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Abstract Three-dimensional (3D) glass chips are promising waveguide platforms for building hybrid 3D photonic circuits due to their 3D topological capabilities, large transparent windows, and low coupling dispersion. At present, the key challenge in scaling down a benchtop optical system to a glass chip is the lack of precise methods for controlling the mode field and optical coupling of 3D waveguide circuits. Here, we propose an overlap-controlled multi-scan (OCMS) method based on laser-direct lithography that allows customizing the refractive index profile of 3D waveguides with high spatial precision in a variety of glasses. On the basis of this method, we achieve variable mode-field distribution, robust and broadband coupling, and thereby demonstrate dispersionless LP21-mode conversion of supercontinuum pulses with the largest deviation of

Industrial computed tomography (CT) is widely used in the measurement field owing to its advantages such as non-contact and high precision. To obtain accurate size parameters, fitting parameters can be obtained rapidly by processing volume data in the form of point clouds. However, due to factors such as artifacts in the CT reconstruction process, many abnormal interference points exist in the point clouds obtained after segmentation. The classic least squares algorithm is easily affected by these points, resulting in significant deviation of the solution of linear equations from the normal value and poor robustness, while the random sample consensus (RANSAC) approach has insufficient fitting accuracy within a limited timeframe and the number of iterations. To address these shortcomings, we propose a spherical point cloud fitting algorithm based on projection filtering and K-Means clustering (PK-RANSAC), which strategically integrates and enhances these two methods to achieve excellent accuracy and robustness. The proposed method first uses RANSAC for rough parameter estimation, then corrects the deviation of the spherical center coordinates through two-dimensional projection, and finally obtains the spherical center point set by sampling and performing K-Means clustering. The largest cluster is weighted to obtain accurate fitting parameters. We conducted a comparative experiment using a three-dimensional ball-plate standard. The sphere center fitting deviation of PK-RANSAC was 1.91 μm, which is significantly better than RANSAC’s value of 25.41 μm. The experimental results demonstrate that PK-RANSAC has higher accuracy and stronger robustness for fitting geometric parameters.

To improve the accuracy of in situ measurement of the standard volumes of pipe provers and to shorten the traceability chain, a new method of in situ pipe prover volume measurement was developed alongside a supporting measurement device. This method is based on the geometric dimension approach, which measures the inner diameter and length of a pipe prover to calculate its volume. For inner diameter measurement, a three-probe inner-diameter algorithm model was established. This model was calibrated using a standard ring gauge of Φ313 mm, with the parameters calculated through fitting. Another standard ring gauge of Φ320 mm was used to verify the inner diameters determined by the algorithmic model. A laser interferometer was employed for the segmented measurement of the pipe prover length. The comprehensive measurement system was then used for in situ measurement of the standard pipe prover. The newly developed system achieved an expanded uncertainty of 0.012% (k = 2) in volume measurement, with the deviation between the measured and nominal pipe prover volumes being merely 0.007%. These results demonstrate that the proposed in situ measurement method offers ultra-high-precision measurement capabilities.

Despite all the efforts made in tissue engineering for tendon repair, the management of tendon injuries still poses a challenge, as current treatments are unable to restore the function of tendons following injuries. Hydrogels, due to their exceptional biocompatibility and plasticity, have been extensively applied and regarded as promising candidate biomaterials in tissue regeneration. Varieties of approaches have designed functionally-adapted hydrogels and combined hydrogels with other factors (e.g., bioactive molecules or drugs) or materials for the enhancement of tendon repair. This review first summarized the current state of knowledge on the mechanisms underlying the process of tendon healing. Afterward, we discussed novel strategies in fabricating hydrogels to overcome the issues frequently encountered during the applications in tendon repair, including poor mechanical properties and undesirable degradation. In addition, we comprehensively summarized the rational design of hydrogels for promoting stem-cell-based tendon tissue engineering via altering biophysical and biochemical factors. Finally, the role of macrophages in tendon repair and how they respond to immunomodulatory hydrogels were highlighted.

