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The accumulation of coal gangue results in serious environmental pollution, it is urgent and necessary to comprehensive, high value and efficient utilization of coal gangue. The resource utilization of coal gangue by calcination is important. In terms of the problems of high energy consumption and low efficiency, the use of sodium salt types and calcination process for coal gangue whitening has been investigated. Raw and calcined coal gangue were thoroughly characterized with respect to phases constituent, microstructures, pore structures and chemical bonds.Based on above investigations, the whitening mechanism and volatile products obtained from sodium chloride calcined coal gangue process were further analyzed by simultaneous thermogravimetry-Fourier transform infrared spectroscopy-Mass spectrometer (TG-FTIR-MS). Results show that after being calcined with sodium chloride at 860 ℃, the whiteness of raw coal gangue was upgraded from 38.5% to 86.0%. All the carbon and pyrite (FeS2) contained in coal gangue was oxidized and correspondingly converted into hematite (Fe2O3) by desulfurization and the total amount of hematite and rutile (TiO2) was reduced to 0.27%. The pore structural characteristics changed little at calcination temperature between 800 and 860 ℃. However, the calcination at 950 ℃ resulted in generation of spherical mullite, and a significant decrease in specific surface area and pore volume from 12.91 m2/g and 0.056 cm3/g for raw coal gangue to 6.58 m2/g and 0.031 cm3/g, respectively. The whiteness increased slightly at calcination time between 30 and 90 min (85.3% to 86.6%). Meanwhile, the whiteness changed little at calcination time between 90 and 150 min (86.6% to 86.7%). The addition of NaCl had little impact on the chemical bonds of calcined coal gangue. The evolution of mineral components in the calcination stage was relatively low, and the main volatile products were H2O, HCl, CO2 and H2S. Moreover, NaCl reacted with SiO2 and H2O to decompose into HCl gas, which removes iron and titanium by the volatilization of the respective chlorides. The chlorinated products escaped from the surface of the material layer and discharged, resulting in a purified and whitened coal gangue.

Abstract Background Intratumoral hemorrhage, though less common, could be the first clinical manifestation of glioma and is detectable via MRI; however, its exact impacts on patient outcomes remain unclear and controversial. The 2021 WHO CNS 5 classification emphasised genetic and molecular features, initiating the necessity to establish the correlation between hemorrhage and molecular alterations. This study aims to determine the prevalence of intratumoral hemorrhage in glioma subtypes and identify associated molecular and clinical characteristics to improve patient management. Methods Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications. Results 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p

BackgroundIschemic stroke (IS) is a global health issue linked to lipid metabolism and immune cell responses. This study uses Mendelian randomization (MR) to identify genetic risk factors for IS subtypes using comprehensive genetic data from lipidomic and immune cell profiles.MethodsWe assessed genetic susceptibility to IS across 179 lipids and 731 immune cell phenotypes using instrumental variables (IVs) from recent genome-wide association studies. A two-sample MR approach evaluated correlations, and a two-step MR mediation analysis explored the role of immune cell phenotypes in the lipid-IS pathway. Sensitivity analyses, including MR-Egger and Cochran Q tests, ensured robust results.ResultsGenetic IVs for 162 lipids and 614 immune cell phenotypes were identified. Significant genetic causality was found between 35 lipids and large artery stroke (LAS), with 12 as risk factors (sterol esters, phosphatidylcholines, phosphatidylethanolamines) and 23 as protective factors (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols). For small vessel stroke (SVS), 8 as risk factors (sterol esters, phosphatidylcholines), and 2 as protective factors (phosphatidylinositol, sphingomyelin). For cardioembolic stroke (CS), 2 as risk factors, and 4 as protective factors. Mediation analysis revealed that CCR2 on granulocytes, CD11c on CD62L+ myeloid dendritic cells, and FSC-A on granulocytes mediated the lipid-immune cell-LAS pathway, while CD4 on activated CD4 regulatory T cells and CD4 on activated & secreting CD4 regulatory T cells mediated the lipid-immune cell-SVS pathway.ConclusionThis study identifies genetic links between specific lipids and IS subtypes, highlights immune cells’ role in IS risk and mediation, suggests new therapeutic targets, and uncovers IS genetic drivers.

Objectives: We aimed to evaluate the analytical performance of second-trimester maternal serum screening in China, and to compare if there are differences in sigma levels across different methods and months. Methods: A retrospective study was conducted to assess the analytical quality levels of laboratories by calculating the Sigma metrics with prenatal screening biomarkers: AFP, Total β-hCG, free β-hCG, uE3. Data from 591 laboratories were selected. Sigma metrics were computed using the formula: Sigma metrics(σ) = (%TEa - |%Bias|)/%CV. The Friedman test and Mann-Whitney test were used to compare differences across various methods and different months. The Hodges–Lehmann was used for determining 95 % confidence intervals of pseudo-medians. Results: Only uE3 showed significant monthly variations in sigma calculations. However, around 8 % of laboratories across all four analytes demonstrated sigma levels both above 6 and below 3 in different months. Laboratories utilizing time-resolved fluorescence methods significantly outperformed those using chemiluminescence in sigma level. For AFP, the pseudo-median difference between these methods lies within a 95 % confidence interval of (−3.22, −1.93), while for uE3, it is at (−2.30, −1.40). Notably, the median sigma levels for all analytes reached the 4-sigma threshold, with free β-hCG even attaining the 6-sigma level. Conclusion: With current standards, China's second-trimester maternal serum screening is of relatively high analytical quality, and variations in sigma levels exist across different months and methods.

Abstract Predictive markers and prognostic models are useful for the individualization of cancer treatment. In this study, we sought to identify clinical and molecular factors to predict overall survival in recurrent glioma patients receiving bevacizumab-containing regimens. A cohort of 102 patients was retrospectively collected from June 2011 to January 2022 at our institution. A nomogram was generated by Cox regression and feature selection algorithms based on 19 clinicopathological and 60 molecular variables. The model's performance was internally evaluated by bootstrapping in terms of discrimination and calibration. The median overall survival from the initiation of bevacizumab administration to death or last follow-up was 11.6 months (95% CI: 9.2–13.8 months) for all 102 patients, 10.2 months (95% CI: 6.4–13.3 months) for 66 patients with grade 4 tumors, and 13.8 months (lower limit of 95% CI: 11.5 months) for 36 patients with tumors of grade lower or not available. In the final model, a lower WHO 2021 grade (Grade lower or not available vs. Grade 4, HR: 0.398, 95% CI: 0.223–0.708, p = 0.00172), having received adjuvant radiochemotherapy (Yes vs. No, HR: 0.488, 95% CI: 0.268–0.888, p = 0.0189), and wildtype EGFR (Wildtype vs. Altered, HR: 0.193, 95% CI: 0.0506–0.733, p = 0.0157; Not available vs. Altered, HR: 0.386, 95% CI: 0.184–0.810, p = 0.0118) were significantly associated with longer overall survival in multivariate Cox regression. The overall concordance index was 0.652 (95% CI: 0.566–0.714), and the areas under the time-dependent curves for 6-, 12-, and 18-month overall survival were 0.677 (95% CI: 0.516–0.816), 0.654 (95% CI: 0.470–0.823), and 0.675 (95% CI: 0.491–0.860), respectively. A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-based therapy was established and internally validated. It could serve as a reference tool for clinicians to assess the extent the patients may benefit from bevacizumab and stratify their treatment response.

