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Treatments of inflammatory bowel disease (IBD) are diverse, but their efficacy is limited, and it is therefore urgent to find better therapies. Controlling mucosal inflammation is a must in IBD drug treatment. The occurrence of anti-tumor necrosis factor α (TNF-α) monoclonal antibodies has provided a safer and more efficacious therapy. However, this kind of treatment still faces failure in the form of loss of response. β-Carboline alkaloids own an anti-inflammatory pharmacological activity. While Kumujan B contains β-carboline, its biological activity remains unknown. In this study, we attempted to determine the anti-inflammatory effects of Kumujan B using both the TNF-α- induced in vitro inflammation and DSS-induced in vivo murine IBD models. Our data show that Kumujan B attenuated the expression of interleukin 1β (IL-1β) and interleukin 6 (IL-6) induced by TNF-α in mouse peritoneal macrophages. Kumujan B suppressed c-Jun N-terminal protein kinases (JNK) signaling, especially c-Jun, for anti-inflammatory response. Furthermore, Kumujan B promoted K11-linked ubiquitination and degradation of c-Jun through the proteasome pathway. In an in vivo study, Kumujan B inhibited the expression of IL-1β, IL-6, and TNF-α and improved the colon barrier function in dextran sulfate sodium salt (DSS)-induced experimental mice colitis. Kumujan B exhibited in vivo and in vitro anti-inflammatory effects, making it a potential therapeutic candidate for treating IBD.

Objectives This study aimed to quantitatively evaluate optic nerve head and retinal vascular parameters in children with hyperopia in relation to age and spherical equivalent refraction (SER) using artificial intelligence (AI)-based analysis of colour fundus photographs (CFP).Methods and analysis This cross-sectional study included 324 children with hyperopia aged 3–12 years. Participants were divided into low hyperopia (SER+0.5 D to+2.0 D) and moderate-to-high hyperopia (SER≥+2.0 D) groups. Fundus parameters, such as optic disc area and mean vessel diameter, were automatically and quantitatively detected using AI. Significant variables (p

The challenge of mitigating adverse climatic conditions is a critical issue that affects worker safety and operational efficiency in underground engineering. This study introduces an innovative approach using pumping wet shotcrete as an insulating material, incorporated with microencapsulated phase change materials (MPCMs) and filled within fluorine rubber tubes to address this concern. The MPCMs were synthesized via suspension polymerization, utilizing paraffin as the core material and modified SiO2-poly (lauryl methacrylate) as the shell material. To determine the optimal composition for practical application, an orthogonal experimental design was employed, complemented by comprehensive performance testing. The results indicated that a mix of 1375 kg/m3 of sand, 120 kg/m3 of ceramsite, and 1 g/cm of SiO2-MPCMs in each fluorine rubber tube having an inner diameter of 13 mm, provided the best balance between multiple properties. Notably, the insulation performance improved by 60–75 % compared to traditional pumping wet shotcrete, demonstrating a significant enhancement in thermal management capabilities. The findings contribute substantially to the field of thermal management in mines, presenting a novel technique that could be instrumental in improving safety and efficiency in deep underground operations.

Abstract Background The meticulous selection of appropriate vaccine adjuvants is crucial for optimizing immune responses. Traditionally, pemphigus vulgaris (PV), an autoimmune disorder, has been modelled using complete Freund's adjuvant (CFA). In this study, we aimed to discern potential variations in immune responses elicited by Toll‐like receptor (TLR) ligands as compared to CFA. Methods A comprehensive investigation was conducted, comparing the effects of these adjuvants in conjunction with ovalbumin or desmoglein‐3. Flow cytometry was employed to analyse distinct cell subsets, while enzyme‐linked immunosorbent assay quantified antigen‐specific antibodies and cytokine levels. Histological examination of harvested skin tissues and transcriptome analysis of skin lesions were performed to identify differentially expressed genes. Results TLR ligands demonstrated efficacy in inducing PV‐like symptoms in wild‐type mice, in contrast to CFA. This underscored the substantial impact of the adjuvant on self‐antigen tolerance. Furthermore, we proposed an enhanced method for establishing a PV model through adoptive transfer, substituting CFA with TLR ligands. Our results revealed that in contrast to the perception that CFA being the most potent immunopotentiator reported, CFA promoted regulatory T cells (Treg), follicular regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10. This suggested potential implications for the recruitment and activation of Treg subsets. While B cell and CD8+ T cell responses exhibited similarity, CFA induced less activation in dendritic cell subsets. A novel mouse model of PV and systemic comparison of immunostimulatory effects of adjuvants were provided by this study. Conclusions The systematic comparison of CFA and TLR ligands shed light on the distinctive properties of these adjuvants, presenting innovative mouse models for the investigation of pemphigus. This study significantly contributes to adjuvant research and advances our understanding of PV pathogenesis. Key points/highlights Immunization with desmoglein 3 and Toll‐like receptor (TLR) ligands effectively induces pemphigus symptoms in wild‐type mice, whereas complete Freund's adjuvant (CFA) fails. TLR ligands heightened the autoreactivity of donor cells in the adoptive transfer pemphigus model. CFA promoted regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10, leading to more effective immune responses.