Ventilation rate is a physical index that is strictly controlled during cigarette manufacturing because an abnormal ventilation rate can affect the release of mainstream smoke, tar, and other components harmful to human health. Therefore, the standard rod is used for measuring the ventilation rate, which necessitates accurate and effective periodic inspections. In this study, we designed and built a set of special tobacco ventilation rate standard rods to assess the standard device during its verification period and used a digital thermal flowmeter as the flow standard.We determined the micro-pressure adjustment interval through fluid simulation, and conducted an experimental verification based on the simulation results. At the adjustment point where the differential pressure value was 0 Pa, the period verification device was tested under the standard values of 27.38%, 58.83%, and 71.95%. The results show that the measurement errors of the device are –0.42%, 0.55%, and –0.13% respectively, which all meet the verification regulation requirements and indicate that the device is applicable in practical situations.

Abstract Deubiquitinases (DUBs) are enzymes that control the stability, interactions or localization of most cellular proteins by removing their ubiquitin modification. In recent years, some DUBs, such as USP7, USP9X and USP10, have been identified as promising therapeutic targets in hematological malignancies. Importantly, some potent inhibitors targeting the oncogenic DUBs have been developed, showing promising inhibitory efficacy in preclinical models, and some have even undergone clinical trials. Different DUBs perform distinct function in diverse hematological malignancies, such as oncogenic, tumor suppressor or context-dependent effects. Therefore, exploring the biological roles of DUBs and their downstream effectors will provide new insights and therapeutic targets for the occurrence and development of hematological malignancies. We summarize the DUBs involved in different categories of hematological malignancies including leukemia, multiple myeloma and lymphoma. We also present the recent development of DUB inhibitors and their applications in hematological malignancies. Together, we demonstrate DUBs as potential therapeutic drug targets in hematological malignancies.

In this paper, we forecasted the ionospheric total electron content (TEC) over the region of China using the bidirectional convolutional gated recurrent unit (BiConvGRU) model. We first generated the China Regional Ionospheric Maps (CRIMs) using GNSS observations provide by the Crustal Movement Observation Network of China (CMONOC). We then used gridded TEC maps from 2015 to 2018 with a 1 h interval from the CRIMs as the dataset, including quiet periods and storm periods of ionospheric TEC. The BiConvGRU model was then utilized to forecast the ionospheric TEC across China for the year 2018. The forecasted TEC was compared with the TEC from the International Reference Ionosphere (IRI-2016), Convolutional Long Short-Term Memory (ConvLSTM), Convolutional Gated Recurrent Unit (ConvGRU), Bidirectional Convolutional Long Short-Term Memory (BiConvLSTM), and the 1-day Predicted Global Ionospheric Map (C1PG) provided by the Center for Orbit Determination in Europe (CODE). In addition, indices including Kp, ap, Dst and F10.7 were added to the training dataset to improve the forecasting accuracy of the model (-A indicates no indices, while -B indicates with indices). The results verified that the prediction accuracies of the models integrated with these indices were significantly improved, especially during geomagnetic storms. The BiConvGRU-B model presented a decrease of 41.5%, 22.3%, and 13.2% in the root mean square error (RMSE) compared to the IRI-2016, ConvGRU, and BiConvLSTM-B models during geomagnetic storm days. Furthermore, at a specific grid point, the BiConvGRU-B model showed a decrease of 42.6%, 49.1%, and 31.9% in RMSE during geomagnetic quiet days and 30.6%, 34.1%, and 15.1% during geomagnetic storm days compared to the IRI-2016, C1PG, and BiConvLSTM-B models, respectively. In the cumulative percentage analysis, the BiConvGRU-B model had a significantly higher percentage of mean absolute error (MAE) within the range of 0–1 TECU in all seasons compared to the BiConvLSTM-B model. Meanwhile, the BiConvGRU-B model outperformed the BiConvLSTM-B model with lower RMSE for each month of 2018.

