Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

The Quantitative Biotinylproteomics Studies Reveal a WInd-Related Kinase 1 (Raf-Like Kinase 36) Functioning as an Early Signaling Component in Wind-Induced Thigmomorphogenesis and Gravitropism.

Wind is one of the most prevalent environmental forces entraining plants to develop various mechano-responses, collectively called thigmomorphogenesis. Largely unknown is how plants transduce these versatile wind force signals downstream to nuclear events and to the development of thigmomorphogenic phenotype or anemotropic response. To identify molecular components at the early steps of the wind force signaling, two mechanical signaling-related phosphoproteins, identified from our previous phosphoproteomic study of Arabidopsis touch response, mitogen-activated protein kinase kinase 1 (MKK1) and 2 (MKK2), were selected for performing in planta TurboID (ID)-based quantitative proximity-labeling (PL) proteomics. This quantitative biotinylproteomics was separately performed on MKK1-ID and MKK2-ID transgenic plants, respectively, using the genetically engineered TurboID biotin ligase expression transgenics as a universal control. This unique PTM proteomics successfully identified 11 and 71 MKK1 and MKK2 putative interactors, respectively. Biotin occupancy ratio (BOR) was found to be an alternative parameter to measure the extent of proximity and specificity between the proximal target proteins and the bait fusion protein. Bioinformatics analysis of these biotinylprotein data also found that TurboID biotin ligase favorably labels the loop region of target proteins. A WInd-Related Kinase 1 (WIRK1), previously known as rapidly accelerated fibrosarcoma (Raf)-like kinase 36 (RAF36), was found to be a putative common interactor for both MKK1 and MKK2 and preferentially interacts with MKK2. Further molecular biology studies of the Arabidopsis RAF36 kinase found that it plays a role in wind regulation of the touch-responsive TCH3 and CML38 gene expression and the phosphorylation of a touch-regulated PATL3 phosphoprotein. Measurement of leaf morphology and shoot gravitropic response of wirk1 (raf36) mutant revealed that the WIRK1 gene is involved in both wind-triggered rosette thigmomorphogenesis and gravitropism of Arabidopsis stems, suggesting that the WIRK1 (RAF36) protein probably functioning upstream of both MKK1 and MKK2 and that it may serve as the crosstalk point among multiple mechano-signal transduction pathways mediating both wind mechano-response and gravitropism.

Incidence rate of occult lymph node metastasis in clinical T1-2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study : Original research.

BACKGROUND: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS: The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.

Synergistic Effect of Betaines and Dialkyl Chain Anionic Surfactants on Interfacial Arrangement: A Molecular Dynamics Simulation Study.

Mixed systems of betaines and anionic surfactants can have a significant synergistic effect and greatly reduce the interfacial tension (IFT), which has attracted an extensive amount of attention. However, this synergistic effect requires an anionic surfactant and betaine molecular size matching, which limits the scope of its application. In this work, we studied three mixed systems of sodium dialkyl sulfosuccinate (AOT) and betaines with different sizes by molecular dynamics simulation and an IFT experiment and explored the interfacial behavior and synergistic mechanism of AOT in single and mixed systems. The hydrophobic tail chain center angle, average rising height of carbon atoms, stretch degree and distance between the terminal carbon atoms of AOT, and tilt angles of betaine were calculated and analyzed in detail. Simulation results showed that the hydrophobic tail chain center angle of AOT in the single system was smaller, and it tended to extend into the oil phase. After being mixed with different betaines, AOT can adjust its size according to the interfacial vacancies of different betaine systems by changing the alkyl chain orientation and forming tighter interfacial films. The IFT experiment showed that betaine/AOT mixed systems achieved a lower IFT value compared with that of the single system, indicating that AOT showed a synergistic effect with betaines with different structures. This study will be importantly instructively significant for the design and research of betaine mixed systems in crude oil exploitation.

Parkin deficiency promotes liver cancer metastasis by TMEFF1 transcription activation via TGF-ß/Smad2/3 pathway.

