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1.
Front Psychol ; 15: 1433331, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39233883

RESUMEN

Purpose: The present study aimed to further examine the factor structure and measurement invariance of the UDRQ among a sample of Hungarian university students. Methods: Firstly, the factor structure of the UDRQ was examined among 837 Hungarian university students. Specifically, two measurement models (first-order model and second-order model) were constructed and compared. Secondly, the internal consistency reliability of the UDRQ was examined. Thirdly, measurement invariance of the UDRQ was evaluated across genders. Finally, measurement invariance of the UDRQ was evaluated across two different samples. Results: It was found that the first-order model outperformed the second-order model and better represented the factor structure of the UDRQ subscales. Results of Cronbach's alpha and Composite Reliability suggested that the internal consistency reliabilities of the two UDRQ subscales were satisfactory. Measurement invariance analysis revealed that the UDRQ measurement model was strict invariant across genders and samples. Conclusion: The findings of the present study indicated that the UDRQ displayed satisfactory reliability and validity and could be used to assess demands and resources of Hungarian university students.

2.
Blood Sci ; 6(4): e00206, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39281854

RESUMEN

Hematopoietic stem cells (HSCs) maintain homeostasis in the hematopoietic ecosystem, which is tightly regulated at multiple layers. Acute myeloid leukemia (AML) is a severe hematologic malignancy driven by genetic and epigenetic changes that lead to the transformation of leukemia stem cells (LSCs). Since somatic mutations in DNA methylation-related genes frequently occur in AML, DNA methylation is widely altered and functions as a starting engine for initiating AML. Additionally, RNA modifications, especially N6-methyladenosine (m6A), also play an important role in the generation and maintenance of the hematopoietic ecosystem, and AML development requires reprogramming of m6A modifications to facilitate cells with hallmarks of cancer. Given the complex pathogenesis and poor prognosis of AML, it is important to fully understand its pathogenesis. Here, we mainly focus on DNA methylation and RNA m6A modification in hematopoiesis and AML and summarize recent advances in this field.

3.
Rheumatol Adv Pract ; 8(4): rkae094, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282623

RESUMEN

Objectives: Gout may disturb renal hemodynamics by promoting uric acid deposition; however, this relationship has not been elucidated with adequate clinical evidence. In this study, we measured the renal artery resistance index (ARI) in patients with gout to identify the risk factors and establish predictive models for elevated renal ARI in these patients. Methods: Renal artery ultrasound examination was performed in 235 primary gout patients and 50 healthy controls (HCs); subsequently, their renal interlobar ARI (RIARI), renal segmental ARI (RSARI) and overall intrarenal ARI (OIARI) were recorded. Each ARI > 0.7 was considered elevated. Results: RIARI, RSARI and OIARI were higher in patients with gout than in HCs (all P < 0.001). Nineteen (8.1%), 24 (10.2%) and 18 (7.7%) patients had elevated RIARI, RSARI and OIARI scores, respectively. Multivariate logistic regression analyses disclosed that: age ≥ 60 years (P = 0.000), abnormal beta2 microglobulin (ß2MG) (P = 0.028), and abnormal high-density lipoprotein cholesterol (HDLC) (P = 0.030) were independently associated with elevated RIARI; age ≥ 60 years (P = 0.000), and abnormal ß2MG (P = 0.013) were independently related to elevated RSARI; abnormal total protein (TP) (P = 0.014) were independently linked with elevated OIARI in gout patients. Consequently, predictive models for elevated ARI were established using nomograms based on the aforementioned independent risk factors, which showed a satisfactory value for estimating elevated RIARI [area under the curve (AUC):0.929], RSARI (AUC: 0.926) and OIARI (AUC: 0.660) in patients with gout, as validated by receiver operating characteristic curves. Conclusion: Renal ARI were elevated in patients with gout, whose independent risk factors included older age and abnormal ß2MG, HDLC and TP levels.

4.
J Am Chem Soc ; 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39324482

RESUMEN

The activity of the electrocatalytic CO2 reduction reaction (CO2RR) is substantially affected by alkali metal cations (AM+) in electrolytes, yet the underlying mechanism is still controversial. Here, we employed electrochemical scanning tunneling microscopy and in situ observed Au(111) surface roughening in AM+ electrolytes during cathodic polarization. The roughened surface is highly active for catalyzing the CO2RR due to the formation of surface low-coordinated Au atoms. The critical potential for surface roughening follows the order Cs+ > Rb+ > K+ > Na+ > Li+, and the surface proportion of roughened area decreases in the order of Cs+ > Rb+ > K+ > Na+ > Li+. Electrochemical CO2RR measurements demonstrate that the catalytic activity strongly correlates with the surface roughness. Furthermore, we found that AM+ is critical for surface roughening to occur. The results unveil the unrecognized effect of AM+ on the surface structural evolution and elucidate that the AM+-induced formation of surface high-activity sites contributes to the enhanced CO2RR in large AM+ electrolytes.

