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ObjectiveTo explore the application value and related factors of serum carbonic anhydrase Ⅲ (CAⅢ) in the clinical diagnosis of mild to moderate Alzheimer disease (AD). MethodsA total of 106 elderly patients initially diagnosed with mild to moderate AD at Huashan Hospital, Fudan University from October 2020 to November 2022 were enrolled as the AD group, and 89 healthy elderly people during the same period were enrolled as the control group. The serum biochemical indicators including liver and kidney function, blood lipids, blood glucose, folic acid and homocysteine were detected in both groups. Cognitive function was assessed by Mini-mental State Examination (MMSE). Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to assess psychological status. The activities of daily living (ADL) were assessed by modified Barthel Index (BI). Serum CAⅢ levels were measured by enzyme-linked immunosorbent assay (ELISA). Correlation analysis and multivariate linear regression analysis were used to identify factors influencing serum CAⅢ levels, and receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of serum CAⅢ levels in elderly patients with mild to moderate AD. ResultsThe MMSE score of the AD group was significantly lower than that of the control group (P＜0.001), and the PHQ-9 and GAD-7 scores were significantly higher than those of the control group (P＜0.001). The serum CAⅢ level in the AD group was significantly lower than that in the control group (P＜0.000 1). In patients with AD, serum CAⅢ levels in patients with a disease course ＞3 years, accompanied by depression or anxiety, moderate AD, and serum creatinine≤111 μmol/L were significantly lower than those in patients with a disease course ≤3 years, normal emotions, mild AD, and serum creatinine ＞111 μmol/L (P＜0.05). Correlation analysis and multivariate linear regression analysis showed that serum CAⅢ levels were negatively correlated with disease duration, PHQ-9 score, GAD-7 scores and severity degree, positively correlated with serum creatinine level (P＜0.05). The PHQ-9 score, severity degree, and serum creatinine level were independent related factors for serum CAⅢ level in mild to moderate AD elderly patients (P＜0.05). ROC curve result showed that the area under the curve (AUC) of serum CAⅢ in diagnosing mild to moderate AD in elderly patients was 0.946, with sensitivity and specificity of 88.79% and 96.74%, respectively. ConclusionsSerum CAⅢ levels in elderly patients with mild to moderate AD are higher than those in healthy individuals. Mild AD, without depressive mood, and elevated serum creatinine levels are related factors for elevated serum CAⅢ levels in elderly AD patients. Serum CAⅢ may serve as a novel biological marker for the diagnosis of mild to moderate AD in the elderly.

Abstract Background Most patients with osteoporosis experience vertebral compression fracture (VCF), which significantly reduces their quality of life. These patients are at a high risk of secondary VCF regardless of treatment. Thus, accurate diagnosis of VCF is important for treating and preventing new fractures. We aimed to investigate the diagnostic and predictive value of quantitative bone imaging techniques for fresh VCF. Methods From November 2021 to March 2023, 34 patients with VCF were enrolled in this study, all of whom underwent routine 99mTc-MDP whole-body bone planar scan and local SPECT/CT imaging. The maximum standard uptake value (SUVmax) of 57 fresh VCF, 57 normal adjacent vertebrae, and 19 old VCF were measured. Based on the site of the fracture, fresh VCFs were regrouped into the intervertebral-type group and the margin-type group. Meanwhile, 52 patients who had no bone metastasis or VCFs in their bone scan were assigned to the control group. The SUVmax of 110 normal vertebral bodies and 10 old VCFs in the control group were measured. Results The median SUVmax of fresh VCF was 19.80, which was significantly higher than the SUVmax of other groups. The receiver operator characteristic (ROC) curve showed that the cut-off value of SUVmax was 9.925 for diagnosing fresh VCF. The SUVmax in the intervertebral-type group was significantly higher than that in the margin-type group (P = 0.04). The SUVmax of normal vertebrae was higher among patients than among the control group (P

Abstract To enhance the capability of identifying unknown emitters in open spaces, an open‐multiscale attention kernel (MSAK)‐convolutional neural network‐long short‐term memory (CNN‐LSTM) structure is proposed. To this end, first, a MSAK module and CNN‐LSTM structure are introduced, and then, the depth and complexity of the feature extraction network are improved to enhance its representation capability. To classify unknown emitters accurately, the MSAK‐CNN‐LSTM model is improved to obtain an open‐MSAK‐CNN‐LSTM model with open‐set recognition capability. Additionally, the two preprocessing procedures are summarised, and their strengths and weaknesses are compared. Experimental results show that the proposed open‐MSAK‐CNN‐LSTM model achieves satisfactory accuracy in identifying unknown emitters in open space. In addition, it has significant advantages in low signal‐to‐noise ratio (SNR) scenarios.

Abstract Background The therapeutic advantage of thoracic radiotherapy (tRT) as an adjunct to first‐line immunotherapy and chemotherapy in patients with extensive‐stage small cell lung cancer (ES‐SCLC) remains unclear. We sought to elucidate this in a retrospective cohort study comparing the effectiveness and safety of tRT in combination with first‐line immunotherapy and chemotherapy. Methods Our retrospective study included patients with ES‐SCLC, treated at the West China Hospital between January 2019 and December 2022. They received first‐line immunotherapy and chemotherapy and were categorized into two cohorts based on the administration of tRT. The primary outcomes were overall survival (OS) and progression‐free survival (PFS). Cox regression analysis was utilized to identify potential independent predictors of prognosis and to compare the treatment outcomes across various patient subgroups. Treatment‐related toxicities across both cohorts were compared using the Chi‐squared test. Results A total of 99patients were eligible for the study, out of which 55 received tRT. The medianduration of follow‐up was 39 months. Remarkably, patients who received tRTdemonstrated superior OS and PFS in comparison to those who did not (P

Abstract Silicon carbide (SiC) polytypes are emerging for integrated nonlinear and quantum photonics due to their wide-bandgap energies, second-order optic nonlinearity and process compatibility with complementary metal-oxide-semiconductor technologies. Among polytypes, 3C-SiC is the only one epitaxially grown on wafer-scale silicon substrates. However, on-chip nonlinear and quantum light sources leveraging the second-order nonlinearity of 3C-SiC have not been reported to our knowledge. Here, we design and fabricate an elliptical microring on 3C-SiC. We demonstrate a nonlinear light source with a second-harmonic generation efficiency of $$17.4\pm 0.2 \% {W}^{-1}$$ 17.4 ± 0.2 % W − 1 and difference-frequency generation with a signal-idler bandwidth of 97 nm. We demonstrate a spontaneous parametric down-conversion source with a photon-pair generation rate of 4.8 MHz and a coincidence-to-accidental ratio of $$3361\pm 84$$ 3361 ± 84 . We measure a low heralded single-photon second-order coherence $${g}_{H}^{\left(2\right)}=0.0007$$ g H 2 = 0.0007 . We observe time-bin entanglement with a visibility of $$86.0\pm 2.4 \%$$ 86.0 ± 2.4 % using this source. Our work paves a way toward SiC-based on-chip nonlinear and quantum photonic circuits.

Abstract Reconstructive phase transitions involving breaking and reconstruction of primary chemical bonds are ubiquitous and important for many technological applications. In contrast to displacive phase transitions, the dynamics of reconstructive phase transitions are usually slow due to the large energy barrier. Nevertheless, the reconstructive phase transformation from β- to λ-Ti3O5 exhibits an ultrafast and reversible behavior. Despite extensive studies, the underlying microscopic mechanism remains unclear. Here, we discover a kinetically favorable in-plane nucleated layer-by-layer transformation mechanism through metadynamics and large-scale molecular dynamics simulations. This is enabled by developing an efficient machine learning potential with near first-principles accuracy through an on-the-fly active learning method and an advanced sampling technique. Our results reveal that the β−λ phase transformation initiates with the formation of two-dimensional nuclei in the a b-plane and then proceeds layer-by-layer through a multistep barrier-lowering kinetic process via intermediate metastable phases. Our work not only provides important insight into the ultrafast and reversible nature of the β−λ transition, but also presents useful strategies and methods for tackling other complex structural phase transitions.