Abstract Triboelectric nanogenerators (TENGs), a promising strategy for harvesting distributed low‐quality power sources, face inevitable bottlenecks regarding long‐term abrasion and poor durability. Herein, both issues are addressed by selecting an earthworm‐inspired self‐replenishing bionic film (ERB) as the tribo‐material of sliding‐freestanding TENGs (SF‐TENGs), it consists of an interconnected 3D porous network structure capable of storing and releasing lubricant under cyclic mechanical stimuli. Thanks to the superiority of self‐replenishing property, there is no need for periodic replenishment and accurate content control of lubricant over the interfacial‐lubricating SF‐TENGs based on dense tribo‐layers. Additionally, an SF‐TENG based on ERB film (ERB‐TENG) demonstrates remarkable output stability with only a slight attenuation of 1% after continuous operation for 100 000 cycles. Moreover, the ERB‐TENG displays a distinguished anti‐wear property, exhibiting no distinct abrasion with an ultra‐low coefficient of friction (0.077) and maintaining output stability over a prolonged period of 35 days. Furthermore, integration with an energy management circuit enables the ERB‐TENG to achieve a 39‐fold boost in charging speed. This work proposes a creative approach to enhance the durability and extend the lifespan of TENG devices, which is also successfully applied to wind energy harvesting and intelligent sports monitoring.

Airway epithelial cells play a crucial role in investigating the physiological and pathological mechanisms of the respiratory tract in yaks, a species whose unique respiratory system has garnered extensive interest. Despite this growing interest, there currently are no available airway epithelial cell lines from yaks, underscoring the crucial need to establish a yak respiratory epithelial cell line. Therefore, our objective was to isolate a population of primary yak nasopharyngeal epithelial cells (pYNE) and transform them into immortalized yak nasopharyngeal epithelial cells (iYNE), assessing their suitability as an in vitro model. Employing a combined method of physical elimination and differential adhesion, we successfully isolated a population of high-purity pYNE, and developed an iYNE line through pCI-neo-hTERT plasmid transfection. Karyotype and transmission electron microscopy analyses confirmed that pYNE and iYNE share identical morphologies and structures. Gel electrophoresis and real-time PCR analyses demonstrated that pYNE and iYNE expressed similar levels of KRT18 and CDH1 genes (p ≥ 0.541). Notably, iYNE expressed a significantly high level of TERT gene expression (p

Lung cancer is a leading cause of cancer-related death, and the most common type of lung cancer is non-small cell lung cancer, which accounts for approximately 85 % of lung cancer diagnoses. Recent studies have revealed that ubiquitination acts as a crucial part of the development and progression of lung cancer. The E1-E2-E3 three-enzyme cascade has a core function in ubiquitination, so targeted adjustments of E3 ligases could be used in lung cancer treatment. Hence, we elucidate research advances in lung cancer-related E3 ligases by briefly describing the structure and categorization of E3 ligases. Here, we provide a detailed review of the mechanisms by which lung cancer-related E3 ligases modify substrate proteins and regulate signaling pathways to facilitate or suppress cancer progression. We hope to show a new perspective on targeted precision therapy for lung cancer.

In order to enhance the utilization efficiency of reclaimed asphalt pavement (RAP) and contribute to sustainable waste management, the implementation of hot recycling technique is employed to produce semi-flexible pavement materials. This research endeavor aims to scrutinize the performance characteristics of semi-flexible pavement materials manufactured through hot recycling. To attain this objective, the grout construction issue is simulated with the aid of ABAQUS software, enabling a comprehensive investigation into the impact of various load positions, surface areas, and grout heights on the horizontal and bending features of the pavement. The findings of the study indicate that the judicious incorporation of reclaimed asphalt pavement (RAP) into the hot recycled asphalt mixture as a semi-flexible pavement material exhibits an acceptable grouting rate, outstanding resistance to high temperatures, water stability, and fatigue resistance. Such exceptional properties render these materials qualified for usage in road surfaces under heavy traffic conditions, elevated summer temperatures, and other challenging utilization scenarios [1]. Moreover, it is demonstrated that higher grouting fullness contributes to superior road performance characteristics in the context of semi-flexible pavement.

Background Fibroblast growth factor 21 (FGF21) is a key hormone factor that regulates glucose and lipid homeostasis. Exercise may regulate its effects and affect disease states. Therefore, we sought to determine how exercise affects FGF21 concentrations in adults. Methods The review was registered in the International Prospective Systematic Review (PROSPERO, CRD42023471163). The Cochrane Library, PubMed, and Web of Science databases were searched for studies through July 2023. Studies that assessed the effects of exercise training on FGF21 concentration in adults were included. The random effect model, data with standardized mean difference (SMD), and 95% confidence intervals (CI) were used to evaluate the pooled effect size of exercise training on FGF21. The risk of heterogeneity and bias were evaluated. A total of 12 studies involving 401 participants were included. Results The total effect size was 0.3 (95% CI [−0.3–0.89], p = 0.33) when comparing participants who exercised to those who were sedentary. However, subgroup analysis indicated that concurrent exercise and a duration ≥10 weeks significantly decreased FGF21 concentrations with an effect size of −0.38 (95% CI [−0.74–−0.01], p < 0.05) and −0.38 (95% CI [−0.63–−0.13], p < 0.01), respectively. Conclusion Concurrent exercise and longer duration may be more efficient way to decrease FGF21 concentrations in adults with metabolic disorder.