5.
J Am Chem Soc ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292646

RESUMEN

Chemical synapse completes the signaling through neurotransmitter-mediated ion flux, the emulation of which has been a long-standing obstacle in neuromorphic exploration. Here, we report metal-organic framework (MOF) nanofluidic synapses in which conjugated MOFs with abundant ionic storage sites underlie the ionic hysteresis and simultaneously serve as catalase mimetics that sensitively respond to neurotransmitter glutamate (Glu). Various neurosynaptic patterns with adaptable weights are realized via Glu-mediated chemical/ionic coupling. In particular, nonlinear Hebbian and anti-Hebbian learning in millisecond time ranges are achieved, akin to those of chemical synapses. Reversible biochemical in-memory encoding via enzymatic Glu clearance is also accomplished. Such results are prerequisites for highly bionic electrolytic computers.

6.
Int J Ophthalmol ; 17(9): 1665-1674, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296557

RESUMEN

AIM: To study functional brain abnormalities in patients with hypertensive retinopathy (HR) and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations (fALFFs) method. METHODS: Twenty HR patients and 20 healthy controls (HCs) were respectively recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the fALFF method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Further, we used Pearson's correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR. RESULTS: The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus (RO-MFG) and right lingual gyrus. In contrast, the values of fALFFs in the left middle temporal gyrus (MTG), left superior temporal pole (STP), left middle frontal gyrus (MFG), left superior marginal gyrus (SMG), left superior parietal lobule (SPL), and right supplementary motor area (SMA) were higher in the HR group. The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group (P<0.001). The fALFF values of the left middle frontal gyrus in HR patients were positively correlated with anxiety scores (r=0.9232; P<0.0001) and depression scores (r=0.9682; P<0.0001). CONCLUSION: fALFF values in multiple brain regions of HR patients are abnormal, suggesting that these brain regions in HR patients may be dysfunctional, which may help to reveal the pathophysiological mechanisms of HR.

7.
Inorg Chem ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298271

RESUMEN

Bismuth is a good constituent element for many quantum materials due to its large atomic number, 6s26p3 orbitals, and strong spin-orbital coupling. In this work, three new bismuthides, NdZn0.6Bi2, (La0.5Pr0.5)Zn0.6Bi2, and (La0.5Nd0.5)Zn0.6Bi2, were grown by a metal flux method, and their crystal structures were accurately determined by single-crystal X-ray diffraction. These new bismuthides belong to the RE-T-Pn2 (RE = La-Lu, T = Mn, Fe, Co, Ni, or Zn, and Pn = P, As, Sb, or Bi) family, are isostructural, and crystallize in the HfCuSi2 structure type. The bismuth elements have two possible oxidation states, Bi3- and Bi-, which were studied by X-ray photoelectron spectroscopy (XPS). Two binding energy peaks of 155.91 and 161.23 eV were observed for Bi atoms within NdZn0.6Bi2, and similar binding energy peaks were detected in NdBi and LiBi. XPS also confirmed the trivalent nature of Nd, which was further verified by magnetic measurements. Additionally, magnetic measurements revealed that NdZn0.6Bi2 exhibits an antiferromagnetic transition around 3 K, while the mixed-cation compounds do not show any magnetic transition down to 2 K. Electronic transport measurements reveal weak magnetoresistance in all three compounds, with a maximum value of ∼25% at 2 K and 9 T for (La0.5Nd0.5)Zn0.6Bi2.

