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Iron-anchored nitrogen/doped carbon single-atom nanozymes (Fe-N/C), which possess homogeneous active sites and adjustable catalytic environment, represent an exemplary model for investigating the structure-function relationship and catalytic activity. However, the development of pyrolysis-free synthesis technique for Fe-N/C with adjustable enzyme-mimicking activity still presents a significant challenge. Herein, Fe-N/C anchored three carrier morphologies were created via a pyrolysis-free approach by covalent organic polymers. The peroxidase-like activity of these Fe-N/C nanozymes was regulated via the pores of the anchored carrier, resulting in varying electron transfer efficiency due to disparities in contact efficacy between substrates and catalytic sites within diverse microenvironments. Additionally, a colorimetric sensor array for identifying antioxidants was developed: (1) the Fe-N/C catalytically oxidized two substrates TMB and ABTS, respectively; (2) the development of a colorimetric sensor array utilizing oxTMB and oxABTS as sensing channels enabled accurate discrimination of antioxidants such as ascorbic acid (AsA), glutathione (GSH), cysteine (Cys), gallic acid (GA), and caffeic acid (CA). Subsequently, the sensor array underwent rigorous testing to validate its performance, including assessment of antioxidant mixtures and individual antioxidants at varying concentrations, as well as target antioxidants and interfering substances. In general, the present study offered valuable insights into the active origin and rational design of nanozyme materials, and highlighting their potential applications in food analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Attosecond chronoscopy enables the exploration of correlated electron dynamics in real time. One key observable of attosecond physics is the determination of "time zero" of photoionization, the time delay with which the wave packet of the ionized electron departs from the ionic core. This observable has become accessible by experimental advances in attosecond streaking and reconstruction of attosecond beating by interference of two-photon transitions (RABBIT) techniques. In this Letter, we explore photoionization time delays by strong extreme ultraviolet fields beyond the linear-response limit. We identify novel signatures in time delays signifying strong coupling between atoms and light fields and the light-field dressing of the ion. As a prototypical case, we study the interelectronic coherence and entanglement in helium driven by a strong extreme ultraviolet field. By the numerical solution of the time-dependent Schrödinger equation in its full dimensionality, we show that the time delay of the photoionized electron allows one to monitor the ultrafast variations of coherence dynamics and entanglement in real time.

We propose a directionality orthogonal double-slit interferometry to control photoelectron dynamics in energy- and angle-resolved fashion. The two orthogonal components of polarization-skewed (PS) laser pulse, in which the total polarization vector rotates as time evolves, can be regarded as the double-slit in the time domain. Our results demonstrate that the peak splitting and shift in photoelectron momentum distributions can be controlled by the relative optical phase between two components of the PS pulse. Based on the analysis from time-dependent perturbation theory, the behaviors of photoelectrons in angle-integrated energy spectra between 1s and 2p initial states can be attributed to the significant discrepancy of an interference pattern, which is reflected in energy- and angle-dependent phase difference of transition amplitudes from two orthogonal components of PS pulse. In addition, the influences of time delay and intensity ratio between two subpulses on this coherent control are also discussed. Our work provides a feasible protocol for controlling photoelectron dynamics in energy and angular resolutions and enriches the potential applications of the double-slit interference in the time domain.

Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events. Recent studies have emphasized the role of MAMs in regulating mitochondrial quality control. This review will delve into the molecular mechanisms underlying the imbalance in mitochondrial quality control in AD and provide a comprehensive overview of the role of MAMs in regulating mitochondrial quality control., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Single-atom nanozymes have garnered significant attention due to their exceptional atom utilization and ability to establish well-defined structure-activity relationships. However, conventional pyrolytic synthesis methods pose challenges such as high energy consumption and random local environments at the active sites, while achieving non-pyrolytic synthesis of single-atom nanozymes remains a formidable technical hurdle. The present study focuses on the synthesis of laccase-like iron-based single-atom nanozymes (Fe-SAzymes) using a non-pyrolysis method facilitated by microwave irradiation. Under low iron loading conditions, Fe-SAzymes exhibited significantly enhanced laccase activity (12.1 U/mg), surpassing that of laccase by 24-fold. Moreover, Fe-SAzymes demonstrated efficient catalytic oxidation of epinephrine (EP), enabling its colorimetric detection. Owing to the remarkable laccase activity of Fe-SAzymes, the conventional nanozymes EP detection time was reduced from 60 min to 20 min, with an impressive low detection limit as low as 2.95 μM. In addition, an ultra-sensitive fluorescence method for EP detection was developed using the internal filter effect of EP oxidation products and CDs combined with carbon dots probe. The detection limit of fluorescence method was only 0.39 μM. Therefore, an visual, fast, and highly sensitive dual-mode EP detection strategy has great potential in the clinical diagnostic industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To establish and verify a diagnostic model for distinguishing multiple sclerosis (MS) from other neurological diseases with similar symptoms by usingcerebrospinal fluid oligoclonal band (CSF-OCB)combined with IgG intrathecal synthesis indicators and biochemical markers. Methods: Multiple sclerosis (MS) patients admitted to the Neurology Department of Beijing Tiantan Hospital affiliated with Capital Medical University from January 2014 to December 2022 were selected as the case group, while patients with similar neurological symptoms were selected as the control group. Using the case-control study design, a retrospective analysis was conducted on the detection of age, gender, oligoclonal bands in cerebrospinal fluid, IgG intrathecal synthesis indicators and biochemical indicators for all study subjects. The differential diagnosis model was determined by the multiple logistic regression analysis, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of the differential diagnosis model for neurological diseases with similar symptoms to MS and other conditions. Results: This study included 167 patients in the case group and 335 patients in the control group, of which 128 patients in the case group and 265 patients in the control group were used to construct the model, and 39 patients in the case group and 70 patients in the control group were used for model validation. The differential diagnostic model constructed by a multivariate logistic regression model was Y=0.871×CSF-OCB-0.051×CSFprotein-0.231×CSFchloride+1.183×gender-0.036×LDH+35.770. The model showed that the area under the curve, sensitivity and specificity were respectively 0.916, 87.3% and 87.6%. The Delong test results showed that the diagnostic efficacy of the model was significantly different from OCB, IgG intrathecal synthesis indicators, and OCB combined with IgG intrathecal synthesis indicators ( P <0.05). The new model validation showed that the actual diagnostic consistency rate for the MS group was 84.6%, while the actual diagnostic consistency rate for the control group was 90.0%. Conclusion: This study combines OCB, IgG intrathecal synthesis indicators, and biochemical indicators to establish a diagnostic prediction model for neurological diseases with similar clinical symptoms in MS. This model may have good differential diagnostic value and can better assist clinical diagnosis in the early stages of disease progression in MS patients.

Single-molecule immunoassay technology represents an ultrasensitive immunoassay method that enables the resolution and detection of individual biomolecules at the nanoscale. This article highlights various representative techniques and clinical applications of single-molecule immunoassay technology, while also discussing the current challenges and future development directions. Through multiple optimizations at both the technical and commercial levels, single-molecule immunoassay technology exhibits unique advantages in real-time detection, disease diagnosis and treatment, and medical research. This technology is poised to contribute to the advancement of precision medicine by integrating individualized detection methods into clinical practice.

