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Abstract The rapid advancement of deep learning has enabled Brain-Computer Interfaces (BCIs) technology, particularly neural decoding techniques, to achieve higher accuracy and deeper levels of interpretation. Interest in decoding imagined speech has significantly increased because its concept akin to “mind reading”. However, previous studies on decoding neural language have predominantly focused on brain activity patterns during human reading. The absence of imagined speech electroencephalography (EEG) datasets has constrained further research in this field. We present the Chinese Imagined Speech Corpus (Chisco), including over 20,000 sentences of high-density EEG recordings of imagined speech from healthy adults. Each subject’s EEG data exceeds 900 minutes, representing the largest dataset per individual currently available for decoding neural language to date. Furthermore, the experimental stimuli include over 6,000 everyday phrases across 39 semantic categories, covering nearly all aspects of daily language. We believe that Chisco represents a valuable resource for the fields of BCIs, facilitating the development of more user-friendly BCIs.

In ophthalmology, the quality of fundus images is critical for accurate diagnosis, both in clinical practice and in artificial intelligence (AI)-assisted diagnostics. Despite the broad view provided by ultrawide-field (UWF) imaging, pseudocolor images may conceal critical lesions necessary for precise diagnosis. To address this, we introduce UWF-Net, a sophisticated image enhancement algorithm that takes disease characteristics into consideration. Using the Fudan University ultra-wide-field image (FDUWI) dataset, which includes 11 294 Optos pseudocolor and 2415 Zeiss true-color UWF images, each of which is rigorously annotated, UWF-Net combines global style modeling with feature-level lesion enhancement. Pathological consistency loss is also applied to maintain fundus feature integrity, significantly improving image quality. Quantitative and qualitative evaluations demonstrated that UWF-Net outperforms existing methods such as contrast limited adaptive histogram equalization (CLAHE) and structure and illumination constrained generative adversarial network (StillGAN), delivering superior retinal image quality, higher quality scores, and preserved feature details after enhancement. In disease classification tasks, images enhanced by UWF-Net showed notable improvements when processed with existing classification systems over those enhanced by StillGAN, demonstrating a 4.62% increase in sensitivity (SEN) and a 3.97% increase in accuracy (ACC). In a multicenter clinical setting, UWF-Net-enhanced images were preferred by ophthalmologic technicians and doctors, and yielded a significant reduction in diagnostic time ((13.17 ± 8.40) s for UWF-Net enhanced images vs (19.54 ± 12.40) s for original images) and an increase in diagnostic accuracy (87.71% for UWF-Net enhanced images vs 80.40% for original images). Our research verifies that UWF-Net markedly improves the quality of UWF imaging, facilitating better clinical outcomes and more reliable AI-assisted disease classification. The clinical integration of UWF-Net holds great promise for enhancing diagnostic processes and patient care in ophthalmology.

Based on the production curves, changes in hydrocarbon composition and quantities over time, and production systems from key trial production wells in lacustrine shale oil areas in China, fine fraction cutting experiments and molecular dynamics numerical simulations were conducted to investigate the effects of changes in shale oil composition on macroscopic fluidity. The concept of “component flow” for shale oil was proposed, and the formation mechanism and conditions of component flow were discussed. The research reveals findings in four aspects. First, a miscible state of light, medium and heavy hydrocarbons form within micropores/nanopores of underground shale according to similarity and intermiscibility principles, which make components with poor fluidity suspended as molecular aggregates in light and medium hydrocarbon solvents, such as heavy hydrocarbons, thereby decreasing shale oil viscosity and enhancing fluidity and outflows. Second, small-molecule aromatic hydrocarbons act as carriers for component flow, and the higher the content of gaseous and light hydrocarbons, the more conducive it is to inhibit the formation of larger aggregates of heavy components such as resin and asphalt, thus increasing their plastic deformation ability and bringing about better component flow efficiency. Third, higher formation temperatures reduce the viscosity of heavy hydrocarbon components, such as wax, thereby improving their fluidity. Fourth, preservation conditions, formation energy, and production system play important roles in controlling the content of light hydrocarbon components, outflow rate, and forming stable “component flow”, which are crucial factors for the optimal compatibility and maximum flow rate of multi-component hydrocarbons in shale oil. The component flow of underground shale oil is significant for improving single-well production and the cumulative ultimate recovery of shale oil.

To quantitatively represent the deterioration law of the mechanical properties of siltstone after exposure to supercritical CO2(SC-CO2), experiments were conducted to test the mechanical parameters of rocks under the coupling effect of CO2–water–rock interactions. The purpose of this study is to determine the evolution law and damage characteristics of each siltstone mechanical parameter under the action of SC-CO2. In combination with numerical simulation results, this study revealed the damage evolution characteristics of rocks in a CO2 geological storage reservoir. The research findings indicate that SC-CO2 exhibits a certain time effect and causes non-uniform damage to siltstone. Both the deterioration law of the mechanical parameters and soaking time exhibited an exponential relationship. With increasing soaking time, both the uniaxial compressive strength and elastic modulus showed a decreasing tendency, whereas the Poisson's ratio showed a varying degree of increase. The total degree of deterioration gradually increased as the soaking time increased and approached a stable value. After exposure to SC-CO2, the damage deformation and failure mode transitioned from brittle to plastic in the siltstone samples. In addition, there was a shift from a single axial crack failure pattern to a complex failure mode with multiple cracks. This study also derived a uniaxial compressive strength prediction model for siltstone based on soaking time, constructed an elastic modulus damage model, and established a fluid–solid coupling model considering damage in the CO2 geological storage process. The experimental and numerical simulation results revealed that microstructural alterations occurred in the siltstone after exposure to SC-CO2. Furthermore, it was discovered that damage accumulation from the micro- to macroscale ultimately led to a gradual deterioration in mechanical properties. The research results provide a theoretical basis for mechanical stability evaluation in CO2 geological storage.

Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.

Abstract When pressure relief mining of a non‐all‐coal protective layer, to realize the accurate regulation of the pressure relief range and pressure release value of mining height, it is necessary to carry out research on the migration of overburden and the stress distribution law of stope under mining height control. Through similar material simulation experiments, four groups of similar material simulation experimental models were established. The laws of rock strata movement and stress distribution at 2, 4, and 5 m mining heights under different geological conditions, and the laws of rock strata movement and stress distribution at 5 and 8 m mining heights under the same geological conditions were obtained. The research results show that the geological conditions and mining height do not affect the evolution of the rock strata movement range. The highest position of the strata movement and deformation is linearly related to the advancing distance of the coalface. The maximum height of rock strata movement increases abruptly when encountering the key strata, but it still has a linear relationship. The highest position of each expansion of the fracture zone has an exponential relationship with the advancing distance of the coalface. When the key strata are encountered, the maximum height of the fracture zone increases abruptly. The change in mining height only affects the distribution range of the “three zones.” The mining height controls the stress distribution of stope by adjusting the “three zones” of the roof. With the increase in mining height, the caving zone and fracture zone range increase. The corresponding pressure relief range and pressure relief value show the change law of first increasing and then decreasing. There is an optimal mining height, which can make the pressure relief effect of stope best.

Abstract Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) is an N6-methyladenosine (m6A) demethylase that demethylates RNAs involved in energy homeostasis, though its influence on DR is not well studied. Herein, we detected elevated FTO expression in vitreous fibrovascular membranes of patients with proliferative DR. FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC–microglia interactions to induce retinal inflammation and neurodegeneration in vivo and in vitro. Mechanistically, FTO affected EC features via modulating CDK2 mRNA stability in an m6A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by lactate-mediated histone lactylation. FB23-2, an inhibitor to FTO’s m6A demethylase activity, suppressed angiogenic phenotypes in vitro. To allow for systemic administration, we developed a nanoplatform encapsulating FB23-2 and confirmed its targeting and therapeutic efficiency in mice. Collectively, our study demonstrates that FTO is important for EC function and retinal homeostasis in DR, and warrants further investigation as a therapeutic target for DR patients.