Abstract Background PYGL mutations can cause liver phosphorylase deficiency, resulting in a glycogenolysis disorder, namely, glycogen storage disease (GSD) VI. The disease is rarely reported in the Chinese population. GSD VI is mainly characterized in untreated children by hepatomegaly, growth retardation and elevated liver transaminases. Case presentation In this study, we report two GSD VI patients with growth retardation and abnormal liver function. There was no obvious hepatomegaly for one of them. Whole exome sequencing (WES) combined with copy number variation analysis was performed. We found a novel homozygous gross deletion, c.1621-258_2178-23del, including exons 14–17 of PYGL in patient 1. The exons 14–17 deletion of PYGL resulted in an in-frame deletion of 186 amino acids. Compound heterozygous mutations of PYGL were identified in patient 2, including a novel missense mutation c.1832C > T/p.A611V and a recurrent nonsense mutation c.280C > T/p.R94X. After treatment with uncooked cornstarch (UCS) 8 months for patient 1 and 13 months for patient 2, the liver transaminases of both patients decreased to a normal range and their stature was improved. However, patient 1 still showed mild hypertriglyceridemia. Conclusions We describe two GSD VI patients and expand the spectrum of PYGL mutations. Patient 1 in this study is the first GSD VI case that showed increased transaminases without obvious hepatomegaly due to a novel homozygous gross deletion of PYGL identified through WES.

Let k and n be two positive integers. Firefighting is a discrete dynamical process of preventing the spread of fire. Let G be a connected graph G with n vertices. Assuming a fire starts at one of the vertices of G, the firefighters choose k unburned vertices at each step, and then the fire spreads to all unprotected neighbors of the burning vertices. The process continues until the fire stops spreading. The goal is to protect as many vertices as possible. When a fire breaks out randomly at a vertex of G, its k-surviving rate, ρk(G), is the expected number of saved vertices. A graph is IC-planar if it has a drawing in which each edge cross once and their endpoints are disjoint. In this paper, we prove that ρ4(G)>1124 for every IC-planar graph G. This is proven by the discharging method and the locally symmetric of the graph.

Skraban-Deardorff syndrome is a rare autosomal dominant genetic disease caused by variants in the WDR26 gene. Here, we report two Chinese patients diagnosed with Skraban-Deardorff syndrome caused by novel de novo, heterozygous pathogenic WDR26 variants c.977delA (p. 12 N326Ifs*2) and c.1020-2A>G (p. R340Sfs*29). Their clinical features were characterized by intellectual disability (ID), developmental delay, abnormal facial features and the absence of early-onset seizure, which expands the phenotype spectrum associated with Skraban-Deardorff syndrome. By comparing our cases with current reported cases of WDR26-related intellectual disability, we suggest that developmental delay, particularly in speech, and facial features including rounded palpebral fissures, depressed nasal root, full nasal tip and abnormal gums, represent the prominent clinical phenotypes for diagnosis of Skraban-Deardorff syndrome. Together, WDR26 variants and 1q41q42 deletions should feature prominently on the differential diagnosis of ID with distinctive facial features.

Gallbladder cancer (GBC) is the most common malignancy in the biliary tract. Without effective treatment, its prognosis is notoriously poor. Tea polyphenols (TPs) have many pharmacological and health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-thrombotic, antibacterial, and vasodilatory properties. However, the anti-cancer effect of TPs in human gallbladder cancer has not yet been determined. Cell viability and colony formation assay were used to investigate the cell growth. Cell cycle and apoptosis were evaluated by flow cytometry analysis. Western blot assay was used to detect the expression of proteins related to cell cycle and apoptosis. Human tumor xenografts were used to examine the effect of TPs on gallbladder cancer cells in vivo. TPs significantly inhibited cell growth of gallbladder cancer cell lines in a dose- and time-dependent manner. Cell cycle progression in GBC cells was blocked at the S phase by TPs. TPs also induced mitochondrial-related apoptosis in GBC cells by upregulating Bax, cleaved caspase-3, and cleaved PARP expressions and downregulating Bcl-2, cyclin A, and Cdk2 expressions. The effects of TPs on GBC were further proven in vivo in a mouse xenograft model. Our study is the first to report that TPs inhibit GBC cell growth and these compounds may have potential as novel therapeutic agents for treating gallbladder cancer.

