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Abstract Objective Currently, the association between smoking, alcohol, and coffee intake and the risk of ovarian cancer (OC) remains conflicting. In this study, we used a two-sample mendelian randomization (MR) method to evaluate the association of smoking, drinking and coffee consumption with the risk of OC and prognosis. Methods Five risk factors related to lifestyles (cigarettes per day, smoking initiation, smoking cessation, alcohol consumption and coffee consumption) were chosen from the Genome-Wide Association Study, and 28, 105, 10, 36 and 36 single-nucleotide polymorphisms (SNPs) were obtained as instrumental variables (IVs). Outcome variables were achieved from the Ovarian Cancer Association Consortium. Inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). Results The two-sample MR analysis supported the causal association of genetically predicted smoking initiation (OR: 1.15 per SD, 95%CI: 1.02–1.29, P = 0.027) and coffee consumption (OR: 1.40 per 50% increase, 95%CI: 1.02–1.93, P = 0.040) with the risk of OC, but not cigarettes per day, smoking cessation, and alcohol consumption. Subgroup analysis based on histological subtypes revealed a positive genetical predictive association between coffee consumption and endometrioid OC (OR: 3.01, 95%CI: 1.50–6.04, P = 0.002). Several smoking initiation-related SNPs (rs7585579, rs7929518, rs2378662, rs10001365, rs11078713, rs7929518, and rs62098013), and coffee consumption-related SNPs (rs4410790, and rs1057868) were all associated with overall survival and cancer-specific survival in OC. Conclusion Our findings provide the evidence for a favorable causal association of genetically predicted smoking initiation and coffee consumption with OC risk, and coffee consumption is linked to a greater risk of endometrioid OC.

Abstract Background For elderly adults undergoing hip arthroplasty, fascia iliaca compartment block (FICB) is often used before spinal anesthesia to reduce the pain of posture placement. However, the impact of FICB within 48 h needs further study. Methods 89 elderly adults scheduled to undergo arthroplasty for hip fracture were enrolled and randomized into the FICB group (n = 45) and the control group (n = 44). The fascia iliaca on the operated side was located using ultrasound, and a puncture needle was placed under the fascia iliaca. The FICB group was injected with 40 ml of 0.5% ropivacaine, and the control group was injected with 40 ml of normal saline. Spinal anesthesia was performed after 20 min. Our primary outcome measures were: duration of analgesia, muscle strength, and Quality of Recovery (QoR). Results The duration of analgesia in the FICB group was 403.5 ± 39.6 min, which was longer than that (357.5 ± 35.9 min) of the control group (P = 0.012). There were 19 (42.2%) patients with muscle strength of grade 4 in the FICB group and 36 (81.8%) patients with muscle strength of grade 4 in the control group. FICB group was lower (P

Wireless communication network (WCN) is very important for providing convenient mobile network communication services. Random Phase Multiple Access (RPMA) WCN under heterogeneous network architecture is widely used in wireless network construction worldwide due to its low power consumption and high cell density. However, this kind of WCN cannot meet the application scenario of high communication quality. Therefore, this research builds an RPMA communication quality prediction model for big data wireless base stations, which combines the convolutional neural network (CNN) algorithm and the lifting regression tree algorithm. It can be used to find the elements that have obvious influence on the communication quality. The reason for choosing the convolutional neural network algorithm is that its nonlinear feature relationship search and processing ability is excellent, and its computational complexity is relatively small. However, it is a black box algorithm and cannot obtain the importance coefficients of each feature, which is not conducive to subsequent analysis. Therefore, it is also necessary to select a relatively simple modified regression tree algorithm to participate in the calculation. The model constructed by integrating convolutional neural network and lifting regression tree algorithm is the RPMA wireless big data base station communication quality prediction model. A base station planning and deployment model based on weighted K-centroids algorithm is designed to obtain a better base station deployment scheme. In the CNN-DT model, the importance coefficients of T_B_diff, P_La and P_Lo are the largest and significantly larger than those of other features, which are 0.352, 0.289 and 0.264 respectively. The weighted K-centroids clustering algorithm designed in this study has the best overall downlink reception signal (RSSI) value distribution. For RSSI bucket “- 140 $\sim $ - 130”, the number of test points of WK centroids model, K-means model, GMC model, Mean Shift model and spectral clustering model accounted for 1.95%, 6.25%, 4.25%, 8.22% and 7.13% respectively. The model constructed in this study based on CNN and improved regression tree algorithm can accurately predict the communication quality of wireless big data base stations. This study’s main contribution is that it can be used in conjunction with the base station planning and deployment model based on weighted K-centroids algorithm to improve the accuracy and effectiveness of location selection for the RPMA wireless communication network base station.

Abstract Background To compare the characteristics of corneal thickness measurements among the RTVue, Casia-2, and Pentacam in patients with mild-to-moderate keratoconus. Methods We recruited 46 eyes of 46 patients diagnosed with mild-to-moderate keratoconus at our hospital between January and March 2022. The central corneal thickness (CCT) and thinnest corneal thickness (TCT) were measured using two optical coherence tomography (OCT) instruments (RTVue and Casia-2) and the more conventional Pentacam. Differences and correlations between the CCTs and TCTs, based on the device and influencing factors, were explored. Results The CCTs were highly consistent among the groups (p = 0.434) and correlated with one another (p 0.05). Multivariate analysis identified that the TCT measurement difference between the RTVue and Pentacam was related to the difference between the CCT and TCT (b = 0.490, 95% confidence interval [CI]: 0.033 to 0.948, p = 0.036), whereas the difference between the Casia-2 and Pentacam was related to the anterior radius for curvature (A) grade (b = 3.9, 95% CI: 1.753 to 6.074, p = 0.001), corneal pachymetry at the thinnest (C) grade (b = − 7.875, 95% CI: − 11.404 to − 4.346, p

Abstract Background Gilteritinib is the only drug approved as monotherapy for acute myeloid leukemia (AML) patients harboring FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation throughout the world. However, drug resistance inevitably develops in clinical. Sitravatinib is a multi-kinase inhibitor under evaluation in clinical trials of various solid tumors. In this study, we explored the antitumor activity of sitravatinib against FLT3-ITD and clinically-relevant drug resistance in FLT3 mutant AML. Methods Growth inhibitory assays were performed in AML cell lines and BaF3 cells expressing various FLT3 mutants to evaluate the antitumor activity of sitravatinib in vitro. Immunoblotting was used to examine the activity of FLT3 and its downstream pathways. Molecular docking was performed to predict the binding sites of FLT3 to sitravatinib. The survival benefit of sitravatinib in vivo was assessed in MOLM13 xenograft mouse models and mouse models of transformed BaF3 cells harboring different FLT3 mutants. Primary patient samples and a patient-derived xenograft (PDX) model were also used to determine the efficacy of sitravatinib. Results Sitravatinib inhibited cell proliferation, induced cell cycle arrest and apoptosis in FLT3-ITD AML cell lines. In vivo studies showed that sitravatinib exhibited a better therapeutic effect than gilteritinib in MOLM13 xenograft model and BaF3-FLT3-ITD model. Unlike gilteritinib, the predicted binding sites of sitravatinib to FLT3 did not include F691 residue. Sitravatinib displayed a potent inhibitory effect on FLT3-ITD-F691L mutation which conferred resistance to gilteritinib and all other FLT3 inhibitors available, both in vitro and in vivo. Compared with gilteritinib, sitravatinib retained effective activity against FLT3 mutation in the presence of cytokines through the more potent and steady inhibition of p-ERK and p-AKT. Furthermore, patient blasts harboring FLT3-ITD were more sensitive to sitravatinib than to gilteritinib in vitro and in the PDX model. Conclusions Our study reveals the potential therapeutic role of sitravatinib in FLT3 mutant AML and provides an alternative inhibitor for the treatment of AML patients who are resistant to current FLT3 inhibitors.

