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1.
Phys Rev E ; 109(6-2): 065310, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39020968

ABSTRACT

Electrons are the carriers of heat and electricity in materials and exhibit abundant transport phenomena such as ballistic, diffusive, and hydrodynamic behaviors in systems with different sizes. The electron Boltzmann transport equation (eBTE) is a reliable model for describing electron transport, but it is a challenging problem to efficiently obtain the numerical solutions of the eBTE within one unified scheme involving ballistic, hydrodynamics, and/or diffusive regimes. In this work, a discrete unified gas kinetic scheme (DUGKS) in the finite-volume framework is developed based on the eBTE with the Callaway relaxation model for electron transport. By reconstructing the distribution function at the cell interface, the processes of electron drift and scattering are coupled together within a single time step. Numerical tests demonstrate that the DUGKS can be adaptively applied to multiscale electron transport, across different regimes.

2.
BMC Med Educ ; 24(1): 759, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39010040

ABSTRACT

BACKGROUND: International student education has become an important part of higher education and an important symbol to measure the level of higher education. To change the traditional teaching model, here we introduced a combination of Case-Based Learning (CBL)and Flipped Classroom (FC) into the pathophysiology course for international students. This study aimed to explore whether the active learning ability and critical thinking ability of international students can be improved, based on this new teaching model, improving the innovation ability of teachers' team and students' attitude to the reform. METHODS: The two chapters of Cardiac Insufficiency and Apoptosis in Pathophysiology are designed as a CBL + FC teaching method. Distribute the Self-assessment Scale on Active Learning and Critical Thinking (SSACT) and satisfaction questionnaire to international students to evaluate teaching reform based on CBL + FC. RESULTS: Compared with the traditional classroom, the online flipped classroom based on CBL has significantly improved the learning enthusiasm, as these students are required to independently complete literature review, actively participate in classroom teaching, learn to use multiple learning strategies, and collaborate with other students to complete PowerPoint (PPT)production. At the same time, the students' ability to raise problems and solve problems has been greatly improved by analyzing clinical cases; By consulting the literature, the theoretical knowledge learned can be better applied to clinical analysis. The results of the satisfaction survey also show that international students are more likely to accept the flipped classroom teaching mode. CONCLUSIONS: This teaching mode will stimulate the learning motivation of international students, enhance teaching attraction and increase teaching interaction; At the same time, the CBL + FC teaching method can strengthen the evaluation of international students' in and out of class and online learning, enhance students' active learning ability and critical thinking ability, promote the development of personalized learning, and integrate with international medical education.


Subject(s)
Problem-Based Learning , Thinking , Humans , Problem-Based Learning/methods , Students, Medical , Curriculum , Models, Educational , Surveys and Questionnaires , Educational Measurement , Education, Medical, Undergraduate/methods , Male
3.
Br J Haematol ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38955502

ABSTRACT

This open-label, prospective trial evaluated the combination of ixazomib, cyclophosphamide and dexamethasone (ICD) in 12 newly diagnosed POEMS syndrome patients. The study is registered with the Chinese Clinical Trials Registry (ChiCTR2000030072). The treatment protocol consisted of 12 cycles of the ICD regimen compromising ixazomib (4 mg on Days 1, 8 and 15), oral cyclophosphamide (300 mg on Days 1, 8 and 15) and dexamethasone (20 mg weekly). A total of 12 patients received a median of 10 (range: 3-23) cycles of the ICD regimen. The haematological response could be evaluated in 10 patients. The overall haematological response rate was 80% (8/10), with 30% (3/10) achieving complete haematological response, and the overall serum VEGF response rate and neurological response were 100% and 83.3% respectively. Two patients experienced grade 3/4 AEs, including diarrhoea (n = 1) and leukopenia (n = 1). The combination of ixazomib, cyclophosphamide and dexamethasone demonstrated both efficacy and safety in newly diagnosed POEMS syndrome, making it a viable treatment option.

