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Abstract Miniaturized on-chip spectrometers with small footprints, lightweight, and low cost are in great demand for portable optical sensing, lab-on-chip systems, and so on. Such miniaturized spectrometers are usually based on engineered spectral response units and then reconstruct unknown spectra with algorithms. However, due to the limited footprints of computational on-chip spectrometers, the recovered spectral resolution is limited by the number of integrated spectral response units/filters. Thus, it is challenging to improve the spectral resolution without increasing the number of used filters. Here we present a computational on-chip spectrometer using electrochromic filter-based computational spectral units that can be electrochemically modulated to increase the efficient sampling number for higher spectral resolution. These filters are directly integrated on top of the photodetector pixels, and the spectral modulation of the filters results from redox reactions during the dual injection of ions and electrons into the electrochromic material. We experimentally demonstrate that the spectral resolution of the proposed spectrometer can be effectively improved as the number of applied voltages increases. The average difference of the peak wavelengths between the reconstructed and the reference spectra decreases from 1.61 nm to 0.29 nm. We also demonstrate the proposed spectrometer can be worked with only four or two filter units, assisted by electrochromic modulation. In addition, we also demonstrate that the electrochromic filter can be easily adapted for hyperspectral imaging, due to its uniform transparency. This strategy suggests a new way to enhance the performance of miniaturized spectrometers with tunable spectral filters for high resolution, low-cost, and portable spectral sensing, and would also inspire the exploration of other stimulus responses such as photochromic and force-chromic, etc, on computational spectrometers.

Non-starch polysaccharides (NSPs) are complex polysaccharides other than starch, mainly including cellulose, hemicellulose, pectin, etc., which have good functional and processing characteristics. Non-starch polysaccharide can be attached to starch surface by mechanical processing, which makes amylose difficult to dissolve and weakens the aging characteristics of starch. In addition, non-starch polysaccharide can enhance the stability of the composite system through hydrogen bond interaction with starch, resist the mechanical shear damage of starch during processing, as well as hinder the direct contact of digestive enzymes with starch and inhibit the digestion of starch, and regulate the glycemic index. In this paper, the composite of non-starch polysaccharides and starch by non-covalent bond, chemical bond crosslinking and processing force are reviewed, which affects the changes of starch particle and crystal structure. In addition, the changes of gelatinization, aging, rheology, and other physicochemical properties as well as digestive properties of the non-starch polysaccharides- starch system are further summarized in order to provide a certain reference for the development of non-starch polysaccharide modified starch functional food.

Abstract Background This study investigates the relationship between triglyceride-glucose (TyG) index trajectories and the results of ablation in patients with stage 3D atrial fibrillation (AF). Methods A retrospective cohort study was carried out on patients who underwent AF Radiofrequency Catheter Ablation (RFCA) at the Cardiology Department of the Fourth Affiliated Hospital of Zhejiang University and Taizhou Hospital of Zhejiang Province from January 2016 to December 2022. The main clinical endpoint was determined as the occurrence of atrial arrhythmia for at least 30 s following a 3-month period after ablation. Using a latent class trajectory model, different trajectory groups were identified based on TyG levels. The relationship between TyG trajectory and the outcome of AF recurrence in patients was assessed through Kaplan-Meier survival curve analysis and multivariable Cox proportional hazards regression model. Results The study included 997 participants, with an average age of 63.21 ± 9.84 years, of whom 630 were males (63.19%). The mean follow-up period for the participants was 30.43 ± 17.75 months, during which 200 individuals experienced AF recurrence. Utilizing the minimum Bayesian Information Criterion (BIC) and the maximum Entropy principle, TyG levels post-AF RFCA were divided into three groups: Locus 1 low-low group (n = 791), Locus 2 low-high-low group (n = 14), and Locus 3 high-high group (n = 192). Significant differences in survival rates among the different trajectories were observed through the Kaplan-Meier curve (P

Nitrogen is the primary limiting factor for crop yield formation. However, excessive application of nitrogen fertilizer not only leads to a decrease in nitrogen utilization efficiency, but also causes serious environmental problems. Therefore, how to balance environmental protection and crop yield when applying nitrogen fertilizer is an important challenge currently faced in agricultural production. Biochar, as a soil amendment, has been widely used in agricultural production. This study used ‘Longyan 101’ tobacco as the experimental material and explored the effects of nitrogen reduction treatment (reducing conventional nitrogen application by half) and combined application of biochar (20 kg/hm2) on tobacco photosynthesis under field experimental conditions. Transcriptome sequencing technology was used to study the changes in the expression levels of photosynthesis-related genes. The results indicate that: reducing the application of nitrogen fertilizer reduces the photosynthetic capacity of tobacco and inhibits its growth, while applying biochar can to some extent alleviate the adverse effects of insufficient nitrogen fertilizer. The results of this experiment have laid the foundation for the rational application of nitrogen fertilizer and the green development of tobacco agriculture.

The return of the Calvo Doctrine, which emphasizes the sovereignty of host states and the primacy of local legal remedies in resolving disputes involving foreign investors, has significant implications for the reform of the Investor-State Dispute Settlement (ISDS) mechanism. This paper explores China’s stance on ISDS reform in the context of this resurgence, offering a detailed analysis of China’s historical approach, recent reforms, and practical applications. Beginning with the exploration of global practices and utilizing theoretical analysis, comparative studies, and case studies, this paper argues that China’s cautious and selective engagement with ISDS reflects a preference for negotiation and local legal remedies over international arbitration. Recent reforms underscore this approach by advocating for a permanent appeal mechanism and emphasizing alternative dispute resolution (ADR) methods such as mediation. China’s ISDS reform strategy aligns with the broader global trend toward enhancing state sovereignty and judicial fairness, potentially influencing other developing countries to adopt similar approaches. The findings of this research contribute to the ongoing debate on ISDS reform and provide practical policy recommendations for strengthening local legal frameworks, promoting alternative dispute resolution methods, and enhancing regional cooperation.

This study investigated the absorption characteristics of

Abstract In order to comprehend the dynamic disaster mechanism induced by overburden rock caving during the advancement of a coal mining face, a physical simulation model is constructed basing on the geological condition of the 21221 mining face at Qianqiu coal mine in Henan Province, China. This study established, a comprehensive monitoring system to investigate the interrelations and evolutionary characteristics among multiple mechanical parameters, including mining-induced stress, displacement, temperature, and acoustic emission events during overburden rock caving. It is suggested that, despite the uniformity of the overburden rock caving interval, the main characteristic of overburden rock lies in its uneven caving strength. The mining-induced stress exhibits a reasonable interrelation with the displacement, temperature, and acoustic emission events of the rock strata. With the advancement of the coal seam, the mining-induced stress undergoes four successive stages: gentle stability, gradual accumulation, high-level mutation, and a return to stability. The variations in other mechanical parameters does not synchronize with the significant changes in mining-induced stress. Before the collapse of overburden rock occurs, rock strata temperature increment decreases and the acoustic emission ringing counts surges with the increase of rock strata displacement and mining-induced stress. Therefore, the collaborative characteristics of mining-induced stress, displacement, temperature, and acoustic emission ringing counts can be identified as the precursor information or overburden rock caving. These results are in good consistent with on-site situation in the coal mine.

