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Titanium and titanium alloys are key basic support materials in the field of engineering technology and high technology, and are widely used in the fields of natural gas transportation, chemical corrosion, and marine development. Titanium alloy ingots are often prepared with more solidification defects such as surface cracks and cold shuts, resulting in lower utilization of titanium metal and higher cost of titanium products. The root of this is the lack of in-depth knowledge of the ingot melting and casting process, and the failure to control the thermal conditions of the billet in the molding process within a reasonable range. In this study, based on the Lagrange Euler algorithm, combined with ProCAST finite element software to establish a numerical model, revealing the solid–liquid interface morphology, the length of the transition region, and the change rule of thermal stress under the influence of different process parameters in the solidification process of titanium slab ingot. The results show that with the increase in pulling speed, the depth of the solid–liquid phase line and the width of the mushy zone of slab ingot increase, and the length of the transition region grows. With the increase in casting temperature, the depth of the solid–liquid phase line of the slab ingot decreases, and the mushy zone gradually becomes narrower. The casting temperature and pulling speed are positively correlated with the value of the thermal stress equivalent stress in slab ingots, and the probability of cracks in the corners and ingot surface is higher. This study provides effective theoretical guidance for the realization of stable mass production of high-quality titanium slab ingot.

MEMS resonant sensing devices require both HF ( f ) and low dissipation or high quality factor ( Q ) to ensure high sensitivity and high speed. In this study, we investigate the resonance properties and energy loss in the first three resonance modes, resulting in a significant increase in f‧Q product at higher orders. The third order resonance exhibits an approximately 15-fold increase in f‧Q product, while the Q factor remains nearly constant. Consequently, we achieved an ultrahigh f‧Q product exceeding 10 ^12 Hz by higher-order resonances in single-crystal diamond cantilevers.

The Closeby Habitable Exoplanet Survey (CHES) is dedicated to the astrometric exploration for habitable-zone Earth-like planets orbiting solar-type stars in close proximity, achieving unprecedented microarcsecond precision. Given the elevated precision, meticulous consideration of photocenter jitters induced by stellar activity becomes imperative. This study endeavors to model the stellar activity of solar-type stars, compute astrometric noise, and delineate the detection limits of habitable planets within the astrometric domain. Simulations were conducted for identified primary targets of CHES, involving the generation of simulated observed data for astrometry and photometry, accounting for the impact of stellar activity. Estimation of activity levels in our sample was achieved through chromospheric activity indices, revealing that over 90% of the stars exhibited photocenter jitters below 1 μ as. Notably, certain proximate stars, such as α Cen A and B, displayed more discernible noise arising from stellar activity. Subsequent tests were performed to evaluate detection performance, unveiling that stellar activity tends to have a less pronounced impact on planetary detectability for the majority of the stars. Approximately 95% of the targets demonstrated a detection efficiency exceeding 80%. However, for several cold stars, e.g., HD 32450 and HD 21531, with the habitable zones close to the stars, a reduction in detection efficiency was observed. These findings offer invaluable insights into the intricate interplay between stellar activity and astrometric precision, significantly advancing our understanding in the search for habitable planets.

Extensive studies have demonstrated the spatiotemporal changes in carbon use efficiency (CUE) and its driving factors over the past three decades. However, how the global CUE will change and to what extent the CUE is affected by the dominant factor in this century is still unclear. Herein, based on CMIP6 model outputs, we estimated the situation and change trends of CUE in baseline (1982–2014) and future (2015–2100), and identified the controlling factor of CUE variation by boosted regression tree. Further, we predicted the CUE-controlling factor sensitivity ( S _value , referring to higher/lower controlling factor producing more/less CUE) and its variation under four representative pathways, and revealed the relationship between S _value and social economy. Results showed decreased CUE at the end of the 21st century, especially in the SSP5-8.5, its decline rate of CUE is 1.2 × 10 ^−2 ± 5.2 × 10 ^−4 /decade, which is 10 times higher than that in the SSP1-2.6. Spatially, 56.9%, 74.5%, 83.1%, and 88.6% of the global land will exhibit a decreased CUE under the SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 scenarios, and primarily concentrates at the middle-high latitudes of the Northern Hemisphere (30°–60° N). Except in Africa, temperature is the controlling factor for CUE variation, and the S _value decreases over time, indicating an enhanced inhibitory effect of temperature on CUE. The turning time of S _value change will advance with increases in CO _2 emission, presenting prolonged high-temperature stress of vegetation ecosystem under high-emission scenarios. A threshold effect can be found between S _value change and precipitation, and the precipitation threshold is higher under the SSP5-8.5 scenario. The negative effect of temperature on CUE is attenuated by economic development and population control but this effect diminishes with rising CO _2 concentrations; in the future, developing clean energy and formulating population management policies can be used to enhance the carbon sink ability of the global ecosystem.

The extensive consumption of energy in manufacturing has led to a large amount of greenhouse gas emissions that have caused an enormous effect on the environment. Therefore, investigating how to reduce energy consumption in manufacturing is of great significance to cleaner production. This paper considers an energy-conscious unrelated parallel batch processing machine scheduling problem under time-of-use (TOU) electricity prices. Under TOU, electricity prices vary for different periods of a day. This problem is grouping jobs into batches, assigning the batches to machines and allocating time to the batches so as to minimize the total electricity cost. A mixed-integer linear programming model and two groups of heuristics are proposed to solve this problem. The first group of heuristics first forms batches, assigns the batches to machines and finally allocates time to the batches, while the second group of heuristics first assigns jobs to machines, batches the jobs on each machine and finally allocates time to each batch. The computational results show that the SPT-FBLPT-P1 heuristic in the second group can provide high-quality solutions for large-scaled instances in a short time, in which the jobs are assigned to the machines based on the shortest processing time rule, the jobs on each machine are batched following the full-batch longest processing time algorithm, and the time is allocated to each batch following an integer programming approach. The MDEC-FBLPT-P1 heuristic that uses the minimum difference of the power consumption algorithm to assign the jobs also performed well.

Significant progress has been made in the functions of auxin efflux transporter PIN-FORMED (PIN) genes for the regulation of growth and development in rice. However, knowledge on the roles of OsPIN genes in abiotic stresses is limited. We previously reported that the mutation of OsPIN1b alters rice architecture and root gravitropism, while the role of OsPIN1b in the regulation of rice abiotic stress adaptations is still largely elusive. In the present study, two homozygous ospin1b mutants (C1b-1 and C1b-2) were employed to investigate the roles of OsPIN1b in regulating abiotic stress adaptations. Low temperature gradually suppressed OsPIN1b expression, while osmotic stress treatment firstly induced and then inhibited OsPIN1b expression. Most OsPIN genes and auxin biosynthesis key genes OsYUC were up-regulated in ospin1b leaves, implying that auxin homeostasis is probably disturbed in ospin1b mutants. The loss of function of OsPIN1b significantly decreased rice chilling tolerance, which was evidenced by decreased survival rate, increased death cells and ion leakage under chilling conditions. Compared with the wild-type (WT), ospin1b mutants accumulated more hydrogen peroxide (H2O2) and less superoxide anion radicals (O2−) after chilling treatment, indicating that reactive oxygen species (ROS) homeostasis is disrupted in ospin1b mutants. Consistently, C-repeat binding factor (CBF)/dehydration-responsive element binding factor (DREB) genes were downregulated in ospin1b mutants, implying that OsDREB genes are implicated in OsPIN1b-mediated chilling impairment. Additionally, the mutation of OsPIN1b led to decreased sensitivity to abscisic acid (ABA) treatment in seed germination, impaired drought tolerance in the seedlings and changed expression of ABA-associated genes in rice roots. Taken together, our investigations revealed that OsPIN1b is implicated in chilling and drought tolerance in rice and provide new insight for improving abiotic stress tolerance in rice.