4.
J Clin Lipidol ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38960813

ABSTRACT

BACKGROUND: The aim of this study was to explore the associations of serum remnant cholesterol (RC) levels with the progression and regression of metabolic dysfunction-associated steatotic liver disease (MASLD) in Chinese adults. METHODS: We conducted a cross-sectional study in 13,903 individuals who underwent transient elastography tests (cohort 1) and a longitudinal study in 17,752 individuals who underwent at least two health check-up exams with abdominal ultrasound (cohort 2). Anthropometric and biochemical parameters were collected. Serum RC levels were calculated. Noninvasive fibrosis indices such as FIB-4 were evaluated in cohort 2. RESULTS: In cohort 1, serum RC levels were positively and independently associated with the severity of hepatic steatosis and liver fibrosis according to logistic regression analysis. In cohort 2, baseline serum RC levels were increased in participants with the incidence of MASLD and decreased in participants with the regression of MASLD during the follow-up period. Baseline serum RC levels were independently associated with an increased risk of development and a decreased likelihood of regression of MASLD: the fully adjusted hazard ratios (HR) were 2.785 (95 % CI 2.332-3.236, P < 0.001) and 2.925 (95 % CI 2.361-3.623, P < 0.001), respectively. In addition, when we used FIB-4 to evaluate liver fibrosis, baseline serum RC levels were positively correlated with the incidence of high-intermediate probability of advanced fibrosis. However, we did not find an association between serum RC levels and the regression of liver fibrosis. CONCLUSION: Serum RC levels are independently correlated with the progression and regression of MASLD in Chinese adults, suggesting that RC may participate in the pathophysiological process of MASLD.

5.
Dent Traumatol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38989999

ABSTRACT

Pulp necrosis is the most common complication following dental trauma and is often associated with apical periodontitis. The management of these teeth is challenging in terms of large root canals, open apices, thin dentinal walls, and short roots. Over decades the conventional treatment for these teeth was calcium hydroxide apexification, a time-consuming procedure despite high success rates. Subsequently after the introduction of mineral trioxide aggregate and hydraulic calcium silicate materials single visit apical plug procedures became increasingly practiced with comparable success rates to the conventional apexification. The search continued afterward for a clinical procedure that may stimulate further root development and apical closure to avoid the long-term complication of root fracture after apexification. Regenerative procedures using stem cells derived from the apical papilla and blood clots as scaffolds were then introduced for the management of immature teeth, with variable protocols and success rates. This review will cover the evidence available and current position of regenerative endodontic procedures in traumatized immature teeth with apical periodontitis, in terms of clinical protocols, outcome, and potential prognostic factors.

6.
Sci Adv ; 10(28): eado1125, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38996014

ABSTRACT

Chirality is an important aspect of nature, and numerous macroscopic methods have been developed to understand and control chirality. For the chiral tertiary amines, their flexible flipping process makes it possible to achieve high chiral controllability without bond formation and breaking. Here, we present a type of stable chiral single-molecule devices formed by tertiary amines, using graphene-molecule-graphene single-molecule junctions. These single-molecule devices allow real-time, in situ, and long-time measurements of the flipping process of an individual chiral nitrogen center with high temporal resolution. Temperature- and bias voltage-dependent experiments, along with theoretical investigations, revealed diverse chiral intermediates, indicating the regulation of the flipping dynamics by energy-related factors. Angle-dependent measurements further demonstrated efficient enrichment of chiral states using linearly polarized light by a symmetry-related factor. This approach offers a reliable means for understanding the chirality's origin, elucidating microscopic chirality regulation mechanisms, and aiding in the design of effective drugs.

7.
Plant Cell Environ ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007434

ABSTRACT

Plant-mediated interactions between herbivores play an important role in regulating the composition of herbivore community. The fall armyworm (FAW), Spodoptera frugiperda, which has become one of the most serious pests on corn in China since it invaded in 2018, has been found feeding rice in the field. However, how FAW interacts with native rice insect pests remains largely unknown. Here, we investigated the interaction between FAW and a resident herbivore, striped stem borer (SSB, Chilo suppressalis) on rice. The infestation of rice leaf sheaths (LSs) by SSB larvae systemically enhanced the level of jasmonic acid (JA), abscisic acid (ABA), and trypsin proteinase inhibitors (TPIs), reduced relative water content (RWC) in leaf blades (LBs), and suppressed the growth of FAW larvae. In contrast, because FAW larvae infested LBs and did not affect defence responses in LSs, they did not influence the performance of SSB larvae. Using different mutants, together with bioassays and chemical analysis, we revealed that SSB-induced suppression of FAW larvae growth depended on both the SSB-activated JA pathway and RWC in LBs, whereas the ABA pathway activated by SSB larvae promoted the growth of FAW larvae by impeding water loss. These results provide new insights into mechanisms underlying plant-mediated interactions between herbivores.

