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BACKGROUND: Dry eye is a common eye disease. Artificial tears supplements are widely used for the treatment of dry eyes. However, multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears, which may affect the therapeutic effect. AIM: To analyze the characteristics of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A. METHODS: A total of 124 dry eye patients treated at The First People's Hospital of Xining from April 2020 to April 2022 were selected as the observation group, while 20 healthy individuals served as the control group during the same period. Levels of inflammatory markers, including IL-1ß, IL-6, and TNF-α, were analyzed. The observation group was further divided into a study group and a control group, each consisting of 62 patients. The control group received artificial tears, whereas the study group received a combination of artificial tears and cyclosporine A. Inflammatory markers, Schirmer's test (SIT), tear break-up time (TBUT), corneal fluorescein staining (CFS), National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) scores, and adverse events (AEs) were compared between the two groups. RESULTS: The observation group exhibited significantly elevated serum levels of IL-1ß, IL-6, and TNF-α in comparison to the healthy group. Following treatment, the study group demonstrated substantial reductions in IL-1ß, IL-6, and TNF-α levels relative to the control group. Moreover, after treatment, the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group. Additionally, significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia, foreign body sensation, fatigue, red eye, and burning sensation within the study group. Furthermore, post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group (P < 0.05). It is noteworthy that significant AEs were reported in both groups throughout the treatment period. CONCLUSION: Cyclosporine A combined with artificial tears is effective in treating dry eye, yielding enhanced outcomes by improving SIT and TBUT levels, reducing CFS scores, and ameliorating vision-related quality of life.

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[This corrects the article DOI: 10.1039/C6RA07480D.].

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Inflammatory bowel disease (IBD) has high prevalence in Western counties. The high fat content in Western diets is one of the leading causes for this prevalence; however, the underlying mechanisms have not been fully defined. Here, we find that high-fat diet (HFD) induces ferroptosis of intestinal regulatory T (Treg) cells, which might be the key initiating step for the disruption of immunotolerance and the development of colitis. Compared with effector T cells, Treg cells favor lipid metabolism and prefer polyunsaturated fatty acids (PUFAs) for the synthesis of membrane phospholipids. Therefore, consumption of HFD, which has high content of PUFAs such as arachidonic acid, cultivates vulnerable Tregs that are fragile to lipid peroxidation and ferroptosis. Treg-cell-specific deficiency of GPX4, the key enzyme in maintaining cellular redox homeostasis and preventing ferroptosis, dramatically aggravates the pathogenesis of HFD-induced IBD. Taken together, these studies expand our understanding of IBD etiology.

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The manipulation of biocompatible supramolecular nanostructures at subcellular and cellular levels has become one of the increasingly significant topics but remains a formidable challenge in chemical and biological science. In this work, a controllable supramolecular aggregate based on host-guest competitive binding is elaborately constructed using cucurbit[8]uril, methionine-containing amphiphilic peptide, and perylene diimide, displaying in situ oxidation-driven macrocycle-confined fluorescence enhancement for cell imaging and morphological reconstruction for cancer cell death. The experimental results demonstrate that cucurbit[8]uril possesses a high binding affinity with the methionine peptide, while this value sharply decreases after the methionine residue is oxidized to sulfoxide or sulfone. Therefore, perylene diimide can be competitively included by cucurbit[8]uril in the co-assemblies, eventually resulting in a 10-fold fluorescence enhancement and the conversion of topological morphology from nano-sized particles to micron-sized sheets. Moreover, the obtained ternary assemblies can be oxidized by endogenous reactive oxygen species in cancer cells, thus not only providing enhanced fluorescence for cell imaging, but also leading to endoplasmic reticulum dysfunction and significant cell death. Therefore, the controllable and oxidation-responsive morphological transformation based on the host-guest competitive binding in biological media can be viewed as a feasible means for efficient disease theragnosis.