Objective: To investigate the risk factors for lymph node metastasis in patients with early gastric cancer and establish a model for prediction of risk. Methods: The cohort of this retrospective observational study comprised 1096 patients who had undergone radical gastric cancer surgery combined with standard D1 lymphadenectomy and been diagnosed with early gastric cancer by postoperative pathology in Zhongshan Hospital affiliated with Fudan University from January 2016 to July 2022. The patients were allocated to groups with and without lymph node metastases. Clinicopathological characteristics were compared between the two groups and multi-factor logistic regression analysis used to identify independent risk factors for lymph node metastasis in patients with early gastric cancer. Indications for endoscopic resection in the Japanese Gastric Cancer Association (JGCA) guideline were also incorporated into construction of the model. The patient cohort was divided into training and validation sets in a 6:4 ratio. The identified independent risk factors were used to construct a predictive nomogram. Receiver operating characteristic curves were plotted separately and the difference between them in predictive efficacy was compared using the area under the curve (AUC). Results: A total of 1,096 patients with early gastric cancer were included, with 750 males and 346 females. Their average age was (61.4±10.9) years old, and the mean tumor diameter was (23.8±11.4) mm. Among them, 188 patients (17.2%) had positive lymph node metastasis, with 109 cases in N1 stage, 42 cases in N2 stage, and 37 cases in N3 stage. Additionally, 462 patients were in T1a stage, while 634 patients were in T1b stage. Univariate analysis showed that tumor diameter, location, Lauren classification, gross morphology, histological type, intravascular invasion, ulceration, differentiation type and tumor T stage were associated with lymph node metastasis after radical gastrectomy for early gastric cancer (all P <0.05). Multifactorial analysis showed that the presence of intravascular invasion (OR=14.822, 95%CI: 9.323-23.572, P <0.001), undifferentiated type (OR=3.095, 95%CI: 1.649-5.811, P <0.001), tumor T1b (OR=1.798, 95%CI: 1.053-3.079, P =0.032), and tumor diameter ≥2 cm (OR=1.229, 95%CI: 1.031-1.469, P =0.022) were independent risk factors for lymph node metastasis. The baseline data of the training set and validation set were consistent in terms of balance (all P >0.05). We used the above variables to establish a predictive nomogram for lymph node metastasis in patients with early gastric cancer. The AUC values obtained from the validation of the model in the training and validation sets were 0.880 (95%CI: 0.849-0.911) and 0.881 (95%CI: 0.841-0.921), respectively, and were significantly better than the predictive efficacy based on the JGCA guideline (AUC=0.777, 95%CI: 0.746-0.809, P <0.001). Conclusions: Patients with early gastric cancer and intravascular invasion, undifferentiated tumors, tumor T1b, and diameter ≥2 cm are at higher risk of postoperative lymph node metastasis than other patients. The predictive model developed in this study more accurately predicts lymph node metastasis in patients with early gastric cancer than previously proposed methods.

Background: Psoriasis is a long-lasting, inflammatory, continuous illness caused through T cells and characterized mainly by abnormal growth and division of keratinocytes. Currently, corticosteroids are the preferred option. However, prolonged use of traditional topical medication can lead to adverse reactions and relapse, presenting a significant therapeutic obstacle. Improved alternative treatment options are urgently required. Formononetin (FMN) is a representative component of isoflavones in Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.]. It possesses properties that reduce inflammation, combat oxidation, inhibit tumor growth, and mimic estrogen. Although FMN has been shown to ameliorate skin barrier devastation via regulating keratinocyte apoptosis and proliferation, there are no reports of its effectiveness in treating psoriasis., Objective: Through transcriptomics clues and experimental investigation, we aimed to elucidate the fundamental mechanisms underlying FMN's action on psoriasis., Materials and Methods: Cell viability was examined using CCK8 assay in this study. The results of analysis of differentially expressed genes (DEGs) between FMN-treated HaCaT cells and normal HaCaT cells using RNA-sequencing (RNA-seq) were presented on volcano plots and heatmap. Enrichment analysis was conducted on DEGs using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), and results were validated through RT-qPCR verification. After 12 days of FMN treatment in psoriasis mouse model, we gauged the PASI score and epidermis thickness. A variety of techniques were used to assess FMN's effectiveness on inhibiting inflammation and proliferation related to psoriasis, including RT-qPCR, HE staining, western blot, and immunohistochemistry (IHC)., Results: The findings indicated that FMN could suppress the growth of HaCaT cells using CCK8 assay (with IC 50 = 40.64 uM) and 20 uM FMN could reduce the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to the greatest extent. FMN-treated HaCaT cells exhibited 985 up-regulated and 855 down-regulated DEGs compared to normal HaCaT cells. GO analysis revealed that DEGs were linked to interferon (IFN) signaling pathway. Furthermore, FMN improved pathological features, which encompassed decreased erythema, scale, and thickness scores of skin lesions in psoriasis mouse model. In vivo experiments confirmed that FMN down-regulated expression of IFN-α, IFN-β, IFN-γ, decreased secretion of TNF-α and IL-17 inflammatory factors, inhibited expression of IFN-related chemokines included Cxcl9, Cxcl10, Cxcl11 and Cxcr3 and reduced expression of transcription factors p-STAT1, p-STAT3 and IFN regulatory factor 1 (IRF1) in the imiquimod (IMQ) group., Conclusions: In summary, these results suggested that FMN played an anti-inflammatory and anti-proliferative role in alleviating psoriasis by inhibiting IFN signaling pathway, and FMN could be used as a potential therapeutic agent., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The Shexiang Zhuifeng Zhitong Ointment with the effects of dispelling wind, removing dampness, dissipating cold, and relieving pain is used for treating arthralgia, muscular pain, and sprain pain caused by cold-dampness obstruction. To evaluate the efficacy and safety of Shexiang Zhuifeng Zhitong Ointment in relieving the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction), a randomized, double-blind, parallel controlled, multicenter clinical trial was conducted. The stratified randomization method was used to randomize the 240 subjects into a treatment group and a control group in a ratio of 1∶1. In each group, 60 patients received external application for 12 h and the other 60 patients received external application for 6 h. The treatment group received external application of Shexiang Zhuifeng Zhitong Ointment, while the control group received external application of Shexiang Zhuifeng Ointment. The treatment lasted for 21 days in both groups. Follow-up was conducted on days 7, 14, and 21 of treatment. The results based on the full analysis set were as follows.(1)In visual analog scale(VAS) score, the mean difference in the VAS score between baseline and 12 h post-treatment was 3.02 in the treatment group and 2.31 in the control group, with a significant difference(P&lt;0.05). The mean difference in the VAS score between baseline and 6 h post-treatment was 3.19 in the treatment group and 2.48 in the control group, with a significant difference(P&lt;0.05).(2)Response rate in terms of VAS score, after treatment for 12 h, the response rate was 93.22% in the treatment group and 73.33% in the control group, with a significant difference(P&lt;0.05). After treatment for 6 h, theresponse rate in the treatment group was 88.33%, which was higher than that(63.33%) in the control group(P&lt;0.05).The results showed that Shexiang Zhuifeng Zhitong Ointment applied for 12 and 6 h effectively relieved the knee joint pain of patients with knee osteoarthritis due to cold-dampness obstruction, as demonstrated by the reduced VAS score, Western Ontario and McMaster Universities Arthritis Index(WOMAC), stiffness, and joint function score. Moreover, Shexiang Zhuifeng Zhitong Ointment outperformed the positive control Shexiang Zhuifeng Ointment in terms of reducing the VAS score, demonstrating a definitetherapeutic effect on the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction).In addition, Shexiang Zhuifeng Zhitong Ointment did not cause other adverse reactions except for mild allergic reactions, which were common in the external application of traditional Chinese medicine plasters on the skin, inseveral patients.Neither other adverse reactions nor abnormalities of liver and kidney functions and electrocardiogram were observed. This ointment had high safety and could be popularized in clinical application.

