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We obtained Peripheral blood mononuclear cells (PBMCs) from a peripheral blood sample of a 19-year-old male schizophrenia patient and successfully established induced pluripotent stem cell (iPSC) line using non-integrated reprogramming technology. This cell line possesses the correct karyotype, shape of an embryonic stem cell, the ability to express particular pluripotency markers, and the capacity to differentiate into three germ layers in vitro. This cell line will serve as an in vitro model for upcoming studies on the etiology of schizophrenia and the creation of novel treatment.

AbstractBackground The effectiveness of nirmatrelvir–ritonavir has mainly been shown in non-hospitalized patients with mild-to-moderate coronavirus disease 2019 (COVID-19). The real-world effectiveness of nirmatrelvir-ritonavir urgently needs to be determined using representative in-hospital patients with COVID-19 during the Omicron wave of the pandemic.Methods We performed a multicentre, retrospective study in five Chinese PLA General Hospital medical centers in Beijing, China. Patients hospitalized with COVID-19 from 10 December 2022 to 20 February 2023 were eligible for inclusion. A 1:1 propensity score matching was performed between the nirmatrelvir-ritonavir group and the control group.Results 1010 recipients of nirmatrelvir-ritonavir and 1010 matched controls were finally analyzed after matching. Compared with matched controls, the nirmatrelvir-ritonavir group had a lower incidence rate of all-cause death (4.6/1000 vs. 6.3/1000 person-days, p = 0.013) and a higher incidence rate of clinical improvement (47.6/1000 vs. 45.8/1000 person-days, p = 0.012). Nirmatrelvir-ritonavir was associated with a 22% lower all-cause mortality and a 14% higher incidence of clinical improvement. Initiation of nirmatrelvir-ritonavir within 5 days after symptom onset was associated with a 50% lower mortality and a 26% higher clinical improvement rate. By contrast, no significant associations were identified among patients receiving nirmatrelvir-ritonavir treatment more than 5 days after symptom onset. Nirmatrelvir-ritonavir was also associated with a 50% increase in survival days and a 12% decrease in days to clinical improvement.Conclusion Among hospitalized patients with COVID-19 during the Omicron wave in Beijing, China, the early initiation of nirmatrelvir-ritonavir was associated with clinical benefits of lowering mortality and improving clinical recovery.

Abstract Background and aim Two oral antivirals (Nirmatrelvir- ritonavir and Azvudine) are widely used in China practice during the Omicron wave of the pandemic. However, little evidence regarding the real-world effectiveness of these two oral antivirals in in-hospital patients. We aimed to evaluate the clinical effectiveness of nirmatrelvir-ritonavir versus azvudine among adult hospitalized patients with COVID-19. Methods This retrospective cohort study used data from three Chinese PLA General Hospital medical centres. Hospitalized patients with COVID-19 treated with azvudine or nirmatrelvir-ritonavir from Dec 10, 2022, to February 20, 2023, and did not require invasive ventilation support on admission were eligible for inclusion. Results After exclusions and propensity-score matching, the final analysis included 486 azvudine recipients and 486 nirmatrelvir-ritonavir recipients. By 28 days of initiation of the antivirus treatment, the crude incidence rate of all-cause death was similar in both types of antivirus treatment (nirmatrelvir-ritonavir group 2.8 events 1000 person-days [95% CI, 2.1–3.6] vs azvudine group 3.4 events/1000 person-days [95% CI, 2.6–4.3], P = 0.38). Landmark analysis showed that all-cause death was lower in the nirmatrelvir-ritonavir (3.5%) group than the azvudine (6.8%, P = 0.029) within the initial 10-day admission period, while no significant difference was observed for results between 10 and 28 days follow-up. There was no significant difference between the nirmatrelvir-ritonavir group and the azvudine group in cumulative incidence of the composite disease progression event (8.6% with nirmatrelvir-ritonavir vs. 10.1% with azvudine, HR, 1.22; 95% CI 0.80–1.86, P = 0.43). Conclusion Among patients hospitalized with COVID-19 during the omicron wave in Beijing, similar in-hospital clinical outcomes on 28 days were observed between patients receiving nirmatrelvir-ritonavir and azvudine. However, it is worth noticing that nirmatrelvir-ritonavir appears to hold an advantage over azvudine in reducing early mortality. Further randomized controlled trials are needed to verify the efficacy of those two antivirus medications especially in early treatment.