Abstract The increasing integration of distributed energy resources (DERs) to power grids has fostered the emergence of advanced control technologies for energy management. This study focuses on distributed solutions to economic dispatch considering asynchrony and non‐ideal communications. A distributed consensus‐based algorithm is developed for general directed networks, where heavy‐ball momentum is incorporated into the algorithm design to accelerate convergency. Subsequently, an asynchronous version is proposed based on a general asynchronous communication model with unpredictable, non‐uniform, and bounded time delays. Without a global clock in conventional synchronous distributed algorithms, distributed generators (DGs) are allowed to exchange information through local communications at any moment and use out‐sync information to execute new updates. Simulations are presented to demonstrate the performance of the proposed algorithm and verify its robustness against time delays.

Ma et al. profile the dynamic landscape of m6A during pancreatic differentiation, and identify ALKBH5 as an essential m6A regulator supporting pancreatic differentiation, indicating a role for m6A-mediated mRNA metabolism in cell-fate specification.

The dried ammonium polyvanadate (APV) can be used to produce high-purity Vanadium pentoxide (V2O5) by calcination. Therefore, drying is a necessary process. The advantages of microwave drying are uniform heating, selective heating, high heating efficiency and the operation process is clean and hygienic. This study uses a microwave to dry APV and discusses the effect of the initial mass, microwave power, initial moisture content on the drying efficiency of APV. The results display that the average drying rate is positively correlated with the microwave output power. When the initial mass is 35 g, the average rate is shown as 0.000263%/s. As the initial moisture content and power of APV increases to 25% and 560W, the average drying rate increases to 0.00036231%/s and 0.003125%/s, respectively. At the same time, through the analysis of APV drying kinetics and the fitting of experimental data, it is found that the APV microwave drying process can be precisely described by the Modified Page model. The microwave heating process saves energy and time, directly penetrates the product, and has certain advantages in green metallurgy.

Purpose of this paper is to prepare monodispersed plate-shaped silver particles with high density and low radius-thickness ratio through wet-chemical reduction. This shape is suitable for preparing high silver content conductive paste with fine electrical conductivity. In this study, the reactant solutions were added by two parallel pipes to mix the two solutions evenly in the contact area. The sulfuric acid was used as a pH regulator, and polyvinylpyrrolidone (PVP K-30) was used as a capping agent, to control the morphology and particle size distribution of silver particles. The result shows that the combination of sulfuric acid and PVP play an important role on controlling the uniform crystal growth of silver particle. This probably because PVP are adsorbed on the surface of (111) plane to prevent the deposition of silver particles, and the PVP used as dispersant also slow the speed of reducing reaction. This make the flake silver particles grow slowly, and the plate-shaped silver particles with high tap-density and low radius-thickness ratio can be obtained. In addition, the resistivity of conductive silver paste that prepared with the as-synthesized plate-shaped flake silver particle was discussed in detail.

To solve the problem of environmental pollution, Distiller's dried grains (DDGS), a biomass, is used as a clean reducing agent for the leaching process of pyrolusite. Experimental results have shown that the leaching rate of manganese can reach 92.1% with the optimized conditions including a sulfuric acid concentration of 3.5 mol/L, a DDGS to pyrolusite ratio of 0.4, a liquid–solid ratio of 3 mL/g, a temperature of 363K, a time of 3 h, and a rotation speed of 400 rpm. This article explored the mechanism of the entire leaching process: the crude fiber in DDGS is hydrolyzed into reducing sugars, and the MnO2 in pyrolusite undergoes an oxidation–reduction reaction to generate Mn2+ and studied the kinetics of the leaching process following the unreacted shrinkage nuclear reaction model controlled by the surface chemical reaction (1-(1-X)1/3 = kt). The equation of leaching kinetics is 1−1−X13=3738.06·[H2SO4]0.57·[LS]0.78·[DDGSpyrolusite]0.25·[rpm]0.09·exp(−48.448/(RT)) This work provides a green and effective leaching process for the leaching of pyrolusite.

Graph neural networks (GNNs) have developed rapidly in recent years because they can work over non-Euclidean data and possess promising prediction power in many real-word applications. The graph classification problem is one of the central problems in graph neural networks, and aims to predict the label of a graph with the help of training graph neural networks over graph-structural datasets. The graph pooling scheme is an important part of graph neural networks for the graph classification objective. Previous works typically focus on using the graph pooling scheme in a linear manner. In this paper, we propose the real quadratic-form-based graph pooling framework for graph neural networks in graph classification. The quadratic form can capture a pairwise relationship, which brings a stronger expressive power than existing linear forms. Experiments on benchmarks verify the effectiveness of the proposed graph pooling scheme based on the quadratic form in graph classification tasks.

BackgroundCutaneous melanoma (CM) is one of the malignant tumors with a relative high lethality. Necroptosis is a novel programmed cell death that participates in anti-tumor immunity and tumor prognosis. Necroptosis has been found to play an important role in tumors like CM. However, the necroptosis-associated lncRNAs’ potential prognostic value in CM has not been identified.MethodsThe RNA sequencing data collected from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) was utilized to identify differentially expressed genes in CM. By using the univariate Cox regression analysis and machine learning LASSO algorithm, a prognostic risk model had been built depending on 5 necroptosis-associated lncRNAs and was verified by internal validation. The performance of this prognostic model was assessed by the receiver operating characteristic curves. A nomogram was constructed and verified by calibration. Furthermore, we also performed sub-group K-M analysis to explore the 5 lncRNAs’ expression in different clinical stages. Function enrichment had been analyzed by GSEA and ssGSEA. In addition, qRT-PCR was performed to verify the five lncRNAs’ expression level in CM cell line (A2058 and A375) and normal keratinocyte cell line (HaCaT).ResultsWe constructed a prognostic model based on five necroptosis-associated lncRNAs (AC245041.1, LINC00665, AC018553.1, LINC01871, and AC107464.3) and divided patients into high-risk group and low-risk group depending on risk scores. A predictive nomogram had been built to be a prognostic indicator to clinical factors. Functional enrichment analysis showed that immune functions had more relationship and immune checkpoints were more activated in low-risk group than that in high-risk group. Thus, the low-risk group would have a more sensitive response to immunotherapy.ConclusionThis risk score signature could be used to divide CM patients into low- and high-risk groups, and facilitate treatment strategy decision making that immunotherapy is more suitable for those in low-risk group, providing a new sight for CM prognostic evaluation.