Objective To construct a prognostic model of a breast cancer-related oxidative stress-related gene (OSRG) signature using machine learning algorithms. Methods The OSRGs of breast cancer were constructed by least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. The Cancer Genome Atlas (TCGA) was used to analyse the gene expression and prognostic value. The Human Protein Atlas was used to analyse the protein expression of hub genes. Receiver operating characteristic analysis, calibration curve and decision curve analysis were used to predict the stability of this model. Results The area under the curve of 1-, 3- and 5-year overall survival were 0.751, 0.707 and 0.645 in the TCGA training dataset; and 0.692, 0.678 and 0.602 in the TCGA testing dataset, respectively. Calibration plot showed good agreement between predicted probabilities and observed outcomes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) pathway analysis indicated that multiple cancer-related pathways were highly enriched in the high-risk group. Immune infiltration analysis showed immune cells and their functions may play a key role in the development and mechanism of breast cancer. Conclusions This new OSRG signature was associated with the immune infiltration and it might be useful in predicting the prognosis in patients with breast cancer.

Abstract Night-time warming is vital for human production and daily life. Conventional methods like active heaters are energy-intensive, while passive insulating films possess restrictions regarding space consumption and the lack of heat gain. In this work, a nanophotonic-based night-time warming strategy that passively inhibits thermal radiation of objects while actively harnessing that of atmosphere is proposed. By using a photonic-engineered thin film that exhibits high reflectivity (~0.91) in the atmospheric transparent band (8–14 μm) and high absorptivity (~0.7) in the atmospheric radiative band (5–8 and 14–16 μm), temperature rise of 2.1 °C/4.4 °C compared to typical low-e film and broadband absorber is achieved. Moreover, net heat loss as low as 9 W m−2 is experimentally observed, compared to 16 and 39 W m−2 for low-e film and broadband absorber, respectively. This strategy suggests an innovative way for sustainable warming, thus contributes to addressing the challenges of climate change and promoting global carbon neutrality.

Femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)and small incision lenticule extraction(SMILE)are the mainstream corneal refractive surgeries at present. Despite efficacy, safety and predictability they have showed in refractive error correction, there are still complications relating to femtosecond laser, such as suction loss and opaque bubble layer(OBL), due to that the production of corneal flap or lenticule is dependent on the femtosecond laser. OBL is a complication that is unique to femtosecond laser surgery and the bubbles are generated from photo-disruptive effect towards corneal tissues which consisted of water vapor and carbon dioxide, and OBL gradually formed when the bubbles are trapped in the stroma. The bubbles can influence the intraoperative manipulation and postoperative visual quality. This review discusses the mechanism, grading, classification, and influencing factors of OBL and its effects on intraoperative manipulations and postoperative recovery, in the hope of providing reference and basis for further clinical studies.

Abstract Background Cerebral microbleeds (CMBs) serve as neuroimaging biomarkers to assess risk of intracerebral hemorrhage and diagnose cerebral small vessel disease (CSVD). Therefore, detecting CMBs can evaluate the risk of intracerebral hemorrhage and use its presence to support CSVD classification, both are conducive to optimizing CSVD management. This study aimed to develop and test a deep learning (DL) model based on susceptibility-weighted MR sequence (SWS) to detect CMBs and classify CSVD to assist neurologists in optimizing CSVD management. Patients with arteriolosclerosis (aSVD), cerebral amyloid angiopathy (CAA), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) treated at three centers were enrolled between January 2017 and May 2022 in this retrospective study. The SWSs of patients from two centers were used as the development set, and the SWSs of patients from the remaining center were used as the external test set. The DL model contains a Mask R-CNN for detecting CMBs and a multi-instance learning (MIL) network for classifying CSVD. The metrics for model performance included intersection over union (IoU), Dice score, recall, confusion matrices, receiver operating characteristic curve (ROC) analysis, accuracy, precision, and F1-score. Results A total of 364 SWS were recruited, including 336 in the development set and 28 in the external test set. IoU for the model was 0.523 ± 0.319, Dice score 0.627 ± 0.296, and recall 0.706 ± 0.365 for CMBs detection in the external test set. For CSVD classification, the model achieved a weighted-average AUC of 0.908 (95% CI 0.895–0.921), accuracy of 0.819 (95% CI 0.768–0.870), weighted-average precision of 0.864 (95% CI 0.831–0.897), and weighted-average F1-score of 0.829 (95% CI 0.782–0.876) in the external set, outperforming the performance of the neurologist group. Conclusion The DL model based on SWS can detect CMBs and classify CSVD, thereby assisting neurologists in optimizing CSVD management.

Abstract Advanced multispectral detection technologies have emerged as a significant threat to objects, necessitating the use of multiband camouflage. However, achieving effective camouflage and thermal management across the entire infrared spectrum, especially the short-wave infrared (SWIR) band, remains challenging. This paper proposes a multilayer wavelength-selective emitter that achieves effective camouflage across the entire infrared spectrum, including the near-infrared (NIR), SWIR, mid-wave infrared (MWIR), and long-wave infrared (LWIR) bands, as well as the visible (VIS) band. Furthermore, the emitter enables radiative heat dissipation in two non-atmospheric windows (2.5–3 μm and 5–8 μm). The emitter’s properties are characterized by low emittance of 0.270/0.042/0.218 in the SWIR/MWIR/LWIR bands, and low reflectance of 0.129/0.281 in the VIS/NIR bands. Moreover, the high emittance of 0.742/0.473 in the two non-atmospheric windows ensures efficient radiative heat dissipation, which results in a temperature decrement of 14.4 °C compared to the Cr reference at 2000 W m−2 input power density. This work highlights the role of solar radiance in camouflage, and provides a comprehensive guideline for developing multiband camouflage compatible with radiative heat dissipation, from the visible to LWIR.

IntroductionArtificial intelligence (AI) technology has made rapid progress for disease diagnosis and triage. In the field of ophthalmic diseases, image-based diagnosis has achieved high accuracy but still encounters limitations due to the lack of medical history. The emergence of ChatGPT enables human-computer interaction, allowing for the development of a multimodal AI system that integrates interactive text and image information.ObjectiveTo develop a multimodal AI system using ChatGPT and anterior segment images for diagnosing and triaging ophthalmic diseases. To assess the AI system's performance through a two-stage cross-sectional study, starting with silent evaluation and followed by early clinical evaluation in outpatient clinics.Methods and analysisOur study will be conducted across three distinct centers in Shanghai, Nanjing, and Suqian. The development of the smartphone-based multimodal AI system will take place in Shanghai with the goal of achieving ≥90% sensitivity and ≥95% specificity for diagnosing and triaging ophthalmic diseases. The first stage of the cross-sectional study will explore the system's performance in Shanghai's outpatient clinics. Medical histories will be collected without patient interaction, and anterior segment images will be captured using slit lamp equipment. This stage aims for ≥85% sensitivity and ≥95% specificity with a sample size of 100 patients. The second stage will take place at three locations, with Shanghai serving as the internal validation dataset, and Nanjing and Suqian as the external validation dataset. Medical history will be collected through patient interviews, and anterior segment images will be captured via smartphone devices. An expert panel will establish reference standards and assess AI accuracy for diagnosis and triage throughout all stages. A one-vs.-rest strategy will be used for data analysis, and a post-hoc power calculation will be performed to evaluate the impact of disease types on AI performance.DiscussionOur study may provide a user-friendly smartphone-based multimodal AI system for diagnosis and triage of ophthalmic diseases. This innovative system may support early detection of ocular abnormalities, facilitate establishment of a tiered healthcare system, and reduce the burdens on tertiary facilities.Trial registrationThe study was registered in ClinicalTrials.gov on June 25th, 2023 (NCT 05930444).