Abstract Objective The aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. Methods Post hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China. Results A total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0–2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947–0.982; p

Abstract RNA splicing is a dynamic molecular process in response to environmental stimuli and is strictly regulated by the spliceosome. Sm proteins, constituents of the spliceosome, are key components that mediate splicing reactions; however, their potential role in hepatocellular carcinoma (HCC) is poorly understood. In the study, SNRPD2 (PD2) is found to be the most highly upregulated Sm protein in HCC and to act as an oncogene. PD2 modulates DDX39A intron retention together with HNRNPL to sustain the DDX39A short variant (39A_S) expression. Mechanistically, 39A_S can mediate MYC mRNA nuclear export to maintain high MYC protein expression, while MYC in turn potentiates PD2 transcription. Importantly, digitoxin can directly interact with PD2 and has a notable cancer‐suppressive effect on HCC. The study reveals a novel mechanism by which DDX39A senses oncogenic MYC signaling and undergoes splicing via PD2 to form a positive feedback loop in HCC, which can be targeted by digitoxin.

Aging is a contributor to liver disease. Hence, the concept of liver aging has become prominent and has attracted considerable interest, but its underlying mechanism remains poorly understood. In our study, the internal mechanism of liver aging was explored via multi-omics analysis and molecular experiments to support future targeted therapy. An aged rat liver model was established with d-galactose, and two other senescent hepatocyte models were established by treating HepG2 cells with d-galactose and H2O2. We then performed transcriptomic and metabolomic assays of the aged liver model and transcriptome analyses of the senescent hepatocyte models. In livers, genes related to peroxisomes, fatty acid elongation, and fatty acid degradation exhibited down-regulated expression with aging, and the hepatokine Fgf21 expression was positively correlated with the down-regulation of these genes. In senescent hepatocytes, similar to the results found in aged livers, FGF21 expression was also decreased. Moreover, the expressions of cell cycle-related genes were significantly down-regulated, and the down-regulated gene E2F8 was the key cell cycle-regulating transcription factor. We then validated that FGF21 overexpression can protect against liver aging and that FGF21 can attenuate the declines in the antioxidant and regenerative capacities in the aging liver. We successfully validated the results from cellular and animal experiments using human liver and blood samples. Our study indicated that FGF21 is an important target for inhibiting liver aging and suggested that pharmacological prevention of the reduction in FGF21 expression due to aging may be used to treat liver aging-related diseases.

Abstract Introduction This study aimed to analyze the association between baseline National Institutes of Health Stroke Scale (NIHSS) scores and clinical outcomes in patients with large core infarctions undergoing endovascular treatment (EVT), a relationship that remains unclear. Methods Data were obtained from the MAGIC study, a prospective multicenter cohort study focusing on patients with acute large core ischemic stroke. This analysis evaluated the impact of NIHSS scores on EVT outcomes in patients with large core infarctions. Primary outcome metrics included favorable outcomes (modified Rankin Scale [mRS] of 0–3 at 90 days), while secondary outcomes encompassed shifts in mRS scores, functional independence (mRS score of 0–2), mRS score of 0–4, and successful recanalization rates. Adverse events considered were symptomatic intracranial hemorrhage (sICH) and mortality. Results A total of 490 patients were enrolled in this study. Higher baseline NIHSS scores were inversely correlated with favorable outcomes (adjusted odds ratio [OR] in model 3, 0.848 [0.797–0.903], P