Abstract Fluorescent analysis of bone provides valuable insights into bone structures. However, conventional dyes suffer from low specificity on bone tissue, small stokes shift, short fluorescent lifetime, and aggregation‐caused quenching effect, which result in low efficacy and artifacts. In this work, we design an aggregation‐induced emission (AIE)‐active iridium(III) complex (Ir‐BP2) as a highly selective, convenient, nondestructiveness, and dual‐mode staining agent for bone analysis. Ir‐BP2 containing phosphonate groups selectively binds to hydroxyapatites, the main component of bone matrix, and exhibits turn‐on AIE phosphorescence with prolonged lifetime. Ir‐BP2 exhibits promising biosafety and offers higher accuracy in staining calcium deposits than conventional Alizarin Red S staining assay when it is employed in real‐time monitoring of osteogenesis differentiation process. A ready‐to‐use staining spray of Ir‐BP2 is fabricated. By using fluorescent imaging and lifetime imaging, Ir‐BP2 staining provides valuable insights into bone microstructure analysis, microdamage diagnosis, and bone growth state identification. Further, Ir‐BP2 is successfully applied on a human spine vertebra for diagnosing bone invasiveness of eosinophilic granuloma, validating its clinical practice. This work presents a powerful tool in bone analysis and will lead to new approaches for the diagnosis and treatment of bone‐related diseases.

Hydroquinone (HQ) was used to catalyze Methanobactin (Mb) to reduce chlorauric acid to prepare Gold Nanoparticles (AuNPs). Mb@AuNPs was modified onto the surface of a bare gold electrode via electrodeposition to prepare the Mb@AuNPs/Au electrode. Subsequently, differential pulse voltammetry was conducted for the simultaneous determination of nitrite and ascorbic acid concentrations as well as condition optimization. For the electrode assembly, electrodeposition was performed with a 0.20 mol/L and pH6.5 PBS at a 100 mV/s scan rate for 40 cycles. In the linear range of 2~5600 μmol/L and 1~6000 μmol/L, the oxidation peak current of both nitrite and ascorbic acid detected by Mb@AuNPs/Au showed a good linear relationship with the concentration (R2>0.9928), and the limit of detection (LOD) was 0.31 and 0.57 μmol/L, respectively. The recovery rates of standard addition for the actual samples were 92.59%~109.26%, 90.01%~103.51%. The method has good reproducibility and stability and can be used for simultaneous determination of nitrite and ascorbic acid in fruits and vegetables.

The level of fluoride ions (F−) in the human body is closely related to various pathological and physiological states, and the rapid detection of F− is important for studying physiological processes and the early diagnosis of diseases. In this study, the detailed sensing mechanism of a novel high-efficiency probe (PBT) based on 2-(2′-hydroxyphenyl)-benzothiazole derivatives towards F− has been fully investigated based on density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods. F− attacks the O-P bond of PBT to cleavage the dimethylphosphinothionyl group, and the potential products were evaluated by Gibbs free energy and spectroscopic analyses, which ultimately identified the product as HBT-Enol1 with an intramolecular hydrogen bond. Bond parameters, infrared vibrational spectroscopy and charge analysis indicate that the hydrogen bond is enhanced at the excited state (S1), favoring excited state intramolecular proton transfer (ESIPT). The mild energy barrier further evidences the occurrence of ESIPT. Combined with frontier molecular orbital (FMO) analysis, the fluorescence quenching of PBT was attributed to the photoinduced electron transfer (PET) mechanism and the fluorescence turn-on mechanism of the product was attributed to the ESIPT process of HBT-Enol1.

BackgroundThere are various cross-sectional studies that concluded that vitamin D is associated with blood pressure, but randomized controlled studies have not yielded consistent conclusions. Considering many limitations indeed, our study aimed to examine whether concentrations of 25(OH)D are inversely associated with blood pressure in people without a previous diagnosis of hypertension.MethodWe analyzed data from the 2005–2018 National Health and Nutrition Examination Survey. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by applying multivariable logistic regression models. The dose–response relationship was assessed by means of restricted cubic spline regression, and stratification analyses were employed to test the consistency between the subgroups.ResultsOf 17,467 participants aged ≥ 20 years without a previous diagnosis of hypertension, 4,769 had higher blood pressure. Compared with individuals whose 25(OH)D levels were in the bottom quartile (

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

BackgroundChronic schizophrenia is significantly influenced by negative symptoms, with several known contributors to secondary negative symptoms. However, the impact of these factors and negative symptoms on social functioning warrants further exploration.MethodsWe assessed the clinical symptoms, antipsychotic adverse reactions, and social functioning of 283 hospitalized patients with chronic schizophrenia using various standardized interviews and scales. We conducted multiple regression and mediation analyses to elucidate the impact of secondary factors on negative symptoms, and the relationship among these “secondary factors,” negative symptoms, and social functioning.ResultsOur findings identified depressive symptoms, extrapyramidal symptoms, and positive symptoms as significant contributors to secondary negative symptoms. We found that negative symptoms play a notable mediating role in the effect of depressive and positive symptoms on social functioning. However, the relationship between positive symptoms, negative symptoms, and social functioning proved to be intricate.ConclusionOur findings propose that negative symptoms act as pivotal mediators in the correlation between “secondary factors” (including the depressive symptoms and positive symptoms) and social functioning. The treatment of chronic schizophrenia necessitates focusing on key factors such as depressive and positive symptoms, which might significantly contribute to the development of secondary negative symptoms. Further research is essential to clarify the complex relationship among positive symptoms, negative symptoms, and social functioning in schizophrenia.

Abstract Visualization of complex geological structures can technically support the accurate prediction and prevention of coal mine disasters. This study proposed a new digital reconstruction method to visualize geological structures based on establishing a virtual model in the digital twin system. This methodology for the digital reconstruction of complex fault structures comprises the following four aspects: (1) collection and fidelity of multi-physical field data of the fault structures, (2) the transmission of multi-physical field data, (3) the normalization of multi-physical field data, and (4) digital model reconstruction of fault structures. The key scientific issues of this methodology to be resolved include in situ fidelity of multi-field data and normalized programming of multi-source data. In addition, according to the geological background and conditions in Da’anshan coal mine in western Beijing, China, a preliminary attempt is made to reconstruct a digital model of fault and fold structures using the methodology proposed in this study.