The properties of cg-N with point defects and an interface are investigated based on the first-principles method. Our results show that at 0 GPa, the stability of cavities depends on their size. A smaller cavity has higher stability than the larger case. The decomposition of N2 molecules mainly occurs on the (110) surface of the cavity. However, the decomposition process will be suppressed by applying high-pressure. For the interface constructed by (110) surfaces, N2 molecules will be released at low pressure, and polymerization of N2 molecules with surfaces is triggered by loading pressures of 80–100 Gpa, giving rise to a stable polymerized interface, which is also stable after decreasing the pressure to 0 GPa. The results indicate that the existence of polymeric nitrogen networks can enhance the polymerization of N2 molecules at low-temperature.

Introduction A patient record review study conducted in 2006 in a random sample of 21 Dutch hospitals found that 51%–77% of adverse events are related to perioperative care, while Centers for Disease Control and Prevention data in USA in 2013 estimated that the medical error is the third-leading cause of mortality. To capitalise on the potential of apps to enhance perioperative medical quality, there is a need for interventions developed in consultation with real-world users designed to support integrated management for perioperative adverse events (PAEs). This study aims: (1) to access the knowledge, attitude and practices for PAEs among physicians, nurses and administrators, and to identify the needs of healthcare providers for a mobile-based PAEs tool; (2) to develop a data-driven app for integrated PAE management that meets those needs and (3) to test the usability, clinical efficacy and cost-effectiveness of the developed app.Methods and analysis We will adopt an embedded mixed-methods research technique; qualitative data will be used to assess user needs and app adoption, while quantitative data will provide crucial insights to establish the demand for the app, and measure the app effects. Phase 1 will enrol surgery-related healthcare providers from the West China Hospital and identify their latent demand for mobile-based PAEs management using a self-designed questionnaire underpinned by the knowledge, attitude and practice model, as well as expert interviews. In phase 2, we will develop the app for integrated PAE management and test its effectiveness and sustainability. In phase 3, the effects on the total number and severity of reported PAEs will be evaluated using Poisson regression with interrupted time-series analysis over a 2-year period, while users’ engagement, adherence, process evaluation and cost-effectiveness will be evaluated using quarterly surveys and interviews.Ethics and dissemination The West China Hospital of Sichuan University’s Institutional Review Board authorised this study after approving the study protocol, permission forms and questionnaires (number: 2022-1364). Participants will be provided with study information, and informed written consent will be obtained. Study findings will be disseminated through peer-reviewed publications and conference presentations.

Influences of Glycyrrhetinic acid on expression of inflammatory factors in interleukin (IL)-1β-induced SW982 cells and its anti-inflammatory effects were discussed in this study. MTT results showed that Glycyrrhetinic acid (≤80 μmol·L−1) almost has no toxicity on SW982 cells. The results of ELISA and real-time PCR showed that Glycyrrhetinic acid (10, 20 and 40 μmol · L-1) can significantly inhibit the expression of inflammatory factors such as IL-6, IL-8 and matrix metalloproteinase-1 (MMP-1). Western blot analysis showed that Glycyrrhetinic acid remarkably blocked the NF-κB signaling pathway in vitro. Molecule docking showed that Glycyrrhetinic acid could bind to the active site (NLS Polypeptide) of NF-κB p65. Furthermore, observation of rat foot swelling proved that Glycyrrhetinic acid had a significant therapeutic effect on adjuvant-induced arthritis (AIA) in rats in vivo. Collectively, all these findings suggested that Glycyrrhetinic acid might be a promising lead compound worthy of further pursuit as anti-inflammation agent.

Abstract Background Neuroblastoma (NB) is the most common extracranial malignancy in childhood; however, the mechanisms underlying its aggressive characteristics still remain elusive. Methods Integrative data analysis was performed to reveal tumour‐driving transcriptional regulators. Co‐immunoprecipitation and mass spectrometry assays were applied for protein interaction studies. Real‐time reverse transcription‐polymerase chain reaction, western blotting, sequential chromatin immunoprecipitation and dual‐luciferase reporter assays were carried out to explore gene expression regulation. The biological characteristics of NB cell lines were examined via gain‐ and loss‐of‐function assays. For survival analysis, the Cox regression model and log‐rank tests were used. Results Cellular nucleic acid‐binding protein (CNBP) was found to be an independent factor affecting NB outcome, which exerted oncogenic roles in ribosome biogenesis, tumourigenesis and aggressiveness. Mechanistically, karyopherin subunit beta 1 (KPNB1) was responsible for nuclear transport of CNBP, whereas liquid condensates of CNBP repressed the activity of switch/sucrose‐nonfermentable (SWI/SNF) core subunits (SMARCC2/SMARCC1/SMARCA4) via interaction with SMARCC2, leading to alternatively increased activity of SMARCC1/SMARCA4 binary complex in facilitating gene expression essential for 18S ribosomal RNA (rRNA) processing in tumour cells, extracellular vesicle‐mediated delivery of 18S rRNA and subsequent M2 macrophage polarisation. A cell‐penetrating peptide blocking phase separation and interaction of CNBP with SMARCC2 inhibited ribosome biogenesis and NB progression. High KPNB1, CNBP, SMARCC1 or SMARCA4 expression or low SMARCC2 levels were associated with poor survival of NB patients. Conclusions These findings suggest that CNBP phase separation is a target for inhibiting ribosome biogenesis and tumour progression in NB via modulating SWI/SNF complex activity.

Keloid is a pathological scar formed by abnormal wound healing, characterized by the persistence of local inflammation and excessive collagen deposition, where the intensity of inflammation is positively correlated with the size of the scar formation. The pathophysiological mechanisms underlying keloid formation are unclear, and keloid remains a therapeutic challenge in clinical practice. This study is the first to investigate the role of glycosphingolipid (GSL) metabolism pathway in the development of keloid. Single cell sequencing and microarray data were applied to systematically analyze and screen the glycosphingolipid metabolism related genes using differential gene analysis and machine learning algorithms (random forest and support vector machine), and a set of genes, including ARSA,GBA2,SUMF2,GLTP,GALC and HEXB, were finally identified, for which keloid diagnostic model was constructed and immune infiltration profiles were analyzed, demonstrating that this set of genes could serve as a new therapeutic target for keloid. Further unsupervised clustering was performed by using expression profiles of glycosphingolipid metabolism genes to discover keloid subgroups, immune cells, inflammatory factor differences and the main pathways of enrichment between different subgroups were calculated. The single-cell resolution transcriptome landscape concentrated on fibroblasts. By calculating the activity of the GSL metabolism pathway for each fibroblast, we investigated the activity changes of GSL metabolism pathway in fibroblasts using pseudotime trajectory analysis and found that the increased activity of the GSL metabolism pathway was associated with fibroblast differentiation. Subsequent analysis of the cellular communication network revealed the existence of a fibroblast-centered communication regulatory network in keloids and that the activity of the GSL metabolism pathway in fibroblasts has an impact on cellular communication. This contributes to the further understanding of the pathogenesis of keloids. Overall, we provide new insights into the pathophysiological mechanisms of keloids, and our results may provide new ideas for the diagnosis and treatment of keloids.

