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Neuroblastoma (NB), a rare childhood cancer originating in nerve tissue. YTHDF3, a member of the YTH domain protein family, is involved in RNA m6A modification and cancer progression. Polymorphisms in YTHDF3 may influence its expression and biological function. Herein, this study estimated the association between YTHDF3 polymorphisms (rs2241753, rs2241754, and rs7464) and NB susceptibility in a multicenter study comprising 898 cases and 1734 controls. We genotyped YTHDF3 candidate polymorphisms by the TaqMan assay. Logistic regression analysis was applied to indicate the possible relationships between these polymorphisms and NB susceptibility, using odds ratios (ORs) and 95% confidence intervals (CIs). Logistic regression analysis revealed that the rs2241753 GA versus GG decreased NB risk (Adjusted OR = 0.84, 95% CI = 0.71-0.997, p = .047), while the rs7464 GG versus AA enhanced NB risk (Adjusted OR = 1.62, 95% CI = 1.20-2.18, p = .002). Additionally, rs7464 GG versus AA/AG showed a higher risk (Adjusted OR = 1.66, 95% CI = 1.24-2.22, p = .0006). Combination analysis showed that having 1-3 risk genotypes versus 0 was associated with increased NB risk (Adjusted OR = 1.28, 95%CI = 1.09-1.51, p = .003). The significance of rs7464 and the risk genotypes combination persisted across multiple subgroups, whereas rs2241754 was significant only in mediastinal NB. False-positive report probability (FPRP) confirmed the reliability of results. Notably, the interaction between rs7464 and rs2241754 may increase NB risk dramatically. Our study demonstrated that YTHDF3 rs7464 A > G significantly affected NB susceptibility, warranting validation in larger sample sizes., (© 2024 International Union of Biochemistry and Molecular Biology.)

Selective withdrawal is an effective measure to mitigate the adverse effects caused by reservoir construction. The main types of selective withdrawal include multi-level withdrawal and internal weir withdrawal, each with distinct characteristics. It is urgent to elucidate the thermal response differences between these two types of selective withdrawal to improve scheduling accuracy. Taking the Xiluodu Reservoir (XLDR) as a representative of monomictic reservoirs in this study, a hydrodynamic-thermal numerical model is employed to investigate the thermal response of large deep monomictic reservoirs under different selective withdrawal types and schemes. Additionally, we also explore the regulatory mechanisms of selective withdrawal on water temperature and its applicability under different hydrological conditions. The results indicated an asynchrony in the variations of the vertical temperature gradient (VTG) and the Schmidt stability index (SSI). SSI is identified as the optimal index for comprehensively reflecting the characteristics of water temperature stratification. The multi-level withdrawal generates a strong velocity zone and a strong temperature gradient zone near the intake, enhancing the overall stratification strength and surface water temperature and increasing the thermocline thickness but weakening its strength. In contrast, internal weir withdrawal accelerates the downward movement of the thermocline and strengthens it but reduces the thermocline thickness. As the withdrawal depth increases, the surface water temperature gradually increases, the thermocline position moves downward, and the duration of strong stratification extends. Different selective withdrawal schemes should be matched with different water demands, based on water quality health and ecological temperature requirements, we provided selective withdrawal strategy recommendations for large monomictic reservoirs, considering the thermal response characteristics of each withdrawal scheme, including changes in temperature structure and outflow temperature characteristics. The findings of this study provide a theoretical basis and technical support for reservoir optimal management and the design of selective withdrawal engineering., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Identification of futile recanalisation following endovascular therapy (EVT) in patients with acute ischaemic stroke is both crucial and challenging. Here, we present a novel risk stratification system based on hybrid machine learning method for predicting futile recanalisation., Methods: Hybrid machine learning models were developed to address six clinical scenarios within the EVT and perioperative management workflow. These models were trained on a prospective database using hybrid feature selection technique to predict futile recanalisation following EVT. The optimal model was validated and compared with existing models and scoring systems in a multicentre prospective cohort to develop a hybrid machine learning-based risk stratification system for futile recanalisation prediction., Results: Using a hybrid feature selection approach, we trained and tested multiple classifiers on two independent patient cohorts (n=1122) to develop a hybrid machine learning-based prediction model. The model demonstrated superior discriminative ability compared with other models and scoring systems (area under the curve=0.80, 95% CI 0.73 to 0.87) and was transformed into a web application (RESCUE-FR Index) that provides a risk stratification system for individual prediction (accessible online at fr-index.biomind.cn/RESCUE-FR/)., Conclusions: The proposed hybrid machine learning approach could be used as an individualised risk prediction model to facilitate adherence to clinical practice guidelines and shared decision-making for optimal candidate selection and prognosis assessment in patients undergoing EVT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Polylactic acid (PLA) composites with high straw content face several challenges, primarily due to the inherent brittleness of straw and its poor compatibility with the polymer matrix. In this study, scanning electron microscopy (SEM) was used to analyze the microscopic structure of wheat straw chemically modified by NaOH and the silane coupling agent, and it was concluded that both treatments effectively removed waxes and silica from the surface of the straw, enhanced fiber roughness, and improved interfacial adhesion. Notably, the silane coupling agent treatment not only facilitated the formation of chemical bonds between the straw fibers and the PLA matrix but also filled the interfiber pores, significantly increasing the structural density. Furthermore, the mechanical properties of composites synthesized by hot pressing 60 % pretreated straw, 33 % PLA and 7 % compatibilizer were evaluated, and the results demonstrated that the silane coupling agent-modified composites exhibited superior mechanical properties, with tensile, flexural and impact strengths of 15.07 MPa, 30.83 MPa and 9.95 kJ/m², respectively-approximately 1.2 times higher than those of the NaOH-treated composites. These findings highlight the significant improvement in the mechanical performance of PLA composites through the use of silane coupling agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Stretchable fibers with high conductivity are vital components for smart textiles and wearable electronics. However, embedding solid conductive materials in polymers significantly reduces conductive pathways when stretched, causing a sharp drop in conductivity. Here, a stretchable metastructured fiber with dynamic liquid metal-microfiber interlocking interface is reported to realize highly conductive yet ultrastable conductance. The Cu-EGaIn mixture is partially embedded within the porous microfiber mat, thereby enabling its roll-up into a spiral-layered metastructured fiber with self-compensating conductive pathways. The metastructured fiber shows outstanding performance, including high conductivity of 1.5 × 10 6  S m -1 , large stretchability up to 629%, and ultrastable conductance with only 16% relative resistance change at 100% strain, which far surpasses the theoretical value. Moreover, these fibers have served as versatile platforms for wearable temperature-visualizing electrothermal fiber heaters and fully stretchable smart sensing-display fabrics. This dynamic solid-liquid interfacial interlocking strategy is promising for stretchable electronics., (© 2024 Wiley‐VCH GmbH.)