Abstract Noncanonical pyroptosis is triggered by Caspase 4/5/11, which cleaves Gasdermin D (GSDMD), leading to cell lysis. While GSDMD has been studied previously in systemic lupus erythematosus (SLE), the role of pyroptosis in SLE pathogenesis remains unclear and contentious, with limited understanding of Caspase 11‐mediated pyroptosis in this condition. In this study, we explored the level of Caspase 11‐mediated pyroptosis in SLE, identifying both the upstream pathways and the interaction between pyroptosis and adaptive immune responses. We observed increased Caspase 5/11 and GSDMD‐dependent pyroptosis in the macrophages/monocytes of both lupus patients and mice. We identified serum lipopolysaccharide (LPS), released from the gut due to a compromised gut barrier, as the signal that triggers Caspase 11 activation in MRL/lpr mice. We further discovered that pyroptotic macrophages promote the differentiation of mature B cells independently of T cells. Additionally, inhibiting Caspase 11 and preventing LPS leakage proved effective in improving lupus symptoms in MRL/lpr mice. These findings suggest that elevated serum LPS, resulting from a damaged gut barrier, induces Caspase 11/GSDMD‐mediated pyroptosis, which in turn promotes B cell differentiation and enhances autoimmune responses in SLE. Thus, targeting Caspase 11 could be a viable therapeutic strategy for SLE.

Coupling the San Diego gas phase reaction mechanism and the Moss Brookes soot model using FLUENT14.0 software, the effect of adding H2/CO on the fuel side on soot formation in an ethylene/air laminar diffusion flame was studied. A specific analysis was conducted on the effects of H2, CO and its chemical effects on flame temperature, soot volume fraction, mole fractions of important intermediate products OH, H, and C2H2, as well as rate of soot mass nucleation, surface growth, and oxidation. In the numerical calculation, the virtual substances FH2 and FCO are set to separate the chemical effect of H2 and CO and to analyze the chemical effect of adding H2 and CO on soot formation. The results show that the flame temperature increases slightly, and the soot volume fraction decreases monotonically with adding H2 and CO. The chemical effect of H2 increases the temperature, the mole fraction of C2H2 and H, the soot nucleation rate, and the surface growth rate, and finally, it promotes soot formation. The chemical effect of CO increases the temperature and H mole fraction, reduces the OH mole fraction, and then increases the soot surface growth rate and reduces the soot oxidation rate. The higher soot nucleation, surface growth rate, and lower oxidation rate jointly promote soot formation.

The morphology of lettuce roots in hydroponics is affected by the flow environment of nutrient solutions. Regulating the flow rate therefore ensures quality and yield; however, the mechanisms underlying this impact have not been fully elucidated, and breakthroughs in regulatory methods are thus lacking. Herein, lettuce was grown in a hydroponic solution at three different flow rates, the root morphology indicators (such as root length and surface area) were evaluated, the hormone levels of roots grown under different flow conditions were measured, and the correlations between plant hormones and root morphology were analyzed. Transcriptomic analysis was conducted on roots at varying flow rates to investigate the differential expression of genes involved in the synthesis and signal transduction pathways of auxin, abscisic acid (ABA), ethylene, and jasmonic acid. Results showed that these plant hormones were closely related to root morphology. Compared to a non-flow environment, a flow environment promoted the synthesis of plant hormones in the roots and enhanced the signal transduction of certain hormones, such as auxin. However, it had a negative impact on the signal transduction of certain hormones, specifically ethylene. The flow of the nutrients regulated root morphogenesis by influencing the synthesis and transduction of plant hormones, which affected overall plant growth. During the same growth period, lettuce grown under suitable flow conditions had a higher fresh weight than lettuce grown under no-flow conditions. Although such flow would increase the electricity cost of operating water pumps, lettuce could be harvested in advance at appropriate flow rates, thereby reducing the energy consumed in plant factories through lighting and temperature regulation, which are the largest contributors to energy consumption. This study examined the impact of the nutrient solution flow environment as a positive stimulus for plant growth, and it provides a reference for strategically regulating the flow rate in plant factories to improve yield and save energy. Future research should explore the effects of other cultivation and flow methods on the growth of different plants and apply these findings to practical production.

Ultra-high temperature ceramic (UHTC) coatings are used to protect the hot-end components of hypervelocity aerocrafts from thermal ablation. This study provides a new approach to fabricate UHTC coatings with high speed laser cladding (HSLC) technology, and places more emphasis on investigating the formation mechanism, phase compositions, and mechanical properties of HSLC-UHTC coatings. Results show that a well-bonded interface between the coating and the tantalum alloy substrate can be formed. The coating is mainly composed of (Zr,Ta)C ceramic solid solution phase with a content of higher than 90% by volume and Ta(W) metal solid solution phase. At a relatively high powder feeding rate, the ZrC ceramic phase appears in the coating while a dense ZrC UHTC top layer with a thickness of up to ~50 μm is successfully fabricated. As for the mechanical properties of the HSLC coatings, the fracture toughness of the coating decreases with the increase of powder feeding rate. The increase of carbide solid solution phase can significantly improve the high temperature microhardness (552.7±1.8 HV0.5@1000 ℃). The innovative design of HSLC ZrC-based coatings on refractory alloys accomplishes continuous transitions on microstructure and properties from the substrate to the UHTC top layer, which is a very promising candidate scheme for thermal protection coating.