Abstract Background The complex pathophysiology of epilepsy hampers the development of effective treatments. Although more than ten kinds of anti-seizures drugs (ASDs) have good effects on seizure control worldwide, about 30% of patients still display pharmacoresistance against ASDs. Neuroinflammation seems to play a crucial role in disease progression. G protein-coupled receptor 120 (GPR120) has been shown to negatively regulate inflammation and apoptosis. However, the role of GPR120 in epilepsy remains unclear. In this study, we aimed to explore the mechanism of GPR120 in epilepsy. Methods Male adult C57BL/6 mice were intracranially injected with kainic acid (KA) to establish epilepsy model, and the adeno associated virus (AAV) was administered intracranially at 3 weeks before KA injection. VX765 was administered by intragastric administration at 30 min before KA induced and an equal dose administrated twice a day (10 a.m. and 4 p.m.) lasting 7 days until the mice were killed. Western blot analysis, immunofluorescence staining, video monitoring of seizure, LFP recording, Nissl staining were performed. Results GPR120 was increased in both the hippocampus and cortex in the KA-induced model with temporal lobe epilepsy (TLE), and both were most highly expressed at 7 days after KA injection. Overexpression of GPR120 significantly alleviated epileptic activity, reduced neuronal death after status epilepticus (SE), downregulated the expression of IL-1β, IL-6, IL-18, and pyrin domain-containing protein 3 (NLRP3) inflammasome, whereas knockdown GPR120 showed the opposite effect. The effects of GPR120 knockdown were reversed by VX765 inhibition cysteinyl aspartate specific proteinase-1 (Caspase-1). Conclusion GPR120 modulates epileptic seizure activity and affects neuronal survival in KA-induced mouse model of temporal lobe epilepsy. Furthermore, GPR120 regulated neuroinflammation in epileptic animals through NLRP3/Caspase-1/IL-1β signaling pathway.

Abstract Background Critical trauma patients are particularly prone to increased mortality risk; hence, an accurate prediction of their conditions enables early identification of patients' mortality status. Thus, we aimed to develop and validate a real-time prediction model for physiological changes, organ dysfunctions and mortality risk in critical trauma patients. Methods We used Dynamic Bayesian Networks (DBNs) to model complicated relationships of physiological variables across time slices, accessing data of trauma patients from the Medical Information Mart for Intensive Care database (MIMIC-III) (n = 2915) and validated with patients' data from ICU admissions at the Changhai Hospital (ICU-CH) (n = 1909). The DBN model's evaluation included the predictive ability of physiological changes, organ dysfunctions and mortality risk. Results Our DBN model included two static variables (age and sex) and 18 dynamic physiological variables. The differences in ratios between the real values and the 24- and 48-h predicted values of most physiological variables were within 5% in the two datasets. The accuracy of our DBN model for predicting renal, hepatic, cardiovascular and hematologic dysfunctions was more than 0.8.The calculated area under the curve (AUC) from receiver operating characteristic curves and 95% confidence interval for predicting the 24- and 48-h mortality risk were 0.977 (0.967–0.988) and 0.958 (0.945–0.971) in the MIMIC-III and 0.967 (0.947–0.987) and 0.946 (0.925–0.967) in ICU-CH. Conclusions A DBN is a promising method for predicting medical temporal data such as trauma patients' mortality risk, demonstrated by high AUC scores and validation by a real-life ICU scenario; thus, our DBN prediction model can be used as a real-time tool to predict physiological changes, organ dysfunctions and mortality risk during ICU admissions.

Ginseng residue is a by-product stemming from the commercial extraction of ginsenosides. To assess the disparities between ginseng residue and ginseng tablet, we employed the ultra-high-performance liquid chromatography–quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) technique for sample analysis. The analyses revealed the presence of 39 compounds in both ginseng residue and ginseng tablets. Subsequently, the contents of total ginsenosides and total ginseng polysaccharides in the ginseng residue and ginseng tablet were determined. The results indicate that while only a small fraction of ginsenosides remained in the ginseng residue, a significant amount of polysaccharides was retained. Furthermore, our evaluation encompassed the antioxidant activities of both ginseng residue and ginseng tablets. Notably, ginseng residue exhibited robust antioxidant effects, thereby showcasing its potential for recycling as a functional food raw material.

BackgroundEpilepsy is a common neurological disease, and excessive mitophagy is considered as one of the major triggers of epilepsy. Mitophagy is a crucial pathway affecting reactive oxygen species. Phosphoglycerate mutase 5 (PGAM5) is a protein phosphatase present in mitochondria that regulates many biological processes including mitophagy and cell death. However, the mechanism of PGAM5 in epilepsy remains unclear. The purpose of the present study was to examine whether PGAM5 affects epilepsy through PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy.MethodsAfter the knockdown of PGAM5 expression by the adeno-associated virus, an epilepsy model was created by kainic acid. Next, the seizure activity was recorded by local field potentials before evaluating the level of mitochondrial autophagy marker proteins. Lastly, the ultrastructure of mitochondria, neuronal damage and oxidative stress levels were further observed.ResultsA higher PGAM5 level was found in epilepsy, and its cellular localization was in neurons. The interactions between PGAM5 and PINK1 in epilepsy were further found. After the knockdown of PGAM5, the level of PINK1 and light chain 3B was decreased and the expression of the translocase of the inner mitochondrial membrane 23 and translocase of the outer mitochondrial membrane 20 were both increased. Knockdown of PGAM5 also resulted in reduced neuronal damage, decreased malondialdehyde levels, decreased reactive oxygen species production and increased superoxide dismutase activity. In addition, the duration of spontaneous seizure-like events (SLEs), the number of SLEs and the time spent in SLEs were all reduced in the epilepsy model after inhibition of PGAM5 expression.ConclusionInhibition of PGAM5 expression reduces seizures via inhibiting PINK1-mediated mitophagy.

The precise segmentation of the optic cup (OC) and the optic disc (OD) is important for glaucoma screening. In recent years, medical image segmentation based on convolutional neural networks (CNN) has achieved remarkable results. However, many traditional CNN methods do not consider the cross-domain problem, i.e., generalization on datasets of different domains. In this paper, we propose a novel unsupervised domain-adaptive segmentation architecture called CAE-BMAL. Firstly, we enhance the source domain with a convolutional autoencoder to improve the generalization ability of the model. Then, we introduce an adversarial learning-based boundary discrimination branch to reduce the impact of the complex environment during segmentation. Finally, we evaluate the proposed method on three datasets, Drishti-GS, RIM-ONE-r3, and REFUGE. The experimental evaluations outperform most state-of-the-art methods in accuracy and generalization. We further evaluate the cup-to-disk ratio performance in OD and OC segmentation, which indicates the effectiveness of glaucoma discrimination.