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Celiac disease (CD), a gluten-related disease, is a multi-system rare disorder mainly involving the gastrointestinal tract. The clinical signs of CD are exceedingly heterogeneous, which increases the difficulty of clinical differential diagnosis. Neurological manifestations are one of the non-classical CD symptoms. As some patients present only neurological symptoms at early stages, the diagnosis of CD is always delayed. Correct diagnosis and management could decrease patient morbidity and deaths. A 32-year-old male was admitted to the hospital due to progressive muscle atrophy of both lower limbs and lumbar stiffness. Based on positive gluten-sensitive enteropathy autoantibody profiles and gastroscopy foundation, the diagnosis of CD was established. The patient was instructed to gluten-free diet. The antibody titer of gluten-sensitive enteropathy autoantibodies decreased, and the patient's symptoms alleviated. We emphasize the importance of CD screening in patients with neurological disorders of unknown aetiology.

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Meningiomas are the most common primary intracranial tumors and account for nearly 30% of all nervous system tumors. Approximately half of meningioma patients exhibit neurofibromin 2 (NF2) gene inactivation. Here, NF2 was shown to interact with the endoplasmic reticulum (ER) calcium (Ca2+) channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in IOMM-Lee, a high-grade malignant meningioma cell line, and the F1 subdomain of NF2 plays a critical role in this interaction. Functional assays indicated that NF2 promotes the phosphorylation of IP3R (Ser 1756) and IP3R-mediated endoplasmic reticulum (ER) Ca2+ release by binding to IP3R1, which results in Ca2+-dependent apoptosis. Knockout of NF2 decreased Ca2+ release and promoted resistance to apoptosis, which was rescued by wild-type NF2 overexpression but not by F1 subdomain deletion truncation overexpression. The effects of NF2 defects on the development of tumors were further studied in mouse models. The decreased expression level of NF2 caused by NF2 gene knockout or mutation affects the activity of the IP3R channel, which reduces Ca2+-dependent apoptosis, thereby promoting the development of tumors. We elucidated the interaction patterns of NF2 and IP3R1, revealed the molecular mechanism through which NF2 regulates IP3R1-mediated Ca2+ release, and elucidated the new pathogenic mechanism of meningioma-related NF2 variants. Our study broadens the current understanding of the biological function of NF2 and provides ideas for drug screening of NF2-associated meningioma.

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This study proposes a novel tracking differentiator and applies it to the sliding-mode control (SMC) algorithm to address the unsatisfactory disturbance suppression and low tracking accuracy of magnetic levitation (maglev) systems. First, to assess performance in terms of filtering, tracking, and differentiation, an inverse hyperbolic sine function and a two-phase power function are introduced to improve the tracking differentiator. This can accelerate the global convergence speed, ensure smooth convergence at the equilibrium point, reduce system jitter, and enhance the noise-suppression ability of the system. The differentiator parameter-adjustment rules are derived from a system sweep. A comparison of the simulation results show that the proposed differentiator effectively suppresses noise and performs signal tracking and differentiation. Finally, the new differentiator is applied to the SMC of a maglev system. Simulation and experimental results show that the response speed of the maglev system under the SMC based on the new tracking differentiator is high, the jitter is effectively reduced, and the noise-suppression ability is improved.

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Lipid droplets (LDs) and lysosomes play key roles in autophagy and cell apoptosis, and the discriminative visualization of the two organelles and simultaneously of autophagy and apoptosis is very helpful to understand their internal relationships. However, fluorescent probes that can concurrently achieve these tasks are not available currently. Herein, we delicately fabricate a robust probe CAQ2 for multiple tasks: illumination of LDs and lysosomes in dual emission colors as well as discriminative visualization of cell apoptosis and autophagy. The probe exhibited both lipophilic and basic properties and displayed different emission colors in neutral and protonated forms; thus, LDs and lysosomes emitted blue and red fluorescence colors, respectively. Because of the lysosomal acidification during autophagy, CAQ2 detected autophagy with evidently enhanced red emission. Because of the lysosomal alkalization during apoptosis, CAQ2 imaged apoptosis with a drastically decreased red fluorescence intensity. With the robust probe, the autophagy under starvation and lipidless conditions was visualized, and the apoptosis induced by H2O2, ultraviolet (UV) irradiation, and rotenone treatment was successfully observed. The efficient detoxification of Na2S against rotenone treatment was successfully revealed.