The blood-brain barrier (BBB) is an important barrier separating the central nervous system from the periphery. The composition includes endothelial cells, pericytes, astrocytes, synapses and tight junction proteins. During the perioperative period, anesthesia and surgical operations are also a kind of stress to the body, which may be accompanied by blood-brain barrier damage and brain metabolism dysfunction. Perioperative blood-brain barrier destruction is closely associated with cognitive impairment and may increase the risk of postoperative mortality, which is not conducive to enhanced recovery after surgery. However, the potential pathophysiological process and specific mechanism of blood-brain barrier damage during the perioperative period have not been fully elucidated. Changes in blood-brain barrier permeability, inflammation and neuroinflammation, oxidative stress, ferroptosis, and intestinal dysbiosis may be involved in blood-brain barrier damage. We aim to review the research progress of perioperative blood-brain barrier damage and its potential adverse effects and potential molecular mechanisms, and provide ideas for the study of homeostasis maintenance of brain function and precision anesthesia.

Large-scale implementation of the Grain for Green Project since 1999, which took the Yellow River Basin (YRB) as the core ecological restoration area, has had an important impact on the hydrological processes and ecological environment. Whether such forest restoration construction is conducive to achieving land degradation neutrality as well as improving water conservation capacity has become a hot research topic. The Yiluo River basin (YLRB), one of the most important water conservation areas in the YRB, was selected as the study area. Firstly, the transfer matrix was used to analyze the changes in the two land use maps in 1990 and 2015 and to determine the transformation relationship between different land use types. Furthermore, land degradation was also investigated for further exploration of the correlation between land degradation neutrality and water conservation. The effects of land use and cover changes (LUCC) on the water conservation capacity across the YLRB were investigated by combining the Soil and Water Assessment Tool (SWAT) model, water conservation assessment method and land use change scenarios method. The results showed that the land degradation area was mainly located in the residential area and agricultural land in the downstream of the YLRB, and the execution of the Grain for Green Project is beneficial in promoting land degradation neutrality and increasing the water conservation capacity. The water conservation capacity across the YLRB approximately increased by 19.30 mm yr−1 as every 10% of agricultural land converted to forest, showing a greater increase in the upstream than that in the downstream. Rainfall, Normalized Difference Vegetation Index (NDVI), and temperature were the primary factors affecting water conservation in the YLRB, while geological lithology also affects the spatial distribution of water conservation. The findings of this study could provide a theoretical basis for water resources and ecological environment protection.

The effect of local atmospheric conditions on aquatic photochemical reactions has been rarely explored because of the difficulty in field observation. Thus, this study aimed to elucidate the effects of atmospheric conditions, which are inorganic air pollution, aerosol pollution, and ozone layer depletion, on the incident light and photo-production of reactive intermediates (RIs). Models of SMARTS (Simple Model for the Atmospheric Radiative Transfer of Sunshine) and APEX (Aqueous Photochemistry of Environmentally occurring Xenobiotics) were used to simulate the changes in wavelength profile and steady-state concentrations of RIs, which are hydroxyl radical, carbonate radical, singlet oxygen, and triplet-state of dissolved organic matter. Results showed that inorganic air pollution and aerosol pollution have a reduction effect on the production of RIs, while ozone layer depletion increases the production of RIs. Among them, inorganic air pollution has the largest influence on the production of RIs which were expected to reduce by 80%–90% in extreme pollution. This study also investigated the potential effect of water constituents (i.e., NO3−, dissolved organic matter, and HCO3−) on the relation between atmospheric conditions and the production of RIs. NO3− concentration under different atmospheric conditions showed the most influence on the production of RIs. This study highlighted the importance of considering atmospheric conditions when assessing the photochemical persistence of organic pollutants. Even though these results are model output, they quantitatively revealed the potential influence of atmospheric conditions on the production of RIs in freshwater systems.

ObjectivesThis retrospective study aimed to describe our institutional experience with cytoreductive cystectomy (Cx) in patients with pathological T4 (pT4) bladder cancer (BCa) and to investigate the clinicopathologic factors that can predict patient survival outcomes.MethodsWe reviewed the baseline demographics, clinicopathologic features, perioperative complications, and follow-up data of 44 patients who underwent Cx for pT4 BCa at our institution between 2013 and 2021. The Kaplan–Meier curve and the log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analyses were performed using the Cox regression model.ResultsThe median age of the patients was 68 years [95% confidence interval (CI) 49–81]. Overall, 21 patients (47.7%) were estimated to have a high age-adjusted Charlson comorbidity index (ACCI) score (>4), and nine patients (20.5%) had pT4b substage BCa. None of the patients died of complications within 30–90 days after surgery. Severe complications occurred in 16% (n = 7) of patients within 30–90 days. During a median follow-up of 51 months, disease progression was detected in 25 patients (56.8%), and 29 patients (65.9%) died of any cause. The median PFS and OS were 15.0 and 21.0 months, respectively. The Kaplan–Meier analysis indicated that patients with high ACCI scores or pT4b BCa had worse PFS (P = 0.003 and P = 0.002, respectively) and OS (P = 0.016 and P = 0.034, respectively) than those with low ACCI scores or pT4a BCa. On multivariate analysis, pT4b substage [hazard ratio (HR), 4.166; 95% CI, 1.549–11.206; P = 0.005] and ACCI score >4 (HR, 2.329; 95% CI, 1.105–4.908; P = 0.026) remained independent risk factors for PFS and OS, respectively.ConclusionOur study revealed that the pT4b substage is associated with a poor prognosis and that the ACCI score is a relevant and practical method to evaluate survival outcomes in patients with pT4 BCa after Cx.

There are large-scale thermal utilization needs in rural and urban fringes in China that can provide many employment opportunities. However, due to the limited use of small and medium-sized coal-fired boilers, thermal energy is actually in short supply. If embedding these spaces including plantations with solar heliostat fields, a large number of nodes for cheap thermal energy supply can be obtained through solar energy, which can create more small-scale industrial and commercial employment opportunities near user side. However, to ensure the crop harvest, plantations are often prohibited from being used for other purposes. In order to verify the idea of coexistence between tower concentrating solar system with sparse heliostat field and plantation, the clean-sky model was used to analyze the shading rate of the heliostat to the ground in each month and the proportion of the area with a relative sunshine duration of less than 80% for the heliostat fields at low, middle, and high latitude areas, and further gave the correction of the above analysis results using typical meteorological year conditions. The results show that heliostats in mid latitude area have obvious adverse effects on overwintering crops. In high latitude area, although the heliostats are more severely blocked in the cold season, there is no planting activity in this season, so the impact on planting can be ignored. The shade ratio of the heliostats to the ground in low, middle and high latitude regions is tolerable in the months suitable for planting, and shade-tolerant crops can also be interplanted in the shaded area to enrich the variety structure. Therefore, by embedding the tower concentrating solar system with a sparse heliostat field, the plantation can meet the two functions of planting and thermal energy supply at the same time to further increase its income.