Objective The aim of this study was to clarify whether Protein kinase B (PKB)/AKT is nitrated in myocardial ischemia and reperfusion injury (MIRI) resveratrol (RSV)’s protective effect during this process.Methods We blocked blood flow of the left coronary artery (LAD) of mice and used H9c2 cells under an oxygen-glucose deprivation (OGD) environment as animal and cell models of MIRI. N-methyl-D-aspartic acid receptor (NMDAR) inhibitor MK801, neuronal nitric oxide synthase (nNOS) inhibitor 7-NI and RSV were used as interventions. Nitration of proteins, infarction area, cardiomyocyte apoptosis and AKT nitration sites were detected during this study.Results During in-vivo study, AKT nitration was induced through the NMDAR/nNOS/peroxynitrite (ONOO–) pathway, leading to decreased phosphorylation of AKT and increased cardiomyocyte apoptosis. AKT nitration was decreased and phosphorylation was elevated when administrated with RSV, MK801 and 7-NI. In in-vitro study, AKT nitration and TUNEL positive cells was elevated when administrated with NO donor H9c2 cells after OGD/R, when administrated with RSV, MK801 and 7-NI, AKT nitration and apoptosis was deceased in H9c2 cells. Mass spectrometry revealed that nitration sites of AKT included 14 Tyrosine residues.Discussion RSV could inhibit AKT nitration and elevated phosphorylation through suppressing NMDAR/nNOS/ONOO– pathway and further reduce the apoptosis of cardiomyocytes in of myocardial I/R.

Lycium ruthenicum Murray (LR), known as “black goji berry” or “black wolfberry”, is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness. Besides elevated intraocular pressure (IOP), oxidative stress and neuroinflammation were recognized to contribute to the pathogenesis of glaucoma. This study investigated the treatment effects of LR water extract (LRE) on retinal ganglion cells (RGCs) threatened by sustained IOP elevation in a laser-induced chronic ocular hypertension (COH) mouse model and the DBA/2J mouse strain. The antioxidation and anti-inflammation effects of LRE were further tested in the H2O2-challenged immortalized microglial (IMG) cell line in vitro. LRE oral feeding (2 g/kg) preserved the function of RGCs and promoted their survival in both models mimicking glaucoma. LRE decreased 8-hydroxyguanosine (oxidative stress marker) expression in the retina. LRE reduced the number of Iba-1+ microglia in the retina of COH mice, but not in the DBA/2J mice. At the mRNA level, LRE reversed the COH induced HO-1 and SOD-2 overexpressions in the retina of COH mice. Further in vitro study demonstrated that LRE pretreatment to IMG cells could significantly reduce H2O2 induced oxidative stress through upregulation of GPX-4, Prdx-5, HO-1, and SOD-2. Our work demonstrated that daily oral intake of LRE can be used as a preventative/treatment agent to protect RGCs under high IOP stress probably through reducing oxidative stress and inhibiting microglial activation in the retina.

In recent years, burgeoning research has underscored the pivotal role of non-coding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein–protein interaction networks, mRNA–lncRNA co-expression networks, and circRNA–microRNA–mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field.

Objectives To analyze the factors influencing myopia and construct a nomogram to forecast the risk of myopia among school-age children, providing a reference for identifying high-risk groups to aid prevention and control.Methods This case-control study enrolled 3512 students from three primary schools in Shenzhen using random cluster sampling for a questionnaire survey, myopia screening and ocular biometric parameter measurement. Logistic regression was used to analyze the influencing factors of myopia, and a nomogram was constructed to forecast myopia risk. Bootstrap resampling was used to verify the practicability of the nomogram.Results Older age (odds ratio[OR] = 1.164; 95% confidence interval [CI]: 1.111–1.219), female sex (OR = 2.405; 95% CI: 2.003–2.887), maternal myopia (OR = 1.331; 95% CI: 1.114–1.589), incorrect posture during reading and writing (OR = 1.283; 95% CI: 1.078–1.528) and axial length (OR = 7.708; 95% CI: 6.044–8.288) are risk factors for myopia, whereas an increase in corneal radius (OR = 0.036; 95% CI: 0.025–0.052) is a protective factor against myopia. The area under the receiver operating characteristic (ROC) curve of the nomogram was 0.857, and the net benefit was high when the risk threshold of the decision curve analyses (DCA) ranged from 0.20 to 1.00. The measured values were consistent with the prediction.Conclusion The nomogram was accurate in predicting the risk of myopia among schoolchildren. This study provides a reference for screening high-risk students and for individualized myopia prevention and control.

Abstract Purpose To evaluate the efficacy and safety of selective aneurysmal sac neck-targeted embolization in endovascular aneurysm repair (EVAR) in patients with a hostile neck anatomy (HNA). Materials and methods Between October 2020 and June 2022, patients with an abdominal aortic aneurysm (AAA) and HNA who underwent EVAR with a low-profile stent graft and a selective aneurysmal sac neck-targeted embolization technique were analysed. An HNA was defined by the presence of any of the following parameters: infrarenal neck angulation > 60°; neck length

The use of computer vision to estimate the Body Condition Score for cow has demonstrated to be feasible. However, most research has been limited to fixed camera positions, which restricts the technique’s usefulness. This research acquired cow data at various distances and angles to investigate the impact of distance and different depth images restoration method on scoring accuracy. A U-Net neural network-based model was employed for background segmentation. The model proposed in this study performs best among SegNet, UNet, UNet++ and DeeplabV3, with significant performance improvement and superior overall segmentation accuracy, and has stronger foreground object identification capability. Additionally, we utilize the concept of human feature point localization to pinpoint the positions of cow feature points. The results show that compared to Hourglass, CPN, and Hrnet, the model in this study has significant advantages in three core indicators: accuracy, recall, and mAP. Moreover, we presented an unsupervised depth image reconstruction model based on the Denoising Diffusion Probabilistic Model and Unet++ Mode, facilitating the measurement and scoring of cow characteristics. Finally, the measurement results of cow body size using the Lerp model, autoregressive model, GAN model, and the depth image completion model proposed in this study were compared. The method proposed in this study was found to be effective and feasible for meeting actual production requirements at a camera distance of 1–2 m from the cow, achieving high accuracy with a coefficient of determination above 0.9. Additionally, the three models used were effective in handling small-scale depth deficits, with a high degree of agreement between machine and manual measurements. The DDPM-based depth image reconstruction model was found to produce the most accurate results when the camera distance from the cow was between 1-3m. Therefore, this research makes it possible to make flexible measurements in the near range using existing methods. Accurate measurements at longer ranges are influenced by depth image quality and feature point localization accuracy, which require more advanced techniques for further investigation.

