels of VGLUT2 protein were decreased. Following fluoxetine intervention, the above behavioral phenotypes improved; pathological damage showed varying degrees of recovery; and the concentration, relative expression, and mRNA expression levels of VGLUT2 protein increased. Finally, there was a significant correlation between VGLUT2 protein expression and pathological changes in the prefrontal cortex. Conclusion: After 28 days of CUMS combined with isolation rearing, rats exhibited impairments in mood, cognition, learning, and social abilities, with neuronal damage and decreased VGLUT2 protein levels in the prefrontal cortex. Following fluoxetine intervention, VGLUT2 protein expression increased, neuronal repair in the prefrontal cortex occurred, depressive-like behavior improved, and cognitive learning and social abilities were restored.

5.
Sci Rep ; 14(1): 21933, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39304704

RESUMEN

The terminal mining is an essential part of fully mechanized mining, and the reasonable length of the flap roof during the terminal mining is an important basis for the smooth operation of the terminal mining. With the research background of the 213 working face of the Longde Coal Mine, the contribution of this study is the influence law of hydraulic fracturing on the terminal mining mechanical behavior of the working face. Four different numerical calculation models of terminal mining hydraulic fracturing are established, and the optimal hydraulic fracturing site plan is determined according to the length of the terminal mining flap top and the working resistance of hydraulic support. The effect of hydraulic fracturing construction and the law of mechanical behavior in the terminal mining stage in the field test are analyzed. The results show that through hydraulic fracturing technology, the control of the length of the flap roof of the working face during the terminal mining period has been realized.

6.
Brain Behav Immun ; 123: 229-243, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39288893

RESUMEN

Neuroinflammation and autoimmunity are pivotal in the pathogenesis of neurodegenerative diseases. Complement activation and involvement of astrocyte-neuron C3/C3aR pathway have been observed, yet the mechanisms influencing α-synuclein (α-syn) pathology and neurodegeneration remain unclear. In this study, elevated levels of complement C3 were detected in the plasma of α-syn PFF-induced mice and the substantia nigra of A53T transgenic mice. Colocalization of complement C3 with astrocytes was also observed. Overexpression of complement C3 exacerbated motor dysfunction, dopaminergic neuron loss, and phosphorylated α-syn expression in mice injected with α-syn preformed fibrils (α-syn PFFs). Conversely, downregulation of complement C3 protected α-syn PFF-induced mice. Molecular investigations revealed that inhibition of Toll-like receptor 2 (TLR2) or NF-κB reduced complement C3 expression in primary astrocytes following α-syn PFF treatment. Astrocyte-neuron communication via the C3/C3aR pathway influenced α-syn PFF-induced neuronal apoptosis and α-syn pathology, potentially through modulation of GSK3ß. These findings underscore the critical role of astrocyte-neuron communication via the C3/C3aR pathway in PD pathogenesis, highlighting its potential as a therapeutic target.

7.
Int J Biol Macromol ; 280(Pt 1): 135728, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293632

RESUMEN

Intestinal inflammation is a common feature of many digestive diseases, and intestinal metabolic disorders further aggravate the pathological state. The aim of this study was to investigate the regulatory effect of saponins on TNF-α protein and its effect on intestinal metabolism in the model of intestinal inflammation induced by sodium dextran sulfate. Through cell culture and biochemical detection, appropriate cell lines were selected to simulate intestinal inflammatory environment, induce inflammatory response, observe cell morphological changes and growth status, and evaluate the protective effect of TNF-α protein on cells. The level of TNF-α protein was quantitatively determined by biochemical assay, and the effect of saponins on its secretion and activity was investigated. Saponin treatment can restore the expression of intestinal metabolism-related enzymes and improve metabolic disorders. Therefore, by regulating the expression of TNF-α protein and its signaling pathway, saponins show a alleviating effect on intestinal inflammation and help restore intestinal metabolic balance.