Metal–organic frameworks (MOFs) receive wide attention owing to their high specific surface area, porosity, and structural designability. In this paper, ZC-Ru and ZC-Cu electrodes loaded with monatomic Ru and Cu doped with nitrogen were prepared by pyrolysis, ion impregnation, and carbonization process using ZIF-8 synthesized by static precipitation as a precursor. ZC-Cu has a high specific surface area of 859.78 m2 g−1 and abundant heteroatoms O (10.04%) and N (13.9%), showing the specific capacitance of 222.21 F g−1 at 0.1 A g−1 in three-electrode system, and low equivalent series resistance (Rct: 0.13 Ω), indicating excellent energy storage capacity and electrical conductivity. After 10,000 cycles at 1 A g−1 in 6 M KOH electrolyte, it still has an outstanding capacitance retention of 99.42%. Notably, symmetric supercapacitors ZC-Cu//ZC-Cu achieved the maximum power density and energy density of 485.12 W·kg−1 and 1.61 Wh·kg−1, respectively, positioning ZC-Cu among the forefront of previously known MOF-based electrode materials. This work demonstrates the enormous potential of ZC-Cu in the supercapacitor industry and provides a facile approach to the treatment of transition metal.

Abstract Introduction The mortality rate of hospitalized patients with severe hospital-acquired pneumonia (SHAP) remains high. Empirical broad-spectrum antibiotic coverage and the misuse of high-grade antibiotics could lead to the emergence of multi-drug and even pandrug-resistant bacteria. In addition to metagenomic next-generation sequencing (mNGS), microbiological rapid on-site evaluation (M-ROSE) might be a useful technique to identify the pathogens in the early stage; however, the effect of M-ROSE guiding anti-infection treatment on prognostic outcomes of SHAP patients is still unclear. Methods/design This is a multicenter, single-blind, prospective, randomized controlled trial to evaluate the effect of M-ROSE guiding anti-infection treatment in SHAP patients, which will provide new strategies for the prevention and control of clinical multi-drug resistance bacteria. A total of 166 patients with SHAP, aged 18 years and over, will be recruited from seven centers in Beijing and randomly assigned to the intervention group (M-ROSE combined with mNGS) or the control group (mNGS only) in a 1:1 ratio using the central randomization system. Patients in the intervention group will accept M-ROSE and mNGS analysis, and the control group will accept mNGS analysis. Individualized anti-infective treatment and routine treatment will be selected according to the analysis results. The primary outcome is the ICU outcome (mortality). The safety of the intervention measures will be evaluated during the entire trial period. This trial will be the first randomized controlled trial to evaluate the effect of M-ROSE guiding treatment on mortality in patients with SHAP and may change the prevalence of multi-drug resistant bacteria. Ethics and dissemination This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Chinese PLA General Hospital (Approval Number: 20220322001). Trial registration ClinicalTrials.gov NCT05300776. Registered on 25 March 2022.

Abstract Background Microelectrode array (MEA) systems are valuable for in vitro assessment of neurotoxicity and drug efficiency. However, several difficulties such as protracted functional maturation and high experimental costs hinder the use of MEA analysis requiring human induced pluripotent stem cells (hiPSCs). Neural network functional parameters are also needed for in vitro to in vivo extrapolation. Methods In the present study, we produced a cost effective nanofiber culture platform, the SCAD device, for long-term culture of hiPSC-derived neurons and primary peripheral neurons. The notable advantage of SCAD device is convenient application on multiple MEA systems for neuron functional analysis. Results We showed that the SCAD device could promote functional maturation of cultured hiPSC-derived neurons, and neurons responded appropriately to convulsant agents. Furthermore, we successfully analyzed parameters for in vitro to in vivo extrapolation, i.e., low-frequency components and synaptic propagation velocity of the signal, potentially reflecting neural network functions from neurons cultured on SCAD device. Finally, we measured the axonal conduction velocity of peripheral neurons. Conclusions: Neurons cultured on SCAD devices might constitute a reliable in vitro platform to investigate neuron functions, drug efficacy and toxicity, and neuropathological mechanisms by MEA.