Abstract Background Type 2 innate lymphoid cells (ILC2) are upregulated in childhood allergic rhinitis (AR) and are associated with AR severity. This study aimed to investigate changes in the ILC2 milieu in pediatric patients with AR after sublingual immunotherapy (SLIT). Methods Forty- pediatric patients with AR received house dust mite (HDM) allergen extract for SLIT group and thirty pediatric patients received placebo in the study, respectively. The levels of ILC2, ILC2-related cytokines (IL-5/IL-13) and their transcription factors (GATA binding protein 3, retinoic acid-related orphan receptor α) in the circulation were assessed after 1- and 2-year SLIT. Moreover, peripheral blood mononuclear cells (PBMCs) in patients were prepared and stimulated by recombinant thymic stromal lymphopoietin, IL-25, and IL-33 after 2-year SLIT. Subsequently, the levels of ILC2, IL-5, and IL-13 were tested. Results The frequency of ILC2 and the levels of their transcription factors in the circulation were significantly decreased after SLIT in the SLIT group. The levels of ILC2-related cytokines in the SLIT group showed the same trend. The frequency of ILC2 was positively correlated with transcription factors and cytokines after SLIT. SLIT was observed to reduce the ability of HDM sensitization to generate the ILC2 milieu in PBMCs. Conclusions Changes in the ILC2 milieu may be correlated with the curative effect and immune regulation function of SLIT. Our results suggested that the regulatory effect on ILC2 is part of the therapeutic mechanism of SLIT.

The frequency of forest fires has increased dramatically due to climate change. The occurrence of forest fires affects the carbon and nitrogen cycles and react to climate change to form a positive feedback mechanism. These effects further impact the distribution of microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) and the soil microbial community structure. In addition, permafrost degradation can significantly affect the microorganisms in the soil. Based on these findings, this review examines the effects of fire intensity and post-fire recovery time on permafrost, the soil microbial community, MBC, MBN, and their interrelationships. This review demonstrated that (1) fires alter the condition of surface vegetation, reduce the organic layer thickness, redistribute snow, accelerate permafrost degradation, and even lead to permanent changes, where the restoration of the pre-fire state would require several decades or even centuries; (2) soil microbial community structure, soil MBC, and MBN negatively correlate with fire intensity, and the effects become more pronounced with increasing fire intensity; and (3) the structural diversity and stability of the soil microbial community were improved with time, and the amount of MBC and MBN increases as the years after a fire go by; it would still take more than ten years to recover to the pre-fire level. However, the relationship between permafrost degradation and soil microbes after forest fires is still unclear due to a lack of quantitative research on the mechanisms underlying the changes in soil microorganisms resulting from fire-induced permafrost degradation. Therefore, expanding quantitative studies and analyses of the mechanisms of interactions between forest fires, permafrost, and soil microorganisms can provide a scientific basis for understanding ecosystem carbon pools and dual-carbon targets in Arctic–boreal permafrost regions.

Air pollution severely threatens people’s health and sustainable economic development. In the era of the digital economy, modern information technology is profoundly changing the way governments govern, the production mode of enterprises, and the living behavior of residents. Whether digital technology can bring ecological welfare needs to be further studied. Based on panel data from 269 Chinese cities from 2006 to 2021, this study empirically examines the impact of digital technology on air pollution by using the two-way fixed effect model. The results show that digital technology will significantly reduce the concentration of fine particles in the air and help protect the atmospheric environment. The results are still valid after using the interactive fixed effect model and the two-stage least square method after the robustness test and causality identification. Digital technology can also reduce the air pollution by promoting green innovation, improving energy efficiency, and easing market segmentation. The effect of digital technology on reducing the concentration of fine particles in the air is heterogeneous. Digital technology plays a more substantial role in reducing pollution in resource-based cities and areas with a high degree of modernization of the commodity supply chain. The positive effect of digital technology in reducing air pollution is affected by the amount of air pollutants emitted. When the concentration of PM2.5 in the air is high, the role of digital technology in protecting the atmosphere will be strongly highlighted. This research is a beneficial exploration of protecting the atmospheric environment by using digital technology while building an ecological civilization society. The conclusion will help urban managers, the public, and business operators entirely use modern equipment such as 5G, remote sensing, and the Internet of Things in their respective fields to protect the atmospheric environment.

Rice production in the Anhui province is threatened by fungal diseases. We obtained twenty-five fungal isolates from rice and wild rice leaves showing leaf spot disease collected along the Yangtze River. A phylogenetic analysis based on internal transcribed spacer (ITS), translation elongation factor 1 alpha (TEF1-α), and beta tubulin (TUB2) sequences revealed one isolate (SS-2-JB-1B) grouped with Nigrospora sphaerica, one (QY) with Nigrospora chinensis, twenty-two with Nigrospora oryzae, and one isolate (QY-2) grouped in its own clade, which are related to but clearly different from N. oryzae. Nineteen tested isolates, including sixteen strains from the N. oryzae clade and the three isolates of the other three clades, caused disease on detached rice leaves. The three isolates that did not belong to N. oryzae were also able to cause disease in rice seedlings, suggesting that they were rice pathogens. Isolate QY-2 differed from the other isolates in terms of colony morphology, cell size, and susceptibility to fungicides, indicating that this isolate represents a new species that we named Nigrospora anhuiensis. Our analysis showed that N. sphaerica, N. chinensis, and the new species, N. anhuiensis, can cause rice leaf spot disease in the field. This research provides new knowledge for understanding rice leaf spot disease.

The gas sensitivity of the W defect in WS2 (VW/WS2) to five toxic gases—HCHO, CH4, CH3HO, CH3OH, and CH3CH3—has been examined in this article. These five gases were adsorbed on the VW/WS2 surface, and the band, density of state (DOS), charge density difference (CDD), work function (W), current–voltage (I–V) characteristic, and sensitivity of adsorption systems were determined. Interestingly, for HCHO-VW/WS2, the energy level contribution of HCHO is closer to the Fermi level, the charge transfer (B) is the largest (0.104 e), the increase in W is more obvious than other adsorption systems, the slope of the I–V characteristic changes more obviously, and the calculated sensitivity is the highest. To sum up, VW/WS2 is more sensitive to HCHO. In conclusion, VW/WS2 has a great deal of promise for producing HCHO chemical sensors due to its high sensitivity and selectivity for HCHO, which can aid in the precise and efficient detection of toxic gases.

Abstract Liu et al. (2022, https://doi.org/10.1029/2021GL093691) used Rayleigh waves extracted from the cross‐correlation of ambient noise recorded by two stations to monitor the seismic velocity variations associated with the 2018 Kı̄lauea eruption. However, their study ignored the fact that the tremors on the Island of Hawai'i were dominated by a source at the Kı̄lauea summit before the eruption. Close inspection of the waveforms of the station pair PAUD‐STCD shows a simple, mistakenly identified wave traveling direction in Liu et al. (2022, https://doi.org/10.1029/2021GL093691). A correct wave traveling direction agrees with the noise source model, where the dominant tremor source should be at the Kı̄lauea summit. Because of the drastic change in the tremor source after the eruption, the cross‐correlation of the tremor records may reflect predominantly changes in the source rather than in the medium properties between the two stations.

Introduction: Improving energy efficiency is significant for achieving carbon emission reduction and promoting the transformation of green economic development. In the sustainable development framework set out in the 2030 Agenda for Sustainable Development, Goal 7.3 explicitly aims to double the global rate of energy efficiency improvement by 2030. The rapid development of digital technology, along with its universality and penetrative characteristics, has provide a feasible solution for improving energy efficiency and environmental conditions. However, the theoretical understanding of the impact and underlying logic of digital technology on energy efficiency remains unclear.Methods: Based on the panel data of 30 provinces in China from 2006 to 2021, this paper adopts econometric methods, including two-way fixed effect, instrumental variable method, and Driscoll-Kraay standard error. It investigates the influence of digital technology on energy efficiency and its internal mechanism from single factor and all factor levels.Result: The results show that Digital technology, represented by industrial robots, significantly improves energy efficiency, whether measured by the energy consumption intensity of GDP or the total-factor energy efficiency estimated using the SBM-GML model. The results still hold even after conducting endogeneity tests and robustness tests. Digital technology can improve energy efficiency by increasing virtual industrial agglomeration and promoting outward foreign direct investment.Discussion: In addition to promoting the theoretical understanding of the impact of digital technology on energy efficiency and exploring its mechanism, this paper also provides empirical evidence for policy makers and enterprises to formulate effective measures and strategies to improve energy efficiency under the background of digital economy.

