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Abstract Pipe contaminant detection holds considerable importance within various industries, such as the aviation, maritime, medicine, and other pertinent fields. This capability is beneficial for forecasting equipment potential failures, ascertaining operational situations, timely maintenance, and lifespan prediction. However, the majority of existing methods operate offline, and the detectable parameters online are relatively singular. This constraint hampers real-time on-site detection and comprehensive assessments of equipment status. To address these challenges, this paper proposes a sensing method that integrates an ultrasonic unit and an electromagnetic inductive unit for the real-time detection of diverse contaminants and flow rates within a pipeline. The ultrasonic unit comprises a flexible transducer patch fabricated through micromachining technology, which can not only make installation easier but also focus the sound field. Moreover, the sensing unit incorporates three symmetrical solenoid coils. Through a comprehensive analysis of ultrasonic and induction signals, the proposed method can be used to effectively discriminate magnetic metal particles (e.g., iron), nonmagnetic metal particles (e.g., copper), nonmetallic particles (e.g., ceramics), and bubbles. This inclusive categorization encompasses nearly all types of contaminants that may be present in a pipeline. Furthermore, the fluid velocity can be determined through the ultrasonic Doppler frequency shift. The efficacy of the proposed detection principle has been validated by mathematical models and finite element simulations. Various contaminants with diverse velocities were systematically tested within a 14 mm diameter pipe. The experimental results demonstrate that the proposed sensor can effectively detect contaminants within the 0.5−3 mm range, accurately distinguish contaminant types, and measure flow velocity.

Abstract UBE2M, a NEDD8-conjugating enzyme, is dysregulated in various human cancers and promotes tumor cell proliferation. However, its role in estrogen receptor-positive (ER+) breast cancer remains unknown. We found that UBE2M expression was significantly higher in ER+ breast cancer tissues than in ER-negative (ER-) breast cancer tissues. Higher expression of UBE2M indicated a poorer prognosis in patients with ER+ breast cancer but not in those with ER- breast cancer. Of interest, a positive feedback loop was observed between UBE2M and ERα. Specifically, ERα enhanced the HIF-1α-mediated transcription of UBE2M. In turn, UBE2M maintained ERα expression by inhibiting its ubiquitination and degradation through UBE2M-CUL3/4A-E6AP-ERα axis. Functionally, silencing of UBE2M suppressed the growth of breast cancer cells by inducing cell cycle arrest and apoptosis and improved their sensitivity to fulvestrant both in vitro and in vivo. Altogether, our findings reveal that the UBE2M-ERα feedback loop drives breast cancer progression and fulvestrant resistance, suggesting UBE2M as a viable target for endocrine therapy of ER+ breast cancer.

Abstract With the increasing development of intelligent robots and wearable electronics, the demand for high-performance flexible energy storage devices is drastically increasing. In this study, flexible symmetric microsupercapacitors (MSCs) that could operate in a wide working voltage window were developed by combining laser-direct-writing graphene (LG) electrodes with a phosphoric acid-nonionic surfactant liquid crystal (PA-NI LC) gel electrolyte. To increase the flexibility and enhance the conformal ability of the MSC devices to anisotropic surfaces, after the interdigitated LG formed on the polyimide (PI) film surface, the devices were further transferred onto a flexible, stretchable and transparent polydimethylsiloxane (PDMS) substrate; this substrate displayed favorable flexibility and mechanical characteristics in the bending test. Furthermore, the electrochemical performances of the symmetric MSCs with various electrode widths (300, 400, 500 and 600 μm) were evaluated. The findings revealed that symmetric MSC devices could operate in a large voltage range (0–1.5 V); additionally, the device with a 300 μm electrode width (MSC-300) exhibited the largest areal capacitance of 2.3 mF cm−2 at 0.07 mA cm−2 and an areal (volumetric) energy density of 0.72 μWh cm− 2 (0.36 mWh cm− 3) at 55.07 μW cm−2 (27.54 mW cm−3), along with favorable mechanical and cycling stability. After charging for ~20 s, two MSC-300 devices connected in series could supply energy to a calculator to operate for ~130 s, showing its practical application potential as an energy storage device. Moreover, the device displayed favorable reversibility, stability and durability. After 12 months of aging in air at room temperature, its electrochemical performance was not altered, and after charging-discharging measurements for 5000 cycles at 0.07 mA cm−2, ~93.6% of the areal capacitance was still retained; these results demonstrated its practical long-term application potential as an energy storage device.