Incinerated sewage sludge ash (ISSA) with high P 2 O 5 content is a potential phosphorus resource that can replace the non-renewable phosphorus rocks. However, extracting phosphorus from ISSA using hydrometallurgical methods also dissolves a large amount of impurity metals into the leachate. Therefore, this study proposes a new method combining high-temperature reaction with CaO addition, selective leaching, and chemical precipitation for efficient and low-cost phosphorus recovery from ISSA. During thermal treatment at 1050 °C, the addition of CaO significantly influenced the types and amounts of phosphate mineral phases in ISSA. When 20 % CaO was added, the Al/Fe-phosphate phases were completely converted into acid-soluble Ca-phosphate phases, while Al and Fe were retained in acid-insoluble phases (e.g., Al- and Fe-containing oxides and silicates). Subsequently, by controlling the pH of acidic leachate (2.0 to 1.5), Ca-phosphate phases were selectively dissolved. At a pH of 1.5, better selective leaching was achieved, with a leaching efficiency of 94.71 % for P and less than 10 % for Al, Fe and Si. The XRF results showed that the majority of SiO 2 (38.39 %), Al 2 O 3 (33.26 %) remained in the post-leaching solid residue, which was expected to be further resource utilization. Without purification treatment to remove Al, Fe and Si, almost all phosphate ions were precipitated at pH = 8.5, with P recovery efficiency of 94.07 %. XRD results showed that the precipitate was mainly composed of HAP, with a P 2 O 5 content of 37.51 % and low level of contaminants, thereby realizing the effective recovery of phosphorus from ISSA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Vertical mass exchange hugely changes the solute distribution with the effects of shear layers and multiple-scale turbulent vortices, and then impacts the effectiveness of wetlands in purifying eutrophic water bodies. This study aims to investigate vertical mass exchange mechanisms in wetland systems and to provide theoretical guidance for optimizing the purification efficiency of wetland water quality. We simulate solute diffusion behaviors originating from a continuous point source with vegetated shear layers and bed absorptions through the adopted numerical simulation method, random walk method. The simulated results mainly contributed to three findings: (1) Vegetation features (density and height) inhibit solute diffusion, resulting in a prolonged steady time required for the cross-sectional concentration to reach equilibrium. (2) There is a threshold for the bed absorption probabilities to impact near-bed concentration distribution, that is the 10% absorption probability, over which the variation of bed absorption has few effects on the solute concentration. (3) The shear layer at the top of vegetation promotes vertical mass exchange while preventing solutes above the wake zone from being absorbed by the bed. In practice, the dual effects of submerged vegetation on vertical mass exchange should be comprehensively considered to ensure the effective functioning of wetland ecosystems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Zhonghua Yang reports financial support was provided by National Natural Science Foundation of China. Zhonghua Yang reports financial support was provided by Department of Science and Technology of Hubei Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Clear cell renal cell carcinoma (ccRCC) is a malignant tumor needs more effective treatments. TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D) is a member of the selective factor 1 complex and functions in RNA polymerase I-dependent transcription. Higher TAF1D expression was found in ccRCC tumor tissues and indicated worse survival. Our study aimed to investigate the therapeutic potential of TAF1D in ccRCC. The proliferation and migration of ccRCC cells were significantly inhibited after TAF1D knockdown, while TAF1D overexpressing had opposite effects. Moreover, TAF1D knockdown induced cells to undergo G 0 /G 1 cell cycle arrest and blockade of the epithelial-mesenchymal transition (EMT) process. Mechanistically, TAF1D affect the cell cycle and EMT through the PI3K/AKT/mTOR signaling pathway, thereby promoting the proliferation and metastasis of ccRCC cells in vivo and in vitro. The inhibitory effect of TAF1D knockdown could be reverted by the AKT activator SC79 in ccRCC cells, confirming this mechanism. Besides, TAF1D knockdown in ccRCC cells had a sensitizing effect on sunitinib and enhanced tumor cell inhibiting induced by sunitinib. In conclusion, TAF1D may be a promising target for the treatment of ccRCC and for overcoming sunitinib resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The Pollution source identification (PSI) is an important issue on river water quality management especially for urban receiving water. Numerical inversion method is theoretically an effective PSI technique, which employs monitored downstream pollutant breakthrough curves to identify the pollution source. In practice, it is important to know how much monitoring data should be accumulated to provide PSI results with acceptable accuracy and uncertainty. However, no literature reports on this key point and it seriously handers the numerical PSI technology to mature practical applications. To seek a monitoring guideline for PSI, we conducted extensively numerical experiments for single-point source instantaneous release taking Bayesian-MCMC method as the baseline inversion technique. The crucial time (T c ) phenomenon was found during the data accumulation process for Bayesian source inversion. After T c , estimated source parameters subsequent sustained low error levels and uncertainty convergence. Results shown the presence of T c impacted by the number and location of monitoring sections, while monitoring frequency and data error do not. Under different river hydrodynamic conditions, relative crucial time (Λ) is determined by the river's Peclet number, and minimum effective Λ was controlled by dispersion coefficient (D x ). Analytic spatial structure of Λ(U, D x ) was uncovered and this relationship successfully explained by the information entropy theory. Based on these findings, a novel design method of PSI emergency monitoring network for preparedness plan and a practical framework of PSI for emergency response were established. These findings fill the important knowledge gap in PSI applications and the guidelines provide valuable references for river water quality management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Management of intractable childhood constipation is still challenging. The efficacy of retrograde colonic enema (RCE) with fecal microbiota transplantation (FMT) in intractable childhood constipation has not been established, although both have demonstrated potential in gastrointestinal diseases. The aim of this study was to determine the safety and efficacy of RCE-based FMT in the treatment of intractable constipation in children., Methods: A randomized, double-blind, controlled trial with 110 children was conducted. The patients were randomly assigned to the FMT with RCE group or the placebo with RCE group. All participants received a daily RCE, followed by a 4-week FMT treatment (twice a week) and a 12-week follow-up period. Spontaneous bowel movements ≥ 3 per week were the main outcomes, and the risk ratio with 95% confidence interval (CI) was calculated. Changes in intestinal bacterial profile were analyzed by BOX-PCR-based DNA fingerprinting and sequencing. The adverse effects were assessed based on symptoms., Results: At the end of the follow-up period, 22 patients (40.0%) in the FMT with RCE group and 10 patients (18.2%) in the placebo with RCE group had ≥ 3 spontaneous bowel movements per week (net difference = 21.8%, 95% CI: 13.2%-30.4%; risk ratio: 1.364, 95% CI: 1.063-1.749; P < 0.05). Both RCE and FMT enriched the intestinal bacterial diversity of patients with constipation. The adverse events were all mild self-limiting gastrointestinal symptoms., Discussion: FMT enhances the efficacy of RCE, and the use of RCE-based FMT is a safe and effective method in the treatment of intractable constipation in children., (Copyright © 2024 by The American College of Gastroenterology.)

Competing Interests: No conflicts of interest.

Ethylene thiourea (ETU), a metabolite of the fungicide ethylene bisdithiocarbamate (EBDC), has received great concern because of its harmful effects. ETU-induced anorectal malformations (ARMs) in rat models have been reported and widely used in the study of ARMs embryogenesis. Dysplasia of the lumbosacral spinal cord (LSSC), pelvic floor muscles (PFMs), and hindgut (HG) during intrauterine life affects postoperative defecation in patients with ARMs. However, the underlying toxic effects of ETU and pathological mechanisms in the three defecation-related tissues of fetuses with ARMs have not been reported. Thus, this study aimed to elucidate the molecular mechanisms involved in ARMs, with a focus on the dysregulation of miR-200b-3p and its downstream target tropomodulin 3 (TMOD3). The mRNA and protein levels of miR-200b-3p and TMOD3 in LSSC, PFMs, and HG of fetal rats with ARMs were evaluated by reverse transcription quantitative polymerase chain reaction and Western blotting (WB) on embryonic day 17 (E17). Further, a dual-luciferase reporter assay confirmed their targeting relationship. Gene silencing and overexpression of miR-200b-3p and TMOD3 were performed to verify their functions in HEK-293 T cells. Fetal rats with ARMs also received intra-amniotic microinjection of Ad-TMOD3 on E15, and key molecules in nuclear factor kappa (NF-κB) signaling and apoptosis were evaluated by WB on E21. Abnormally high levels of miR-200b-3p inhibited TMOD3 expression by binding with its 3'-untranslated region, leading to the activation of the non-canonical NF-κB signaling pathway, which is critical in the maldevelopment of LSSC, PFMs, and HG in ARMs rats. Furthermore, miR-200b-3p triggered apoptosis by directly targeting TMOD3. Notably, intra-amniotic Ad-TMOD3 microinjection revealed that the upregulation of TMOD3 expression mitigates the effects of miR-200b-3p on the activation of non-canonical NF-κB signaling and apoptosis in fetal rat model of ARMs. A novel miR-200b-3p/TMOD3/non-canonical NF-κB signaling axis triggered the massive apoptosis in LSSC, PFMs, and HG of ARMs, which was restored by the intra-amniotic injection of Ad-TMOD3 during embryogenesis. Our results indicate the potential of TMOD3 as a treatment target to restore defecation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

N1-methyladenosine (m 1 A) is a reversible epigenetic modification of RNAs. Aberrant m 1 A modification levels due to dysregulation of m 1 A regulators have been observed in multiple cancers. tRNA methyltransferase 10C (TRMT10C) can install m 1 A in RNAs; however, its role in hepatoblastoma remains unknown. We conducted this study to identify causal polymorphisms in the TRMT10C gene for hepatoblastoma susceptibility in a cohort of Chinese children (313 cases vs. 1446 controls). The genotypes of four potential functional polymorphisms (rs7641261 C>T, rs2303476 T>C, rs4257518 A>G, and rs3762735 C>G) were determined in participants using TaqMan real-time PCR. The associations of these polymorphisms with hepatoblastoma susceptibility were estimated by logistic regression analysis adjusted for age and sex. All four polymorphisms were significantly associated with hepatoblastoma risk. In particular, under the recessive genetic model, these polymorphisms conferred an increased risk of hepatoblastoma: rs7641261 C>T [adjusted odds ratio (OR)=1.64, 95% confidence interval (CI)=1.04-2.58, P =0.033], rs2303476 T>C (adjusted OR=1.87, 95% CI=1.16-3.02, P =0.010), rs4257518 A>G (adjusted OR=1.45, 95% CI=1.09-1.94, P =0.012), and rs3762735 C>G (adjusted OR=3.83, 95% CI=2.15-6.82, P <0.0001). Combined analysis revealed that kids had an increased risk of developing hepatoblastoma if they harbored at least one risk genotype (adjusted OR=1.94, 95% CI=1.48-2.54, P <0.0001). In addition, the combined risk effects of the four SNPs persisted across all the subgroups. We identified four hepatoblastoma susceptibility loci in the TRMT10C gene. Identifying more disease-causing loci may facilitate the development of genetic marker panels to predict individuals' hepatoblastoma predisposition., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The most prevalent hip disease in neonates is developmental dysplasia of the hip (DDH). A timely and accurate diagnosis is required to provide the most effective treatment for pediatric patients with DDH. Heredity and gene variation have been the subject of increased attention and research worldwide as one of the factors contributing to the pathogenesis of DDH. Genome-wide association studies (GWAS), genome-wide linkage analyses (GWLA), and exome sequencing (ES) have identified variants in numerous genes and single-nucleotide polymorphisms (SNPs) as being associated with susceptibility to DDH in sporadic and DDH family patients. Furthermore, the DDH phenotype can be observed in animal models that exhibit susceptibility genes or loci, including variants in CX3CR1 , KANSL1 , and GDF5 . The dentification of noncoding RNAs and de novo gene variants in patients with DDH-related syndrome has enhanced our understanding of the genes implicated in DDH. This article reviews the most recent molecular mechanisms and genetic factors that contribute to DDH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Liu, Yang and Li.)