Abstract Background This study aimed to assess the knowledge, attitudes and practices among medical workers toward outpatient diabetes information platform. Methods This web-based cross-sectional study was conducted between May 2023 and June 2023 at the First Hospital of Zhangjiakou, China. A self-designed questionnaire was developed to collect demographic information of medical workers, and assess their knowledge, attitudes and practices toward outpatient diabetes information platform. Results A total of 685 questionnaires were collected. Among the participants, 603 (88.03%) were female, 432 (63.07%) work in a tertiary hospital, 548 (80.00%) have a bachelor degree, 270 (39.42%) of them work in the department of internal medicine and 315 (45.99%) of them received previous training on outpatient diabetes information platform. The mean knowledge, attitudes and practices scores were 4.32 ± 1.27 (possible range: 0–6), 56.76 ± 5.72 (possible range: 14–70), and 32.22 ± 8.42 (possible range: 9–45), respectively. 350 (51.09%) of them have sufficient knowledge, 168 (24.53%) have positive attitudes and 395 (57.66%) have active practices. Pearson correlation analysis showed that knowledge was positively correlated with attitudes (r = 0.397, P

In this paper, we develop a profit-sharing-based optimal routing mechanism to incentivize horizontal collaboration among urban goods distributors. The core of this mechanism is based on exchanging goods at meet points, which is optimally planned en route. We propose a Collaborative Electric Vehicle Routing Problem with Meet Points (CoEVRPMP) considering constraints such as time windows, opportunity charging, and meet-point synchronization. The proposed CoEVRPMP is formulated as a mixed-integer nonlinear programming model. We present an exact method via branching and a matheuristic that combines adaptive large neighborhood search with linear programming. The viability and scalability of the collaborative method are demonstrated through numerical case studies, including a real-world case and a large-scale experiment with up to 500 customers. The findings underscore the significance of horizontal collaboration among delivery companies in attaining both higher individual profits and lower total costs. Moreover, collaboration helps to reduce the environmental footprint by decreasing travel distance.

Background FOXP3 is a transcription factor that regulates the development and function of Treg, playing an essential role in preventing autoimmune diseases. Variation in FOXP3 can impair the function of Treg cells, thus destroying their inhibitory capacity and leading to autoimmune diseases. This paper investigated whether the three SNPs in the FOXP3 gene (-3279 C/A, -924 A/G and -6054 del/ATT) are associated with systemic lupus erythematosus (SLE) susceptibility in the Han Chinese population.Materials and methods The study cohort comprised 122 SLE patients and 268 healthy controls. Genotyping was performed by polymerase chain reaction sequence-specific primer (PCR-SSP). Furthermore, we examined the potential clinical manifestations associated with FOXP3 polymorphisms in SLE patients.Results The results showed that the -3279 (C > A) was significantly associated with the SLE risk in a homozygote (OR = 3.24, 95% CI = 1.23–8.52, p = .013, AA vs. CC), dominant (OR = 1.68, 95% CI = 1.07–2.65, p = .025, AC + AA vs. CC), recessive (OR = 2.90, 95% CI = 1.12–7.55, p = .023, AA vs. AC + CC) and allelic (OR = 1.72, 95% CI = 1.18–2.53, p = .005, A vs. C) models. In addition, -924 (A > G) was positively associated with SLE risk in the heterozygote (OR = 1.66, 95% CI = 1.04–2.66, p = .033, AG vs. AA) and dominant (OR = 1.59, 95% CI = 1.01–2.49, p = .042, AG + GG vs. AA) models, whereas -6054 (del > ATT) was not associated with SLE. Moreover, the immunological index analysis suggested that decreased complement C4 occurred more frequently in SLE patients carrying the minor allele (A) -3279 (C > A) than those not (p = .005).Conclusions We demonstrated that -3279 (C > A) and -924 (A > G) were associated with an increased risk of SLE and the immunological index, indicating that the FOXP3 variation is potentially related to the occurrence and development of SLE.

Academic papers are the cornerstone of knowledge dissemination and crucial for researchers’ career development. This is particularly true for rapidly evolving research domains such as transportation, as evidenced by the surge of journals and papers in the past decade. While abundant literature offers guidance on successful publication strategies, insights into the reasons for rejection are rare. This study fills in this gap by examining why papers are rejected in the area of transportation. We present concrete evidence based on data from over 5,000 rejected transport papers. Quantitative analyses are conducted to reveal the impacts of similarity rate, duplication submission rate, and topic on desk rejections. Additionally, we shed light on the distinct focus reviewers have when serving different journals. We hope the results could equip transport researchers with a deeper comprehension of publication criteria and a better awareness of common but avoidable mistakes.

Abstract Background The diagnosis of glioma has advanced since the release of the WHO 2021 classification with more molecular alterations involved in the integrated diagnostic pathways. Our study aimed to present our experience with the clinical features and management of astrocytoma, IDH mutant based on the latest WHO classification. Methods Patients diagnosed with astrocytoma, IDH‐mutant based on the WHO 5th edition classification of CNS tumors at our center from January 2009 to January 2022 were included. Patients were divided into WHO 2–3 grade group and WHO 4 grade group. Integrate diagnoses were retrospectively confirmed according to WHO 2016 and 2021 classification. Clinical and MRI characteristics were reviewed, and survival analysis was performed. Results A total of 60 patients were enrolled. 21.67% (13/60) of all patients changed tumor grade from WHO 4th edition classification to WHO 5th edition. Of these, 21.43% (6/28) of grade II astrocytoma and 58.33% (7/12) of grade III astrocytoma according to WHO 4th edition classification changed to grade 4 according to WHO 5th edition classification. Sex (p = 0.042), recurrent glioma (p = 0.006), and Ki‐67 index (p

Abstract This study tests the generalisability of three Brain Tumor Segmentation (BraTS) challenge models using a multi-center dataset of varying image quality and incomplete MRI datasets. In this retrospective study, DeepMedic, no-new-Unet (nn-Unet), and NVIDIA-net (nv-Net) were trained and tested using manual segmentations from preoperative MRI of glioblastoma (GBM) and low-grade gliomas (LGG) from the BraTS 2021 dataset (1251 in total), in addition to 275 GBM and 205 LGG acquired clinically across 12 hospitals worldwide. Data was split into 80% training, 5% validation, and 15% internal test data. An additional external test-set of 158 GBM and 69 LGG was used to assess generalisability to other hospitals’ data. All models’ median Dice similarity coefficient (DSC) for both test sets were within, or higher than, previously reported human inter-rater agreement (range of 0.74–0.85). For both test sets, nn-Unet achieved the highest DSC (internal = 0.86, external = 0.93) and the lowest Hausdorff distances (10.07, 13.87 mm, respectively) for all tumor classes (p

This study systematically investigated three influential factors—water-to-binder ratio, cement/sand ratio, and steel fiber content—that significantly impact the performance of ultra-high-performance concrete (UHPC). Utilizing the Response Surface Methodology (RSM) with a Central Composite Design (CCD), 20 carefully designed mix proportions underwent comprehensive experimental testing. Through rigorous statistical analysis, models were established to elucidate the complex relationships between the specified factors and the overall properties of UHPC. Variance analysis reveals significant effects of the three factors on UHPC performance, with workability and compressive strength increasing with higher cement/sand ratios while flexural strength decreases. Moreover, increased water-to-binder ratios exhibit substantial negative impacts on both 28-day compressive and flexural strengths. Despite adversely affecting workability, higher steel fiber dosages contribute positively to mechanical performance. Furthermore, Monte Carlo sampling and the multi-objective non-dominated sorting genetic algorithm-II (NSGA-II) were employed to validate the reliability of the statistical model and to conduct multi-objective optimization. The final UHPC mix design obtained consists of a cement/sand ratio of 1.12, a water/binder ratio of 0.16, and a steel fiber content of 2.94%. Experimental results yielded a slump flow of 802 mm, compressive strength of 122.7 MPa, and flexural strength of 24.3 MPa.