Based on the laboratory uniaxial compression test, a numerical model was established by particle flow software and the microscopic parameters were calibrated. The stress-strain curves, the number of micro-cracks, the failure process and the change of microscopic displacement field of gangue cemented backfill samples were studied under different loading rates. The results show that the peak strength and elastic modulus of the sample increase with the increase of loading rate. The number of microcracks is proportional to the loading rate; the microcrack-strain curves can be divided into three stages: no crack initiation, rapid crack growth and stable crack number; the failure process of the sample is divided into four stages: compaction, elastic deformation, plastic failure and residual deformation; the particles on both sides of the microcrack of the sample have different forms of combined failure, including tensile failure, shear failure and mixed failure of tensile and shear action.

Abstract Hydraulic technology with smaller sizes and higher reliability trends, including fault prediction and intelligent control, requires high-performance temperature and pressure-integrated sensors. Current designs rely on planar wafer- or chip-level integration, which is limited by pressure range, chip size, and low reliability. We propose a small-size temperature/high-pressure integrated sensor via the flip-chip technique. The pressure and temperature units are arranged vertically, and the sensing signals of the two units are integrated into one plane through silicon vias and gold–gold bonding, reducing the lateral size and improving the efficiency of signal transmission. The flip-chip technique ensures a reliable electrical connection. A square diaphragm with rounded corners is designed and optimised with simulation to sense high pressure based on the piezoresistive effect. The temperature sensing unit with a thin-film platinum resistor measures temperature and provides back-end high-precision compensation, which will improve the precision of the pressure unit. The integrated chip is fabricated by MEMS technology and packaged to fabricate the extremely small integrated sensor. The integrated sensor is characterised, and the pressure sensor exhibits a sensitivity and sensitivity drift of 7.97 mV/MPa and −0.19% FS in the range of 0–20 MPa and −40 to 120 °C. The linearity, hysteresis, repeatability, accuracy, basic error, and zero-time drift are 0.16% FS, 0.04% FS, 0.06% FS, 0.18% FS, ±0.23% FS and 0.04% FS, respectively. The measurement error of the temperature sensor and temperature coefficient of resistance is less than ±1 °C and 3142.997 ppm/°C, respectively. The integrated sensor has broad applicability in fault diagnosis and safety monitoring of high-end equipment such as automobile detection, industrial equipment, and oil drilling platforms.

Abstract Background The relationship between thyroid hormone (TH) levels in vivo and osteoarthritis (OA) remains inconclusive. This study aims to investigate the association between TH levels and OA, analyze the effect of triiodothyronine on hypertrophic chondrocyte differentiation and OA progression, and identify potential target genes of triiodothyronine in OA to evaluate its diagnostic value. Methods Two-sample mendelian randomization method was used to probe the causal links between hyperthyroidism and OA. Differentially expressed genes (DEGs) from two RNA-sequencing data in Gene Expression Omnibus (GSE199847 and GSE114007) and enrichment analysis of DEGs (166 commonly upregulated genes and 71 commonly downregulated genes of GSE199847 and GSE114007) was performed to analyze the effect of triiodothyronine (T3) on hypertrophic chondrocyte differentiation and OA. C28/I2 cells treated with T3 and reverse transcription and quantitative real-time polymerase chain reaction were used to validate T3 targeted genes. The diagnostic performance of target genes was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC). Results There was a positive causal association between hyperthyroidism and OA (IVW result, OR = 1.330, 95% CI 1.136–1.557, P = 0.0004). Weighted median and Weighted mode analysis also demonstrated that hyperthyroidism had a positive causal association with OA (p 1). Bioinformatics analysis indicated T3 can partially induce the emergence of late hypertrophic chondrocyte and promote OA through extracellular matrix organization, blood vessel development, skeletal system development and ossification. Post-T3 treatment, MAFB, C1QTNF1, COL3A1 and ANGPTL2 were significantly elevated in C28/I2 cells. ROC curves in GSE114007 showed that AUC of all above genes were ≥ 0.7. Conclusions This study identified that hyperthyroidism has a positive causal association with OA by MR analysis. T3 induced hypertrophic chondrocytes promote OA progression by upregulating genes such as MAFB, C1QTNF1, COL3A1 and ANGPTL2, which can also serve as OA diagnosis.

