Autophagic cell death induced by pH modulation for enhanced iron-based chemodynamic therapy.

Iron-based chemodynamic therapy (CDT) exhibits commendable biocompatibility and selectivity, but its efficacy is constrained by the intracellular pH of tumors. To overcome this obstacle, we constructed a silica delivery platform loaded with autophagy-inducing reagents (rapamycin, RAPA) and iron-based Fenton reagents (Fe3O4). This platform was utilized to explore a novel strategy that leverages autophagy to decrease tumor acidity, consequently boosting the effectiveness of CDT. Both in vitro and in vivo experiments revealed that RAPA prompted the generation of acidic organelles (e.g., autophagic vacuoles and autophagosomes), effectively changing the intracellular pH in the tumor microenvironment. Furthermore, RAPA-induced tumor acidification significantly amplified the efficacy of Fe3O4-based Fenton reactions, consequently increasing the effectiveness of Fe3O4-based CDT. This innovative approach, which leverages the interplay between autophagy induction and iron-based CDT, shows promise in overcoming the limitations posed by tumor pH, thus offering a more efficient approach to tumor treatments.

Measurements of Thermal Resistance Across Buried Interfaces with Frequency-Domain Thermoreflectance and Microscale Confinement.

Confined geometries are used to increase measurement sensitivity to thermal boundary resistance at buried SiO2 interfaces with frequency-domain thermoreflectance (FDTR). We show that radial confinement of the transducer film and additional underlying material layers prevents heat from spreading and increases the thermal penetration depth of the thermal wave. Parametric analyses are performed with finite element methods and used to examine the extent to which the thermal penetration depth increases as a function of a material's effective thermal resistance and the degree of material confinement relative to the pump beam diameter. To our surprise, results suggest that the measurement technique is not always the most sensitive to the largest thermal resistor in a multilayer material. We also find that increasing the degree to which a material is confined improves measurement sensitivity to the thermal resistance across material interfaces that are buried 10s of µm to mm below the surface. These results are used to design experimental measurements of etched, 200 nm thick SiO2 films deposited on Al2O3 substrates, and offer an opportunity for thermal scientists and engineers to characterize the thermal resistance across a broader range of material interfaces within electronic device architectures that have historically been difficult to access via experiment.

Overexpression of SlWRKY6 enhances drought tolerance by strengthening antioxidant defense and stomatal closure via ABA signaling in Solanum lycopersicum L.

Drought is a major handicap for plant growth and development. WRKY proteins comprise one of the largest families of plant transcription factors, playing important roles in plant growth and stress tolerance. In tomato (Solanum lycopersicum L.), different WRKY transcription factors differentially (positively or negatively) regulate drought tolerance, however, the role of SlWRKY6 in drought response and the associated molecular mechanisms of stress tolerance remain unclear. Here we report that SlWRKY6, a member of the WRKYII-b group, is involved in the functional aspects of drought resistance in tomato. Transcriptional activation assays show that SlWRKY6 is transcriptionally active in yeast cells, while the subcellular localization assay indicates that SlWRKY6 is localized in the nucleus. Overexpression of SlWRKY6 in tomato plants resulted in stronger antioxidant capacity and drought resistance as manifested by increased photosynthetic capacity and decreased reactive oxygen species accumulation, malondialdehyde content and relative electrolyte leakage in transgenic tomato plants compared with wild-type under drought stress. Moreover, increased abscisic acid (ABA) content and transcript abundance of ABA synthesis and signaling genes (NCED1, NCED4, PYL4, AREB1 and SnRK2.6) in the transgenic tomato plants indicated potential involvement of the ABA pathway in SlWRKY6-induced drought resistance in tomato plants. Inspection of 2-kb sequences upstream of the predicted binding sites in the promoter of SlNCED1/4 identified two copies of the core W-box (TTGACC/T) sequence in the promoter of SlNCED1/4, which correlates well with the expression of these genes in response to drought, further suggesting the involvement of ABA-dependent pathway in SlWRKY6-induced drought resistance. The study unveils a critical role of SlWRKY6, which can be useful to further reveal the drought tolerance mechanism and breeding of drought-resistant tomato varieties for sustainable vegetable production in the era of climate change.

Revealing the Role of the Ionomer at the Triple-Phase Boundary in a Proton-Exchange Membrane Water Electrolyzer.