Abstract The commercialization of a polymer membrane H2–O2 fuel cell and its widespread use call for the development of cost‐effective oxygen reduction reaction (ORR) nonplatinum group metal (NPGM) catalysts. Nevertheless, to meet the requests for the real‐world fuel cell application and replacing platinum catalysts, it still needs to address some challenges for NPGM catalysts regarding the sluggish ORR kinetics in the cathode and their poor durability in acidic environment. In response to these issues, numerous efforts have been made to study NPGM catalysts both theoretically and experimentally, developed these into the atomically dispersed coordinated metal–nitrogen–carbon (M–N–C) form over the past decades. In this review, we present a comprehensive summary of recent advancements on NPGM catalysts with high activity and durability. Catalyst design strategies in terms of optimizing active‐site density and enhancing catalyst stability against demetalization and carbon corrosion are highlighted. It is also emphasized the importance of understanding the mechanisms and principles behind those strategies through a combination of theoretical modeling and experimental work. Especially, further understanding the mechanisms related to the active‐site structure and the formation process of the single‐atom active site under pyrolysis conditions is critical for active‐site engineering. Optimizing the active‐site distance is the basic principle for improving catalyst activity through increasing the catalyst active‐site density. Theoretical studies for the catalyst deactivation mechanism and modeling stable active‐site structures provide both mechanisms and principles to improve the NPGM catalyst durability. Finally, currently remained challenges and perspectives in the future on designing high‐performance atomically dispersed NPGM catalysts toward fuel cell application are discussed.

Hydraulic fracturing is a crucial technology for enhancing the recovery of oil and gas from unconventional reservoirs. Accurately describing fracture morphology is essential for accurately predicting production dynamics. This article proposes a new fracture inversion model based on dynamic data-driven methods, which is different from the conventional linear elastic fracture mechanics model. This method eliminates the need to consider complex mechanical mechanisms, resulting in faster simulation speeds. In the model, the fracture morphology is constrained by combining microseismic data and fracturing construction data, and the fracture tip propagation domain is introduced to characterize the multi-directionality of fracture propagation. The simulated fracture exhibits a multi-branch fracture network morphology, aligning more closely with geological understanding. In addition, the influence of microseismic signal intensity on the direction of fracture propagation is considered in this study. The general stochastic approximation (GSA) algorithm is employed to optimize the direction of fracture propagation. The proposed method is applied to both the single-stage fracturing model and the whole well fracturing model. The research findings indicate that in the single-stage fracturing model, the inverted fracture morphology aligns closely with the microseismic data, with a fitting rate of the fracturing construction curve exceeding 95%, and a microseismic data fitting rate exceeding 93%. In the whole well fracturing model, a total of 18 sections were inverted. The fitting rate between the overall fracture morphology and the microseismic data reached 90%. The simulation only took 5 minutes, demonstrating high computational efficiency and meeting the needs of large-scale engineering fracture simulation. This method can effectively support geological modeling and production dynamic prediction.

Silicon carbide (SiC) electronics has seen a rapid development in industry over the last two decades due to its capabilities in handling high powers and high temperatures while offering a high saturated carrier mobility for power electronics applications. With the increased capacity in producing large-size, single-crystalline SiC wafers, it has recently been attracting attention from academia and industry to exploit SiC for integrated photonics owing to its large bandgap energy, wide transparent window, and moderate second-order optical nonlinearity, which is absent in other centrosymmetric silicon-based material platforms. SiC with various polytypes exhibiting second- and third-order optical nonlinearities are promising for implementing nonlinear and quantum light sources in photonic integrated circuits. By optimizing the fabrication processes of the silicon carbide-on-insulator platforms, researchers have exploited the resulting high-quality-factor microring resonators for various nonlinear frequency conversions and spontaneous parametric down-conversion in photonic integrated circuits. In this paper, we review the fundamentals and applications of SiC-based microring resonators, including the material and optical properties, the device design for nonlinear and quantum light sources, the device fabrication processes, and nascent applications in integrated nonlinear and quantum photonics.

Current stomach disease detection and diagnosis is challenged by data complexity and high dimensionality and requires effective deep learning algorithms to improve diagnostic accuracy. To address this challenge, in this paper, an improved strategy based on the Adam algorithm is proposed, which aims to alleviate the influence of local optimal solutions, overfitting, and slow convergence rates by controlling the restart strategy and the gradient norm joint clipping technique. This improved algorithm is abbreviated as the CG-Adam algorithm. The control restart strategy performs a restart operation by periodically checking the number of steps and once the number of steps reaches a preset restart period. After the restart is completed, the algorithm will restart the optimization process. It helps the algorithm avoid falling into the local optimum and maintain convergence stability. Meanwhile, gradient norm joint clipping combines both gradient clipping and norm clipping techniques, which can avoid gradient explosion and gradient vanishing problems and help accelerate the convergence of the optimization process by restricting the gradient and norm to a suitable range. In order to verify the effectiveness of the CG-Adam algorithm, experimental validation is carried out on the MNIST, CIFAR10, and Stomach datasets and compared with the Adam algorithm as well as the current popular optimization algorithms. The experimental results demonstrate that the improved algorithm proposed in this paper achieves an accuracy of 98.59%, 70.7%, and 73.2% on the MNIST, CIFAR10, and Stomach datasets, respectively, surpassing the Adam algorithm. The experimental results not only prove the significant effect of the CG-Adam algorithm in accelerating the model convergence and improving generalization performance but also demonstrate its wide potential and practical application value in the field of medical image recognition.

With the widespread application of Implantable Collamer Lens (ICL) implantation surgery in the field of myopia correction, a comprehensive understanding of its potential complications, especially those related to intraocular pressure (IOP), becomes crucial. This article systematically reviews various complications that may lead to IOP elevation after ICL surgery. Firstly, common complications after ICL surgery, including residual viscoelastic, steroid response, and excessive vault of the ICL, are detailed, emphasizing their potential impact on intraocular pressure. Regarding residual viscoelastic, we delve into its direct relationship with postoperative elevated IOP and possible preventive measures. For steroid response, we stress the importance of timely adjustment of steroid therapy and monitoring intraocular pressure. Additionally, excessive vault of the ICL is considered a significant potential issue, and we elaborate on its mechanism and possible management methods. In further discussion, we focus on relatively rare complications such as Toxic Anterior Segment Syndrome (TASS), Urrets-Zavalia Syndrome (UZS), Pigment Dispersion Syndrome (PDS), and malignant glaucoma. For these relatively rare complications, this review thoroughly explores their potential mechanisms, emphasizes the importance of prevention, and provides guidance for early diagnosis and treatment. This is a comprehensible review that aims to offer eye care professionals a comprehensive understanding and effective management guidance for complications of elevated IOP after ICL surgery, ultimately providing optimal care for patients’ visual health.

Internal short circuits because of deformation or melting down of separators have been recognized as a root cause for many thermal runaway (TR) events of high-energy-density (HED) lithium-ion batteries (LIBs). Ceramic coating of the polyolefin separators is a promising strategy but generally hinders ionic conduction. In this study, we demonstrate that co-coating the separators with boehmite ceramics and Li1.5Al0.5Ti1.5(PO4)3 (LATP) solid-state electrolytes could markedly improve the safety of LIBs while mitigating detrimental effects on electrochemical performance. We assembled HED (~350 Wh/kg) lithium-ion pouch cells with nickel-rich Li(Ni0.9CoxMn0.1-x)O2 cathodes, silicon-based/graphite blended anodes, and co-coated separators of varying thicknesses. It is found that LATP reacts with the organic liquid electrolytes and lithium to generate a robust solid-electrolyte-interface-filled LATP layer during the formation, which can prevent the thermal deformation of separators. During the thermal abusive tests, the battery's TR failure thresholds raised from 146.2 to 162.0 °C. Correspondingly, the direct failure cause of the cell TR hurdled the separator malfunction to the thermochemical reactions of the nickel-rich cathodes. Additionally, pouch cells exhibited impressive electrochemical performance, maintaining a capacity retention of 87.99% after 500 cycles at 1C.