BackgroundThe 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates EGFR amplification (Amp) as one of diagnostic markers for glioblastoma (GBM).PurposeThis study aimed to describe the frequency, clinical value and molecular correlation of EGFR Amp in diffuse gliomas based on the latest classification.MethodsWe reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of EGFR Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of EGFR Amp in different glioma subtypes.Results163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. EGFR Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM.ConclusionOur study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.

Abstract Background The endoplasmic reticulum (ER) regulates critical processes, including lipid synthesis, which are affected by transmembrane proteins localized in the ER membrane. One such protein, transmembrane protein 147 (TMEM147), has recently been implicated for its role in hepatocellular carcinoma (HCC) tumorigenesis; however, the mechanisms remain unclear. We investigated the role of TMEM147 in HCC and the underlying mechanisms. Methods TMEM147 expression was examined in human HCC cells and adjacent non-tumorous tissues using quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. In vitro and in vivo studies were conducted to investigate the impact of TMEM147 on the progression of HCC. Proteins interacting with TMEM147 were identified via RNA-seq, immunoprecipitation, and mass spectrometry analyses. Lipidomic analysis and enzyme-linked immunosorbent assay (ELISA) were employed to determine and analyze cholesterol and 27-hydroxycholesterol (27HC) contents. Extensive experimental techniques were used to study ferroptosis in HCC cells. The fatty acid content of macrophages affected by TMEM147 was quantified using ELISA. Macrophage phenotypes were determined using immunofluorescence assay and flow cytometric analysis. Results TMEM147 mRNA and protein levels were increased in HCC cells, and the increased TMEM147 expression was associated with a poor survival. TMEM147 promoted tumor cell proliferation and metastases in vitro and in vivo. The protein was found to interact with the key enzyme 7-dehydrocholesterol reductase (DHCR7), which affected cellular cholesterol homeostasis and increased the extracellular levels of 27HC in HCC cells. TMEM147 also promoted the expression of DHCR7 by enhancing the activity of signal transducer and activator of transcription 2. 27HC expression upregulated glutathione peroxidase 4 in HCC, leading to ferroptosis resistance and promotion of HCC proliferation. HCC cell-derived 27HC expression increased the lipid metabolism in macrophages and activated peroxisome proliferator-activated receptor-γ signaling, thereby activating M2 macrophage polarization and promoting HCC cell invasion and migration. Conclusions Our results indicate that TMEM147 confers ferroptosis resistance and M2 macrophage polarization, which are primarily dependent on the upregulation of cellular cholesterol homeostasis and 27HC secretion, leading to cancer growth and metastasis. These findings suggest that the TMEM147/STAT2/DHCR7/27HC axis in the tumor microenvironment may serve as a promising therapeutic target for HCC. Graphical Abstract

Abstract Background The latest fifth edition of the World Health Organization (WHO) classification of the central nervous system (CNS) tumors (WHO CNS 5 classification) released in 2021 defined astrocytoma, IDH‐mutant, Grade 4. However, the understanding of this subtype is still limited. We conducted this study to describe the features of astrocytoma, IDH‐mutant, Grade 4 and explored the similarities and differences between histological and molecular subtypes. Methods Patients who underwent surgery from January 2011 to January 2022, classified as astrocytoma, IDH‐mutant, Grade 4 were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis. Results Altogether 33 patients with astrocytoma, IDH‐mutant, Grade 4 were selected, including 20 with histological and 13 with molecular WHO Grade 4 astrocytoma. Tumor enhancement, intratumoral‐necrosis like presentation, larger peritumoral edema, and more explicit tumor margins were frequently observed in histological WHO Grade 4 astrocytoma. Additionally, molecular WHO Grade 4 astrocytoma showed a tendency for relatively longer overall survival, while a statistical significance was not reached (47 vs. 25 months, p = 0.22). TP53, CDK6, and PIK3CA alteration was commonly observed, while PIK3R1 (p = 0.033), Notch1 (p = 0.027), and Mycn (p = 0.027) alterations may affect the overall survival of molecular WHO Grade 4 astrocytomas. Conclusions Our study scrutinized IDH‐mutant, Grade 4 astrocytoma. Therefore, further classification should be considered as the prognosis varied between histological and molecular WHO Grade 4 astrocytomas. Notably, therapies aiming at PIK3R1, Notch 1, and Mycn may be beneficial.

Millimeter-Wave Radar is one promising sensor to achieve robust perception against challenging observing conditions. In this paper, we propose a Radar Inertial Odometry (RIO) pipeline utilizing a long-range 4D millimeter-wave radar for autonomous vehicle navigation. Initially, we develop a perception frontend based on radar point cloud filtering and registration to estimate the relative transformations between frames reliably. Then an optimization-based backbone is formulated, which fuses IMU data, relative poses, and point cloud velocities from radar Doppler measurements. The proposed method is extensively tested in challenging on-road environments and in-the-air environments. The results indicate that the proposed RIO can provide a reliable localization function for mobile platforms, such as automotive vehicles and Unmanned Aerial Vehicles (UAVs), in various operation conditions.

Abstract Insufficient immune cell infiltration into the tumor microenvironment (TME) greatly compromises the clinical application of immune‐checkpoint inhibitors (ICIs)‐based immunotherapy. Recent findings have shown that activation of the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway can enhance natural immunity and increase lymphocyte infiltration into the TME, which presents a promising strategy for cancer immunotherapy. In this study, we constructed hydroxyapatite nanoparticles co‐loaded with curcumin and L‐oxaliplatin (Cur/L‐OHP@HAP NPs). We analyzed the particle‐size distribution, zeta potential, spectral characteristics (Fourier‐transform infrared spectroscopy, X‐ray photoelectron spectroscopy, ultraviolet–visible spectroscopy), and drug‐release properties of the Cur/L‐OHP@HAP NPs. The cellular uptake of the Cur/L‐OHP@HAP NPs detected by flow cytometry and confocal laser‐scanning microscopy. We comprehensively evaluated the anti‐tumor properties and immune‐activating effects of the NPs, both in vitro and in vivo. Physicochemical characterizations demonstrated that the Cur/L‐OHP@HAP NPs were successfully synthesized and were capable of pH‐dependent drug release. Notably, the Cur/L‐OHP@HAP NPs efficiently entered cancer cells, after which the released L‐OHP induced nuclear DNA (nDNA) damage to some extent. HAP promoted the release of intracellular Ca2+ stores in cancer cells, and curcumin inhibited Ca2+ efflux, resulting in intracellular Ca2+ overload and the release of mitochondrial DNA (mtDNA). Damage to both nDNA and mtDNA greatly stimulated the cGAS‐STING pathway, thereby activating natural immunity, accompanied by immune cell recruitment to the TME. In summary, the Cur/L‐OHP@HAP NPs show good prospects for improving cancer immunotherapy.

ABSTRACTGestational diabetes mellitus (GDM) is characterized by the development of hyperglycemia and insulin resistance during the second or third trimester of pregnancy, associated with considerable risks to both the mother and developing fetus. Although emerging evidence suggests an association between the altered gut microbiota and GDM, remarkably little is known about the microbial and metabolic mechanisms that link the dysbiosis of the gut microbiota to the development of GDM. In this study, a metagenome-wide association study and serum metabolomics profiling were performed in a cohort of pregnant women with GDM and pregnant women with normal glucose tolerance (NGT). We identified gut microbial alterations associated with GDM and linked to the changes in circulating metabolites. Blood metabolite profiles revealed that GDM patients exhibited a marked increase in 2-hydroxybutyric acid and L-alpha-aminobutyric acid, but a decrease in methionine sulfoxide, allantoin, and dopamine and dopaminergic synapse, when compared with those in NGT controls. Short-chain fatty acid-producing genera, including Faecalibacterium, Prevotella, and Streptococcus, and species Bacteroides coprophilus, Eubacterium siraeum, Faecalibacterium prausnitzii, Prevotella copri, and Prevotella stercorea, were significantly reduced in GDM patients relative to those in NGT controls. Bacterial co-occurrence network analysis revealed that pro-inflammatory bacteria were over-represented as the core species in GDM patients. These microbial and metabolic signatures are closely associated with clinical parameters of glucose metabolism in GDM patients and NGT controls. In conclusion, we identified circulating dopamine insufficiency, imbalanced production of SCFAs, and excessive metabolic inflammation as gut microbiota-driven multiple parallel hits linked to GDM development. This work might explain in part the mechanistic link between altered gut microbiota and GDM pathogenesis, and suggest that gut microbiota may serve as a promising target to intervene in GDM.