8.
World Neurosurg ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39243970

RESUMEN

BACKGROUND AND OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) is a devastating type of stroke but most favorable treatments to improve patients' neurological outcomes are not clear. Invasive intracranial pressure (ICP) monitoring is a common treatment of ICH, but whether ICH patients could benefit from ICP monitoring is controversial. ICP variability (IPV) has been shown to correlate with poor outcomes in patients with subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI), but this association has not been clearly elucidated in ICH patients. We hypothesized that 72 hour-IPV from time of ICP probe implantation is associated with outcomes in ICH patients. METHODS: A retrospective chart review analysis of adult ICH patients, who received ICP monitoring at Huashan Hospital Fudan University between Jan. 2008 and Jan. 2023, was performed. We included ICH patients within 6 hours of signs or symptoms onset. Outcomes of ICH patients were assessed using 3-month mRS, and were dichotomized into poor (mRS 4 to 6) and good (mRS 0 to 3) outcome group. ICPs were recorded from the implantation of invasive ICP probe until it was removed. ICP was analyzed in the acute period, from 0 to 72 hours after ICP implantation. IPV was analyzed by SD (Standard deviation), CV (Coefficient of variation) and SV (Successive variation) of ICP. RESULTS: We analyzed 597 patients' charts. The 1st ICP assessment, immediately after ICP implantation, at median 117 minutes (interquartile range, 82-231 minutes) after admission was mean 20.5±7.8 mmHg. The 2nd ICP assessment, on NICU arrival after operation, was mean 14.6±8.3 mmHg. Poor outcomes occurred in 213 patients (35.68%). In univariate analysis, univariate quintile analysis or multivariate analysis, ICPSD, ICPCV and ICPSV were associated with poor outcomes. CONCLUSIONS: IPV during the first 72 hours after ICP implantation in patients with ICH was independently associated with poor functional outcome at 3-month. Stabilization of IPV during hyperacute and acute period maybe a potential therapeutic target to improve functional outcomes of these patients.

9.
Artículo en Inglés | MEDLINE | ID: mdl-39278576

RESUMEN

BACKGROUND: Right ventricular (RV) involvement has been reported in type 2 diabetes mellitus (T2DM). The relationship between glycemic control and RV function remains unknown. We aimed to investigate the association between glycemic control and RV function assessed by two-dimensional speckle-tracking echocardiography (2D-STE) and three-dimensional echocardiography (3DE) in T2DM individuals. METHODS: This study prospectively enrolled 207 patients with T2DM and 84 individuals with normal glucose metabolism (NGM). T2DM patients were divided into two subgroups according to glycated hemoglobin (HbA1c) level: controlled (HbA1c < 7.0%, n = 91) and uncontrolled subgroup (HbA1c ≥ 7.0%, n = 116). RV free wall longitudinal strain (RVFWLS) was acquired by 2D-STE, RV volumes and RV ejection fraction (RVEF) were assessed using 3DE. RV coupling to pulmonary circulation was defined as the ratio of RVFWLS/pulmonary artery systolic pressure (PASP). RESULTS: Controlled and uncontrolled T2DM subgroups had impaired RV function as reflected by reduced RVFWLS and RVEF compared to the NGM group. The reduction in RVFWLS was more pronounced in the uncontrolled subgroup than in the controlled subgroup (P < 0.001), whereas no significant difference was found in RVEF between these two T2DM subgroups. Higher PASP and lower RVFWLS/PASP ratio were also noted in uncontrolled T2DM patients. Additionally, the incidence of RV dysfunction was significantly higher in the uncontrolled T2DM patients than in the controlled subgroup (43.1% vs 17.6%, P < 0.001). After adjustment for potential clinical confounders, PASP and left ventricular parameters, HbA1c level was independently associated with RVFWLS (ß = 0.290, P = 0.003) and RVFWLS/PASP ratio (ß = 0.028, P = 0.006). CONCLUSIONS: Subclinical RV myocardial dysfunction is present in T2DM patients and is more pronounced in patients with uncontrolled blood glucose. HbA1c level is independently associated with subclinical RV myocardial dysfunction, providing further insight into a possible link between poor glycemic control and diabetic cardiomyopathy.

10.
Angew Chem Int Ed Engl ; : e202413429, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39252053

RESUMEN

The lanthanide contraction involves a reduction in atomic radius among f-block elements below the expected level. A similar contraction is observed in group-16 elements. The atomic radius of Se (117 pm) is slightly larger than that of S (104 pm) arising from the presence of d electrons, compared to the significant increase in atomic radius from O (73 pm) to S. This lanthanide-like contraction contributes to Se's robust oxidative resistance. Here we report a selective oxidation strategy utilizing Se's strong antioxidative property to remove coexisting narrow-bandgap Te impurities from Se feedstocks. This strategy selectively oxidizes volatile Te impurities into involatile TeO2 that remains in the evaporation source, while only volatile Se deposits onto the substrate during the thermal-evaporation deposition process. This enables the fabrication of high-purity Se films possessing a wide bandgap of 1.88 eV, ideally suited to the optimal bandgap for indoor photovoltaics (IPVs). The resulting Se photovoltaics exhibit an efficiency of 20.1% under 1000-lux indoor illumination, outperforming market-dominant amorphous silicon and all types of lead-free perovskite IPVs. Unencapsulated Se devices show no efficiency degradation after 20,000 hours of storage in ambient atmosphere.