Abstract The aim of this study was to quantitatively analyze the mechanical change of spinal segments (disc, muscle, and ligament) at various postures under microgravity using a full-body musculoskeletal modeling approach. Specifically, in the lumbar spine, the vertebra were modeled as rigid bodies, the intervertebral discs were modeled as 6-degree-of-freedom joints with linear force-deformation relationships, the disc swelling pressure was deformation dependent, the ligaments were modeled as piecewise linear elastic materials, the muscle strength was dependent on its functional cross-sectional area. The neutral posture and the “fetal tuck” posture in microgravity (short as “Neutral 0G” and “Fetal Tuck 0G”, in our simulation, the G constant was set to 0 for simulating microgravity), and for comparison, the relaxed standing posture in 1G and 0G gravity (short as “Neutral 1G” and “Standing 0G”) were simulated. Compared to values at Neutral 1G, the mechanical response in the lower spine changed significantly at Neutral 0G. For example, the compressive forces on lumbar discs decreased 62–70%, the muscle forces decreased 55.7–92.9%, while disc water content increased 7.0–10.2%, disc height increased 2.1–3.0%, disc volume increased 6.4–9.3%, and ligament forces increased 59.5–271.3% at Neutral 0G. The fetal tuck 0G reversed these changes at Neutral 0G back toward values at Neutral 1G, with magnitudes much larger than those at Neutral 1G. Our results suggest that microgravity has significant influences on spinal biomechanics, alteration of which may increase the risks of disc herniation and degeneration, muscle atrophy, and/or ligament failure.

Electroencephalography-to-Text generation (EEG-to-Text), which aims to directly generate natural text from EEG signals has drawn increasing attention in recent years due to the enormous potential for Brain-computer interfaces. However, the remarkable discrepancy between the subject-dependent EEG representation and the semantic-dependent text representation poses a great challenge to this task. To mitigate this, we devise a Curriculum Semantic-aware Contrastive Learning strategy (C- SCL), which effectively recalibrates the subject-dependent EEG representation to the semantic-dependent EEG representation, thereby reducing the discrepancy. Specifically, our C- SCL pulls semantically similar EEG representations together while pushing apart dissimilar ones. Besides, in order to introduce more meaningful contrastive pairs, we carefully employ curriculum learning to not only craft meaningful contrastive pairs but also make the learning progressively. We conduct extensive experiments on the ZuCo benchmark and our method combined with diverse models and architectures shows stable improvements across three types of metrics while achieving the new state-of-the-art. Further investigation proves not only its superiority in both the single-subject and low-resource settings but also its robust generalizability in the zero-shot setting. Our codes are available at: https://github.com/xcfcode/contrastive_eeg2text.

Abstract Purpose To evaluate the accuracy of axial length, keratometry, and refractive measurement with Myopia Master in ametropic children. Methods In this randomized prospective cross-sectional study, 125 children with ametropia (250 eyes) were recruited (55 boys and 70 girls; age range: 3–15 years). All examinations were performed under full cycloplegic conditions. Measurements of axial length (AL), keratometry, and autorefraction acquired with the Myopia Master were compared with those from the IOLMaster 500, IOLMaster 700, Nidek ARK-1, and manifest refraction. The differences between the different methods were analyzed, and their correlation was assessed by interclass correlation coefficients (ICCs), Bland–Altman plot, and correlation test. Results The ALs (mm) measured with Myopia Master, IOLMaster 500, and IOLMaster 700 were 23.67 ± 1.26, 23.68 ± 1.26, and 23.70 ± 1.25, respectively. The mean values and standard deviations for AL and keratometry readings from these devices were similar (P ≥ 0.059). The ICC analysis also revealed high consistency between the measurements (ICC ≥ 0.943). Additionally, the correlation coefficients were relatively high (r > 0.9, p

AIM: To explore the expression levels of long non-coding RNA maternally expressed gene 3(lncRNA MEG3)and Micro RNA-138(miR-138)in serum of patients with wet age-related macular degeneration(ARMD)hemorrhage and their relationship with the prognosis of patients.METHODS: A prospective study. A total of 90 patients with wet ARMD hemorrhage admitted from January 2018 to June 2021 were selected as the observation group, and 78 people who underwent physical examination in our hospital during the same period were selected as the control group. Real-time fluorescent quantitative PCR(qRT-PCR)was used to detect the expression levels of serum lncRNA MEG3 and miR-138 in all subjects. Patients in the observation group were injected with Ranibizumab for treatment once a month, for a total of 3 times. The observation group was followed up for 3mo after treatment, and the patients were divided into good prognosis and poor prognosis group.The levels of lncRNA MEG3 and miR-138 were compared between the two groups. Pearson correlation was used to analyze the correlation between lncRNA MEG3 and miR-138. The receiver operating characteristic curve(ROC)was used to analyze the value of judging the poor prognosis of patients with wet ARMD hemorrhage. Multivariate Logistic regression was used to analyze the factors affecting the poor prognosis of patients with wet ARMD hemorrhage.RESULTS: Compared with the control group, the level of serum lncRNA MEG3 in the observation group decreased(1.13±0.37 vs 0.71±0.21), and the miR-138 level increased(1.05±0.29 vs 2.23±0.54; all P

Abstract Brain tumor (BT) is one of many malignancies that have substantially enhanced global human morbidity and mortality rates. Early detection and characterization of glioma are essential for effective preventive strategies. Currently, the use of Transformers, a deep learning model for BT diagnosis and treatment, is attracting significant attention. The transformer self‐attention mechanism automatically learns the associations between input data for efficient processing and analysis. Research indicates that Transformers could play an essential role in the BT segmentation of magnetic resonance imaging (MRI) images, the MRI and histopathology‐based grading of brain cancer, BT molecular expression prediction, the classification of primary brain metastasis sites, voxel‐level dose and BT radiotherapy outcome prediction, synergistic prediction, and the pathway deconvolution of drug combinations. In this review, the feasibility, accuracy, and applicability of various algorithms are systematically analyzed and their prospects are discussed. Overall, this review aimed to discuss and provide an overview of the increasing applications of Transformers in real‐time BT detection and therapy, indicating their broad prospects and potential. In the future, Transformers are expected to be increasingly used for the diagnosis and subsequent treatment of BT because of the continuous development and improvement of Transformer‐based deep learning technology. However, more work is required to investigate their properties for anomaly detection, medical image classification, network design development, and application to other medical data.

Abstract Adoptive cell therapy (ACT) was one of the most promising anti-tumor modalities that has been confirmed to be especially effective in treating hematological malignancies. However, the clinical efficacy of ACT on solid tumor was greatly hindered by the insufficient tumor-infiltration of cytotoxic CD8 + T cells. Herein, we constructed a nanoplatform termed dual-binding magnetic nanoparticles (DBMN) that comprised PEG-maleimide (Mal), hyaluronic acid (HA) and Fe3O4 for adoptive T cell-modification and ACT-sensitization. After a simple co-incubation, DBMN was anchored onto the cell membrane (Primary linking) via Michael addition reaction between the Mal and the sulfhydryl groups on the surface of T cells, generating magnetized T cells (DBMN-T). Directed by external magnetic field and in-structure Fe3O4, DBMN-T was recruited to solid tumor where HA bond with the highly expressed CD44 on tumor cells (Secondary Linking), facilitating the recognition and effector-killing of tumor cells. Bridging adoptive T cells with host tumor cells, our DBMN effectively boosted the anti-solid tumor efficacy of ACT in a mouse model and simultaneously reduced toxic side effects.