Abstract Glioblastoma (GBM) is the most malignant CNS tumor with a highest incidence rate, and most patients would undergo a recurrence. Recurrent GBM (rGBM) shows an increasing resistance to chemotherapy and radiotherapy, leading to a significantly poorer prognosis and the urgent need for novel treatments. Immunotherapy, a rapidly developing anti-tumor therapy in recent years, has shown its potential value in rGBM. Recent studies on PD-1 immunotherapy and CAR-T therapy have shown some efficacy, but the outcome was not as expected. Tumor vaccination is the oldest approach of immunotherapies, which has returned to the research focus because of the failure of other strategies and subversive understanding of CNS. The isolation effect of blood brain barrier and the immunosuppressive cell infiltration could lead to resistance existing in all phases of the anti-tumor immune response, where novel tumor vaccines have been designed to overcome these problems through new tumor antigenic targets and regulatory of the systematic immune response. In this review, the immunological characteristics of CNS and GBM would be discussed and summarized, as well as the mechanism of each novel tumor vaccine for rGBM. And through the review of completed early-phase studies and ongoing large-scale phase III clinical trials, evaluation could be conducted for potential immune response, biosecurity and initial clinical outcome, which further draw a panorama of this vital research field and provide some deep thoughts for the prospective tendency of vaccination strategy. Video Abstract

Abstract Purpose Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However, the superiority of combination therapy to TACE monotherapy remains controversial. Therefore, here we performed a meta-analysis to evaluate the efficacy and safety of TACE plus TKIs in patients with uHCC. Methods We searched four databases for eligible studies. The primary outcome was time to progression (TTP), while the secondary outcomes were overall survival (OS), tumor response rates, and adverse events (AEs). Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were collected for TTP and OS, and the data were analyzed using random-effects meta-analysis models in STATA software. OR and 95% CIs were used to estimate dichotomous variables (complete remission[CR], partial remission[PR], stable disease[SD], progressive disease[PD], objective response rate[ORR], disease control rate[DCR], and AEs) using RStudio’s random-effects model. Quality assessments were performed using the Newcastle–Ottawa scale (NOS) for observational studies and the Cochrane risk of bias tool for randomized controlled trials (RCTs). Results The meta-analysis included 30 studies (9 RCTs, 21 observational studies) with 8246 patients. We judged the risk of bias as low in 44.4% (4/9) of the RCTs and high in 55.6% (5/9) of the RCTs. All observational studies were considered of high quality, with a NOS score of at least 6. Compared with TACE alone or TACE plus placebo, TACE combined with TKIs was superior in prolonging TTP (combined HR 0.72, 95% CI 0.65–0.80), OS (combined HR 0.57, 95% CI 0.49–0.67), and objective response rate (OR 2.13, 95% CI 1.23–3.67) in patients with uHCC. However, TACE plus TKIs caused a higher incidence of AEs, especially hand-foot skin reactions (OR 87.17%, 95%CI 42.88–177.23), diarrhea (OR 18.13%, 95%CI 9.32–35.27), and hypertension (OR 12.24%, 95%CI 5.89–25.42). Conclusions Our meta-analysis found that TACE plus TKIs may be beneficial for patients with uHCC in terms of TTP, OS, and tumor response rates. However, combination therapy is also associated with a significantly increased risk of adverse reactions. Therefore, we must evaluate the clinical benefits and risks of combination therapy. Further well-designed RCTs are needed to confirm our findings. Trial registration PROSPERO registration number: CRD42022298003.

ObjectiveCognitive frailty (CF) is characterized by physical frailty and potentially reversible cognitive impairment without Alzheimer’s disease and other dementias. Clarifying the prevalence and related factors of cognitive frailty can help researchers understand its epidemiological status and formulate intervention measures. This study aims to conduct a systematic review and meta-analysis of the prevalence and related factors of CF in diabetic patients in Chinas to better understand the current status of CF in diabetic patients in China and develop effective intervention measures for related factors.MethodsPubMed, Web of Science, Embase, Cochrane Library, CNKI, Weipu(VIP), WANFANG, China Biology Medicine (CBM) and DUXIU were searched to collect epidemiological data on Chinese diabetic patients. Articles published through May 29, 2023, were searched. The number of diabetes with CF and the total number of diabetes in the included studies were extracted to estimate the prevalence of diabetes with CF. For factors related to diabetes with CF, odds ratios (OR) and 95% confidence intervals (CI) were used for estimation.ResultsA total of 248 records were screened, of which 18 met the inclusion criteria. The results of meta-analysis showed that the prevalence of Chinese diabetic patients with CF was 25.8% (95% CI = 19.7 to 31.9%). Subgroup analysis showed that hospital prevalence was higher than in the community and in women than in men. Combined estimates showed that depression, malnutrition, advanced age (≥70, ≥80), combined chronic diseases ≥4 and glycated hemoglobin ≥8.5 were risk factors for CF in diabetics patients in China, with regular exercise and high education level (≥ college) as protective factors.ConclusionCognitive frailty was common in diabetic patients in China. Such populations should be screened early and intervened with relevant factors.Systematic review registration: A systematic review of this study evaluated the registered websites as https://www.crd.york.ac.uk/PROSPERO/, CRD42023431396.

ObjectiveZolbetuximab is a “first-in-class” chimeric lgG1 monoclonal antibody targeting Claudin18.2 (CLDN 18.2). In recent years, several important trials have been published showing that zolbetuximab is associated with improved prognosis in patients with advanced gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. This promises great change to the current treatment landscape. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zolbetuximab for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma.MethodsThe following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane library (updated 10 June 2023). All randomized trials comparing zolbetuximab plus chemotherapy versus first-line chemotherapy alone for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).ResultsThis systematic review and meta-analysis included three randomized controlled studies involving 1,402 patients (699 receiving zolbetuximab plus chemotherapy and 703 receiving chemotherapy alone). Compared with chemotherapy alone, zolbetuximab plus chemotherapy significantly improved OS (HR = 0.73; 95% CI: 0.68–0.84) and PFS (HR = 0.64; 95% CI: 0.50–0.82), but did not result in a higher ORR (RR = 0.92; 95% CI: 0.82–1.03). Further analysis of CLDN 18.2 expression showed a more significant benefit for OS (HR = 0.69; 95% CI: 0.55–0.87; p = 0.002) and PFS (HR = 0.61; 95% CI: 0.44–0.84; p = 0.003) from zolbetuximab in patients with high expression, while there was significant benefit in patients with lower expression. In terms of AEs, zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but increased risk of nausea and vomiting were more common.ConclusionThis systematic review and meta-analysis revealed that the effect of zolbetuximab plus chemotherapy was superior to that of chemotherapy alone for first-line treatment of advanced CLDN 18.2-positive G/GEJ adenocarcinoma. Thus, zolbetuximab plus chemotherapy represents a new first-line treatment for these patients. Zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but was generally manageable.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42023437126).