11.
Chem Biodivers ; : e202401520, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39221607

RESUMEN

A previously undescribed triterpenoid (fortunefuroic acid J, 1) was isolated from the endangered conifer Keteleeria hainanensis, along with 20 other known terpenoids. Compound 1 is characterized by an unusual 3,4-seco-9ßH-lanost-3-oic acid motif, featuring a rare furoic acid moiety in its lateral chain. The structure elucidation of this compound was achieved through a combination of spectroscopic and computational methods. The C-15 epimers of 15-methoxypinusolidic acid (15R-8 and 15S-9) were successfully separated and identified for the first time. Compound 1 demonstrated dual inhibitory effects against ATP-citrate lyase (ACL, IC50: 0.92 µM) and acetyl-CoA carboxylase 1 (ACC1, IC50: 10.76 µM). Compounds 2 and 11 exclusively inhibited ACL, exhibiting IC50 values of 2.64 and 6.35 µM, respectively. Compound 1 is classified among the fortunefuroic acid-type compounds, previously isolated from K. fortunei, distinguished by the presence of a rare furoic acid moiety in their lateral chain. The chemotaxonomic significance of the 9ßH-lanost-26-oic acids in Keteleeria was briefly discussed. These findings highlight the importance of conserving plant species diversity, thereby enhancing the exploration of structurally diverse compounds and potential avenues for developing new therapeutics targeting ACL/ACC1-associated diseases.

12.
Bioelectrochemistry ; 160: 108794, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39142024

RESUMEN

Accurate, convenient, label-free, and cost-effective biomolecules detection platforms are currently in high demand. In this study, we showcased the utilization of electrolyte-gated InGaZnO field-effect transistors (IGZO FETs) featuring a large on-off current ratio of over 106 and a low subthreshold slope of 78.5 mV/dec. In the DNA biosensor, the modification of target DNA changed the effective gate voltage of IGZO FETs, enabling an impressive low detection limit of 0.1 pM and a wide linear detection range from 0.1 pM to 1 µM. This label-free detection method also exhibits high selectivity, allowing for the discrimination of single-base mismatch. Furthermore, the reuse of gate electrodes and channel films offers cost-saving benefits and simplifies device fabrication processes. The electrolyte-gated IGZO FET biosensor presented in this study shows great promise for achieving low-cost and highly sensitive detection of various biomolecules.


Asunto(s)
Técnicas Biosensibles , ADN , Electrólitos , Límite de Detección , Transistores Electrónicos , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , ADN/análisis , Electrólitos/química , Indio/química , Electrodos
13.
Phytochemistry ; 228: 114259, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39186996

RESUMEN

A comprehensive phytochemical investigation of the flower buds and leaves/twigs of Heptacodium miconioides, a cultivated ornamental plant native to China and categorized as 'vulnerable', has led to the isolation of 45 structurally diverse compounds, which comprise 18 phenylpropanoids (1-4, 7-20), 11 pentacyclic triterpenoids (5, 6, 21-29), eight secoiridoid glycosides (30-37), three quinic acid derivatives (38-40), and a few miscellaneous components (41-45). Among them, (+)-α-intermedianol (1), (+)-holophyllol A (2), and (-)-pseudolarkaemin A (3) represent previously unreported enantiomeric lignans, while (+)-7'(R)-hydroxymatairesinol (4) is an undescribed naturally occurring lignan. Heptacoacids A (5) and B (6) are undescribed 24-nor-urs-28-oic acid derivatives. Their chemical structures were determined by 2D-NMR, supplemented by evidence from specific rotations and circular dichroism spectra. Given the uncertainty surrounding the systematic position of Heptacodium, integrative taxonomy (ITA), a method utilized to define contentious species, is applied. Chemotaxonomy, a vital aspect of ITA, becomes significant. By employing hierarchical clustering analysis (HCA) and syntenic pattern analysis methods, a taxonomic examination based on the major specialized natural products from the flower buds of H. miconioides and two other Caprifoliaceae plants (i.e., Lonicera japonica and Abelia × grandiflora) could offer enhanced understanding of the systematic placement of Heptacodium. Additionally, compounds 39 and 40 displayed remarkable inhibitory activities against ATP-citrate lyase (ACL), with IC50 values of 0.11 and 1.10 µM, respectively. In summary, the discovery of medical properties and refining systematic classification can establish a sturdy groundwork for conservation efforts aimed at mitigating species diversity loss while addressing human diseases.