In the anodic catalyst layer of a proton-exchange membrane (PEM) water electrolyzer, the triple-phase boundary (TPB) is mainly distributed on the surface of ultrafine iridium-based catalysts encapsulated by the ionomer within the catalyst-ionomer agglomerate. It is found that the ionomer at the TPB acts as a barrier to mass transport and a buffer for the bubble coverage during the oxygen evolution reaction (OER). The barrier effect can decrease the OER performance of the catalysts inside the agglomerate by ≤23%, while the buffer effect can separate the bubble evolution sites from the OER sites, turning the instant deactivation caused by the bubble coverage into a gradual performance loss caused by local water starvation. However, this local water starvation still deteriorates the catalyst performance because of the affinity of the ionomer surface for bubbles. Introducing additional transport paths into the agglomerate can reduce the barrier effect and regulate the bubble behavior, reducing the overpotential by 0.308 V at 5 A cm-2.

Biochemical Characterization of a Novel Thermostable Ulvan Lyase from Tamlana fucoidanivorans CW2-9.

Ulvan is a complex sulfated polysaccharide extracted from Ulva, and ulvan lyases can degrade ulvan through a ß-elimination mechanism to obtain oligosaccharides. In this study, a new ulvan lyase, EPL15085, which belongs to the polysaccharide lyase (PL) 28 family from Tamlana fucoidanivorans CW2-9, was characterized in detail. The optimal pH and salinity are 9.0 and 0.4 M NaCl, respectively. The Km and Vmax of recombinant EPL15085 toward ulvan are 0.80 mg·mL-1 and 11.22 µmol·min -1 mg-1·mL-1, respectively. Unexpectedly, it is very resistant to high temperatures. After treatment at 100 °C, EPL15085 maintained its ability to degrade ulvan. Molecular dynamics simulation analysis and site-directed mutagenesis analysis indicated that the strong rigidity of the disulfide bond between Cys74-Cys102 in the N-terminus is related to its thermostability. In addition, oligosaccharides with disaccharides and tetrasaccharides were the end products of EPL15085. Based on molecular docking and site-directed mutagenesis analysis, Tyr177 and Leu134 are considered to be the crucial residues for enzyme activity. In conclusion, our study identified a new PL28 family of ulvan lyases, EPL15085, with excellent heat resistance that can expand the database of ulvan lyases and provide the possibility to make full use of ulvan.

A Novel Frameshift Variant of the ELF4 Gene in a Patient with Autoinflammatory Disease: Clinical Features, Transcriptomic Profiling and Functional Studies.

We described the diagnosis and treatment of a patient with autoinflammatory disease, named "Deficiency in ELF4, X-linked (DEX)". A novel ELF4 variant was discovered and its pathogenic mechanism was elucidated. The data about clinical, laboratory and endoscopic features, treatment, and follow-up of a patient with DEX were analyzed. Whole exome sequencing and Sanger sequencing were performed to identify potential pathogenic variants. The mRNA and protein levels of ELF4 were analyzed by qPCR and Western blotting, respectively. The association of ELF4 frameshift variant with nonsense-mediated mRNA decay (NMD) in the pathogenesis DEX was examined. Moreover, RNA-seq was performed to identify the key molecular events triggered by ELF4 variant. The relationship between ELF4 and IFN-ß activity was validated using a dual-luciferase reporter assay and a ChIP-qPCR assay. An 11-year-old boy presented with a Behçet's-like phenotype. The laboratory abnormality was the most obvious in elevated inflammatory indicators. Endoscopy revealed multiple ileocecal ulcers. Intestinal histopathology showed inflammatory cell infiltrations. The patient was treated with long-term immunosuppressant and TNF-α blocker (adalimumab), which reaped an excellent response over 16 months of follow-up. Genetic analysis identified a maternal hemizygote frameshift variant (c.1022del, p.Q341Rfs*30) in ELF4 gene in the proband. The novel variant decreased the mRNA level of ELF4 via the NMD pathway. Mechanistically, insufficient expression of ELF4 disturbed the immune system, leading to immunological disorders and pathogen susceptibility, and disrupted ELF4-activating IFN-ß responses. This analysis detailed the clinical characteristics of a Chinese patient with DEX who harbored a novel ELF4 frameshift variant. For the first time, we used patient-derived cells and carried out transcriptomic analysis to delve into the mechanism of ELF4 variant in DEX.

Analysis of the Relationship between Recent Small Subcortical Infarcts and Autonomic Nervous Dysfunction.