Abstract Introduction Migraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine. Method We used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications. Result The MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93–0.96); p = 2.70e − 10; Replication cohort: OR(95%CI) = 0.93(0.91–0.94); p = 4.21e − 17). Furthermore, GSTM4 passed the SMR at p 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87–0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85–0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83–0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target. Conclusion This study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine.

In post-pandemic period of COVID-19, the increase in the number of sub-healthy population, coupled with factors such as global travel, climate change, and increased contact with wildlife, may lead to a rise in the incidence of central nervous system (Central nervous system, CNS) infections by potential zoonotic pathogens, which has become one of the main reasons for the increase in adjusted life years lost due to human disability. Due to the high case fatality rate of CNS infection and the severe sequelae of the body, it is also one of the most serious global public health challenges at present. To resist pathogen invasion, hosts have constructed a series of barrier structures on their surfaces and within their bodies, including skin barrier, blood-lung barrier, blood-testis barrier and blood-brain barrier (BBB). Among these, the BBB is a complex barrier structure composed of various cellular and non-cellular components. As a biological barrier isolating the CNS from the periphery, BBB can prevent a vast majority of harmful substances from entering the brain, thus ensuring the dynamic equilibrium of the brain's internal environment and the normal functioning of the CNS. However, through long-term evolution, pathogens have developed multiple pathways to cross the BBB and invade the CNS. Currently, five invasion pathways have been confirmed by researchers, including infection or disruption of brain endothelial cells; crossing the BBB through transcellular migration; infiltrating through the BBB as a "Trojan horse" via infected leukocytes; entering the CNS through paracellular spaces; and bypassing the BBB and entering the CNS through axonal transport from the periphery. The severity and complexity of CNS infectious diseases are influenced by the nature of the pathogen itself, the structure and function of the host BBB and the diversity of neural invasion pathways. Furthermore, the molecular mechanisms by which pathogens utilize protein interactions, regulate BBB permeability, and invade the CNS through phagocytosis have been elucidated in detail. This has made CNS delivery of certain drugs possible and also laid a theoretical foundation for the development of entirely new CNS drug delivery systems. Therefore, a comprehensive understanding of the structure of the BBB and the pathways through which pathogens invade the CNS will contribute to the development of strategies to control pathogen invasion, novel brain-targeted drugs, and new delivery systems to mitigate established infections in the host CNS.

Abstract Background β-Arbutin, a hydroquinone glucoside found in pears, bearberry leaves, and various plants, exhibits antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. β-Arbutin has wide applications in the pharmaceutical and cosmetic industries. However, the limited availability of high-performance strains limits the biobased production of β-arbutin. Results This study established the β-arbutin biosynthetic pathway in C. glutamicum ATCC13032 by introducing codon-optimized ubiC, MNX1, and AS. Additionally, the production titer of β-arbutin was increased by further inactivation of csm and trpE to impede the competitive metabolic pathway. Further modification of the upstream metabolic pathway and supplementation of UDP-glucose resulted in the final engineered strain, C. glutamicum AR11, which achieved a β-arbutin production titer of 7.94 g/L in the optimized fermentation medium. Conclusions This study represents the first successful instance of de novo β-arbutin production in C. glutamicum, offering a chassis cell for β-arbutin biosynthesis.