Abstract Objective Renal function can modify the outcomes of large vessel occlusion (LVO) stroke across stroke etiologies in disparate degrees. The presence of renal function deficit can also impair the pharmacokinetics of tirofiban. Hence, this study aimed to investigate the roles of renal function in determining efficacy and safety of intravenous tirofiban before endovascular treatment (EVT) for acute ischemic stroke patients with large vessel occlusion (LVO). Methods This study was a post hoc exploratory analysis of the RESCUE‐BT trial. The primary outcome was the proportion of patients achieving functional independence (modified Rankin scale 0–2) at 90 days, and the primary safety outcome was the rate of symptomatic intracranial hemorrhage (sICH). Results Among 908 individuals with available serum creatinine, decreased estimated glomerular filtration rate (eGFR) status was noted more commonly in patients with cardioembolic stroke (CE), while large artery atherosclerosis (LAA) was predominant in patients with normal renal function. In LAA with normal renal function, tirofiban was associated with higher rates of functional independence at 90 days (41.67% vs 59.80%, p = 0.003). However, for LVO patients with renal dysfunction, tirofiban did not improve functional outcomes for any of the etiologies (LAA, p = 0.876; CE, p = 0.662; others, p = 0.894) and significantly increased the risk of sICH among non‐LAA patients (p = 0.020). Mediation analysis showed tirofiban reduced thrombectomy passes (12.27%) and drug/placebo to recanalization time (14.25%) mediated its effects on functional independence. Conclusion This present study demonstrated the importance of evaluating renal function before administering intravenous tirofiban among patients with LVO who are planned to undergo EVT.

Sulfamethoxazole (SMX) is an extensively applied antibacterial drug, and it is also a pollutant that poses a serious threat to human and ecosystem health. In this research, a 3D hierarchical hollow ball-flower structure catalyst (CoAl-LDHs@CoSx-rGO) was tailored for the first time to efficiently degrade SMX via visible light coupling PMS activation. A series of characterizations confirm that the target catalyst is successfully prepared and the optimized 0.1CoAl-LDHs@CoSx-rGO sample possesses superior specific surface area of 306.0 m2/g, and significantly higher photocurrent response and lower electrochemical impedance. More importantly, 0.5 g/L of the sample can degrade 98.59 % of SMX within 50 min via visible light coupling PMS activation, and after 7 degradation cycles, the degradation rate only decreased by 8.49 %. A series of parameters that affect degradation rate have been optimized in detail. Capture experiments and ESR indicate that e−, •OH and SO4•− make major contributions to degradation, and visible light coupling PMS activation generates stronger signals than alone visible-light or PMS system. LC-MS, TEST toxicity assessment and theoretical calculation were conducted to elucidate degradation route and intermediate toxicity. The research provides a new approach to design catalysts with highly exposed activity sites for efficiently removing SMX from environmental water.

Adversarial examples, which are inputs deliberately perturbed with imperceptible changes to induce model errors, have raised serious concerns for the reliability and security of deep neural networks (DNNs). While adversarial attacks have been extensively studied in continuous data domains such as images, the discrete nature of text presents unique challenges. In this paper, we propose Irony-based Adversarial Examples (IAE), a method that transforms straightforward sentences into ironic ones to create adversarial text. This approach exploits the rhetorical device of irony, where the intended meaning is opposite to the literal interpretation, requiring a deeper understanding of context to detect. The IAE method is particularly challenging due to the need to accurately locate evaluation words, substitute them with appropriate collocations, and expand the text with suitable ironic elements while maintaining semantic coherence. Our research makes the following key contributions: (1) We introduce IAE, a strategy for generating textual adversarial examples using irony. This method does not rely on pre-existing irony corpora, making it a versatile tool for creating adversarial text in various NLP tasks. (2) We demonstrate that the performance of several state-of-the-art deep learning models on sentiment analysis tasks significantly deteriorates when subjected to IAE attacks. This finding underscores the susceptibility of current NLP systems to adversarial manipulation through irony. (3) We compare the impact of IAE on human judgment versus NLP systems, revealing that humans are less susceptible to the effects of irony in text.