Abstract With the trend of supply chain globalisation, competition among enterprises is becoming more intense. Enterprises urgently need to improve their core competitiveness, and the enhancement of the competencies can depend on technologies services and the quality of suppliers. Since external factors are less controllable, this study starts with the quality of suppliers and proposes a supplier evaluation method that combines particle swarm optimisation with neural network algorithm to maximise the interests of enterprises. The particle swarm algorithm to lock the approximate location of the global optimum is first employed. Based on this, we establish an evaluation model of suppliers to train for the minimum errors between the desired and predicted values by constructing a back propagation (BP) neural network. Finally, the output results of the proposed method is compared with the BP neural network without the particle swarms optimisation. The proposed model is less empirically sensitive to the initialisation and can quickly converge to the local optimums, which overcomes the shortage of traditional neural networks and is more applicable to supplier evaluation.

Abstract With the rapid development of China's economy, enterprises need to plan their logistics transportation routes reasonably in advance. This will make the transportation service more efficient. For the supplier's transportation service problem, an analysis method of critical path nodes is provided and a multi‐supplier collaborative transportation strategy is designed in this article. First, a model for minimising the transportation cost was established, then a path diagram was simulated and the optimal and alternative transportation paths of suppliers based on the k‐shortest path algorithm were calculated. In addition, path node availability during COVID‐19 is used as a research context in this article. A multi‐stage path analysis method was provided by discussing different cases of critical path nodes, which can make a reasonable selection of paths in a timely and effective manner. Finally, simulations of collaborative transportation for suppliers were performed in three scenarios and the results verified the effectiveness of the collaborative transportation strategy. The proposed collaborative transportation strategy of suppliers not only strengthened the synergistic cooperation among suppliers, but also cultivated the potential customer for suppliers in this article. Furthermore, the strategy could improve the flexibility of the supply chain, maximise the overall efficiency and also provide a new solution for the development of logistics and transportation services.

The fusion of camera and LiDAR perception has become a research focal point in the autonomous driving field. Existing image–point cloud fusion algorithms are overly complex, and processing large amounts of 3D LiDAR point cloud data requires high computational power, which poses challenges for practical applications. To overcome the above problems, herein, we propose an Instance Segmentation Frustum (ISF)–PointPillars method. Within the framework of our method, input data are derived from both a camera and LiDAR. RGB images are processed using an enhanced 2D object detection network based on YOLOv8, thereby yielding rectangular bounding boxes and edge contours of the objects present within the scenes. Subsequently, the rectangular boxes are extended into 3D space as frustums, and the 3D points located outside them are removed. Afterward, the 2D edge contours are also extended to frustums to filter the remaining points from the preceding stage. Finally, the retained points are sent to our improved 3D object detection network based on PointPillars, and this network infers crucial information, such as object category, scale, and spatial position. In pursuit of a lightweight model, we incorporate attention modules into the 2D detector, thereby refining the focus on essential features, minimizing redundant computations, and enhancing model accuracy and efficiency. Moreover, the point filtering algorithm substantially diminishes the volume of point cloud data while concurrently reducing their dimensionality, thereby ultimately achieving lightweight 3D data. Through comparative experiments on the KITTI dataset, our method outperforms traditional approaches, achieving an average precision (AP) of 88.94% and bird’s-eye view (BEV) accuracy of 90.89% in car detection.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major adverse event of anti-cancer drugs, which still lack standardized measurement and treatment methods. In the present study, we attempted to evaluate neuronal dysfunctions in cultured rodent primary peripheral neurons using a microelectrode array system. After exposure to typical anti-cancer drugs (i.e., paclitaxel, vincristine, oxaliplatin, and bortezomib), we successfully detected neurotoxicity in dorsal root ganglia neurons by measuring electrical activities, including impedance value and spontaneous activity. The impedance value decreased significantly for all compounds, even at low concentrations, which indicated cell loss and/or neurite degeneration. The spontaneous activity was also suppressed after exposure, which suggested neurotoxicity again. However, an acute response was observed for paclitaxel and bortezomib before toxicity, which showed different mechanisms based on compounds. Therefore, MEA measurement of impedance value could provide a simple assessment method for CIPN, combined with neuronal morphological changes.