Abstract In the process of lower coal roadway support under double gobs in close coal seams, there are problems such as the whole destruction of the lower coal seam and the intermediate strata, the thin roof of the lower coal roadway with the smaller support space, the upper rock of the lower coal roadway without anchor bearing layer, the roof falling, the anchor cable offing, and so on. On the basis of the engineering background of No. 11103 haulage roadway in Fenxi coal mine, the research methods of theoretical modeling analysis, numerical simulation analysis and field engineering test are comprehensively adopted. In this paper, the layout of the roadway with floor insertion in the lower coal seam, the distribution characteristics of surrounding rock deviatoric stress, the control principle of broken surrounding rock and the coupling support method of shed–cable–prop are systematically studied. The study shows that many measures are needed to ensure the stability of the surrounding rock in the strong mining roadway of the lower coal seam. The lower coal seam roadway section was modified from the original rectangular section to adopt an arched section to counteract the broken roof. The staggered position of the lower coal seam roadway layout was modified from the original coal roadway position to a coal–rock roadway, so as to avoid the area of high deviatoric stress in the coal pillar and the area of crushed coal body, and to leave an effective support space for the roof. The support scheme of the lower coal seam roadway was improved to use anchor cable and single prop to support the weak section of U‐type steel shed with local coupling, and realize unequal force coupling by adjusting the size of the force at different coupling points. In the field monitoring the deformation of the roadway is small, and the support effect is good.

Acinetobacter baumannii is a pathogenic bacterium widespread in human environments, especially in intensive care units, and is associated with high morbidity and infection rates. Multiple drug resistance in A. baumannii frequently leads to the death of patients, making the development of multi-effect antibacterial agents against this bacterium a research hotspot. We have previously found that the X33 antimicrobial oligopeptide can effectively inhibit the growth of Penicillium digitatum and Candida albicans. Herein, we evaluated the antibacterial activity of X33 antimicrobial oligopeptide against A. baumannii by determining the minimum inhibitory concentration, inhibition zone, and growth curve. The increase in extracellular alkaline phosphatase and the leakage of intracellular compounds confirmed the effect of X33 antimicrobial oligopeptide on the cell wall and membrane. Changes in reactive oxygen species, malondialdehyde, ATP, reducing sugar, soluble protein, and pyruvate content demonstrated that the incubation with X33 antimicrobial oligopeptide affected energy metabolism and oxidative stress. Consistent with the physiological characteristics, transcriptomics analysis indicated that incubation with X33 antimicrobial oligopeptide significantly induced changes in the expression of 2339 genes, including 1262 upregulated and 1077 downregulated genes, which participate in oxidative phosphorylation, ribosome, quorum sensing, fatty acid degradation, glycolysis/gluconeogenesis, and citrate cycle pathways. These results provide a fundamental basis for investigating the mechanism of X33 antimicrobial oligopeptide as a potential drug against A. baumannii.

An enclosed microgroove is a vital surface microstructure that is difficult to prepare on the surfaces of difficult-to-machine electrically conductive materials using conventional methods. Electrical discharge machining (EDM) is suitable for this task. It is obtained primarily through layer-by-layer scanning EDM with micro-column electrodes or reciprocating EDM with foil electrodes. However, owing to the small cross-sectional size of the electrodes, a stable machining process is challenging to achieve, which seriously reduces the machining efficiency. To solve these problems, this study proposed ultrasonic vibration-assisted EDM using a laminated electrode possessed strong anti-interference properties for enclosed microgrooves. The effects of ultrasonic vibration on the EDM of microgrooves with single foil and laminated electrodes were investigated. The results show that ultrasonic vibration could improve the machining efficiency of the two types of electrodes and significantly improve the profile quality of the microgrooves prepared using laminated electrodes. When the amplitude was 3 μm and the frequency was 30 kHz, the bottom sidewall corner radius of microgrooves machined by brass foils in laminated electrodes was 28 μm, the width, depth, and roughness of microgrooves machined by copper foils in laminated electrodes were approximately 78 μm, 229 μm and 0.7 μm, the material removal rate was 0.0072 mm3/min. Based on the optimized parameters, inverted “convex” microgrooves with fine consistency were successfully prepared using laminated electrodes on Ti–6Al–4V alloy surfaces. The machining time was reduced by 40% for each microgroove compared with using the single foil electrode. This study provides a new method for preparing complex microgrooves.