AIM: To identify the disease-causing mutation in a four-generation Chinese family diagnosed with Nance-Horan syndrome (NHS). METHODS: A Chinese family, including four affected patients and four healthy siblings, was recruited. All family members received ophthalmic examinations with medical histories provided. Targeted next-generation sequencing approach was conducted on the two affected males to screen for their disease-causing mutations. RESULTS: Two male family members diagnosed with NHS manifested bilateral congenital cataracts microcornea, strabismus and subtle facial and dental abnormalities, while female carriers presented posterior Y-sutural cataracts. A novel frameshift mutation (c.3916_3919del) in the NHS gene was identified. This deletion was predicted to alter the reading frame and generate a premature termination codon after a new reading frame. CONCLUSION: The study discovers a new frameshift mutation in a Chinese family with NHS. The findings broaden the spectrum of NHS mutations that can cause NHS in Chinese patients.

Abstract Active temperature control devices are widely used for the thermal management of enclosures, including vehicles and buildings. Passive radiative cooling has been extensively studied; however, its integration with existing actively temperature regulated and decorative enclosures has slipped out of the research at status quo. Here, we present a photonic-engineered dual-side thermal management strategy for reducing the active power consumption of the existing temperature-regulated enclosure without sacrificing its aesthetics. By coating the exterior and interior of the enclosure roof with two visible-transparent films with distinctive wavelength-selectivity, simultaneous control over the energy exchange among the enclosure with the hot sun, the cold outer space, the atmosphere, and the active cooler can be implemented. A power-saving of up to 63% for active coolers of the enclosure is experimentally demonstrated by measuring the heat flux compared to the ordinary enclosure when the set temperature is around 26°C. This photonic-engineered dual-side thermal management strategy offers facile integration with the existing enclosures and represents a new paradigm toward carbon neutrality.

Objective. This study aimed to evaluate conjunctival vessels in patients with dry eye disease (DED) using optical coherence tomography angiography (OCTA). Methods. This was a cross-sectional, observational clinical study. Twenty-three eyes of 18 patients with DED and 28 eyes of 23 healthy controls were included for examination in this study. The evaluation included the application of an Ocular Surface Disease Index Questionnaire, Schirmer Basic Secretion Test, and anterior OCTA targeting the temporal conjunctiva. AngioTool software was used to quantify the total vessel length and vessel density in the 3 × 3 mm temporal region of interest. Results. Blood vessel density measurements were compared across the OCTA systems. The total vessel length within the conjunctiva of the DED group (4799.34 ± 834.36) exceeded that of the control eye (3864.89 ± 1455.70) group (P

Nowadays, adolescents would like to share their daily lives via social media platforms, which presents an excellent opportunity for us to leverage these data to develop techniques to measure their mental health status, such as depression. Previous researches focus on the more accurate detection of depression through statistical learning and ignore psychological understanding of depression. However, psychologists have given lots of theoretical evidence for depression. Such as according to cognitive psychology research, cognitive distortions will result in depression. Thus, in this study, we propose a new task, explainable depression detection, to not only automatically detect depression but also try to give clues to depression based on cognitive distortion theory. For this purpose, we construct a multi-task learning model based on a pre-trained model to detect depression and identify cognitive distortion. And we use many analytical means including word clouds for data analysis to draw our conclusion. Previous social media users' depression corpus and our cognitive distortion corpus are utilized for analysis and experiment. Our experimental results outperform the baseline results and interesting conclusions about adolescent depression are drawn.

Abstract Background Gene therapy shows great promise for a broad array of diseases. However, we found that hypoxic tumor microenvironment (TME) exerted significant inhibitory effects on transfection efficiency of a variety of gene vectors (such as Lipo 2000 and PEI) in an oxygen-dependent manner. Solid tumors inevitably resulted in acute hypoxic areas due to the rapid proliferation of tumor cells and the aberrant structure of blood vessels. Thus, the hypoxic TME severely limited the efficiency and application of gene therapy. Methods In our previous study, we constructed endoplasmic reticulum-targeted cationic liposomes, PAR-Lipo, which could effectively deliver genes and ensure high transfection efficiency under normoxia. Unsatisfactorily, the transfection efficiency of PAR-Lipo was rather poor under hypoxia. We believed that reoxygenation was the most direct and effective means to rescue the low transfection under hypoxia. Hence, we fabricated liposomes modified with perfluorooctyl bromide (PFOB@Lipo) to load oxygen and deliver it to tumor sites, which effectively alleviated the hypoxic nature of tumor. Then PAR-Lipo were applied to mediate high-efficiency delivery of tumor suppressor gene pTP53 to inhibit tumor progression. Results The results showed that such staged strategy augmented the expression of P53 protein in tumors and extremely suppressed tumor growth. Conclusion This work was the first attempt to utilize an oxygen nanocarrier to assist the therapeutic effect of gene therapy under hypoxia, providing a new reference for gene therapy in malignant tumors. Graphical Abstarct

Abstract Background Photothermal therapy (PTT) is a highly effective treatment for solid tumors and can induce long-term immune memory worked like an in situ vaccine. Nevertheless, PTT inevitably encounters photothermal resistance of tumor cells, which hinders therapeutic effect or even leads to tumor recurrence. Naïve CD8+ T cells are mainly metabolized by oxidative phosphorylation (OXPHOS), followed by aerobic glycolysis after activation. And the differentiate of effector CD8+ T cell (CD8+ Teff) into central memory CD8+ T cell (CD8+ TCM) depends on fatty acid oxidation (FAO) to meet their metabolic requirements, which is regulated by adenosine monophosphate activated protein kinase (AMPK). In addition, the tumor microenvironment (TME) is severely immunosuppressive, conferring additional protection against the host immune response mediated by PTT. Methods Metformin (Met) down-regulates NADH/NADPH, promotes the FAO of CD8+ T cells by activating AMPK, increases the number of CD8+ TCM, which boosts the long-term immune memory of tumor-bearing mice treated with PTT. Here, a kind of PLGA microspheres co-encapsulated hollow gold nanoshells and Met (HAuNS-Met@MS) was constructed to inhibit the tumor progress. 2-Deoxyglucose (2DG), a glycolysis inhibitor for cancer starving therapy, can cause energy loss of tumor cells, reduce the heat stress response of tumor cell, and reverse its photothermal resistance. Moreover, 2DG prevents N-glycosylation of proteins that cause endoplasmic reticulum stress (ERS), further synergistically enhance PTT-induced tumor immunogenic cell death (ICD), and improve the effect of immunotherapy. So 2DG was also introduced and optimized here to solve the metabolic competition among tumor cells and immune cells in the TME. Results We utilized mild PTT effect of HAuNS to propose an in situ vaccine strategy based on the tumor itself. By targeting the metabolism of TME with different administration strategy of 2DG and perdurable action of Met, the thermotolerance of tumor cells was reversed, more CD8+ TCMs were produced and more effective anti-tumor was presented in this study. Conclusion The Step-by-Step starving-photothermal therapy could not only reverse the tumor thermotolerance, but also enhance the ICD and produce more CD8+ TCM during the treatment. Graphical Abstract

Cancer cells circumvent immune surveillance via diverse strategies. In accordance, a large number of complex studies of the immune system focusing on tumor cell recognition have revealed new insights and strategies developed, largely through major histocompatibility complexes (MHCs). As one of them, tumor-specific MHC-II expression (tsMHC-II) can facilitate immune surveillance to detect tumor antigens, and thereby has been used in immunotherapy, including superior cancer prognosis, clinical sensitivity to immune checkpoint inhibition (ICI) therapy and tumor-bearing rejection in mice. NK cells play a unique role in enhancing innate immune responses, accounting for part of the response including immunosurveillance and immunoregulation. NK cells are also capable of initiating the response of the adaptive immune system to cancer immunotherapy independent of cytotoxic T cells, clearly demonstrating a link between NK cell function and the efficacy of cancer immunotherapies. Eosinophils were shown to feature pleiotropic activities against a variety of solid tumor types, including direct interactions with tumor cells, and accessorily affect immunotherapeutic response through intricating cross-talk with lymphocytes. Additionally, microbial sequencing and reconstitution revealed that commensal microbiota might be involved in the modulation of cancer progression, including positive and negative regulatory bacteria. They may play functional roles in not only mucosal modulation, but also systemic immune responses. Here, we present a panorama of the cancer immune network mediated by MHCI/II molecules, immune cells and commensal microbiota and a discussion of prospective relevant intervening mechanisms involved in cancer immunotherapies.