Abstract Human ocular toxocariasis (OT), caused by pet roundworm Toxocara canis (Nematoda Ascaridoidea), is a worldwide ocular parasitic infection that poses a severe threat to eyesight, especially in school-aged children. However, the infection process and pathological mechanism of Toxocara are difficult to study in the human body. This study was designed to explore long-term ocular manifestations in different rodents infected with Toxocara canis, uncovering the specific pathological mechanism and migration pathway of larvae after infection. The three types of experimental animals we selected were C57BL/6 mice, Mongolian gerbils and Brown Norway rats. Mice were randomly divided into five groups and infected orally with 1000, 2000, 4000, 8000 and 10,000 T. canis eggs; gerbils were randomly divided into four groups and infected orally with 1000, 2000, 4000 and 10,000 T. canis eggs; rats were randomly divided into three groups and infected orally with 2000, 6000 and 10,000 T. canis eggs. Their ocular changes were closely observed and recorded for at least 2 months. We also enucleated the eyeballs of some animals to perform pathological sectioning and hematoxylin-eosin staining. After 3 dpi (days post-infection), hemorrhagic lesions, mechanical injury of the retina and larval migration could be observed in some infected animals. The ocular infection and mortality rates tended to be stable at 7 dpi. Larval tissue, structure disorder and inflammation could be observed in the pathological sections. In conclusion, the mice infected with 2000 T. canis eggs and gerbils infected with 1000, 2000 and 4000 T. canis eggs showing obvious ocular lesions and lower mortality rates could provide a basis for long-term observation. Graphical Abstract

Abstract Lung adenocarcinoma (LUAD) is a prevalent form of non-small cell lung cancer with a rising incidence in recent years. Understanding the mutation characteristics of LUAD is crucial for effective treatment and prediction of this disease. Among the various mutations observed in LUAD, KRAS mutations are particularly common. Different subtypes of KRAS mutations can activate the Ras signaling pathway to varying degrees, potentially influencing the pathogenesis and prognosis of LUAD. This study aims to investigate the relationship between different KRAS mutation subtypes and the pathogenesis and prognosis of LUAD. A total of 63 clinical samples of LUAD were collected for this study. The samples were analyzed using targeted gene sequencing panels to obtain sequencing data. To complement the dataset, additional clinical and sequencing data were obtained from TCGA and MSK. The analysis revealed significantly higher Ki67 immunohistochemical scores in patients with missense mutations compared to controls. Moreover, the expression level of KRAS was found to be significantly correlated with Ki67 expression. Enrichment analysis indicated that KRAS missense mutations activated the SWEET_LUNG_CANCER_KRAS_DN and CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2 pathways. Additionally, patients with KRAS missense mutations and high Ki67 IHC scores exhibited significantly higher tumor mutational burden levels compared to other groups, which suggests they are more likely to be responsive to ICIs. Based on the data from MSK and TCGA, it was observed that patients with KRAS missense mutations had shorter survival compared to controls, and Ki67 expression level could more accurately predict patient prognosis. In conclusion, when utilizing KRAS mutations as biomarkers for the treatment and prediction of LUAD, it is important to consider the specific KRAS mutant subtypes and Ki67 expression levels. These findings contribute to a better understanding of LUAD and have implications for personalized therapeutic approaches in the management of this disease.

Abstract Metallic 2M or 1T′-phase transition metal dichalcogenides (TMDs) attract increasing interests owing to their fascinating physicochemical properties, such as superconductivity, optical nonlinearity, and enhanced electrochemical activity. However, these TMDs are metastable and tend to transform to the thermodynamically stable 2H phase. In this study, through systematic investigation and theoretical simulation of phase change of 2M WS2, we demonstrate that ultrathin 2M WS2 has significantly higher intrinsic thermal stabilities than the bulk counterparts. The 2M-to-2H phase transition temperature increases from 120 °C to 210 °C in the air as thickness of WS2 is reduced from bulk to bilayer. Monolayered 1T′ WS2 can withstand temperatures up to 350 °C in the air before being oxidized, and up to 450 °C in argon atmosphere before transforming to 1H phase. The higher stability of thinner 2M WS2 is attributed to stiffened intralayer bonds, enhanced thermal conductivity and higher average barrier per layer during the layer(s)-by-layer(s) phase transition process. The observed high intrinsic phase stability can expand the practical applications of ultrathin 2M TMDs.