Abstract Ferroptosis is a regulated iron-dependent cell death characterized by the accumulation of lipid peroxidation. A myriad of facets linking amino acid, lipid, redox, and iron metabolisms were found to drive or to suppress the execution of ferroptosis. However, how the cells decipher the diverse pro-ferroptotic stress to activate ferroptosis remains elusive. Here, we report that protein O-GlcNAcylation, the primary nutrient sensor of glucose flux, orchestrates both ferritinophagy and mitophagy for ferroptosis. Following the treatment of ferroptosis stimuli such as RSL3, a commonly used ferroptosis inducer, there exists a biphasic change of protein O-GlcNAcylation to modulate ferroptosis. Pharmacological or genetic inhibition of O-GlcNAcylation promoted ferritinophagy, resulting in the accumulation of labile iron towards mitochondria. Inhibition of O-GlcNAcylation resulted in mitochondria fragmentation and enhanced mitophagy, providing an additional source of labile iron and rendering the cell more sensitive to ferroptosis. Mechanistically, we found that de-O-GlcNAcylation of the ferritin heavy chain at S179 promoted its interaction with NCOA4, the ferritinophagy receptor, thereby accumulating labile iron for ferroptosis. Our findings reveal a previously uncharacterized link of dynamic O-GlcNAcylation with iron metabolism and decision-making for ferroptosis, thus offering potential therapeutic intervention for fighting disease.

Abstract Interstitial cystitis (IC) is a severely debilitating and chronic disorder with unclear etiology and pathophysiology, which makes the diagnosis difficult and treatment challenging. To investigate the role of immunity in IC bladders, we sequenced 135,091 CD45+ immune cells from 15 female patients with IC and 9 controls with stress urinary incontinence using single-cell RNA sequencing (scRNA-seq). 22 immune subpopulations were identified in the constructed landscape. Among them, M2-like macrophages, inflammatory CD14+ macrophages, and conventional dendritic cells had the most communications with other immune cells. Then, a significant increase of central memory CD4+ T cells, regulatory T cells, GZMK+CD8+ T cells, activated B cells, un-switched memory B cells, and neutrophils, and a significant decrease of CD8+ effector T cells, Th17 cells, follicular helper T cells, switched memory B cells, transitional B cells, and macrophages were noted in IC bladders. The enrichment analysis identified a virus-related response during the dynamic change of cell proportion, furthermore, the human polyomavirus-2 was detected with a positive rate of 95% in urine of patients with IC. By integrating the results of scRNA-seq with spatial transcriptomics, we found nearly all immune subpopulations were enriched in the urothelial region or located close to fibroblasts in IC bladders, but they were discovered around urothelium and smooth muscle cells in control bladders. These findings depict the immune landscape for IC and might provide valuable insights into the pathophysiology of IC.

Abstract Background Fracture nonunion/delayed union seriously affects physical and mental health and quality of life. The aim of this study was to evaluate the relative efficacy of different adjuvant treatments for nonunion/delayed union by network meta-analysis. Methods A comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating adjuvant treatment in the management of nonunion/delayed union. A network meta-analysis reporting on healing rate, healing time, and adverse effect (AE) outcomes was conducted to assess and compare different interventions. Results Thirty studies were included in the analysis. For the healing rate outcome, bone marrow aspirate (BMA) + autologous cancellous bone (ACB) was found to be significantly better than ACB alone (odds ratio: 0.12; 95% confidence interval: 0.03, 0.59). In the ranking results, BMA+ platelet-rich plasma (PRP) (96%), BMA + ACB (90%), and BMA alone (82%) showed relative advantages in the healing rate. Low-intensity pulsed ultrasonography (LIUS) intervention significantly shortened the healing time compared with ACB (SMD: -9.26; 95% CI: − 14.64, − 3.87). LIUS (100%), BMA + PRP (74%), and bone morphogenetic proteins (BMPs) (69%) have relative advantages. Compared with the control, electromagnetic field (EMF) (OR: 13.21; 95% CI: 1.58, 110.40) and extracorporeal shock wave (ESWT) (OR: 4.90; 95% CI: 1.38, 17.43) had a higher AE risk. Conclusions Among the current intervention strategies, BMA in combination with PRP and ACB can improve the healing rate of nonunion/delayed union. LIUS can significantly shorten the healing time. EMF and ESWT may have a high risk of AE. However, large-scale, well-designed studies are still needed to confirm the results. Trial registration Retrospectively registered.

As consumers’ demands for mobile services have become more abundant and diversified, the architecture and functions of mobile network have become more complex.With the development of 5G technology, 5G mobile network could realize on-demand orchestration and flexible exposure of network capabilities, which made higher requirements for network lifecycle management.Digital twins technology could be used to assist the network lifecycle management, so as to improve the network management quality, reduce network risks and costs, and achieve the visual perception and the real-time closed-loop control.The network digital twin platform and application cases show that the proposed network digital twins platform can realize visual monitoring and analysis of mobile network operation key performance indicators and quickly diagnosis of network faults.

Abstract Background Tumour angiogenesis is an independent risk factor for bladder urothelial carcinoma (BUC) progression, but viable and promising antiangiogenic targets are understudied. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play prominent role in the tumour microenvironment and tumour angiogenesis. Methods The clinical data of BUC patients were obtained from TCGA database and clinical specimens of 138 BUC patients. Univariate and multivariate COX regression analyses were used to identify survival-related ARLNRs (sARLNRs) from The Molecular Signatures Database v4.0. Fisher’s exact probability method was used to detect the correlations between sARLNRs levels and clinicopathological characteristics. A chain of experiments including FACS, qPCR, immunohistochemistry, tube formation, migration and invasion assays, combining with co-culture models, were utilized to validate the clinical significance and angiogenetic correlation of sARLNRs. Results Five sARLNRs were employed to establish an angiogenesis-related risk score model, by which patients in the low-risk group obtained better overall survival than those in the high-risk group. The expression of AC005625.1 and AC008760.1 was significantly related to ECs percentage, tumour size and muscle invasion status. Besides, AC005625.1 and AC008760.1 expressed lower in BUC cell lines and tumour tissues than that in normal urothelial cells and adjacent normal tissues, with much lower levels in more advanced T stages. A prominently higher proportion of ECs was detected in tumour tissues with lower expression of AC005625.1 and AC008760.1. In the co-culture models, we found that knockdown of AC005625.1 and AC008760.1 in BUC cells increased the tube formation, migration and invasion abilities of HUVEC. The expression levels of CD31, VEGF-A, VIMENTIN and N-CADHERIN were also enhanced in HUVEC cells co-cultured with siR-AC005625.1 and siR-AC008760.1-treated T24 cells. Conclusion In the study, we identify five sARLNRs and validate their clinical significance, angiogenesis correlation and prognosis-predictive values in BUC. These findings may provide a new perspective and some promising antiangiogenic targets for clinical diagnosis and treatment strategies of BUC.