Background: Atopic eczema (AE) is a common atopic inflammatory skin disease affecting 2.1-4.9% of the population in different countries. Pruritus, one of the most burdensome symptoms, is often underestimated for the problems it can cause, creating a vicious loop of itching, scratching, and lichenification. Therefore, further research into practical and safe treatments that relieve itchy symptoms and enhance skin protection is key to overcoming AE. Acupuncture, with or without electrical stimulation, is one of the most commonly used therapeutic measures to treat AE. This trial aimed to objectively evaluate the efficacy and safety of the electroacupuncture (EA) antipruritic technique in AE pruritus and obtain high-level clinical evidence for the popularization and application of EA for AE., Methods and Analysis: This multicenter, single-blinded, randomized controlled trial is planned to transpire from April 15, 2023, to June 30, 2025. We will recruit 132 participants with AE (44 per group). Participants will be assigned randomly to three equal-sized groups: EA, sham electroacupuncture, and sham acupuncture. Treatment will be administered three times a week during the 2-week intervention phase. The primary outcome measure is the Visual Analog Scale, with a numeric rating scale to evaluate pruritus. Secondary outcome measures include the Eczema Area and Severity Index and Dermatology Life Quality Index. Other outcome measures include physical examination, serum IgE, and safety evaluation. The number, nature, and severity of adverse events will be carefully recorded., Trial Registration: ClinicalTrials.gov, 22Y11922200. Registered 3 September 2022, https://register.clinicaltrials.gov., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Liang, Yang, Cai, Wang, Sun, Chen, Wang, Jiang and Li.)

In response to injury, vascular smooth muscle cells (VSMCs) of the arterial wall dedifferentiate into a proliferative and migratory phenotype, leading to intimal hyperplasia. The ERK1/2 pathway participates in cellular proliferation and migration, while dual-specificity phosphatase 6 (DUSP6, also named MKP3) can dephosphorylate activated ERK1/2. We showed that DUSP6 was expressed in low baseline levels in normal arteries; however, arterial injury significantly increased DUSP6 levels in the vessel wall. Compared with wild-type mice, Dusp6 -deficient mice had smaller neointima. In vitro, IL-1β induced DUSP6 expression and increased VSMC proliferation and migration. Lack of DUSP6 reduced IL-1β-induced VSMC proliferation and migration. DUSP6 deficiency did not affect IL-1β-stimulated ERK1/2 activation. Instead, ERK1/2 inhibitor U0126 prevented DUSP6 induction by IL-1β, indicating that ERK1/2 functions upstream of DUSP6 to regulate DUSP6 expression in VSMCs rather than downstream as a DUSP6 substrate. IL-1β decreased the levels of cell cycle inhibitor p27 and cell-cell adhesion molecule N-cadherin in VSMCs, whereas lack of DUSP6 maintained their high levels, revealing novel functions of DUSP6 in regulating these two molecules. Taken together, our results indicate that lack of DUSP6 attenuated neointima formation following arterial injury by reducing VSMC proliferation and migration, which were likely mediated via maintaining p27 and N-cadherin levels.

Ferroelectric (FE) materials, including BiFeO 3 , P(VDF-TrFE), and CuInP 2 S 6 , are a type of dielectric material with a unique, spontaneous electric polarization that can be reversed by applying an external electric field. The combination of FE and low-dimensional materials produces synergies, sparking significant research interest in solar cells, photodetectors (PDs), nonvolatile memory, and so on. The fundamental aspects of FE materials, including the origin of FE polarization, extrinsic FE materials, and FE polarization quantification are first discussed. Next, the state-of-the-art of FE-based optoelectronic devices is focused. How FE materials affect the energy band of channel materials and how device structures influence PD performance are also summarized. Finally, the future directions of this rapidly growing field are discussed., (© 2023 Wiley-VCH GmbH.)

Objective: To establish a quantitative immunoassay method based on stable element labeling and inductively coupled plasma mass spectrometry (ICP-MS) for the detection of serum amyloid A (SAA) and evaluate its performance. Methods: An immunoassay system based on sandwich method was established with magnetic bead as carrier and holmium (Ho) as element tags. The binding ratio of hydrophilic streptavidin magnetic beads and biotinylated antibody, the amount of elemental antibody, and the reaction time were optimized to choose the optimal reaction conditions. According to the documents of Clinical and Laboratory Standards Institute (CLSI), the analytical performance was evaluated, including the limit of blank (LOB), linearity, accuracy, specificity, imprecision and interference test. Finally, 82 SAA plasma samples were collected after the turbidimetric inhibition immunoassay, and the newly established method was used for detection. Moreover, the detection results of the two methods were analyzed by Pearson correlation analysis. Results: The optimal binding ratio of hydrophilic streptavidin and biotinylated antibody was 1∶0.15, the amount of Ho-labeled antibody was 3 μl and the incubation time of the two reaction steps was 40 min and 30 min, respectively. The LOB was 0.6 ng/ml. The linearity was good within the range of 0-1 200 μg/L ( R 2 =0.998 9, P <0.001). The inter-batch precision of high-value samples and low-value samples was 9.42% and 7.95%, respectively, and the intra-batch precision was 14.56% and 13.56%, respectively. The recovery was 96.01%-104.76%. The cross-reaction rates with procalcitonin (PCT) and C-reactive protein (CRP) were 0.45% and 0.015%, respectively. When the concentration of triglyceride≤35.5 mg/L, bilirubin≤0.52 mg/L and hemoglobin≤2.4 g/L, the interference bias was less than 10%. The results of 82 SAA plasma samples were 12.65 (4.45, 59.03) mg/L by ICP-MS immunoassay and 18.23 (9.33, 68.72) mg/L by turbidimetric inhibition immunoassay, respectively. The newly established system was well correlated with turbidimetric inhibition immunoassay ( R 2 =0.983, P <0.001). Conclusion: The quantitative immunoassay for SAA with Ho as marker established in this study has high precision, good accuracy, high specificity, and wide linear range, which can meet the clinical testing requirements.

Animals learn trajectories to rewards in both spatial, navigational contexts and relational, non-navigational contexts. Synchronous reactivation of hippocampal activity is thought to be critical for recall and evaluation of trajectories for learning. Do hippocampal representations differentially contribute to experience-dependent learning of trajectories across spatial and relational contexts? In this study, we trained mice to navigate to a hidden target in a physical arena or manipulate a joystick to a virtual target to collect delayed rewards. In a navigational context, calcium imaging in freely moving mice revealed that synchronous CA1 reactivation was retrospective and important for evaluation of prior navigational trajectories. In a non-navigational context, reactivation was prospective and important for initiation of joystick trajectories, even in the same animals trained in both contexts. Adaptation of trajectories to a new target was well-explained by a common learning algorithm in which hippocampal activity makes dissociable contributions to reinforcement learning computations depending upon spatial context., (© 2022. The Author(s).)