Abstract Absent in melanoma 2 (AIM2) is implicated in neuroinflammation. Here, we explored the prognostic significance of serum AIM2 in human aneurysmal subarachnoid hemorrhage (aSAH). We conducted a consecutive enrollment of 127 patients, 56 of whom agreed with blood-drawings not only at admission but also at days 1, 2, 3, 5, 7 and 10 days after aSAH. Serum AIM2 levels of patients and 56 healthy controls were measured. Disease severity was assessed using the modified Fisher scale (mFisher) and World Federation of Neurological Surgeons Scale (WFNS). Neurological outcome at poststroke 90 days was evaluated via the modified Rankin Scale (mRS). Univariate analysis and multivariate analysis were sequentially done to ascertain relationship between serum AIM2 levels, severity, delayed cerebral ischemia (DCI) and 90-day poor prognosis (mRS scores of 3–6). Patients, in comparison to controls, had a significant elevation of serum AIM2 levels at admission and at days 1, 2, 3, 5, 7 and 10 days after aSAH, with the highest levels at days 1, 2, 3 and 5. AIM2 levels were independently correlated with WFNS scores and mFisher scores. Significantly higher serum AIM2 levels were detected in patients with a poor prognosis than in those with a good prognosis, as well as in patients with DCI than in those without DCI. Moreover, serum AIM2 levels independently predicted a poor prognosis and DCI, and were linearly correlated with their risks. Using subgroup analysis, there were no significant interactions between serum AIM2 levels and age, gender, hypertension and so on. There were substantially high predictive abilities of serum AIM2 for poor prognosis and DCI under the receiver operating characteristic curve. The combination models of DCI and poor prognosis, in which serum AIM2, WFNS scores and mFisher scores were incorporated, showed higher discriminatory efficiencies than anyone of the preceding three variables. Moreover, the models are delineated using the nomogram, and performed well under the calibration curve and decision curve. Serum AIM2 levels, with a substantial enhancement during early phase after aSAH, are closely related to bleeding severity, poor 90-day prognosis and DCI of patients, substantializing serum AIM2 as a potential prognostic biomarker of aSAH.

Abstract Abnormal cardiac fibrosis is the main pathological change of post-myocardial infarction (MI) heart failure. Although the E3 ubiquitin ligase FBXL8 is a key regulator in the cell cycle, cell proliferation, and inflammation, its role in post-MI ventricular fibrosis and heart failure remains unknown. FBXL8 was primarily expressed in cardiac fibroblasts (CFs) and remarkably decreased in CFs treated by TGFβ and heart subjected to MI. The echocardiography and histology data suggested that adeno-associated viruses (AAV9)-mediated FBXL8 overexpression had improved cardiac function and ameliorated post-MI cardiac fibrosis. In vitro, FBXL8 overexpression prevented TGFβ-induced proliferation, migration, contraction, and collagen secretion in CFs, while knockdown of FBXL8 demonstrated opposite effects. Mechanistically, FBXL8 interacted with Snail1 to promote Snail1 degradation through the ubiquitin–proteasome system and decreased the activation of RhoA. Moreover, the FBXL8ΔC3 binding domain was indispensable for Snail1 interaction and degradation. Ectopic Snail1 expression partly abolished the effects mediated by FBXL8 overexpression in CFs treated by TGFβ. These results characterized the role of FBXL8 in regulating the ubiquitin-mediated degradation of Snail1 and revealed the underlying molecular mechanism of how MI up-regulated the myofibroblasts differentiation-inducer Snail1 and suggested that FBXL8 may be a potential curative target for improving post-MI cardiac function.