The thermal anisotropy of materials holds significant theoretical and practical implications in the domains of thermal transport and thermoelectricity. Black phosphorene, a novel two-dimensional (2D) semiconductor, is notable for its exceptional chemical and physical properties, attracting substantial attention for its thermal transport characteristics. Similar to other 2D materials, black phosphorene exhibits pronounced in-plane thermal anisotropy. Given its expanding applications in nanoelectronics, optoelectronics, and thermoelectrics, there is a growing need to manipulate its anisotropic thermal transport. Current methods for adjusting anisotropy or isotropy typically involve structural engineering or materials processing, which are often costly, time-consuming, and irreversible. In contrast, little progress has been made with methods that are intact, robust, and reversible. Driven by the intrinsic relationship between interatomic interaction-mediated phonon transport and electronic charges, we conduct a comprehensive investigation into the impact of an external electric field on the thermal transport properties of 2D black phosphorene using first-principles calculations and the phonon Boltzmann transport equation. Our findings reveal that applying an electric field in the Zigzag direction reduces the lattice thermal conductivity of black phosphorene, with the Zigzag direction being more responsive to the electric field than the Armchair direction. By adjusting the electric field to a maximum of E (f&#95; xx ) = 0.2 V Å -1 , the anisotropic thermal conductivity of black phosphorene decreases by more than 28%, demonstrating effective manipulation of anisotropy. This significant transition in anisotropic thermal transport arises from the substantial reduction in thermal conductivity along the Zigzag direction at moderate electric field strengths. The underlying cause of this variation in anisotropy can be attributed to changes in group velocity, with the phonon lifetime serving as a scaling factor for reducing anisotropy. Analysis of the electronic structures shows that stronger electric fields induce more charges, enhancing the screening effect. The electric field significantly alters thermal conductivity by affecting bond ionicity and anharmonicity. Our study introduces a robust approach for tuning the anisotropy of phonon transport in materials using an external electric field, without altering the atomic structure, thus offering considerable advantages for applications in nanoelectronics and thermoelectric energy conversion.

Bladder cancer(BC) is one of the most prevalent cancers in the urinary tract, with high recurrence and fatality rates. Research indicates that go-ichi-ni-san complex subunit 1 (GINS1) crucially influences cancer progression by regulating DNA replication through cell cycle modulation. Thus, suppressing the active proliferation of cells in tumor tissues may require silencing GINS1. However, the consequences of GINS1 in bladder cancer aren't to be determined. In this paper, we examine the role and mechanism of GINS1 in the development of bladder cancer. GINS1 expression levels and prognostic relevance in bladder cancer were validated using Western blotting, immunohistochemistry, and Kaplan-Meier survival analysis. The influence of GINS1 on bladder cancer was investigated using a variety of approaches, including cell transfection, cell counts, transwell migrations, colony formation, and flow cytometry. Immunohistochemistry studies demonstrate that GINS1 expression is increased in bladder cancer tissues. GINS1 silencing resulted in an arrest of the cell cycle at the phase of G0/G1, which inhibited BC cell growth both in vitro and in vivo. GINS1 knockdown also hindered the AKT/mTOR pathway. Furthermore, increased GINS1 expression affects the cell cycle and stimulates the AKT/mTOR pathway, allowing BC to develop more quickly. Consequently, GINS1 occurs as a latent therapeutic target, particularly for individuals with BC., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neuroblastoma (NB) is a common extracranial solid malignancy in children. The N7-methylguanosine (m 7 G) modification gene METTL1/WDR4 polymorphisms may serve as promising molecular markers for identifying populations susceptible to NB., Methods: TaqMan probes was usded to genotype METTL1/WDR4 single nucleotide polymorphisms (SNPs) in 898 NB patients and 1734 healthy controls. A logistic regression model was utilized to calculate the odds ratio (OR) and 95% confidence interval (CI), evaluating the association between genotype polymorphisms and NB susceptibility. The analysis was also stratified by age, sex, tumor origin site, and clinical stage., Results: Individual polymorphism of the METTL1/WDR4 gene investigated in this study did not show significant associations with NB susceptibility. However, combined genotype analysis revealed that carrying all 5 WDR4 protective genotypes was associated with a significantly lower NB risk compared to having 0-4 protective genotypes (AOR = 0.82, 95% CI = 0.69-0.96, P = 0.014). Further stratified analyses revealed that carrying 1-3 METTL1 risk genotypes, the WDR4 rs2156316 CG/GG genotype, the WDR4 rs2248490 CG/GG genotype, and having all five WDR4 protective genotypes were all significantly correlated with NB susceptibility in distinct subpopulations., Conclusions: In conclusion, our findings suggest significant associations between m 7 G modification gene METTL1/WDR4 SNPs and NB susceptibility in specific populations., Impact: Genetic variation in m 7 G modification gene is associated with susceptibility to NB. Single nucleotide polymorphisms in METTL1/WDR4 are associated with susceptibility to NB. Single nucleotide polymorphisms of METTL1/WDR4 can be used as a biomarker for screening NB susceptible populations., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: The relationship between post-endovascular thrombectomy (EVT) blood pressure (BP) and outcomes in patients with acute ischemic stroke (AIS) remains contentious. We aimed to explore whether this association differs with different cerebral perfusion statuses post-EVT., Methods: In a multicenter observational study of patients with AIS with large vessel occlusion who underwent EVT, we enrolled those who accepted CT perfusion (CTP) imaging within 24 hours post-EVT. We recorded post-EVT systolic (SBP) and diastolic BP. Patients were stratified into favorable perfusion and unfavorable perfusion groups based on the hypoperfusion intensity ratio (HIR) on CTP. The primary outcome was good functional outcome (90-day modified Rankin Scale score of ≤3). Secondary outcomes included early neurological deterioration, infarct size growth, and symptomatic intracranial hemorrhage., Results: Of the 415 patients studied (mean age 62 years, 75% male), 233 (56%) achieved good functional outcomes. Logistic regression showed that post-EVT HIR and 24-hour mean SBP were significantly associated with functional outcomes. Among the 326 (79%) patients with favorable perfusion, SBP <140 mmHg was associated with a higher percentage of good functional outcomes compared with SBP ≥140 mmHg (68% vs 52%; aOR 1.70 (95% CI 1.00 to 2.89), P=0.04). However, no significant difference was observed between SBP and functional outcomes in the unfavorable perfusion group. There was also no discernible difference between SBP and secondary outcomes across the different perfusion groups., Conclusions: In patients with favorable perfusion post-EVT, SBP <140 mmHg was associated with good functional outcomes, which underscores the need for further investigations with larger sample sizes or a more individualized BP management strategy., Clinical Trial Registration: ChiCTR1900022154., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: The effect of X (X = O, Se, N, P, F, Cl) doping on the adsorption of Zn atoms by WS 2 was investigated based on first principles. The electronic structure and optical properties of the adsorbed system after atomic doping were calculated. It is found that the Zn atom adsorbed on the W top (T w ) site has the most stable structure. When an S atom is replaced with an X atom based on the adsorption system, where the adsorption energy decreases after doping of O, P, F, and Cl atoms compared to the undoped system, it means that each system is more stable after doping of these atoms; charge transfer shows that the adsorption system after P-atom doping the system around the Zn atom loses electrons while S-atom gains electrons, which indicates that P-atom doping is favorable for the adsorption of Zn by WS 2 , N, P-atom is introduced as p-type doping and F, Cl-atom is introduced undoped by n-type doping, and the band gap of the doped system is less than that of the undoped one. With the introduction of different dopant atoms, certain impurity energy levels are introduced into the adsorption system. The prohibited bandwidth around the Fermi energy level reduces the density of states, causing the doped system's density of states to shift to lower energies, among which the shifts of N, P, F, and Cl are more pronounced. The P-doped adsorption system shows a new peak near the energy of - 11 eV. In addition, the study of optical properties showed that the peak reflections of both doped and non-doped systems adsorbing Zn atoms appeared in the ultraviolet region; the absorbance coefficient of the doped system is moved in the lower energy direction and red-shifted after atom doping; in addition, the absorption coefficients and reflectance of the P, Se doped systems are enhanced in the wavelength range of 200-300 nm compared with that before doping, the dielectric function and CBM and VBM positions were also calculated further indicating the potential of Se-doped systems in improving photocatalytic efficiency., Methods: In this paper, the structure optimization of X (X = O, Se, N, P, F, Cl) doping on WS 2 adsorbed Zn atom model is performed based on the CASTEP module in Materials-Studio software under the first principles using GGA and PBE generalized function. The corresponding binding energies, bond lengths, bond angles, charge densities, energy band structures, densities of states, and optical properties were also analyzed. The Monkhorst-Pack particular K-point sampling method is used in the calculations; the K-point grid is 6 × 6 × 1, and the cutoff energy for the plane wave expansion is 500 eV. After geometric optimization, the iterative accuracy converges to a value of less than 1 × 10 -5 eV/atom for the total energy of each atom and less than 0.03 eV/Å for all atomic forces. The thickness of the vacuum layer was set to 20 Å to avoid the effect of interlayer interaction forces. In this paper, 27 atoms were used to form a 3 × 3 × 1 supercellular tungsten disulfide system consisting of 18 S atoms and 9 W atoms., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT., Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3-5 or infarct core volume 70-100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664., Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18-2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06-2.54; 0.01); but not in the two clinical-radiological mismatched subgroups., Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT., Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology]., Competing Interests: We declare no competing interests., (© 2024 The Authors.)