Abstract Defects in ataxin-3 proteins and CAG repeat expansions in its coding gene ATXN3 cause Spinocerebellar Ataxia Type 3 (SCA3) or Machado-Joseph disease (MJD) polyglutamine neurodegenerative disease. The mutant proteins aggregate as inclusion bodies in cells and compete with wild-type ataxin-3, which leads to neuronal dysfunction or death and impairs Beclin1-mediated autophagy. It has been reported that Mesenchymal stem cells (MSCs) can reliably treat several neurodegenerative diseases. Herein, we used a Transcription Factor EB (TFEB) nuclear translocation-mediated MSCs co-culture approach to reconstitute autophagy and lysosomal biogenesis, and reduce SCA3-like behaviors in induced pluripotent stem cells (iPSCs)-derived neuron cells models. Our iPSCs model showed enhanced expression of autophagy proteins, attenuated the expression and toxic effects of mutant ataxin-3 on neurons, and alleviated the effects of ataxin-3 on autophagy. Therefore, MSCs are associated with autophagy-inducing therapy and compared to animal models, our MSCs co-culture could be used as a novel and potential therapeutic approach to study SCA3 disease and other neurodegenerative diseases.

Abstract Background Non-pathological cognitive decline is a neurodegenerative condition associated with brain aging owing to epigenetic changes, telomere shortening, stem cells exhaustion, or altered differentiation. Human umbilical cord mesenchymal stem cells (hUCMSCs) have shown excellent therapeutic prospects on the hallmarks of aging. In this study, we aimed to elucidate the role of hUCMSCs with down-regulated miRNA-206 (hUCMSCs anti-miR-206) on cognitive decline and the underlying mechanism. Methods After daily subcutaneous injection of D-gal (500 mg/kg/d) for 8 weeks, 17-week-old male C57BL/6 J mice were stem cells transplanted by lateral ventricular localization injection. During the 10-day rest period, were tested the behavioral experiments applied to cognitive behavior in the hippocampus. And then, the mice were sacrificed for sampling to complete the molecular and morphological experiments. Results Our behavioral experiments of open field test (OFT), new object recognition test (NOR), and Y-maze revealed that D-galactose (D-gal)-induced aging mice treated with hUCMSCs anti-miR-206 had no obvious spontaneous activity disorder and had recovery in learning and spatial memory ability compared with the PBS-treated group. The hUCMSCs anti-miR-206 reconstituted neuronal physiological function in the hippocampal regions of the aging mice with an increase of Nissl bodies and the overexpression of Egr-1, BDNF, and PSD-95. Conclusion This study first reports that hUCMSCs anti-miR-206 could provide a novel stem cell-based antiaging therapeutic approach.

Abstract In the digital era, realising intelligent digital transformation is a major challenge in the manufacturing field. Digital transformation means bringing more profit appreciation. To improve the analysis reliability of value‐added processes, this study proposes a method for assessing enterprises value‐adding activities. For this purpose, a hybrid model is constructed based on data and mathematics, bridged by a server. The research builds an element group model that identifies data from different sources, and also gives a mathematical model to describe the relationship of the supply, marketing and service. Taking an automobile manufacturing value chain as an example, to theoretically analyse the composition of value‐added activities. Then, the assembly process of an automobile manufacturing plant was used as a value‐added case study. The simulation results show the impact of changing production layout and product handling angle on the whole value chain. The study can provide new ideas for the intelligent digital transformation of the manufacturing industry.

The layered materials have demonstrated great prospects as cost-effective substitutes for precious electrocatalysts in hydrogen evolution reaction. Research efforts have been devoted to synthesizing highly conductive MoS2 with the substantial cardinal plane and edge active sites. Here, we successfully synthesized a hierarchical 1T/2H–MoS2 with sodium ion insertion via a facile hydrothermal method. The contents of the 1T-phase can be flexibly controlled by different hydrothermal temperatures (160 ∼ 200 °C). And the modified uniformly dispersed 1T/2H–MoS2 nanospheres with different d spacings were designed to enhance the electrocatalytic efficiency by adding SiO2 and through the ion exchange process of NaOH and HF solution. The as-synthesized Na+ intercalated 1T-MoS2 nanosphere with an expanded interlayer of 0.95 nm obtained at 160 °C exhibits a prominent electrocatalytic performance of hydrogen evolution reaction with a comparable overpotential of 255 mV and a remarkably small Tafel slope of 44 mV/decade. Therefore, this study provides a facile and controllable strategy to yield interlayer-expanded 1T-MoS2 nanospheres, making it a potentially competitive hydrogen evolution catalyst for the hydrogen cell.

