Explore the vast range of titles available.

Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to various forms of cell death. It is believed that irreversible myocardial damage resulted from I/R occurs due to oxidative stress evoked during the reperfusion phase. Here we demonstrate that ischemia triggers a specific redox reaction of polyunsaturated fatty acids (PUFA)-phospholipids in myocardial cells, which acts as a priming signaling that initiates the outbreak of robust oxidative damage in the reperfusion phase. Using animal and in vitro models, the crucial lipid species in I/R injury were identified to be oxidized PUFAs enriched phosphatidylethanolamines. Using multi-omics, arachidonic acid 15-lipoxygenase-1 (ALOX15) was identified as the primary mediator of ischemia-provoked phospholipid peroxidation, which was further confirmed using chemogenetic approaches. Collectively, our results reveal that ALOX15 induction in the ischemia phase acts as a “burning point” to ignite phospholipid oxidization into ferroptotic signals. This finding characterizes a novel molecular mechanism for myocardial ischemia injury and offers a potential therapeutic target for early intervention of I/R injury.

Although water‐soluble graphene quantum dots (GQDs) have shown various promising bio‐applications due to their intriguing optical and chemical properties, the large heterogeneity in compositions, sizes, and shapes of these GQDs hampers the better understanding of their structure‐properties correlation and further uses in terms of large‐scale manufacturing practices and safety concerns. It is shown here that a water‐soluble atomically‐precise GQD (WAGQD‐C96) is synthesized and exhibits a deep‐red emission and excellent sonodynamic sensitization. By decorating sterically hindered water‐soluble functional groups, WAGQD‐C96 can be monodispersed in water without further aggregation. The deep‐red emission of WAGQD‐C96 facilitates the tracking of its bio‐process, showing a good cell‐uptake and long‐time retention in tumor tissue. Compared to traditional molecular sonosensitizers, WAGQD‐C96 generates superior reactive oxygen species and demonstrates excellent tumor inhibition potency as an anti‐cancer sonosensitizer in in vivo studies. A good biosafety of WAGQD‐C96 is validated in both in vitro and in vivo assays. A water‐soluble atomically‐precise graphene quantum dot (WAGQD) with deep‐red emission is synthesized and shows a superior sensitizing potency for cancer sonodynamic therapy. The general synthetic strategy will enable the synthesis of WAGQDs with different sizes, edges, and tailored properties for further bio‐applications.

Mitochondria play an essential role in energy metabolism. Oxygen deprivation can poison cells and generate a chain reaction due to the free radical release. In patients with sepsis, the kidneys tend to be the organ primarily affected and the proximal renal tubules are highly susceptible to energy metabolism imbalances. Dynamin-related protein 1 (DRP1) is an essential regulator of mitochondrial fission. Few studies have confirmed the role and mechanism of DRP1 in acute kidney injury (AKI) caused by sepsis. We established animal and cell sepsis-induced AKI (S-AKI) models to keep DRP1 expression high. We found that Mdivi-1, a DRP1 inhibitor, can reduce the activation of the NOD-like receptor pyrin domain-3 (NLRP3) inflammasome-mediated pyroptosis pathway and improve mitochondrial function. Both S-AKI models showed that Mdivi-1 was able to prevent the mitochondrial content release and decrease the expression of NLRP3 inflammasome-related proteins. In addition, silencing NLRP3 gene expression further emphasized the pyroptosis importance in S-AKI occurrence. Our results indicate that the possible mechanism of action of Mdivi-1 is to inhibit mitochondrial fission and protect mitochondrial function, thereby reducing pyroptosis. These data can provide a potential theoretical basis for Mdivi-1 potential use in the S-AKI prevention.

Understanding the impacts of climate change and land use dynamics on parasitic plants is crucial for ecological restoration and sustainable resource management in arid regions. This study proposes a two-dimensional modeling framework that integrates parasitic constraints and land use dynamics to predict the potential suitable habitat of , a medicinal plant obligately parasitic on Haloxylon ammodendron. Using an optimized MaxEnt model, host suitability probability was incorporated as a continuous probabilistic constraint, and high-resolution land use data were coupled to enhance ecological realism. The framework was applied to assess habitat suitability under current (1970-2000) and future climate scenarios (2050s, 2070s, 2090s, SSP126, SSP370, SSP585). The inclusion of parasitic constraints reduced the suitable habitat area by 4.5% (from 138.20 × 104 km² to 131.92 × 104 km²) and exacerbated habitat fragmentation, particularly in Northwest China. Future projections reveal a decrease in the total suitable habitat area but an increase in the area of highly suitable regions, with the centroid shifting towards the northwest. Land use analysis demonstrated that unused land (70.21%) and grassland (13.81%) constitute the primary habitats, highlighting their significance for sustainable cultivation. Key environmental drivers identified include July precipitation, soil pH, and temperature of the warmest quarter. The model exhibited high predictive accuracy (AUC: 0.947-0.949). The framework provides a reliable tool for assessing host-parasite interactions and land use impacts. These findings offer valuable insights for adaptive management strategies that balance ecological restoration and the sustainability of medicinal resources in arid ecosystems.