OBJECTIVE: Autonomic Nervous System (ANS) dysfunction may be involved in the pathogenesis of Cerebral Small Vessel Disease (CSVD). The study aimed to explore the relationship between Recent Small Subcortical Infarct (RSSI) and Blood Pressure Variability (BPV), and Heart Rate Variability (HRV). METHODS: A total of 588 patients from the CSVD registration research database of Henan Province were included in this study, and were divided into two groups according to the presence of RSSI. Clinical data, including demographic characteristics, disease history, laboratory indexes, 24-hour ambulatory blood pressure and electrocardiogram indicators, and imaging markers of CSVD, were collected. Univariate and binary logistic regression analyses were used to study the relationship between RSSI and indicators of laboratory, HRV and BPV in the CSVD population. RESULTS: Multivariate analysis showed that higher 24-hour mean Diastolic Blood Pressure (DBP)[Odds Ratios (OR)=1.083,95% Confidence Intervals (CI)=(1.038,1.129), p < 0.001], Standard Deviation (SD) of 24-hour DBP [OR=1.059,95%CI=(1.000,1.121), p = 0.049], nocturnal mean Systolic Blood Pressure (SBP) [OR=1.020,95%CI=(1.004,1.035), p = 0.012], nocturnal mean DBP [OR=1.025,95%CI=(1.009,1.040), p = 0.002] were independent risk factors for RSSI. In contrast, the decrease of the standard deviation of N-N intervals (SDNN) [OR=0.994,95%CI=(0.989,1.000), p = 0.035] was beneficial to the occurrence of RSSI. In addition, neutrophil counts [OR=1.138,95%CI=(1.030,1.258), p = 0.011], total cholesterol (TC) [OR=1.203,95%CI=(1.008,1.437), p = 0.041] and High-Density Lipoprotein (HDL) [OR=0.391, 95%CI=(0.195,0.786), p = 0.008] were also independently associated with the occurrence of RSSI. After adjusting for confounding factors, except for TC, the other factors remained associated with the occurrence of RSSI. CONCLUSION: Increased 24-hour mean DBP, nocturnal mean SBP and DBP, SD of 24-hour DBP and decreased SDNN were independently correlated with RSSI occurrence, suggesting that sympathetic overactivity plays a role in the pathogenesis of RSSI.

Discussion on Ethics of Public Health Policy / 中国医学伦理学

The ethical basis of public health policy is relatively weakness, which is mainly reflected in the conflict between individual rights and public interests, the lack of moral norm, the short of ethical review, the low level of relevant legislation, the weak of ethical consciousness and so on. Therefore, it is necessary to take measures to improve relevant ethical policies and regulations, establish an ethical framework for evaluating public health policies, highlight ethical values and strengthen ethical awareness in public health policy-making. Make it carry a certain ethical dimension to achieve the purposes of maintaining and improving health.

A rare case of primary central nervous system histiocytic sarcoma harboring a novel ARHGAP45::BRAF fusion: a case report and literature review.

INTRODUCTION: Patients with histiocytic sarcoma occurring in the central nervous system (CNS) are rare and have a very poor prognosis. The increased use of molecular diagnostic approaches in solid tumors has brought more opportunities for the diagnosis and treatment of central nervous system histiocytic sarcoma (CNSHS). CASE DESCRIPTION: A 9-year-old girl was admitted to the hospital with pain in her head and neck, as well as vomiting. Imaging scans showed a prominent abnormality in the anterior falciform region, and histopathology revealed the presence of CD68 (+) and CD163 (+) cells, leading to a preliminary diagnosis of primary intracerebral CNSHS. Molecular profiling tests identified a new variant of ARHGAP45::BRAF fusion in this case, which has not been reported in any other tumor. The patient underwent surgical removal of the tumor and will require long-term monitoring. CONCLUSION: The presence of the BRAF point mutation, predominantly BRAF p.V600E, has been documented in prior literature of CNSHS. This is the first case of pediatric histiocytic sarcoma in the anterior falciform region who has a unique ARHGAP45::BRAF fusion. The findings of our study indicate that a broader range of molecular assays should be employed in the diagnosis of CNSHS and opens up new possibilities for the treatment of the patient.

Frontiers and advances in N-heterocycle compounds as corrosion inhibitors in acid medium: Recent advances.