Parkin (PARK2) deficiency is frequently observed in various cancers and potentially promotes tumor progression. Here, we showed that Parkin expression is downregulated in liver cancer tissues, which correlates with poor patient survival. Parkin deficiency in liver cancer cells promotes migration and metastasis as well as changes in EMT and metastasis markers. A negative correlation exists between TMEFF1 and Parkin expression in liver cancer cells and tumor tissues. Parkin deficiency leads to upregulation of TMEFF1 which promotes migration and metastasis. TMEFF1 transcription is activated by Parkin-induced endogenous TGF-ß production and subsequent phosphorylation of Smad2/3 and its binding to TMEFF1 promotor. TGF-ß inhibitor and TMEFF1 knockdown can reverse shParkin-induced cell migration and changes of EMT markers. Parkin interacts with and promotes the ubiquitin-dependent degradation of HIF-1α/HIF-1ß and p53, which accounts for the suppression of TGF-ß production. Our data have revealed that Parkin deficiency in cancer leads to the activation of the TGF-ß/Smad2/3 pathway, resulting in the expression of TMEFF1 which promotes cell migration, EMT, and metastasis in liver cancer cells.

Complex interplay of science reasoning and vaccine hesitancy among parents in Shanghai, China.

The psychosocial underpinnings of vaccine hesitancy are complex. Research is needed to pinpoint the exact reasons why people hesitate to vaccinate themselves or their children against vaccine-preventable diseases. One possible reason are concerns that arise from a misunderstanding of vaccine science. We examined the impact of scientific reasoning on vaccine hesitancy and human papillomavirus (HPV) vaccination intent through a cross-sectional study of parents of vaccine-eligible children (N = 399) at immunization clinics in Shanghai, China. We assessed the relationship between science reasoning and both vaccine hesitancy and HPV vaccine acceptance using general additive models. We found a significant association between scientific reasoning and education level, with those with less than a high school education having a significantly lower scientific reasoning that those with a college education (ß = -1.31, p-value = 0.002). However, there was little evidence of a relationship between scientific reasoning and vaccine hesitancy. Scientific reasoning therefore appears not to exert primary influence on the formation of vaccine attitudes among the respondents surveyed. We suggest that research on vaccine hesitancy continues working to identify the styles of reasoning parents engage in when determining whether or not to vaccinate their children. This research could inform the development and implementation of tailored vaccination campaigns.

Acteoside ameliorates learning and memory impairment in APP/PS1 transgenic mice by increasing Aß degradation and inhibiting tau hyperphosphorylation.

Alzheimer's disease (AD) is a neurodegenerative disease. Senile plaques and intracellular neurofibrillary tangles are pathological hallmarks of AD. Recent studies have described the improved cognitive and neuroprotective functions of acteoside (AS). This study aimed to investigate whether the improved cognition of AS was mediated by Aß degradation and tau phosphorylation in APP/PS1 mice. The open field, Y maze, and novel object recognition tests were used to assess cognitive behavioral changes. We evaluated the levels of Aß40 and Aß42 in serum, cortex, and hippocampus, and Aß-related scavenging enzymes, phosphorylated GSK3ß and hyperphosphorylated tau in the cortex and hippocampus of APP/PS1 mice by western blotting. Our results revealed that AS treatment ameliorated anxious behaviors, spatial learning, and memory impairment in APP/PS1 mice and significantly reduced Aß deposition in their serum, cortex, and hippocampus. AS significantly increased Aß degradation, inhibited the hyperphosphorylation of tau, and significantly decreased the activity of GSK3ß, which is involved in tau phosphorylation. Altogether, these findings indicated that the beneficial effects of AS on AD-associated anxious behaviors and cognitive impairments could be attributed to promoting Aß degradation and inhibiting tau hyperphosphorylation, which might be partly mediated by GSK3ß.