Objective: Therapy for hepatocellular carcinoma (HCC) is a major challenge, and targeted therapies provide only a modest benefit in terms of overall survival. Treatment with antibodies to programmed cell death protein 1 (PD-1)/PD-L1 can restore the functions of tumor-infiltrating T cells in HCC and has shown clinical efficacy in 20% of patients with advanced HCC. Novel approaches are urgently needed to treat HCC and to augment the efficacy of immunotherapy. Methods: Tumor-bearing mice were treated with Agrocybe aegerita galectin (AAGL) alone or in combination with anti-PD-1, and the tumor sizes and lifespans of mice were determined. Transcriptome analysis, cytokine analysis, flow cytometry analysis of the number and proportion of immune cell subsets in the liver and spleen, and molecular and cellular analyses of tumors were used to define the underlying mechanisms. Results: AAGL significantly inhibited the growth of liver tumors in a dose-dependent manner. Furthermore, AAGL increased the expression of multiple cytokines and chemokines in tumor-bearing mouse livers; this effect was associated with the activation and migration of T cells and macrophages, in agreement with the in vitro results. Importantly, the aggregation of T cells and macrophages induced by AAGL in tumor-bearing mouse livers clearly enhanced the response to PD-1 blockade immunotherapy. Conclusions: The results showed that AAGL induced the activation and migration of lymphocytes to the liver, and that the combination of AAGL and anti-PD-1 may be a promising strategy for HCC treatment.

Abstract Background The role of postoperative radiotherapy (PORT) in cardiovascular-pulmonary disease mortality in patients with stage IIIA-N2 resected non-small cell lung cancer (NSCLC) remains uncertain. The purpose of this population-based analysis was to explore the effect of PORT on cardiovascular-pulmonary disease mortality in these patients. Methods Patients aged ≥ 18 years with stage IIIA-N2 resected NSCLC were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 and were grouped according to the use of PORT. Propensity score matching (PSM) was used to account for differences in baseline characteristics between the Non-PORT and PORT groups. The cumulative risk for cardiovascular-pulmonary disease death was estimated using the cumulative incidence curve. Competing risk regression was used to run univariate and multivariate analyses to evaluate risk factors. Results A total of 3981 patients were included in the study population. Among them, 1446 patients received PORT, and 2535 did not. A total of 1380 patients remained in each group after PSM, and the baseline characteristics were not significantly different between the two groups. The cumulative incidence of cardiovascular-pulmonary mortality was 10.93% in the Non-PORT group compared with 9.85% in the PORT group. There was no significant difference in the cumulative risk between the two groups (HR 1.07, 95% CI 0.77–1.48, p = 0.703). Multivariate analysis indicated that PORT had no significant impact on increased risk, with an HR of 1.18 (p = 0.377). Conclusions No significant differences between the PORT and Non-PORT groups were found in cardiovascular-pulmonary-specific modalities in this study. Further studies are required to validate these results. This study highlights the importance of long-term surveillance for NSCLC patients.

Lung cancer is the most common cause of cancer-related deaths worldwide. More efficient treatments are desperately needed. For decades, the success of platinum-based anticancer drugs has promoted the exploration of metal-based agents. Four ruthenium-based complexes have also entered clinical trials as candidates of anticancer metallodrugs. However, systemic toxicity, severe side effects and drug-resistance impeded their applications and efficacy. Stimuli-responsiveness of Pt- and Ru-based complexes provide a great chance to weaken the side effects and strengthen the clinical efficacy in drug design. This review provides an overview on the stimuli-responsive Pt- and Ru-based metallic anticancer drugs for lung cancer. They are categorized as endo-stimuli-responsive, exo-stimuli-responsive, and dual-stimuli-responsive prodrugs based on the nature of stimuli. We describe various representative examples of structure, response mechanism, and potential medical applications in lung cancer. In the end, we discuss the future opportunities and challenges in this field.

Graph burning was introduced to simulate the spreading of news/information/rumors in social networks. The symmetric undirected graph is considered here. That is, vertex u can spread the information to vertex v, and symmetrically vertex v can also spread information to vertex u. When it is modeled as a graph burning process, a vertex can be set on fire directly or burned by its neighbor. Thus, the task is to find the minimum sequence of vertices chosen as sources of fire to burn the entire graph. This problem has been proved to be NP-hard. In this paper, from a new perspective, we introduce a generalized model called the Independent Cascade Graph Burning model, where a vertex v can be burned by one of its burning neighbors u only if the influence that u gives to v is larger than a given threshold β≥0. We determine the graph burning number with this new Independent Cascade Graph Burning model for several graphs and operation graphs and also discuss its upper and lower bounds.

Measuring the carrying capacity of water resources and identifying obstacle factors are critical prerequisites for the rational allocation of regional water resources and the high-quality development of economic society. This study took Longnan City, a typical city in northwest China with abundant water resources but an underdeveloped economy, as the research object. Based on the DPSR (Driving–Pressure–State–Response), an evaluation indicator system was constructed. TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution) and an obstacle model were used to calculate the water resource carrying capacity and main obstacle factors of Longnan City from 2009 to 2019. The results showed that the carrying capacity of water resources in Longnan City had steadily improved, and the comprehensive closeness had increased from 0.44 (2009) to 0.60 (2019). From the perspective of the ruler layer, the carrying capacity of the driving force system increased from 0.05 in 2009 to 1.00 in 2019. The capacity of the state system increased during the change, with the highest value (0.85) appearing in 2013 and the lowest value appearing in 2016. All subsystems, except the pressure system, had a load-carrying capacity of 0.60 or more in 2019. The utilization of unconventional water resources, the proportion of eco-environmental water use, the volume of wastewater discharge, and the per capita urban daily water consumption are the primary factors affecting the water resource carrying capacity of Longnan City. Developing unconventional water sources, improving sewage treatment technology, promoting efficient water-saving technology, and strengthening environmental protection is the key to improving the water resources carrying capacity of Longnan City. This research provides the basis for enhancing the carrying capacity of water resources and sustainable urban development in Longnan City and other cities in China and water scarcity cities in other countries.