The discovery of N6-methyladenosine (m 6 A) methylation and its role in translation has led to the emergence of a new field of research. Despite accumulating evidence suggesting that m 6 A methylation is essential for the pathogenesis of cancers and aging diseases by influencing RNA stability, localization, transformation, and translation efficiency, its role in normal and abnormal embryonic development remains unclear. An increasing number of studies are addressing the development of the nervous and gonadal systems during embryonic development, but only few are assessing that of the immune, hematopoietic, urinary, and respiratory systems. Additionally, these studies are limited by the requirement for reliable embryonic animal models and the difficulty in collecting tissue samples of fetuses during development. Multiple studies on the function of m 6 A methylation have used suitable cell lines to mimic the complex biological processes of fetal development or the early postnatal phase; hence, the research is still in the primary stage. Herein, we discuss current advances in the extensive biological functions of m 6 A methylation in the development and maldevelopment of embryos/fetuses and conclude that m 6 A modification occurs extensively during fetal development. Aberrant expression of m 6 A regulators is probably correlated with single or multiple defects in organogenesis during the intrauterine life. This comprehensive review will enhance our understanding of the pivotal role of m 6 A modifications involved in fetal development and examine future research directions in embryogenesis., Competing Interests: Declaration of Competing Interest Please declare any financial or personal interests that might be potentially viewed to influence the work presented. Interests could include consultancies, honoraria, patent ownership or other. If there are none state 'there are none'., (Copyright © 2024. Published by Elsevier Masson SAS.)

The mechanism underlying anorectal malformations (ARMs)-related VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, and renal and limb abnormalities) remains unclear. Copy number variation (CNV) contributed to VACTERL pathogenicity. Here, we report a novel CNV in 8p23 and 12q23.1 identified in a case of ARMs-related VACTERL association. This 12-year-old girl presented a cloaca (urethra, vagina, and rectum opening together and sharing a single tube length), an isolated kidney, and a perpetuation of the left superior vena cava at birth. Her intelligence, growth, and development were slightly lower than those of normal children of the same age. Array comparative genomic hybridization revealed a 9.6-Mb deletion in 8p23.1-23.3 and a 0.52-Mb duplication in 12q23.1 in her genome. Furthermore, we reviewed the cases involving CNVs in patients with VACTERL, 8p23 deletion, and 12q23.1 duplication, and our case was the first displaying ARMs-related VACTERL association with CNV in 8p23 and 12q23.1. These findings enriched our understanding between VACTERL association and the mutations of 8p23 deletion and 12q23.1 duplication. IMPACT: This is a novel case of a Chinese girl with anorectal malformations (ARMs)-related VACTERL with an 8p23.1-23.3 deletion and 12q23.1 duplication. Cloaca malformation is presented with novel copy number variation in 8p23.1-23.3 deletion and 12q23.1 duplication., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Anorectal malformations (ARMs) are congenital diseases that lead to postoperative fecal incontinence, constipation, and soiling, despite improvements in surgery; however, their pathological mechanisms remain unclear. Here, we report the role of microRNA-141-3p in maintaining homeostasis between apoptosis and autophagy in the lumbosacral defecation center of fetal rats with ARMs. Elevated microRNA-141-3p expression inhibited YIN-YANG-1 expression by binding its 3' UTR, and repressed autophagy and triggered apoptosis simultaneously. Then, adenylate cyclase 3 was screened to be the downstream target gene of YIN-YANG-1 by chromatin immunoprecipitation sequencing experiments, and Yin Yang 1 could positively activate the transcription of adenylate cyclase 3 by directly interacting with the motif GAGATGG and ATGG in its promoter. Intraamniotic microinjection of adeno-rno-microRNA-141-3p-sponge-GFP in fetal rats with ARMs on embryonic day 15 restored apoptosis-autophagy homeostasis. These findings reveal that microRNA-141-3p upregulation impaired homeostasis between apoptosis and autophagy by inhibiting the YIN-YANG-1/adenylate cyclase 3 axis, and that intraamniotic injection of anti-microRNA-141-3p helped maintain homeostasis in the lumbosacral defecation center of ARMs during embryogenesis., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Context: A first-principles approach based on density functional theory was used to explore the effect of bending deformation on the electrical structure of molybdenum ditelluride doped with nonmetallic atoms X (X = B, C, N, and O). The study included alternate doping of nonmetallic atoms, as well as a comparison of the effects of intrinsic bending deformation and nonmetallic doping deformation. The results demonstrate that boron atom doping raises the Fermi energy level. Examining the energy band structure indicates that the intrinsic molybdenum ditelluride is a direct band gap semiconductor, which is transformed from a direct band gap to an indirect band gap after doping. We selected boron-doped systems for bending deformation and compared them with the intrinsic systems. With increasing deformation, all systems start to shift from semiconductor to metal. When the deformation reaches 8°, the energy levels fill and the electron energy increases. The intrinsically bent systems transition from direct band gap to indirect band gap and eventually to metal. The indirect band gap semiconductor-to-metal transition process occurs after the bending deformation of the boron-doped atoms. The analytical results show that the absorption and reflection peaks of the molybdenum ditelluride system are blue-shifted after the bending deformation of the boron-doped atoms., Methods: Under fundamental principles, this research depends on the density functional theory framework (DFT) using the CASTEP module in the Materials-Studio software. The plane-wave pseudopotential approach with modified gradient approximation and the Perdew-Burke-Ernzerhof (PBE) generalized function is used for structure optimization and total energy calculations of the X-doped (X = B, C, N, O) MoTe 2 system at different shape variables. Geometry optimization of the 27-atom superlattice MoTe 2 was carried out, followed by alternative doping of tellurium atoms in the molybdenum ditelluride with B, C, N, and O. In this paper, the intrinsic bending deformation and B-doping of molybdenum ditelluride were selected for deformation analysis. Intrinsic bending deformations and boron-doped molybdenum ditelluride with bending angles ranging from 2° to 8° were employed for deformation investigation. In Fig. 1, pink is used to represent doped B atoms, orange is used to describe Te atoms, and green is used to represent Mo atoms. For the degree of deformation of molybdenum ditelluride, in this paper, it is expressed by the bending angle, i.e., the angle of the plane of molybdenum ditelluride after bending and deformation of a single layer of molybdenum ditelluride concerning the angle of the plane folded for the deformed plane. How to do it: For ease of presentation, the atomic chains are set to different colors. The purple part on both sides of the figure is bent and deformed, 3-5 atoms are fixed appropriately, and the middle part is deformed. On this basis, the bending deformation of intrinsically doped and boron-doped MoTe 2 is comparatively analyzed. The effect of boron-doped atoms on the structure of MoTe 2 is systematically investigated to study its structural stability and electronic structure. Fig. 1 a1 and a2 The main and side views of intrinsic MoTe 2 ; b1 and (b2) the main and side views of MoTe 2 doped with boron atoms bent by 8°., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: To lessen the impact of the dangerous metal Cr, this paper applies the first principles to investigate the adsorption behavior and photoelectric properties of GaS on Cr. The effects of doped GaS on Cr adsorption behavior are investigated with four GaS systems, which are pure, boron (B)-doped, nitrogen (N)-doped, and oxygen (O)-doped, in order to maximize the characteristics of GaS for use in novel sectors, to obtain understanding of the impact of doping on the electronic structure and optical properties of GaS adsorption of Cr, as well as to promote the development of the material. Four GaS adsorbed Cr systems, pure, B-doped, N-doped, and O-doped, are optimized, and the optimized results show that the stable adsorption position of Cr on both pure and doped GaS is the top position of Ga atoms, whereas doped elements B, N, and O can promote the adsorption of Cr on GaS, and the order of the strength of this promotion is B > N > O., Method: In this paper, molecular simulation calculations and analyses using the CASTEP module in the software Materials Studio are performed to simulate the structure optimization of GaS-adsorbed Cr materials doped with B, N, and O atoms by using the generalized gradient approximation (GGA) plane-wave pseudopotential approach [1] and the Perdew-Burke-Ernzerhof (PBE) generalized function [2]. From the convergence test, it is reasonable to set the K-point network to 4 × 4 × 1 and the truncation energy to 500 eV [3]. In this paper, a 3 × 3 × 1 supercell structure with 18 S atoms and 18 Ga atoms is selected. The convergence value of the iterative accuracy is 1.0e - 5 eV/atom, and all the atomic forces are less than 0.02 eV/Å. A vacuum layer of 16 Å is also set in the C direction to avoid interlayer interactions of GaS. First, we optimize the geometry of the model and then analyze the nature of the adsorption energy and electronic structure corresponding to the model., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: This study explores, for the first time, using first principles, the impact of substitutional doping with boron (B), carbon (C), and nitrogen (N) on the adsorption of chromium (Cr) on monolayer MoS 2 . The effects of doping on the Cr adsorption behavior of MoS 2 were investigated using four MoS 2 systems, namely, pure, boron (B)-doped, carbon (C)-doped, and nitrogen (N)-doped, in order to gain an in-depth understanding of the mechanism of the effects of doping on the electronic structure and optical properties of Cr adsorbed by MoS 2 , to optimize the properties of MoS 2 , to explore new areas of application, and to promote the development of materials science. Four MoS 2 adsorption systems of Cr adsorption on pure, B-doped, C-doped, and N-doped MoS 2 were optimized, and the optimized results showed that the stable adsorption location of Cr on both pure and doped MoS 2 was the hollow location at the top of the folded hexagon. The findings reveal that pure MoS 2 has an adsorption effect on Cr, and doped elements B, C, and N can promote the adsorption of Cr on MoS 2 , and the strong and weak order of this promotion is B > C > N., Methods: In this paper, we use the CASTEP module in the simulation software Materials Studio to perform simulation calculations and analyses to optimize the simulation of Cr adsorption by MoS 2 doped with B, C, and N atoms using the generalized gradient approximation (GGA) plane-wave pseudo-potential method (Perdew et al. Phys Rev Lett 77(18):3865-3968, 1996), as well as Perdew-Burke-Ernzerhof (PBE) generalized functionals (Segall et al. J Phys: Condens Matter 14(11):2717-2744, 2022). The convergence test reveals that it is more reasonable to set the K-point network to 3 × 3 × 1 and the truncation energy to 400 eV. In this paper, a 3 × 3 × 1 supercell structure with 18 S atoms and 9 Mo atoms is selected. The convergence value of the iteration accuracy is 1.0e - 5eV/atom, and all the atomic forces are less than 0.02eV/Å. Additionally, to prevent MoS 2 interlayer interaction, a vacuum layer with a thickness of 18 Å is set in the C direction. The geometrical optimization of the model is performed first, and then the corresponding adsorption energies of the model and the nature of the electronic structure are analyzed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Based on the growth-promoting effect of plant growth promoting bacteria on plants and the mobilization of Cd by citric acid, an experiment was designed in which the combined treatment of Bacillus megaterium and citric acid promoted ryegrass to repair Cd-contaminated soil. This study aimed to evaluate the effects of different treatments on the antioxidant enzyme activity, photosynthesis intensity, Cd accumulation, and rhizosphere cadmium migration under cadmium contamination conditions. And the soil morphology and structure changes were studied by infrared spectroscopy FourierTransformInfrared(FT-IR) and scanning electron microscope Energy Dispersive Spectrometer(SEM-EDS) before and after different treatments. The results show that the combined treatment of Bacillus megaterium and citric acid significantly improved the oxidative stress defense and plant photosynthesis and increased of rye biomass. rye biomass 1.28 times higher than CK treatment. Joint treatment significantly increased the amount of shoot accumulation of Cd, 2.31 times higher than CK treatment, increased the migration and accumulation of cadmium. FTIR and SEM-EDS also showed that the organic constituents such as O-H, C-O and C-N in soils as a major mechanism for mobilization of the heavy metal Cd. Thus, the combined treatment of Bacillus megaterium and citric acid can promote plant growth, improve the damage to ryegrass caused by single organic acid addition, and improve the plant extraction efficiency, which is a feasible way to repair Cd-contaminated soil through activated extraction system.