PUM2 promoted osteoarthritis progression through PTEN-mediated chondrocyte ferroptosis by facilitating NEDD4 mRNA degradation.

Osteoarthritis (OA) is a prevalent degenerative joint disease with a lack of effective therapeutic. Chondrocyte ferroptosis contributes to the progression of OA. PUM2 is shown to exacerbate ischemia-reperfusion-induced neuroinflammation by promoting ferroptosis, but its role in OA remains unexplored. Here, primary mouse chondrocytes were stimulated with IL-1ß to mimic OA chondrocyte injury in vitro. And PUM2 was upregulated in OA cartilage tissues and IL-1ß-induced chondrocytes. Silencing PUM2 alleviated IL-1ß-induced chondrocyte inflammation and ECM degradation. Mechanistically, PUM2 facilitated the degradation of NEDD4 mRNA by binding to the 3'UTR of NEDD4 mRNA, which in turn inhibited NEDD4 induced PTEN ubiquitination and degradation. Consistently, NEDD4 silencing reversed the ameliorative effect of PUM2 knockdown on chondrocyte injury, and overexpression of PTEN abolished the improved role of NEDD4 in chondrocyte injury. Moreover, PTEN aggravated IL-1ß-induced ferroptosis in chondrocytes through the Nrf2/HO-1 pathway by increasing the levels of Fe2+, ROS, MDA, and ACSL4 protein, decreasing the activity of SOD and the levels of GSH and GPX4 protein, and aggravating mitochondrial damage. Additionally, destabilized medial meniscus (DMM) were conducted to establish the OA mouse model, and adenovirus-mediated PUM2 shRNA was administered intra-articularly. Silencing PUM2 attenuated OA-induced cartilage damage in vivo. In conclusion, PUM2 promoted OA progression through PTEN-mediated chondrocyte ferroptosis by facilitating NEDD4 mRNA degradation.

Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury: A review.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

[Mechanism of resveratrol in protecting ovary in poor ovarian response mice by regulating Hippo signaling pathway].

This study observed the protective effect of resveratrol(Res) on ovarian function in poor ovarian response(POR) mice by regulating the Hippo signaling pathway and explored the potential mechanism of Res in inhibiting ovarian cell apoptosis. Female mice with regular estrous cycles were randomly divided into a blank group, a model group, and low-and high-dose Res groups(20 and 40 mg·kg~(-1)), with 20 mice in each group. The blank group received an equal volume of 0.9% saline solution by gavage, while the model group and Res groups received suspension of glycosides of Triptergium wilfordii(GTW) at 50 mg·kg~(-1) by gavage for two weeks to induce the model. After modeling, the low-and high-dose Res groups were continuously treated with drugs by gavage for two weeks, while the blank group and the model group received an equal volume of 0.9% saline solution by gavage. Ovulation was induced in all groups on the day following the end of treatment. Finally, 12 female mice were randomly selected from each group, and the remaining eight female mice were co-housed with male mice at a ratio of 1∶1. Changes in the estrous cycle of mice were observed using vaginal cytology smears. The number of ovulated eggs, ovarian wet weight, ovarian index, and pregnancy rate of mice were measured. The le-vels of anti-Mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in serum were determined using enzyme-linked immunosorbent assay(ELISA). Ovarian tissue morphology and ovarian cell apoptosis were observed using hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining, respectively. The protein expression levels of yes-associated protein(YAP) 1 and transcriptional coactivator with PDZ-binding motif(TAZ) were detected by immunohistochemistry(IHC), while the changes in protein expression levels of mammalian sterile 20-like kinase(MST) 1/2, large tumor suppressor(LATS) 1/2, YAP1, TAZ, B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were determined by Western blot. The results showed that compared with the blank group, the model group had an increased rate of estrous cycle disruption in mice, a decreased number of normally developing ovarian follicles, an increased number of blocked ovarian follicles, increased ovarian granulosa cell apoptosis, decreased ovulation, reduced ovarian wet weight and ovarian index, increased serum FSH and LH levels, decreased AMH and E_2 levels, decreased protein expression levels of YAP1 and TAZ in ovarian tissues, increased relative expression levels of MST1/2, LATS1/2, and Bax proteins, and decreased relative expression levels of YAP1, TAZ, and Bcl-2 proteins. Additionally, the number of embryos per litter significantly decreased after co-housing. Compared with the model group, the low-and high-dose Res groups exhibited reduced estrous cycle disruption rates in mice, varying degrees of improvement in the number and morphology of ovarian follicles, reduced numbers of blocked ovarian follicles, improved ovarian granulosa cell apoptosis, increased ovulation, elevated ovarian wet weight and ovarian index, decreased serum FSH and LH levels, increased AMH and E_2 levels, elevated protein expression levels of YAP1 and TAZ in ovarian tissues, decreased relative expression levels of MST1/2, LATS1/2, and Bax proteins, and increased relative expression levels of YAP1, TAZ, and Bcl-2 proteins. Furthermore, the number of embryos per litter increased to varying degrees after co-housing. In conclusion, Res effectively inhibits ovarian cell apoptosis in mice and improves ovarian responsiveness. Its mechanism may be related to the regulation of key molecules in the Hippo pathway.