The prevalence of diabetes is rapidly increasing worldwide and can lead to a range of severe health complications that have the potential to be life-threatening. Patients need to monitor and control blood glucose levels as it has no cure. The development of non-invasive techniques for the measurement of blood glucose based on photoacoustic spectroscopy (PAS) has advanced tremendously in the last couple of years. Among them, PAS in the mid-infrared (MIR) region shows great promise as it shows the distinct fingerprint region for glucose. However, two problems are generally encountered when it is applied to monitor real samples for in vivo measurements in this MIR spectral range: (i) low penetration depth of MIR light into the human skin, and (ii) the effect of other interfering components in blood, which affects the selectivity of the detection system. This review paper systematically describes the basics of PAS in the MIR region, along with recent developments, technical challenges, and data analysis strategies, and proposes improvements for the detection sensitivity of glucose concentration in human bodies. It also highlights the recent trends of incorporating machine learning (ML) to enhance the detection sensitivity of the overall system. With further optimization of the experimental setup and incorporation of ML, this PAS in the MIR spectral region could be a viable solution for the non-invasive measurement of blood glucose in the near future.

BackgroundThe high prevalence of Internet gaming disorder among children and adolescents and its severe psychological, health, and social consequences have become a public emergency. A high efficiency and cost-effective early recognition method are urgently needed.ObjectiveWe aim to develop and internally validate a nomogram model for predicting Internet gaming disorder (IGD) risk in Chinese adolescents and children.MethodsThrough an online survey, 780 children and adolescents aged 7–18 years who participated in the survey from June to August 2021 were selected. The least absolute shrinkage and selection operator regression model was used to filter the factors. Multivariate logistic regression analysis was used to establish the prediction model and generate nomograms and a website calculator. The area under the receiver operating characteristic curve, calibration plot, and decision curve analysis were used to evaluate the model's discrimination, calibration, and clinical utility. Bootstrapping validation was used to verify the model internally.ResultsMale sex and experience of game consumption were the two most important predictors. Both models exhibited good discrimination, with an area under the curve >0.80. The calibration plots were both close to the diagonal line (45°). Decision curve analyses revealed that two nomograms were clinically useful when the threshold probability for the intervention was set to 5–75%.ConclusionTwo prediction models appear to be reliable tools for Internet gaming disorder screening in children and adolescents, which can also help clinicians to personalize treatment plans. Moreover, from the standpoint of simplification and cost, Model 2 appears to be a better alternative.

ObjectiveTo investigate the effects of sport stacking on the overall cognition and brain function in patients with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI).MethodsA single-blind randomized controlled design was performed using sport stacking for 30 min, 5 days/week for 12 weeks. Forty-eight subjects with mild AD or MCI were randomly divided into the sport stacking group (T-mAD = 12, T-MCI = 12) and the active control group (C-mAD = 11, C-MCI = 13). Auditory Verbal Learning Test (AVLT), Alzheimer's Disease Cooperative Study–Activities of Daily Living scale (ADCS-ADL), Geriatric Depression Scale (GDS-30), and Pittsburgh Sleep Quality Index (PSQI) were performed, the level of amyloid β-protein-40 (Aβ-40), Aβ-42, brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1(IGF-1), tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and soluble trigger receptor expressed on myeloid cells 2 (sTREM2) in plasma were tested, and brain functional connectivity in resting state and activation under finger movement task were analyzed by functional near-infrared spectroscopy (fNIRS).ResultsThirty-nine patients completed the trial. After 4 weeks, we found a significant increase in AVLT score in T-MCI (6.36 ± 5.08 vs. −1.11 ± 4.23, p = 0.004), and T-mAD group (4.60 ± 4.77 vs. −0.11 ± 2.89, p = 0.039). After 12 weeks, there was a significantly improved in AVLT (9.64 ± 4.90 vs. −0.33 ± 6.10, p = 0.002) and ADCS-ADL (3.36 ± 3.59 vs. −1.89 ± 2.71, p = 0.003) in T-MCI. There was a significant improvement in AVLT (5.30 ± 5.42 vs. 0.44 ± 2.40) in T-mAD (p < 0.05). Plasma levels of BDNF were upregulated in both T-MCI and T-mAD, and IGF-1 increased in T-MCI (P < 0.05) compared to the control groups. The functional connectivity in MCI patients between DLPFC.R and SCA.R, SMA.L, and SCA.R was decreased. In contrast, in mAD patients, the brain regional function connection was increased between DLPFC.R and Broca's.L. The activation of channel 36 located in the left primary somatosensory cortex was significantly increased after 12-week training, which was correlated with the improved AVLT and the increase of BDNF.ConclusionOur findings suggested that sport stacking is effective for patients with MCI and mild AD, possibly through increasing the expression of neuroprotective growth factors and enhancing neural plasticity to improve neurocognitive performance.Clinical Trial Registrationhttps://www.ClinicalTrials.gov, ChiCTR.org.cn, identifier: ChiCTR-2100045980.

In this paper, a fast parameter estimation algorithm for near-field non-circular signals is proposed, which is based on symmetric, uniform, and linear array, that decouple the near-field steering vector via non-circularity and symmetry. Then, the position parameters are estimated based upon polynomial rooting technique instead of traditional spectral search. After fixing the array structure, the parameters for estimation equation are ascertained. Then the values of position parameters are obtained by solving the polynomial equations; consequently, computational difficulty is alleviated effectively. In addition, the Degree-Of-Freedom (DOF) is increased by utilizing the non-circularity characteristics of the impinging sources. It can be seen from the performance analysis and computer simulation experiments that the proposed algorithm can resolve more near-field non-circular signals and can improve parameter estimation performance, which is closer to the Cramer–Rao Bound (CRB) estimation.

Abstract Background Working memory deficit is one of the most critical complex cognitive impairments in schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy, but not still unsatisfactory. Intermittent theta burst stimulation (iTBS), which has recently been used in clinical practice, may have faster and stronger effects comparing the traditional model (10-Hz high-frequency rTMS). A large number of studies have showed that rTMS, especially iTBS, can enhance the neural plasticity of the brain, and cognitive training can improve the cognitive function of schizophrenia. Is there any facilitation effect of iTBS add on cognitive training (such as working memory training, WMT) on cognitive function enhancement in schizophrenia is still unknown. Methods/design The proposed study is designed of a double-center, double-blinded, randomized controlled trial that will include 200 schizophrenia patients between 18 and 45 years of age. The patients will be randomized to four groups, i.e., the study group (iTBS+WMT), WMS control group (iTBS+ Simple Response Training (SRT)), iTBS control group (sham iTBS+WMT), and placebo control (sham iTBS+SRT). The patients will receive 3 min 20 s of real or sham stimulation, followed by a short 1–2-min rest and 40 min of WMT training or SRT immediately. Neuropsychological and clinical symptom assessments, with functional and structural MRI, will be performed on baseline, post-treatment, and 3- and 6-month follow-up periods. The primary outcome is cognitive function measured by the MATRICS Consensus Cognitive Battery (MCCB). The secondary outcomes are changes in neuroplasticity, as measured by MRI and other behavioral assessments. Discussion The aim of our study is to explore the facilitation effects of iTBS added on WMT in improving cognitive function of schizophrenia. That means, patients with schizophrenia will benefit more in cognitive function improvement from the combination training mode of “preheating (iTBS stimulation changes the neural activity of working memory-related brain regions) and ironning (working memory training).” And the long-term effects of this combined training model will be assessed at a 6-month follow-up period. In case of a significant improvement of working memory with a prolonged effect, the iTBS combined with WMT protocol could be considered as a first-line clinical protocol in schizophrenia treatment. More broadly, the potential for increased universality and efficiency of rTMS with the iTBS model to enhance the neural plasticity of the brain should have a more positive effect on cognitive function in schizophrenia. Trial registration chictr.org.cn ChiCTR1900023405 . Registered on 25 May 2019