GM1 ganglioside is particularly abundant in the mammalian central nervous system and has shown beneficial effects on neurodegenerative diseases. In this study, we investigated the therapeutic effect of GM1 ganglioside in experimental models of Parkinson’s disease (PD) in vivo and in vitro. Mice were injected with MPTP (30 mg·kg -1 ·d −1 , i.p.) for 5 days, resulting in a subacute model of PD. PD mice were treated with GM1 ganglioside (25, 50 mg·kg − 1 ·d −1 , i.p.) for 2 weeks. We showed that GM1 ganglioside administration substantially improved the MPTP-induced behavioral disturbance and increased the levels of dopamine and its metabolites in the striatal tissues. In the MPP + -treated SH-SY5Y cells and α-synuclein (α-Syn) A53T-overexpressing PC12 (PC12 α-Syn A53T ) cells, treatment with GM1 ganglioside (40 μM) significantly decreased α-Syn accumulation and alleviated mitochondrial dysfunction and oxidative stress. We further revealed that treatment with GM1 ganglioside promoted autophagy, evidenced by the autophagosomes that appeared in the substantia nigra of PD mice as well as the changes of autophagy-related proteins (LC3-II and p62) in the MPP + -treated SH-SY5Y cells. Cotreatment with the autophagy inhibitor 3-MA or bafilomycin A1 abrogated the in vivo and in vitro neuroprotective effects of GM1 ganglioside. Using GM1 ganglioside labeled with FITC fluorescent, we observed apparent colocalization of GM1-FITC and α-Syn as well as GM1-FITC and LC3 in PC12 α-Syn A53T cells. GM1 ganglioside significantly increased the phosphorylation of autophagy regulatory proteins ATG13 and ULK1 in doxycycline-treated PC12 α-Syn A53T cells and the MPP + -treated SH-SY5Y cells, which was inhibited by 3-MA. Taken together, this study demonstrates that the anti-PD role of GM1 ganglioside resulted from activation of autophagy-dependent α-Syn clearance.

Multiple infections are a key component of HPV pathogenesis and have a direct impact on how an infection turns out. It’s crucial to look at the associations between HPV multiple infections and both age and HPV genotypes in the Chinese population, searching for the causative factors of multiple infections with a view to providing new ideas for the treatment and prevention of multiple infections. In this study, we retrospectively analyzed the data of HPV infections among outpatients from the 2019 year to the 2021 year of Shandong Maternal and Child Health Hospital. Analyzed the correlation between HPV multiple infections and age using logistic regression. Differences in the percentage of multiple infections between age groups were compared using the chi-square test. The chi-square test compared the differences in the distribution of 15 common HPV genotypes in mono- versus multiple infections. A two-dimensional matrix presented the frequency of HPV genotype combinations. Logistics regression analysis showed that age was significantly associated with the occurrence of multiple infections, with a dominance ratio OR 1.026 (95% CI 1.02–1.04). Interestingly, the proportion of HPV multiple infections among HPV-positive individuals increases with age in people older than 30 years of age. The chi-square test showed there was a difference in the distribution of HPV genotypes between multiple infections and mono- HPV infection (χ 2  = 76.4; p = 0.000), a difference in the composition of HPV genotypes for dual versus single infections (χ 2  = 90.6; p = 0.000) and a difference in HPV genotypes for triple versus single infections (χ 2  = 56.7; p = 0.000). A 2 × 2 matrix showed that the combination of HPV52/HPV58 (30; 6.4%) was the combination of the highest frequency of infection for dual infections; The HPV52/HPV58 (21; 4.8%) combination was the highest frequency of HPV triple infection combination. HPV multiple infections were positively correlated with age; increasing age was positively correlated with the proportion of HPV multiple infections in the total infected population; the distribution of the 15 common genotypes of HPV differed between multiple infections and single infections; and HPV52:58 was a common type of infection combination in the Shandong population.