Pterygium and subconjunctival hemorrhage are two common types of ocular surface diseases that can cause distress and anxiety in patients. In this study, 2855 ocular surface images were collected in four categories: normal ocular surface, subconjunctival hemorrhage, pterygium to be observed, and pterygium requiring surgery. We propose a diagnostic classification model for ocular surface diseases, dual-branch network reinforced by PFM block (DBPF-Net), which adopts the conformer model with two-branch architectural properties as the backbone of a four-way classification model for ocular surface diseases. In addition, we propose a block composed of a patch merging layer and a FReLU layer (PFM block) for extracting spatial structure features to further strengthen the feature extraction capability of the model. In practice, only the ocular surface images need to be input into the model to discriminate automatically between the disease categories. We also trained the VGG16, ResNet50, EfficientNetB7, and Conformer models, and evaluated and analyzed the results of all models on the test set. The main evaluation indicators were sensitivity, specificity, F1-score, area under the receiver operating characteristics curve (AUC), kappa coefficient, and accuracy. The accuracy and kappa coefficient of the proposed diagnostic model in several experiments were averaged at 0.9789 and 0.9681, respectively. The sensitivity, specificity, F1-score, and AUC were, respectively, 0.9723, 0.9836, 0.9688, and 0.9869 for diagnosing pterygium to be observed, and, respectively, 0.9210, 0.9905, 0.9292, and 0.9776 for diagnosing pterygium requiring surgery. The proposed method has high clinical reference value for recognizing these four types of ocular surface images.

Acute kidney injury (AKI) is a common disorder without effective therapy yet. Renal ischemia/reperfusion (I/R) injury is a common cause of AKI. MicroRNA miR-192-5p has been previously reported to be upregulated in AKI models. However, its functional role in renal I/R injury is not fully understood. This study aimed to investigate the effects and the underlying mechanism of miR-192-5p in renal I/R progression. Hypoxia/reoxygenation (H/R)-induced cell injury model in HK-2 cells and I/R-induced renal injury model in mice were established in this study. Cell counting kit-8 assay was performed to determine cell viability. Quantitative real-time PCR and western blot analysis were performed to detect gene expressions. Hematoxylin-eosin and periodic acid-Schiff staining were performed to observe the histopathological changes. Enzyme-linked immunosorbent assay was performed to detect the kidney markers’ expression. In vivo and in vitro results showed that miR-192-5p was up-regulated in the I/R-induced mice model and H/R-induced cell model, and miR-192-5p overexpression exacerbated I/R-induced renal damage. Then, the downstream target of miR-192-5p was analyzed by combining the differentially expressed mRNAs and the predicted genes and confirmed using a dual-luciferase reporter assay. It was found that miR-192-5p was found to regulate fat mass and obesity-associated (FTO) protein expression by directly targeting the 3’ untranslated region of FTO mRNA. Moreover, in vivo and in vitro studies unveiled that FTO overexpression alleviated renal I/R injury and promoted HK-2 cell viability via stimulating autophagy flux. In conclusion, miR-192-5p aggravated I/R-induced renal injury by blocking autophagy flux via down-regulating FTO.

High-entropy alloys (HEAs) have gained significant attentions in recent years, due to their unique properties derived from the combination of multiple elements in equimolar or near-equimolar ratios. The mechanical properties of HEAs are influenced by microstructural characteristics. In this study, MnCrFeCoNi HEA ribbons were produced using a technique called melt spinning, for which the wheel speed was adjusted to control the undercooling levels. The rapid solidification process under undercooling condition resulted in refined grain sizes to micrometers in the ribbons. One notable feature was the appearance of twin boundaries, which especially accounted for approximately 7.36 % of the microstructure for the ribbons produced at a wheel speed of 10 m/s. For the ribbons with thickness of micrometer scale, the mechanical properties (ultimate tensile strength up to 2.5 GPa and hardness up to 300 MPa) were analyzed by microstructure (grain boundaries and homogeneity) and exterior factors (e.g. thickness). Overall, this study provides a new approach for tailoring the microstructures and mechanical properties of HEAs via melt spinning technique. The HEA ribbons present a novel form that could potentially broaden the scope of applications for these materials.

This paper introduces an enhanced variant of the Adam optimizer—the BGE-Adam optimization algorithm—that integrates three innovative technologies to augment the adaptability, convergence, and robustness of the original algorithm under various training conditions. Firstly, the BGE-Adam algorithm incorporates a dynamic β parameter adjustment mechanism that utilizes the rate of gradient variations to dynamically adjust the exponential decay rates of the first and second moment estimates (β1 and β2), the adjustment of β1 and β2 is symmetrical, which means that the rules that the algorithm considers when adjusting β1 and β2 are the same. This design helps to maintain the consistency and balance of the algorithm, allowing the optimization algorithm to adaptively capture the trending movements of gradients. Secondly, it estimates the direction of future gradients by a simple gradient prediction model, combining historic gradient information with the current gradient. Lastly, entropy weighting is integrated into the gradient update step. This strategy enhances the model’s exploratory nature by introducing a certain amount of noise, thereby improving its adaptability to complex loss surfaces. Experimental results on classical datasets, MNIST and CIFAR10, and gastrointestinal disease medical datasets demonstrate that the BGE-Adam algorithm has improved convergence and generalization capabilities. In particular, on the specific medical image gastrointestinal disease test dataset, the BGE-Adam optimization algorithm achieved an accuracy of 69.36%, a significant improvement over the 67.66% accuracy attained using the standard Adam algorithm; on the CIFAR10 test dataset, the accuracy of the BGE-Adam algorithm reached 71.4%, which is higher than the 70.65% accuracy of the Adam optimization algorithm; and on the MNIST dataset, the BGE-Adam algorithm’s accuracy was 99.34%, surpassing the Adam optimization algorithm’s accuracy of 99.23%. The BGE-Adam optimization algorithm exhibits better convergence and robustness. This research not only demonstrates the effectiveness of the combination of these three technologies but also provides new perspectives for the future development of deep learning optimization algorithms.

Abstract Background Renal fibrosis (RF) is the main pathological pathway of acute kidney injury and chronic kidney disease. Its main pathological feature is extracellular matrix aggregation in the renal stroma and glomerulus. There is currently no effective treatment to delay or treat RF. Mesenchymal stem cells (MSCs) are multipotent somatic stem cells that can direct differentiation, direct cell‐cell interactions and have secretory activity. The most important secretory activity of MSCs is mediated by extracellular vesicles (EVs). At present, there is increasing evidence that EVs produced by MSCs may be used in regenerative methods of tissue repair. Aim The goal of this review is to present the latest efficacy of MSC‐EVs in the prevention, treatment and improvement of RF caused by acute and chronic kidney injury and reveals the molecular mechanism of MSCs in various models. Results and discussion MSC‐EVs show potential for RF by regulating autophagy, inhibiting apoptosis, countering oxidation, suppressing inflammation, reducing EMT and modulating angiogenesis. Conclusion MSC‐EVs show potential for treating RF. However, more studies establishing their safety, efficiency and specific mechanisms in the context of RF are still needed before further clinical application.