8.
Sci Rep ; 14(1): 21838, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294415

RESUMEN

Formulating a course of action (COA) before a combat is crucial for operational command. Research in command and control (C2) artificial intelligence is currently focused on using intelligent auxiliary decision-making methods to implement COA. This paper proposes a COA planning method based on line of operation (LOO) and uses planning domain definition language (PDDL) to describe combat scenarios and COA. Following the effect-based optimization (EBO) principle, an effect evaluation model for COA was constructed, and dynamic bayesian networks (DBNs) was used to determine the reasoning and calculate the results of the effect evaluation network. To further improve the execution efficiency of the effect evaluation model in practical applications, the network was optimized through a back propagation neural network (BPNN). Relevant experiments based on the coordinated distributed air defense and anti-missile scenario were carried out using the LOO model to complete the planning of COA. A BPNN evaluation model based on the DBNs evaluation model was built. After training and fine-tuning, it achieved similar evaluation results, with a mean absolute percentage error (MAPE) of less than 0.02%. Compared with the DBNs model, the BPNN model achieved an efficiency improvement of no less than 65%, effectively reducing the consumption of computing resources. This research is the first time to realize the modeled description of COA planning, automatic evaluation, and calculation optimization of COA effects. It can support the development of decision support systems (DSS) and has the potential for practical application.

9.
JAMA Oncol ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298141

RESUMEN

Importance: Chimeric antigen receptor (CAR) T-cell therapy (CART) has transformed the treatment landscape of hematologic cancer, but has negligible effects for adult solid cancers. In this trial, an autologous CAR T-cell product demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer (mCRC). Objective: To evaluate the safety and efficacy of guanylate cyclase-C (GCC19) CART in participants with metastatic colorectal cancer (mCRC). Design, Setting, and Participants: This single-arm, nonrandomized, phase 1 trial was conducted at the First Hospital of Jilin University from December 3, 2020, to April 13, 2022. Data analysis was conducted from May 2022 to April 2024. Adults with relapsed and refractory mCRC expressing GCC were treated with GCC19CART, a mixture of autologous CAR T cells transduced with lentiviral vectors expressing genes that encode either CD-19 CAR or GCC CAR. Main Outcomes and Measures: Safety and tolerability of CAR T-cell therapy targeting GCC in patients with mCRC without therapeutic options is capable of conferring a reasonable likeliness of clinical benefit. Other outcomes included objective response rate, progression-free survival, overall survival, and immune activation. Results: Of 15 patients 9 (60%) were women, and the median (range) age was 44 (33-61) years. Treatment with GCC19CART was associated with the development of cytokine release syndrome and diarrhea in most patients, all of which were self-limited and manageable. The objective response rate was 40%, with a partial response in 2 of 8 and 4 of 7 patients treated with either 1 × 106 cells/kg or 2 × 106 cells/kg. Median overall survival was 22.8 months (95% CI, 13.4-26.1) at data cutoff; the median progress-free survival was 6.0 months in the high dose level group (95% CI, 3.0 to not available). Conclusions and Relevance: The results of this nonrandomized clinical trial suggest that GCC19CART was safe and tolerable in heavily pretreated patients with mCRC and is the first CAR T-cell therapy known to produce objective clinical activity in refractory cancer. Given the paucity of effective therapeutics developed for colorectal cancer in recent decades, the observation that CD-19 CART target engagement can robustly induce GCC19CART target engagement sufficient to produce objective activity may serve as a foundation to develop effective cellular therapy in mCRC and other solid cancers. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000040645.

10.
Chem Sci ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39290589

RESUMEN

Controllable ß-carbon elimination to extrude norbornene remains a long-standing challenge in palladium and norbornene chemistry. Herein, this manuscript describes a switchable synthesis of biologically active C4-ethylaminoindole and C7-aminoindoline scaffolds by controlling ß-carbon elimination, utilizing aziridine as a C-H ethylamination reagent through a C-N bond cleavage reaction. Furthermore, the protecting groups of the product can be easily removed, offering an unusual method for the synthesis of dopamine receptor agonists.