Abstract Purpose Previous reports argue that preoperative sleep conditions of patients can influence the dosage of general anaesthesia drugs. Therefore, we aimed to investigate the dose-effect relationship of preoperative sleep disorders on the induction of general anaesthesia with remimazolam tosilate and calculate the Median effective (ED50) and 95% effective (ED95) dosages. Methods Included in our study were 56 patients who underwent laparoscopic cholecystectomy at our hospital. A separate group of 27 patients with sleep disorders (SD group) and 29 patients without sleep disorders (NSD group) using the Pittsburgh Sleep Quality Index (PSQI) were also included. According to the Dixon ‘up-and-down’ design, patients received remimazolam at preselected concentrations starting at 0.2 mg/kg. After the administration of remimazolam, loss of consciousness was observed. By observing whether consciousness disappeared within a minute, we adjusted the dose of remimazolam by 0.1 mg/kg (up and down) in the following patient. The Median effective dose (ED50), 95% effective dose (ED95), and 95% confidence interval (CI) of remimazolam for effective sedation were calculated. Results The ED50 of remimazolam was 0.226 mg/kg (95%CI 0.221–0.232 mg/kg) in the SD group and 0.191 mg/kg (95%CI, 0.183–0.199 mg/kg) in the NSD group. The ED95 of remimazolam was 0.237 mg/kg (95%CI 0.231–0.262 mg/kg) in the SD group and 0.209 mg/kg (95%CI 0.200–0.254 mg/kg) in the NSD group. Conclusions In the SD group, the ED50 and ED95 of remimazolam during anaesthesia induction were 0.226 and 0.237 mg/kg, respectively. The induction dose of remimazolam in the SD group was significantly higher than that in the NSD group.

BackgroundThe very small-angle neutron scattering (VSANS) spectrometer is currently being constructed at the China spallation neutron source (CSNS). The neutron detector plays a key role in meeting the detection requirements of the spectrometer.PurposeThis study aims to achieve accurate measurement of neutron diffraction in the small angle scattering mode which requires the position resolution of the neutron detector to be ≤2 mm, and the detection efficiency to be ≥60%@0.4 nm.MethodsA large-area position-sensitive neutron scintillator detector mainly composed of 6LiF/ZnS(Ag) scintillation screen, wavelength shift fiber (WLSF), and a silicon photomultiplier (SiPM) was designed and developed to achieve high efficiency and high-resolution real-time detection of thermal neutrons. The optical transmission performance of the 0.5-mm-diameter wavelength shift fiber was investigated in detail. The gain and the thermal noise characteristics of various SiPMs were examined. Finally, a 300 mm×300 mm engineering prototype of the detector was developed and tested by experiments. The detection efficiency was calculated with comparison of the incident neutron counts of the stander 3He tube whilst the detector's position resolution was tested using a boron-doped aluminum plate with a narrow slit bearing the label 'CSNS'.ResultsThe neutron beam test results show that the position resolution of the detector is 1.2 mm×1.2 mm and that the neutron detection efficiency is (61.8±0.2)%@0.4 nm.ConclusionsThe high-resolution neutron scintillator detector developed in this study satisfies the engineering design target, and meets the neutron scintillator detector meets the neutron diffraction measurement needs for the VSANS spectrometer of the CSNS.

Exploring the pattern of block vitality within cities and its influencing factors is an important topic in urban vitality research, which has great significance in promoting high-quality urban development. However, existing research has paid little attention to the spatial difference characteristics of daytime and night urban vitality and the differences in their influencing factors. Using the urban area of Kunming, China, as a case study, this study explores the differences in spatial patterns of daytime and night vitality at the intra-city block scale and analyses the differences in the main influencing factors of daytime and night block vitality using spatial regression models. The study obtains the following findings: (1) daytime block vitality in Kunming’s urban district (the urban Dist. of KM) is higher than night block vitality. The First Ring Area has the highest daytime block vitality, whereas the Second Ring Area has the highest night block vitality. (2) Block vitality in the urban Dist. of KM presents a polycentric structure. (3) There are obvious differences in the factors influencing urban vitality between daytime and night, with work accessibility, functional mixing, daily consumption accessibility, floor area ratio, and average building age, having different directions of influence on daytime and night urban vitality. (4) Daytime urban vitality in the urban Dist. of KM relies on work activities, while night urban vitality relies on residential activities. The results provide a scientific basis for urban land use layout, facility construction, and higher-quality urban planning and management, thus promoting sustainable urban development.

In this paper, a space-time line code (STLC) is combined with offset spatial modulation (OSM) for reaping both their advantages toward efficient multiple-input multiple-output (MIMO) transmission. Specifically, the spatial diversity offered by STLC increases the resilience against fading channels, while the simplified radio frequency (RF) switching processing merits of OSM inherently are preserved. As a further advancement in the pursuit of enhancing the performance of index detection, angle rotation is conceived and optimized for various transmit conditions. Subsequently, based on the approximation of the Q-function, an upper bound for the average bit error rate (BER) of STLC-OSM is derived in the context of an equispaced (ES) angle arrangement. Eventually, we demonstrate that STLC-OSM achieves considerable BER performance while achieving a unique single RF structure with a low implementation cost. Simulation results confirm the tightness of the derived BER bound and the advantages of the proposed scheme.