Insights into Advanced Neurological Dysfunction Mechanisms Following DBS Surgery in Parkinson's Patients: Neuroinflammation and Pyroptosis.

Parkinson's disease is a severe neurodegenerative disorder. Currently, deep brain electrical stimulation (DBS) is the first line of surgical treatment. However, serious neurological impairments such as speech disorders, disturbances of consciousness, and depression after surgery limit the efficacy of treatment. In this review, we summarize the recent experimental and clinical studies that have explored the possible causes of neurological deficits after DBS. Furthermore, we tried to identify clues from oxidative stress and pathological changes in patients that could lead to the activation of microglia and astrocytes in DBS surgical injury. Notably, reliable evidence supports the idea that neuroinflammation is caused by microglia and astrocytes, which may contribute to caspase-1 pathway-mediated neuronal pyroptosis. Finally, existing drugs and treatments may partially ameliorate the loss of neurological function in patients following DBS surgery by exerting neuroprotective effects.

Reconfigurable three multi-mode terahertz metasurface.

We designed a three reconfigurable multi-mode terahertz metasurface based on a concentric elliptical ring structure. The proposed unit cell is a concentric elliptical ring composed of copper, vanadium oxide and photosensitive silicon from the inside ring to the outside ring. The conductivity of photosensitive silicon and vanadium oxide can be adjusted by changing the external operating temperature and pump light intensity. The same unit cell can reconstruct three kinds of states with different properties, and they have completely different transmission characteristics in various terahertz bands. By encoding the arrangement, through changing external stimulus and operating frequencies, the reconfigurable terahertz metasurface can achieve multiple functions including terahertz focusing with adjustable focal length, vortex beam with different topological charge, and near-field imaging with different patterns. It provides what we believe to be a new idea for the field of information security and the design of multifunctional and multifrequency terahertz devices.

Dilational Rheology of Extended Surfactants at the Air/Water and Oil/Water Interfaces: Effect of Propylene Oxide Group Numbers.

In this paper, the interfacial properties of extended surfactants with different oxypropylene (PO) groups were comprehensively investigated by using interfacial dilational rheology. The differences in molecular orientation, spatial configuration, and relaxation process were compared at the gas-water interface and oil-water interface. The influences of the PO groups on the interface viscoelasticity were analyzed, providing important theoretical support for the wide application of extended surfactants. Experimental results show that the lower number of PO groups in extended surfactants does not cause differences in their presence states on the interface; however, once it increases, the longer PO segment will spiral up in the direction perpendicular to the interface, forming a spatial configuration like a thin cylinder. Compared with air, the PO group has better solubility in the oil phase. The chain segment can still maintain a helical extension from the beginning to the end as a result. However, the upper layer of the thin cylinder will collapse to a certain extent at the surface. Moreover, the orientation of the hydrophobic side has a dynamic process of "tilting to upright" with the increase of adsorption amount or in response to interfacial dilation and compression. The increase of PO number or the insertion of oil molecules has little effect on dilational modulus, and the interfacial film strength is generally relatively low. That is to say, the better emulsifying and solubilizing ability of PO-containing extended surfactants may be more attributed to the matching steric effect at interface or better packing action in bulk phase than to higher film strength.