11.
Int J Med Inform ; 192: 105630, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39293162

RESUMEN

BACKGROUND: New cases of lymphoma are rising, and the symptom burden, like cancer-related fatigue (CRF), severely impacts the quality of life of lymphoma survivors. However, clinical diagnosis and treatment of CRF are inadequate and require enhancement. OBJECTIVE: The main objective of this study is to construct machine learning-based CRF prediction models for lymphoma survivors to help healthcare professionals accurately identify the CRF population and better personalize treatment and care for patients. METHODS: A cross-sectional study in China recruited lymphoma patients from June 2023 to March 2024, dividing them into two datasets for model construction and external validation. Six machine learning algorithms were used in this study: Logistic Regression (LR), Random Forest, Single Hidden Layer Neural Network, Support Vector Machine, eXtreme Gradient Boosting, and Light Gradient Boosting Machine (LightGBM). Performance metrics like the area under the receiver operating characteristic (AUROC) and calibration curves were compared. The clinical applicability was assessed by decision curve, and Shapley additive explanations was employed to explain variable significance. RESULTS: CRF incidence was 40.7 % (dataset I) and 44.8 % (dataset II). LightGBM showed strong performance in training and internal validation. LR excelled in external validation with the highest AUROC and best calibration. Pain, total protein, physical function, and sleep disturbance were important predictors of CRF. CONCLUSION: The study presents a machine learning-based CRF prediction model for lymphoma patients, offering dynamic, data-driven assessments that could enhance the development of automated CRF screening tools for personalized management in clinical practice.

12.
J Hazard Mater ; 480: 135790, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39276744

RESUMEN

Agricultural soils are important source and sink of antibiotic resistance genes (ARGs). However, little is known about the fate of ARGs in dryland soils, while its human exposure risks were seriously overlooked. Taking the northern Ningxia Plain as a case, this study explored the occurrence of ARGs and its relationship with mobile genetic elements (MGEs), pathogens, and environmental factors. Furthermore, the concentrations of airborne ARGs by soil wind erosion and the human exposure doses of soil ARGs were evaluated. The results showed the abundances of different regions ranged from 4.0 × 105 to 1.6 × 106 copies/g. Soil ARGs are driven by MGEs, but multiply impacted by soil properties, nutrition, and bacterial community. Vibrio metschnikovii, Acinetobacter schindleri, and Serratia marcescens are potential pathogenic hosts for ARGs. Further exploration revealed the concentration of ARGs loaded in dust by soil wind erosion reached more than 105 copies/m3, which were even higher than those found in sewage treatment plants and hospitals. Skin contact is the primary route of ARGs exposure, with a maximum dose of 24071.33 copies/kg/d, which is largely attributed to ARGs loaded in dust. This study bridged the gap on ARGs in dryland soils, and provided reference for human exposure risk assessment of soil ARGs.

13.
Environ Res ; 262(Pt 2): 119943, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276835

RESUMEN

Understanding polychlorinated biphenyl (PCB) degradation in sequential anaerobic-aerobic remediation is crucial for effective remediation strategies. In this study, microcosm and greenhouse experiments were conducted to dissect the effects of organic amendments (carbon-based) and plant treatments (ryegrass) on soil PCB dissipation under oxic and sequential anoxic-oxic conditions. We analyzed the soil bacterial community in greenhouse experiments using high-throughput sequencing to explore plant-pollutant-microbe interactions. Microcosm results showed that organic amendments alone did not facilitate aerobic PCB removal, but significantly accelerated PCB dechlorination under anoxic conditions altering the profiles of PCB congeners. In standard greenhouses, plant treatments substantially increased PCB dissipation to 50.8 ± 3.9%, while organic amendments aided phytoremediation by promoting plant growth, increasing PCB removal to 65.9 ± 3.2%. In sequential anaerobic-aerobic greenhouses, plant growth was inhibited by flooding treatment while flooding stress was markedly alleviated by organic amendments. Plant treatments alone during sequential treatments did not lead to PCB dissipation; however, dissipation was significantly promoted following organic amendments, achieving a removal of 41.2 ± 5.7%. This PCB removal was primarily due to anaerobic dechlorination during flooding (27.8 ± 0.5% removal), rather than from plant growth stimulation in subsequent planting phase. Co-occurrence network and functional prediction analyses revealed that organic amendments recruited specific bacterial clusters with distinct functions under different conditions, especially stimulating plant-microbe interactions and xenobiotics biodegradation pathways in planted systems. The findings provide valuable guidance for the design of practical remediation strategies under various remedy scenarios, such as in arable or paddy fields.