Abstract Background Stress hyperglycemia ratio (SHR) reflects a true acute hyperglycemic state during acute basilar artery occlusion (ABAO). We aimed to investigate the association between SHR and short-term and long-term outcomes in patients with ABAO receiving endovascular treatment (EVT). Methods We selected patients treated with EVT from the BASILAR study, a nationwide prospective registry. A total 250 patients with documented glucose and glycated hemoglobin (HbA1C) values at admission were included. SHR was calculated as the ratio of glucose/HbA1C. All 250 patients completed 90 days of follow-up and 234 patients (93.6%) completed 1 year of follow-up. The primary outcome was the favorable outcome defined as modified Rankin Scale (mRS) score ≤ 3 at 90 days. Safety outcomes included mortality at 90 days and 1 year, and intracranial hemorrhage. Results Among the 250 patients included, patients with higher tertiles of SHR were associated with decreased odds of a favorable functional outcome at 90 days (adjusted OR, 0.26; 95% CI, 0.12–0.56; P = 0.001 and adjusted OR, 0.37; 95% CI, 0.18–0.80; P = 0.01; respectively) and 1 year (adjusted OR, 0.34; 95% CI, 0.16–0.73; P = 0.006 and adjusted OR, 0.38; 95% CI, 0.18–0.82; P = 0.01; respectively) after adjusting for confounding covariates. The mortality was comparable across tertiles of SHR groups at 90 days and 1 year. Conclusions Our study showed that SHR was associated with a decreased probability of favorable functional outcome both at 90 days and 1 year after EVT in patients with ABAO. The relationship was more pronounced in non-diabetes patients. Trial registration Clinical Trial Registry Identifier: ChiCTR1800014759 (November 12, 2013).

Abstract Organoids, three-dimensional structures cultured in vitro, can recapitulate the microenvironment, complex architecture, and cellular functions of in vivo organs or tissues. In recent decades, liver organoids have been developed rapidly, and their applications in biomedicine, such as drug screening, disease modeling, and regenerative medicine, have been widely recognized. However, the lack of repeatability and consistency, including the lack of standardized culture conditions, has been a major obstacle to the development and clinical application of liver organoids. It is time-consuming for researchers to identify an appropriate medium component scheme, and the usage of some ingredients remains controversial. In this review, we summarized and compared different methods for liver organoid cultivation that have been published in recent years, focusing on controversial medium components and discussing their advantages and drawbacks. We aimed to provide an effective reference for the development and standardization of liver organoid cultivation.

Abstract Objective This study aimed to investigate whether treatment with adjunct intravenous tirofiban is associated with improved outcomes following successful reperfusion in patients with intracranial atherosclerotic stroke. Methods Patients with intracranial large artery atherosclerotic (LAA) stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 from the Effect of Intravenous Tirofiban versus Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke (RESCUE BT) trial were included. The primary outcome was the difference in proportion of independent functional outcome (modified Rankin score of 0–2 at 90 days). Safety outcomes included the rates of symptomatic intracranial hemorrhage (sICH) and 90‐day mortality. Results Among the 382 patients with intracranial LAA stroke and successful reperfusion, 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95 out of 175) with tirofiban and 44.0% (91 out of 207) with placebo (adjusted odds ratio [aOR], 1.58; 95% CI, 1.02–2.44; p = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of sICH (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59–3.34; p = 0.44) or 90‐day mortality (21/175 [12.0%] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38–1.31; p = 0.27). Interpretation Among patients with acute intracranial LAA stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of sICH or mortality. Confirmatory randomized trials in these patients are desirable.