This article reports a case of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) misdiagnosed as Kawasaki disease and summarizes the clinical features and therapeutic progress of TRAPS and the relationship between its clinical manifestations and gene mutations. We retrospectively analyzed a patient with tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) -mutated auto-inflammatory disease who was misdiagnosed with Kawasaki disease in another hospital. The clinical features and therapeutic progress of TRAPS were analyzed by combining clinical features and gene reports of this case and literature review. TRAPS onset occurred in a female pediatric patient at the age of 4 months. The child and in his father at the age of 6 years, both of whom manifested periodic fever, and recurrent rash, as well as elevated leukocytes, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) during episodes but normal between episodes. This child carried a heterozygous mutation in TNFRSF1A located in the region 6442923–6442931 on chromosome 12. The nucleic acid alteration was: c.298 (exon3) _c.306 (exon3) 291 delCTCAGCTGC, resulting in a 3 amino acid deletion p.L100_C 102del 292 (p.Leu100_Cys102del) (NM_001065). After etanercept treatment, the symptoms of fever and rash disappeared, and the levels of ESR, CRP, interleukin (IL)-1, IL-6, and TNF-α levels were normal. Subsequently, no liver, kidney, or cardiac amyloidosis and severe etanercept-related adverse events were observed at 1-year follow-up. TRAPS pathogenesis is associated with TNFRSF1A mutation, which is characterized by periodic episodes of fever, mostly accompanied by recurrent rashes, periorbital edema, abdominal pain, and serious complications of organ amyloidosis. Moreover, etanercept can effectively alleviate the clinical symptoms and high inflammation level of TRAPS.

IntroductionGlobal warming presents significant challenges to the sustainable development of human society. Accelerating the achievement of carbon peak and neutrality is the vision for creating a global ecological community with a shared future. The development of digital technology provides us with the direction of action.MethodsBased on panel data from 276 cities in China from 2011 to 2020, principal component analysis was used to measure the basic state of digital technology at the city level, and the twoway fixed effects model and instrumental variable method to verify the impact of digital technology on carbon emissions from the perspective of technology diffusion.ResultsThe results show that the deep diffusion of digital technology in the real economy sector is helpful to improve productivity and carbon efficiency, thus significantly reducing carbon emissions. The role of digital technologies in reducing carbon emissions is heterogeneous. The results of the sub-sample test show that digital technology has a stronger emission reduction effect in large-scale cities, resource-based cities, smart cities and emission trading policy pilot areas. Digital technology can reduce carbon emissions by improving energy efficiency, promoting green technology innovation, and promoting virtual agglomeration.DiscussionsThe contribution of this paper is that it not only reveals that digital technology can reduce carbon emissions but also analyzes the emission reduction path of digital technology from a new perspective. The conclusion of this paper has implications for accelerating the diffusion of digital technology in the real economy sector to accelerate the realization of green production and cope with climate change.

Hemangioma (HA) is one of the most common benign vascular tumors among children. Propranolol is used as the first-line treatment for hemangioma and is a non-selective blocker of the β-adrenergic receptor. β-elemene is a compound extracted from Rhizoma zedoariae and has been approved for the treatment of tumors in clinical practice. However, the combinatorial effects of β-elemene and propranolol in the treatment of HA remains unclear. This study explored the combinative effects and mechanisms of β-elemene and propranolol using hemangioma-derived endothelial cells (HemECs). Cytotoxic assays showed that the combinatorial treatment of β-elemene and propranolol did not increase the cytotoxic effects of HemECs. Furthermore, functional analysis showed that the combinatorial treatment with β-elemene and propranolol significantly inhibited the proliferation, migration, and tube formation of the HemECs compared to the single treatment regimens. Mechanistic analysis showed that combinative treatment with β-elemene and propranolol synergistically down-regulated the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor-A (HIF-1-α/VEGFA) signaling pathway. Additionally, in a xenograft tumor model, angiogenesis in the combinatorial treatment group was significantly lower than in the control, propranolol, and β-elemene treatment alone groups. Our results suggest that β-elemene combined with propranolol can significantly inhibit the proliferation, migration, and tube formation of HemECs via synergistically down-regulating the HIF-1-α/VEGFA signaling pathway without increasing any cytotoxic side effects.

Summary: Hotspots in electronic devices can cause overheating and reduce performance. Enhancing the thermal spreading ability is critical for reducing device temperature to improve the reliability. However, as devices shrink, phonon ballistic effects can increase thermal resistance, making conventional optimization methods less effective. This paper presents a topology optimization method that combines the phonon Boltzmann transport equation with solid isotropic material with penalization method to optimize high thermal conductivity (HTC) material distributions for thermal spreading problems. Results show that the contraction-expansion structure can effectively reduce thermal resistance. Optimal distributions differ from that based on Fourier’s heat conduction law, and only the trunk structure appears in optimized layouts due to the size effect. Additionally, HTC material with longer mean free paths tends to be filled around the heat source with a gap in a ballistic-diffusive regime. This work deepens understanding of thermal spreading and aids in thermal optimization of microelectronic chips.

Intelligent manufacturing offers opportunities for green technology innovation at a low cost, helps eliminate outdated equipment, and improves pollution efficiency, which is essential for environmental protection. From the perspective of the industrial sector, based on the data of 269 Chinese cities, this study empirically examines the impacts of intelligent manufacturing on ecological environment using the fixed effect model and unconditional quantile model. The research results show that intelligent manufacturing can significantly reduce the concentration of PM2.5 in the air and environmental pollution by optimizing resource allocation during production and operation. The results of the external mechanism show that green technological innovation plays a positive mediating role in the impact mechanism of intelligent manufacturing to improve air quality. The marginal impact of intelligent manufacturing on environmental pollution is nonlinear, and the main trend is the M-type distribution trend of increasing first, then decreasing, and then rising. In particular, intelligent manufacturing has a greater welfare effect on the ecological environment at the lower quantiles. The results provide a viable path for the government to actively plan a strategic layout to improve the ecological environment and achieving the goal of high-quality economic development.

Abstract The study of metal‐hydrogen interaction is essential for hydrogen‐related applications. Due to the small permittivity variation of palladium (Pd), it is difficult to visualize its hydrogenation processes. Soft substrates can release the expansion stress of Pd membrane and form wrinkling during hydrogenation, which can be utilized to track the hydrogen diffusion. Here, we investigate the hydrogenation processes of Pd membranes with various shapes and sizes on polydimethylsiloxane (PDMS) substrates. It was found that the Pd membranes priorly wrinkles from the edges during hydrogenation and the saturation time of hydrogen absorption reduces with the decreasing size of Pd membranes. With these measurements, we fabricate a high‐performance optical hydrogen sensor consisted of a Pd nanostripe array on PDMS. Due to the transition from specular reflection to scattering during the surface wrinkling of the Pd nanostripe, when exposed to 4% hydrogen gas mixed with nitrogen gas, the sensor shows a high‐reflectance contrast of more than 800% with the absolute reflectance change exceeding 32% over the visible band, and the response time t90 is about 1.5 seconds. These results suggest that the Pd membranes on an elastic substrate is a promising platform for visualization of hydrogen diffusion and hydrogen detection.