Gastrointestinal (GI) tumor is a serious disease with high mortality rates and morbidity rates worldwide. Chemotherapy is a key treatment for GI, however, systematic side effects and inevitable drug resistance complicate the situation. In the process of therapy, P-glycoprotein (P-gp) could remove chemotherapy drugs from cells, thus causing multi-drug resistance. Chemodynamic therapy (CDT) utilizing Fenton chemistry has been used for cancer therapy, along with various combination therapies. The reactive oxygen species produced by CDT could inhibit P-gp’s efflux pump function, which reduce chemoagents excretion and reverse drug resistance. In the present study, we developed novel nanocrystals (Cu2O@Pt NCs) to overcome drug resistance by reducing mitochondria-derived ATP through chemo/CDT in GI cancer. Furthermore, in vivo results in tumor-bearing mice demonstrated that treatment with Cu2O@Pt NCs with CDT and chemotherapy could achieve the most effective antitumor therapeutic effect with the least amounts of adverse effects. As a result, Cu2O@Pt NCs could provide a promising strategy for chemo/CDT-synergistic therapy.

Purpose – This paper aims to review the studies on intersection control with connected and automated vehicles (CAVs). Design/methodology/approach – The most seminal and recent research in this area is reviewed. This study specifically focuses on two categories: CAV trajectory planning and joint intersection and CAV control. Findings – It is found that there is a lack of widely recognized benchmarks in this area, which hinders the validation and demonstration of new studies. Originality/value – In this review, the authors focus on the methodological approaches taken to empower intersection control with CAVs. The authors hope the present review could shed light on the state-of-the-art methods, research gaps and future research directions.

Surrounding rock pressure is a crucial parameter in tunnel engineering design, and its calculation is a classic challenge. The surrounding rock pressure is influenced by geostress, but existing calculation methods often do not take into account the effect of geostress. In this paper, finite discrete element method (FDEM) is used to study the design values of tunnel surrounding rock pressure under different geostress fields. Firstly, a set of calibration methods for input parameters of FDEM is summarized based on previous studies. Then, taking a high-speed railway tunnel in IV-level surrounding rock as an example, the excavation-induced failure process of the tunnel under the influence of gravity stress field and geostress field is simulated using the FDEM. By comparing the results with those of the finite element method simulation, the rationality of applying FDEM to the simulation of tunnel excavation is demonstrated. Next, a calculation method of surrounding rock pressure design value based on FDEM is proposed by introducing tunnel displacement criterion, and its validity is verified by comparing with the results of the theoretical formula. Finally, the surrounding rock pressure design values under different geostress are analyzed by using this calculation method. The results show that there are significant differences between the gravity stress field and the geostress field in the maximum principal stress distribution, failure zone form and crack distribution. The geostress directly influences the design value of surrounding rock pressure. As the geostress varies from 4MPa to 12MPa, the corresponding design value increases from 49KPa to 1,288KPa, illustrating a quadratic relationship between them. With the corresponding design support force, the displacement of the surrounding rock is controlled within a reasonable range, ensuring the stability of the tunnel is maintained.

IntroductionGlioblastoma (GBM), the most lethal primary brain malignancy, is divided into histological (hist-GBM) and molecular (mol-GBM) subtypes according to the 2021 World Health Organization classification of central nervous system tumors. This study aimed to characterize the clinical, radiological, molecular, and survival features of GBM under the current classification scheme and explore survival determinants.MethodsWe re-examined the genetic alterations of IDH-wildtype diffuse gliomas at our institute from 2011 to 2022, and enrolled GBMs for analysis after re-classification. Univariable and multivariable analyses were used to identify survival determinants.ResultsAmong 209 IDH-wildtype gliomas, 191 were GBMs, including 146 hist-GBMs (76%) and 45 mol-GBMs (24%). Patients with mol-GBMs were younger, less likely to develop preoperative motor dysfunction, and more likely to develop epilepsy than hist-GBMs. Mol-GBMs exhibited lower radiographic incidences of contrast enhancement and intratumoral necrosis. Common molecular features included copy-number changes in chromosomes 1, 7, 9, 10, and 19, as well as alterations in EGFR, TERT, CDKN2A/B, and PTEN, with distinct patterns observed between the two subtypes. The median overall survival (mOS) of GMB was 12.6 months. Mol-GBMs had a higher mOS than hist-GBMs, although not statistically significant (15.6 vs. 11.4 months, p=0.17). Older age, male sex, tumor involvement of deep brain structure or functional area, and genetic alterations in CDK4, CDK6, CIC, FGFR3, KMT5B, and MYB were predictors for a worse prognosis, while MGMT promoter methylation, maximal tumor resection, and treatment based on the Stupp protocol were predictive for better survival.ConclusionThe definition of GBM and its clinical, radiological, molecular, and prognostic characteristics have been altered under the current classification.

IntroductionThe fifth edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors released in 2021 formally defines pediatric-type diffuse gliomas. However, there is still little understanding of pediatric-type diffuse gliomas, and even less attention has been paid to adult patients. Therefore, this study describes the clinical radiological, survival, and molecular features of adult patients with pediatric-type glioma.MethodsAdult patients who underwent surgery from January 2011 to January 2022, classified as pediatric-type glioma, were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis.ResultsAmong 596 adult patients, 20 patients with pediatric-type glioma were screened, including 6 with diffuse astrocytoma, MYB- or MYBL1-altered, 2 with diffuse midline glioma, H3 K27-altered, and 12 with diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype. Pediatric high-grade glioma (pHGG) frequently showed tumor enhancement, peritumoral edema, and intratumoral necrosis. Adult patients with pHGG showed a longer life expectancy than adult patients with glioblastoma. Common molecular alterations included chromosome alterations and CDKN2A/B, PIK3CA, and PTEN, while altered KMT5B and MET were found to affect the overall survival.ConclusionOur study demonstrated adult patients with pediatric-type glioma. Notably, our research aims to expand the current understanding of adult patients with pediatric-type diffuse gliomas. Furthermore, personalized therapies consisting of targeted molecular inhibitors for MET and VEGFA may exhibit beneficial effects in the corresponding population.

ObjectiveThis paper aims to analyze the horizontal trajectory tracking of an underwater vehicle.MethodsFirst, the 3-DOFs motion equation is derived based on the plane trajectory tracking control target of the underwater vehicle, and the damping term parameters and additional mass term parameters of the vehicle are obtained through the commercial CFD software STAR-CCM+ and ANSYS AQWA respectively. Combined with the dynamic configuration of the vehicle and calculated hydrodynamic parameters, a control strategy is designed on the basis of backstepping and sliding mode control technology. Finally, using the designed control strategy, the trajectory tracking simulation calculation is carried out on the Matlab/Simulink platform for both the linear and nonlinear motion trajectories of the vehicle on the horizontal plane.ResultsThe numerical simulation results show that the underwater vehicle can achieve good tracking effects for both kinds of motion trajectories, and the propeller thrust changes smoothly.ConclusionsThe controller designed in this paper can enable an underwater vehicle to track its target trajectory quickly and maintain a good continuous tracking effect.

Purpose – This paper aims to address the longitudinal control problem for person-following robots (PFRs) for the implementation of this technology. Design/methodology/approach – Nine representative car-following models are analyzed from PFRs application and the linear model and optimal velocity model/full velocity difference model are qualified and selected in the PFR control. Findings – A lab PFR with the bar-laser-perception device is developed and tested in the field, and the results indicate that the proposed models perform well in normal person-following scenarios. Originality/value – This study fills a gap in the research on PRFs longitudinal control and provides a useful and practical reference on PFRs longitudinal control for the related research.