Context: In this study, the electronic structures and optical properties of the pure MoSe 2 and O-doped MoSe 2 systems under different shear deformations are calculated based on the first-principles approach. It is hoped to provide new possibilities for the design of novel controllable optoelectronic devices and to provide guidance for the application of MoSe 2 in the field of optoelectronic devices. The findings indicate that both pure MoSe 2 and O-doped MoSe 2 systems are somewhat impacted by shear deformation. The pure MoSe 2 undergoes a transition from direct to indirect and then to direct bandgap under shear deformation, but still maintains the semiconductor properties. The bandgap of the doped system changes from a direct to an indirect bandgap at 8% shear deformation. According to the examination of the density of states, we find that the density of states of the pure MoSe 2 system is mainly contributed by the Mo-d and Se-p orbitals, and the total density of states of the system after O-atom doping mainly originates from the results of the contributions of the Mo-d, Se-p, and O-p orbitals. Optical property analysis reveals that the conductivity and peak value of the pure MoSe 2 system are gradually red-shifted toward the low-energy region with the increase of shear deformation. The dielectric function of the O-doped MoSe 2 system is red-shifted in the region of 6~10% shear deformation, and the degree of red-shift rises with deformation amount. The findings demonstrate that the electrical structure and optical characteristics of the O-doped MoSe 2 system may be modulated effectively by shear deformation, providing a theoretical foundation for expanding the usage of MoSe 2 materials in the field of optoelectronic devices., Methods: This study is founded on the CASTEP module in the Materials-Studio software within the first-principles of the density-functional theory framework. The photoelectric properties of the intrinsic and doped systems under shear deformation are calculated using the Perdew-Burke-Ernzerh (PBE) of generalized function under the generalized gradient approximation (GGA). The Monkhorst-Pack special K-point sampling method is used in the calculations, and a 5 × 5 × 1 K-point grid is used for the calculations with a plane-wave truncation energy of 400 eV in the optimization of the structure of each model. After geometrical optimization, the energy convergence criterion for each atom is 1 × 10 -5 eV/atom, the force convergence criterion is 0.05 eV/Å, and a vacuum layer of 20 Å in the c-direction is set., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: In this paper, the structural stability, electronic structure, and optical properties of monolayer MoSe 2 doped with C, O, Si, S, and Te atoms, respectively, under defective conditions are investigated based on first principles. It is found that the system is more structurally stable when defecting a single Se atom as compared to defecting a single Mo or two Se atoms. The electronic structure analysis of the system reveals that intrinsic MoSe 2 is a direct bandgap semiconductor. The bandgap value of the system decreases with a single Se atom defect and introduces two new impurity energy levels in the conduction band. The defective systems doped with C and Si atoms all exhibit P-type doping. The total density of states of intrinsic MoSe 2 is mainly contributed by the Mo-d and Se-p orbitals, and new density of state peaks appears near the conduction band after the defects of Se atoms. The total density of states of the defective system doped by each atom is mainly contributed by Mo-d, Se-p, and the result of the p orbital contribution of each dopant atom. By analyzing the dielectric function of each system, it is found that the intrinsic MoSe 2 has the lowest static permittivity and the C-doped defect system has the highest static permittivity, which reaches 21.42. The C- and Si-doped defect systems are the first to start absorbing the light, and the intrinsic MoSe 2 absorbs the light later, with its absorption edge starting at 1.25 eV. In the visible range, the reflection peaks of the systems move toward the high-energy region and the blue-shift phenomenon occurs. It is hoped that applying modification means to modulate the physical properties of the two-dimensional materials will provide some theoretical basis for broadening the application of monolayer MoSe 2 in the field of optoelectronic devices., Methods: This study utilizes the first principle computational software package MS8.0 (Materials studio8.0) under density functional theory (DFT). The exchange-correlation potential (GGA-PBE) is described by the Perdew-Burke-Ernzerhof correlation function in CASTEP, and the potential function adopts the ultrasoft pseudopotential in the inverse space formulation. The plane wave truncation energy E cut is set to 400 eV, the K-point is taken as 5 × 5 × 1, and the force convergence criterion is 0.05 eV/Å. The convergence accuracy of the total energy of the system is less than 1.0 × 10 -5  eV/atom, the tolerance shift is less than 0.002 Å, and the stress deviation is less than 0.1 GPa. The vacuum layer is taken as 15 Å, which is intended to minimize the interlayer force. The vacuum layer was set to 15 Å to avoid the effect of layer-to-layer interaction forces in the crystal cell., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Reprogramming of energy metabolism is one of the most important characteristics of tumors. Bladder cancer (BLCA) cells contain higher levels of cholesterol content compared to normal cells, and acyl-coenzyme A (CoA): cholesterol acyltransferase-1 (ACAT1) plays a crucial role in the esterification of cholesterol. Avasimibe is a drug that has been used in the treatment of atherosclerosis, and it can effectively inhibit ACAT1. We observed that ACAT1 was significantly up-regulated in BLCA and positively correlated with tumor grade. By avasimibe administration, the proliferation and migration ability of BLCA cells were reduced, while the production of ROS was strongly increased, accompanied by the up-regulated expression of ROS metabolism-related proteins SOD2 and catalase. Furthermore, BLCA cell cycle was arrested at the G1 phase, accompanied by the downregulation of cell cycle-related proteins (CCNA1/2, CCND1, CDK2 and CDK4), while the PPARγ was found to be up-regulated at both transcriptional and protein levels after avasimibe treatment. Then we found that the PPARγ antagonist GW9662 could reverse the effect of avasimibe on the cell cycle. Moreover, xenograft and pulmonary metastasis models further demonstrated that avasimibe could inhibit tumor cell growth and metastasis in vivo . Taken together, our results for the first time revealed that avasimibe can inhibit BLCA progression and metastasis, and PPARγ signaling pathway may play a key role in regulation of cell cycle distribution induced by avasimibe., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Hepatoblastoma, the most frequently diagnosed primary paediatric liver tumour, bears the lowest somatic mutation burden among paediatric neoplasms. Therefore, it is essential to identify pathogenic germline genetic variants, especially those in oncogenic genes, for this disease. The tRNA methyltransferase 6 noncatalytic subunit (TRMT6) forms a tRNA methyltransferase complex with TRMT61A to catalyse adenosine methylation at position N1 of RNAs. TRMT6 has displayed tumour-promoting functions in several cancer types. However, the contribution of its genetic variants to hepatoblastoma remains unclear. In this study, we investigated the association between four TRMT6 polymorphisms (rs236170 A > G, rs451571 T > C, rs236188 G > A and rs236110 C > A) and the risk of hepatoblastoma in a cohort of 313 cases and 1446 healthy controls. Germline DNA was subjected to polymorphism genotyping via the TaqMan qPCR method. Odds ratio (OR) and 95% confidence interval (CI) were used to determine hepatoblastoma susceptibility variants. The rs236170 A > G, rs236188 G > A and rs236110 C > A polymorphisms were significantly associated with hepatoblastoma risk. Combination analysis of the four polymorphisms revealed that children bearing 1-4 risk genotypes were at significantly enhanced hepatoblastoma risk compared to those without risk genotype (adjusted OR = 1.52, 95% CI = 1.19-1.95, p = 0.0008). We also conducted stratification analyses by age, sex and clinical stage. Ultimately, we found that the rs236110 C > A was significantly associated with the downregulation of MCM8, a neighbouring gene of TRMT6. In conclusion, we identified three susceptibility loci in the TRMT6 gene for hepatoblastoma. Our findings warrant further validation by extensive case-control studies across different ethnicities., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Vaccination remains the cornerstone of defense against COVID-19 globally. This study aims to assess the safety and immunogenicity profile of innovative vaccines LYB001., Research Design and Methods: This was a randomized, double-blind, parallel-controlled trial, in 100 healthy Chinese adults (21 to 72 years old). Three doses of 30 or 60 µg of SARS-CoV-2 RBD-based VLP vaccine (LYB001), or the SARS-CoV-2 RBD-based protein subunit vaccine (ZF2001, control group) were administered with a 28-day interval. Differences in the incidence of adverse events (AEs) and indicators of humoral and cellular immunity among the different groups were measured., Results: No severe adverse events were confirmed to be vaccine-related, and there was no significant difference in the rate of adverse events between the LYB001 and control group or the age subgroups ( p  > 0.05). The LYB001 groups had significantly higher or comparable levels of seroconversion rates, neutralization antibody, S protein-binding antibody, and cellular immunity after whole vaccination than the control group., Conclusions: Our findings support that LYB001 developed on the VLP platform is safe and well tolerated with favorable immunogenicity for fundamental vaccination in healthy adults. Therefore, further larger-scale clinical studies are warranted., Trial Registration: This trial was registered with ClinicalTrials.gov (NCT05552573).