This paper aims to inquiry on the dialectical relationships between Chinese architecture's form and function in the horizon of long-term historical evolution, by clarifying how the histories of imperial main halls and state ceremonies relate to and interact with each other during the Tang and Song dynasties.The imperial main halls are the most archetypical and accomplished ones among traditional Chinese buildings, and their function is primarily ritual rather than practical. Although these magnificent buildings are indisputably considered the crowning achievement of Chinese architectural history, how the built space cooperates with ritual practices did not receive deserved attention.With the thorough reading of voluminous official ritual documents and comprehensive utilization of archaeological discoveries together with visual materials, the research presents a broad understanding of the asynchronous developments of the ground-level architectural arrangement and the ritual configuration across these centuries. Also specifically depicted are details of how architecture engaged in the ritual narration and was used as an apparatus to articulate emperor-courtier relationships.

Abstract Background Secreted phosphoprotein 1 (SPP1), an extracellular secreted glycol phosphoprotein, is closely related to tumor biologies, such as proliferation, migration, and invasion. However, the role and biological function of SPP1 in lung adenocarcinoma (LUAD) was still ambiguous. Methods SPP1 expression in LUAD tissues and its associations with clinical features and prognosis was investigated using meta-analysis, immunohistochemistry (IHC) staining methods, and quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the potential mechanism related to SPP1 was identified by using the Gene Set Enrichment Analysis (GSEA) method. A series of function assays were conducted to determine the biological role of SPP1 in LUAD cell migration and invasion in vitro and vivo. The co-expressed genes of SPP1 were obtained and verified by western blot assays. The influence of SPP1 on Collagen type XI alpha 1 (COL11A1) expression and epithelial-mesenchymal transition (EMT) markers was analyzed using western blot assays. Results The expression of SPP1 in LUAD tissues and cells was significantly higher than that in normal tissues and cells. And positively associations of SPP1 expression with TNM stage, lymph node metastasis, and invasion depth were observed. Patients with high SPP1 expression had unfavorable survival. The multivariable Cox regression analysis revealed that SPP1 expression was an independent prognostic factor of LUAD patients. Furthermore, downregulation of SPP1 could inhibit cell migration and invasion both in vitro and vivo, reduce the expression of epithelial marker (E-cadherin), and increase the expression of mesenchymal markers (N-cadherin and vimentin). Using bioinformatics and western blot assays, we confirmed that COL11A1 acted as the downstream of SPP1, and SPP1 knockdown could significantly downregulate the COL11A1 expression. Importantly, suppression of cell migration and invasion and the expression changes of EMT markers induced by SPP1 downregulation could be reversed by COL11A1 overexpression. Conclusions SPP1 facilitates cell migration and invasion by upregulating COL11A1 expression and that acts as a potential biomarker of metastasis and prognosis for LUAD.

While most studies of mechanical stimulation of cells are focused on two-dimensional (2D) and three-dimensional (3D) systems, it is rare to study the effects of cyclic stretching on cells under a quasi-3D microenvironment as a linkage between 2D and 3D. Herein, we report a new method to prepare an elastic membrane with topographic microstructures and integrate the membrane into a microfluidic chip. The fabrication difficulty lay not only in the preparation of microstructures but also in the alignment and bonding of the patterned membrane to other layers. To resolve the problem, we designed and assembled a fast aligner that is cost-effective and convenient to operate. To enable quasi-3D microenvironment of cells, we fabricated polydimethylsiloxane (PDMS) microwell arrays (formed by micropillars of a few microns in diameter) with the microwell diameters close to the cell sizes. An appropriate plasma treatment was found to afford a coating-free approach to enable cell adhesion on PDMS. We examined three types of cells in 2D, quasi-3D, and 3D microenvironments; the cell adhesion results showed that quasi-3D cells behaved between 2D and 3D cells. We also constructed transgenic human mesenchymal stem cells (hMSCs); under cyclic stretching, the visualizable live hMSCs in microwells were found to orientate differently from in a 3D Matrigel matrix and migrate differently from on a 2D flat plate. This study not only provides valuable tools for microfabrication of a microfluidic device for cell studies, but also inspires further studies of the topological effects of biomaterials on cells.

The low-fat stabilized compound sesame paste was prepared with pure sesame paste and chia seed extract as the main raw materials, and with monoglyceride and sucrose ester as emulsifier. Taking centrifugal oil yield and hardness as evaluation indicators, single factor experiments were conducted to study the effects of emulsifier addition, compound ratio of monoglyceride and sucrose ester , stirring time, and stirring temperature on the stability of compound sesame paste. On this basis, the response surface optimization and the research on the rheological properties of the product were conducted. Results showed that, adding 5% chia seed extract could effectively reduce the crude fat content of pure sesame paste by 10.82%. The oil yield of the compound sesame paste could be reduced to 2.61%, much lower than that of pure sesame paste, and the overall sensory experience could be upgraded, on the condition that the added amount of emulsifier was 1.6%, the compound ratio of monoglyceride to sucrose ester was 2.6:1, the stirring temperature was 71 ℃, and the stirring time was 9.5 min. The chia compound sesame paste was a non-Newtonian pseudoplastic fluid, and the temperature had a low effect on its viscosity. The stability of the compound sesame paste was better than that of the current sesame paste on the market.

Based on the first principles calculation method, we explored the impacts of p-type doping on the electronic characteristics of Al0.5Ga0.5N nanowire. Firstly, Al0.5Ga0.5N nanowires are simulated with different doping elements (Be, Mg and Zn), as well as different doping strategies (interstitial doping and substitutional doping). The estimated formation energies show that the p-type doping of Al0.5Ga0.5N nanowire is an endothermic process. Also, in the substitutional doping process, it is easier for dopant atoms to replace Ga atoms than Al atoms. The substitutional doping of Mg atom drops the nanowire electron affinity obviously, which promotes the transition of surface photoelectrons. Furthermore, it can be concluded that the substitutional doping contributes to the Fermi level cross the valence band and causing the nanowires to exhibit distinct p-type properties. Also, the charge density maps show that for Be and Mg substitutional doping system, the electron density around the dopant significantly decreases, which further verifies the p-type conductivity. Meanwhile, the p-type characteristic of Mg atom substitution doping is the most obvious. This work not only thoroughly explored the impacts of different doping schemes on the electronic characteristics of Al0.5Ga0.5N nanowires but also serves as a significant resource for developing high-quality p-type AlxGa1-xN nanowire photocathodes.

Abstract Background Genetic mutations of IKZF1 have been frequently delineated in B‐lineage acute leukaemia (B‐ALL) but rarely elucidated in acute myeloid leukaemia (AML). IKZF1 mutations confer a poor prognosis in AML, and hotspot mutations of IKZF1, N159Y and N159S tend to occur in B‐ALL and AML respectively. However, the pathogenesis of IKZF1 N159S in AML and IKZF1 lineage susceptibility are largely unknown. Methods The genetic and clinical characteristics of IKZF1‐mutated AML patients were evaluated. Multi‐omics analysis and functional assays were performed in vitro using IKZF1 mutations knock‐in AML cell lines. Results 23 (4.84%) small sequence variants of IKZF1 were identified in 475 newly diagnosed AML (non‐M3) patients. Based on RNA sequencing, three classes of IKZF1‐related AML were defined, including 9 patients (39.13%) with IKZF1 N159S mutations, 10 (43.47%) with CEBPA mutations and 4 others (17.39%). IKZF1 N159S may define a unique subgroup with higher HOXA/B expression and native B‐cell immune fractions. Gene expression data of multiple knock‐in cell lines indicate that the lymphocyte differentiation‐related MME and CD44 kept high expression in IKZF1 N159Y but were downregulated in N159S. CUT&TAG sequencing showed that IKZF1 N159S reshaped the binding profiles of IKZF1. Integration analysis suggested that the pathogenesis of IKZF1 N159S may depend on the deregulation of several cofactors, such as oncogenic MYC and CPNE7 targets. Conclusions Collectively, we dissected the molecular spectrum and clinical features of IKZF1‐related AML, which may promote an in‐depth understanding of the pathogenesis, lineage susceptibility and clinical research of AML.

Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) was potentially due to the epithelial barrier injury. YES‐associated protein (YAP) is a multifunctional transcriptional factor and plays versatile roles in the regulation and maintenance of epithelial barrier in different organs and tissues. The purpose of this study is to elucidate possible effect and mechanism of YAP on the epithelial barrier of CRSwNP. Methods Patients were divided into CRSwNP group (n = 12) and control group (n = 9). The location of YAP, PDZ‐binding transcriptional co‐activator (TAZ), and Smad7 were estimated by immunohistochemistry and immunofluorescence. Meanwhile, the expression of YAP, TAZ, Zona occludens‐1 (ZO‐1), E‐cadherin, and transforming growth factor‐beta1 (TGF‐β1) were detected by Western blot. After primary human nasal epithelial cells were treated with YAP inhibitor, the expression level of YAP, TAZ, ZO‐1, E‐cadherin, TGF‐β1, and Smad7 were measured by Western blot. Results Compared with the control group, the protein levels of YAP, TAZ, and Smad7 were significantly upregulated, while TGF‐β1, ZO‐1, and E‐cadherin were downregulated in CRSwNP. YAP and Smad7 demonstrated lower levels, while the expression of ZO‐1, E‐cadherin, and TGF‐β1 rose slightly after YAP inhibitor treatment in primary nasal epithelial cells. Conclusions Higher level of YAP may lead to CRSwNP epithelial barrier injury via the TGF‐β1 signaling pathway, and the inhibition of YAP can partially reverse epithelial barrier function.

Background and AimsAnesthetics such as propofol, esketamine and nalbuphine are used during the upper gastrointestinal endoscopy to achieve and maintain the desired sedation level. The aim of the study was to evaluate the effectiveness and safety of propofol-nalbuphine and propofol-esketamine in children.MethodsA multi-centered study was performed at three tertiary class-A hospitals. Children between 3 and 12 years old undergoing diagnostic painless upper gastrointestinal endoscopy were included and randomly divided into esketamine or nalbuphine group to estimate the primary outcome of successful endoscope insertion. The patients were given esketamine 0.5 mg/kg and propofol 2 mg/kg intravenously in esketamine group, with nalbuphine 0.2 mg/kg and propofol 2 mg/kg in the nalbuphine group. The primary outcome was success rate for the first attempt of endoscope insertion in each group. Secondary outcomes included the safety of both anesthesia regimens and gastroenterologist's satisfaction. We used the Face, Leg, Activity, Cry and Consolability (FLACC) scale to evaluate the level of pain before and during the procedure and the Pediatric Anesthesia Emergence Delirium (PAED) scale to assess the level of agitation and delirium after awakening from anesthesia.ResultsAmong 246 patients, 200 were randomly included in the final intention-to-treat analysis, with 100 patients in each group. The success rate for the first attempt of endoscope insertion in the esketamine group was higher than the nalbuphine group (97% vs. 66%; P

IntroductionTo investigate the clinical characteristics and disease outcomes of a pedigree with compound heterozygous mutations in the SLC22A5 gene.MethodsSerum acylcarnitine profiles of patients were analyzed using tandem mass spectrometry. DNA samples isolated from patients and their first-degree relatives were subjected to high-throughput sequencing, and mutations were validated using Sanger sequencing.ResultsThe proband, a 4-month-old girl, presented with seizure episodes and mild cardiac hypertrophy and was diagnosed with primary carnitine deficiency (PCD), with carnitine levels of 5.165 mol/L. Her brother, a 6-year-and 4-month-old boy, was also diagnosed with PCD with serum-free carnitine levels of 1.014 mol/L (reference values 10–60 mol/L). Compound heterozygous mutations (c.760C > T [p.R254X] and c.825G > A [p.W275X]) were detected in the SLC22A5 gene in both patients and were inherited from the mother and father, respectively. Oral L-carnitine significantly improved or resolved the clinical symptoms.ConclusionChildren with compound mutations in SLC22A5 may present different clinical manifestations, particularly at different ages. Early clinical manifestations have a greater impact on the organs and may cause irreversible damage. PCD can cause epilepsy and dilated cardiomyopathy. Tandem mass spectrometry and high-throughput sequencing are recommended to confirm the diagnosis. Early L-carnitine supplementation can improve symptoms and reverse organ damage in some children. Tandem mass spectrometry should be used to screen for newborns with a family history of PCD.

Abstract Understanding the electromechanical breakdown mechanisms of polycrystalline ceramics is critical to texture engineering for high‐energy‐density dielectric ceramics. Here, an electromechanical breakdown model is developed to fundamentally understand the electrostrictive effect on the breakdown behavior of textured ceramics. Taking the Na0.5Bi0.5TiO3‐Sr0.7Bi0.2TiO3 ceramic as an example, it is found that the breakdown process significantly depends on the local electric/strain energy distributions in polycrystalline ceramics, and reasonable texture design could greatly alleviate electromechanical breakdown. Then, high‐throughput simulations are performed to establish the mapping relationship between the breakdown strength and different intrinsic/extrinsic variables. Finally, machine learning is conducted on the database from the high‐throughput simulations to obtain the mathematical expression for semi‐quantitatively predicting the breakdown strength, based on which some basic principles of texture design are proposed. The present work provides a computational understanding of the electromechanical breakdown behavior in textured ceramics and is expected to stimulate more theoretical and experimental efforts in designing textured ceramics with reliable electromechanical performances.

Purpose: To compare bilateral differences in corneal biomechanics between keratoconus and normal eyes.Methods: In this case-control study, 346 eyes of 173 patients (aged 22.1 ± 6.1 years) with keratoconus (KC group) and 378 eyes of 189 patients (aged 26.7 ± 5.6 years) with ametropia (control group) were enrolled. Corneal tomography and biomechanical properties were examined using Pentacam HR and Corvis ST, respectively. The corneal biomechanical parameters were compared between eyes with forme fruste keratoconus (FFKC) and normal eyes. Bilateral differences in corneal biomechanical parameters were compared between the KC and control groups. Receiver operating characteristic (ROC) analysis was used to assess discriminative efficacies.Results: The areas under the ROC curves (AUROCs) of stiffness parameter at the first applanation (SP-A1) and Tomographic and Biomechanical Index (TBI) for identifying FFKC were 0.641 and 0.694, respectively. The bilateral differential values of major corneal biomechanical parameters were significantly increased in the KC group (all p < 0.05), except for the Corvis Biomechanical Index (CBI). The AUROCs of the bilateral differential values of the deformation amplitude ratio at 2 mm (ΔDAR2), Integrated Radius (ΔIR), SP-A1 (ΔSP-A1), and the maximum inverse concave radius (ΔMax ICR) for discriminating keratoconus were 0.889, 0.884, 0.826, and 0.805, respectively. The Logistic Regression Model-1 (comprising of ΔDAR2, ΔIR, and age) and the Logistic Regression Model-2 (comprising of ΔIR, ΔARTh, ΔBAD-D, and age) had AUROCs of 0.922 and 0.998, respectively, for discriminating keratoconus.Conclusion: The bilateral asymmetry of corneal biomechanics was significantly increased in keratoconus compared with normal eyes, which may be helpful for the early detection of keratoconus.