8.
Polymers (Basel) ; 16(13)2024 Jul 04.
Article in English | MEDLINE | ID: mdl-39000770

ABSTRACT

The utilization of polyamide 10,12 (PA10,12) composites in various industries has been limited constrained by their inherent low toughness, making it a challenge to achieve a balance between toughness and structural integrity through conventional elastomer addition strategies. Herein, we introduce a straightforward method for the concurrent toughening and reinforcement of PA10,12 composites. This is accomplished by blending polyolefin elastomer (POE) and 3-pentadecylphenol (PDP) with the PA10,12 matrix. The incorporation of 5 wt% PDP effectively blurred the PA10,12/POE interface due to PDP's role as a compatibilizer. This phenomenon is attributed to the formation of intermolecular hydrogen bonds, as evidenced by Fourier Transform Infrared Spectroscopy (FTIR) analysis. Further investigation, using differential scanning calorimetry (DSC), elucidated the crystallization thermodynamics and kinetics of the resulting binary PA10,12/POE and ternary PA10,12/POE/PDP composites. Notably, the crystallization temperature (Tc) was observed to decrease from 163.1 °C in the binary composite to 161.5 °C upon the addition of PDP. Increasing the PDP content to 10% led to a further reduction in Tc to 159.5 °C due to PDP's capacity to slow down crystallization. Consequently, the ternary composite of PA10,12/POE/PDP (92/3/5 wt%) demonstrated a synergistic improvement in mechanical properties, with an elongation at break of 579% and a notch impact strength of 61.54 kJ/m2. This represents an approximately eightfold increase over the impact strength of unmodified PA10,12. Therefore, our work provides the potential of PDP as a compatibilizer to develop nylon composites with enhanced stiffness and toughness.

9.
J Clin Transl Hepatol ; 12(6): 562-570, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38974956

ABSTRACT

Background and Aims: Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA are structural somatic variants that indicate clonal hematopoiesis. This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score (PRS) on cirrhosis risk prediction. Methods: mCA call sets of individuals with European ancestry were obtained from the UK Biobank. The PRS was constructed based on 12 susceptible single-nucleotide polymorphisms for cirrhosis. Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk. Results: Among 448,645 individuals with a median follow-up of 12.5 years, we identified 2,681 cases of cirrhosis, 1,775 cases of compensated cirrhosis, and 1,706 cases of decompensated cirrhosis. Compared to non-carriers, individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.12-1.81). This risk was higher in patients with expanded cell fractions of mCAs (cell fractions ≥10% vs. cell fractions <10%), especially for the risk of decompensated cirrhosis (HR 2.03 [95% CI 1.09-3.78] vs. 1.14 [0.80-1.64]). In comparison to non-carriers of mCAs with low genetic risk, individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk (HR 5.39 [95% CI 2.41-12.07]). Conclusions: The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.

10.
iScience ; 27(7): 110163, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38974966

ABSTRACT

Aging-related cardiac fibrosis represents the principal pathological progression in cardiovascular aging. The Muscleblind-like splicing regulator 2 (MBNL2) has been unequivocally established as being associated with cardiovascular diseases. Nevertheless, its role in aging-related cardiac fibrosis remains unexplored. This investigation revealed an elevation of MBNL2 levels in the aged heart and senescent cardiac fibroblasts. Notably, the inhibition of MBNL2 demonstrated a capacity to mitigate H2O2-induced myofibroblast transformation and aging-related cardiac fibrosis. Further mechanistic exploration unveiled that aging heightened the expression of SENP1 and impeded the SUMO1 binding with KLF4, and SUMOylation of KLF4 effectively increased by the inhibition of MBNL2. Additionally, the inhibition of TGF-ß1/SMAD3 signaling attenuated the impact of over-expression of MBNL2 in inducing senescence and cardiac fibrosis. MBNL2, by orchestrating SUMOylation of KLF4, upregulating the TGF-ß1/SMAD3 signaling pathway, emerges as a significant promoter of aging-related cardiac fibrosis. This discovery identifies a novel regulatory target for managing aging-related cardiac fibrosis.