The aspiration of chemists has always been to design and achieve control over nanoparticle morphology at the atomic level. Here, we report a synthesis strategy and crystal structure of a perfect cubic Ag-Cu alloyed nanocluster, [Ag 55 Cu 8 I 12 (S-C 6 H 3 2,4 (CH 3 ) 2 ) 24 ][(PPh 4 )] (Ag 55 Cu 8 I 12 for short). The structure of this cluster was determined by single-crystal X-ray diffraction (SCXRD) and further validated by X-ray photoelectron spectroscopy (XPS), inductively coupled plasma (ICP), Energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), and 1 H and 31 P nuclear magnetic resonance (NMR). The surface deviation of the cube was measured to be 0.291 Å, making it the flattest known cube to date.

LYB001 is an innovative recombinant SARS-CoV-2 vaccine that displays a repetitive array of the spike glycoprotein's receptor-binding domain (RBD) on a virus-like particle (VLP) vector to boost the immune system, produced using Covalink plug-and-display protein binding technology. LYB001's safety and immunogenicity were assessed in 119 participants receiving a booster with (1) 30 μg LYB001 (I-I-30 L) or CoronaVac (I-I-C), (2) 60 μg LYB001 (I-I-60 L) or CoronaVac in a ratio of 2:1 after two-dose primary series of inactivated COVID-19 vaccine, and (3) 30 μg LYB001 (I-I-I-30 L) after three-dose inactivated COVID-19 vaccine. A well-tolerated reactogenicity profile was observed for LYB001 as a heterologous booster, with adverse reactions being predominantly mild in severity and transient. LYB001 elicited a substantial increase in terms of the neutralizing antibody response against prototype SARS-CoV-2 28 days after booster, with GMT (95%CI) of 1237.8 (747.2, 2050.6), 554.3 (374.6, 820.2), 181.9 (107.6, 307.6), and 1200.2 (831.5, 1732.3) in the I-I-30 L, I-I-60 L, I-I-C, and I-I-I-30 L groups, respectively. LYB001 also elicited a cross-neutralizing antibody response against the BA.4/5 strain, dominant during the study period, with GMT of 201.1 (102.7, 393.7), 63.0 (35.1, 113.1), 29.2 (16.9, 50.3), and 115.3 (63.9, 208.1) in the I-I-30 L, I-I-60 L, I-I-C, and I-I-I-30 L groups, respectively, at 28 days after booster. Additionally, RBD-specific IFN-γ, IL-2, IL-4 secreting T cells dramatically increased at 14 days after a single LYB001 booster. Our data confirmed the favorable safety and immunogenicity profile of LYB001 and supported the continued clinical development of this promising candidate that utilizes the VLP platform to provide protection against COVID-19.

Substrates like sand or gravels and aquatic nutrient concentrations of rivers are highly heterogeneous, influencing the abundance of functional genes in epilithic biofilms where nitrification-denitrification processes take place. To analyze how the relative abundance of nitrifying/denitrifying genes and the associated microbes changes with the physical properties of substrates and aquatic concentrations of nutrients, this paper utilized metagenomics to comprehensively characterize these functional genes (i.e., amoA, hao, and nxrB involved in nitrification, and napA, narG, nirS, norB, and nosZ associated with denitrification) from epilithic biofilms collected along the Shitingjiang River in Southwest China and further obtained the relative abundance of major nitrifiers and denitrifiers. The results show that substrate size most significantly affects the relative abundance of hao and norB by altering the hydrodynamic conditions. In sampling sites with high heterogeneity in substrate size distribution, the relative abundance of most denitrifying genes is also higher. The carbon-nitrogen ratio negatively correlates with the relative abundance of all the nitrifying genes, while ammonium, total inorganic carbon, and total organic carbon concentrations positively affect the relative abundance of amoA and nxrB. As to the relative abundance of nitrifiers and denitrifiers, mainly belonging to phyla Proteobacteria and Actinobacteria, substrate heterogeneity and the aquatic concentrations of nutrients have greater influences than substrate size. Also, the substrate heterogeneity exerted positive influence on functional species of Pseudogemmobacter bohemicus and Paracoccus zhejiangensis. Considering the genes' functions and the dominant species linked to denitrification, nitrous oxide is more likely to occur in rivers with higher heterogeneity and larger substrates., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: In this study, the effects of different shear deformations on the structural stability, electronic structure, and optical properties of a Mg atom adsorption system of S vacancy defect SnS 2 are systematically investigated based on density functional theory. It is shown that the presence of an S-vacancy defect makes the band gap of the SnS 2 system significantly smaller than that of the perfect SnS 2 system, and the SnS 2 system is changed from a direct band gap semiconductor to an indirect band gap semiconductor. The optimal adsorption position of a Mg atom on the S-vacancy SnS 2 system is above the S atom where the adsorption energy is the largest and the system is the most stable. The density of states of the adsorption system is predominantly contributed by the S-3p and Sn-5 s orbital electrons. The imposition of shear deformation leads to the introduction of certain impurity energy levels in the adsorption system, and the forbidden bandwidth near the Fermi energy level decreases. As compared to the intrinsic SnS 2 , the absorption and reflection peaks of adsorption systems under different shear deformation are red-shifted and appear in the ultraviolet region. This improves the utilization of the adsorption system for ultraviolet light to a great extent., Methods: The model calculations in this paper are performed using the CASTEP module of the Material Studio (MS) software based on the first principles of Density Functional Theory (DFT) (Wei et al. in Physica B 545:99-106, 2018) for plane wave artifacts. Geometrical optimization and computational procedures are used to calculate the exchange-correlation energy using the Perdew-Burke-Ernzerhof (PBE) generalized function (Perdew et al. in Phys Rev B Condens Matter 48:4978, 1993) of the generalized gradient approximation (GGA). The Monkhorst-Pack method (Monkhorst and Pack in Phys Rev B 13:5188-5192, 1976) was used to rationalize the sampling of the highly symmetric k-points in the Brillouin zone. The grid of k-points is set to be 6 × 6 × 1. The plane-wave truncation energy is set to be 400 eV. The energy convergence criterion is 1.0 × 10 -5  eV. The residual stress of all atoms is 0.01 eV/Å. A vacuum layer with a thickness of 15 Å is set up in the z-direction, which ensures that the interactions of the system along the z-axis between the top and the bottom layers can be ignored during the whole simulation process. We construct a 3 × 3 × 1 SnS 2 system containing 27 atoms as the computational model. The intrinsic SnS 2 contains 9 Sn atoms and 18 S atoms., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In response to the market demand for therapeutic antibodies, the upstream cell culture scale and expression titer of antibodies have been significantly improved, while the production efficiency of downstream purification process is relatively fall behind, and the downstream processing capacity has become a bottleneck limiting antibody production throughput. Using monoclonal antibody mab-X as experimental material, we optimized the caprylic acid (CA) precipitation process conditions of cell culture fluid and low pH virus inactivation pool, and studied two applications of using CA treatment to remove aggregates and to inactivate virus. Based on the lab scale study, we carried out a 500 L scale-up study, where CA was added to the low pH virus inactivation pool for precipitation, and the product quality and yield before and after precipitation were detected and compared. We found that CA precipitation significantly reduced HCP residuals and aggregates both before and after protein A affinity chromatography. In the aggregate spike study, CA precipitation removed about 15% of the aggregates. A virus reduction study showed complete clearance of a model retrovirus during CA precipitation of protein A purified antibody. In the scale-up study, the depth filtration harvesting, affinity chromatography, low pH virus inactivation, CA precipitation and depth filtration, and cation exchange chromatography successively carried out. The mixing time and stirring speed in the CA precipitation process significantly affected the CA precipitation effect. After CA precipitation, the HCP residue in the low pH virus inactivation solution decreased 895 times. After precipitation, the product purity and HCP residual meet the quality criteria of monoclonal antibodies. CA precipitation can reduce the chromatography step in the conventional purification process. In conclusion, CA precipitation in the downstream process can simplify the conventional purification process, fully meet the purification quality criterion of mab-X, and improve production efficiency and reduce production costs. The results of this study may promote the application of CA precipitation in the purification of monoclonal antibodies, and provide a reference for solving the bottleneck of the current purification process.