To address the problem of low fault diagnosis accuracy caused by insufficient fault samples of rolling bearings, a dual-input deep anomaly detection method with zero fault samples is proposed for early fault warning of rolling bearings. First, the main framework of dual-input feature extraction based on a convolutional neural network (CNN) is established, and the two outputs of the main frame are subjected to the autoencoder structure. Then, the secondary feature extraction is performed. At the same time, the experience pool structure is introduced to improve the feature learning ability of the network. A new objective loss function is also proposed to learn the network parameters. Then, the vibration acceleration signal is preprocessed by wavelet to obtain multiple signals in different frequency bands, and the two signals in the high-frequency band are two-dimensionally encoded and used as the network input. Finally, the unsupervised learning of the model is completed on five sets of actual full-life rolling bearing fault data sets relying only on some samples in a normal state. The verification results show that the proposed method can realize earlier than the RMS, Kurtosis, and other features. The early fault warning and the accuracy rate of more than 98% show that the method is highly capable of early fault warning and anomaly detection.

Since the 21st century, the term "scene" has been widely used in various fields, mainly involving sociology, communication, education, the Internet, commercial marketing and so on. Academic circles have also carried out scene-related research to form their own definitions and theories. With the continuous innovation of technical means, the connotation of a scene is constantly enriched, from the face-to-face physical space dimension to the multi-dimensional information space, and gradually evolved into the scene characteristics of spatio-temporal integration. However, there is still a lack of complete theoretical research and practical discussion on what is the scene, what are the elements of the scene, and how to combine the specific scene to guide and carry out the scene planning and design in different fields. The existing scene theory cannot be well applied in the field of urban development, and cannot help the scene related research of coordinated development of urban agglomeration. By combing the development context of scene theory at home and abroad, this study makes an in-depth interpretation and analysis of the connotation and characteristics of the scene. It is believed that the scene contains six characteristic elements, such as time, space, object, problem, path and value. The scene is a kind of specific interactive relationship formed by a series of actions, based on the key issues and objectives of the events under specific spatio-temporal conditions, with technology and resources as the media. The construction of the scene can meet the needs of stakeholders and create and realize value. The theoretical system of scene planning including scene elements, scene hierarchy characteristics and scene planning methods is constructed. It is considered that scene planning is a systematic process to realize specific social, economic or ecological functions and values by integrating existing resources and technologies to carry out scene construction and design, focusing on key issues and objectives with stakeholders as its center, under the environmental factors of social and economic development, government policies and technological innovation. From the perspectives of scene recognition, scene construction, scene evaluation and scene application, the new exploration of scene planning tools is realized to guide scene practice in different fields. Taking the coordinated development of urban agglomeration in the Guangdong-Hong Kong-Macao Greater Bay Area as an example, this study excavates the current problems and development objectives of the Greater Bay Area based on the scene planning method, identifies 100 important scene units representing the coordinated development direction of urban agglomeration in the Greater Bay Area, and identifies and analyzes each scene element for these scene units, so as to provide basic support for further scene construction. Finally, taking the ecological corridor construction of urban agglomeration in the Guangdong-Hong Kong-Macao Greater Bay Area as an application example, the scene planning method is preliminarily applied to analyze the scene elements, so as to provide a basis for the next practical exploration work such as scene evaluation and scene application demonstration. The theoretical system of scene planning is not only a further extension of the scene concept, but also an overall coordination tool to promote the coordinated development of urban agglomeration. It can provide theoretical basis and practical guidance for the future scene research on the coordinated development of urban agglomeration, and help the collaborative construction of urban agglomeration. In the future, it is suggested to carry out specific scene analysis and scene design on the industry, population, transportation, environment, infrastructure and public services of the GBA urban agglomeration, and gradually realize the in-depth exploration of the coordinated development theory and mechanism innovation of the Guangdong-Hong Kong-Macao Greater Bay Area through the scene planning theory.

Abstract Background Non-Invasive Continuous Arterial Pressure system (NICAP) allows continuous monitoring, timely detection of hypotension, and avoiding risks from invasive procedures. A previous study showed good comparability of NICAP with arterial line in people with no evidence of cardiovascular disease. Therefore, the goal of this study was to investigate whether NICAP could be accurately applied to elderly patients. Methods In this single-centered observational study, forty-one patients above 65 undergoing elective surgeries requiring artery catheterizations were enrolled from July 17, 2020, to June 25, 2021. Radial artery cannulation and NICAP monitoring were started before anesthesia. Blood pressure during the anesthesia induction and the whole surgery, trend of blood pressure changes, time needed for establishing continuous monitoring, and complications were recorded. Results A total of 6751 valid pairs of blood pressure measurements were analyzed. In the Bland-Altman analysis, the arithmetic means for systolic, diastolic, and mean arterial pressure were 2.2, 3.3, and 2.8 mmHg, respectively. NICAP and arterial line correlation coefficients for systolic, diastolic, and mean arterial pressure were 0.49, 0.33, and 0.45, respectively. In the trending analysis, the polar concordance rates at 30 degrees were 70.9% for systolic, 67.7% for diastolic, and 69.3% for mean arterial blood pressure. During the anesthesia induction, the arithmetic means for systolic, diastolic, and mean arterial pressure in the Bland-Altman analysis were 1.7, -0.2, and 0.5 mmHg, respectively. NICAP and arterial line correlation coefficients for systolic, diastolic, and mean arterial pressure were 0.78, 0.61 and 0.75, respectively. No severe complications occurred. Conclusions NICAP has a poor correlation with the arterial line in elderly patients for the whole surgery or during anesthesia induction. Moreover, it showed poor comparability in the detection of blood pressure change trends with arterial lines. Our findings suggest that NICAP might not be sufficiently accurate to be applied clinically in elderly patients with comorbidities. More accurate calibration and iteration are needed.

Graph Neural Networks (GNNs) have been intensively studied in recent years because of their promising performance over graph-structural data and have provided assistance in many fields. Recalling recent works on graph neural networks, we found that imposing graph smoothing via Frobenius norm was proven to be effective in the architecture of graph neural networks from the standpoint of the graph signal processing. In this paper, we aim to model the graph smoothness of graph neural networks using a Schatten $p$ -norm with $p$ in the interval $[1,2$ ) to characterize smoothness and propose a novel architecture called Schatten graph neural networks. This architecture stems from a primal-dual solution scheme for a graph signal denoising problem. There is difficulty in solving subproblems with respect to the Schatten $p$ -norm. We propose a fixed point iteration scheme and prove that it tracks with the linear convergence rate with solid mathematical analysis. Extensive experiments demonstrate the effectiveness of the proposed architecture of graph neural networks and their robustness to the graph adversarial attacks.