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The recurrent brown tide phenomenon, attributed to Aureococcus anophagefferens (A. anophagefferens), constitutes a significant threat to the Qinhuangdao sea area in China, leading to pronounced ecological degradation and substantial economic losses. This study utilized machine learning and deep learning techniques to predict A. anophagefferens population density, aiming to elucidate the occurrence mechanism and influencing factors of brown tide. Specifically, Random Forest (RF) algorithm was utilized to impute missing water quality data, facilitating its direct application in subsequent algal population prediction models. The results revealed that all four models-RF, Support Vector Regression (SVR), Multilayer Perceptron (MLP), and Convolutional Neural Network (CNN)-exhibited high accuracy in predicting A. anophagefferens population densities, with R2 values exceeding 0.75. RF, in particular, showed exceptional accuracy and reliability, with an R2 value surpassing 0.8. Additionally, the study ascertained five critical factors influencing A. anophagefferens population density: ammonia nitrogen, pH, total nitrogen, temperature, and silicate.

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Normally, small-molecule fluorescent probes dependent on the mitochondrial membrane potential (MMP) are invalid for fixed cells and tissues, which limits their clinical applications when the fixation of pathological specimens is imperative. Given that mitochondrial morphology is closely associated with disease, we developed a long-chain mitochondrial probe for fixed cells and tissues, DMPQ-12, by installing a C12-alkyl chain into the quinoline moiety. In fixed cells stained with DMPQ-12, filament mitochondria and folded cristae were observed with confocal and structural illumination microscopy, respectively. In titration test with three major phospholipids, DMPQ-12 exhibited a stronger binding force to mitochondria-exclusive cardiolipin, revealing its targeting mechanism. Moreover, mitochondrial morphological changes in the three lesion models were clearly visualized in fixed cells. Finally, by DMPQ-12, three kinds of mitochondria with different morphologies were observed in situ in fixed muscle tissues. This work breaks the conventional concept that organic fluorescent probes only stain mitochondria with normal membrane potentials and opens new avenues for comprehensive mitochondrial investigations in research and clinical settings.

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The addition of hydrogen to natural gas is an effective approach to broaden the range of applications for hydrogen and address the issue of global warming. However, the inclusion of hydrogen alters the combustion properties of natural gas. The paper established a simplified mechanism consisting of 19 components and a 67-step reaction for hydrogen-doped natural gas combustion. With this simplified mechanism, the effects of hydrogen doping and the utilization of porous media combustion techniques on the combustion characteristics of natural gas were investigated numerically. The results suggested that the utilization of porous media combustion technology is beneficial for achieving the complete combustion of hydrogen-doped natural gas and reducing pollutant emissions. Additionally, the total gas cost and environmental impact of domestic gas water heaters with hydrogen-doping natural gas were estimated. The findings show that the use of 20% hydrogen-doped natural gas contributes to a decrement in fuel costs and reduced emissions of CO by 25.4%, NOX by 53.9%, and CO2 by 6.78%.

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Possessing four cationic pyridium groups, phenyl-bridged bis(triphenylamine) derivatives (G1, G2) were encapsulated by cucurbit[8]uril (CB[8]) at a 1:2 stoichiometry to form the network-like organic two-dimensional nanosheet, which could efficiently enhance the near-infrared (NIR) luminescence and companies with a red-shift from 750 to 810 nm for G1. Benefiting from the supramolecular multivalent interaction, α-cyclodextrin modified hyaluronic acid (HACD) and G1/CB[8] formed nanoparticles to further enhance NIR luminescence behaviors. Compared with the short rigid aromatic bridged bis(triphenylamine) derivative (G2), the supramolecular assembly derived from G1 with long flexible cationic arms gives a larger Stokes shift, which further coassembles with the phosphorescent bromophenylpyridinium derivative/CB[8] pseudorotaxane, leading to efficient phosphorescent resonance energy transfer (PRET). Especially, the nanoparticle showed delayed NIR fluorescence under 308 nm light excitation with an ultralarge Stokes shift up to 502 nm, which was successfully applied in targeted NIR cell imaging.