Purpose – This study aims to make full use of the advantages of connected and autonomous vehicles (CAVs) and dedicated CAV lanes to ensure all CAVs can pass intersections without stopping. Design/methodology/approach – The authors developed a signal coordination model for arteries with dedicated CAV lanes by using mixed integer linear programming. CAV non-stop constraints are proposed to adapt to the characteristics of CAVs. As it is a continuous problem, various situations that CAVs arrive at intersections are analyzed. The rules are discovered to simplify the problem by discretization method. Findings – A case study is conducted via SUMO traffic simulation program. The results show that the efficiency of CAVs can be improved significantly both in high-volume scenario and medium-volume scenario with the plan optimized by the model proposed in this paper. At the same time, the progression efficiency of regular vehicles is not affected significantly. It is indicated that full-scale benefits of dedicated CAV lanes can only be achieved with signal coordination plans considering CAV characteristics. Originality/value – To the best of the authors’ knowledge, this is the first research that develops a signal coordination model for arteries with dedicated CAV lanes.

BackgroundThe 5th edition of the World Health Organization (WHO) classification of central nervous system tumors incorporated specific molecular alterations into the categorization of gliomas. The major revision of the classification scheme effectuates significant changes in the diagnosis and management of glioma. This study aimed to depict the clinical, molecular, and prognostic characteristics of glioma and its subtypes according to the current WHO classification.MethodsPatients who underwent surgery for glioma at Peking Union Medical College Hospital during 11 years were re-examined for tumor genetic alterations using next-generation sequencing, polymerase chain reaction-based assay, and fluorescence in situ hybridization methods and enrolled in the analysis.ResultsThe enrolled 452 gliomas were reclassified into adult-type diffuse glioma (ntotal=373; astrocytoma, n=78; oligodendroglioma, n=104; glioblastoma, n=191), pediatric-type diffuse glioma (ntotal=23; low-grade, n=8; high-grade, n=15), circumscribed astrocytic glioma (n=20), and glioneuronal and neuronal tumor (n=36). The composition, definition, and incidence of adult- and pediatric-type gliomas changed significantly between the 4th and the 5th editions of the classification. The clinical, radiological, molecular, and survival characteristics of each subtype of glioma were identified. Alterations in CDK4/6, CIC, FGFR2/3/4, FUBP1, KIT, MET, NF1, PEG3, RB1, and NTRK2 were additional factors correlated with the survival of different subtypes of gliomas.ConclusionsThe updated WHO classification based on histology and molecular alterations has updated our understanding of the clinical, radiological, molecular, survival, and prognostic characteristics of varied subtypes of gliomas and provided accurate guidance for diagnosis and potential prognosis for patients.

In this work, the effect of cellulose ether (CE), tartaric acid (TA), and polycarboxylate superplasticizer (PCE) on the working performance and mechanical properties of cement-based self-leveling mortar is investigated. According to the orthogonal experiment analysis, TA is identified as the most influential factor affecting the working performance, as indicated by factors such as fluidity, fluidity loss, and viscosity. Upon conducting a comprehensive assessment of the working performance and mechanical properties, the optimal parameters are found to be CE = 0.6 wt.‰, TA = 0.5 wt.‰, and PCE = 2.0 wt.‰. A univariate test highlights that that the working performance improves with the higher TA dosages. Specifically, the exponential reduction of fluidity loss corresponds with an increased TA content. Regarding the mechanical properties of cement-based self-leveling mortar, the compressive and flexural strength exhibit enhancement when the TA dosage remains below 0.4 wt.‰ at the early stage, implying that TA has some influence on the hydration process. Impressively, the 1 d compressive and flexural strengths surpass 7 MPa and 2 MPa, respectively, ensuring the viability of subsequent construction activities. Through an analysis of hydration heat, the effect mechanism of TA on the cement-based self-leveling mortar is derived. The result shows that the addition of TA decelerates the hydration process within the initial 10 h, followed by acceleration in the subsequent 20 h to 30 h. Consequently, this delayed formation of the early hydration product, ettringite, contributes to a more porous structure in the slurry, with low friction leading to a better working performance. A large number of hydration products, such as alumina gel and calcium–silicon–hydrate gel, presented in the hardened paste results in the good mechanical properties at 1 d. This study may lay a foundation for the optimization of the dosage of chemical admixtures in the self-leveling mortar and high-performance cement-based materials, and also impart valuable insights for practical applications extending to the realm of building construction and decoration.

Rehabilitation medicine (RM) requires more personalisation than any other treatment in the medical domain. Additive manufacturing (AM) is a promising candidate for providing customised tools to improve performance but reduce cost and complexity of personalisation. Research and applications of AM in the RM field are receiving increasing attention. This paper aims to identify the research status and development trend via visual analysis of literature. At first, core publications from representative domain journals and conference proceedings were extracted as source data for the inputs of statistical analysis. Secondly, keyword visualisation analysis provides research hotspots and technological developments to summarise the research frontiers. Finally, visual knowledge graphs were constructed to show the emerging trends, including digital solutions, lifecycle treatment, and multiple-supporter rehabilitation services, in this special interdisciplinary field. Specially, digital methods with AM and associated services will be one of the principle roadmaps for personalised RM in the future.

BackgroundThe addition of endocrine therapy to salvage radiotherapy (SRT) is expected to further improve the prognosis of patients with biochemical recurrence of prostate cancer after radical prostatectomy (RP). The quantitative synthesis of clinical outcomes of SRT combined with endocrine therapy is limited. Whether salvage radiotherapy plus endocrine therapy remains inconclusive. We performed a systematic review and meta-analysis of existing randomized controlled trials to evaluate the efficacy and safety of salvage radiotherapy combined with endocrine therapy in patients with biochemical recurrence after radical prostatectomy.MethodsA systematic search of PubMed, EMBASE, and the Cochrane library was performed for articles published between January 1, 2012 and October 10, 2022. Data were analyzed using Review Manager 5.4.1 (Cochrane Collaboration Software). Main outcome and measures included biochemical progression-free survival (bPFS), metastasis free survival (MFS), overall survival (OS), and Grade 3 or higher adverse events (3+AEs), including acute and late adverse events.ResultsIn this systematic review and meta-analysis, 4 randomized controlled studies enrolling 2731 male (1374 of whom received SRT combined with endocrine therapy and 1357 controls) met the inclusion criteria. SRT combined with endocrine therapy were related to significantly improve bPFS (HR=0.52; 95% CI: 0.46 0.59; p

Central nervous system (CNS) diseases have been a growing threat to the health of humanity, emphasizing the urgent need of exploring the pathogenesis and therapeutic approaches of various CNS diseases. Primary neurons are directly obtained from animals or humans, which have wide applications including disease modeling, mechanism exploration and drug development. However, traditional two-dimensional (2D) monoculture cannot resemble the native microenvironment of CNS. With the increasing understanding of the complexity of the CNS and the remarkable development of novel biomaterials, in vitro models have experienced great innovation from 2D monoculture toward three-dimensional (3D) multicellular culture. The scope of this review includes the progress of various in vitro models of primary neurons in recent years to provide a holistic view of the modalities and applications of primary neuron models and how they have been connected with the revolution of biofabrication techniques. Special attention has been paid to the interaction between primary neurons and biomaterials. First, a brief introduction on the history of CNS modeling and primary neuron culture was conducted. Next, detailed progress in novel in vitro models were discussed ranging from 2D culture, ex vivo model, spheroid, scaffold-based model, 3D bioprinting model, and microfluidic chip. Modalities, applications, advantages, and limitations of the aforementioned models were described separately. Finally, we explored future prospects, providing new insights into how basic science research methodologies have advanced our understanding of the CNS, and highlighted some future directions of primary neuron culture in the next few decades.