The acid solution is widely used in chemical cleaning, oil well acidifying, and other fields, which also brings the problem of metal corrosion that cannot be underestimated. However, adding an inhibitor is one of the most convenient and effective ways to slow down metal corrosion. N-heterocyclic compounds with high stability and durability, in line with the strategy of sustainable development, have been widely studied in an acidic environment. Imidazole, pyridine, and quinoline compounds, as the most commonly used corrosion inhibitors, can form a compact protective film via π electron cloud shifting towards the N atoms to generate coordination function. In particular, flexible modifiability makes N-heterocyclic compounds adapt to different corrosion environments readily, conducive to the formation of chemical bonds between compounds with metal surfaces to be better adsorption, so as to avoid the blemish of traditional inhibitors (such as inorganic salt and organic amines inhibitors) due to excessive usage, surface roughness of metal or environmental factor (for instance, temperature, pH and metallic) causing loose bonding between film and metal surface. More importantly, the efficient corrosion inhibition and toxicity of N-heterocyclic compounds have close to do with their own functional groups. Combined with the latest research achievement, the effects of different substituents on the corrosion inhibition and corrosion inhibition mechanisms were systematically reviewed in the acid-corrosive solution of imidazole, pyridine, and quinoline and their derivatives in this review article, respectively. In addition, the application and function of density functional theory in predicting the corrosion inhibition effect of corrosion inhibitors are also discussed. The future development trend was prospected according to the summarized research results.

The Positional Relationship between Lacunae and White Matter Hyperintensity in Patients with Cerebral Small Vessel Disease.

BACKGROUND: Lacunae and white matter hyperintensity (WMH) are two crucial imaging biomarkers of cerebral small vessel disease (CSVD). Multiple studies have revealed a close relationship between WMH and lacunae and found that a double penumbra existed at the edge of WMH that affects lacunae formation. The study aimed to explore the spatial distribution characteristics and possible influencing factors of lacuna in relation to white matter hyperintensity in patients with CSVD. METHODS: A total of 480 CSVD patients with WMH and with or without lacunae were included. Data about blood biochemical indicators, cerebrovascular CT angiography, 24-hour ambulatory blood pressure and ambulatory electrocardiogram, brain magnetic resonance imaging, and transcranial Doppler ultrasound were gathered from all subjects. They were categorised into four groups based on the spatial interaction between lacunae and WMH. Univariate analyses and multiple logistic regression analyses were used to compare the differences in traditional vascular risk factors, heart rate and blood pressure indicators, arterial pulsatility index (PI) values, and arterial stenosis among different groups. RESULTS: The average age of 480 patients was (58.63 ± 11.91) years, with 347 males (72.3%). Univariate analysis indicated that age, fasting blood glucose, triglycerides, total cholesterol, highdensity lipoprotein, 24-hour and daytime and night systolic and diastolic blood pressure, nocturnal heart rate, heart rate variability, PI values of ipsilateral and contralateral MCA (middle cerebral artery) and ICA (Internal carotid artery) of the lacunae, Fazekas score of PWMH (periventricular white matter hyperintensities), the proportion of MCA or ICA with stenosis rate over 50% on the ipsilateral side of the lacunae were significantly different between different groups (p < 0.05). High fasting blood glucose (OR=1.632, 95% CI= (1.128, 2.361), p =0.009), (OR=1.789, 95%CI= (1.270, 2.520), p = 0.001), (OR=1.806, 95% CI= (1.292, 2.524), p =0.001) was identified as a risk factor for lacunae formation by logistic regression analysis. CONCLUSION: High fasting blood glucose can be considered a risk factor for lacunae formation in patients with WMH. The more severe the PWMH and the higher the nocturnal heart rate, the more likely the lacunae, as well as PWMH, overlap completely. Ipsilateral arteriosclerosis and stenosis are independent risk factors for no contact between lacunae and PWMH.

Tumor microenvironment-mediated NIR-I-to-NIR-II transformation of Au self-assembly for theranostics.