Prognostic and predictive impact of abnormal signal volume evolution early after chemoradiotherapy in glioblastoma.

INTRODUCTION: This study was designed to explore the feasibility of semiautomatic measurement of abnormal signal volume (ASV) in glioblastoma (GBM) patients, and the predictive value of ASV evolution for the survival prognosis after chemoradiotherapy (CRT). METHODS: This retrospective trial included 110 consecutive patients with GBM. MRI metrics, including the orthogonal diameter (OD) of the abnormal signal lesions, the pre-radiation enhancement volume (PRRCE), the volume change rate of enhancement (rCE), and fluid attenuated inversion recovery (rFLAIR) before and after CRT were analyzed. Semi-automatic measurements of ASV were done through the Slicer software. RESULTS: In logistic regression analysis, age (HR = 2.185, p = 0.012), PRRCE (HR = 0.373, p < 0.001), post CE volume (HR = 4.261, p = 0.001), rCE1m (HR = 0.519, p = 0.046) were the significant independent predictors of short overall survival (OS) (< 15.43 months). The areas under the receiver operating characteristic curve (AUCs) for predicting short OS with rFLAIR3m and rCE1m were 0.646 and 0.771, respectively. The AUCs of Model 1 (clinical), Model 2 (clinical + conventional MRI), Model 3 (volume parameters), Model 4 (volume parameters + conventional MRI), and Model 5 (clinical + conventional MRI + volume parameters) for predicting short OS were 0.690, 0.723, 0.877, 0.879, 0.898, respectively. CONCLUSION: Semi-automatic measurement of ASV in GBM patients is feasible. The early evolution of ASV after CRT was beneficial in improving the survival evaluation after CRT. The efficacy of rCE1m was better than that of rFLAIR3m in this evaluation.

Dehydroaromatization of Indolines and Cyclohexanones with Thiol Access to Aryl Sulfides under Basic Conditions.

Aryl sulfides are common and ubiquitous motifs in natural products and pharmaceuticals. Presented herein is the first example of the synthesis of diaryl sulfide derivatives via dehydroaromatization under simple basic conditions. Dehydroaromatization reactions between indolines or cyclohexanones with aryl thiols are performed in an environmentally benign manner by the use of air (molecular oxygen) as the oxidant, with producing water as the only byproduct. The methodology provides a simple and practical route to diaryl sulfides with wide functional groups in good to excellent yields. Preliminary mechanistic studies suggest that a radical process is involved in the transformation.

The Plasma Concentration of Ticagrelor and Aspirin as a Predictor of Bleeding Complications in Chinese Acute Coronary Syndrome Patients With Dual Antiplatelet Therapy: A Prospective Observational Study.