Abstract. Rationale:. For locally advanced non-small cell lung cancer (NSCLC), the neoadjuvant therapy strategy of preoperative nivolumab combined with chemotherapy has great potential, especially for locally advanced NSCLC which are initially unresectable. They may be cured after neoadjuvant immunotherapy, and this may become a new direction of treatment. We hope that this representative medical record and literature review can provide some assistance for clinicians using immune checkpoint inhibitors to treat lung cancer. Patient concerns:. A 50-year-old male patient was admitted to Zhongshan Hospital of Traditional Chinese Medicine on April 27, 2020 due to “coughing for more than one month.”. The patient had nothing of note in either his medical history or that of his family, and no history of smoking. Diagnosis:. The diagnosis was cT4N2M0IIIB stage right lower lung NSCLC with right hilar and mediastinal lymph node metastasis. The stage was inoperable stage IIIB NSCLC, but the patient had a strong willingness for doing surgery. Interventions:. The patient received 3 rounds of the neoadjuvant nivolumab therapy combined with TP (paclitaxel plus cisplatin) regimen, on 5-14-21, 06-07-21 and 07-07-21. Outcomes:. The tumor's area shrunk. Then the patient underwent thoracoscopic radical resection of the cancer in the right upper lung and postoperative pathology achieved pathological complete response (pCR) Lessons:. In this case, combined with the wishes of the patient and the latest research results, we confirmed pCR by radical surgery after 3 rounds of the neoadjuvant nivolumab therapy combined with chemotherapy. This may be a modality to cure more lung cancer patients in the future.

The phase-shifted full-bridge (PSFB) converter has been widely used in power supply modules due to its simple control and high output power. However, with the market’s increasing demand for higher power sources, the PSFB converter needs to face challenges in increasing its output power level. Compared to redesigning a larger power module or a larger single converter, it will be more cost-effective to achieve a higher power output by paralleling the existing converters. However, due to the manufacturing differences in circuit components, the output imbalance in parallel PSFB converter systems may damage the power modules. Thus, the influence of differences in circuit components is analyzed in this paper, and it is found that the leakage inductance and transformer ratio are the main factors resulting in errors in current sharing control. Consequently, a dynamic hybrid compensator (DHC) is proposed in this paper, that can significantly reduce the error in current sharing control via the compensation of the duty cycle of a slave module. Furthermore, the DHC is verified on an 800 W two-phase PSFB converter, which shows that even when the difference in components is as large as 20%, the proposed method can still reduce the error in current sharing control to less than 2% under both half and full load conditions.

Synaptic plasticity is essential for cognitive functions such as learning and memory. One of the mechanisms involved in synaptic plasticity is the dynamic delivery of AMPA receptors (AMPARs) in and out of synapses. Mutations of SPAST, which encodes SPASTIN, a microtubule-severing protein, are considered the most common cause of hereditary spastic paraparesis (HSP). In some cases, patients with HSP also manifest cognitive impairment. In addition, mice with Spastin depletion exhibit working and associative memory deficits and reduced AMPAR levels. However, the exact effect and molecular mechanism of Spastin on AMPARs trafficking has remained unclear. Here, we report that Spastin interacts with AMPAR, and phosphorylation of Spastin enhances its interaction with AMPAR subunit GluA2. Further study shows that phosphorylation of Spastin can increase AMPAR GluA2 surface expression and the amplitude and frequency of miniature excitatory synaptic currents (mEPSC) in cultured hippocampal neurons. Moreover, phosphorylation of Spastin at Ser210 is crucial for GluA2 surface expression. Phosphorylation of Spastin K353A, which obliterates microtubule-severing activity, also promotes AMPAR GluA2 subunit trafficking to the surface and increases the amplitude and frequency of mEPSCs in cultured neurons. Taken together, our data demonstrate that Spastin phosphorylation promotes the surface delivery of the AMPAR GluA2 subunit independent of microtubule dynamics.

This paper presents a personalized stochastic optimal adaptive cruise control (ACC) algorithm for automated vehicles (AVs) incorporating human drivers' risk-sensitivity under system and measurement uncertainties. The proposed controller is designed as a linear exponential-of-quadratic Gaussian (LEQG) problem, which utilizes the stochastic optimal control mechanism to feedback the deviation from the design car-following target. With the risk-sensitive parameter embedded in LEQG, the proposed method has the capability to characterize risk preference heterogeneity of each AV against uncertainties according to each human drivers' preference. Further, the established control theory can achieve both expensive control mode and non-expensive control mode via changing the weighting matrix of the cost function in LEQG to reveal different treatments on input. Simulation tests validate the proposed approach can characterize different driving behaviors and its effectiveness in terms of reducing the deviation from equilibrium state. The ability to produce different trajectories and generate smooth control of the proposed algorithm is also verified.

BackgroundIn recent decades, tranexamic acid (TXA) antifibrinolytic therapy before aneurysm clipping or embolization has been widely reported, but its safety and efficacy remain controversial. This meta-analysis evaluated the efficacy and safety of TXA therapy in aneurysmal subarachnoid hemorrhage (aSAH) patients, aiming to improve the evidence-based medical knowledge of treatment options for such patients.MethodsPubmed, Web of Science, and Cochrane Library databases were searched up to 1 March 2021 for randomized controlled trials (RCTs). We extracted safety and efficacy outcomes and performed a meta-analysis using the Review Manager software. We performed two group analyses of TXA duration and daily dose.ResultsTen RCT studies, enrolling a total of 2,810 participants (1,410 with and 1,400 without TXA therapy), matched the selection criteria. In the TXA duration group: TXA did not reduce overall mortality during the follow-up period [RR 1.00 (95% CI 0.81–1.22)]. The overall rebleeding rate in the TXA group was 0.53 times that of the control group, which was statistically significant [RR 0.53 (95% CI 0.39–0.71)]. However, an RR of 0.43 was not statistically significant in the subgroup analysis of short-term therapy [RR 0.43 (95% CI 0.13–1.39)]. The overall incidence of hydrocephalus was significantly higher in the TXA group than in the control group [RR 1.13 (95% CI 1.02–1.24)]. However, the trend was not statistically significant in the subgroup analysis [short-term: RR 1.10 (95% CI 0.99–1.23); long-term: RR 1.22 (95% CI 0.99–1.50)]. Treatment with TXA did not cause significant delayed cerebral ischemia [RR 1.18 (95% CI 0.89–1.56)], and its subgroup analysis showed an opposite and insignificant effect [short-term: RR 0.99 (95% CI 0.79–1.25); long-term: RR 1.38 (95% CI 0.86–2.21)]. Results in the daily dose group were consistent with those in the TXA duration group.ConclusionsTranexamic acid does not reduce overall mortality in patients with aSAH, nor does it increase the incidence of delayed cerebral ischemia. Tranexamic acid in treating aSAH can reduce the incidence of rebleeding. However, there is no statisticalsignificance in the ultra-early short-term and low daily dose TXA therapy, which may be due to the lack of relevant studies, and more RCT experiments are needed for further study.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.asp? PROSPERO, identifier: 244079.

We introduce a voltage-gated conductance model for an artificial neuron that exhibits tonic, fast, and two types of intrinsic burst spiking. The spike generation is achieved with a single voltage-gated channel that exploits the conductance commutation properties of a two-terminal memristive device. Our circuit implementation is of unprecedented simplicity, using just four electronic components, all conventional, cheap and out-of-the-shelf. Our bursting neuron is a two-compartment model, similar to the Pinsky–Rinzel model. We obtain the full phase diagram and discuss the origin of the different regions. We find that the spike traces of the model bare striking similarity to experimental biological neuronal recordings. Our work may open a new way to investigate neural pathologies, such as epilepsy and Parkinson’s disease, from the study of the phase diagram and the transitions between spiking states of physical neuron models.