Background: Time in range (TIR) is one of the basic indicators to assess glycemic control. In this study, the TIR of DPN patients was used as the observation index to further evaluate the correlation between TIR and DPN, so as to provide new ideas for preventing the occurrence of DPN and delaying its disease progression., Methods: A total of 120 patients with T2DM (T2DM) who were hospitalized in the Endocrinology Department of our hospital from October 2018 to February 2020 were included and divided into two groups according to whether the nerve conduction velocity was normal or not, the diabetic peripheral neuropathy group (DPN) and the other groups. No diabetic peripheral neuropathy group (NDPN). According to the corresponding inclusion and exclusion criteria, the baseline data were recorded, and test indicators such as homocysteine and blood lipids were collected at the same time, and TIR was collected by a transient blood glucose meter. To explore the relationship between TIR and other indicators and peripheral neuropathy in T2DM., Results: A total of 120 T2DM patients participated in the study, including 82 in the DPN group and 38 in the NDPN group. There were no statistically significant differences in basic indicators such as age, height, and weight between the two groups. Glycated hemoglobin (HbA1c) and homocysteine (Hcy) in DPN group were higher than those in NDPN group, while TIR and HDL-C were lower than those in NDPN group ( P < 0.05). Logistic regression analysis showed that HbA1c and Hcy were risk factors for DPN, and TIR and HDL-C were protective factors for DPN, with statistical significance ( P < 0.05). The prediction results of TIR, Hcy, HDL-C, and HbA1c on diabetic peripheral neuropathy were analyzed by ROC curve, and the prediction results of the five variables were all statistically significant ( P < 0.05) and have a better prediction effect., Conclusion: (1) The results of TIR level suggest that the longer the blood sugar is in the good control range, the more beneficial it is to reduce the occurrence of DPN. (2) TIR and HDL-C are protective factors for DPN, and HbA1c and Hcy are risk factors for DPN. (3) The results of ROC curve analysis showed that TIR, Hcy, HbA1c, and HDL-C had a good predictive effect on the occurrence of DPN., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Ming Li et al.)

Background: Abdominal aortic aneurysm (AAA) is a relatively common and often fatal condition. A major histopathological hallmark of AAA is the severe degeneration of aortic media with loss of vascular smooth muscle cells (VSMCs), which are the main source of extracellular matrix (ECM) proteins. VSMCs and ECM homeostasis are essential in maintaining structural integrity of the aorta. Cysteine-rich protein 2 (CRP2) is a VSMC-expressed protein; however, the role of CRP2 in AAA formation is unclear., Methods: To investigate the function of CRP2 in AAA formation, mice deficient in Apoe (Apoe -/- ) or both CRP2 (gene name Csrp2) and Apoe (Csrp2 -/- Apoe -/- ) were subjected to an angiotensin II (Ang II) infusion model of AAA formation. Aortas were harvested at different time points and histological analysis was performed. Primary VSMCs were generated from Apoe -/- and Csrp2 -/- Apoe -/- mouse aortas for in vitro mechanistic studies., Results: Loss of CRP2 attenuated Ang II-induced AAA incidence and severity, accompanied by preserved smooth muscle α-actin expression and reduced elastin degradation, matrix metalloproteinase 2 (MMP2) activity, deposition of collagen, particularly collagen III (Col III), aortic tensile strength, and blood pressure. CRP2 deficiency decreased the baseline MMP2 and Col III expression in VSMCs and mitigated Ang II-induced increases of MMP2 and Col III via blunting Erk1/2 signaling. Rescue experiments were performed by reintroducing CRP2 into Csrp2 -/- Apoe -/- VSMCs restored Ang II-induced Erk1/2 activation, MMP2 expression and activity, and Col III levels., Conclusions: Our results indicate that in response to Ang II stimulation, CRP2 deficiency maintains aortic VSMC density, ECM homeostasis, and structural integrity through Erk1/2-Col III and MMP2 axis and reduces AAA formation. Thus, targeting CRP2 provides a potential therapeutic strategy for AAA., (© 2022. The Author(s).)

An imposing task for a reinforcement learning agent in an uncertain environment is to expeditiously learn a policy or a sequence of actions, with which it can achieve the desired goal. In this article, we present an incremental model learning scheme to reconstruct the model of a stochastic environment. In the proposed learning scheme, we introduce a clustering algorithm to assimilate the model information and estimate the probability for each state transition. In addition, utilizing the reconstructed model, we present an experience replay strategy to create virtual interactive experiences by incorporating a balance between exploration and exploitation, which greatly accelerates learning and enables planning. Furthermore, we extend the proposed learning scheme for a multiagent framework to decrease the effort required for exploration and to reduce the learning time in a large environment. In this multiagent framework, we introduce a knowledge-sharing algorithm to share the reconstructed model information among the different agents, as needed, and develop a computationally efficient knowledge fusing mechanism to fuse the knowledge acquired using the agents' own experience with the knowledge received from its teammates. Finally, the simulation results with comparative analysis are provided to demonstrate the efficacy of the proposed methods in the complex learning tasks.

Background: Differentiating and counting various types of white blood cells (WBC) in bone marrow smears allows the detection of infection, anemia, and leukemia or analysis of a process of treatment. However, manually locating, identifying, and counting the different classes of WBC is time-consuming and fatiguing. Classification and counting accuracy depends on the capability and experience of operators., Results: This paper uses a deep learning method to count cells in color bone marrow microscopic images automatically. The proposed method uses a Faster RCNN and a Feature Pyramid Network to construct a system that deals with various illumination levels and accounts for color components' stability. The dataset of The Second Affiliated Hospital of Zhejiang University is used to train and test., Conclusions: The experiments test the effectiveness of the proposed white blood cell classification system using a total of 609 white blood cell images with a resolution of 2560 × 1920. The highest overall correct recognition rate could reach 98.8% accuracy. The experimental results show that the proposed system is comparable to some state-of-art systems. A user interface allows pathologists to operate the system easily., (© 2021. The Author(s).)

Development of transplantable engineered tissue has been hampered by lacking vascular network within the engineered tissue. Three-dimensional (3D) printing has emerged as a new technology with great potential in fabrication and customization of geometric microstructure. In this study, utilizing digital light processing system, we manufactured a recently designed novel 3D architecture scaffold with poly(glycerol sebacate) acrylate (PGSA). Vascular construct was subsequently generated by seeding stem cells within this scaffold. PGSA provided inductive substrate in terms of supporting three-germ layer differentiation of embryonic stem cells (ESCs) and also promoting ESCs-derived vascular progenitor cells (VPCs) differentiation into endothelial cells (ECs). Furthermore, the differentiation efficiency of VPCs into ECs on PGSA was much higher than that on collagen IV or fibronectin. The results from seeding VPCs in the rotating hexagonal PGSA scaffold suggest that this architectural framework is highly efficient for cell engraftment in 3D structures. After long-term suspension culture of the VPCs in scaffold under directed EC differentiation condition, VPC-differentiated ECs were populated in the scaffold and expressed EC markers. Transplantation of the vascular construct in mice resulted in formation of new vascular network and integration of the microvasculature within the scaffold into the existing vasculature of host tissue. Importantly, in a mouse model of wound healing, ECs from the transplanted vascular construct directly contributed to revascularization and enhanced blood perfusion at the injured site. Collectively, this transplantable vascular construct provides an innovative alternative therapeutic strategy for vascular tissue engineering., (Creative Commons Attribution license.)

A compact G e 11.5 A s 24 S e 64.5 chalcogenide microring resonator is fabricated with an intrinsic quality factor of 3.0×10 5 in the telecom band. By taking advantage of the strong nonlinearity and cavity enhancement, highly efficient wavelength conversion via four-wave mixing is demonstrated using a microring resonator. Conversion efficiency of -33.7 d B is obtained by using an ultra-low pump power of 63.8 µW. This work shows that G e 11.5 A s 24 S e 64.5 chalcogenide microring devices are promising for quantum photonics.