Our study compares immune cell profiles in preterm infants with and without severe ROP, identifying risk factors for its development to explore both immunological aspects and determinants of ROP in preterm infants. Infants born between January 2023 to December 2023 at the Children's Hospital of Shanxi were enrolled in this study according to the inclusion criteria. Patients were divided into a test group or a control group based on the need for Type 1 ROP treatment. Baseline data for both groups were compared. Neutrophil, lymphocyte, and monocyte subsets in the peripheral blood were analyzed using immunophenotypic analysis via multicolor flow cytometry. This method allowed for the quantification of specific cell subset proportions. A total of 2,110 preterm infants were screened for inclusion in the study. Multivariate logistic regression analysis identified gestational age below 28 weeks, birth weight less than 1,000 g, and neonatal sepsis as independent risk factors for severe ROP. Furthermore, flow cytometry analysis was performed on blood samples from 45 preterm patients. Comparative analysis revealed that the test group had a lower percentage of neutrophils and higher expression of cluster of differentiation 81 (CD81) compared to the control group. Additionally, the test group showed a higher percentage of lymphocytes and a greater proportion of Th17 cells than the control group. Preterm gestational age, low birth weight, and neonatal sepsis increase severe ROP risk. Elevated CD81 and Th17 levels suggest inflammation linked to neutrophils and lymphocytes.

IntroductionClinical trials of Compound danshen dripping pills (CDDP) indicated distinct improvement in patients with chronic stable angina. Daily fluctuation of therapeutic effect agreed with a peak-valley PK profile during a 4-week CDDP regimen, but stabilized after 8-week treatment.ObjectivesThis article aims to explore the underlying mechanism for the time-dependent drug efficacy of the up-down fluctuation or stabilization in clinic trials.MethodsA rat model of myocardial ischemia was established via isoproterenol induction. Metabolomics was employed to analyze the energy-related substances both in circulatory system and myocardium in the myocardial ischemia model.ResultsCDDP treatment ameliorated myocardial ischemia, reversed the reprogramming of the metabolism induced by ISO and normalized the level of most myocardial substrates and the genes/enzymes associated with those metabolic changes. After 1- or 2-week treatment, CDDP regulated plasma and myocardial metabolome in an analogous, time-dependent way, and modulated metabolic patterns of ischemic rats that perfectly matched with the fluctuated or stabilized effects observed in clinical trials with 4 or 8-week treatment, respectively.ConclusionMetabolic modulation by CDDP contributes to the fluctuated or stabilized therapeutic outcome, and is a potential therapeutic approach for myocardial ischemia diseases.

High repetition frequency (HRF) ultrashort pulse fiber laser has been widely used in laser cold processing. The technical solutions such as short cavity length fiber laser have been proposed to achieve HRF ultrashort pulse output recently. However, the application of material-based saturable absorbers in this field has been astricted due to the low modulation depth, low damage resistance threshold, and high saturation fluence. Here, we designed a one-dimensional asymmetric photonic crystal with defect layer (1D-APCDL) as a novel saturable absorber, where the defect layer is Bi Sb Te with high modulation depth. The harmonic pulse with 3.82 GHz repetition frequency is achieved at the wavelength of 1562 nm, which is the highest repetition frequency of the topological insulator-based ring fiber laser so far to the best of our knowledge. The research provides a new saturable absorber solution, and provides a new idea for the application of material-based nonlinear optical chip in high-repetition frequency ultrashort pulse fiber lasers.

BackgroundPhalangeal microgeodic syndrome is an uncommon benign self-limiting condition that often occurs during cold weather. The etiology and the pathogenesis of the disease remain unclear.ObjectiveTo report a series of children with phalangeal microgeodic syndrome.Materials and methodsTwenty children with phalangeal microgeodic syndrome were retrospectively identified at our hospital after 2007. The clinical data, radiologic manifestation and pathologic appearance were analyzed.ResultsThe average age was 10.3 years (range: 6.5–14.6 years). Twelve patients were boys. Twenty-five phalanges were affected radiographically (23 middle phalanges [92%] and 2 proximal phalanges [8%]). On radiographs, there were multiple small phalangeal lacunae in all cases. Metaphyseal rarefaction was seen in 15 phalanges, and metaphyseal transverse lucent bands were found in 7 phalanges. Epiphyseal rarefaction was seen in three phalanges. On magnetic resonance imaging (MRI), diffuse signal abnormalities of affected phalanges were observed in all cases. Multiple other phalanges and metacarpals also showed marrow edema in three cases.ConclusionPhalangeal microgeodes may represent bone absorption and destruction in response to exaggerated peripheral circulatory impairment following chilblain, and mainly occur in bone growth spurts.