Several anticancer drugs used in cancer therapy induce chemotherapy-induced peripheral neuropathy (CIPN), leading to dose reduction or therapy cessation. Consequently, there is a demand for an in vitro assessment method to predict CIPN and mechanisms of action (MoA) in drug candidate compounds. In this study, a method assessing the toxic effects of anticancer drugs on soma and axons using deep learning image analysis is developed, culturing primary rat dorsal root ganglion neurons with a microphysiological system (MPS) that separates soma from neural processes and training two artificial intelligence (AI) models on soma and axonal area images. Exposing the control compound DMSO, negative compound sucrose, and known CIPN-causing drugs (paclitaxel, vincristine, oxaliplatin, suramin, bortezomib) for 24 h, results show the somatic area-learning AI detected significant cytotoxicity for paclitaxel (* p < 0.05) and oxaliplatin (* p < 0.05). In addition, axonal area-learning AI detected significant axonopathy with paclitaxel (* p < 0.05) and vincristine (* p < 0.05). Combining these models, we detected significant toxicity in all CIPN-causing drugs (** p < 0.01) and could classify anticancer drugs based on their different MoA on neurons, suggesting that the combination of MPS-based culture segregating soma and axonal areas and AI image analysis of each area provides an effective evaluation method to predict CIPN from low concentrations and infer the MoA.

Abstract Background Alopecia areata (AA) is a common autoimmune hair loss disease with increasing incidence. Corticosteroids are the most widely used for hair loss treatment; however, long-term usage of hormonal drugs is associated with various side effects. Mesenchymal stem cells (MSCs) therapy has been studied extensively to curb autoimmune diseases without affecting immunity against diseases. Methods Hair follicle-derived MSCs (HF-MSCs) were harvested from the waste material of hair transplants, isolated and expanded. The therapeutic effect of HF-MSCs for AA treatment was investigated in vitro AA-like hair follicle organ model and in vivo C3H/HeJ AA mice model. Results AA-like hair follicle organ in vitro model was successfully established by pre-treatment of mouse vibrissa follicles by interferon-γ (IFN-γ). The AA-like symptoms were relieved when IFN-γ induced AA in vitro model was co-cultured with HF-MSC for 2 days. In addition, when skin grafted C3H/HeJ AA mice models were injected with 106 HF-MSCs once a week for 3 weeks, the transcription profiling and immunofluorescence analysis depicted that HF-MSCs treatment significantly decreased mouse hair loss and reduced inflammation around HF both in vitro and in vivo. Conclusions This study provides a new therapeutic approach for alopecia areata based on HF-MSCs toward its future clinical application.

Abstract Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) is a progressive autosomal dominant neurodegenerative disease caused by abnormal CAG repeats in the exon 10 of ATXN3. The accumulation of the mutant ataxin-3 proteins carrying expanded polyglutamine (polyQ) leads to selective degeneration of neurons. Since the pathogenesis of SCA3 has not been fully elucidated, and no effective therapies have been identified, it is crucial to investigate the pathogenesis and seek new therapeutic strategies of SCA3. Induced pluripotent stem cells (iPSCs) can be used as the ideal cell model for the molecular pathogenesis of polyQ diseases. Abnormal CAG expansions mediated by CRISPR/Cas9 genome engineering technologies have shown promising potential for the treatment of polyQ diseases, including SCA3. In this study, SCA3-iPSCs can be corrected by the replacement of the abnormal CAG expansions (74 CAG) with normal repeats (17 CAG) using CRISPR/Cas9-mediated homologous recombination (HR) strategy. Besides, corrected SCA3-iPSCs retained pluripotent and normal karyotype, which can be differentiated into a neural stem cell (NSCs) and neuronal cells, and maintained electrophysiological characteristics. The expression of differentiation markers and electrophysiological characteristics were similar among the neuronal differentiation from normal control iPSCs (Ctrl-iPSCs), SCA3-iPSCs, and isogenic control SCA3-iPSCs. Furthermore, this study proved that the phenotypic abnormalities in SCA3 neurons, including aggregated IC2-polyQ protein, decreased mitochondrial membrane potential (MMP) and glutathione expressions, increased reactive oxygen species (ROS), intracellular Ca2+ concentrations, and lipid peroxidase malondialdehyde (MDA) levels, all were rescued in the corrected SCA3-NCs. For the first time, this study demonstrated the feasibility of CRISPR/Cas9-mediated HR strategy to precisely repair SCA3-iPSCs, and reverse the corresponding abnormal disease phenotypes. In addition, the importance of genetic control using CRISPR/Cas9-mediated iPSCs for disease modeling. Our work may contribute to providing a potential ideal model for molecular mechanism research and autologous stem cell therapy of SCA3 or other polyQ diseases, and offer a good gene therapy strategy for future treatment.