ObjectiveThe purpose of this study is to investigate the independent influencing factors of the transition from normal population to prediabetes, and from prediabetes to diabetes, and to further construct clinical prediction models to provide a basis for the prevention and management of prediabetes and diabetes.Materials and methodsThe data for this study were based on clinical information of participants from the Health Management Center of Peking University Shenzhen Hospital. Participants were classified into normal group, prediabetes group, and diabetes group according to their functional status of glucose metabolism. Spearman’s correlation coefficients were calculated for the variables, and a matrix diagram was plotted. Further, univariate and multivariate logistic regression analysis were conducted to explore the independent influencing factors. The independent influencing factors were used as predictors to construct the full-variable prediction model (Full.model) and simplified prediction model (Simplified.model).ResultsThis study included a total of 5310 subjects and 22 variables, among which there were 1593(30%) in the normal group, 3150(59.3%) in the prediabetes group, and 567(10.7%) in the diabetes group. The results of the multivariable logistic regression analysis showed that there were significant differences in 9 variables between the normal group and the prediabetes group, including age(Age), body mass index(BMI), systolic blood pressure(SBP), urinary glucose(U.GLU), urinary protein(PRO), total protein(TP), globulin(GLB), alanine aminotransferase(ALT), and high-density lipoprotein cholesterol(HDL-C). There were significant differences in 7 variables between the prediabetes group and the diabetes group, including Age, BMI, SBP, U.GLU, PRO, triglycerides(TG), and HDL.C. The Full.model and Simplified.model constructed based on the above influencing factors had moderate discriminative power in both the training set and the test set.ConclusionAge, BMI, SBP, U.GLU, PRO, TP, and ALT are independent risk factors, while GLB and HDL.C are independent protective factors for the development of prediabetes in the normal population. Age, BMI, SBP, U.GLU, PRO, and TG are independent risk factors, while HDL.C is an independent protective factor for the progression from prediabetes to diabetes. The Full.model and Simplified.model developed based on these influencing factors have moderate discriminative power.

The balance jack is the key component of the two-column shield hydraulic support connecting the top beam and the shield beam. The failure of the balance jack under the impact ground pressure in the fully mechanized coal mining face can easily lead to its failure and affect the safety support. In order to improve the impact resistance and safety support performance of hydraulic support and solve the problem of easily damaged balance jack, a new structure of balance jack is proposed in this paper. The performance of the pressure relief and buffer protection process is verified based on AMESim, and the unloading hole is optimized. The results show that, compared with the traditional balance jack, this new balanced jack can achieve fast buffer unloading when the hydraulic support is under impact, and has better impact resistance. The optimized unloading hole diameter is 3 mm and the number is 10.The results provide a reference for solving the impact failure problem of the balance jack and improving the reliability of hydraulic support.

Abstract To analyse the pathogenic genes and mutations of a family with hereditary deafness. We recruited a three-generation family with NSHL. A detailed medical history inquiry and related examinations were performed. Next-generation sequencing (NGS) was used to confirm the gene mutation in the proband, and Sanger sequencing was used for verification. The effect of the WFS1 mutation on the function and structure of the wolframin protein was predicted by multiple computational software. From the Gene Expression Omnibus (GEO) database, we obtained GSE40585 dataset and performed enrichment analyses. The family clinically manifested as autosomal dominant NSHL. A novel WFS1 c.2421C>G (p.Ser807Arg) mutation was identified in four affected individuals in the pedigree . The p.Ser807Arg mutation is a highly conserved residue and causes an increase in protein stability. It had an important influence on not only amino acid size, charge and hydrophobicity but also protein intermolecular hydrogen bonding and spatial structure. There were differentially expressed genes (DEGs) in GSE40585 dataset. Enrichment analysis revealed that DEGs mainly functioned in amino acid metabolism, signal transduction and dephosphorylation. We reported a novel mutation c.2421C>G (p.Ser807Arg in WFS1. This study expands the mutation spectrum of WFS1.

ObjectiveThis study aims to develop and evaluate a non-imaging clinical data-based nomogram for predicting the risk of vision-threatening diabetic retinopathy (VTDR) in diabetes mellitus type 2 (T2DM) patients.MethodsBased on the baseline data of the Guangdong Shaoguan Diabetes Cohort Study conducted by the Zhongshan Ophthalmic Center (ZOC) in 2019, 2294 complete data of T2DM patients were randomly divided into a training set (n=1605) and a testing set (n=689). Independent risk factors were selected through univariate and multivariate logistic regression analysis on the training dataset, and a nomogram was constructed for predicting the risk of VTDR in T2DM patients. The model was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC) in the training and testing datasets to assess discrimination, and Hosmer-Lemeshow test and calibration curves to assess calibration.ResultsThe results of the multivariate logistic regression analysis showed that Age (OR = 0.954, 95% CI: 0.940-0.969, p = 0.000), BMI (OR = 0.942, 95% CI: 0.902-0.984, p = 0.007), systolic blood pressure (SBP) (OR =1.014, 95% CI: 1.007-1.022, p = 0.000), diabetes duration (10-15y: OR =3.126, 95% CI: 2.087-4.682, p = 0.000; >15y: OR =3.750, 95% CI: 2.362-5.954, p = 0.000), and glycated hemoglobin (HbA1C) (OR = 1.325, 95% CI: 1.221-1.438, p = 0.000) were independent risk factors for T2DM patients with VTDR. A nomogram was constructed using these variables. The model discrimination results showed an AUC of 0.7193 for the training set and 0.6897 for the testing set. The Hosmer-Lemeshow test results showed a high consistency between the predicted and observed probabilities for both the training set (Chi-square=2.2029, P=0.9742) and the testing set (Chi-square=7.6628, P=0.4671).ConclusionThe introduction of Age, BMI, SBP, Duration, and HbA1C as variables helps to stratify the risk of T2DM patients with VTDR.

Neoadjuvant targeted therapy is an alternative treatment for locally advanced non-small cell lung cancer (NSCLC) patients with driver gene mutation. MET ex14 mutation is considered a driver gene, and crizotinib is the first oral tyrosine kinase inhibitor (TKI) for metastatic MET ex14 mutation-positive NSCLC patients. Here, we reported a case of a locally advanced NSCLC patient harboring MET ex14 mutation who achieved pathological complete response following neoadjuvant crizotinib therapy but developed rapid metastasis due to discontinuation of short-term postoperative adjuvant crizotinib therapy. Although no driver gene mutation was found via next-generation sequencing (NGS) with blood samples before discontinuation of adjuvant crizotinib, the patient was given crizotinib rechallenge. Fortunately, the patient achieved durable complete response. This suggested that neither pathological complete response nor negative circulating tumor DNA (ctDNA) could be an effective predictor for discontinuation of adjuvant targeted therapy. This case report demonstrated the potential of crizotinib as neoadjuvant therapy in MET ex14 mutation-positive NSCLC patients as well as the importance of long-term postoperative therapy even with negative ctDNA in blood.

PurposeTo assess the effect of pterygium on corneal densitometry (CD) values.MethodsOne hundred and nine patients (155 eyes) with primary pterygium were divided into a severe pterygium group (79 eyes) and a mild-to-moderate pterygium group (76 eyes) according to pterygium severity. Among them, 63 patients had monocular pterygium; and 25 patients (38 eyes) underwent pterygium excision combined with conjunctival autograft follow-up. A Pentacam anterior segment analyzer was used to obtain the CD values and corneal morphological parameters, including central corneal thickness (CCT), flat-axis keratometry (K1), steep-axis keratometry (K2), corneal astigmatism, irregular astigmatism, and spherical aberration. CD was subdivided into four concentric radial regions based on corneal diameter and three layers according to depth.ResultsCD values at 0–12 mm of the anterior 120 μm layer, 0–10 mm of the center layer and full thickness, and 2–6 mm of the posterior 60 μm layer were significantly higher in eyes affected by pterygium than in the contralateral unaffected eyes (all P < 0.05). CD values were significantly higher in the severe pterygium group than in the mild to moderate pterygium group (all P < 0.05). Corneal astigmatism, irregular astigmatism, K1, K2, CCT, and spherical aberration correlated with CD values in eyes with pterygium (all P < 0.05). CD values at 6–10, 0–12 mm in the anterior 120 μm layer and full thickness, 10–12 and 0–12 mm in the center layer were significantly decreased 1 month after pterygium surgery compared with those before surgery (all P < 0.05).ConclusionPatients with pterygium had increased CD values, particularly in the anterior and central layers. CD values were correlated with pterygium severity grading and corneal parameters. Pterygium surgery partially reduced the CD values.