Objective Irrigation is a conventional treatment for acute and chronic periprosthetic joint infections (PJI). However, there has been no unified standard for irrigation during surgery for PJI in the past, and the efficacy is uncertain. The purpose of this study is to create a new irrigation protocol to enhance the infection control rate and reduce the postoperative recurrence rate of PJI patients. Methods We conducted a single‐institution retrospective review with a total of 56 patients who underwent revision total hip or knee arthroplasties due to PJI from January 2011 to January 2022. Conventional irrigation (CI) was used in 32 cases, and standard operating procedure of irrigation (SOPI) was used in 24. The CI protocol carries out an empirical irrigation after debridement, which is quite random. Our SOPI protocol clearly stipulates the soaking concentration and time of hydrogen peroxide and povidone‐iodine. The irrigation is carried out three times, and tissue samples are taken from multiple parts before and after irrigation, which are sent for microbial culture. The important statistical indicators were the rate of positive microbiological culture and postoperative recurrence rate with an average follow‐up of 24 average months. Results The drainage volume was lower in the SOPI group than in the CI group on postoperative day 3 (p

Electrode wear during electrical discharge machining (EDM) is inevitable, and tool electrodes of different materials exhibit different wear rates. Unlike a single-material tool electrode, for a laminated electrode consisting of various material foils (LE-VMF), the components suffer from significantly different amounts of wear and also influence each other in EDM, however, the form and cause of the wear are not clear. Thus, the LE-VMFs including symmetric and asymmetric LE-VMFs were prepared and used in EDM in this paper. The wear of foils in LE-VMFs and their mutual influence during the EDM process were investigated through experiments. The wear forms of a single foil electrode and a foil of the same material in the LE-VMF were also compared. The experimental results show that copper foil with a lower wear rate had a protective effect on an adjacent brass foil with a larger wear rate in the LE-VMF, while the protective effect of the brass foil in the symmetric LE-VMF was larger than that in the asymmetric LE-VMF. The closer the distance from the copper foil, the stronger was the protection effect and the smaller was the wear. In addition, the working surface of the brass foil in the LE-VMF did not show any concavity-like wear in the middle region of its thickness after EDM, as was the case for the single brass foil electrode, even if the thickness of the brass foil was greater than 150 μm.

BackgroundThe objective of this study was to examine whether the combination of elevated levels of C-reactive protein (CRP) and dyslipidemia increased the risk of stroke among middle-aged and older adult individuals in China.MethodsThis study utilized longitudinal data from the China Health and Nutrition Survey (CHNS) collected in 2009, 2015, and 2018. A total of 8,023 participants aged ≥40 years (3,595 males and 4,428 females) were included. The Generalized Estimating Equation (GEE) method was employed to examine the association between inflammation, dyslipidemia, their combined effects, and stroke in the Chinese population.ResultsA total of 174 stroke events occurred during follow-up. Compared with those with normal CRP levels (CRP ≤ 3 mg/L), the adjusted ORs and 95%CI were 2.13 (1.25, 3.64) for the female with elevated CRP level. Compared with those with non-dyslipidemia, the adjusted ORs and 95%CI were 1.56 (1.03, 2.37) for the individuals with high LDL cholesterol, 1.93 (1.12, 3.33) for the male with high LDL cholesterol. Compared with those with normal CRP levels and non-dyslipidemia, the adjusted ORs and 95%CI were 1.74 (1.08, 2.78) for the individuals with elevated CRP levels and dyslipidemia, 2.41 (1.29, 4.49) for the male with elevated CRP levels and dyslipidemia. People with the coexistence of elevated CRP levels and dyslipidemia had the highest risk of stroke among male.ConclusionIn females, higher levels of inflammation are associated with an increased incidence of stroke. In males, individuals with dyslipidemia characterized by high LDL cholesterol levels are more susceptible to stroke. In the general population, the joint effect of inflammation and dyslipidemia predisposes individuals to a higher risk of stroke, particularly among males.