Edge data centers (EDCs) have been widely developed recently to supply delay-sensitive computing services, which impose prohibitively increasing electricity costs for EDC operators. This paper presents a new spatiotemporal reallocation (STR) method for energy management in EDCs. This method uses spare resources, including servers and energy storage systems (ESSs) within EDCs to reduce energy costs based on both spatial and temporal features of spare resources. This solution: 1) reallocates flexible workload between EDCs within one cluster; and 2) coordinates the electricity load of data processing, ESSs and distributed energy resources (DERs) within one EDC cluster to gain benefits from flexible electricity tariffs. In addition, this paper for the first time develops a Bit-Watt transformation to simplify the STR method and represent the relationship between data workload and electricity consumption of EDCs. Case studies justifying the developed STR method delivers satisfying cost reductions with robustness. The STR method fully utilized both spatial and temporal features of spare resources in EDCs to gain benefits from 1) varying electricity tariffs, and 2) maximumly consuming DER generation.

There is a close relationship between potassium (K) and nitrogen (N). However, the roles of K under high N conditions remain unclear. Using a hydroponics approach, we monitored the morphological, physiological, and molecular changes in M9T337 apple (Malus domestica) rootstocks under different nitrate (10 and 30 mmol·L−1 NO3−) and K supply (0.5, 6, 10, and 20 mmol·L−1 K+) conditions. Results revealed that high nitrate inhibited the root growth of M9T337 rootstocks, downregulated the expressions of K transporter genes (MdPT5, MdHKT1, and MdATK1), and reduced the net NO3− and K+ influx at the surface of roots, thereby resulting in an N/K imbalance in rootstocks. Further investigation showed that 10 mmol·L−1 K increased the activity of N metabolic enzymes (NR, GS, NiR, and GOGAT), upregulated the expressions of genes related to nitrate uptake and transport (MdNRT1.1, MdNRT1.2, MdNRT1.5, and MdNRT2.4), promoted 15N transport from the roots to the shoots, optimized leaf N distribution, and improved photosynthetic N utilization efficiency under high nitrate conditions. These results suggest that the negative effects of high nitrate may be related to the N/K imbalance and that reducing N/K in plants by increasing K supply level can effectively alleviate the inhibition of N assimilation by high nitrate stress.

Abstract Organic light-emitting diodes (OLEDs) exploiting simple binary emissive layers (EMLs) blending only emitters and hosts have natural advantages in low-cost commercialization. However, previously reported OLEDs based on binary EMLs hardly simultaneously achieved desired comprehensive performances, e.g., high efficiency, low efficiency roll-off, narrow emission bands, and high operation stability. Here, we report a molecular-design strategy. Such a strategy leads to a fast reverse intersystem crossing rate in our designed emitter h-BNCO-1 of 1.79×105 s−1. An OLED exploiting a binary EML with h-BNCO-1 achieves ultrapure emission, a maximum external quantum efficiency of over 40% and a mild roll-off of 14% at 1000 cd·m−2. Moreover, h-BNCO-1 also exhibits promising operational stability in an alternative OLED exploiting a compact binary EML (the lifetime reaching 95% of the initial luminance at 1000 cd m−2 is ~ 137 h). Here, our work has thus provided a molecular-design strategy for OLEDs with promising comprehensive performance.

Abstract Background Information is limited regarding the prevalence and importance of hepatic histologic abnormalities in dogs with gallbladder mucocele (GBM). Objectives To (a) report prevalence of hepatic histologic abnormalities in dogs with GBM (b) evaluate for association between hepatic abnormalities and outcome in dogs with GBM (c) evaluate whether neutrophil‐to‐lymphocyte ratio (NLR) differs in dogs with GBM with and without specific hepatic lesions. Animals Fifty‐two dogs with grossly and histologically confirmed GBM. Methods Multicenter, retrospective study of dogs with GBM undergoing cholecystectomy with concurrent liver biopsy. Archived histological sections of gallbladder and liver evaluated by investigators blinded to data. Proportions of dogs with each histologic abnormality alive vs deceased at 1, 3, and 12 months post‐cholecystectomy compared. Mann‐Whitney U performed to determine if NLR differed in dogs with or without selected lesions. Results 51/52 (98%, 95% CI [89%, 99%]) dogs with GBM had at least 1 hepatic histologic abnormality. Hepatic fibrosis (37/51; 73%, 95% CI [59%, 83%]), biliary hyperplasia (29/52; 56%, 95% CI [42%, 68%]), and portal inflammation (25/52; 48%, 95% CI [35%, 61%]) were most common. The proportion of dogs alive vs dead differed based on the fibrosis score at 1, 3, and 12 (P ≤ .04) months post‐cholecystectomy. Dogs with hepatic necrosis (P = .006) and cholangitis/cholangiohepatitis (P = .02) had higher NLRs compared to dogs without these lesions. Conclusions and Clinical Importance Histologic abnormalities of the liver are common in dogs with GBM. A higher portal fibrosis score might be associated with shortened long‐term survival after cholecystectomy for dogs with GBM. An increase in NLR might predict hepatic necrosis and cholangitis/cholangiohepatitis in dogs with GBM.