Introduction Awake tracheal intubation (ATI) involves placing a tracheal tube in an awake, spontaneously breathing patient. Superior laryngeal nerve block (SLNB) can effectively abolish the glottic closure reflex, and blunt the sensation of the structures above the cords. A method that consists of SLNB along with translaryngeal injection (TLI) can provide satisfactory anaesthesia and intubating conditions. We present a novel modified access of SLNB, ultrasound (US)-guided anterior SLNB, to aid awake videolaryngoscopes-assisted endotracheal intubation in adult elective surgery patients, and we compare the effectiveness and safety to traditional US-guided posterior SLNB.Methods and analysis A total of 100 adult elective surgery patients requiring general endotracheal anaesthesia will be randomly assigned to the modified group (modified US-guided anterior SLNB) or the traditional group (traditional US-guided posterior SLNB). After SLNB, all participants will be performed with TLI. The primary outcome is the proportion of acceptable intubation conditions based on intubation scores. Secondary outcomes include: (a) the first-attempt intubation success rate, (b) haemodynamic changes during ATI, (c) time taken for airway anaesthesia and intubation, (d) recall of intubation, (e) participant perception of comfort during intubation, (f) perioperative complication rate. This report describes the study design of this randomised controlled trial.Ethics and dissemination The study protocol has been approved by an ethical committee of the West China Hospital (Sichuan University), and registered at the Chinese Clinical Trials Register (www.chictr.org.cn). Results will be published in a peer-reviewed journal.Trial registration number ChiCTR2200058086.

BackgroundThe evidence for the effectiveness of acupuncture for patients with carpal tunnel syndrome (CTS) is insufficient. Therefore, this systematic review and meta-analysis aimed to evaluate the effectiveness of acupuncture on CTS through a comprehensive literature search.MethodsEnglish and Chinese databases were searched from their inceptions until 27 October 2022 to collect randomized controlled trials (RCTs) that investigated the effect of acupuncture on CTS. Two reviewers independently selected studies that met the eligibility criteria, extracted the required data, assessed the risk of bias using version 2 of the Cochrane risk-of-bias tool for randomized trials (ROB 2), and evaluated the quality of reporting for acupuncture interventions using the Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). The primary outcomes were symptom severity and functional status, while secondary outcomes included pain intensity, responder rate, and electrophysiological parameters. Review Manager software (version 5.4.1) was used for data analysis. The certainty of the evidence was rated with GRADEpro (version 3.6) software.ResultsWe included 16 RCTs with a total of 1,025 subjects. The overall risk of bias was rated as low in one RCT, some concerns in 14, and high in one. Compared with night splints, acupuncture alone was more effective in relieving pain, but there were no differences in symptom severity and functional status. Acupuncture alone had no advantage over medicine in improving symptom severity and electrophysiological parameters. As an adjunctive treatment, acupuncture might benefit CTS in terms of symptom severity, functional status, pain intensity, and electrophysiological parameters, and it was superior to medicine in improving the above outcomes. Few acupuncture-related adverse events were reported. The above evidence had a low or very low degree of certainty.ConclusionAcupuncture as an adjunctive treatment may be effective for patients with CTS. Additionally, more rigorous studies with objective outcomes are needed to investigate the effect of acupuncture in contrast with sham acupuncture or other active treatments.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=329925, identifier CRD42022329925.

Objective This study was performed to evaluate the outcomes of 25-gauge (25-G) pars plana vitrectomy (PPV) with air tamponade for primary rhegmatogenous retinal detachment (RRD). Methods This retrospective consecutive case series included 126 eyes of 125 patients with primary RRD who underwent 25-G PPV with air tamponade. The patients were followed up for at least 6 months following surgery. The main outcome measures were the primary and final anatomical success rates and postoperative complications. Results The mean age of the 125 patients (80 men and 45 women) was 53.7 ± 10.0 years. The mean follow-up period was 8.3 ± 2.2 months (range, 6–18 months). Twenty-four eyes (19.0%) presented with high myopia, and 13 eyes (10.3%) were pseudophakic. Of the 126 eyes, 37 (29.4%) had inferior breaks, 2 (1.6%) had choroidal detachment, and 86 (68.3%) had macular detachment. The single- and final-operation success rates were 96.0% and 100%, respectively. Postoperative complications included macular hole formation in two eyes. During follow-up, secondary cataract surgery was performed in 27 (23.9%) of the 113 phakic eyes. Conclusion 25-G PPV with air tamponade is effective and safe in treating selected patients with primary RRD with a high anatomical success rate.

Previous studies have demonstrated that REBACIN® intervention eliminates persistent high-risk human papillomavirus (hrHPV) infection. The initial establishment and subsequent progression of cervical cancer mainly depends on two major oncogenes, E6/E7, and previous studies have proposed E6/E7 oncogenes as a target for therapeutic drug development. The aim of this study was to investigate in vitro and in vivo whether REBACIN® inhibits E6/E7 oncogenes for elucidating the mechanism of REBACIN® in the clearance of persistent hrHPV infection. In vitro, after REBACIN® treatment, the growth of both Ca Ski and HeLa cervical cancer cells containing the E6/E7 oncogenes was prevented. In line with this finding is that E6/E7 expression was inhibited, which can be counteracted by the co-application of anti-REBACIN® antibody. These studies demonstrated that REBACIN® can effectively inhibit the growth of cervical cancer cells via targeting HPV E6/E7 expression. To further verify this finding in clinic, 108 volunteer patients with persistent hrHPV infections were randomly divided into REBACIN®, recombinant human interferon alpha-2b (Immunological drug control), or no-treatment blank control groups, received intravaginal administration of REBACIN®, interferon or no-treatment every other day for three months, and then followed up for E6/E7 mRNA assay. In REBACIN® group, 68.57% of patients showed complete clearance of HPV E6/E7 mRNA, which was significantly higher compared to 25.00% in the interferon immunological drug control group and 20.00% in blank control group, confirming that REBACIN® is potently efficacious on clearing persistent hrHPV infections via inhibition of HPV E6/E7 oncogenes.Clinical trial registrationhttp://www.chictr.org.cn/historyversionpuben.aspx?regno=ChiCTR2100045911, identifier ChiCTR2100045911.

Healing of large calvarial bone defects remains challenge but may be improved by stimulating bone regeneration of implanted cells. The aim of this study is to specially co-activate transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF-A) genes expressions in pre-osteoblast MC3T3-E1 cells through the non-viral CRISPR activation (CRISPRa) system to promote osteogenesis. A cationic copolymer carrying nucleus localizing peptides and proton sponge groups dimethyl-histidine was synthesized to deliver CRISPRa system into MC3T3-E1 cells with high cellular uptake, lysosomal escape, and nuclear translocation, which activated VEGF-A and TGF-β1 genes expressions and thereby additively or synergistically induced several osteogenic genes expressions. A tunable dual-crosslinked hydrogel was developed to implant the above engineered cells into mice calvaria bone defect site to promote bone healing in vivo. The combination of multi-genes activation through non-viral CRISPRa system and tunable dual-crosslinked hydrogel provides a versatile strategy for promoting bone healing with synergistic effect.