Abstract Abdominal aortic aneurysm (AAA) is a common and potentially life‐threatening condition. Chronic aortic inflammation is closely associated with the pathogenesis of AAA. Nerve injury‐induced protein 1 (NINJ1) is increasingly acknowledged as a significant regulator of the inflammatory process. However, the precise involvement of NINJ1 in AAA formation remains largely unexplored. The present study finds that the expression level of NINJ1 is elevated, along with the specific expression level in macrophages within human and angiotensin II (Ang II)‐induced murine AAA lesions. Furthermore, Ninj1flox/flox and Ninj1flox/floxLyz2‐Cre mice on an ApoE−/− background are generated, and macrophage NINJ1 deficiency inhibits AAA formation and reduces macrophage infiltration in mice infused with Ang II. Consistently, in vitro suppressing the expression level of NINJ1 in macrophages significantly restricts macrophage adhesion and migration, while attenuating macrophage pro‐inflammatory responses. Bulk RNA‐sequencing and pathway analysis uncover that NINJ1 can modulate macrophage infiltration through the TLR4/NF‐κB/CCR2 signaling pathway. Protein‐protein interaction analysis indicates that NINJ1 can activate TLR4 by competitively binding with ANXA2, an inhibitory interacting protein of TLR4. These findings reveal that NINJ1 can modulate AAA formation by promoting macrophage infiltration and pro‐inflammatory responses, highlighting the potential of NINJ1 as a therapeutic target for AAA.

Abstract The advancement of Zn–Se batteries has been hindered by significant challenges, such as the sluggish kinetics of Se cathodes, limited Se loading, and uncontrollable formation of Zn dendrites. In this study, a bidirectional optimization strategy is devised for both cathode and anode to bolster the performance of Zn–Se batteries. A novel bowl‐in‐ball structured carbon (BIBCs) material is synthesized to serve as a nanoreactor, in which tin‐based materials are grown and derived in situ to construct cathodes and anodes. Within the cathode, the multifunctional host material (SnSe@BIBCs) exhibits large adsorption capacity for selenium, and demonstrates supreme catalytic properties and spatially confined characteristics toward the selenium reduction reaction (SeRR). On the anode, Sn@BIBCs displays triple‐induced properties, including the zincophilic of the internal metallic Sn, the homogenized spatial electric field from the 3D spatial structure, and the curvature effect of the bowl‐shaped carbon. Collectively, these factors induce preferential nucleation of Zn, ensuring its uniform deposition. As a result, the integrated Zn–Se battery system achieves a remarkable specific capacity of up to 603 mAh g−1 and an impressive energy density of 581 W kg−1, highlighting its tremendous potential for practical applications.

TANK-binding kinase 1 (TBK1) is a member of the IKK family and plays a crucial role in the activation of non-canonical NF-κB signaling and type I interferon responses. The aberrant activation of TBK1 contributes to the proliferation and survival of various types of tumor cells, particularly in specific mutational or tumorous contexts. Inhibitors targeting TBK1 are under development and application in both in vivo and in vitro settings, yet their clinical efficacy remains limited. Numerous literatures have shown that TBK1 can exhibit both tumor promoting and tumor inhibiting effects. TBK1 acts as a pivotal node within the innate immune pathway, mediating anti-tumor immunity through the activation of innate immune responses. Facilitating interferon-I (IFN-I) production represents a critical mechanism through which TBK1 bridges these processes. IFN has been shown to exert both beneficial and detrimental effects on tumor progression. Hence, the paradoxical role of TBK1 in tumor development may necessitate acknowledgment in light of its downstream IFN-I signaling cascade. In this paper, we review the signaling pathways mediated by TBK1 in various tumor contexts and summarize the dual roles of TBK1 and the TBK1-IFN pathways in both promoting and inhibiting tumor progression. Additionally, we highlight the significance of the TBK1-IFN pathway in clinical therapy, particularly in the context of immune response. We anticipate further advancements in the development of TBK1 inhibitors as part of novel cancer treatment strategies.