Objective: The morphology and functions of the human trabecular meshwork (HTM) are dysregulated in glaucoma, and the molecular mechanisms of this dysregulation remain unknown. According to an established in vitro model, whose function was to study the regulatory networks sustaining the response of HTM cells to the increased substrate stiffness, we systematically analyzed the expression pattern of long noncoding RNAs (lncRNAs), the important regulatory RNAs in cells. Methods: Bioinformatics analysis was performed to identify the dysregulated lncRNAs in response to increased substrate stiffness using transcriptome sequencing data (RNA-seq). Then we interfered with the expression of several dysregulated lncRNAs in HTM cells to explore their molecular targets. The cross-linking immunoprecipitation and sequencing method (CLIP-seq) was used to identify enhancer of zeste homolog 2 (EZH2)-targeted RNAs in HTM cells. The chromatin IP and sequencing method (ChIP-seq) was used to identify the targets of EZH2 and histone H3 at lysine 27 (H3K27me3). Results: The response of thousands of dysregulated lncRNAs to increased substrate stiffness was identified through RNA-seq. Functional prediction of these lncRNAs revealed that they potentially regulated key biological processes, including extracellular matrix (ECM) organization. By interfering with the expression of lncRNA SHNG8, ZFHX4-AS1, and RP11-552M11.4, the results demonstrated that those lncRNAs extensively regulated the expression levels of ECM-associated genes. Moreover, we found that EZH2 expression was significantly decreased at high substrate stiffness. Using CLIP-seq to identify EZH2-targeted RNAs in HTM cells, we found that SNHG8 was bound by EZH2. According to the CLIP-seq data of EZH2, we found that EZH2 binding sites were observed in the transcripts of SNHG8-regulated genes, but not in the ChIP-seq results of EZH2 and H3K27me3. Conclusion: Our results suggest that SNHG8 and EZH2 may cooperate to regulate the expression of a subset of genes by influencing their RNA abundance, explaining how they support HTM cell morphology and high density. This study contributes to the understanding of the alteration of HTM during the progression of glaucoma by identifying functional lncRNAs, especially SNHG8, and suggests novel therapeutic targets to treat glaucoma.

Abstract Background Congenital ectopia lentis (EL) refers to the congenital dysplasia or weakness of the lens suspensory ligament, resulting in an abnormal position of the crystalline lens, which can appear as isolated EL or as an ocular manifestation of a syndrome, such as the Marfan syndrome. The fibrillin‐1 protein encoded by the FBN1 gene is an essential component of the lens zonules. Mutations in FBN1 are the leading causes of congenital EL and Marfan syndrome. Owing to the complexity and individual heterogeneity of FBN1 gene mutations, the correlation between FBN1 mutation characteristics and various clinical phenotypes remains unclear. Methods This study describes the clinical characteristics and identifies possible causative genes in eight families with Marfan syndrome or isolated EL using Sanger and whole‐exome sequencing. Results Eight FBN1 mutations were identified in these families, of which three (c.5065G > C, c.1600 T > A, and c.2210G > C) are reported for the first time. Based on in silico analyses, we hypothesized that these mutations may be pathogenic by affecting the fibrillin‐1 protein structure and function. Conclusion These findings expand the number of known mutations involved in EL and provide a reference for the research on their genotype and phenotype associations.

Objective It is of great importance to recognize bio-markers for cancer prognosis. However, the association between solute carrier family 7 member 11 (SLC7A11) and prognosis is still controversial. Therefore, we conducted this systematic review and meta-analysis to identify the prognostic and clinicopathological significance of SLC7A11 in human cancers. Methods PubMed, Web of Science, Scopus, the Cochrane Library and Embase database were searched from database inceptions to March 19th 2022. Hand searches were also conducted in references. Prognosis and clinicopathological data were extracted and analyzed. Results A total of 12 eligible studies with 1,955 patients were included. The results indicated that SLC7A11 expression is associated with unfavorable overall survival (OS), unfavorable recurrence-free survival (RFS) and unfavorable progression free survival (PFS). And SLC7A11 expression is also associated with more advanced tumor stage. Conclusions SLC7A11 expression is associated with more unfavorable prognosis and more advanced tumor stage. Therefore, SLC7A11 could be a potential biomarker for human cancer prognosis.

Long noncoding RNAs (lncRNAs) have an effect on the occurrence and progression of a considerable number of diseases, especially cancer. Existing research has suggested that MAGI2 antisense RNA 3 (MAGI2-AS3) takes on a critical significance in the development of hepatocellular carcinoma and lung cancer. However, the functions of MAGI2-AS3 in laryngeal squamous cell carcinoma (LSCC) remain unclear. In this study, MAGI2-AS3 expression level in LSCC tissue and cell lines was detected, and the effect of MAGI2-AS3 overexpressed on LSCC phenotypes and the possible influence mechanisms were examined. MAGI2-AS3 was downregulated in the tissues of LSCC patients versus non-tumor tissues, and it was correlated with advanced TNM (tumor, node, metastasis) stage and lymph node metastases, as indicated by the results of this study. MAGI2-AS3 inhibited the proliferation, migration, and invasion of LSCC cells in vitro and in vivo . Furthermore, the hypermethylation level of the MAGI2-AS3 promoter region was indicated by bisulfite genomic sequencing and methylation-specific polymerase chain reaction, such that MAGI2-AS3 expression was downregulated. Besides, MAGI2-AS3 promoter hypermethylation was regulated by DNA methyltransferase 1 (DNMT1), and MAGI2-AS3 expression was reversed by 5-Aza-2′-deoxycytidine (5-Aza). Moreover, the result of the RNA pull-down experiment suggested that 38 proteins were enriched in the MAGI2-AS3 group versus the control group in TU177 cells. To be specific, SPT6 (ie, a conserved protein) was enriched by fold change >10. SPT6 knockdown reduced the antitumor effect of MAGI2-AS3 in TU177 and AMC-HN-8 cells. Meanwhile, SPT6 overexpression inhibited the proliferation, metastasis, and invasion of TU177 and AMC-HN-8 cells. As revealed by the above findings, DNMT1-regulated MAGI2-AS3 promoter hypermethylation led to downregulated MAGI2-AS3 expression, such that the presence and progression of LSCC were inhibited in an SPT6 binding-dependent manner.

Tear meniscus height (TMH) is an important reference parameter in the diagnosis of dry eye disease. However, most traditional methods of measuring TMH are manual or semi-automatic, which causes the measurement of TMH to be prone to the influence of subjective factors, time consuming, and laborious. To solve these problems, a segmentation algorithm based on deep learning and image processing was proposed to realize the automatic measurement of TMH. To accurately segment the tear meniscus region, the segmentation algorithm designed in this study is based on the DeepLabv3 architecture and combines the partial structure of the ResNet50, GoogleNet, and FCN networks for further improvements. A total of 305 ocular surface images were used in this study, which were divided into training and testing sets. The training set was used to train the network model, and the testing set was used to evaluate the model performance. In the experiment, for tear meniscus segmentation, the average intersection over union was 0.896, the dice coefficient was 0.884, and the sensitivity was 0.877. For the central ring of corneal projection ring segmentation, the average intersection over union was 0.932, the dice coefficient was 0.926, and the sensitivity was 0.947. According to the evaluation index comparison, the segmentation model used in this study was superior to the existing model. Finally, the measurement outcome of TMH of the testing set using the proposed method was compared with manual measurement results. All measurement results were directly compared via linear regression; the regression line was y0.98x−0.02, and the overall correlation coefficient was r20.94. Thus, the proposed method for measuring TMH in this paper is highly consistent with manual measurement and can realize the automatic measurement of TMH and assist clinicians in the diagnosis of dry eye disease.