The misdiagnosis of tumors due to insufficient penetration depth or signal interference and damage to normal tissues due to indiscriminate treatment are the biggest challenges in using photothermal agents for clinical translation. To overcome these limitations, a strategy of switching from the near-infrared (NIR)-I region to the NIR-II region was developed based on tumor microenvironment (TME)-mediated gold (Au) self-assembly. Using zeolitic imidazolate framework-8 (ZIF-8) metal-organic framework-coated gold nanorods (AuNRs@ZIF-8) as a model photothermal agent, we demonstrated that only a NIR-I photoacoustic imaging signal was observed in normal tissue because ZIF-8 could prevent the aggregation of AuNRs. However, when ZIF-8 dissociated in the TME, the AuNRs aggregated to activate NIR-II photoacoustic imaging and attenuate the NIR-I signal, thereby allowing an accurate diagnosis of tumors based on signal transformation. Notably, TME-activated NIR-II photothermal therapy could also inhibit tumor growth. Therefore, this TME-activated NIR-I-to-NIR-II switching strategy could improve the accuracy of deep-tumor diagnoses and avoid the injury caused by undifferentiated treatment. STATEMENT OF SIGNIFICANCE: Photothermal agents used for photoacoustic imaging and photothermal therapy have garnered great attention for tumor theranostics. However, always "turned on" near-infrared (NIR)-I laser (700-1000 nm)-responsive photothermal agents face issues of penetration depth and damage to normal tissues. In contrast, tumor microenvironment-activated NIR-II "smart" photothermal agents exhibit deeper penetration depth and tumor selectivity. Therefore, a NIR-I-to-NIR-II switching strategy was developed based on tumor microenvironment-mediated Au self-assembly. This work provides a new strategy for developing tumor microenvironment-activated NIR-II smart photothermal agents.

Satellite record reveals 1960s acceleration of Totten Ice Shelf in East Antarctica.

Wilkes Land and Totten Glacier (TG) in East Antarctica (EA) have been losing ice mass significantly since 1989. There is a lack of knowledge of long-term mass balance in the region which hinders the estimation of its contribution to global sea level rise. Here we show that this acceleration trend in TG has occurred since the 1960s. We reconstruct ice flow velocity fields of 1963-1989 in TG from the first-generation satellite images of ARGON and Landsat-1&4, and build a five decade-long record of ice dynamics. We find a persistent long-term ice discharge rate of 68 ± 1 Gt/y and an acceleration of 0.17 ± 0.02 Gt/y2 from 1963 to 2018, making TG the greatest contributor to global sea level rise in EA. We attribute the long-term acceleration near grounding line from 1963 to 2018 to basal melting likely induced by warm modified Circumpolar Deep Water. The speed up in shelf front during 1973-1989 was caused by a large calving front retreat. As the current trend continues, intensified monitoring in the TG region is recommended in the next decades.

Correlation between neutrophil gelatinase phase lipocalin and cerebral small vessel disease.

Background: Cerebral small vessel disease (CSVD) is common in the elderly population. Neutrophil gelatinase-associated lipocalin (NGAL) is closely related to cardiovascular and cerebrovascular diseases. NGAL causes pathological changes, such as damage to the vascular endothelium, by causing inflammation, which results in other related diseases. The purpose of this study was to investigate whether serum NGAL levels could predict disease severity in patients with CSVD. Methods: The patients with CSVD who visited the Department of Neurology at the First Affiliated Hospital of Zhengzhou University between January 2018 and June 2022 were prospectively included. The total CSVD burden score was calculated using whole-brain magnetic resonance imaging (MRI), and the patients were divided into a mild group (total CSVD burden score < 2 points) and a severe group (total CSVD burden score ≥ 2 points). Age, sex, height, smoking and alcohol consumption history, medical history, and serological results of patients were collected to perform the univariate analysis. Multivariate logistic regression was used to analyze the risk factors that affect CSVD severity. The multiple linear regression method was used to analyze which individual CSVD markers (periventricular white matter hyperintensities, deep white matter hyperintensities, lacune, and cerebral microbleed) play a role in the association between total CSVD burden score and NGAL. Results: A total of 427 patients with CSVD (140 in the mild group and 287 in the severe group) were included in the study. A multivariate logistic regression analysis showed that the following factors were significantly associated with CSVD severity: male sex [odds ratio(OR), 1.912; 95% confidence interval (CI), 1.150-3.179], age (OR, 1.046; 95% CI, 1.022-1.070), history of cerebrovascular disease (OR, 3.050; 95% CI, 1.764-5.274), serum NGAL level (OR, 1.005; 95% CI, 1.002-1.008), and diabetes (OR, 2.593; 95% CI, 1.424-4.722). A multivariate linear regression shows that periventricular white matter hyperintensities and cerebral microbleed are associated with serum NGAL concentrations (P < 0.05). Conclusion: Serum NGAL level is closely related to CSVD severity and is a risk factor for the burden of CSVD brain damage. Serum NGAL has high specificity in reflecting the severity of CSVD.