PURPOSE: This study evaluated the association among the plasma concentration of ticagrelor, ARC124910XX, aspirin, and salicylic acid with the risk of recent bleeding in patients with the acute coronary syndrome. To this end, we developed an accurate model to predict bleeding. METHODS: A total of 84 patients included in this study cohort between May 2021 and November 2021. The risk factors were identified by univariate and multivariate analyses, and statistically significant risk factors identified in the multivariate analysis were included in the nomogram. We used the calibration curve and the receiver operating characteristic curve to verify the accuracy of the prediction model. RESULTS: Multivariable logistic analysis showed that ticagrelor concentration (odds ratio [OR]: 2.47, 95% confidence interval [CI], 1.51-4.75, P = 0.002), ST-segment elevation acute myocardial infarction (OR: 32.2, 95% CI, 2.37-780, P = 0.016), and lipid-lowering drugs (OR: 11.52, 95% CI, 1.91-110, P = 0.015) were positively correlated with bleeding. However, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (OR: 0.04, 95% CI, 0.004-0.213, P < 0.001) was negatively correlated with bleeding. The receiver operating characteristic curve analysis showed that ticagrelor concentration and these factors together predict the occurrence of bleeding (area under receiver operating characteristic curve = 0.945, 95% CI, 0.896-0.994) and that ticagrelor concentration >694.90 ng/mL is the threshold of bleeding concentration (area under receiver operating characteristic curve = 0.696, 95% CI, 0.558-0.834). CONCLUSION: In patients with acute coronary syndrome treated with dual antiplatelet therapy, ticagrelor concentration >694.90 ng/mL was an independent risk factor for bleeding (OR: 2.47, 95% CI, 1.51-4.75, P = 0.002), but ARC124910XX and salicylic acid concentration did not affect bleeding risk ( P > 0.05).

New Insight into the Natural Detoxification of Cr(VI) in Fe-Rich Surface Soil: Crucial Role of Photogenerated Silicate-Bound Fe(II).

Photoexcitation of natural semiconductor Fe(III) minerals has been proven to generate Fe(II), but the photogeneration of Fe(II) in Fe-rich surface soil as well as its role in the redox biogeochemistry of Cr(VI) remains poorly understood. In this work, we confirmed the generation of Fe(II) in soil by solar irradiation and proposed a new mechanism for the natural reductive detoxification of Cr(VI) to Cr(III) in surface soil. The kinetic results showed that solar irradiation promoted the reduction of Cr(VI) in Fe-rich soils, while a negligible Cr(VI) reduction was observed in the dark. Fe(II), mainly in the form of silicate-bound Fe(II), was generated under solar irradiation and responsible for the reduction of Cr(VI) in soils, which was evidenced by sequential extraction, transmission electron microscopy with electron energy loss spectroscopy, and electron transfer calculation. Photogenerated silicate-bound Fe(II) resulted from the massive clay-iron (hydr)oxide associations, consisting of iron (hydr)oxides (e.g., hematite and goethite) and kaolinite. These associations could generate Fe(II) under solar irradiation either via intrinsic excitation to produce photoelectrons or via the ligand-to-metal charge transfer process after the formation of clay-iron (hydr)oxide-organic matter complexes, which was proven by photoluminescence spectroscopy and X-ray photoelectron spectroscopy. These findings highlight the important role of photogenerated Fe(II) in Cr(VI) reduction in surface soil, which advances a fundamental understanding of the natural detoxification of Cr(VI) as well as the redox biogeochemistry of Cr(VI) in soil.

Perception of risk of relapse among patients with first episode and recurrent schizophrenia: a descriptive phenomenological study.

BACKGROUND: Patients suffering from schizophrenia are at a higher risk of relapse. The perception of the risk of relapse in patients is critical for relapse prevention. In the field of psychiatry, the study of risk perception of relapse has been neglected. METHODS: We carried out a qualitative study using a descriptive phenomenological approach. Data were collected at two psychiatric hospitals in China. In total, 22 patients with schizophrenia were recruited through purposive sampling. Face to face semi-structured in-depth interviews were conducted. Interview recordings were transcribed by the research team, and transcripts were analysed by two independent coders with Colaizzi's descriptive analysis framework. The consolidated criteria for reporting qualitative research checklist were used for reporting. RESULTS: The data of first-episode patients yielded three themes: (i) lack of knowledge about disease recognition and medical treatment; (ii) overoptimistic estimation of the risk of relapse; (iii) perceived importance of treatment. For first-relapse patients : (i) initial awareness of relapse warning signs; (ii) lack of systematic and accurate assessment of disease information; (iii) the perception that drug withdrawal is related to relapse. Patients with multiple relapses: (i) susceptibility to relapse: confusion and powerlessness; (ii) the severity of relapse: suicidal thoughts and behavior; (iii) effects of perceived benefits and barriers of medication behaviour. CONCLUSIONS: In schizophrenic patients with first-episode, first-relapse, and multiple relapses, there were dynamic changes in the perception of disease relapse risk and medication behaviour. Medical workers must improve risk awareness education. They should provide patients with scientific, accurate, and timely communication channels, and dynamically assess and manage the risk of relapse in various patients.