BackgroundSnail family transcriptional repressor 2 (SNAI2) is a transcription factor that induces epithelial to mesenchymal transition in neoplastic epithelial cells. It is closely related to the progression of various malignancies. However, the significance of SNAI2 in human pan-cancer is still largely unknown.MethodsThe Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases were taken to examine the SNAI2 expression pattern in tissues and cancer cells. The link between SNAI2 gene expression levels and prognosis, as well as immune cell infiltration, was investigated using the Kaplan-Meier technique and Spearman correlation analysis. We also explored the expression and distribution of SNAI2 in various tumor tissues and cells by the THPA (Human Protein Atlas) database. We further investigated the relationship between SNAI2 expression levels and immunotherapy response in various clinical immunotherapy cohorts. Finally, the immunoblot was used to quantify the SNAI2 expression levels, and the proliferative and invasive ability of pancreatic cancer cells was determined by colony formation and transwell assays.ResultsWe discovered heterogeneity in SNAI2 expression in different tumor tissues and cancer cell lines by exploring public datasets. The genomic alteration of SNAI2 existed in most cancers. Also, SNAI2 exhibits prognosis predictive ability in various cancers. SNAI2 was significantly correlated with immune-activated hallmarks, cancer immune cell infiltrations, and immunoregulators. It’s worth noting that SNAI2 expression is significantly related to the effectiveness of clinical immunotherapy. SNAI2 expression was also found to have a high correlation with the DNA mismatch repair (MMR) genes and DNA methylation in many cancers. Finally, the knockdown of SNAI2 significantly weakened the proliferative and invasive ability of pancreatic cancer cells.ConclusionThese findings suggested that SNAI2 could be used as a biomarker in human pan-cancer to detect immune infiltration and poor prognosis, which provides a new idea for cancer treatment.

BackgroundIt has been well acknowledged that disordered intestinal microflora and their fermented products play crucial role during the development of hypertension (HTN). Aberrant profiles of fecal bacteria have been documented in subjects with isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) previously. Nevertheless, evidence regarding the association of metabolic products in the bloodstream with ISH, IDH and combined systolic and diastolic HTN (SDH) remains scarce.MethodsWe performed a cross-sectional study and conducted untargeted liquid chromatography-mass spectrometry (LC/MS) analysis on serum samples of 119 participants, including 13 subjects with normotension (SBP

Abaqus is a commercial software suite for numerical simulation and ParaView is an open-source software application for 3D scientific data visualization. While the Abaqus suite provides Abaqus/Viewer for post-processing, it is not open-source, and custom visualization features can only be implemented using Abaqus official APIs (e.g., Python APIs). ParaView has a robust rendering pipeline, such that complicated post-processing operations can be implemented using filters. Due to ParaView’s openness and plugin architectures, highly tailored data processing and visualization are made possible. However, visualizing Abaqus output database (.odb extension) in ParaView is a nontrivial task. ODB files are proprietary binary files that can only be read by Abaqus. Without reverse engineering, the option is to extract data from ODB files using Abaqus’ official APIs (C++ or Python) and write them to a file format compatible with ParaView. There have been some efforts to achieve this, but none of them are satisfactory in terms of extensibility and generality. Our converter is designed to address this issue by providing a compact, robust, and extensible solution for converting Abaqus ODB files to a format that can be read by ParaView. Our converter stands out due to the following benefits: (1) It can handle a variety of element types, including linear elements, high-order elements, and elements with multiple integration or section points; (2) It extracts data at integration and section points; (3) It includes a separate script that utilizes Python multiprocessing; (4) A C++ version is also provided, which offers a significant increase in speed compared to the Python version.

IntroductionPromoting the development of digital technology is an important step in meeting the challenge of global climate change and achieving carbon peaking and carbon neutrality goals.MethodsBased on panel data of Chinese cities from 2006 to 2020, this paper used econometrics to investigate the impact and mechanism of digital technology on carbon emissions.ResultsThe results showed that digital technology can significantly reduce carbon emission intensity and improve carbon emission efficiency. These results remained robust after changing the estimation method, adding policy omission variables, replacing core variables, and solving the endogeneity problem. Digital technology can indirectly reduce carbon emissions by promoting green technological innovation and reducing energy intensity, and it plays a significant role in the carbon emission reduction practices of carbon emission trading policies and comprehensive national big data pilot zones. The replicability, non-exclusivity, and high mobility of digital technology help to accelerate the spread of knowledge and information between different cities, which leads to a spillover effect on carbon emission reductions. Our unconditional quantile regression model results showed that digital technology’s carbon emission reduction effect continuously decreases with increases in carbon dioxide emissions.DiscussionThe results of this paper provide evidence for the potential use of digital technology in achieving the goal of carbon neutrality, which is of great significance for achieving high-quality innovation and promoting the green transformation of the economy and society.

This paper presents an in-depth analysis of the robust optimization of the China–Europe freight train transportation organization under uncertain cargo transportation demand. The study commences by constructing a robust optimization model tailored for specific environments, which is further extended to address the complexities of uncertain freight demand. A notable aspect of this research is the adoption of an innovative approach to manage the uncertainties in freight transportation demand at each node, employing a box-type uncertainty set distribution. This methodology allows for an effective and balanced optimization strategy that accommodates the dynamic nature of demand fluctuations. The research findings underscore that increased robustness in the optimization model is associated with higher transportation costs within the China–Europe freight train network, especially under conditions of variable demand. The model demonstrates a preference for adjusting transportation costs to maintain the stability of the transportation scheme, particularly in response to wider variations in cargo demand. This strategy, prioritizing cost-effectiveness and adaptability, highlights the importance of a comprehensive approach to managing demand uncertainties. The significant contributions of this paper include the development of a robust, economically viable, and efficient transportation organization plan for China–Europe freight trains, equipped to navigate the challenges posed by uncertain cargo demand at the originating nodes. The study’s emphasis on the practical application of advanced optimization techniques and uncertainty management methods marks a notable advancement in the field of freight train transportation. Additionally, the paper suggests avenues for further research in the intricate and evolving landscape of freight transportation, providing valuable insights for future studies.

In recent decades, with the rising living standards of rural China, the amount and volume of household waste has increased continuously, causing serious environmental and human health risks. Effective garbage classification reduces garbage volume, decreases the difficulty of garbage disposal, and facilitates the recycling of resources, thereby improving environmental quality. Domestic garbage classification (DGC) has been practiced frequently in developed countries and is now at a relatively mature stage. There is no robust model for garbage classification available globally as of yet, and each country has its policy frameworks to reduce, recycle, and reuse (3R) garbage. Little attention has been paid to knowing whether and to what extent incentive-based policies called “rewards and punishments” improve garbage classification and further help achieve targets of sustainable development goals (SDGs). Recently, developing countries, like China, have begun to incorporate DGC into their laws and promote enforcement measures in a few cities. However, empirical studies on residents’ willingness to accept DGC punishments and rewards are still relatively scarce and a hot topic of global scientific discussion. To enrich the knowledge, this study collected datasets from 9983 valid questionnaires from east China (16 selected independent variables), and analyzed the key factors affecting residents’ acceptance of punishments and rewards, employing logit models. The results found that the level of education plays an important role for residents that are more inclined to accept DGC rewards and punishments. Moreover, farmers were insensitive to DGC rewards but very sensitive and unsupportive of punishments, and the hardware facilities of the quarter had a greater impact on residents’ willingness to accept DGC rewards and punishments. Findings recommend that rewards be the main focus and punishments be supplemented, thus the incentive-based policies should be improved through law enforcement and implementation of robust policy frameworks in order to promote residents’ acceptance of rewards and punishments and to accelerate better garbage classification.

Flexible capacity applications demand a large energy storage density and high breakdown electric field strength of flexible films. Here, P(VDF-HFP) with ultra-thin Al2O3 nanosheet composite films were designed and fabricated through an electrospinning process followed by hot-pressing into a sandwich structure. The results show that the insulating ultra-thin Al2O3 nanosheets and the sandwich structure can enhance the composites’ breakdown strength (by 24.8%) and energy density (by 30.6%) compared to the P(VDF-HFP) polymer matrix. An energy storage density of 23.5 J/cm3 at the ultrahigh breakdown strength of 740 kV/mm can be therefore realized. The insulating test and phase-field simulation results reveal that ultra-thin nanosheets insulating buffer layers can reduce the leakage current in composites; thus, it affects the electric field spatial distribution to enhance breakdown strength. Our research provides a feasible method to increase the breakdown strength of ferroelectric polymers, which is comparable to those of non-ferroelectric polymers.