This study aimed to compare the postoperative analgesic efficacy and motor recovery of a novel lumbar plexus block (LPB) with that of a femoral nerve block (FNB) after total knee arthroplasty (TKA). Forty patients who underwent TKA were randomised equally into an lumbar plexus and sciatic nerve (LS) group (receiving novel LPB) and an femoral and sciatic nerves (FS) group (receiving FNB). The assessed variables were the onset time of pain, time to the first analgesic request, pain scores, motor block at 6, 12, and 24 h after TKA, and the number of patients receiving successful blockade for each branch of the lumbar plexus. In the LS group, the femoral, lateral femoral cutaneous, genitofemoral, iliohypogastric, ilioinguinal, and obturator nerves were blocked in 18, 20, 16, 18, 15, and 19 patients. Compared to the FS group, the LS group had a significantly shorter onset time of pain and time to the first analgesic request, a significantly larger total postoperative dose of sufentanil, significantly higher numeric rating scale scores for both rest and dynamic pain at 6, 12, and 24 h, and faster motor recovery. Novel ultrasound-guided LPB has a high blocking success rate and provides inferior postoperative analgesia, but faster motor recovery after TKA than FNB.

Abstract Mutant KRAS (KRASMUT) is often exploited by cancers to shape tumor immunity, but the underlying mechanisms are not fully understood. Here we report that tumor-specific cytotoxic T lymphocytes (CTLs) from KRASMUT cancers are sensitive to activation-induced cell death (AICD). circATXN7, an NF-κB-interacting circular RNA, governs T cell sensitivity to AICD by inactivating NF-κB. Mechanistically, histone lactylation derived from KRASMUT tumor cell-produced lactic acid directly activates transcription of circATXN7, which binds to NF-κB p65 subunit and masks the p65 nuclear localization signal motif, thereby sequestering it in the cytoplasm. Clinically, circATXN7 upregulation in tumor-specific CTLs correlates with adverse clinical outcomes and immunotherapeutic resistance. Genetic ablation of circAtxn7 in CD8+ T cells leads to mutant-selective tumor inhibition, while also increases anti-PD1 efficacy in multiple tumor models in female mice. Furthermore, targeting circATXN7 in adoptively transferred tumor-reactive CTLs improves their antitumor activities. These findings provide insight into how lymphocyte-expressed circRNAs contribute to T-cell fate decisions and anticancer immunotherapies.

Activating mutations in Ras proteins are present in about 30% of human cancers. Despite tremendous progress in the study of Ras oncogenes, many aspects of the molecular mechanisms underlying Ras-induced tumorigenesis remain unknown. Through proteomics analysis, we previously found that the protein Gankyrin, a known oncoprotein in hepatocellular carcinoma, was upregulated during Ras-mediated transformation, although the functional consequences of this were not clear. Here we present evidence that Gankyrin plays an essential role in Ras-initiated tumorigenesis in mouse and human cells. We found that the increased Gankyrin present following Ras activation increased the interaction between the RhoA GTPase and its GDP dissociation inhibitor RhoGDI, which resulted in inhibition of the RhoA effector kinase Rho-associated coiled coil-containing protein kinase (ROCK). Importantly, Gankyrin-mediated ROCK inhibition led to prolonged Akt activation, a critical step in activated Ras-induced transformation and tumorigenesis. In addition, we found that Gankyrin is highly expressed in human lung cancers that have Ras mutations and that increased Gankyrin expression is required for the constitutive activation of Akt and tumorigenesis in these lung cancers. Our findings suggest that Gankyrin is a key regulator of Ras-mediated activation of Akt through inhibition of the downstream RhoA/ROCK pathway and thus plays an essential role in Ras-induced tumorigenesis., Introduction Carcinogenesis involves sequential mutations in genes that play key roles in the control of cell growth and proliferation (1). These mutations usually lead to either the loss of tumor [...]

Abstract Background Obesity is a risk factor for breast cancer, and women with obesity that develop breast cancer have a worsened prognosis. Within the mammary gland, obesity causes chronic, macrophage-driven inflammation and adipose tissue fibrosis. Weight loss is a recommended intervention to resolve obesity, but the impact of weight loss on the mammary gland microenvironment and in tumors has not been well identified. Methods To examine the effects of weight loss following obesity, mice were fed a high-fat diet for 16 weeks to induce obesity, then switched to a low-fat diet for 6 weeks. We examined changes in immune cells, including fibrocytes, which are myeloid lineage cells that have attributes of both macrophages and myofibroblasts, and collagen deposition within the mammary glands of non-tumor-bearing mice and within the tumors of mice that were transplanted with estrogen receptor alpha positive TC2 tumor cells. Results In formerly obese mice, we observed reduced numbers of crown-like structures and fibrocytes in mammary glands, while collagen deposition was not resolved with weight loss. Following transplant of TC2 tumor cells into the mammary glands of lean, obese, and formerly obese mice, diminished collagen deposition and cancer-associated fibroblasts were observed in tumors from formerly obese mice compared to obese mice. Within tumors of obese mice, increased myeloid-derived suppressor cells and diminished CD8+ T cells were identified, while the microenvironment of tumors of formerly obese mice were more similar to tumors from lean mice. When TC2 tumor cells were mixed with CD11b+CD34+ myeloid progenitor cells, which are the cells of origin for fibrocytes, and transplanted into mammary glands of lean and obese mice, collagen deposition within the tumors of both lean and obese was significantly greater than when tumor cells were mixed with CD11b+CD34− monocytes or total CD45+ immune cells. Conclusions Overall, these studies demonstrate that weight loss resolved some of the microenvironmental conditions within the mammary gland that may contribute to tumor progression. Additionally, fibrocytes may contribute to early collagen deposition in mammary tumors of obese mice leading to the growth of desmoplastic tumors.