Signaling mechanisms of growth hormone-releasing hormone receptor in LPS-induced acute ocular inflammation.

Ocular inflammation is a major cause of visual impairment attributed to dysregulation of the immune system. Previously, we have shown that the receptor for growth-hormone-releasing hormone (GHRH-R) affects multiple inflammatory processes. To clarify the pathological roles of GHRH-R in acute ocular inflammation, we investigated the inflammatory cascades mediated by this receptor. In human ciliary epithelial cells, the NF-κB subunit p65 was phosphorylated in response to stimulation with lipopolysaccharide (LPS), resulting in transcriptional up-regulation of GHRH-R. Bioinformatics analysis and coimmunoprecipitation showed that GHRH-R had a direct interaction with JAK2. JAK2, but not JAK1, JAK3, and TYK2, was elevated in ciliary body and iris after treatment with LPS in a rat model of endotoxin-induced uveitis. This elevation augmented the phosphorylation of STAT3 and production of proinflammatory factors, including IL-6, IL-17A, COX2, and iNOS. In explants of iris and ciliary body, the GHRH-R antagonist, MIA-602, suppressed phosphorylation of STAT3 and attenuated expression of downstream proinflammatory factors after LPS treatment. A similar suppression of STAT3 phosphorylation was observed in human ciliary epithelial cells. In vivo studies showed that blocking of the GHRH-R/JAK2/STAT3 axis with the JAK inhibitor Ruxolitinib alleviated partially the LPS-induced acute ocular inflammation by reducing inflammatory cells and protein leakage in the aqueous humor and by repressing expression of STAT3 target genes in rat ciliary body and iris and in human ciliary epithelial cells. Our findings indicate a functional role of the GHRH-R/JAK2/STAT3-signaling axis in acute anterior uveitis and suggest a therapeutic strategy based on treatment with antagonists targeting this signaling pathway.

Multisequence magnetic resonance imaging-based radiomics models for the prediction of microsatellite instability in endometrial cancer.

PURPOSE: To evaluate the performance of multisequence magnetic resonance imaging (MRI)-based radiomics models in the assessment of microsatellite instability (MSI) status in endometrial cancer (EC). MATERIALS AND METHODS: This retrospective multicentre study included 338 EC patients with available MSI status and preoperative MRI scans, divided into training (37 MSI, 123 microsatellite stability [MSS]), internal validation (15 MSI, 52 MSS), and external validation cohorts (30 MSI, 81 MSS). Radiomics features were extracted from T2-weighted images, diffusion-weighted images, and contrast-enhanced T1-weighted images. The ComBat harmonisation method was applied to remove intrascanner variability. The Boruta wrapper algorithm was used for key feature selection. Three classification algorithms, logistic regression (LR), random forest (RF), and support vector machine (SVM), were applied to build the radiomics models. The area under the receiver operating characteristic curve (AUC) was calculated to compare the diagnostic performance of the models. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the models. RESULTS: Among the 1980 features, Boruta finally selected nine radiomics features. A higher MSI prediction performance was achieved after running the ComBat harmonisation method. The SVM algorithm had the best performance, with AUCs of 0.921, 0.903, and 0.937 in the training, internal validation, and external validation cohorts, respectively. The DCA results showed that the SVM algorithm achieved higher net benefits than the other classifiers over a threshold range of 0.581-0.783. CONCLUSION: The multisequence MRI-based radiomics models showed promise in preoperatively predicting the MSI status in EC in this multicentre setting.