N 1 -methyladenosine (m 1 A) is an essential chemical modification of RNA. Dysregulation of RNA m 1 A modification and m 1 A-related regulators is detected in several adult tumors. Whether aberrant RNA m 1 A modification is involved in hepatoblast carcinogenesis has not been reported. tRNA methyltransferase 61B (TRMT61B) is responsible for mitochondrial RNA m 1 A modification. Some evidence has shown that genetic variants of TRMT61B might contribute to cancer susceptibility; however, its roles in hepatoblastoma are unknown. This study attempted to discover novel hepatoblastoma susceptibility loci. With the TaqMan method, we examined genotypes of the TRMT61B rs4563180 G>C polymorphism among germline DNA samples from 313 cases and 1446 controls. The association of the rs4563180 G>C polymorphism with hepatoblastoma risk was estimated based on odds ratios (ORs) and 95% confidence intervals (CIs). We found that the TRMT61B rs4563180 G>C polymorphism correlated significantly with a reduction in hepatoblastoma risk (GC vs. GG: adjusted OR=0.65, 95% CI=0.49-0.85, P =0.002; GC/CC vs. GG: adjusted OR=0.66, 95% CI=0.51-0.85, P =0.002). In stratified analysis, significant associations were detected in children younger than 17 months old, girls, and subgroups with stage I+II or III+IV tumors. False-positive report probability analysis validated that children with the GC or CC genotype, particularly in those <17 months of age, had a decreased risk of hepatoblastoma. The rs4563180 G>C polymorphism also correlated with expression of TRMT61B and the nearby gene PPP1CB . We identified a high-quality biomarker measuring hepatoblastoma susceptibility, which may contribute to future screening programs.

Objective: AlkB homolog 5 (ALKBH5) has been proven to be closely related to tumors. However, the role and molecular mechanism of ALKBH5 in neuroblastomas have rarely been reported., Methods: The potential functional single-nucleotide polymorphisms (SNPs) in ALKBH5 were identified by National Center for Biotechnology Information (NCBI) dbSNP screening and SNPinfo software. TaqMan probes were used for genotyping. A multiple logistic regression model was used to evaluate the effects of different SNP loci on the risk of neuroblastoma. The expression of ALKBH5 in neuroblastoma was evaluated by Western blotting and immunohistochemistry (IHC). Cell counting kit-8 (CCK-8), plate colony formation and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays were used to evaluate cell proliferation. Wound healing and Transwell assays were used to compare cell migration and invasion. Thermodynamic modelling was performed to predict the ability of miRNAs to bind to ALKBH5 with the rs8400 G/A polymorphism. RNA sequencing, N6-methyladenosine (m 6 A) sequencing, m 6 A methylated RNA immunoprecipitation (MeRIP) and a luciferase assay were used to identify the targeting effect of ALKBH5 on SPP1., Results: ALKBH5 was highly expressed in neuroblastoma. Knocking down ALKBH5 inhibited the proliferation, migration and invasion of cancer cells. miR-186-3p negatively regulates the expression of ALKBH5, and this ability is affected by the rs8400 polymorphism. When the G nucleotide was mutated to A, the ability of miR-186-3p to bind to the 3'-UTR of ALKBH5 decreased, resulting in upregulation of ALKBH5 . SPP1 is the downstream target gene of the ALKBH5 oncogene. Knocking down SPP1 partially restored the inhibitory effect of ALKBH5 downregulation on neuroblastoma. Downregulation of ALKBH5 can improve the therapeutic efficacy of carboplatin and etoposide in neuroblastoma., Conclusions: We first found that the rs8400 G>A polymorphism in the m 6 A demethylase-encoding gene ALKBH5 increases neuroblastoma susceptibility and determines the related mechanisms. The aberrant regulation of ALKBH5 by miR-186-3p caused by this genetic variation in ALKBH5 promotes the occurrence and development of neuroblastoma through the ALKBH5-SPP1 axis., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Changes in land-use patterns may increase the ecological risks faced by Eco-Fragile regions. It is vital for regional ecological restoration and management of Eco-Fragile regions to reasonably assess ecological risk and study its response to typical land-use patterns. Existing study on regional ecological risk largely ignored the internal representation of ecosystem health and ecosystem services to ecological risk, and also ignored the internal relationship between ecological risk and land use patterns. This study developed a regional ecological assessment model by describing the relationship between ecosystem health, ecosystem services and ecological risks. Among them, the ecosystem health assessment used the Net Primary Productivity, landscape index and ecosystem elasticity coefficient based on different land use patterns to build Vigor-Organization-Resilience (VOR) model, and the improved equivalent factor method was used to calculate the ecosystem service value. Taking the Fen River Basin (FRB), a typical Eco-Fragile region of the Loess Plateau, as a study region, spatial auto-correlation analysis was used to reveal the temporal and spatial changes and spatial clustering characteristics of regional ecological risk, and regression analysis was used to study the relationship between typical land use patterns and ecological risks, which was included in the consideration of ecological and environmental risk management strategies. The results show that the regions with high ecological risk are mainly distributed in the middle and southwest of the FRB; the regions with low ecological risk are mainly distributed in the north, east and west of the FRB. Both high-risk and low-risk areas show significant spatial clustering effects. The change of ecological risk in FRB is related to the land use patterns. The ecological risk is negatively related to the expansion of construction land and cultivated land at the county and patch scales. On this basis, the environmental management strategies at different scales are discussed. This study can helpful deepen the understanding of the impact of land use patterns on ecological risk, and can also provide important reference for regional ecological risk management and land use policies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Transrectal (TR) ultrasound guided prostate biopsy and transperineal (TP) ultrasound guided prostate biopsy are the two most commonly used methods to detect prostate cancer, the detection rate of the two biopsy approaches may differ in patients with different clinical characteristics. Here we aimed to compare the prostate cancer detection rate and positive rate of biopsy cores between TR and TP prostate biopsy in patients with different clinical characteristics., Methods: We retrospectively analyzed and compared the clinical data of 452 patients underwent TR or TP prostate biopsy in our hospital from June 2017 to September 2021. And patients were stratified according to several clinical characteristic (serum PSA level, prostate volume, PSA density, T stage and ISUP grade), cancer detection rate and positive rate of biopsy cores were compared in different stratified groups., Results: There was no significant difference in age, PSA level, prostate volume, and PSA density between the TR and TP groups. TR group had a higher overall cancer detection rate and positive rate of biopsy cores than TP group. Further subgroup analysis showed that TR group had a higher cancer detection rate in patients with prostate volumes 30-80 mL, and that the TR group had a higher positive rate of biopsy cores among the patients with T3-T4 stages, while TP group had a higher positive rates of biopsy cores among the patients with T1-T2 stages. There were no significant differences between the TR and TP groups for each subgroup when stratified by PSA level, PSA density and ISUP grade., Conclusions: TR approach may have advantage in patients with prostate volumes 30-80 mL and T3-T4 stages, while TP approach may have advantage in patients with T1-T2 stages., (© 2023. The Author(s).)

The accurate calibration of large-scale switch networks is critical for integrated photonics, in which the integrated optical true time delay chip is typical. In this work, a novel self-calibration method without extra testing ports is proposed by introducing lossless thermo-optic phase shifters instead to calibrate the network. As a demonstration, a 5-bit delay line based on silicon nitride is fabricated and calibrated. The extinction ratio of all the switches is greater than 30.9 dB at the cross and bar states. Using this method, the 5-bit optical delay line which can be tuned in a range of 118.53 ps and reach a low delay time deviation less than ±0.4 ps.

The gravitational search algorithm is a global optimization algorithm that has the advantages of a swarm intelligence algorithm. Compared with traditional algorithms, the performance in terms of global search and convergence is relatively good, but the solution is not always accurate, and the algorithm has difficulty jumping out of locally optimal solutions. In view of these shortcomings, an improved gravitational search algorithm based on an adaptive strategy is proposed. The algorithm uses the adaptive strategy to improve the updating methods for the distance between particles, gravitational constant, and position in the gravitational search model. This strengthens the information interaction between particles in the group and improves the exploration and exploitation capacity of the algorithm. In this paper, 13 classical single-peak and multi-peak test functions were selected for simulation performance tests, and the CEC2017 benchmark function was used for a comparison test. The test results show that the improved gravitational search algorithm can address the tendency of the original algorithm to fall into local extrema and significantly improve both the solution accuracy and the ability to find the globally optimal solution.