11.
Brain Res Bull ; 215: 111027, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38971477

ABSTRACT

BACKGROUND: The limited understanding of the physiology and psychology of polar expedition explorers has prompted concern over the potential cognitive impairments caused by exposure to extreme environmental conditions. Prior research has demonstrated that such stressors can negatively impact cognitive function, sleep quality, and behavioral outcomes. Nevertheless, the impact of the polar environment on neuronal activity remains largely unknown. METHODS: In this study, we aimed to investigate spatiotemporal alterations in brain oscillations of 13 individuals (age range: 22-48 years) who participated in an Arctic expedition. We utilized electroencephalography (EEG) to record cortical activity before and during the Arctic journey, and employed standardized low resolution brain electromagnetic tomography to localize changes in alpha, beta, theta, and gamma activity. RESULTS: Our results reveal a significant increase in the power of theta oscillations in specific regions of the Arctic, which differed significantly from pre-expedition measurements. Furthermore, microstate analysis demonstrated a significant reduction in the duration of microstates (MS) D and alterations in the local synchrony of the frontoparietal network. CONCLUSION: Overall, these findings provide novel insights into the neural mechanisms underlying adaptation to extreme environments. These findings have implications for understanding the cognitive consequences of polar exploration and may inform strategies to mitigate potential neurological risks associated with such endeavors. Further research is warranted to elucidate the long-term effects of Arctic exposure on brain function.

12.
J Agric Food Chem ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38857427

ABSTRACT

3-Monochloropropane-1,2-diol (3-MCPD) is a chloropropyl alcohol contaminant mainly from the thermal processing of food and could affect kidneys. Pyroptosis is programmed cell death mediated by inflammasomes and gasdermins, and excessive cellular pyroptosis and inflammation can lead to tissue injury. In the present study, we found that 3-MCPD increased lactate dehydrogenase (LDH) levels in vitro and in vivo, increased the protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), N-terminal domain of GSDMD (GSDMD-N), and cleaved caspase-1 and promoted the release of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), which induced renal cell pyroptosis and inflammation. Mechanistic studies indicated that the addition of N-acetylcysteine (NAC), a ROS scavenger, inhibited NLRP3 activation and attenuated pyroptosis. Furthermore, we revealed that 3-MCPD induced ROS accumulation by inhibiting ESCRT-III-mediated mitophagy. These results were further validated by the overexpression of charged multivesicular body protein 4B (CHMP4B), a key subunit of ESCRT-III, and the addition of the mitophagy activator carbonyl cyanide m-chlorophenylhydrazone (CCCP) and rapamycin (Rapa). Thus, our results showed that 3-MCPD could induce mitochondrial damage and produce ROS. 3-MCPD suppressed mitophagy, leading to the accumulation of damaged mitochondria and ROS, thereby activating NLRP3 and pyroptosis. Meanwhile, 3-MCPD-mediated suppression of ESCRT-III hindered the repair of GSDMD-induced cell membrane rupture, which further caused the occurrence of pyroptosis. Our findings provide new perspectives for studying the mechanisms underlying 3-MCPD-induced renal injury.

13.
Research (Wash D C) ; 7: 0384, 2024.
Article in English | MEDLINE | ID: mdl-38826566

ABSTRACT

Consuming a high-fat diet (HFD) is widely recognized to cause obesity and result in chronic brain inflammation that impairs cognitive function. Repetitive transcranial magnetic stimulation (rTMS) has shown effectiveness in both weight loss and cognitive improvement, although the exact mechanism is still unknown. Our study examined the effects of rTMS on the brain and intestinal microecological dysfunction. rTMS successfully reduced cognitive decline caused by an HFD in behavioral assessments involving the Y maze and novel object recognition. This was accompanied by an increase in the number of new neurons and the transcription level of genes related to synaptic plasticity (spindlin 1, synaptophysin, and postsynaptic protein-95) in the hippocampus. It was reached that rTMS decreased the release of high mobility group box 1, activation of microglia, and inflammation in the brains of HFD rats. rTMS also reduced hypothalamic hypocretin levels and improved peripheral blood lipid metabolism. In addition, rTMS recovered the HFD-induced gut microbiome imbalances, metabolic disorders, and, in particular, reduced levels of the microvirus. Our research emphasized that rTMS enhanced cognitive abilities, resulting in positive impacts on brain inflammation, neurodegeneration, and the microbiota in the gut, indicating the potential connection between the brain and gut, proposing that rTMS could be a new approach to addressing cognitive deficits linked to obesity.