Therapeutic Effect of Polaprezinc on Reflux Esophagitis in the Rat Model.

BACKGROUND/AIMS: To explore the protective effects and therapeutic mechanism of Esomeprazole (PPI), polaprezinc granule (PZ), and PPI + PZ on reflux esophagitis (RE) in the rat model. METHODS: Wistar rats were randomly divided into 9 groups, which contain the control group, the acid cessation group (0.7% HCl, Q3D × 4), and the acid persistence group (0.7% HCl, Q3D × 11). PPI was administered by gavage at 8 mg·kg-1 body weight and PZ was administered by gavage at 120 mg·kg-1 body weight once a day for 15 days. The gastric cardia tissue of the feeding tube was observed under the light microscope, and the levels of interleukin-8 (IL-8) and prostaglandin E2 (PGE2) were measured by ELISA. The expression of EGFR, Akt, p-Akt, and p-mTOR was detected by Western blot. RESULTS: The ELISA results showed that the levels of IL-8 and PGE2 were significantly increased in the model group, but decreased in all groups after treatment. In the acid cessation group, PZ treatment had the most significant effect on reducing IL-8 levels and PPI + PZ treatment had the most significant effect on reducing PGE2 levels. In the acid persistence group, the PPI treatment had the most significant effect on reducing the levels of IL-8 and PGE2, and the PZ treatment could also significantly reduce their levels, close to the normal value. Western blot results showed that the expression of PI3K/Akt/mTOR pathway protein was increased in the model group, while its expression was decreased after treatment. CONCLUSIONS: Polaprezinc has a significant therapeutic effect on RE in rats, which can reduce the levels of IL-8 and PGE2 and downregulate the expression of PI3K/Akt/mTOR signal pathway protein. The efficacy of polaprezinc in the treatment of reflux esophagitis is comparable to that of PPI, and the combination of them is more effective in the reflux esophagitis treatment.

Amniotic fluid stem cell attenuated necrotizing enterocolitis progression by promoting Rspo3/AMPKα axis.

R-spondin 3 (Rspo3) is involved in various cellular processes. The alteration of Rspo3 participates in the differentiation of intestinal epithelial cells which are the crucial effector cells during necrotizing enterocolitis (NEC) development. Amniotic fluid stem cells (AFSCs) were recently indicated as a potential approach for NEC therapy. This study aimed to illustrate the regulatory role and mechanism of Rspo3 in the pathogenesis of NEC and whether AFSCs therapy would impact NEC by mediating Rspo3. First, the alteration of Rspo3 was investigated in the serum and tissues of NEC patients, and an in vitro cell model induced by LPS. A gain-of-function assay was conducted to explore the function of Rspo3 in NEC. Through the analysis of adenosine 5'-monophosphate-activated protein kinase α (AMPKα) activation, the mechanism of Rspo3-mediated NEC progression was demonstrated. Finally, AFSCs were used to coculture human intestinal epithelial cells (HIECs) and the impacts on NEC development were also explored. The results found that Rspo3 was dramatically depressed during NEC progression and reversing Rspo3 expression ameliorated LPS-induced injury, inflammation, oxidative stress and tight junction dysregulation in HIECs. Besides, Rspo3 overexpression reversed AMPKα inactivation induced by NEC and an AMPKα inhibitor, Compound C, blocked the effect of Rspo3 overexpression on NEC. AFSCs treatment was beneficial for NEC therapy by restoring Rspo3 expression which was counteracted by exosome inhibitor. Generally, AFSCs attenuated NEC progression by promoting the Rspo3/AMPKα axis which might exert via the secretion of exosomes. Our conclusions might be valuable for NEC diagnosis and therapy.

Melt rates in the kilometer-size grounding zone of Petermann Glacier, Greenland, before and during a retreat.