15.
ISA Trans ; : 1-8, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39237395

RESUMEN

This paper investigates safety-critical event-triggered control (ETC) for nonlinear systems. It proposes a new ETC strategy that ensures event-triggered safety by using a tunable input-to-state safe barrier function. Then, a method is devised to effectively save communication resources and reduce computational load through the construction of a suitable dynamic event-triggered mechanism. Furthermore, the exclusion of Zeno behavior is guaranteed for the closed-loop system. Finally, this paper culminates by presenting two illustrative examples that showcase the effectiveness of proposed control strategies.

16.
J Clin Invest ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39264847

RESUMEN

Current research reports that lactate affects Treg metabolism, although the precise mechanism has only been partially elucidated. In this study, we presented evidence demonstrating that elevated lactate levels enhanced cell proliferation, suppressive capabilities, and oxidative phosphorylation (OXPHOS) in human Tregs. The expression levels of Monocarboxylate Transporters 1/2/4 (MCT1/2/4) regulate intracellular lactate concentration, thereby influencing the varying responses observed in naive Tregs and memory Tregs. Through mitochondrial isolation, sequencing, and analysis of human Tregs, we determined that Alpha-1,3-Mannosyl-Glycoprotein 2-Beta-N-Acetylglucosaminyltransferase (MGAT1) served as the pivotal driver initiating downstream N-glycosylation events involving progranulin (GRN) and hypoxia-upregulated 1 (HYOU1), consequently enhancing Treg OXPHOS. The mechanism by which MGAT1 was upregulated in mitochondria depended on elevated intracellular lactate that promoted the activation of XBP1s, which, in turn, supported MGAT1 transcription as well as the interaction of lactate with the translocase of the mitochondrial outer membrane 70 (TOM70) import receptor, facilitating MGAT1 translocation into mitochondria. Pre-treatment of Tregs with lactate reduced mortality in a xenogeneic graft-versus-host disease (GvHD) model. Together, these findings underscored the active regulatory role of lactate in human Treg metabolism through the upregulation of MGAT1 transcription and its facilitated translocation into the mitochondria.

17.
Environ Res ; 262(Pt 1): 119854, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39197488

RESUMEN

Irrigation practices and groundwater levels are critical factors contributing to soil salinization in arid and semi-arid regions. However, the impact of soil salinization resulting from Yellow River water irrigation and recharge on microbial communities and their functions in the Huinong District has not been thoroughly documented. In this study, high-throughput sequencing technology was employed to analyze the diversity, composition, and structure of bacterial and fungal communities across a gradient of salinized soils. The results indicated that the alpha diversity of bacterial communities was significantly higher in slightly saline soils compared to highly saline soils. Soil salinization notably influenced the composition of both bacterial and fungal communities. Highly salinized soils were enriched with bacterial taxa such as Halomonas, Salinimicrobium, Pseudomonas, Solibacillus, and Kocuria, as well as fungal taxa including Emericellopsis, Alternaria, and Podospora. In these highly saline soils, bacterial taxa associated with iron respiration, sulfur respiration, and hydrocarbon degradation were more prevalent, whereas fungal taxa linked to functions such as soil animal pathogens, arbuscular mycorrhizal symbiosis, endophytes, dung saprotrophy, leaf saprotrophy, soil saprotrophy, fungal parasitism, and plant pathogenicity were less abundant. Random forest analysis identified nine bacterial and eighteen fungal taxa as potential biomarkers for salinity discrimination in saline soils. Symbiotic network analysis further revealed that soil salinization pressure reduced the overall complexity and stability of bacterial and fungal communities. Additionally, bacterial community assembly showed a tendency shift from stochastic to deterministic processes in response to increasing salinity, while fungal community assembly remained dominated by deterministic processes. provide robust evidence that soil salinity is a major inhibitor of soil biogeochemical processes in the Huinong District and plays a critical role in shaping bacterial and fungal communities, their symbiotic networks, and their assembly processes.

18.
Chem Commun (Camb) ; 60(71): 9586-9589, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39140226

RESUMEN

An organic cathode material for zinc-ion batteries shows a reliable proton transport mechanism. It uses a pyrazine ring as the energy storage unit and H+ as the shuttle ion, enabling high functionality utilization with rapid redox kinetics.