Asunto(s)
Productos Biológicos , Productos Biológicos/química , Productos Biológicos/farmacología , Productos Biológicos/aislamiento & purificación , Estructura Molecular , Especies en Peligro de Extinción , Plantas Medicinales/química , Hojas de la Planta/química
14.
Nanoscale ; 16(34): 15851-15883, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39129678

RESUMEN

Over the past two decades, significant progress in two-dimensional (2D) materials has invigorated research in condensed matter and material physics in low dimensions. While traditionally studied in three-dimensional systems, magnetism has now been extended to the 2D realm. Recent breakthroughs in 2D magnetism have attracted substantial interest from the scientific community, owing to the stable magnetic order achievable in atomically thin layers of the van der Waals (vdW)-type layered magnetic materials. These advances offer an exciting platform for investigating related phenomena in low dimensions and hold promise for spintronic applications. Consequently, vdW magnetic materials with tunable magnetism have attracted significant attention. Specifically, antiferromagnetic metal thiophosphates MPX3 (M = transition metal, P = phosphorus, X = chalcogen) have been investigated extensively. These materials exhibit long-range magnetic order spanning from bulk to the 2D limit. The magnetism in MPX3 arises from localized moments associated with transition metal ions, making it tunable via substitutions and intercalations. In this review, we focus on such tuning by providing a comprehensive summary of various metal- and chalcogen-substitution and intercalation studies, along with the mechanism of magnetism modulation, and a perspective on the development of this emergent material family.

15.
Plant Cell ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39167833

RESUMEN

Autoluminescent plants have been genetically modified to express the fungal bioluminescence pathway (FBP). However, a bottleneck in precursor production has limited the brightness of these luminescent plants. Here, we demonstrate the effectiveness of utilizing a computational model to guide a multiplex five-gene-silencing strategy by an artificial microRNA array to enhance caffeic acid and hispidin levels in plants. By combining loss-of-function-directed metabolic flux with a tyrosine-derived caffeic acid pathway, we achieved substantially enhanced bioluminescence levels. We successfully generated eFBP2 plants that emit considerably brighter bioluminescence for naked-eye reading by integrating all validated DNA modules. Our analysis revealed that the luminous energy conversion efficiency of the eFBP2 plants is currently very low, suggesting that luminescence intensity can be improved in future iterations. These findings highlight the potential to enhance plant luminescence through the integration of biological and information technologies.

16.
Cell Commun Signal ; 22(1): 409, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169379

RESUMEN

BACKGROUND: Melanoma, one of the most lethal forms of skin cancer, has the potential to develop in any area where melanocytes are present. Currently, postoperative recurrence due to the emergence of systemic drug resistance represents a significant challenge in the treatment of melanoma. In this study, terphenyllin (TER), a distinctive inhibitory impact on melanoma cells was identified from the natural p-terphenyl metabolite. This study aimed to elucidate the intrinsic mechanism of this inhibitory effect, which may facilitate the discovery of novel chemotherapeutic agents. METHODS: A transcriptome sequencing and metabolomic analysis of TER-treated A375 cells was conducted to identify potential pathways of action. The key proteins were knocked out and backfilled using CRISPR-Cas9 technology and molecular cloning. Subsequently, the results of cytosolic viability, LDH release, immunofluorescence and flow cytometry were employed to demonstrate the cell death status of the drug-treated cells. RESULTS: The p53 signalling pathway was markedly upregulated following TER treatment, leading to the activation of CASP3 via the intrinsic apoptotic pathway. The activated CASP3 initiated apoptosis, while simultaneously continuing to cleave the GSDME, thereby triggering pyroptosis. The knockout of p53, a key protein situated upstream of this pathway, resulted in a significant rescue of TER-induced cell death, as well as an alleviation of the decrease in cell viability. However, the knockout of key proteins situated downstream of the pathway (CASP3 and GSDME) did not result in a rescue of TER-induced cell death, but rather a transformation of the cells from apoptosis and pyroptosis. CONCLUSIONS: The induction of apoptosis and pyroptosis in A375 cells by TER is mediated via the p53-BAX/FAS-CASP3-GSDME signalling pathway. This lays the foundation for TER as a potential anti-melanoma drug in the future. It should be noted that CASP3 and GSDME in this pathway solely regulate the mode of cell death, rather than determine whether cell death occurs. This distinction may prove valuable in future studies of apoptosis and pyroptosis.