14.
J Acoust Soc Am ; 155(6): 3678-3689, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38847592

ABSTRACT

Numerous advanced and lightweight signal processing methods have been presented for single-channel speech enhancement (SE). It is imperative to carefully explore how to efficiently combine, integrate, and balance these methods. This paper proposes a more effective and less resource-intensive SE system, focused on the integration and adaptation of several approaches, especially the temporal cepstrum smoothing (TCS). First, a more robust fundamental frequency estimator is employed within TCS, mitigating the performance limitations caused by the inaccuracy of the original estimator. Additionally, a harmonic enhancement mechanism is introduced, effectively recovering the weak harmonic components. By incorporation of the modified TCS in the a posteriori speech presence probability estimation, the unbiased minimum mean square error noise power spectral density estimator can be refined. The modified TCS is also utilized for the a priori signal-to-noise ratio estimation. Moreover, this paper enhances the log-spectral amplitude estimator by applying both super-Gaussian speech priors and speech presence uncertainty for further improvement. Experimental evaluations demonstrate that the proposed method yields an improvement in speech quality while maintaining modest computational and storage requirements. Furthermore, the proposed system exhibits comparable performance to several baseline systems based on lightweight deep neural networks.

15.
Int J Ophthalmol ; 17(6): 991-1000, 2024.
Article in English | MEDLINE | ID: mdl-38895691

ABSTRACT

AIM: To develop a classifier for traditional Chinese medicine (TCM) syndrome differentiation of diabetic retinopathy (DR), using optimized machine learning algorithms, which can provide the basis for TCM objective and intelligent syndrome differentiation. METHODS: Collated data on real-world DR cases were collected. A variety of machine learning methods were used to construct TCM syndrome classification model, and the best performance was selected as the basic model. Genetic Algorithm (GA) was used for feature selection to obtain the optimal feature combination. Harris Hawk Optimization (HHO) was used for parameter optimization, and a classification model based on feature selection and parameter optimization was constructed. The performance of the model was compared with other optimization algorithms. The models were evaluated with accuracy, precision, recall, and F1 score as indicators. RESULTS: Data on 970 cases that met screening requirements were collected. Support Vector Machine (SVM) was the best basic classification model. The accuracy rate of the model was 82.05%, the precision rate was 82.34%, the recall rate was 81.81%, and the F1 value was 81.76%. After GA screening, the optimal feature combination contained 37 feature values, which was consistent with TCM clinical practice. The model based on optimal combination and SVM (GA_SVM) had an accuracy improvement of 1.92% compared to the basic classifier. SVM model based on HHO and GA optimization (HHO_GA_SVM) had the best performance and convergence speed compared with other optimization algorithms. Compared with the basic classification model, the accuracy was improved by 3.51%. CONCLUSION: HHO and GA optimization can improve the model performance of SVM in TCM syndrome differentiation of DR. It provides a new method and research idea for TCM intelligent assisted syndrome differentiation.