ObjectiveA number of studies in adults and children with generalized tonic-clonic seizure (GTCS) have reported the alterations in morphometry, functional activity, and functional connectivity (FC) in the thalamus. However, the neural mechanisms underlying the alterations in the thalamus of patients with GTCS are not well understood, particularly in children. The aim of the current study was to explore the temporal properties of functional pathways connecting thalamus in children with GTCS.MethodsHere, we recruited 24 children with GTCS and 36 age-matched healthy controls. Static and dynamic FC approaches were used to evaluate alterations in the temporal variability of thalamo-cortical networks in children with GTCS. The dynamic effective connectivity (dEC) method was also used to evaluate the directions of the fluctuations in effective connectivity. In addition, the relationships between the dynamic properties and clinical features were assessed.ResultsThe static FC analysis presented significantly decreased connectivity patterns between the bilateral thalamus and between the thalamus and right inferior temporal gyrus. The dynamic connectivity analysis found decreased FC variability in the thalamo-cortical network of children with epilepsy. Dynamic EC analyses identified increased connectivity variability from the frontal gyrus to the bilateral thalamus, and decreased connectivity variability from the right thalamus to the left thalamus and from the right thalamus to the right superior parietal lobe. In addition, correlation analysis revealed that both static FC and connectivity temporal variability in the thalamo-cortical network related to the clinical features (epilepsy duration and epilepsy onset time).SignificanceOur findings of both increased and decreased connectivity variability in the thalamo-cortical network imply a dynamic restructuring of the functional pathways connecting the thalamus in children with GTCS. These alterations in static and temporal dynamic pathways connecting the bilateral thalamus may extend our understanding of the neural mechanisms underlying the GTCS in children.

IntroductionThe aim of the present study was to examine interhemispheric functional connectivity (FC) and topological organization within the default-mode network (DMN) in children with generalized tonic-clonic seizures (GTCS).MethodsResting-state functional MRI was collected in 24 children with GTCS and 34 age-matched typically developing children (TDC). Between-group differences in interhemispheric FC were examined by an automated voxel-mirrored homotopic connectivity (VMHC) method. The topological properties within the DMN were also analyzed using graph theoretical approaches. Consistent results were detected and the VMHC values were extracted as features in machine learning for subject classification.ResultsChildren with GTCS showed a significant decrease in VMHC in the DMN, including the hippocampal formation (HF), lateral temporal cortex (LTC), and angular and middle frontal gyrus. Although the patients exhibited efficient small-world properties of the DMN similar to the TDC, significant changes in regional topological organization were found in the patients, involving the areas of the bilateral temporal parietal junction, bilateral LTC, left temporal pole, and HF. Within the DMN, disrupted interhemispheric FC was found between the bilateral HF and LTC, which was consistent with the VMHC results. The VMHC values in bilateral HF and LTC were significantly correlated with clinical information in patients. Support vector machine analysis using average VMHC information in the bilateral HF and LTC as features achieved a correct classification rate of 89.34% for the classification.ConclusionThese results indicate that decreased homotopic coordination in the DMN can be used as an effective biomarker to reflect seizure effects and to distinguish children with GTCSs from TDC.

Data-to-text generation plays an important role in natural language processing by processing structured data and helping people understand those data by generating user-friendly descriptive text. It can be applied to news generation, financial report generation, customer service, etc. However, in practice, it needs to adapt to different domains that may lack an annotated training corpus. To alleviate this dataset scarcity problem, distantly-supervised data-to-text generation has emerged, which constructs a training corpus automatically and is more practical to apply to new domains when well-aligned data is expensive to obtain. However, this distant supervision method of training induces an over-generation problem since the automatically aligned text includes hallucination. These expressions cannot be inferred from the data, misguiding the model to produce unfaithful text. To exploit the noisy dataset while maintaining faithfulness, we empower the neural data-to-text model by dynamically increasing the weights of those well-aligned training instances and reducing the weights of the low-quality ones via meta learning. To our best knowledge, we are the first to alleviate the noise in distantly-supervised data-to-text generation via meta learning. In addition, we rewrite those low-quality texts to provide better training instances. Finally, we construct a new distantly-supervised dataset, DIST-ToTTo (abbreviation for Distantly-supervised Table-To-Text), and conduct experiments on both the benchmark WITA (abbreviation for the data source Wikipedia and Wikidata) and DIST-ToTTo datasets. The evaluation results show that our model can improve the state-of-the-art DSG (abbreviation for Distant Supervision Generation) model across all automatic evaluation metrics, with an improvement of 3.72% on the WITA dataset and 3.82% on the DIST-ToTTo dataset in terms of the widely used metric BLEU (abbreviation for BiLingual Evaluation Understudy). Furthermore, based on human evaluation, our model can generate more grammatically correct and more faithful text compared to the state-of-the-art DSG model.

Status epilepticus (SE) is a medical emergency associated with acute severe systemic damage and high mortality. Moreover, symptomatic SE is one of the highest risk factors for epileptogenesis. While the antiepileptic drugs (AEDs) are chosen in favor of acute control of SE, the potential short-term and long-term effects of such AEDs have been ignored in clinics. In this study, we hypothesized that AEDs that are used to control acute SE might affect the feasibility for the chronic development of epileptogenesis after SE. Therefore, we sought to compare the epileptogenic effects of SE that are terminated by three AEDs, i.e., diazepam, midazolam, and pentobarbital, which are widely used as first-line anti-SE AEDs. For this purpose, we used a mouse model of SE induced by intraperitoneal (i.p.) injection of lithium chloride (LiCl)-pilocarpine. The pilocarpine-induced SE was terminated with diazepam, midazolam, or pentobarbital. Then we compared short-term and long-term effects of SE with different AED treatments by examining SE-associated mortality and behavioral spontaneous recurrent seizures (SRSs) and by using magnetic resonance imaging (MRI) and immunohistochemistry to evaluate pathological and cellular alterations of mice in the different treatment groups. We found that i.p. injections of diazepam (5 mg/kg), midazolam (10 mg/kg), and pentobarbital (37.5 mg/kg) were able to terminate acute pilocarpine-SE effectively, while pentobarbital treatment showed less neuroprotective action against lethality in the short phase following SE. Long-term evaluation following SE revealed that SE treated with midazolam had resulted in relatively less behavioral SRS, less hippocampal atrophy, and milder neuronal loss and gliosis. Our data revealed an obvious advantage of midazolam vs. diazepam or pentobarbital in protecting the brain from epileptogenesis. Therefore, if midazolam provides as strong action to quench SE as other AEDs in clinics, midazolam should be the first choice of anti-SE AEDs as it provides additional benefits against epileptogenesis.