Abstract Background Neural stem cell (NSC) therapy remains one of the most potential approaches for the treatment of neurological disorders. The discovery of human induced pluripotent stem cells (hiPSCs) and the establishment of hiPSC-derived human neural stem cells (hiNSCs) have revolutionized the technique of cell therapy. Meanwhile, it is often required that NSCs are stored and transported to a long distance for research or treatment purposes. Although high survival rates could be maintained, conventional methods for cell transportation (dry ice or liquid nitrogen) are inconvenient and expensive. Therefore, the establishment of a safe, affordable, and low-cost strategy to store and transport easily accessible hiPSCs and hiNSCs, with characteristics that match fetal hNSCs, is incredibly urgent. Methods We reprogrammed human urinary cells to iPSCs using a non-integrating, virus-free technique and differentiated the iPSCs toward iNSCs/neurospheres and neurons, under Good Manufacturing Practice (GMP)-compatible conditions. The pluripotency of iPSCs and iNSCs was characterized by a series of classical methods (surface markers, karyotype analysis, and in vitro as well as in vivo differentiation capabilities, etc.). Results Here, our results showed that we successfully generated hiNSCs/neurospheres from more available, non-invasive, and more acceptable urinary cells by a virus-free technique. Next, we demonstrated that the iNSCs differentiated into mature cerebral cortical neurons and neural networks. Interestingly, hiNSCs survived longer as neurospheres at ambient temperature (AT) than those cultured in a monolayer. Within 7 days approximately, the neural viability remained at > 80%, while hiNSCs cultured in a monolayer died almost immediately. Neurospheres exposed to AT that were placed under standard culture conditions (37 °C, 5% CO2) recovered their typical morphology, and retained their proliferation and differentiation abilities. Conclusions In this study, we provided a simple method for the storage of NSCs as neurospheres at AT as an alternative method to more costly and inconvenient traditional methods of cryopreservation. This will enable hiNSCs to be transported over long distances at AT and facilitate the therapeutic application of NSCs as neurospheres without any further treatment.

Background and Objectives: To identify factors that influence the sample adequacy of solid thyroid nodules based on ultrasound-guided fine-needle aspiration (FNA) with subsequent liquid-based cytology. Materials and Methods: We retrospectively reviewed 855 patients who underwent ultrasound-guided FNA at our hospital between July 2019 and July 2020. The final analysis included 801 solid thyroid nodules in 801 patients. After reviewing the demographic data, ultrasonic features, and FNA technique-related factors, we defined 14 potential variables. For cytological results, the Bethesda categories II–VI were defined as adequate sample results. Univariate and multivariate analyses were performed to identify factors that influenced sample adequacy. Results: The adequate sample rate was 87.1%. The univariate analysis showed that four factors were related to adequate sampling in patients with thyroid FNA. These factors included age (p < 0.001), nodule orientation (p = 0.0232), calcification (p = 0.0034), and operator experience (p = 0.0286). After the multivariate analysis, five independent factors were identified to improve the diagnostic results of FNA for solid thyroid nodules: (1) the presence of Hashimoto’s thyroiditis (odds ratio (OR) = 1.810; 95% confidence interval (CI): 1.076–3.045; p = 0.0254), (2) a taller-than-wide orientation (OR = 2.038; 95% CI: 1.260–3.296; p = 0.0037), (3) the presence of calcification (OR = 1.767; 95% CI: 1.115–2.799; p = 0.0153), (4) four needle passes to obtain material (OR = 1.750; 95% CI: 1.094–2.799; p = 0.0196), and (5) an experienced operator (OR = 0.561; 95% CI: 0.319–0.987; p = 0.0451). Conclusions: A taller-than-wide orientation, the presence of calcification, and the presence of Hashimoto’s thyroiditis were found to affect the sample adequacy of ultrasound-guided FNA with liquid-based cytology. The sample adequacy could be improved when FNA is performed with four needle passes by experienced doctors.

Urine epithelial cells were harvested from a 32-year old female patient with spinocerebellar ataxia type 3 (SCA3) and reprogrammed into induced pluripotent stem cells (iPSCs) by non-integration system. The SCA3 derived iPSCs line, CSUXHi005-A, maintained 76 CAG expansions in the ATXN3 gene, was characterized by the expression of pluripotency markers and normal karyotype. The newly generated iPSCs retain the ability to differentiate into three germ layers by teratoma test, which provide an ideal tool for disease modeling, drug screening, and cellular therapy.