Warming of the ocean waters surrounding Greenland plays a major role in driving glacier retreat and the contribution of glaciers to sea level rise. The melt rate at the junction of the ocean with grounded ice-or grounding line-is, however, not well known. Here, we employ a time series of satellite radar interferometry data from the German TanDEM-X mission, the Italian COSMO-SkyMed constellation, and the Finnish ICEYE constellation to document the grounding line migration and basal melt rates of Petermann Glacier, a major marine-based glacier of Northwest Greenland. We find that the grounding line migrates at tidal frequencies over a kilometer-wide (2 to 6 km) grounding zone, which is one order of magnitude larger than expected for grounding lines on a rigid bed. The highest ice shelf melt rates are recorded within the grounding zone with values from 60 ± 13 to 80 ± 15 m/y along laterally confined channels. As the grounding line retreated by 3.8 km in 2016 to 2022, it carved a cavity about 204 m in height where melt rates increased from 40 ± 11 m/y in 2016 to 2019 to 60 ± 15 m/y in 2020 to 2021. In 2022, the cavity remained open during the entire tidal cycle. Such high melt rates concentrated in kilometer-wide grounding zones contrast with the traditional plume model of grounding line melt which predicts zero melt. High rates of simulated basal melting in grounded glacier ice in numerical models will increase the glacier sensitivity to ocean warming and potentially double projections of sea level rise.

Association of Blood Lipid Profile Components with White Matter Hyperintensity Burden in Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) refers to a common cerebrovascular disease and white matter hyperintensities (WMHs) constitute a typical feature of CSVD. However, there has not been a large number of studies investigating the relationship between lipid profile components and WMHs. METHODS: Altogether, 1019 patients with CSVD were enrolled at the First Affiliated Hospital of Zhengzhou University between April 2016 to December 2021. Baseline data were collected for all patients, including demographic characteristics and clinical data. WMH volumes were evaluated by two experienced neurologists using the MRIcro software. Multivariate regression analysis was used to investigate the relationship among the severity of WMHs, blood lipids and common risk factors. RESULTS: Altogether, 1019 patients with CSVD were enrolled, including 255 in the severe WMH group and 764 in the mild WMH group. After including age, sex and blood lipids to construct a multivariate logistic regression equation, we observed that the severity of WMHs was independently predicted by low-density lipoprotein (LDL), homocysteine level and history of cerebral infarction. CONCLUSION: We used WMH volume, a highly accurate measure, to assess its relationship with lipid profiles. The WMH volume increased with a decrease in LDL. This relationship was more significant, especially among the subgroups of patients aged <70 years and men. Patients with cerebral infarction and higher homocysteine levels were more likely to have higher WMH volumes. Our study has provided a reference for clinical diagnosis and therapy, especially for discussing the role of blood lipid profiles in the pathophysiology of CSVD.

Tumor microenvironment responsive T1-T2 dual-mode contrast agent Fe3O4@ZIF-8-Zn-Mn NPs for in vivo magnetic resonance imaging.

Activated T1-T2 contrast agents can effectively improve the sensitivity and diagnosis accuracy of magnetic resonance imaging (MRI), but the construction of such contrast agents still remains a great challenge. In this work, a pH- and glutathione (GSH)-responsive T1-T2 dual-mode contrast agent, Fe3O4@ZIF-8-Zn-Mn nanoparticles (NPs), with simple components was constructed via simply assembly of paramagnetic Mn2+ ions (as T1 contrast agent) and Fe3O4 NPs (as T2 contrast agent) into a pH- and GSH-sensitive Zn-zeolitic imidazole framework (ZIF-8) matrix. Under neutral conditions, Fe3O4@ZIF-8-Zn-Mn NPs show good stability and weak T1-T2 dual-mode MRI contrast effect (r1 = 0.82 mM-1 s-1, r2 = 21.28 mM-1 s-1) due to the magnetic interference between Fe3O4 NPs and paramagnetic Mn2+ ions. In contrast, under acidic environment (pH = 6.5-5.5) and in the present GSH (0-4 mM), Fe3O4@ZIF-8-Zn-Mn NPs can be disassembled and release Fe3O4 NPs and paramagnetic Mn2+ ions, which causes simultaneous recovery of T1 and T2 imaging performances with enhanced r1 and r2 relaxation values up to 6.9 and 9.9 times, respectively. Moreover, in vivo MRI experiments showed that after the intravenous injection of Fe3O4@ZIF-8-Zn-Mn NPs for about one hour, the T1-weighted imaging of the tumor site becomes brighter with T1 signal enhanced by about 31%, while the T2-weighted imaging of the tumor site becomes darker with T2 signal enhanced by nearly 30%, suggesting the great potential of Fe3O4@ZIF-8-Zn-Mn NPs to be used as a tumor microenvironment-responsive T1-T2 dual-mode contrast agent for sensitive tumor imaging.