Photocurable polymers have become increasingly important for their quick prototyping and high accuracy when used in three dimensional (3D) printing. However, some of the common photocurable polymers are known to be brittle, cytotoxic and present low impact resistance, all of which limit their applications in medicine. In this study, thermal treatment was studied for its effect and potential applications on the mechanical properties, degradability and biocompatibility of glycerol-based photocurable polymers, poly(glycerol sebacate) acrylate (PGSA). In addition to the slight increase in elongation at break, a two-fold increase in both Young's modulus and ultimate tensile strength were also observed after thermal treatment for the production of thermally treated PGSA (tPGSA). Moreover, the degradation rate of tPGSA significantly decreased due to the increase in crosslinking density in thermal treatment. The significant increase in cell viability and metabolic activity on both flat films and 3D-printed scaffolds via digital light processing-additive manufacturing (DLP-AM) demonstrated high in vitro biocompatibility of tPGSA. The histological studies and immune staining indicated that tPGSA elicited minimum immune responses. In addition, while many scaffolds suffer from instability through sterilization processes, it was proven that once glycerol-based polymers have been treated thermally, the influence of autoclaving the scaffolds were minimized. Therefore, thermal treatment is considered an effective method for the overall enhancement and stabilization of photocurable glycerol-based polymeric scaffolds in medicine-related applications.

Nanophotonic modes within rectangular cross sections are typically considered to have transverse rectangular field profiles. In this work, we show that, despite the rectangular cross section of most integrated waveguides and microring resonators, there exists considerable hybridization of transverse rectangular modes and transverse circular modes. These hybridized modes can be advantageous in nonlinear wave mixing processes. We use third-harmonic generation as an example to confirm that such a hybridized mode is advantageous in combining reasonable mode overlap and waveguide coupling to a fundamental mode in a silicon nitride microring. Our work illuminates the potential of using transverse circular modes in nanophotonic applications.

The potential roles of solar ultraviolet radiation (UVR) as an environmental risk factor in inducing atopic dermatitis (AD) have not been well quantified. To determine the short-term associations between UVR and AD outpatient visits, we obtained daily outpatient visits of AD in Shanghai Skin Disease Hospital from 2013 to 2018. Data of hourly ground UVR were collected. We applied overdispersed generalized additive model to explore its associations. We found that daily exposure to UVR-A rather than UVR-B was positively associated with AD outpatient visits. The visits increased on the present day (lag 0 days) and decreased appreciably with longer lags and became insignificant at lag 4 days. For 10 w/m 2 increase in daytime mean and noontime mean exposure to overall UVR and UVR-A from lag 0 to 6 days, the cumulative relative risk of AD was 1.12/1.13 and 1.08/1.08, respectively. Stronger effects of UVR exposure on AD occurred in patients aged 0-7 and > 45 years and in the cold seasons. This study contributed to the few epidemiological evidences that acute exposure to solar UVR may elevate the risks of AD.

Background: Posterior atlantoaxial fixation with screw rod forms an approximate "II" shape or "H" increasing transverse link for better stability. In order to improve stability and in consideration of difficult placement of transverse connecting rod, possibility of inadequate bone graft, some scholars have preliminarily researched biomechanics of a novel crossed rod as an approximate "X" configuration of screw rod., Purpose: The aim of this study was to evaluate and compare the biomechanics of the crossed and parallel rod configurations in the screw rod system for posterior atlantoaxial fixation on a cadaveric model., Methods: Six fresh cervical specimens were used to complete the range of motion (ROM) testing by applying pure moments of ± 2.0 nm. Following intact state and under destabilization testing, screws were implanted. The specimens were then tested in the following sequence: Group BLS + PR (C2 bilateral laminar screws + parallel rod), Group BLS + CR (C2 bilateral laminar screws + crossed rod), LPRLS + PR (C2 left pedicle screw and right laminar screw + parallel rod), LPRLS + CR (C2 left pedicle screw and right laminar screw + crossed rod), BPS + PR (C2 bilateral pedicle screws + parallel rod) and BPS + CR (C2 bilateral pedicle screws + crossed rod). The ROM of the C1-2 segments was measured in flexion-extension, lateral bending and axial rotation. Six surgical constructs were compared between the groups and with intact condition, respectively., Results: The six fixed modes significantly increased stability compared with both the intact and destabilization group in flexion-extension, lateral bending and axial rotation (p < .05). In extension, BPS + CR and BLS + CR showed greater stability than BLS + PR (p < .05). During flexion, the six fixation methods showed no statistical significance (p > .05). In left lateral bending, stability of the other five screw rod fixation techniques significantly increased when compared with BLS + PR (p < .05). In the right lateral bending direction, the stability of BLS + PR was worse than that of BPS + CR and BPS + PR (p < .05). In the left axial rotation, stability of BLS + CR, LPRLS + CR and BPS + CR was greater than that of BLS + PR, LPRLS + PR and BPS + PR (p < .05). In the right axial rotation, the stability of BPS + CR and BLS + CR was greater than that of BLS + PR (p < .05)., Conclusion: The six investigated fixation methods provide sufficient biomechanical stability. The crossed rod configuration can further enhance the axial rotation stability of the screw rod system, which consists of C1 bilateral pedicle and C2 pedicle, or C2 lamina screws. The crossed rod can also improve the stability of the screw rod system made up of C1 bilateral pedicle and C2 lamina screws in lateral bending and extension. The crossed rod configuration is reliable and provides superior stability for clinical application.

Abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA) are serious arterial diseases in the aorta and brain, respectively. AAA and IA are associated with old age in males and females, respectively, and if rupture occurs, they carry high morbidity and mortality. Aneurysmal subarachnoid hemorrhage (SAH) due to IA rupture has a high rate of complication and fatality. Despite these severe clinical outcomes, preventing or treating these devastating diseases remains an unmet medical need. Inflammation and oxidative stress are shared pathologies of these vascular diseases. Therefore, therapeutic strategies have focused on reducing inflammation and reactive oxygen species levels. Interestingly, in response to cellular stress, the inducible heme oxygenase-1 (HO-1) is highly upregulated and protects against tissue injury. HO-1 degrades the prooxidant heme and generates molecules with antioxidative and anti-inflammatory properties, resulting in decreased oxidative stress and inflammation. Therefore, increasing HO-1 activity is an attractive option for therapy. Several HO-1 inducers have been identified and tested in animal models for preventing or alleviating AAA, IA, and SAH. However, clinical trials have shown conflicting results. Further research and the development of highly selective HO-1 regulators may be needed to prevent the initiation and progression of AAA, IA, or SAH.

Conventional computer-aided detection systems (CADs) for colonoscopic images utilize shape, texture, or temporal information to detect polyps, so they have limited sensitivity and specificity. This study proposes a method to extract possible polyp features automatically using convolutional neural networks (CNNs). The objective of this work aims at building up a light-weight dual encoder-decoder model structure for polyp detection in colonoscopy Images. This proposed model, though with a relatively shallow structure, is expected to have the capability of a similar performance to the methods with much deeper structures. The proposed CAD model consists of two sequential encoder-decoder networks that consist of several CNN layers and full connection layers. The front end of the model is a hetero-associator (also known as hetero-encoder) that uses backpropagation learning to generate a set of reliably corrupted labeled images with a certain degree of similarity to a ground truth image, which eliminates the need for a large amount of training data that is usually required for medical images tasks. This dual CNN architecture generates a set of noisy images that are similar to the labeled data to train its counterpart, the auto-associator (also known as auto-encoder), in order to increase the successor's discriminative power in classification. The auto-encoder is also equipped with CNNs to simultaneously capture the features of the labeled images that contain noise. The proposed method uses features that are learned from open medical datasets and the dataset of Zhejiang University (ZJU), which contains around one thousand images. The performance of the proposed architecture is compared with a state-of-the-art detection model in terms of the metrics of the Jaccard index, the DICE similarity score, and two other geometric measures. The improvements in the performance of the proposed model are attributed to the effective reduction in false positives in the auto-encoder and the generation of noisy candidate images by the hetero-encoder., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In December 2019, an outbreak of pneumonia of unknown origin was reported in Wuhan, Hubei Province, China. Pneumonia cases were epidemiologically linked to the Huanan Seafood Wholesale Market. Inoculation of respiratory samples into human airway epithelial cells, Vero E6 and Huh7 cell lines, led to the isolation of a novel respiratory virus whose genome analysis showed it to be a novel coronavirus related to SARS-CoV, and therefore named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus belonging to the subgenus Sarbecovirus . The global spread of SARS-CoV-2 and the thousands of deaths caused by coronavirus disease (COVID-19) led the World Health Organization to declare a pandemic on 12 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. In this review, we provide information regarding the epidemiology, serological and molecular diagnosis, origin of SARS-CoV-2 and its ability to infect human cells, and safety issues. Then we focus on the available therapies to fight COVID-19, the development of vaccines, the role of artificial intelligence in the management of the pandemic and limiting the spread of the virus, the impact of the COVID-19 epidemic on our lifestyle, and preparation for a possible second wave.