A novel series of composite hydrogels, built from the three components 1), hyaluronic acid methacryloyl (HAMA); 2), gelatin methacryloyl (GelMA), and 3), extracellular cartilage matrix (ECM), was prepared and studied regarding the possible utility in the surgical repair of damaged (perforated) tympanic membrane (TM). Noteworthy is component 3), which was harvested from the ribs of α-1,3-galactosidyltransferase-knockout (α-1,3 GalT-KO) pigs. The absence of α-1,3-galactosyl glycoprotein is hypothesized to prevent rejection due to foreign-body immunogenicity. The composite hydrogels were characterized by various aspects, using a variety of physicochemical techniques: aqueous swelling, structural degradation, behavior under compression, and morphology, e.g., in vitro biocompatibility was assessed by the CCK-8 and live–dead assays and through cytoskeleton staining/microscopy. Alcian blue staining and real-time PCR (RT-PCR) were performed to examine the chondrogenic induction potential of the hydrogels. Moreover, a rat TM defect model was used to evaluate the in vivo performance of the hydrogels in this particular application. Taken together, the results from this study are surprising and promising. Much further development work will be required to make the material ready for surgical use.

Shared electric scooters (e-scooter) are booming across the world and widely regarded as a sustainable mobility service. An increasing number of studies have investigated the e-scooter trip patterns, safety risks, and environmental impacts, but few considered the energy efficiency of e-scooters. In this research, we collected the operational data of e-scooters from a major provider in Gothenburg to shed light on the energy efficiency performance of e-scooters in real cases. We first develop a multiple logarithmic regression model to examine the energy consumption of single trips and influencing factors. With the regression model, a Monte Carlo simulation framework is proposed to estimate the fleet energy consumption in various scenarios, taking into account both trip-related energy usage and energy loss in idle status. The results indicate that 40% of e-scooter battery energy was wasted in idle status in the current practice, mainly due to the relatively low usage rate (0.83) of e-scooters. If the average usage rate drops below 0.5, the wasted energy could reach up to 53%. In the end, we present a field example to showcase how to optimally integrate public transport with e-scooters from the perspective of energy efficiency. We hope the findings of this study could help understand and resolve the current and future challenges regarding the ever-growing e-scooter services.

Small nuclear RNAs (snRNAs) are vital for eukaryotic cell activities and play important roles in pre-mRNA splicing. The molecular mechanism underlying the transcription of snRNA, regulated via upstream/downstream cis-elements and relevant trans-elements, has been investigated in detail using cell-free extracts. However, the processing of precursor snRNA (pre-snRNA), which is required by 3’ end maturation of pre-snRNA, remains unclear as a proper processing assay is difficult to develop in vitro. Here, we present an in vitro method using synthetic labeled RNA as substrates to study the 3’ cleavage of pre-snRNA.

BackgroundUnfolded protein response (UPR)-mediated tumor-promoting functions have been identified in multiple cancers, and this study focused on investigating the role and molecular mechanisms of UPR in modulating gastric cancer (GC) pathogenesis.MethodsThe bioinformatics analysis was performed to examine the expression status of cancer associated genes in patients with stomach adenocarcinoma (STAD) and predict the targeting sites of miR-224-5p with LncRNA MIR503HG and TUSC3. Genes expressions were quantified by Real-Time qPCR, Western Blot and immunohistochemistry (IHC). Cell proliferation, viability, apoptosis and mobility were evaluated by MTT assay, trypan blue staining assay, flow cytometer and transwell assay, respectively. The binding sites were validated by dual-luciferase reporter gene system assay.ResultsLncRNA MIR503HG and TUSC3 were downregulated, but miR-224-5p was upregulated in GC tissues and cells, in contrast with their normal counterparts. Further gain- and loss-of-function experiments validated that the malignant phenotypes in GC cells, including cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and tumorigenesis, were negatively regulated by LncRNA MIR503HG. Mechanistically, LncRNA MIR503HG upregulated TUSC3 in GC cells through sponging miR-224-5p, resulting in the repression of GC progression. Finally, we validated that knock-down of ATF6, but not other two branches of UPR (PERK1 and IRE1), partially rescued cell proliferation and EMT in the GC cells with LncRNA MIR503HG overexpression.ConclusionsTargeting the LncRNA MIR503HG/miR-224-5p/TUSC3 signaling cascade suppressed ATF6-mediated UPR, resulting in the blockage of GC development.

In this paper, we study the finite-time stability of permanent magnet synchronous motors (PMSMs) with noise perturbation. To eliminate the chaos in a PMSM and allow it to reach a steady state more quickly within a finite time, we propose a novel adaptive controller based on finite-time control theory. Finite-time stability implies optimal convergence time and better robustness. Finally, numerical simulations are performed to demonstrate the effectiveness and feasibility of our new results.

The direct femtosecond laser writing has been proved to be one of the most efficient techniques for micro-structuring of transparent materials, which can induce refractive index modifications to construct waveguide structures. In this work, laser-induced tracks with single-line configuration are formed inside the BK7 glass by using inscription of femtosecond laser pulses with 1 MHz repetition rate at wavelength of 1030 nm and 515 nm, respectively. The high-resolution confocal Raman spectra are obtained in the track regions to investigate the physical mechanisms of the modification. The results indicate that the specified regions inside the tracks induced by 1030-nm femtosecond laser expand and squeeze the adjacent area under certain writing conditions, leading to a refractive index increase in the core region. The 515-nm femtosecond laser brings out relatively more severe damage in comparison to the 1030-nm laser irradiation. A directional coupler structure has been fabricated by using the optimized writing parameters, showing a nearly balanced output with a ratio of 49.7:50.3 and an insertion loss of 1.36 dB for the single-line waveguide at 1064 nm.

With the rapid development of infrastructure construction, geotechnical engineering has always been worthy of attention due to its complexity and diversity. Accelerating the informatization of geotechnical engineering will contribute to the project management, but the information contained in geotechnical engineering cannot be well integrated because of the lack of unified data standards. Building Information Modeling (BIM) has been considered as an effective technology to manage information, and Industry Foundation Classes (IFC) in BIM serves as a neutral and open standard for the exchange of information. However, it was found that BIM cannot express the information of some structure objects and geological objects well during the construction process of geotechnical engineering. Combined with the characteristics of geotechnical engineering, taking advantage of the good extensibility of IFC, this paper proposes a “Built-In Generation Schema” for geotechnical structure models and a “Plug-In Extension Schema” for three-dimensional (3D) geological models, ultimately forming the basic data system of geotechnical engineering information models based on IFC. Applying extended IFC to the modeling process, the BIM-based modeling method of geotechnical models is proposed. In addition, an IFC-based platform is developed to integrate geological models and structure models for further displaying and analyzing of geotechnical engineering models. The work in this paper provides a feasible way and technical support for promoting the integration and sharing of geotechnical engineering information and enhancing the multiprofessional collaborative work.

The alkaline components in red mud represent one of the crucial factors restricting its application, especially for the construction and building industry. The phase state of alkaline components has a significant influence on the dealkalization of red mud. In this work, an environmentally friendly acid leaching strategy is proposed by controlling the phase transformation of red mud during active roasting pretreatment. With a moderate roasting temperature, the alkaline component is prevented from converting into insoluble phases. After acid leaching with a low concentration of 0.1 M, a high dealkalization rate of 92.8% is obtained. Besides, the leachate is neutral (pH = 7) and the valuable metals in red mud are well preserved, manifesting a high selectivity and efficiency of diluted acid leaching. The calcination experiment further confirms the practicability of the strategy in the construction field, where the cementitious minerals can be formed in large quantities. Compared with the traditional acid leaching routes, the diluted acid leaching strategy in this work is acid saving with low valuable element consumption. Meanwhile, the secondary pollution issue can be alleviated. Hence, the findings in this work provide a feasible approach for the separation and recovery of alkali and resource utilization of red mud.