Alumina–based refractory is widely used as lining material of rotary hearth furnace (RHF) in the direct reduction process. However, corrosion of refractory by the burden is a crucial problem which affects the RHF production. In this study, a sessile drop technique was used to investigate the wetting and corrosion behavior of Al2O3 substrate against SiO2–MgO–FeO–CaO–Al2O3 slag, whose composition was determined according to the slag obtained from smelting nickel laterite in the RHF process. The experimental results showed that the slags with basicity ((MgO + CaO)/SiO2) of 0.43 and 0.63 had a low apparent contact angle of approximately 25° and 30°, respectively. It indicated the slag samples could wet well on the Al2O3 substrate. The spreading of slag on the substrate was mainly ascribed to the decrease of surface tension at the initial stage. As the wetting process proceeded, Al2O3 dissolved into the slag forming an interfacial layer which gradually covered the substrate surface under the droplet and inhibited further dissolution of Al2O3. Good wettability and the dissolution of Al2O3 are two main factors that caused the corrosion of substrate. Separating the burden from the Al2O3 substrate was restrained after cooling, which would possibly bring severe sticking problems between the burden and alumina refractories. Keywords: Corrosion behavior, Wetting, Al2O3 substrate, Apparent contact angle, Slag.

Leptin involved in the regulation of dopaminergic neurons of the central nervous system may confirm the hypothesis of neurodevelopment in schizophrenic patients. However, specific genetic mechanisms are undefined. Therefore, we aimed to explore the regulation of DNA methylation of leptin promoters and mRNA expression in patients with schizophrenia. A cross-sectional study enrolled 40 patients and 40 healthy controls from the Beijing Huilongguan Hospital in China. The leptin methylation levels and mRNA expression were examined by highly sensitive mass spectrometry based on the MassARRAY System and real-time quantitative polymerase chain reaction (qPCR). The Positive and Negative Symptoms Scale (PANSS) was applied to estimate the clinical symptoms of patients. The LEP-CpG7 and CpG15 methylation in patients were significantly higher than in healthy controls (P < 0.05). The LEP-CpG11, CpG33.34.35, CpG36 methylation, and mRNA expression decreased significantly in patients compared with healthy controls (P < 0.05). After controlling gender, age, BMI, dose of antipsychotic and duration of illness, LEP-CpG7 methylation was negatively associated with PANSS positive symptoms subscore (r = −0.485, P = 0.005). In addition, LEP-mRNA expression was negatively correlated with PANSS total score (r = −0.385, P = 0.03) and positive subscale (r = −0.392, P = 0.026). Nevertheless, only the LEP-CpG7 methylation level remained negatively correlated to the PANSS positive subscore following multiple stepwise regression (β = −17.071, P = 0.037). These results suggest that leptin methylation and mRNA expression might contribute to the pathogenesis of schizophrenia. LEP-CpG7 methylation may be negatively associated with positive symptoms in patients with schizophrenia.

BackgroundThe follow-up study on neuropsychiatric changes after the lifting of coronavirus disease 2019 (COVID-19) quarantine in patients with cognitive impairment and their caregivers is still lacking, and relative information is needed to formulate more comprehensive healthcare prevention measures worldwide.AimsTo provide data on the changes in neuropsychiatric performance after the lifting of COVID-19 quarantine in patients with cognitive disorders and their caregivers.MethodsTwo surveys in Chongqing, China were conducted via telephonic interview with 531 patients and their caregivers. The baseline survey was performed from February 11 to 23, 2020, and the follow-up was from October 24 to November 9, 2020. The data of neuropsychiatric symptoms (NPSs), sleep, nutrition, and chronic diseases of patients, as well as the burden of care, anxiety, and depression of caregivers were evaluated.ResultsSignificant alleviation of NPSs after the lifting of COVID-19 quarantine was observed in patients with mild cognitive impairment (MCI) and dementia (both P < 0.05). Compared with baseline, the prevalence for NPSs of all participants dropped from 57.94 to 38.82%. Among NPS subdomains, apathy displayed the biggest decline at follow-up by 10.72%, followed by nighttime behavior by 8.65%. Mixed effect generalized estimation equation analysis showed significant amelioration in hallucination, depression, apathy, irritability, aberrant motor behavior, and nighttime behavior (all P < 0.05), with the most prominent changes in nighttime behavior and apathy. Among the patients with unsatisfactory control of chronic disease, the medication adherence rate dropped by approximately 30% after the lifting of quarantine. More importantly, around 13% increase of care burden was observed among the caregivers at follow-up, with both depression and anxiety rising by nearly 4%.ConclusionThe prolonged quarantine may exacerbate NPS in patients with memory disorders, while the care burden and mental stability of the caregivers after the pandemic should also be concerned.

Inspired by lots of applications like viral marketing of products and transmitting information in a network, ranking the spreading ability of nodes in the network has been widely studied. At present, the above problem is mostly studied on unsigned networks which only contain positive relationships (e.g., friend or trust) between users. In real-world networks, there usually exist both positive relationships and negative relationships (e.g., foe or distrust) between users. Based on this, we aim to find the influential spreaders in a signed network which meet the requirement of real scene. Moreover, when the spreading only aims to affect a specific group of nodes instead of all nodes, such as promoting cigarette, a new problem called localized targets spreading problem was come up with. Localized targets spreading problem has been studied on unsigned networks, but it is still open for signed networks. Thus, in this paper, we propose a new method, called local influence matrix (LIM) method, which aims to find the seed nodes set with maximum positive influence on a specific group of targets but with minimum influence on the non-target nodes in signed social networks. Simulation results show that our method performs well on real networks.