Severe mycological epilepsy of infancy is a catastrophic disease with preferential dysfunction of interneurons, frequent episode rate, cognitive and sudden death. The disease is mainly caused by heterozygous loss-of-function mutation of SCN1A gene encoding α subunit of the sodium channel Nav1.1. To generate mutations in normal iPSC, Transcription activator-like effector nucleases was used to introduce the epilepsy-causing mutation A5768G into the endogenous locus of SCN1A gene. The gene editing induced pluripotent stem cell line and normal iPSC were obtained from the same donor to eliminate significantly the genetic background noise.

Dravet syndrome is an epileptic encephalopathy largely due to haploinsufficiency of the voltage-gated sodium channel Nav1.1 that is expressed primarily in GABAergic neurons. In order to distinguish the different subtypes, we used gene editing to introduce tdTomato gene into the genome of iPSCs to label the GABAergic neurons in the differentiated neuronal networks. The gene-edited cell line demonstrates normal karyotype, expresses the main pluripotency markers, and shows the presence of differentiation into the three embryonic germ layers in teratomas.

Dravet syndrome is a neurological disorder characterized by treatment-resistant polymorphic seizures, primarily caused by loss-of-function in the SCN1A gene. To develop an in vitro model of this disease, in a previously study we generated an induced pluripotent stem cell line from a 10-year-old boy carrying the NM_001165963.1:c.5768A to G (Q1923R) mutation in SCN1A. Using TALEN-mediated genome editing, we have now generated an isogenic control line in which the disease-causing mutation found in the epilepsy patient iPSCs was corrected, in order to eliminate the interference of different genetic backgrounds in future analyses.

Epilepsy is a neurological disorder, characterized by recurrent (two or more) epileptic seizures resulting from excessive and abnormal cortical neural activity.Fibroblasts were collected from a 10-year-old male with antecedent febrile seizures (PEFS+) and carrying a heterozygous A > G mutation of Nav1.1 α subunit gene. The induced USTCi001-A retained the mutation, expressed pluripotent markers, showed normal karyotype, and displayed in vitro differentiation potential toward cells of the three embryonic germ layers.

Spinocerebellar ataxia type 1 (SCA1) is a hereditary neurodegenerative disease caused by CAG repeated expansion in ATXN1 gene. We generated induced pluripotent stem cells (iPSCs) from the urine exfoliated epithelial cells of SCA1 patient by using the integration-free methods. The patient derived iPSCs retained the mutation (the 65 CAG expansion tracts in ATXN1 gene), displayed normal karyotypes, expressed pluripotency markers and had the potential to differentiate towards three germ layers in vivo. This type of stem cell model will be valuable for elucidating the pathological mechanism and screening potential drugs of SCA1.

Abstract Background Identifying typical odor-causing compounds is essential for odor problem control in drinking water. In this study, aiming at a major water source reservoir in hot and humid areas in southern China, which encountered seasonable odor problems in recent years, an integrated approach including comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC × GC–TOFMS), flavor profile analysis (FPA) and quantitative real-time polymerase chain reaction (qPCR) was adopted to investigate the odor occurrence. Results The results indicated that earthy–musty odor is blamed to the seasonable odor problems, and it is consistent with the complaints results from consumers. Fifty-four typical odor compounds were investigated in the reservoir and twelve were detected, of which, 2-methylisoborneol (2-MIB) was significantly increased during the odor event. Pseudanabaena sp. is the dominant species in the reservoir, which can be further represented by the number of mic gene with qPCR method (R 2 = 0.746, P