Prostate cancer (PCa) is one of the most prevalent malignancies in adult males. However, PCa is resistant to multi-kinase inhibitors-based anti-angiogenic therapies, and the mechanism and effective targeting thereof remains unclear. In this study, single-cell and bulk-transcriptomic datasets analysis revealed that KIAA1199, a hyaluronic acid (HA) binding protein, was involved in glycolysis, hypoxia and angiogenesis pathways. Moreover, boosted KIAA1199 expression in PCa tissues was positively correlated with tumor stage, hypoxia-inducible factor (HIF)-1α overexpression, as well as angiogenesis markers. Tube formation, Western blot, enzyme-linked immunosorbent assay, and in vivo tumorigenesis results demonstrated that KIAA1199 silencing significantly inhibited angiogenesis and vasculogenic mimicry (VM), both in vitro and in vivo, by increasing semaphoring 3A (sema3A) expression while decreasing expressions of VEGFA, VE-cadherin, phosphorylated EphA2, and depolymerized HA levels. KIAA1199 overexpression was also found to promote angiogenesis and VM via increasing secretory VEGFA, however, this activity could be reversed by the HA biosynthesis inhibitor 4-methylumbelliferone (4MU). Furthermore, dual-luciferase and ChIP-PCR revealed that HIF1α is the transcriptional enhancer of KIAA1199, while lactate imported to PCa cells by monocarboxylate transporter 1 (MCT1) stabilizes HIF1α under normoxia via HIF1α lactylation. Our findings may provide a better understanding of angiogenesis and a promising therapeutic target of PCa., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Despite improvements in anorectal malformation (ARM) therapy, patients might still experience post-operative problems such as fecal incontinence, constipation, and soiling. In particular, the dysplasia of the lumbosacral spinal cord in ARM patients is a major disorder that affects fecal function post-operation. However, the pathological mechanisms involved are still unclear., Methods: The non-coding RNAs (ncRNAs) in the lumbosacral spinal cord of fetal rats with ethylenethiourea-induced ARM were identified using RNA sequencing (RNA-seq) and examined to determine their potential function. The lumbosacral spinal cord was isolated on embryonic day 17 for subsequent RNA extraction and RNA-seq. The transcriptome data was analyzed using bioinformatics analysis, followed by validation using quantitative reverse transcription PCR., Results: Compared to the control group, 26 differentially expressed microRNAs (DEMs; 22 upregulated, 4 downregulated) and 112 differentially expressed long non-coding RNAs (63 upregulated, 49 downregulated) were identified in the ARM group. Several DEMs related to development, namely miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-200a-5p, and miR-429, were selected for further analysis. Notably, compared to the control, the relative expression of miR-200 family members was highly upregulated in ARM fetal rats. Furthermore, GO and KEGG enrichment and miRNA-transcription factor-lncRNA/mRNA network analysis was explored to show molecular mechanism underlying DEMs., Conclusions: Our findings suggest the involvement of ncRNAs, especially the miR-200 family members, in the pathogenesis of lumbosacral spinal cord dysplasia in ARM fetal rats., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: We aimed to investigate the correlation between an overall cerebral small vessel disease (CSVD) burden and outcomes after endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO)., Methods: In a multicenter registry study, we enrolled patients with EVT for anterior-circulation LVO-stroke. In 3.0-T MR imaging, we assessed 4 CSVD imaging markers, lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces, each assigned a score of 0 or 1 and summed up to an overall CSVD burden score of 0-4. We dichotomized the overall CSVD severity as none to mild (score 0-2) and moderate to severe (3-4). Primary outcome was 90-day functional dependence or death (modified Rankin Scale (mRS) 3-6). Secondary outcomes included increase in NIH Stroke Scale ≥ 4 within 24 h (early neurological deterioration (END)) and within 7 days, symptomatic intracranial hemorrhage, 90-day mRS 2-6, and 90-day mortality., Results: Among 311 patients (63.0% male; mean age 65.1 ± 12.7 years), 260 (83.6%) had none-to-mild and 51 (16.4%) had moderate-to-severe overall CSVD burden. Moderate-to-severe CSVD burden was not significantly associated with the primary outcome (47.1% versus 45.4%; p > 0.05 in univariate and multivariate logistic regression), or the secondary outcomes except for a higher risk of END (11.8% versus 3.1%; p < 0.05 in multivariate analyses). Sensitivity analyses with 0-1 versus 2-4 of the CSVD burden score, and the score as an ordinal variable, showed similar results., Conclusions: An overall moderate-to-severe CSVD burden was not associated with 90-day functional dependence or death, after EVT for anterior-circulation LVO., Trial Registration: ChiCTR1900022154 KEY POINTS: • Moderate-to-severe cerebral small vessel disease burden on MRI should not be an exclusion indicator in determining the eligibility of an acute ischemic stroke patient for endovascular treatment., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: The role of serum uric acid (SUA) in affecting outcomes after endovascular treatment (EVT) in patients with ischemic stroke remains unclear. This study investigated the association of SUA with outcomes of patients with acute large vessel occlusion (LVO) who had received EVT., Methods: Patients with acute LVO stroke who underwent EVT within 24 hours were enrolled from a prospective, nationwide registry study. Baseline characteristics and SUA level within 24 hours of EVT were collected. The primary outcome was an excellent 90-day functional outcome [modified Rankin Scale (mRS) score 0-1]. Secondary outcomes included a favorable 90-day outcome (mRS score 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. The SUA level was analyzed in quartiles and as a continuous variable. We investigated the independent association of SUA with the primary outcome using multivariable logistic regression., Results: Among 780 patients (mean age 64 years; 66.28% males), 230 (29.49%) had an excellent 90-day outcome. A higher SUA level was significantly associated with an excellent outcome in univariate logistic regression (P=0.045) and after adjusting for confounders in multivariate analysis [adjusted odds ratio (aOR), 0.998; 95% confidence interval (CI), 0.996-1.000; P=0.018]. Multivariate logistic regression analysis showed patients with SUA level in the fourth quartile had an excellent 90-day outcome (aOR, 0.367; 95% CI, 0.154-0.876; P=0.024). There was no significant association for SUA level with favorable 90-day outcome, sICH, or 90-day mortality (P>0.05)., Conclusions: Among patients with acute LVO type of stroke who received EVT, baseline high SUA level may predict a better 90-day functional outcome., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4494/coif). All authors report that this research was supported by the National Key R&D Program of China (grant Nos. 2016YFC1307301, 2018YFC1312402), the National Natural Science Foundation of China (grant No. 81820108012), Medical Science Research Project of Hebei Province (grant No. 20211242) and partially supported by Boehringer-Ingelheim China. The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

The non-SMC condensin I complex subunit G (NCAPG) is a subunit of the condensin complex, many studies have shown that NCAPG is aberrantly expressed in different tumors and closely associated with poor prognosis, but its role in bladder cancer is unclear. In this paper, we found that NCAPG expression was upregulated in bladder cancer in tumor-related databases, and further verified the expression of NCAPG in bladder cancer tissues as well as bladder cancer cell lines by tissue microarray, qPCR, and WB. Next, we explored the changes in bladder cancer cell proliferation as well as migration after NCAPG knockdown by cell growth curve, colony formation, soft agar assay, and xenograft model. Finally, we examined the changes in downstream signaling pathways after NCAPG knockdown using RNA-Seq, and we found that the NF-κB signaling pathway was inhibited with NCAPG gene knockdown, which was verified by luciferase reporter assay as well as WB. In conclusion, our results illustrate that NCAPG knockdown can inhibit the proliferation of bladder cancer cells through the NF-κB signaling pathway. This finding demonstrates that NCAPG could be a potential target for the treatment of bladder cancer., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hepatoblastoma, originating from hepatoblasts, is the most common hepatic malignancy. WD repeat domain 4 (WDR4) is a subunit of RNA N(7)-methylguanine (m7G) methyltransferase complex. Recently, WDR4 has shown oncogenic potential in various adult cancers, but its roles in pediatric cancers have not been reported. We performed a case-control study (313 cases vs. 1446 controls) to investigate whether genetic variants in the WDR4 gene influence hepatoblastoma susceptibility in the Chinese Han nationality. We first determine the genotypes of five WDR4 gene polymorphisms (rs2156315 C>T, rs2156316 C>G, rs6586250 C>T, rs15736 G>A, rs2248490 C>G) in participants, using the Taqman assay. And then, an unconditional logistic regression analysis was performed to assess the association between WDR4 gene polymorphisms and hepatoblastoma risk. Overall, we did not find any polymorphism significantly associated with the risk of developing hepatoblastoma. Instead, the stratified analysis revealed that the co-existence of 2-5 risk genotypes increased hepatoblastoma risk by 2.23 folds in girls (adjusted odds ratio=2.23, 95% confidence interval=1.17-4.23, P =0.014). In conclusion, our results demonstrate that single selected polymorphisms were too weak to exert a significant effect on the whole study population. However, in combination, two or more WDR4 gene polymorphisms significantly conferred increased hepatoblastoma risk in girls. Our findings may encourage more genetic association studies to discover significant polymorphisms in the WDR4 gene for hepatoblastoma., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)