Abstract Background Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Emerge evidence suggests that circular RNA (circRNA) is a pivotal player in cancer progression. However, its role in CRC liver metastasis remains largely unknown. Methods Circ-YAP expression was detected by qRT-PCR and in situ hybridization. The function of circ-YAP was tested by wound healing, transwell and CCK-8 assays. RNA immunoprecipitation, pull-down, luciferase reporter, chromatin immunoprecipitation assays were used to investigate the mechanism underlying circ-YAP promoting CRC liver metastasis. CRC liver metastasis animal model was established to assess the effect of circ-YAP in vivo. Results Circ-YAP was notably upregulated in CRC with liver metastasis, which was associated with dismal prognosis. Circ-YAP promoted CRC cell migration and invasion in vitro, and facilitated liver metastasis in patient-derived xenografts (PDX) models in vivo. Mechanistically, circ-YAP encoded a novel truncated protein containing 220 amino acids, termed as YAP-220aa, which competitively bound to LATS1, resulting in YAP dephosphorylation and nuclear translocation, thereby activating a cohort of metastasis-promoting genes. Importantly, N6-methyladenosine (m6A) modification orchestrated efficient initiation of circ-YAP translation, requiring m6A reader YTHDF3 and eIF4G2 translation initiation complex. Intriguingly, circ-YAP was transcriptionally enhanced by YAP/TEAD complex, thus forming a positive regulatory feed-forward loop. Conclusions Our findings reveal a previously uncharacterized oncoprotein encoded by circ-YAP, implying a promising biomarker and therapeutic target for CRC patients with liver metastasis.

Abstract Background Complete reporting is essential for clinical research. However, the endorsement of reporting guidelines in radiological journals is still unclear. Further, as a field extensively utilizing artificial intelligence (AI), the adoption of both general and AI reporting guidelines would be necessary for enhancing quality and transparency of radiological research. This study aims to investigate the endorsement of general reporting guidelines and those for AI applications in medical imaging in radiological journals, and explore associated journal characteristic variables. Methods This meta-research study screened journals from the Radiology, Nuclear Medicine & Medical Imaging category, Science Citation Index Expanded of the 2022 Journal Citation Reports, and excluded journals not publishing original research, in non-English languages, and instructions for authors unavailable. The endorsement of fifteen general reporting guidelines and ten AI reporting guidelines was rated using a five-level tool: “active strong”, “active weak”, “passive moderate”, “passive weak”, and “none”. The association between endorsement and journal characteristic variables was evaluated by logistic regression analysis. Results We included 117 journals. The top-five endorsed reporting guidelines were CONSORT (Consolidated Standards of Reporting Trials, 58.1%, 68/117), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 54.7%, 64/117), STROBE (STrengthening the Reporting of Observational Studies in Epidemiology, 51.3%, 60/117), STARD (Standards for Reporting of Diagnostic Accuracy, 50.4%, 59/117), and ARRIVE (Animal Research Reporting of In Vivo Experiments, 35.9%, 42/117). The most implemented AI reporting guideline was CLAIM (Checklist for Artificial Intelligence in Medical Imaging, 1.7%, 2/117), while other nine AI reporting guidelines were not mentioned. The Journal Impact Factor quartile and publisher were associated with endorsement of reporting guidelines in radiological journals. Conclusions The general reporting guideline endorsement was suboptimal in radiological journals. The implementation of reporting guidelines for AI applications in medical imaging was extremely low. Their adoption should be strengthened to facilitate quality and transparency of radiological study reporting.

Highlights The working principle of the asymmetric electrolyte and the long-term-seated contradictory issues were analyzed. The characterization methods for the interfaces of anolyte/catholyte and electrolyte/electrode were summarized for revealing the fundamental mechanism of asymmetric electrolytes. The future research directions for asymmetric electrolyte systems were proposed.

Abstract In the three‐phase grid‐connected current‐source inverters (CSIs), the resonance result from the AC‐side CL filter and the quality of the grid‐current waveform under the unbalanced and harmonic grid voltage conditions are two issues deserving attention. To solve the two problems, a continuous control set‐model predictive control (CCS‐MPC) method based on the optimization theory is proposed in the two‐phase synchronous coordinate frame in this paper. The constructed cost function takes grid‐connected current and output current of the inverter as control target, and obtains its optimal solution under the least‐squares method, where the optimal inverter‐side current reference is composed of inductor‐current proportional feedback, capacitor‐voltage proportional feedback, and inverter‐side current steady‐state value feedforward. The proposed method can easily realize the normal operation of three‐phase grid‐connected CSIs because the method can be determined by only one parameter under the unbalanced and distorted grids. Furthermore, in the proposed method, the proportional feedback of capacitor voltage can effectively suppress the CL filter resonance. Finally, simulation and experimental results verify the effectiveness of the proposed control strategy.