Objectives: To study the epidemiological characteristics and influencing factors of myopia to provide a scientific basis for the prevention and control of myopia.Methods: 7,597 students studying in grades 1–3 were followed up. Eye examinations and questionnaire surveys were conducted annually from 2019 to 2021. The influencing factors of myopia were analyzed by logistic regression model.Results: The prevalence of myopia among students in grades 1–3 in 2019 was 23.4%, which increased to 41.9% and 51.9% after the 1-and 2-year follow-up, respectively. The incidence of myopia and change in the spherical equivalent refraction (SER) were higher in 2020 than in 2021. The 2-year cumulative incidences of myopia were 2.5%, 10.1%, 15.5%, 36.3%, and 54.1% in students with a baseline SER >+1.50D, +1.00D to +1.50D, +0.50D to +1.00D, 0.00D to +0.50D, and -0.50D to 0.00D, respectively. Outdoor activities, sex, age, baseline SER, parental myopia, sleep time, and digital device exposure were associated with myopia.Conclusion: The prevalence of myopia demonstrated a rapid increase; thus, healthy habits and outdoor activities should be promoted for the prevention and control of myopia.

All-solid-state lithium batteries are considered as the priority candidates for next-generation energy storage devices due to their better safety and higher energy density. As the key part of solid-state batteries, solid-state electrolytes have made certain research progress in recent years. Among the various types of solid-state electrolytes, sulfide electrolytes have received extensive attention because of their high room-temperature ionic conductivity and good moldability. However, sulfide-based solid-state batteries are still in the research stage. This situation is mainly due to the fact that the application of sulfide electrolytes still faces challenges in particular of interfacial issues, mainly including chemical and electrochemical instability, unstable interfacial reaction, and solid–solid physical contact between electrolyte and electrode. Here, this review provides a comprehensive summary of the existing interfacial issues in the fabrication of sulfide-based solid-state batteries. The in-depth mechanism of the interfacial issues and the current research progress of the main coping strategies are discussed in detail. Finally, we also present an outlook on the future development of sulfide-based solid-state batteries to guide the rational design of next-generation high-energy solid-state batteries.

Recently, sulfide-based solid-state electrolytes (SSEs) have attracted much attention owing to their high ionic conductivity and feasible mechanical features. The environmental stability of sulfide-based SSEs is one of the critical aspects due to the possible decomposition, and ionic conductivity change will affect the fabrication and electrochemical performance of the batteries. Thus, important efforts have been made to reveal and improve their environmental stability, and a timely summary of the progress is urgently needed. In this review, we first clarify the definition of environmental stability and its significance in the context of practical use. After indicating the degradation mechanisms of sulfide-based SSEs, we summarize several effective strategies to improve their stability and also highlight the related theoretical studies. The stability of organic solvents of sulfide SSEs is also summarized and discussed, which may help reliable sulfide SSEs in the battery system. The main target of this review is to gain insights and provide useful guidance to further improve the environmental stability of sulfide SSEs, which will finally promote the commercialization of sulfide-based all-solid-state batteries.

The broken top coal and gangue in the fully mechanized cave mining will be released from the rear of the hydraulic support in the form of bulk. In this process, the medium properties through the coal opening can be judged by monitoring the vibration signal on the tail beam. Based on the coupling method of the discrete element method (DEM) and the finite element method (FEM) in LS-DYNA, this article simulates the whole process of coal caving, establishes the finite element model of the tail beam of hydraulic support and the discrete element model of coal gangue particles, and analyzes the influence of coal caving step distance, mining and caving ratio, and pitching angle of the mining field on the application effect of the vibration identification method. The coal caving step distance has a great influence on the recognition effect, and some bottom coal should be appropriately sacrificed to reduce the gangue content. The application effect of the vibration identification method is good under different mining and caving ratios. Downward mining can cause gangue to be released in advance, making the recognizable signal lag behind the change of gangue content, while upward mining will lose a part of the coal, but the application of vibration recognition is better than downward mining.

Abstract Perovskite solar cells (PSCs) via two‐step sequential method have received great attention in recent years due to their high reproducibility and low processing costs. However, the relatively high trap‐state density and poor charge carrier extraction efficiency pose challenges. Herein, highly efficient and stable PSCs via a two‐step sequential method are fabricated using organic—inorganic (OI) complexes as multifunctional interlayers. In addition to reduce the under‐coordinated Pb2+ ions related trap states by forming interactions with the functional groups, the complexes interlayer tends to form dipole moment which can enhance the built‐in electric field, thus facilitating charge carrier extraction. Consequently, with rational molecular design, the resulting devices with a vertical dipole moment that parallels with the built‐in electric field yield a champion efficiency of 23.55% with negligible hysteresis. More importantly, the hydrophobicity of the (OI) complexes contributes to an excellent ambient stability of the resulting device with 91% of initial efficiency maintained after 3000 h storage.

With the rapid increase in demand for high-energy-density lithium-ion batteries in electric vehicles, smart homes, electric-powered tools, intelligent transportation, and other markets, high-nickel multi-element materials are considered to be one of the most promising cathode candidates for large-scale industrial applications due to their advantages of high capacity, low cost, and good cycle performance. In response to the competitive pressure of the low-cost lithium iron phosphate battery, high-nickel multi-element cathode materials need to continuously increase their nickel content and reduce their cobalt content or even be cobalt-free and also need to solve a series of problems, such as crystal structure stability, particle microcracks and breakage, cycle life, thermal stability, and safety. In this regard, the research progress of high-nickel multi-element cathode materials in recent years is reviewed and analyzed, and the progress of performance optimization is summarized from the aspects of precursor orientational growth, bulk phase doping, surface coating, interface modification, crystal morphology optimization, composite structure design, etc. Finally, according to the industrialization demand of high-energy-density lithium-ion batteries and the challenges faced by high-nickel multi-element cathode materials, the performance optimization direction of high-nickel multi-element cathode materials in the future is proposed.

Marfan syndrome, an autosomal dominant disorder of connective tissue, is primarily caused by mutations in the fibrillin-1 (FBN1) gene, which encodes the protein fibrillin-1. The protein is composed of epidermal growth factor-like (EGF-like) domains, transforming growth factor beta-binding protein-like (TB) domains, and hybrid (Hyb) domains and is an important component of elastin-related microfibrils in elastic fiber tissue. In this study, we report a cysteine to tyrosine substitution in two different domains of fibrillin-1, both of which cause Marfan syndrome with ocular abnormalities, in two families. Using protease degradation and liquid chromatography-tandem mass spectrometry analyses, we explored the different effects of substitution of cysteine by tyrosine in an EGF-like and a calcium-binding (cb) EGF-like domain on protein stability. The results showed that cysteine mutations in the EGF domain are more likely to result in altered proteolytic sensitivity and thermostability than those in the cbEGF domain. Furthermore, cysteine mutations can lead to new enzymatic sites exposure or hidden canonical cleavage sites. These results indicate the differential clinical phenotypes and molecular pathogenesis of Marfan syndrome caused by cysteine mutations in different fibrillin-1 domains. These results strongly suggest that failure to form disulfide bonds and abnormal proteolysis of fibrillin-1 caused by cysteine mutations may be an important factor underlying the pathogenesis of diseases caused by fibrillin-1 mutations, such as Marfan syndrome.