19.
Adv Mater ; : e2406879, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177117

RESUMEN

Intrinsically stretchable organic photovoltaics (is-OPVs) hold significant promise for integration into self-powered wearable electronics. However, their potential is hindered by the lack of sufficient consistency between optoelectronic and mechanical properties. This is primarily due to the limited availability of stretchable transparent electrodes (STEs) that possess both high conductivity and stretchability. Here, a hybrid STE with exceptional conductivity, stretchability, and thermal stability is presented. Specifically, STEs are composed of the modified PH1000 (referred to as S-PH1000) and silver nanowires (AgNWs). The S-PH1000 endows the STE with good stretchability and smoothens the surface, while the AgNWs enhance the charge transport. The resulting hybrid STEs enable is-OPVs to a remarkable power conversion efficiency (PCE) of 16.32%, positioning them among the top-performing is-OPVs. With 10% elastomer, the devices retain 82% of the initial PCE after 500 cycles at 20% strain. Additionally, OPVs equipped with these STEs exhibit superior thermal stability compared to those using indium tin oxide electrodes, maintaining 75% of the initial PCE after annealing at 85 °C for 390 h. The findings underscore the suitability of the designed hybrid electrodes for efficient and stable is-OPVs, offering a promising avenue for the future application of OPVs.

20.
Microb Pathog ; 195: 106853, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39147214

RESUMEN

Klebsiella pneumoniae (K. pneumoniae) is a gram-negative conditionally pathogenic bacterium that causes disease primarily in immunocompromised individuals. Recently, highly virulent K. pneumoniae strains have caused severe disease in healthy individuals, posing significant challenges to global infection control. Capsular polysaccharide (CPS), a major virulence determinant of K. pneumoniae, protects the bacteria from being killed by the host immune system, suggesting an urgent need for the development of drugs to prevent or treat K. pneumoniae infections. In this study, BY3 compounded traditional Chinese medicine residue (TCMR) was carried out using Lactobacillus rhamnosus as a fermentation strain, and BY3 compounded TCMR fermentation broth (BY3 fermentation broth) was obtained. The transcription of K. pneumoniae CPS-related biosynthesis genes after treatment with BY3 fermentation broth was detected using quantitative real-time polymerase chain reaction. The effects of BY3 fermentation broth on K. pneumoniae serum killing, macrophage phagocytosis, complement deposition and human ß-defensin transcription were investigated. The therapeutic effect of BY3 fermentation broth on K. pneumoniae-infected mice was also observed, and the major active components of BY3 fermentation broth were analysed via LC‒MS analysis, network pharmacology, and molecular docking. The results showed that BY3 fermentation broth inhibited K. pneumoniae CPS production and downregulated transcription of CPS-related biosynthesis genes, which weakened bacterial resistance to serum killing and phagocytosis, while promoting bacterial surface complement C3 deposition and human ß-defensin expression. BY3 fermentation broth demonstrated safety and therapeutic effects in vivo and in vitro, restoring body weight and visceral indices, significantly reducing the organ bacterial load and serum cytokine levels, and alleviating pathological organ damage in mice. In addition, three natural compounds-oleanolic acid, quercetin, and palmitoleic acid-were identified as the major active components in the BY3 fermentation broth. Therefore, BY3 fermentation broth may be a promising strategy for the prevention or treatment of K. pneumoniae infections.


Asunto(s)
Cápsulas Bacterianas , Fermentación , Infecciones por Klebsiella , Klebsiella pneumoniae , Polisacáridos Bacterianos , Klebsiella pneumoniae/inmunología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Animales , Infecciones por Klebsiella/inmunología , Infecciones por Klebsiella/microbiología , Ratones , Cápsulas Bacterianas/inmunología , Cápsulas Bacterianas/metabolismo , Humanos , Polisacáridos Bacterianos/inmunología , Medicina Tradicional China , Evasión Inmune , Modelos Animales de Enfermedad , Fagocitosis , Lacticaseibacillus rhamnosus/inmunología , Porcinos , Simulación del Acoplamiento Molecular , Macrófagos/inmunología , Macrófagos/microbiología
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