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BACKGROUND: In this study, we analyzed intestinal flora in an experimental mouse model of chronic kidney disease (CKD) and investigated whether oral supplementation with probiotic Lactobacillus rhamnosus GG could slow the decline in renal function and inflammatory status of mice with CKD. METHODS: We surgically induced chronic kidney disease in C57BL/6J male mice aged 8-9 weeks. We used dual-stage 5/6 nephrectomy for this, while the mock group underwent a mock procedure. The experimental (CKD mice) and mock group were administered a daily dose of 10 × 109 colony forming unit (CFU) of probiotic L. rhamnosus GG or 2 g of maltodextrin as a placebo by oral gavage, respectively, for 5 weeks. At the end of the experiment, the fecal samples of the mice were collected and prepared for intestinal microbial diversity analysis. We examined the serum chemistry and renal histology of the mice. RESULTS: Important serum and blood biomarkers were associated with the development of CKD, including increased serum concentrations of creatine, cystatin C, blood urea nitrogen (BUN), and a protein-interleukin-6 (denoted as IL-6), whereas decreased serum albumin concentration was also observed in the mice with CKD. The intestinal flora of the mice with CKD significantly declined in terms of diversity, richness, and homogeneity. The consumption of L. rhamnosus GG probiotic via oral gavage significantly decreased the serum concentration level present in creatinine and blood urea nitrogen. However, it increased albumin in the group with CKD. After probiotic treatment, serum IL-6 levels dropped considerably, and the kidney histopathology score in mice with CKD who were given L. rhamnosus GG improved. Moreover, supplementation with the probiotic significantly improved floral richness and lineage diversity in the mice with CKD.Conclusions: In this study, we found that probiotics significantly attenuated renal failure development, reduced serum levels of proinflammatory cytokine IL-6, and increased the abundance and lineage diversity of intestinal flora in mice with chronic kidney disease.

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Seed abortion is a common phenomenon in woody plants, especially in rare and endangered species. Serious seed abortion occurs in the dove tree and largely restricts its natural reproduction. A number of differentially expressed genes (DEGs) between normal and aborted seeds of the dove tree have been previously identified through transcriptome profiling. Among these, most DEGs encoding laccase showed significant upregulation in the aborted seeds. In this study, the laccase gene with the highest expression level in aborted seeds, DiLAC17, was cloned from the dove tree genome and further verified. Overexpression of the DiLAC17 gene in Arabidopsis resulted in retarded growth, deformed siliques, and severe seed abortion. Most Arabidopsis genes involved in seed development, such as AtLEC2, AtANT1, and AtRGE1, were suppressed in the transgenic lines. Laccase activity and lignin content were significantly improved in transgenic lines under ectopic overexpression of the DiLAC17 gene. Excessive lignin accumulation in the early developmental stage was assumed to be a key cause of restricting silique growth and seed expansion, which ultimately led to seed abortion. These results indicate a laccase-mediated pathway for seed abortion, which might be a strategy adopted by this rare and endangered species to reduce the reproductive load.