PurposeTo evaluate the outcomes in corneal higher-order aberrations (HOAs) and microdistortions in the Bowman’s layer after femtosecond laser small incision lenticule extraction (SMILE) for correcting extremely high myopia.MethodsThis prospective study included patients with myopia with spherical equivalent ≥ -9.0 Diopters (D). SMILE was performed in forty eyes of 40 patients. Pentacam was used to evaluate HOAs before and at 1 day, 3 months, 6 months, and 2 years after surgery. Fourier-domain optical coherence tomography was used to evaluate microdistortions at 2 years postoperatively. Thirty-two eyes of 32 patients receiving femtosecond laser-assisted in situ keratomileusis (FS-LASIK) were enrolled as the control group. HOAs were measured before, at 1 day and at least 1 year postoperatively.ResultsAfter SMILE, the long-term safety and effectiveness index was 1.25 and 0.85, respectively. Microdistortions were observed in 73.5% of the eyes at 2 years, with an average number of 1.20 ± 1.22 microdistortions and an average width of 287.37 ± 259.00 μm. We detected more microdistortions in the horizontal meridian than in the vertical meridian (p = 0.035). The average number and width of microdistortions were both higher in the central region (≤4 mm) than in the peripheral region (4–8 mm) (both p < 0.001). With the exception of horizontal trefoil in the SMILE group and vertical trefoil in the FS-LASIK group, significant changes over time were observed in all other HOAs (all p < 0.05). Meanwhile, we detected significant increases in the total corneal HOA, spherical aberration (SA), and coma at all time-points after both surgeries (all p < 0.01). Compared with FS-LASIK, SMILE induced less SA (p < 0.001) and more horizontal coma (p = 0.036). In the SMILE group, the HOA, SA, and trefoil were more in the small optical zone (≤6.0 mm) than in the large optical zone (>6.0 mm) (all p < 0.05). The increase in SA and most trefoil correlated with the mean number of central microdistortions number (all p < 0.05).ConclusionFor myopia over −9.0D, the microdistortions in the Bowman’s layer were still detectable in most eyes long-term after SMILE. Both SMILE and FS-LASIK induced more HOAs, mainly HOA, SA, and coma. The small optical zone and microdistortions may affect postoperative aberrations.

PurposeTo investigate the influence of preoperative adjunctive anti-VEGF drug (Conbercept) on vitreous inflammatory cytokines and chemokines profiles and whether those cytokines were associated with early macular edema (ME) after surgery for patients with proliferative diabetic retinopathy (PDR).MethodsIn this post hoc analysis of the CONCEPT clinical trial, subjects with PDR underwent vitrectomy were included and vitreous samples were collected at the start of vitrectomy. Levels of vitreous VEGF, 17 inflammatory cytokines, and 11 chemokines were measured using Luminex multiplex technology. Subjects were then divided into groups based on with (Pre-IV) or without (No-Pre-IV) preoperative intravitreous injection of Conbercept; with or without early ME after surgery.ResultsThere was no difference between Pre-IV (13/30) and No-Pre-IV (7/29) concerning the ratio of patients with early ME (p = 0.17). After preoperative intravitreous injection of Conbercept, VEGF level dramatically decreased (p = 0.001), TNF-α (p = 0.002), and IP-10 (p = 0.018) increased in Pre-IV group. In patients with early ME after surgery, however, a number of cytokines increased, including IL-1β (p = 0.008), IL-2 (p = 0.023), IL-4 (p = 0.030), IL-9 (p = 0.02), IL-10 (p = 0.002), IL-12 (p = 0.001), IL-13 (p = 0.031), IL-17A (p = 0.008), TNF-α (p = 0.012), CXCL9 (p = 0.023), G-CSF (p = 0.019), MCP-1 (p = 0.048), and RANTES (p = 0.016).ConclusionWe found the preoperative adjunctive Conbercept injection has limited influence on the levels of vitreous inflammatory cytokines and chemokines in PDR. The elevated levels of a series of cytokines might be associated with early inflammation after vitrectomy, which may lead to postoperative ME.

ObjectiveAFF2 mutations were associated with X-linked intellectual developmental disorder-109 and in males with autism spectrum disorder (ASD). The relationship between AFF2 and epilepsy has not been defined.MethodTrios-based whole-exome sequencing was performed in a cohort of 372 unrelated cases (families) with partial (focal) epilepsy without acquired causes.ResultsFive hemizygous missense AFF2 mutations were identified in five males with partial epilepsy and antecedent febrile seizures without intellectual disability or other developmental abnormalities. The mutations did not present in the controls of general populations with an aggregate frequency significantly higher than that in the control populations. Previously, intellectual disability-associated AFF2 mutations were genomic rearrangements and CCG repeat expansion mutations mostly, whereas the mutations associated with partial epilepsy were all missense. Missense AFF2 mutations associated with epilepsy fell into the regions from N-terminal to the nuclear localization signal 1 (NLS1), while ASD-associated missense mutations fell in the regions from NLS1 to C-terminal.ConclusionAFF2 is potentially a candidate causative gene of X-link partial epilepsy with antecedent febrile seizures. The genotype–phenotype correlation and molecular sub-regional effect of AFF2 help in explaining the mechanisms underlying phenotypic variations.

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease with high mortality and disability. Aberrant neuroinflammation has been identified as a critical factor accounting for the poor prognosis of SAH patients. Mast cells (MCs), the sentinel cells of the immune system, play a critical in the early immune reactions and participate in multiple pathophysiological process. However, the exact role of MCs on the pathophysiological process after SAH has not been fully understood. The current study was conducted to determine the role of MCs and MC stabilization in the context of SAH. Mouse SAH model was established by endovascular perforation process. Mice received saline or cromolyn (MC stabilizer) or compound 48/80 (MCs degranulator). Post-SAH evaluation included neurobehavioral test, western blot, immunofluorescence, and toluidine blue staining. We demonstrated that SAH induced MCs activation/degranulation. Administration of MC stabilizer cromolyn conferred a better neurologic outcome and decreased brain edema when compared with SAH+vehicle group. Furthermore, cromolyn significantly inhibited neuroinflammatory response and alleviated neuronal damage after SAH. However, pharmacological activation of MCs with compound 48/80 dramatically aggravated SAH-induced brain injury and exacerbated neurologic outcomes. Notably, pharmacological inhibition of microglial PAR-2 significantly reversed MCs-induced inflammatory response and neurological impairment. Additionally, the effect of MCs-derived tryptase in mediating neuroinflammation was also abolished by the microglial PAR-2 blockage in vitro. Taken together, MCs yielded inflammatory injury through activating microglia-related neuroinflammation after SAH. These data shed light on the notion that MCs might be a novel and promising therapeutic target for SAH.

Objective: The main goal of this study is to clarify the electroencephalogram (EEG) characteristics of the stress response caused by vestibular endurance training under real conditions.Methods: Ten pilot trainees received a series of acute anti-vertigo training stimulations on the rotary ladder while recording electroencephalographic data (64 electrodes). Afterward, the anti-vertigo ability of the subject was tested for the best performance after 1 month of training and verified whether it is related to the EEG signals we collected before.Results: (1) The absolute power of α waves in the C3 and C4 regions is the same as the difference between 1 min before and 2 min after stimulation, and their activity is enhanced by stimulation. Otherwise, the activation of the C3 region after 5 min of stimulation is still significantly changed. (2) Through Spearman's correlation analysis, we found that the α waves in the C3 and C4 the greater the power change, the better the performance of the subject in the proficient stage.Conclusion: C3 and C4 areas are specific brain regions of the stress response of anti-vertigo endurance training, and the absolute power of the α wave can be used as a parameter for identifying the degree of motion sickness (MS). The absolute power changes of α waves in the C3 and C4 areas are positively correlated with their anti-vertigo potential.Significance: Increasing the absolute power of α wave in the C3 and C4 is a manifestation of MS stress adaptability.