Abstract PD-L1(CD274) is a well-known immunosuppressive molecule, which confers immunoescape features to cancer cells and has become one of the major targets in cancer immunotherapies. Understanding the regulatory mechanisms that control PD-L1 protein expression is important for guiding immune checkpoint blockade therapy. Here, we showed that ubiquitin specific peptidase 5 (USP5) was a novel PD-L1 deubiquitinase in non-small cell lung cancer (NSCLC) cells. USP5 directly interacted with PD-L1 and deubiquitinated PD-L1, therefore enhances PD-L1 protein stability. Meanwhile, USP5 protein levels were highly elevated and positively correlated to PD-L1 levels in NSCLC tissues, and were closely correlated with poor prognosis of these patients. In addition, knockdown of USP5 retarded tumor growth in the Lewis lung carcinoma mouse model. Thus, we identified that USP5 was a new regulator of PD-L1 and targeting USP5 is a promising strategy for cancer therapy.

Xanthomonas campestris pv. campestris (Xcc) is the causal agent of black rot for cruciferous vegetables worldwide, especially for the cole crops such as cabbage and cauliflower. Due to the lack of resistant cabbage cultivars, black rot has brought about considerable yield losses in recent years in China. Understanding of the pathogen features is a key step for disease prevention, however, the pathogen diversity, population structure, and virulence are largely unknown. In this study, we studied 50 Xcc strains including 39 Xcc isolates collected from cabbage in 20 regions across China, using multilocus sequence genotyping (MLST), repetitive DNA sequence-based PCR (rep-PCR), and pathogenicity tests. For MLST analysis, a total of 12 allelic profiles (AP) were generated, among which the largest AP was AP1 containing 32 strains. Further cluster analysis of rep-PCR divided all strains into 14 DNA groups, with the largest group DNA I comprising of 34 strains, most of which also belonged to AP1. Inoculation tests showed that the representative Xcc strains collected from diverse regions performed differential virulence against three brassica hosts compared with races 1 and 4. Interestingly, these results indicated that AP1/DNA I was not only the main pathotype in China, but also a novel group that differed from the previously reported type races in both genotype and virulence. To our knowledge, this is the first extensive genetic diversity survey for Xcc strains in China, which provides evidence for cabbage resistance breeding and opens the gate for further cabbage-Xcc interaction studies.

Salmonella: mediated cancer therapy has achieved remarkable anti-tumor effects in experimental animal models, but the detailed mechanism remains unsolved. In this report, the active involvement of the host immune response in this process was confirmed by comparing the tumor-suppressive effects of Salmonella in immunocompetent and immunodeficient mice bearing melanoma allografts. Since flagella are key inducers of the host immune response during bacterial infection, flagella were genetically disrupted to analyse their involvement in Salmonella-mediated cancer therapy. The results showed that flagellum-deficient strains failed to induce significant anti-tumor effects, even when more bacteria were administered to offset the difference in invasion efficiency. Flagella mainly activate immune cells via Flagellin/Toll-like receptor 5 (TLR5) signalling pathway. Indeed, we showed that exogenous activation of TLR5 signalling by recombinant Flagellin and exogenous expression of TLR5 both enhanced the therapeutic efficacy of flagellum-deficient Salmonella against melanoma. Our study highlighted the therapeutic value of the interaction between Salmonella and the host immune response through Flagellin/TLR5 signalling pathway during Salmonella-mediated cancer therapy, thereby suggesting the potential application of TLR5 agonists in the cancer immune therapy.

Abstract Generally, in order to guarantee a good throughput and decrease the complexity of reassembling, the majority of current commodity routers take elaborate closed‐loop flow control schemes such as back pressure to prevent cell loss in the switch fabrics. As commodity router's port number grows larger and link rate becomes faster, the huge I/O pins and memory consumption makes these closed‐loop flow controls very difficult to implement engineeringly. This paper approaches the problem of building ultra‐large‐capacity router from a different angle. Crosspoint‐queued‐based Parallel Packet Switch (CQPPS), a highly scalable switch architecture with no need of any closed‐loop flow control schemes, is proposed. And the authors propose the Padded Frame plus Round‐Robin scheduling scheme for CQPPS architecture. By allowing potential cell loss in the switch fabrics and slightly higher light‐load delay, CQPPS achieves loss rate orders of magnitudes lower than back pressure schemes, and high‐load delay 10 times less than back pressure schemes. It also greatly reduces the complexity of engineering implementation.

Abstract Background Metabolic reprogramming sustains tumorigenesis and aggressiveness of neuroblastoma (NB), the most common extracranial malignancy in childhood, while underlying mechanisms and therapeutic approaches still remain elusive. Methods Circular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation (ChIP) sequencing, and RNA sequencing assays were applied to explore protein interaction and target genes. Gene expression regulation was observed by ChIP, dual-luciferase reporter, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA-encoded protein and its partners on the lipid metabolism, mitochondrial activity, growth, invasion, and metastasis of NB cells. Results A novel 113-amino acid protein (p113) of CUT-like homeobox 1 (CUX1) was identified in NB cells treated by serum deprivation. Further validating studies revealed that nuclear p113 was encoded by circRNA of CUX1, and promoted the lipid metabolic reprogramming, mitochondrial activity, proliferation, invasion, and metastasis of NB cells. Mechanistically, p113 interacted with Zuotin-related factor 1 (ZRF1) and bromodomain protein 4 (BRD4) to form a transcriptional regulatory complex, and mediated the transactivation of ZRF1/BRD4 in upregulating ALDH3A1, NDUFA1, and NDUFAF5 essential for conversion of fatty aldehydes into fatty acids, fatty acid β-oxidation, and mitochondrial complex I activity. Administration of an inhibitory peptide blocking p113-ZRF1 interaction suppressed the tumorigenesis and aggressiveness of NB cells. In clinical NB cases, high expression of p113, ZRF1, or BRD4 was associated with poor survival of patients. Conclusions These results indicate that p113 isoform encoded by CUX1 circular RNA drives tumor progression via facilitating ZRF1/BRD4 transactivation.

Highly precise neuromodulation with a high efficacy poses great importance in neuroscience. Here we developed a candle soot fiber optoacoustic emitter (CSFOE), capable of generating a high pressure of over 10 MPa with a central frequency of 12.8 MHz, enabling highly efficient neuromodulation in vitro. The design of the fiber optoacoustic emitter, including the choice of the material and the thickness of the layered structure, was optimized in both simulations and experiments. The optoacoustic conversion efficiency of the optimized CSFOE was found to be 10 times higher than the other carbon-based fiber optoacoustic emitters. Driven by a single laser, the CSFOE can perform dual-site optoacoustic activation of neurons, confirmed by calcium (Ca2+) imaging. Our work opens potential avenues for more complex and programmed control in neural circuits using a simple design for multisite neuromodulation in vivo.