Background: Following the sufficient studies of the effects of skin barrier impairment and heightened neural reaction on sensitive skin (SS), many scholars have paid great attention to the roles of superficial microvasculature in SS., Methods: By questionnaire survey, lactic acid sting test, and capsaicin test, eligible subjects were classified as normal skin, only lactic acid sting test positive (LASTP), only capsaicin test positive (CATP), and both positive (both LASTP and CATP). D-OCT was used to photograph images for evaluating the cutaneous vessels features each group., Results: Totally 137 subjects completed the study. Compared with LASTN group, the vascular vessels were closer to epidermis in LASTP group. Mesh and branching vessels were more popular in SS than normal skin. High blood vessel density was more prevalent in SS, while low density frequently presented in normal skin. The vascular depth had a closely negative correlation with face flushing and SSS, and vascular shapes had a good positive correlation with face flushing and SSB., Conclusions: Our study indicates that there is a significant difference in vascular depth, shape, and density between SS and normal skin which is valuable to explore SS pathologic mechanism and to further investigate cutaneous microvasculature functions in SS., (© 2019 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Double ionization of helium by a single intense (above 10^{18}  W/cm^{2}) linearly polarized extreme ultraviolet laser pulse is studied by numerically solving the full-dimensional time-dependent Schrödinger equation. For the laser intensities well beyond the perturbative limit, novel gridlike interference fringes are found in the correlated energy spectrum of the two photoelectrons. The interference can be traced to the multitude of two-electron wave packets emitted at different ionization times. A semianalytical model for the dressed two-photon double ionization is shown to qualitatively account for the interference patterns in the joint energy spectrum. Similar signatures of interferences between transient induced time-delayed ionization bursts are expected for other atomic and molecular multielectron systems.

We theoretically and experimentally investigate the photon momentum transfer in single-photon double ionization of helium at various large photon energies. We find that the forward shifts of the momenta along the light propagation of the two photoelectrons are roughly proportional to their fraction of the excess energy. The mean value of the forward momentum is about 8/5 of the electron energy divided by the speed of light. This holds for fast and slow electrons despite the fact that the energy sharing is highly asymmetric and the slow electron is known to be ejected by secondary processes of shake off and knockout rather than directly taking its energy from the photon. The biggest deviations from this rule are found for the region of equal energy sharing where the quasifree mechanism dominates double ionization.

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, particularly among older adults. Despite the advent of medical technology, restenosis is still an issue after interventional procedures. Tryptophan metabolite 5-methoxytryptophan (5-MTP) has recently been shown to protect against systemic inflammatory responses. This study aimed to investigate the function and mechanisms of 5-MTP in interventional procedure-induced restenosis. We found that after mouse femoral artery denudation with a guide wire, 5-MTP accelerated recovery of endothelium in the denuded area and reduced vascular leakage and intimal thickening. 5-MTP increased endothelial cell proliferation in the denuded arteries and rescued TNF-α-reduced endothelial cell proliferation and migration, likely via maintaining vascular endothelial growth factor receptor 2 activation. In contrast, 5-MTP preserved differentiated phenotype of medial vascular smooth muscle cells (VSMCs) and decreased VSMC proliferation and migration. Furthermore, 5-MTP maintained expression levels of critical transcription factors for VSMC marker gene expressions via attenuated activation of p38 MAPK and NFκB-p65. Our findings uncover a novel protective mechanism of 5-MTP in restenosis. In response to denudation injury, 5-MTP attenuates intimal hyperplasia via concerted but opposing actions on endothelial cells and VSMCs. Taken together, our results suggest that 5-MTP is a valuable therapeutic target for arterial injury-induced restenosis.

Optical imaging has become a powerful tool for studying brains in vivo. The opacity of adult brains makes microendoscopy, with an optical probe such as a gradient index (GRIN) lens embedded into brain tissue to provide optical relay, the method of choice for imaging neurons and neural activity in deeply buried brain structures. Incorporating a Bessel focus scanning module into two-photon fluorescence microendoscopy, we extended the excitation focus axially and improved its lateral resolution. Scanning the Bessel focus in 2D, we imaged volumes of neurons at high-throughput while resolving fine structures such as synaptic terminals. We applied this approach to the volumetric anatomical imaging of dendritic spines and axonal boutons in the mouse hippocampus, and functional imaging of GABAergic neurons in the mouse lateral hypothalamus in vivo., Competing Interests: GM, YL, SS, WJ, JD, YA No competing interests declared, RL, NJ The Bessel focus scanning intellectual property has been licensed to Thorlabs, Inc by HHMI, (© 2019, Meng et al.)

We study the ionization of atoms by very intense linearly polarized pulse with moderately high frequency by numerically solving the time-dependent Schrödinger equation (TDSE). In this regime, the photon energy exceeds the ionization potential allowing for one-photon ionization which is, however, strongly influenced by strong nonlinear photon-atom interactions. We find that the onset of atomic stabilization can be monitored by the appearance of a dynamic interference pattern in the photoelectron spectrum.

The occurrence and health risks of organotins (OTs) in the waterworks and source water in the Three Gorges Reservoir Region (TGRR), China were assessed in this study. Water samples were collected at four waterworks (A, B, C, and D) in March and July 2012 to analyze butyltins (BTs) and phenyltins (PTs) using a gas chromatography-mass spectrometry (GC-MS) system. Our results showed that both the waterworks and their nearby water sources were polluted by OTs, with PTs being the most dominant species. Monobutyltin (MBT), monophenyltin (MPT), diphenyltin (DPT), and triphenyltin (TPT) were detected in most of the analyzed water samples. The highest concentrations of OTs in influents, effluents, and source water in March were 52.81, 17.93, and 55.32 ng Sn L -1 , respectively. Furthermore, significant seasonal changes in OTs pollution were observed in all samples, showing pollution worse in spring compared with summer. The removal of OTs by the conventional treatment processes was not stable among the waterworks. The removal efficiency of OTs in July reached 100% at plant B, while that at plant C was only 38.8%. The source water and influents shared similar composition profiles, concentrations, and seasonal change of OTs, which indicated that OTs in the waterworks were derived from the source water. A health risk assessment indicated that the presence of OTs in the waterworks would not pose a significant health risk to the population, yet their presence should not be ignored.