16.
Microbiol Spectr ; : e0031124, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38916312

ABSTRACT

Helicobacter pylori is a microaerophilic Gram-negative bacterium that resides in the human stomach and is classified as a class I carcinogen for gastric cancer. Numerous studies have demonstrated that H. pylori infection plays a role in regulating the function of host cells, thereby contributing to the malignant transformation of these cells. However, H. pylori infection is a chronic process, and short-term cellular experiments may not provide a comprehensive understanding of the in vivo situation, especially when considering the lower oxygen levels in the human stomach. In this study, we aimed to investigate the mechanisms underlying gastric cell dysfunction after prolonged exposure to H. pylori under hypoxic conditions. We conducted a co-culture experiment using the gastric cell line GES-1 and H. pylori for 30 generations under intermittent hypoxic conditions. By closely monitoring cell proliferation, migration, invasion, autophagy, and apoptosis, we revealed that sustained H. pylori stimulation under hypoxic conditions significantly influences the function of GES-1 cells. This stimulation induces epithelial-mesenchymal transition and contributes to the propensity for malignant transformation of gastric cells. To confirm the in vitro results, we conducted an experiment involving Mongolian gerbils infected with H. pylori for 85 weeks. All the results strongly suggest that the Nod1 receptor signaling pathway plays a crucial role in H. pylori-related apoptosis and autophagy. In summary, continuous stimulation by H. pylori affects the functioning of gastric cells through the Nod1 receptor signaling pathway, increasing the likelihood of cell carcinogenesis. The presence of hypoxic conditions further exacerbates this process.IMPORTANCEDeciphering the collaborative effects of Helicobacter pylori infection on gastric epithelial cell function is key to unraveling the development mechanisms of gastric cancer. Prior research has solely examined the outcomes of short-term H. pylori stimulation on gastric epithelial cells under aerobic conditions, neglecting the bacterium's nature as a microaerophilic organism that leads to cancer following prolonged stomach colonization. This study mimics a more genuine in vivo infection scenario by repeatedly exposing gastric epithelial cells to H. pylori under hypoxic conditions for up to 30 generations. The results show that chronic exposure to H. pylori in hypoxia substantially increases cell migration, invasion, and epithelial-mesenchymal transition, while suppressing autophagy and apoptosis. This highlights the significance of hypoxic conditions in intensifying the carcinogenic impact of H. pylori infection. By accurately replicating the in vivo gastric environment, this study enhances our comprehension of H. pylori's pathogenic mechanisms in gastric cancer.

17.
Phytomedicine ; 131: 155765, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38851105

ABSTRACT

BACKGROUND: Infection by Toxoplasma gondii can lead to severe pneumonia, with current treatments being highly inadequate. The NLRP3 inflammasome is one member of the NOD-like receptor family with a pyrin domain, which is crucial in the innate immune defense against T. gondii. Research has shown that resveratrol (RSV) prevents lung damage caused by this infection by inhibiting the T. gondii-derived heat shock protein 70/TLR4/NF-κB pathway, thus reducing the macrophage-driven inflammatory response. However, it should be mentioned that the participation of NLRP3 inflammasome in the immune response to the lung injuries caused by T. gondii infections is not entirely clear. PURPOSE: This study aims to clarify how RSV ameliorates lung damage triggered by Toxoplasma gondii infection, with a particular focus on the pathway involving TLR4, NF-κB, and the NLRP3 inflammasome. METHODS: Both in vitro and in vivo models of infection were developed by employing the RH strain of T. gondii in BALB/c mice and RAW 264.7 macrophage cell lines. The action mechanism of RSV was explored using techniques such as molecular docking, surface plasmon resonance, ELISA, Western blot, co-immunoprecipitation, and immunofluorescence staining. RESULTS: Findings indicate that the suppression of TLR4 or NF-κB impacts the levels of proteins associated with the NLRP3 inflammasome pathway. Additionally, a significant affinity for binding between RSV and NLRP3 was observed. Treatment with RSV led to a marked reduction in the activation and formation of the NLRP3 inflammasome within lung tissues and RAW 264.7 cells, alongside a decrease in IL-1ß concentrations in the bronchoalveolar lavage fluid. These outcomes align with those seen when using the NLRP3 inhibitor CY-09. Moreover, the application of CY-09 prior to RSV negated the latter's anti-inflammatory properties. CONCLUSION: Considering insights from previous research alongside the outcomes of the current investigation, it appears that the TLR4/NF-κB/NLRP3 signaling pathway emerges as a promising target for immunomodulation to alleviate lung injury from T. gondii infection. The evidence gathered in this study lays the groundwork for the continued exploration and potential future clinical deployment of RSV as a therapeutic agent with anti-Toxoplasma properties and the capability to modulate the inflammatory response.