Background: Screening cognitive impairment is complex and not an appliance for early screening. Gait performance is strongly associated with cognitive impairment. Objectives: We aimed to explore gait indicators that could potentially screen cognitive dysfunction. Methods: A total of 235 subjects were recruited from June 2021 to June 2022. Four gait tasks, including the walking test, the timed “Up & Go” test (TUG), foot pressure balance (FPB), and one-legged standing with eyes closed test (OLS-EC), were performed. Moreover, in the walking test, participants were instructed to walk at their usual pace for the single-gait test. For the dual-task tests, participants walked at their usual pace while counting backward from 100 by 1s. The data were analyzed by the independent sample t-test, univariate and multivariate logistic regression, a linear trend, stratified and interaction analysis, the receiver operating characteristic (ROC) curve, and Pearson’s correlations. Results: Among the 235 participants, 81 (34.5%) were men and 154 (65.5%) were women. The mean age of participants was 72 ± 7.836 years. The control, MCI, mild AD, and severe AD groups had means of 71, 63, 71, and 30, respectively. After adjusting for age, sex, education, and body mass index (BMI), the dual-task toe-off-ground angle (TOA) (odds ratio (OR) = 0.911, 95% confidence interval (CI): 0.847, 0.979), single-task TOA (OR = 0.904, 95% CI: 0.841–0.971), and the timed “Up & Go” time (TUGT) (OR = 1.515, 95% CI: 1.243–1.846) were significantly associated with an increased risk of cognitive impairment. In addition, the trend test and stratified analysis results had no significant differences (all p > 0.05). The area under the roc curve (AUC) values of TOA in the dual-task and TUGT were 0.812 and 0.847, respectively. Additionally, TOA < 36.75° in the dual-task, TOA < 38.90° in the single-task, and TUGT > 9.83 seconds (s) are likely to indicate cognitive impairment. The cognitive assessment scale scores were significantly correlated with TOA (all r > 0.3, p < 0.001) and TUGT (all r > 0.2), respectively. Conclusion: TOA and TUGT scores are, in some circumstances, associated with cognitive impairment; therefore, they can be used as simple initial screenings to identify patients at risk.

Hydroxyapatite (HAp) as natural bone composition is highly osteoinductive. To harvest its osteoinductivity in bone regenerative engineering, the HAp-supporting hydrogel is urgently needed to minimize inhomogeneous aggregation of HAp. Here, we developed a HAp-stabilizing hydrogel based on peptide self-assembly. FmocFFRR was efficient for HAp-capping due to arginine-phosphate interaction. Tethering FmocFFRR on the HAp surface facilitated self-assembly to form FmocFFRR/HAp hybrid hydrogel, enabling stable dispersion of HAp in it. The molecular interactions between FmocFFRR and HAp particles were studied using microscopic and spectral characterizations. FmocFFRR/HAp hydrogel exhibited more enhanced mechanical properties than FmocFFRR. The biocompatibility of FmocFFRR/HAp hydrogel was verified using an ATP assay and live-dead staining assay. More importantly, FmocFFRR/HAp hydrogel not only enabled cell attachment on its surface, but also supported 3D cell culturing inside the hydrogel. Further, 3D culturing of MC3T3-E1 preosteoblasts inside FmocFFRR/HAp hydrogel significantly enhanced the expressions of osteogenesis markers, including alkaline phosphate (ALP), type-I collagen (COL1), and osteocalcin (OCN), demonstrating the promoting effect of osteoblast differentiation. These findings inspire its potential application in bone regenerative engineering.

Energy metabolism programming is a hallmark of cancer, and serves as a potent target of cancer therapy. Valproic acid (VPA), a broad Class I histone deacetylases (HDACs) inhibitor, has been used as a therapeutic agent for cancer. However, the detail mechanism about the potential role of VPA on the Warburg effect in breast cancer remains unclear. In this study, we highlight that VPA significantly attenuates the Warburg effect by decreasing the expression of pyruvate kinase M2 isoform (PKM2), leading to inhibited cell proliferation and reduced colony formation in breast cancer MCF-7 and MDA-MB-231 cells. Mechanistically, Warburg effect suppression triggered by VPA was mediated by inactivation of ERK1/2 phosphorylation through reduced HDAC1 expression, resulting in suppressing breast cancer growth. In summary, we uncover a novel mechanism of VPA in regulating the Warburg effect which is essential for developing the effective approach in breast cancer therapy.

As one of the most catastrophic dynamic hazards in underground coal mines, coal bursts have been a major safety concern around the world for many years. Although the coal bursts can occur in all cases of hard to soft coal if the right stress environment is created, the occurrence of coal bursts is closely related to the intrinsic mechanical properties of coal, such as the bursting proneness. In this study, a total of 27 coal specimens are selected in the open literature studies to obtain a group of fundament data, such as the mechanical parameters, four bursting proneness indices, stress-strain curves, and their geological conditions where the specimens were taken. The relationship between bursting proneness indices and the cohesion of the coal specimens is established by numerically fitting the stress-strain curves and theoretically deduction. By taking into account the coal heterogeneity, eight probability distribution functions are employed to assignment nonuniform cohesion to the numerical model and to study the influence of heterogeneity on bursting proneness. The results reveal that the coal cohesion, which combines the common advantages of the four proneness indices, can be used as bursting proneness index. In the research of heterogeneity, the coal bursting proneness will decrease with the increasing of cohesion scatter degree. The larger the cohesion scatter degree increase is, the lower the bursting proneness will be. The failure of coal specimen is more and more severe with the decrease of cohesion scatter degree. In addition, this paper provides two methods for assigning heterogeneous parameters to the numerical model. The contours of shear strain rate and plastic state between homogeneous and heterogeneous coal specimens are compared to study the failure types of coal specimens and to reveal the mechanism of violent failure in coal bursts.

The energy absorption support for impact resistance used in mining engineering is a prefolded energy absorption device. In this paper, through the quasistatic compression test and numerical simulation, the relationship between the deformation process, load-displacement curve, and plastic strain of the original prefolded energy absorbing device is studied. It is found that the concave side stiffness has an obvious effect on the first and second descending sections of the load-displacement curve, and the friction coefficient has an obvious effect on the second ascending section of that. In order to make the prefolded energy absorption device reach the state of constant resistance where the reaction load does not fluctuate or the fluctuation is small in the crushing process, the plastic strain is restrained by thickening the local area of the concave side, which effectively reduces the descending amplitude of the load-displacement curve. Whether continuoues deformation occurs is affected by the friction coefficient. Finally, a constant resistance energy absorption device is designed by thickening the concave side and reducing the friction coefficient. Compared with the original structure, the maximum bearing capacity of the constant resistance energy absorption device is basically unchanged, the average bearing capacity is increased by 29%, the total energy absorption is increased by 111%, the specific energy absorption is increased by 119%, and the load-displacement curve variance is reduced to 3% of the original structure.