Heme oxygenase (HO)-1 is an inducible stress response protein and well known to protect cells and tissues against injury. Despite its important function in cytoprotection against physiological stress, the role of HO-1 in embryonic stem cell (ESC) differentiation remains largely unknown. We showed previously that induced pluripotent stem (iPS) cells that lack HO-1 are more sensitive to oxidant stress-induced cell death and more prone to lose pluripotent markers upon LIF withdrawal. To elucidate the role of HO-1 in ESC differentiation and to rule out the controversy of potential gene flaws in iPS cells, we derived and established mouse HO-1 knockout ESC lines from HO-1 knockout blastocysts. Using wild type D3 and HO-1 knockout ESCs in the 3-dimensional embryoid body (EB) differentiation model, we showed that at an early time point during EB development, an absence of HO-1 led to enhanced ROS level, concomitant with increased expressions of master mesodermal regulator brachyury and endodermal marker GATA6. In addition, critical smooth muscle cell (SMC) transcription factor serum response factor and its coactivator myocardin were enhanced. Furthermore, HO-1 deficiency increased Smad2 in ESCs and EBs, revealing a role of HO-1 in controlling Smad2 level. Smad2 not only mediates mesendoderm differentiation of mouse ESCs but also SMC development. Collectively, loss of HO-1 resulted in higher level of mesodermal and SMC regulators, leading to accelerated and enhanced SMC marker SM α-actin expression. Our results reveal a previously unrecognized function of HO-1 in regulating SMC gene expressions during ESC-EB development. More importantly, our findings may provide a novel strategy in enhancing ESC differentiation toward SMC lineage., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

The gempylid fish genus Epinnula is reviewed and two species are recognized. The type species E. magistralis is considered restricted to the western Atlantic Ocean and a new species from the Pacific Ocean is described. The new species, Epinnula pacifica sp. nov., can be distinguished from E. magistralis by 17 or 18 dorsal-fin rays (vs. 15 or 16 in E. magistralis), 15 or 16 anal-fin rays (vs. 13 or 14), 247-268 total scales on lower lateral line (vs. 285-330), a deeper body, relatively high dorsal fin as reflected by the relatively long fin spines and rays, longer dorsal-fin and anal-fin bases, longer pectoral fin, and longer pelvic fin and pelvic spine.

High angular momentum partial waves are indispensable in the numerical calculations of the time-dependent Schrödinger equation (TDSE) for the interaction between atoms and strong long-wavelength laser pulses. In these cases, the widely-applied Lanczos propagator, used to solve the TDSE, requires an extremely small time step to be convergent. By splitting out the centrifugal potential from the whole Hamiltonian, we demonstrate that the stiffness of the TDSE can be reduced and a rather large time step is allowed for the present Split-Lanczos propagator. Compared with the ordinary Lanczos propagator, the efficiency of the propagation can be improved by more than 100 times for large angular momentum in present tests.

Objective: To investigate the characteristics of distribution and expression profiles of plasma miRNA in childhood acute lymphocytic leukemia (cALL) patients; the association between cALL incidence risk and plasma miRNA levels; the feasibility of plasma miRNA serving as cALL diagnostic biomarker. Methods: A total of 111 pairs of newly diagnosed cALL patients and patients with fractures were collected from Shenzhen Children's Hospital, China, between January 2015 and November 2016. Age and sex of the cases and controls were 1∶ 1 matched and LNA(TM) miRNA microarray was performed using 4 pairs of cALL and controls selected from the sample population. The expression level of miRNA was validated by real time quantitative PCR. Conditional logistic regression analysis was applied to evaluate the association between miRNA expression levels and the incidence risk of cALL. The receiver operating characteristic curve (ROC) and reclassification analysis were conducted to assess the feasibility of miRNAs serving as biomarkers for cALL. Results: A total of 204 differentially expressed miRNA were screened out and let-7f-5p, miR-5100, miR-25-3p and miR-3654 were selected for validation identified according to the inclusion criteria. The expression levels of let-7f-5p, miR-5100 and miR-25-3p in the cALL patients were significantly lower than those of the controls ( P <0.01). After adjusting for confounding factors, 3 miRNAs remained significantly associated with the risk of cALL ( OR and 95 %CI were 0.84 (0.76-0.92), 0.81 (0.73-0.90) and 0.81 (0.74-0.89), respectively. Results from both the ROC analysis and reclassification analysis showed that introduction of one or more miRNA to traditional risk factors improved the area under the curve ( P <0.05) and provided additional values to diagnosis ( P <0.01). Conclusion: The expression levels of let-7f-5p, miR-5100 and miR-25-3p were significantly associated with the incidence rate of cALL, and these miRNAs might serve as promising biomarkers for cALL.

Recent advance of lithium niobate microphotonic devices enables the exploration of intriguing nonlinear optical effects. We show complex nonlinear oscillation dynamics in high-Q lithium niobate microresonators that results from unique competition between the thermo-optic nonlinearity and the photorefractive effect, distinctive to other device systems and mechanisms ever reported. The observed phenomena are well described by our theory. This exploration helps understand the nonlinear optical behavior of high-Q lithium niobate microphotonic devices which would be crucial for future application of on-chip nonlinear lithium niobate photonics.

Background: Nowadays, the diagnosis for sensitive skin relies on subjective assessment or on the combination of subjective and objective evaluation. No quantitative evaluation is available. It could be expected that confocal microscopy imaging could be of interest to better define the condition., Methods: Total 166 healthy female subjects were recruited in this study. Firstly, all subjects completed the sensitive questionnaire. Then, the cutaneous structures were measured by the reflectance confocal microscopy (RCM) on the face and fossa cubitalia. The lactic acid sting test was conducted finally. According to the results of self-perception sensitive skin questionnaire and lactic acid stinging test to evaluate facial skin sensitivity the both positive subjects were regarded as sensitive skin group and both negative group as healthy control group., Result: The results of RCM indicating that the proportion of 'disarranged honeycomb pattern' and 'spongiform edema' in the sensitive group and healthy control group were statistically different (P < 0.05), respectively; The following report 'damaged dermal papilla rings' was not a distinctive pattern, with no significant statistical difference (P > 0.05). The epidermal thickness was 38.88 ± 6.81 μm, healthy control group was 40.31 ± 9.37 μm in, respectively, sensitive skin group and healthy control group, there was no significant statistical difference between the two groups (P > 0.05). The honeycomb structure depth of sensitive group was 20.57 ± 4.86 μm. It was for 23.27 ± 6.38 μm, healthy control group the difference being statistically different between the two groups (P < 0.05)., Conclusion: Based on the RCM results, 'epidermal honeycomb structure' and 'spongiform edema' may be used as new skin signs of RCM evaluation of sensitive skin effectively. Indeed, sensitive skin honeycomb structure depth was thinner compared with healthy control group. Such a specific pattern has good clinical and monitoring value for the further exploration. RCM could provide new data and patterns for the evaluation of sensitive skin., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We develop a chip-scale cavity optomechanical system in single-crystal lithium niobate that exhibits high optical quality factors and a large frequency-quality product as high as 3.6 × 10 12  Hz at room temperature and atmosphere. The excellent optical and mechanical properties together with the strong optomechanical coupling allow us to efficiently excite the coherent regenerative optomechanical oscillation operating at 375 MHz with a threshold power of 174 μW in the air. The demonstrated lithium niobate optomechanical device enables great potential for achieving electro-optic-mechanical hybrid systems for broad applications in sensing, metrology, and quantum physics.