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Accurate predictions of coastal ocean chlorophyll-a (Chl-a) concentrations are necessary for dynamic water quality monitoring, with eutrophication as a critical factor. Prior studies that used the driven-data method have typically overlooked the relationship between Chl-a and marine particulate carbon. To address this gap, marine particulate carbon was incorporated into machine learning (ML) and deep learning (DL) models to estimate Chl-a concentrations in the Yang Jiang coastal ocean of China. Incorporating particulate organic carbon (POC) and particulate inorganic carbon (PIC) as predictors can lead to successful Chl-a estimation. The Gaussian process regression (GPR) model significantly outperforming the DL model in terms of stability and robustness. A lower POC/Chl-a ratio was observed in coastal areas, in contrast to the higher ratios detected in the southern regions of the study area. This study highlights the efficacy of the GPR model for estimating Chl-a and the importance of considering POC in modeling Chl-a concentrations.

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A two-photon excited fluorescent probe CMB-1 has been rationally developed for the detection and regeneration of formaldehyde based on a novel nucleophilic addition of a secondary amine to FA and subsequential alcoholysis reactivity mechanism. It enables a specific turn-on response towards formaldehyde and facilitates the monitoring of exogenous and endogenous formaldehyde in living cells via both one- and two-photon microscopy, with minimal influence on its native homeostasis and local concentration.

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Mitochondrial viscosity is closely associated with intracellular physiological activities yet their abnormality will result in various diseases. In particular, viscosity in cancer cells is different from that in normal cells, which is thought to be an indicator for cancer diagnosis. However, there were few fluorescent probes able to distinguish homologous cancer and normal cells by detecting mitochondrial viscosity. Herein, we designed a viscosity-sensitive fluorescent probe (named NP) based on the twisting intramolecular charge transfer (TICT) mechanism. NP exhibited exquisite sensitivity to viscosity and selectivity to mitochondria and excellent photophysical properties, such as large Stokes shift and high molar extinction coefficient, which enables wash-free, high-fidelity and fast imaging mitochondria. Moreover, it was capable of detecting mitochondrial viscosity in living cells and tissue, as well as monitoring apoptosis process. Significantly, considering numerous breast cancer cases in every country of the world, NP was successfully applied to distinguish human breast cancer cells (MCF-7) from normal cells (MCF-10A) by difference in fluorescence intensity originated from abnormality in mitochondrial viscosity. All the results indicated that NP could serve as a robust tool for effectively detecting mitochondrial viscosity changes in-situ.

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Excess nitrogen in water bodies is associated with a number of environmental problems, including hypoxia and eutrophication. Originating from anthropogenic activities such as fertilizer application, and influenced by watershed characteristics such as the structure of the drainage network, stream discharge, temperature, and soil moisture, factors influencing nitrogen transport and transformation are many and interconnected. This paper describes the development and application of a process-oriented nitrogen model based on the modeling framework of PAWS (Process-based Adaptive Watershed Simulator) that can describe coupled hydrologic, thermal and nutrient processes. The integrated model was tested for an agricultural watershed with complex land use, namely the Kalamazoo River watershed in Michigan, USA. Nitrogen transport and transformations on the landscape were modeled by representing multiple sources and processes (fertilizer/manure application, point sources, atmospheric deposition, nitrogen retention and removal in wetlands and other lowland storage, etc.) across multiple hydrologic domains (streams, groundwater, soil water). The coupled model provides a tool to examine nitrogen budgets and to quantify the impacts of human activities and agricultural practices on the riverine export of nitrogen species. Model results indicate that the river network removed approximately 5.96 % of the total anthropogenic nitrogen input to the watershed, and that the riverine export of nitrogen accounted for 29.22 % of the total anthropogenic inputs during 2004-2009 while the groundwater contribution of nitrogen to the rivers during the same period was found to be 18.53 % highlighting the important role of groundwater within the watershed.

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Possessing dual-targeted agents toward the lysosome and cancer cells, a ternary supramolecular assembly was constructed by a morpholine-modified permethyl ß-cyclodextrin, sulfonated porphyrin, and folic acid-modified chitosan via multivalent interactions. As compared with free porphyrin, the obtained ternary supramolecular assembly showed promoted photodynamic effect and achieved dual-targeted precise imaging in cancer cells.

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