Background: Studies have shown that patients with schizophrenia are at a high risk of developing insulin resistance (IR). We investigated the prevalence of IR and its clinical correlates in hospitalized Chinese patients with schizophrenia. Methods: A total of 193 patients with schizophrenia (113 males and 80 females) were recruited for the study. We collected their demographic and clinical data, including data on their plasma glucose and lipid levels. All patients were rated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess cognitive function, while Positive and Negative Syndrome Scale (PANSS) was used to assess psychopathology. The cut-off value for the homeostasis model assessment of insulin resistance (HOMA-IR) was set at 1.7. Results: The prevalence of IR was 37.82% (73/193). The IR patients had significantly higher waist-to-hip ratio and body mass index (BMI), and higher fasting plasma glucose (FPG), triglyceride (TG), and low density lipoprotein (LDL) levels compared to non-IR patients (all p

The pentose phosphate pathway (PPP) is a branch from glycolysis that begins from glucose-6-phosphate (G6P) and ends up with fructose-6-phosphate (F6P) and glyceraldehyde-3-phosphate (GADP). Its primary physiological significance is to provide nicotinamide adenine dinucleotide phosphate (NADPH) and nucleotides for vital activities such as reactive oxygen species (ROS) defense and DNA synthesis. Glucose-6-phosphate dehydrogenase (G6PD) is a housekeeping protein with 514 amino acids that is also the rate-limiting enzyme of PPP, catalyzing G6P into 6-phosphogluconolactone (6PGL) and producing the first NADPH of this pathway. Increasing evidence indicates that G6PD is upregulated in diverse cancers, and this dysfunction influences DNA synthesis, DNA repair, cell cycle regulation and redox homeostasis, which provides advantageous conditions for cancer cell growth, epithelial-mesenchymal transition (EMT), invasion, metastasis and chemoresistance. Thus, targeting G6PD by inhibitors has been shown as a promising strategy in treating cancer and reversing chemotherapeutic resistance. In this review, we will summarize the existing knowledge concerning G6PD and discuss its role, regulation and inhibitors in cancer development and chemotherapy resistance.

OBJECTIVE: To identify whether the combination of pre-treatment radiological and clinical factors can predict the overall survival (OS) in patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiation and sequential S-1 (a prodrug of 5-FU combined with two modulators) therapy with improved accuracy compared with that of established clinical and radiologic risk models. METHODS: Patients admitted with LAPC underwent diffusion weighted imaging (DWI) scan at 3.0-T (b = 600 s/mm2). The mean signal intensity (SIb = 600) of region-of-interest (ROI) was measured. The Log-rank test was done for tumor location, biliary stent, S-1, and other treatments and the Cox regression analysis was done to identify independent prognostic factors for OS. Prediction error curves (PEC) were used to assess potential errors in prediction of survival. The accuracy of prediction was evaluated by Integrated Brier Score (IBS) and C index. RESULTS: 41 patients were included in this study. The median OS was 11.7 months (2.8-23.23 months). The 1-year OS was 46%. Multivariate analysis showed that pre-treatment SIb = 600 value and administration of S-1 were independent predictors for OS. The performance of pre-treatment SIb = 600 and S-1 treatment in combination was better than that of SIb = 600 or S-1 treatment alone. CONCLUSION: The combination of pre-treatment SIb = 600 and S-1 treatment could predict the OS in patients with LAPC undergoing SBRT and sequential S-1 therapy with improved accuracy compared with that of established clinical and radiologic risk models.

Abstract Background To identify the value of the pre-treatment apparent diffusion coefficient (ADC) derived from diffusion weighted imaging (DWI) in predicting the overall survival (OS) for locally advanced pancreatic cancer (LAPC) treated with Cyberknife followed by sequential S-1 chemotherapy. Methods Patients with UICC-T4 LAPC who underwent DWI scan (3.0 Tesla) using two b-values (0, 600 s/mm2) in our center between 2015 and 2017 were enrolled. Mean ADCs of the region of interest (ROI) drawn manually on DWI imaging were measured by two independent radiologists at an interval of 1 month. The association between prognostic factors and patient survival was determined using univariate and multivariate analyses. Cox proportional hazard model was used for identification of independent prognostic factors of OS. Results A total of 41 patients (28 males and 13 females) were included, with a median age of 64 years, with 5 patients (3 males and 2 females) lost. The median OS was 11.7 months (range 2.8–23.3) among all 41 patients. The 1-year OS was 46% (95% CI 30%–62%). Univariate and multivariate analyses indicated that pre-treatment ADC value (HR 10.652, P = 0.0093), age (HR 0.952, P = 0.015), CA19–9 (HR 1.001, P = 0.0022) and administration of S-1 (HR 0.128, P = 0.0002) were independent predicting factors of OS. Conclusion The mean ADC value of the primary tumor on pre-treatment DWI imaging was an independent predictor of OS in patients with LAPC receiving Cyberknife followed by sequential S-1.

Based on a dual-size shift invariance sparse linear array, this paper presents a novel algorithm for the localization of mixed far-field and near-field sources. First, by constructing a cumulant matrix with only direction-of-arrival (DOA) information, the proposed algorithm decouples the DOA estimation from the range estimation. The cumulant-domain quarter-wavelength invariance yields unambiguous estimates of DOAs, which are then used as coarse references to disambiguate the phase ambiguities in fine estimates induced from the larger spatial invariance. Then, based on the estimated DOAs, another cumulant matrix is derived and decoupled to generate unambiguous and cyclically ambiguous estimates of range parameter. According to the coarse range estimation, the types of sources can be identified and the unambiguous fine range estimates of NF sources are obtained after disambiguation. Compared with some existing algorithms, the proposed algorithm enjoys extended array aperture and higher estimation accuracy. Simulation results are given to validate the performance of the proposed algorithm.

In this work, retinal penetration of fluorescein was achieved in vitro by covalent attachment of taurine to fluorescein, yielding the F–Tau conjugate. Nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) were used to confirm the successful synthesis of F–Tau. The cellular uptake of F–Tau in adult retinal pigment epithelial cells (ARPE-19) and human retinal microvascular endothelial cells (hRMECs) was visualized via confocal scanning microscopy. The results indicated an improvement of solubility and a reduction of logP of F–Tau compared with fluorescein. As compared with fluorescein, F–Tau showed little toxicity, and was retained longer by cells in uptake experiments. F–Tau also displayed higher transepithelial permeabilities than fluorescein in ARPE-19 and hRMECs monolayer cells (P

The authors have retracted this article because Figs. 2, 3 and 4, as well as parts of the text have been previously published [1]. This article is therefore redundant. Yu Zhang, Denghui Liu, Jiaqi Song, Huojun Zhang and Jianping Lu agree to this retraction. Xiaofei Zhu has not responded to any correspondence from the publisher about this retraction.