Long-lived ionic quantum states known as metastable electronic states in highly charged ions (HCIs) are of great interest in fundamental physics. Especially, it generates transitions with very narrow natural linewidth, which is a promising candidate for use in the next-generation HCI atomic clocks to reach an accuracy below 10^{−19}. A recent experiment [Nature (London) 581, 42 (2020)10.1038/s41586-020-2221-0] used Penning trap mass spectrometry to measure the energy of an extremely long-lived metastable electronic state, thus opening doors to search for HCI clock transitions. Building upon prior research, this study introduces an experimental proposal with the goal of measuring lifetimes of the metastable states beyond seconds. Our approach employs a sequential pulse-and-phase measurement scheme, allowing for direct observations of the decay processes from metastable electronic states through single-ion mass spectrometry in a Penning trap. This measurement poses a significant challenge to conventional techniques like fluorescence detection. To demonstrate the effectiveness of this method, we conducted a comprehensive simulation under real experimental conditions, yielding promising results in a specific scenario. Two suitable candidates are proposed for testing this method, and the state-of-the-art MCDHF theory are employed for accurate energy levels and transition rate calculations. Some future prospects in the experimental determinations of a wide range of energy and lifetimes of long-lived metastable electronic states, probing hyperfine and magnetic quenching effects on high-order forbidden transitions and search for high-quality HCI clock transitions are discussed.

This paper proposes a temporary support system for improving the efficiency and safety of underground roadway excavation in coal mines. Firstly, this study establishes a calculation model for the initial supporting force of the excavation of roadway temporary support and a gray system-based automatic prediction model for the initial supporting force level, based on the mechanism of temporary support controlling the roof. These models enable the prediction of the required initial supporting force at different locations along the roadway’s temporary support area, thereby providing a basis for controlling the initial supporting force of the temporary support system. To achieve efficient and adaptive control of the initial supporting force of temporary supports at different locations, this study designs a support force controller based on Simulated Annealing Particle Swarm Optimization Proportional-Integral-Derivative (SAPSO-PID). This study establishes a mathematical model for the hydraulic cylinder pressure system controlled by the temporary support overflow valve and conducts a stability analysis and model verification. The study constructs a simulation control system for the initial supporting force based on SAPSO-PID using the combined simulation platform of AMESim and Matlab. The simulation results demonstrate that the proposed support force control system efficiently achieves adaptive control of the initial supporting force of temporary supports. An experimental system in the underground roadway of a coal mine is constructed to validate the results of the simulation analysis.

Diet plays an important role in diabetes development. The effect of ketogenic diet on type 2 diabetes remains elusive. In this study, we collect diabetes related physiological parameters and abdominal MRI images to evaluate the effect of ketogenic diet after 3-months of consecutive treatment. Ketogenic diet mitigates the diabetes symptom inferring from the statistically significant reduction of key diabetic physiological parameters such as Hemoglobin A1c (HbA1c) concentration, Triglyceride (TG), Fasting blood glucose (FBG), Body Mass Index (BMI), and adipose tissue volume. Moreover, we propose a new parameter to quantify the treating effect of ketogenic diet since Slope and Offset of Oral Glucose Tolerance Test (SOOGTT) incorporate more sampling points by fitting OGTT (Oral Glucose Tolerance Test) curve. SOOGTT shows statistically significant (P < 0.001) treating effect of ketogenic diet on type 2 diabetes. We use artificial intelligence to segment adipose tissue for treatment evaluation, which shows that ketogenic diet reduces the amount of adipose tissue.

Activation of extracellular signal–regulated kinase (ERK) 1/2 promotes hepatocyte proliferation in response to growth stimuli, but whether constitutive hepatocyte ERK1/2 signaling functions in liver physiology is unknown. To examine the role of ERK1/2 in hepatic homeostasis, the effects of a knockout of Erk1 and/or Erk2 in mouse liver were examined. The livers of mice with a global Erk1 knockout or a tamoxifen‐inducible, hepatocyte‐specific Erk2 knockout were normal. In contrast, Erk1/2 double‐knockout mice developed hepatomegaly and hepatitis by serum transaminases, histology, terminal deoxynucleotide transferase‐mediated deoxyuridine triphosphate nick end‐labeling, and assays of hepatic inflammation. Liver injury was associated with biochemical evidence of cholestasis with increased serum and hepatic bile acids and led to hepatic fibrosis and mortality. RNA sequencing and polymerase chain reaction analysis of double‐knockout mouse livers revealed that the rate‐limiting bile acid synthesis gene Cyp7a1 (cholesterol 7α‐hydroxylase) was up‐regulated in concert with decreased expression of the transcriptional repressor short heterodimer partner. Elevated bile acids were the mechanism of liver injury, as bile acid reduction by SC‐435, an inhibitor of the ileal apical sodium–dependent bile acid transporter, prevented liver injury. Conclusion: Constitutive ERK1 and ERK2 signaling has a redundant but critical physiological function in the down‐regulation of hepatic bile acid synthesis to maintain normal liver homeostasis.

Abstract Tubulin alpha-1c chain (TUBA1C), a subtype of α-tubulin, has been shown to be involved in cell proliferation and cell cycle progression in several cancers and to influence cancer development and prognosis. However, a pancancer analysis of TUBA1C to reveal its immunological and prognostic roles has not been performed. In this study, we first downloaded raw data on TUBA1C expression in cancers from The Cancer Genome Atlas (TCGA) database and multiple other databases and analysed these data with R software to investigate the prognostic and immunological value of TUBA1C in cancers. Immunohistochemical analysis was performed in gliomas to further validate our findings. Overall, TUBA1C was overexpressed in most cancers, and overexpression of TUBA1C was linked to poor prognosis and higher tumour grade in patients. In addition, TUBA1C expression was associated with tumour mutation burden (TMB), microsatellite instability (MSI), the tumour microenvironment (TME) and the infiltration of immune cells. TUBA1C was also coexpressed with most immune-related genes and influenced immune-related pathways. Immunohistochemical analysis showed that TUBA1C expression was highest in glioblastoma (GBM) tissues, second highest in low-grade glioma (LGG) tissues and lowest in normal tissues. Our study indicated that TUBA1C might be a biomarker for predicting the immune status and prognosis of cancers, offering new ideas for cancer treatment.

Abstract With its extremely strong capability of data analysis, machine learning has shown versatile potential in the revolution of the materials research paradigm. Here, taking dielectric capacitors and lithium‐ion batteries as two representative examples, we review substantial advances of machine learning in the research and development of energy storage materials. First, a thorough discussion of the machine learning framework in materials science is presented. Then, we summarize the applications of machine learning from three aspects, including discovering and designing novel materials, enriching theoretical simulations, and assisting experimentation and characterization. Finally, a brief outlook is highlighted to spark more insights on the innovative implementation of machine learning in materials science.

Abstract Amyloid‐β (Aβ) and Tau proteins are the main components of Aβ plaques and neurofibrillary tangles in Alzheimer's disease (AD), and their abnormal aggregation is closely related to the pathogenesis of AD. The production of reactive oxygen species (ROS) and the aggregation of Aβ and Tau form a vicious circle, which leads to the aggravation of AD. However, inhibiting the aggregation of Aβ and Tau or scavenging ROS is not able to effectively reverse the progression of AD. Herein, we prepared a H2O2 responsive multifunctional nanocomposite UCNPs@mSiO2‐MB@AuNPs (abbreviated as USMA) to inhibit the aggregation of Aβ and Tau. In this system, USMA could respond to H2O2 to detach gold nanoparticles (AuNPs) and lead to the release of methylene blue (MB) from mesoporous silica (mSiO2), where AuNPs and MB can inhibit Aβ and Tau aggregation, respectively. Furthermore, USMA could consume H2O2 by reacting with them. Meanwhile, upconversion luminescence of UCNPs can be used to track USMA and monitor MB release, which could provide information on the content of MB in the lesion area. Importantly, the USMA can effectively reduce the cytotoxicity induced by Aβ and Tau aggregation. This work opens up a possibility to improve therapeutic efficacy for the treatment of AD.