Background/Aims: Atherosclerosis is a chronic inflammatory cardiovascular disease. Macrophages are major components of atherosclerotic plaques and play a key role in the development of atherosclerosis by secreting a variety of pro-inflammatory factors. Our previous studies have confirmed that upconversion nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) mediated photodynamic therapy (PDT) can promote cholesterol efflux and induce apoptosis in THP-1 macrophages. In this study, we investigated whether reactive oxygen species (ROS) generated by UCNPs-Ce6-mediated PDT can induce autophagy to inhibit the expression of pro-inflammatory factor in M1 peritoneal macrophages. Methods: Peritoneal macrophages were collected from C57/BL6 mice injected with 3% thioglycollate broth medium and induced by lipopolysaccharides and interferon-γ. Intracellular ROS production was assessed by 2’-7’-dichloroforescein diacetate and flow cytometry. Autophagy was assayed by western blot, transmission electron microscopy and immunofluorescence. Pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay and western blot. Results: Model M1 peritoneal macrophages were established after 24 h induction. Protein expression levels of LC3 II and Beclin1, and degradation of p62 increased and peaked at 2 h in the PDT group. Meanwhile, levels of inflammatory cytokines iNOS, IL-12, and TNF-α markedly decreased after PDT. The increase in autophagy levels and decrease in pro-inflammatory cytokines were significantly inhibited by 3-methyladenine. Furthermore, ROS generated by UCNPs-Ce6 mediated PDT activated autophagy. The expression of autophagy related-protein and inflammatory cytokines iNOS, IL-12, and TNF-α were inhibited by the ROS inhibitor N-acetyl cysteine. Conclusions: ROS generated by UCNPs-Ce6-mediated PDT activated autophagy and inhibited the expression of pro-inflammatory factors of M1 peritoneal macrophage via the PI3K/AKT/mTOR signaling pathway.

Autism spectrum disorder (ASD) is a neurological disorder with complex etiologies. In this study, urine cells were collected from a 16-year-old male with ASD and reprogrammed with the human SKOM transcription factors. The patient has a heterozygous C > T mutation of FCGR1B gene that was confirmed by sequencing analysis. The pluripotency was verified by gene expression and capacity of differentiation towards the three germ layers. This kind of iPSC will be valuable for further understanding the pathogenesis of ASD and help to develop drugs for treating ASD.

The induced pluripotent stem cell (iPSC) line XHCSUi001-A generated from urine cells of a female spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) patient by using the integration-free methods. The induced XHCSUi001-A retained the disease-causing ATXN3 mutation, expressed pluripotency markers, exhibited a normal karyotype and retained the ability to differentiate into the three germ layers in-vitro and in-vivo. This newly induced iPSC line could be a potential tool for researching the disease-specific mechanisms and drug screening of SCA3/MJD.

A Fano resonance is experimentally observed in a single silver nanocube separated from a supporting silver film by a thin aluminum oxide film. The resonance spectrum is modulated by changing the size of the silver nanocube and its distance from the silver film. The system is fabricated by a bottom-up process with an accurately controlled nanogap at the sub-6-nm scale. The simulation result shows that the destructive interference between the dipole mode and the quadrupole mode in this “nanocube on mirror” (NCoM) structure is responsible for the resonance. The spectra red-shifted as the size of the silver nanocube increased and its distance from the silver film decreased. In addition, a refractive index sensitivity of the spectrum of 140 meV/RIU (refractive index unit), with a 2.4 figure of merit, is obtained by changing the dielectric environment around the silver nanocube. This work will enable the development of high-performance tunable optical nanodevices based on NCoM structures.

Surface plasmons have been attracting increasing attention and have been studied extensively in recent decades because of their half-light and half-material polarized properties. On the one hand, the tightly confined surface plasmonic mode may reduce the size of integrated optical devices beyond the diffraction limit; on the other hand, it provides an approach toward enhancement of the interactions between light and matter. In recent experiments, researchers have realized promising applications for surface plasmons in quantum information processing, ultra-low-power lasers, and micro-nano processing devices by using plasmonic structures, which have demonstrated their superiority over traditional optics structures. In this paper, we introduce the theoretical principle of surface plasmons and review the research work related to the interactions between plasmons and excitons. Some perspectives with regard to the future development of plasmonic coupling are also outlined.

Organic inorganic hybrid perovskites have potential applications in solar cells, electroluminescent devices and radiation detection because of their unique optoelectronic properties. In this paper, the perovskites (C6H5CH2NH3)2PbBr4 and (C6H5CH2NH3)2PbI4 were synthesized by solvent evaporation. The crystal structure, morphology, absorption spectrum, laser power dependence of the photoluminescence (PL) intensity and lifetime were studied. The results showed that the perovskites (C6H5CH2NH3)2PbBr4 and (C6H5CH2NH3)2PbI4 display a layered stacking structure of organic and inorganic components. The absorption peaks are located at 392 nm (3.16 eV) and 516 nm (2.40 eV), respectively. It was observed that the PL intensity and photoluminescence quantum yield (PLQY) increases with increasing laser power, and that the PL lifetime decreases with increasing laser power, which is mainly due to the non-geminate recombination.