The potential side effects of cabazitaxel (CBZ) in the field of cancer treatment have become a great limitation to its further clinical application. Liposomal delivery is a well-established approach to increase the therapeutic index of hydrophobic drugs. In this study, a PEG-modified liposome was developed for efficiently encapsulating CBZ, thus enhancing its specific tumor inhibition effect and reducing the systemic toxicity. It was found that the loading efficiency of CBZ into the liposome could be improved with the increase of lipophilic materials, as it could be over 80% under the weight ratio of 20:1 (total lipid: CBZ). The diameter of CBZ loaded liposome (CBZ@Lipo) was ∼100 nm. And the liposome suspending in aqueous medium was stable at 4 °C for at least one month, according to the change of its size distribution. The killing ability of CBZ@Lipo to cancer cells was significantly lower comparing to that of CBZ solution, which could be attributed to the slow release of CBZ from the liposomes. However, CBZ@Lipo could induce an obvious apoptosis of the cancer cells at low concentration. Furthermore, CBZ@Lipo exhibited an expressively enhanced tumor growth inhibition effect comparing to CBZ solution. More importantly, CBZ@Lipo showed an obviously higher biosafety proved by lower hemolysis probability, stable body weight of mice during the whole experiment and no obvious lesion in histology analysis. Our work provided a useful reference of the formulation of CBZ, which had potential for greater clinical application. Keywords: Cabazitaxel, Liposome, Stability, Apoptosis, Biosafety

Abstract Background Long non-coding RNA plays a crucial role in the occurrence and progression of glioma. We aimed to explore the function of LINC00174 in cell proliferation, apoptosis, migration, invasion and glycolysis of glioma cells, and investigate the molecular mechanism involved. Methods LINC00174 expression in glioma tissues and peritumoral brain edema (PTBE) tissues was examined by RT-qPCR and in situ hybridization. The CCK-8, TUNEL, wound healing, transwell, and ELISA assays were performed to identify the effects of LINC00174 knockdown on cell viability, apoptosis, migration, invasion, and glycolysis, respectively. RNA immunoprecipitation, dual-luciferase reporter, RNA pull down, and western blot assays were performed to explore the molecular mechanisms of LINC00174 in glioma cells. A nude mouse xenograft model was used to investigate the role of LINC00174 in xenograft glioma growth. Results LINC00174 was overexpressed in glioma tissues and cell lines. LINC00174 knockdown inhibited cell proliferation, migration, invasion and glycolysis of glioma cells, and LINC00174 exerted a tumorigenesis role. LINC00174 could interact with miR-152-3p/SLC2A1 axes. The miR-152-3p inhibitor or the SLC2A1 overexpression could rescue the anti-tumor effect of LINC00174 knockdown on glioma cells. Moreover, downregulation of LINC00174 also inhibited tumor volume and delayed the tumor growth in vivo. Conclusion LINC00174 accelerated carcinogenesis of glioma via sponging miR-1523-3p and increasing the SLC2A1 expression, which could be considered as a molecular target for glioma diagnosis and therapy.

Reactive oxygen species induced by endoplasmic reitculum stress can be exploited for cancer therapy. Here, nanoparticles are targetted to the endoplasmic reticulum and, when accompanied by PDT, produce stress resulting in calreticulin exposure on the cell surface, which activates dendritic cells.

Abstract Background This study compares the clinical outcomes of femtosecond laser small-incision lenticule extraction (SMILE) for the correction of myopia and myopic astigmatism greater than − 10 D, and − 10 D or less respectively. Methods 60 eyes/patients were equally selected into group 1 (myopia and myopic astigmatism of − 10 D or less) and group 2 (myopia and myopic astigmatism of over − 10 D), both of which were treated with SMILE. Visual and refractive outcomes, corneal higher-order aberrations, and Bowman’s layer micro-distortions were evaluated preoperatively, 3 months, and 6 months postoperatively. Results LogMAR corrected distance visual acuity (CDVA) of group 1 and group 2 was − 0.069 ± 0.047 and − 0.053 ± 0.073 6 months postoperatively (P = 0.48). 100% eyes in group 1 and 97% in group 2 were within 1 D of targeted correction (P = 0.45). Meanwhile, 100% eyes in group 1 and 97% in group 2 had an uncorrected distance visual acuity of 20/25 or better (P = 0.20). Changes in corneal higher-order aberrations root mean square, coma, and trefoil were similar between the two groups but spherical aberration was higher in group 2 (P − 10 D and ≤ − 10 D. Refractive outcomes showed slightly under-correction in higher myopic eyes. Higher myopic treatment tends to induce more spherical aberrations. Micro-distortions had no impact in visual and refractive outcomes.

In order to quantitatively evaluate the degree of protection in protective layer mining and provide guidance for the design of a secondary outburst elimination scheme, a variable weight-projection gray target dynamic evaluation model for the effectiveness of protective layer mining is established. The improved order relation analysis method was used to determine the subjective weight of each index toward the decision-making goal based on numerical diversity characteristics, and the initial fixed-weight calculation for mixed multi-attribute metrics was processed through the degree of index action. The variable weight function was used to dynamically adjust the fixed weight through the penalty and incentive index methods. Four indexes (gas content, gas pressure, coal seam permeability coefficient, and expansion deformation) were selected, the outburst elimination and anti-reflection were taken as the guide, and the critical value of each index for eliminating burst and the critical value of pressure relief were taken as the positive and negative bullseyes. Based on the variable weight-projection gray target decision model, the distance between the two target centers of each scheme was calculated; at the same time, the variable weight vector changed dynamically with the evaluation scheme to achieve the dynamic quantitative evaluation of the degree of protection. Additionally, compared with the calculation results of fixed weights, it was found that the variable weight-projection bullseye distance can more accurately reflect the dynamic control effect of differences in numerical combinations of multi-attribute indexes in different decision schemes based on the degree of protection of protective layer mining. Taking a mine in PingMei as the engineering background, Ding protected the Wu area, and the degree of protection in the Wu group coal seam reached 116.29%, eliminating the outburst risk of the coal seam. The Wu protected the Ji group coal seam, with the degree of outburst risk in the Ji group being reduced by 14.27, and the Ding + Wu group protected the Ji group coal seam, with the degree of outburst risk of the Ji group being reduced by 20.71%, but not eliminated. The evaluation model quantifies the degree of protection of protective layer mining, and provides a theoretical basis for further assessing whether the working face should strengthen the enhancing permeability or whether it needs to be used in tandem with high-strength outburst elimination methods.

To characterize human leukocyte antigen (HLA) loci as risk factors in aromatic antiepileptic drug-induced maculopapular exanthema (AED-MPE). A case-control study was performed to investigate HLA loci involved in AED-MPE in a southern Han Chinese population. Between January 2007 and June 2019, 267 patients with carbamazepine (CBZ), oxcarbazepine (OXC), or lamotrigine (LTG) associated MPE and 387 matched drug-tolerant controls from six centers were enrolled. HLA-A/B/C/DRB1 genotypes were determined using sequence-based typing. Potential risk alleles were validated by meta-analysis using data from different populations and in silico analysis of protein-drug interactions. HLA-DRB1*04:06 was significantly associated with OXC-MPE (p = 0.002, pc = 0.04). HLA-B*38:02 was associated with CBZ-MPE (p = 0.03). When pooled, HLA-A*24:02, HLA-A*30:01, and HLA-B*35:01 additionally revealed significant association with AED-MPE. Logistic regression analysis showed a multiplicative interaction between HLA-A*24:02 and HLA-B*38:02 in CBZ-MPE. Meta-analysis of data from different populations revealed that HLA-24*:02 and HLA-A*30:01 were associated with AED-MPE (p = 0.02 and p = 0.04, respectively). In silico analysis of protein-drug interaction demonstrated that HLA-A*24:02 and HLA-A*30:01 had higher affinities with the three aromatic AEDs than the risk-free HLA-A allele. HLA-DRB1*04:06 showed relatively specific high affinity with S-monohydroxy derivative of OXC. HLA-DRB1*04:06 is a specific risk allele for OXC-induced MPE in the Southern Han Chinese. HLA-A*24:02, possibly HLA-A*30:01, are common risk factors for AED-MPE. The multiplicative risk potential between HLA-A*24:02 and HLA-B*38:02 suggests that patients with two risk alleles are at greater risk than those with one risk allele. Inclusion of these HLA alleles in pre-treatment screening would help estimating the risk of AED-MPE.