Objective: This study aimed to investigate the association between exposure to environmental chemicals and the risk of childhood acute lymphocytic leukemia(cALL). Methods: A case-controlled study was conducted in Shenzhen Children's Hospital, China from January 2015 to January 2016. The cases were selected from the section of Hematology and Oncology, and the controls were selected from Orthopedics by 1∶2 matching of cases according to sex and age. A questionnaire including population data and chemical exposure characteristics was conducted on the children's parents, and urine and EDTA-blood were collected from the children. Then, we quantitatively measured the internal dose of formaldehyde(i.e., formaldehyde-human serum albumin)by enzyme-linked immunosorbent assay and the doses of metabolites benzene, toluene, and xylene(i.e., trans-muconic acid, hippuric acid, and methylhippuric acid)by high-performance liquid chromatography. Logistic regression models were used to analyze the relationships between exposure factors measured from children and their parents and cALL. Results: In the study, 71 cases(average age: 6.08±3.61 years), and 142 controls(average age: 5.91±3.57 years)were assessed; there were no differences in general demographics between two groups. The self-reported results showed that living in a home that had been painted in the past 10 years( OR= 4.39, 95% CI : 1.87-10.31), maternal chemical exposure during pregnancy( OR= 11.78, 95% CI : 1.65-83.88), paternal diesel or gasoline exposure( OR= 8.15, 95% CI : 2.68-24.83), paternal dye exposure( OR= 7.77, 95% CI : 1.52-39.67)and trash burning near the child's residence( OR= 6.08, 95% CI : 1.17-31.66)were associated with increased risk of cALL. The positive detection rates of only benzene metabolites were significantly higher in cases(40/44)than controls(81/111)(χ 2 =5.92, P= 0.021). The median formaldehyde and benzene concentrations in cases(32.120 pg/ml, 2.505 μg/gCr)were significantly higher than those in controls(18.705 pg/ml, 0.672 μg/gCr; Z values:-1.98 and-3.95, P values: 0.047 and<0.001, respectively). Multiple logistic regression analysis showed that benzene exposure( OR= 1.09, 95% CI : 1.00-1.19), home painting in the past 10 years( OR= 3.56, 95% CI : 1.20-10.53)and paternal diesel or gasoline exposure( OR= 3.75, 95% CI : 1.06-13.22)were associated with increased risk of cALL. Conclusion: A variety of environmental chemistry factors, such as benzene exposure, increase the risk of cALL, and further studies are warranted to explore their specific roles.

Label-free bio-sensing is a critical functionality underlying a variety of health- and security-related applications. Micro-/nano-photonic devices are well suited for this purpose and have emerged as promising platforms in recent years. Here we propose and demonstrate an approach that utilizes the optical spring effect in a high-Q coherent optomechanical oscillator to dramatically enhance the sensing resolution by orders of magnitude compared with conventional approaches, allowing us to detect single bovine serum albumin proteins with a molecular weight of 66 kDa at a signal-to-noise ratio of 16.8. The unique optical spring sensing approach opens up a distinctive avenue that not only enables biomolecule sensing and recognition at individual level, but is also of great promise for broad physical sensing applications that rely on sensitive detection of optical cavity resonance shift to probe external physical parameters.

We investigated the occurrence of cadmium (Cd), copper (Cu), chromium (Cr), nickel (Ni), lead (Pb), Znic (Zn), iron (Fe), manganese (Mn), and magnesium (Mg) in sediments, as well as in related soils and aquatic plants in the Liangtan River, a typical secondary anabranch of the Yangtze River in the Three Gorges Reservoir Region (TGRR) of China. We found that sediments accumulated more metals than soils and aquatic plants. Concentrations of the nine metals in sediments and soils followed the same sequence, while their concentrations in aquatic plants followed a different sequence. Potential adverse effects of contaminated sediments on benthic fauna were evaluated, and the results showed that the toxic effect on benthic organisms followed the sequence Zn > Ni > Cr > Cu > Cd > Pb. The potential ecological risk index analysis indicated that Cd in sediments had considerable ecological risk, whereas Cr, Cu, Zn, Ni, and Pb had low ecological risk. The potential ecological risk index (RI) of the heavy metals in sediments of the Liangtan River was 174.9, indicating moderate ecological risk. The transfer factor trend of metals for aquatic plants showed that Cd and Ni had the most and least accumulation, respectively. For Cu, Cd, Mg, Pb, and Cr, a significant positive correlation of the metal concentrations was observed between sediments and soils, but no correlations (excluding Cr) were detected between sediments and aquatic plants. Our study indicated that anthropogenic input may be the primary source of metal contamination in the Liangtan River, and that Zn and Cd pollution in the Liangtan River should be further explored.

To investigate the initial symptoms, treatment, prognosis, and 1-, 3-, and 5-year survival of patients with bronchopulmonary carcinoid, clinical and pathological data were collected retrospectively from 74 patients diagnosed with bronchopulmonary neuroendocrine tumors at the Cancer Hospital, Chinese Academy of Medical Science, from January 2004 through December 2009. The data collected included age, initial symptoms, primary tumor sites, pathological types, lymphatic metastasis, and distant metastasis. The Kaplan-Meier method was used for survival analysis and the log-rank test was used for univariate analysis of prognostic factors. A Cox proportional hazard regression model was used for multivariate analysis. The 74 patients included 56 men and 19 women, and their average age was 56.07 years. The most common initial symptom was cough (51.35%), and the major lesion site was the left upper lobe of the lung (38.84%). Of the 59 patients (79.73%) who underwent surgery, most (76.27%) received a pulmonary lobectomy. The patients' 1-, 3-, and 5-year survival rates were 92.7, 80.3, and 71.9%, respectively. Univariate analysis showed that both local lymphatic and distant metastases were prognostic factors (P<0.05), whereas multivariate analysis showed that the pathological type (typical carcinoid and atypical carcinoid) was an independent prognostic factor (P=0.006). These data indicate that cough is the major presenting symptom of patients with bronchopulmonary carcinoid and the left upper lobe of the lung is the most commonly involved site. Following treatment, mostly by pulmonary lobectomy, the 5-year survival rate is 71.9%. The pathological tumor type is an independent prognostic factor.

The ability to image neurons anywhere in the mammalian brain is a major goal of optical microscopy. Here we describe a minimally invasive microendoscopy system for studying the morphology and function of neurons at depth. Utilizing a guide cannula with an ultrathin wall, we demonstrated in vivo two-photon fluorescence imaging of deeply buried nuclei such as the striatum (2.5 mm depth), substantia nigra (4.4 mm depth) and lateral hypothalamus (5.0 mm depth) in mouse brain. We reported, for the first time, the observation of neuronal activity with subcellular resolution in the lateral hypothalamus and substantia nigra of head-fixed awake mice.

By using a model based on the second-order time-dependent perturbation theory, we show that the nonsequential two-photon double ionization of He can be understood in a virtual sequential picture: to excite the final double continuum state |k&#95;{1},k&#95;{2}⟩ by absorbing two photons from the ground state |1s^{2},^{1}S&#95;{0}⟩, the single continuum states |1s,k&#95;{1}⟩ and |1s,k&#95;{2}⟩ serve as the dominant intermediate states. This virtual sequential picture is verified by the perfect agreement of the total ionization cross section, respectively, calculated by this model and by the sophisticated numerical solution to the full-dimensional time-dependent Schrödinger equation. This model, without the consideration of the electron correlation in the final double continuum state, works well for a wide range of laser parameters extending from the nonsequential to the sequential regime. The present Letter demonstrates that the electron correlation in the final double continuum state is not important in evaluating the total cross section, while it is indispensable for an accurate computation of a triply differential cross section. In addition, the virtual sequential picture bridges the sequential and nonsequential two-photon double ionization and reveals connections and distinctions between them.