Objectives The abnormal expression of immune-related genes (IRGs) plays an important role in the occurrence and progression of ovarian cancer (OC), which is the main cause of mortality among gynecological cancer patients. This study aims to establish a prognostic risk model and comprehensively analyze the relationship between OC risk score and prognosis, immune cell infiltration (ICI) and therapeutic sensitivity in OC. Methods We retrospectively evaluated the clinicopathological characteristics of consecutive OC patients in the Cancer Genome Atlas (TCGA) database. First, the prognostic risk model was constructed by bioinformatics methods. And then, we systematically assessed model robustness, and correlations between risk score and prognosis, and immune cell infiltration. The ICGC cohort was used to verify the prognostic risk model. Finally, we evaluated their value in the treatment of OC immunotherapy and chemotherapy. Results A total of 10 IRGs were identified to construct the prognostic risk model. Survival analysis revealed that patients in the low-risk group had a better prognosis ( P < .01), and the risk score might be considered an independent predictor for predicting the prognosis. In addition, risk scores and patient clinical information were used to construct clinical nomograms, improving the prediction’s precision. We also explored the relationship between the risk score and ICI, immunotherapy and drug sensitivity. Conclusions Collectively, we identified a novel ten IRGs signature that may be applied as a prognostic predictor of OC, thereby benefiting clinical decision-making and personalized treatment of patients.

The gastrointestinal tract contains a complex microbial community. Peyer’s patches (PPs) play an important role in inducing mucosal immune responses in the gastrointestinal tract. However, little is known about the effect of commensal microbiota on the host’s PPs. Here, we analyzed the phenotypic-to-transcriptome changes in the intestine PPs of specific pathogen-free (SPF) and germ-free (GF) piglets (fed in an environment with and without commensal microbiota, respectively) to elucidate the role of commensal microbiota in host intestine mucosal immunity. Analyses of anatomical and histological characteristics showed that commensal microbiota deficiency led to PP hypoplasia, especially regarding B and T cells. A total of 12,444 mRNAs were expressed in 12 libraries; 2,156 and 425 differentially expressed (DE) mRNAs were detected in the jejunal PP (JPP) and ileal PP (IPP), respectively (SPF vs. GF). The shared DE mRNAs of the JPP and IPP were mainly involved in basic physiological and metabolic processes, while the specific DE mRNAs were enriched in regulating immune cells in the JPP and microbial responses and cellular immunity in the IPP. Commensal microbiota significantly modulated the expression of genes related to B-cell functions, including activation, proliferation, differentiation, apoptosis, receptor signaling, germinal center formation, and IgA isotype class switching, particularly in the JPP. TLR4 pathway-related genes were induced in response to microbial colonization and in LPS/SCFA-treated B cells. We also detected 69 and 21 DE lncRNAs in the JPP and IPP, respectively, and four one-to-one lncRNA-mRNA pairs were identified. These findings might represent key regulatory axes for host intestine mucosal immunity development during microbial colonization. Overall, the findings of this study revealed that commensal microbiota modulated phenotypic characteristics and gene expression in the piglet intestine PPs and underscored the importance of early microbial colonization for host mucosal immunity development.

Glioblastoma multiforme (GBM) is a brain tumor with high mortality and recurrence rate. Radiotherapy and chemotherapy after surgery are the main treatment options available for GBM. However, patients with glioblastoma have a grave prognosis. The major reason is that most GBM patients are resistant to radiotherapy. UBA1 is considered an attractive potential anti-tumor therapeutic target and a key regulator of DNA double-strand break repair and genome replication in human cells. Therefore, we hypothesized that TAK-243, the first-in-class UBA1 inhibitor, might increase GBM sensitivity to radiation. The combined effect of TAK-243 and ionizing radiation on GBM cell proliferation, and colony formation ability was detected using CCK-8, colony formation, and EdU assays. The efficacy of TAK-243 combined with ionizing radiation for GBM was further evaluated in vivo, and the mechanism of TAK-243 sensitizing radiotherapy was preliminarily discussed. The results showed that TAK-243, in combination with ionizing radiation, significantly inhibited GBM cell proliferation, colony formation, cell cycle arrest in the G2/M phase, and increased the proportion of apoptosis. In addition, UBA1 inhibition by TAK-243 substantially increased the radiation-induced γ-H2AX expression and impaired the recruitment of the downstream effector molecule 53BP1. Therefore, TAK-243 inhibited the radiation-induced DNA double-strand break repair and thus inhibited the growth of GBM cells. Our results provided a new therapeutic strategy for improving the radiation sensitivity of GBM and laid a theoretical foundation and experimental basis for further clinical trials.

Background: Cigarette smoking is an important environmental risk factor for cardiovascular events of hypertension (HTN). Existing studies have provided evidence supporting altered gut microbiota by cigarette smoking, especially in hypertensive patients. Metabolic biomarkers play a central role in the functional potentials of the gut microbiome but are poorly characterized in hypertensive smokers. To explore whether serum metabolomics signatures and compositions of HTN patients were varied in smokers, and investigate their connecting relationship to gut microbiota, the serum metabolites were examined in untreated hypertensive patients using untargeted liquid chromatography-mass spectrometry (LC/MS) analysis.Results: A dramatic difference and clear separation in community features of circulating metabolomics members were seen in smoking HTN patients compared with the non-smoking controls, according to partial least squares discrimination analysis (PLS-DA) and orthogonal partial least squares discrimination analysis (OPLS-DA). Serum metabolic profiles and compositions of smoking patients with HTN were significantly distinct from the controls, and were characterized by enrichment of 12-HETE, 7-Ketodeoxycholic acid, Serotonin, N-Stearoyl tyrosine and Deoxycholic acid glycine conjugate, and the depletion of Tetradecanedioic acid, Hippuric acid, Glyceric acid, 20-Hydroxyeicosatetraenoic acid, Phenylpyruvic acid and Capric acid. Additionally, the metabolome displayed prominent functional signatures, with a majority proportion of the metabolites identified to be discriminating between groups distributed in Starch and sucrose metabolism, Caffeine metabolism, Pyruvate metabolism, Glycine, serine and threonine metabolism, and Phenylalanine metabolic pathways. Furthermore, the observation of alterations in metabolites associated with intestinal microbial taxonomy indicated that these metabolic members might mediate the effects of gut microbiome on the smoking host. Indeed, the metabolites specific to smoking HTNs were strongly organized into co-abundance networks, interacting with an array of clinical parameters, including uric acid (UA), low-denstiy lipoprotein cholesterol (LDLC) and smoking index.Conclusions: In conclusion, we demonstrated disparate circulating blood metabolome composition and functional potentials in hypertensive smokers, showing a linkage between specific metabolites in blood and the gut microbiome.

In our previous paper, we derived a new single bubble model including the effect of bulk viscosity. To confront it to experiments, single bubble dynamics was measured here in 30% (v/v) glycerol-water mixture under different acoustic amplitudes and compared to models including or not the effect of bulk viscosity. The results showed that calculated bubble dynamics were not significantly affected by the bulk viscosity within the experimental conditions used in this study. However, there was a noticeable delay for the first rebound when bulk viscosity was considered. The corresponding sonoluminescence intensities were collected and compared with theoretical predictions. The results did not allow to discriminate between the two models (one includes the effect of bulk viscosity, the other does not), confirming the negligible effect of bulk viscosity in this condition (30% (v/v) glycerol-water mixture). Due to the instability of a single bubble in higher viscosity solutions, we could not implement experiments that can discriminate between the two models.