Asunto(s)
Apoptosis , Caspasa 3 , Piroptosis , Proteína p53 Supresora de Tumor , Regulación hacia Arriba , Humanos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Piroptosis/efectos de los fármacos , Piroptosis/genética , Apoptosis/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular Tumoral , Melanoma/metabolismo , Melanoma/genética , Melanoma/patología , Transducción de Señal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Gasderminas
17.
PLoS Pathog ; 20(8): e1012437, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39102432

RESUMEN

The ability of Staphylococcus aureus (S. aureus) to survive within macrophages is a critical strategy for immune evasion, contributing to the pathogenesis and progression of osteomyelitis. However, the underlying mechanisms remain poorly characterized. This study discovered that inhibiting the MEK1/2 pathway reduced bacterial load and mitigated bone destruction in a mouse model of S. aureus osteomyelitis. Histological staining revealed increased phosphorylated MEK1/2 levels in bone marrow macrophages surrounding abscess in the mouse model of S. aureus osteomyelitis. Activation of MEK1/2 pathway and its roles in impairing macrophage bactericidal function were confirmed in primary mouse bone marrow-derived macrophages (BMDMs). Transcriptome analysis and in vitro experiments demonstrated that S. aureus activates the MEK1/2 pathway through EGFR signaling. Moreover, we found that excessive activation of EGFR-MEK1/2 cascade downregulates mitochondrial reactive oxygen species (mtROS) levels by suppressing Chek2 expression, thereby impairing macrophage bactericidal function. Furthermore, pharmacological inhibition of EGFR signaling prevented upregulation of phosphorylated MEK1/2 and restored Chek2 expression in macrophages, significantly enhancing S. aureus clearance and improving bone microstructure in vivo. These findings highlight the critical role of the EGFR-MEK1/2 cascade in host immune defense against S. aureus, suggesting that S. aureus may reduce mtROS levels by overactivating the EGFR-MEK1/2 cascade, thereby suppressing macrophage bactericidal function. Therefore, combining EGFR-MEK1/2 pathway blockade with antibiotics could represent an effective therapeutic approach for the treatment of S. aureus osteomyelitis.


Asunto(s)
Receptores ErbB , MAP Quinasa Quinasa 1 , Macrófagos , Osteomielitis , Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Osteomielitis/microbiología , Osteomielitis/inmunología , Osteomielitis/metabolismo , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Ratones , Staphylococcus aureus/inmunología , Receptores ErbB/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/microbiología , MAP Quinasa Quinasa 1/metabolismo , MAP Quinasa Quinasa 2/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Transducción de Señal
18.
Sci Rep ; 14(1): 18935, 2024 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-39147923

RESUMEN

Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1-C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.


Asunto(s)
Pancreatitis , Vasos Retinianos , Tomografía de Coherencia Óptica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Relevancia Clínica , Microvasos/diagnóstico por imagen , Microvasos/patología , Microvasos/fisiopatología , Pancreatitis/complicaciones , Pancreatitis/patología , Pancreatitis/fisiopatología , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual
19.
J Am Chem Soc ; 146(33): 23625-23632, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39120638

RESUMEN

The interfacial species-built local environments on Cu surfaces impact the CO2 electroreduction process significantly in producing value-added multicarbon (C2+) products. However, intricate interfacial dynamics leads to a challenge in understanding how these species affect the process. Herein, with ab initio molecular dynamics (AIMD) and finite element method (FEM) simulations, we reveal that the highly concentrated interfacial species, including the *CO, hydroxide, and K+, could synergistically promote the C-C coupling on the one-dimensional (1D) porous hollow structure regulated interfacial environment. The Cu-Ag tandem catalyst was then synthesized with the as-designed structure, exhibiting a high C2+ Faradaic efficiency of 76.0% with a partial current density of 380.0 mA cm-2 in near-neutral electrolytes. Furthermore, in situ Raman spectra validate that the 1D porous structure regulates the concentration of interfacial CO intermediates and ions to increase *CO coverage, local pH value, and ionic field, promoting the CO2-to-C2+ activity. These results provide insights into the design of practical ECR electrocatalysts by regulating interfacial species-induced local environments.

20.
World J Gastrointest Oncol ; 16(8): 3600-3623, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39171160

RESUMEN

BACKGROUND: Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled. AIM: To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps. METHODS: Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators. RESULTS: The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella, Plesiomonas, and Cronobacter, was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones. CONCLUSION: These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.

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