Subject(s)
Inflammasomes , Mice, Inbred BALB C , NF-kappa B , NLR Family, Pyrin Domain-Containing 3 Protein , Pneumonia , Resveratrol , Toll-Like Receptor 4 , Toxoplasma , Resveratrol/pharmacology , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Mice , Inflammasomes/drug effects , Inflammasomes/metabolism , RAW 264.7 Cells , Toll-Like Receptor 4/metabolism , Pneumonia/drug therapy , Pneumonia/parasitology , Toxoplasma/drug effects , NF-kappa B/metabolism , Toxoplasmosis/drug therapy , Lung/drug effects , Lung/parasitology , Molecular Docking Simulation , Female , Signal Transduction/drug effects , Macrophages/drug effects
18.
Cell Rep ; 43(7): 114410, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38923457

ABSTRACT

Polymyxins are often the only effective antibiotics against the "Critical" pathogen Acinetobacter baumannii. Worryingly, highly polymyxin-resistant A. baumannii displaying dependence on polymyxins has emerged in the clinic, leading to diagnosis and treatment failures. Here, we report that arginine metabolism is essential for polymyxin-dependent A. baumannii. Specifically, the arginine degradation pathway was significantly altered in polymyxin-dependent strains compared to wild-type strains, with critical metabolites (e.g., L-arginine and L-glutamate) severely depleted and expression of the astABCDE operon significantly increased. Supplementation of arginine increased bacterial metabolic activity and suppressed polymyxin dependence. Deletion of astA, the first gene in the arginine degradation pathway, decreased phosphatidylglycerol and increased phosphatidylethanolamine levels in the outer membrane, thereby reducing the interaction with polymyxins. This study elucidates the molecular mechanism by which arginine metabolism impacts polymyxin dependence in A. baumannii, underscoring its critical role in improving diagnosis and treatment of life-threatening infections caused by "undetectable" polymyxin-dependent A. baumannii.

19.
ChemSusChem ; : e202400869, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38924363

ABSTRACT

The electrochemical reduction reaction (HMFRR) of 5-hydroxymethylfurfural (HMF) has emerged as a promising avenue for the utilization and refinement of the biomass-derived platform molecule HMF into high-value chemicals, addressing energy sustainability challenges. Transition metal electrocatalysts (TMCs) have recently garnered attention as promising candidates for catalyzing HMFRR, capitalizing on the presence of vacant d orbitals and unpaired d electrons. TMCs play a pivotal role in facilitating the generation of intermediates through interactions with HMF, thereby lowering the activation energy of intricate reactions and significantly augmenting the catalytic reaction rate. In the absence of comprehensive and guiding reviews in this domain, this paper aims to comprehensively summarize the key advancements in the design of transition metal catalysts for HMFRR. It elucidates the mechanisms and pH dependency of various products generated during the electrochemical reduction of HMF, with a specific emphasis on the bond-cleavage angle. Additionally, it offers a detailed introduction to typical in-situ characterization techniques. Finally, the review explores engineering strategies and principles to enhance HMFRR activity using TMCs, particularly focusing on multiphase interface control, crystal face control, and defect engineering control. This review introduces novel concepts to guide the design of HMFRR electrocatalysts, especially TMCs, thus promoting advancements in biomass conversion.

20.
Genes (Basel) ; 15(6)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38927752

ABSTRACT

The Mongolian gerbil is a distinctive experimental animal in China, as its genetic qualities possess significant value in the field of medical biology research. Here, we aimed to establish an economical and efficient panel for genetic quality detection in Mongolian gerbils using single-nucleotide polymorphism (SNP) markers. To search for SNPs, we conducted whole-genome sequencing (WGS) in 40 Mongolian gerbils from outbred populations. Reliable screening criteria were established to preliminarily select SNPs with a wide genome distribution and high levels of polymorphism. Subsequently, a multiple-target regional capture detection system based on second-generation sequencing was developed for SNP genotyping. Based on the results of WGS, 219 SNPs were preliminarily selected, and they were established and optimized in a multiple-amplification system that included 206 SNP loci by genotyping three outbred populations. PopGen.32 analysis revealed that the average effective allele number, Shannon index, observed heterozygosity, expected heterozygosity, average heterozygosity, polymorphism information content, and other population genetic parameters of the Capital Medical University (CMU) gerbils were the highest, followed by those of Zhejiang gerbils and Dalian gerbils. Through scientific screening and optimization, we successfully established a novel, robust, and cost-effective genetic detection system for Mongolian gerbils by utilizing SNP markers for the first time.


Subject(s)
Gerbillinae , Polymorphism, Single Nucleotide , Animals , Gerbillinae/genetics , Polymorphism, Single Nucleotide/genetics , Whole Genome Sequencing/methods , Genotyping Techniques/methods , Genetics, Population/methods , China , Genotype , High-Throughput Nucleotide Sequencing/methods
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