Purpose: To evaluate the long-term safety, efficacy, predictability, and stability of small incision lenticule extraction (SMILE) for the treatment of high myopia and myopic astigmatism >−10.0 D.Methods: This was a prospective study that incorporated 35 consecutive patients (35 eyes) undergoing SMILE from September 2015 to March 2016. These patients had a mean preoperative spherical equivalent refraction of −10.06 ± 0.64 D. Patients were followed over a 4-year period and assessed for outcomes including uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, and corneal topography.Results: At 4 years post-SMILE, respective efficacy and safety indices were 1.01 ± 0.19 and 1.07 ± 0.15. In total, 97% of operated eyes achieved an UDVA of 20/25 or better. ≥1 line was gained for 9 eyes (26%), with 25 eyes (71%) remaining stable. Twenty-four (69%) and 33 (94%) eyes, respectively, were within ±0.50 D and ±1.0 D of target refraction. From 3 months to 4 years postoperatively, a mean refractive regression of −0.22 D (−0.06 D per year) was detected, whereas no significant changes in mean corneal back curvature or posterior central elevation were detected (P = 0.617 and 0.754, respectively). We detected significant increases in higher-order aberrations (HOAs) of the anterior and total cornea (all P < 0.001), with spherical aberrations and vertical coma being particularly common, whereas posterior corneal HOA remained fairly stable (all P < 0.05).Conclusion: SMILE is a safe, effective, predictable, and stable means of correcting high myopia and myopic astigmatism over a 4-year postoperative period.

Apoptosis is a vital pathological factor that accounts for the poor prognosis of traumatic spinal cord injury (t-SCI). The 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is a critical regulator for energy metabolism and proven to have antiapoptotic effects. This study aimed to investigate the neuroprotective role of PFKFB3 in t-SCI. A compressive clip was introduced to establish the t-SCI model. Herein, we identified that PFKFB3 was extensively distributed in neurons, and PFKFB3 levels significantly increased and peaked 24 h after t-SCI. Additionally, knockdown of PFKFB3 inhibited glycolysis, accompanied by aggravated neuronal apoptosis and white matter injury, while pharmacological activation of PFKFB3 with meclizine significantly enhanced glycolysis, attenuated t-SCI-induced spinal cord injury, and alleviated neurological impairment. The PFKFB3 agonist, meclizine, activated cyclin-dependent kinase 1 (CDK1) and promoted the phosphorylation of p27, ultimately suppressing neuronal apoptosis. However, the neuroprotective effects of meclizine against t-SCI were abolished by the CDK1 antagonist, RO3306. In summary, our data demonstrated that PFKFB3 contributes robust neuroprotection against t-SCI by enhancing glycolysis and modulating CDK1-related antiapoptotic signals. Moreover, targeting PFKFB3 may be a novel and promising therapeutic strategy for t-SCI.

Abstract The development of gene delivery has attracted increasing attention, especially when the introduction and application of the CRISPR/Cas9 gene editing system appears promising for gene therapy. However, ensuring biosafety and high gene editing efficiency at the same time poses a great challenge for its in vivo applications. Herein, a pardaxin peptide (PAR)‐modified cationic liposome (PAR‐Lipo) is developed. The results are indicative that significantly enhanced gene editing efficiency can be obtained through the mediation of PAR‐Lipos compared to non‐Lipos (non‐PAR‐modified liposomes) and Lipofectamine 2000, owing to its protection toward carried nucleotide by the prevention of lysosomal capture, prolongation of retention time in cells through the accumulation in the endoplasmic reticulum (ER), and more importantly, facilitation of the nuclear access via an ER‐nucleus route. Accumulation of PAR‐Lipos in the ER may improve the binding of Cas9 and sgRNA, thus further contributing to the eventually enhanced gene editing efficiency. Given their high biosafety, PAR‐Lipos are used to mediate the knockout of the oncogene CDC6 in vivo, which results in significant tumor growth inhibition. This work may provide a useful reference for enhancing the delivery of gene editing systems, thus improving the potential for their future clinical applications.

AIM: To investigate the effects and safety of intravitreal injection of Conbercept combined with macular grid pattern photocoagulation for macular edema secondary to non-ischemic branch retinal vein occlusion(BRVO). METHODS: A total of 38 patients(38 eyes )with macular edema following non-ischemic BRVO were retrospectively analyzed. All patients were given best corrected visual acuity(BCVA), intraocular pressure, slit lamp with preset lens, optic coherent tomography(OCT)and fluorescence fundus angiography(FFA)examination. The BCVA and central macular thickness(CMT)were observed before and 1wk, 1, 2, 3, 6, 9 and 12mo after treatment. The change in pre-treatment and post-treatment were compared, and the related complications were recorded. RESULTS:BCVA before treatment and 1wk, 1, 2, 3, 6, 9 and 12mo after treatment were 0.89±0.62, 0.64±0.59, 0.55±0.62, 0.46±0.43, 0.53±0.67, 0.43±0.38, 0.42±0.29, 0.40±0.30, the difference was statistically significant between that before and after treatment(PP>0.05). CMT were 683.25±236.47, 298.65±116.12, 276.89±107.28, 281.55±99.62, 251.41±119.47, 240.58±88.62, 231.74±75.36, 209.51±84.68μm, the difference was statistically significant between that before and after treatment(PP>0.05). There were 11 eyes received one injection, 18 eyes with two injections, 2 eyes with 3, 3 eyes with 4, and 4 eyes more than 4, the average injection was 2.01±1.42. The CMT decreased after every injection. The intraocular hypertension and other complications were not seen after treatment. CONCLUSION: Intravitreal injection of conbercept combined with macular grid pattern photocoagulation for macular edema to non-ischemic BRVO can reduce the macular edema and improve BCVA, which is effective and safety.

Background/Aims: Atherosclerosis, a multifactorial chronic disease, is the main cause of death and impairment in the world. Endothelial cells (ECs) apoptosis plays a crucial role in the onset and development of atherosclerosis, whereas the underlying molecular mechanisms are unclear. MicroRNA-142-3p (miR-142-3p) is a well-defined tumor suppressor in several types of cancer, while the role of miR-142-3p in ECs apoptosis and the development of atherosclerosis has yet to be elucidated. Therefore, the present study aimed to investigate the role of miR-142-3p in ECs apoptosis during atherosclerosis and the underlying mechanism. Methods: Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox-LDL). The expression level of miR-142-3p was detected using qRT-PCR. Apoptosis was determined via flow cytometry and Caspase-3 activity assay. Prediction of the binding between miR-142-3p and 3’-UTR of Rictor mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-142-3p on endothelial apoptosis and atherosclerosis were further analyzed in an in vivo model using ApoE-/- mice fed with high-fat diet (HFD). Results: MiR-142-3p expression was substantially up-regulated during the ox-LDL-elicited apoptosis in HAECs. Forced expression of miR-142-3p exacerbated apoptosis in ECs whereas inhibition of miR-142-3p could partly alleviate apoptotic cell death mediated by ox-LDL. Further analysis identified Rictor as a direct target of miR-142-3p, and Rictor knockdown abolished the anti-apoptotic effect of miR-142-3p inhibitor. Moreover, the Akt/endothelial nitric oxide synthase (eNOS) signaling pathway was found to mediate the beneficial effect of miR-142-3p inhibitor on endothelial apoptosis. Finally, systemic treatment with miR-142-3p antagomir attenuated endothelial apoptosis and retarded the progression of atherosclerosis in the aorta of ApoE-/- mice. Conclusions: Down-regulation of miR-142-3p inhibited ECs apoptosis and atherosclerotic development by up-regulating the expression of Rictor and activating the Akt/eNOS signaling pathway. This indicates that miR-142-3p may be a potential target for the prevention and treatment of atherosclerosis.