Radiotherapy and/or chemotherapy-induced oral mucositis (RIOM/CIOM) is a common complication in cancer patients, leading to negative clinical manifestations, reduced quality of life, and impacting compliance with anticancer treatment. The composition and metabolic function of the oral microbiome, as well as the innate immune response of the oral mucosa are severely altered during chemotherapy or radiotherapy, promoting the expression of inflammatory mediators by direct and indirect mechanisms. Commensal oral bacteria-mediated innate immune signaling via Toll-like receptors (TLRs) ambiguously shapes radiotherapy- and/or chemotherapy-induced oral damage. To date, there has been no comprehensive overview of the role of TLRs in RIOM/CIOM. This review aims to provide a narrative of the involvement of TLRs, including TLR2, TLR4, TLR5, and TLR9, in RIOM/CIOM, mainly by mediating the interaction between the host and microorganisms. As such, we suggest that these TLR signaling pathways are a novel mechanism of RIOM/CIOM with considerable potential for use in therapeutic interventions. More studies are needed in the future to investigate the role of different TLRs in RIOM/CIOM to provide a reference for the precise control of RIOM/CIOM.

Abstract Background Hepatocellular carcinoma (HCC) is the leading cause of tumor-related death worldwide due to high morbidity and mortality, yet lacking effective biomarkers and therapies. Circular RNAs (circRNAs) are a group of non-coding RNAs that regulate gene expression through interacting with miRNAs, implicating in the tumorigenesis and progression. A novel circRNA, circTP63, was reported to be an oncogene in HCC. However, its role in HCC remains unclear. Methods qRT-PCR was used to assess the mRNA levels of CircTP63 in 90 pairs of tumor and adjacent normal tissues from HCC patients, one human normal hepatic epithelial cell line and HCC cell lines. CCK-8, colony formation, transwell, and flow cytometry assays were performed to detect the cellular function of circTP63/miR-155-5p/ZBTB18 in HCC cells. HCC xenograft mice models were established to assess the in vivo effect of circTP63. Bioinformatic analysis, RNA pull-down and luciferase assays were used to determine the interaction among circTP63/miR-155-5p/ZBTB18. Results circTP63 was significantly upregulated in HCC tissues and cell lines. High circTP63 expression is closely associated with the tumor stages, lymph node metastasis, and poor prognosis of HCC patients. Functionally, knockdown of circTP63 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of HCC. Meanwhile, overexpression of circTP63 enhanced HCC progression. Mechanically, circTP63 was a sponge of miR-155-5p to facilitate the ZBTB18 expression, and the ZBTB18 expression in HCC tissues was negatively associated with the survival rate of HCC patients. Furthermore, rescued assays revealed that the reduced tumor-promoting effect on HCC cells induced by knockdown of circTP63 can be reversed by miR-155-5p inhibitor or ZBTB18 overexpression. Conclusion Our data highlight a critical circTP63-miR-155-5p-ZBTB18 regulatory network involved in the HCC progression, gaining mechanistic insights into the function of circRNAs in HCC progression, and providing effective biomarkers and therapeutic targets for HCC treatment.

Affected by an insufficient understanding of oxidation characteristics and the CO production mechanism in low-rank coal goaf, the safety management of coal spontaneous combustion (CSC) faces severe challenges. In this study, in-depth research was conducted using ambient temperature oxidation (ATO), temperature-programmed, in situ FTIR experiments and DFT simulation after analyzing the oxidation scenario characteristics of low-metamorphic coal goaf. The results show the oxidation of low-rank coal goaf includes two processes of ATO in the dissipation zone and CSC in the oxidation zone. The CO production of ATO increases with a decrease in coal metamorphic degree, and the risk of CSC is influenced by ATO, with an inhibitory effect before the critical temperature, and an encouraging effect after that. The CO production mechanism of low metamorphic coal goaf from ATO to CSC is established. Before the critical temperature, CO mainly comes from the primary aldehyde functional groups, then peroxide-free radicals participate in the reaction, resulting in the production of a large number of secondary aldehyde functional groups, which leads to the sudden change in CO output. The problem of the abnormal, continuous exceedance of CO in the tailgate corner can be solved by developing an ATO inhibitor, which plays an inhibiting role at ambient temperature and decomposes in the event of CSC.

Abstract Background Despite the capability of emergency surgery to reduce the mortality of severe spontaneous intracranial hemorrhage (SSICH) patients, the effect and safety of surgical treatment for severe spontaneous intracranial hemorrhage (SSICH) patients receiving long-term oral antiplatelet treatment (LOAPT) remains unclear. In consideration of this, the cohort study is aimed at figuring out the effect and safety of emergency surgery for SSICH patients on LOAPT. Methods As a multicenter and prospective cohort study, it will be conducted across 7 representative clinical centers. Starting in September 2019, the observation is scheduled to be completed by December 2022, with a total of 450 SSICH patients recruited. The information on clinical, radiological, and laboratory practices will be recorded objectively. All of the patients will be monitored until death or 6 months after the occurrence of primary hemorrhage. Results In this study, two comparative cohorts and an observational cohort will be set up. The primary outcome is the effect of emergency surgery, which is subject to assessment using the total mortality and comparison in the survival rate of SSICH patients on LOAPT between surgical treatment and conservative treatment. The second outcome is the safety of surgery, with the postoperative hemorrhagic complication which is compared between the operated SSICH patients on and not on LOAPT. Based on the observation of the characteristics and outcome of SSICH patients on LOAPT, the ischemic events after discontinuing LOAPT will be further addressed, and the coagulation function assessment system for operated SSICH patients on LOAPT will be established. Conclusions In this study, we will investigate the effect and safety of emergency surgery for SSICH patients on LOAPT, which will provide an evidence for management in the future. Ethics and dissemination The research protocol and informed consent in this study were approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2019-096-02). The results of this study are expected to be disseminated in peer-reviewed journals in 2023. Trial registration Name: Effect and safety of surgical intervention for severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet treatment. ChiCTR1900024406 . Date of registration is July 10, 2019.

Objective The survival and clinicopathological significance of desmoglein 2 (DSG2) in various cancers is controversial. Thus, we performed this systematic review and meta-analysis to explore the preliminary prognostic value of DSG2. Methods Eligible studies were identified from databases including PubMed, the Cochrane Library, Embase, Web of Science and Scopus. Hand searches were also conducted in relevant bibliographies. We then extracted and pooled hazard ratio (HR) of overall survival (OS) and odds ratio (OR) of clinicopathological features. Results A total of 11 eligible studies containing 1,488 patients were included. Our results demonstrated that in non-small cell lung cancer (NSCLC), high DSG2 expression is associated with poor OS. However, in digestive system cancer and female reproductive system cancer, there were no statistically significant associations between OS and DSG2. Conclusions Based on the findings of this study, high DSG2 expression is associated with worse prognosis in patients with NSCLC, and thus DSG2 expression could be a biomarker for prognosis in NSCLC.

Aiming at the problem of poor performance of the classification model in the case of unintentional phase modulation on pulse (UPMOP) to achieve radar specific emitter identification,a method for radar specific emitter identification with long and short-term memory and full convolutional networks (LSTM-FCN) was proposed.Firstly,a simplified observation model of the intrapulse signal phase considering the intentional modulation was presented,and the observation phase sequence was deramp to extract the noisy estimate of the UPMOP.Then Bezier curve was utilized to fit the UPMOP to reduce the influence of noise and obtain a more accurate description of UPMOP.Finally,the LSTM-FCN was used to extract the joint features of UPMOP sequence to realize the radar specific emitter automatic identification.Both the simulation experiments and the measured data experiments verify the feasibility and effectiveness of the proposed algorithm.Moreover,the proposed algorithm has high identification accuracy and short time consumption.