BackgroundThere is little research on the relationship between flavonol consumption and chronic kidney disease (CKD). This study aimed to examine the link between flavonol consumption and the risk of CKD among US adults, using data from the 2007–2008, 2009–2010 and 2017–2018 National Health and Nutrition Examination Survey (NHANES).MethodsA cross-sectional approach was used, drawing on data from three NHANES cycles. The flavonol consumption of the participants in this study was assessed using a 48 h dietary recall interview. CKD was diagnosed based on an estimated glomerular filtration rate below 60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio of 30 mg/g or higher.ResultsCompared to the lowest quartile of flavonol intake (Q1), the odds ratios for CKD were 0.598 (95% CI: 0.349, 1.023) for the second quartile (Q2), 0.679 (95% CI: 0.404, 1.142) for the third quartile (Q3), and 0.628 (95% CI: 0.395, 0.998) for the fourth quartile (Q4), with a p value for trend significance of 0.190. In addition, there was a significant trend in CKD risk with isorhamnetin intake, with the odds ratios for CKD decreasing to 0.860 (95% CI: 0.546, 1.354) in the second quartile, 0.778 (95% CI: 0.515, 1.177) in the third quartile, and 0.637 (95% CI: 0.515, 1.177) in the fourth quartile (p for trend = 0.013).ConclusionOur analysis of the NHANES data spanning 2007–2008, 2009–2010, and 2017–2018 suggests that high consumption of dietary flavonol, especially isorhamnetin, might be linked to a lower risk of CKD in US adults. These findings offer new avenues for exploring strategies for managing CKD.

Abstract Fumarate hydratase (FH) deficient renal cell carcinoma (RCC) is a type of tumor with definite metabolic disorder, but the mechanism of metabolic remodeling is still unclear. LncRNA was reported to closely correlate with cancer metabolism, however the biological role of LncRNA in the development of progression of FH-deficent RCC was not well studied either. FH-deficient RCC samples were collected in my hospital and used for RNA-sequencing and Mass spectrometry analysis. FH-deficient RCC cell line UOK262 and control pFH cells were used for in vitro experiments, including proliferation assay, transwell assay, western-blot, mass spectrometry and so on. PDX mouse model was used for further drug inhibition experiments in vivo. In this study, we analyzed the profiles of LncRNA and mRNA in FH-deficienct RCC samples, and we found that the LncRNA-MIR4435-2GH was specifically highly expressed in FH-deficient RCC compared with ccRCC. In vitro experiments demonstrated that MIR4435-2HG was regulated by Fumarate through histone demethylation, and the deletion of this gene could inhibit glutamine metabolism. RNA-pulldown experiments showed that MIR4435-2HG specifically binds to STAT1, which can transcriptionally activate GLS1. GLS1 inhibitor CB-839 could significantly suppress tumor growth in PDX tumor models. This study analyzed the molecular mechanism of MIR4435-2HG in regulating metabolic remodeling of FH-deficient RCC in clinical samples, cells and animal models by combining transcriptional and metabolic methods. We found that that GLS1 was a therapeutic target for this tumor, and MIR4435-2HG can be used as a drug sensitivity marker.

Abstract Background The management of myocardial ischemia–reperfusion injury (MIRI) presents continuous therapeutic challenges. NAD-dependent deacetylase Sirtuin 6 (Sirt6) plays distinct roles in various disease contexts and is hence investigated for potential therapeutic applications for MIRI. This study aimed to examine the impact of Sirt6-overexpressing exosomes derived from adipose stem cells (S-ASC-Exo) on MIRI, focusing on their influence on AIM2-pyroptosis and mitophagy processes. The sirtuin family of proteins, particularly Sirtuin 6 (Sirt6), play a pivotal role in these processes. This study aimed to explore the potential therapeutic effects of Sirt6-enriched exosomes derived from adipose stem cells (S-ASC-Exo) on regulating MIRI. Results Bioinformatic analysis revealed a significant downregulation of Sirt6 in MIRI subjected to control group, causing a consequential increase in mitophagy and pyroptosis regulator expressions. Therefore, our study revealed that Sirt6-enriched exosomes influenced the progression of MIRI through the regulation of target proteins AIM2 and GSDMD, associated with pyroptosis, and p62 and Beclin-1, related to mitophagy. The introduction of S-ASC-Exo inhibited AIM2-pyroptosis while enhancing mitophagy. Consequently, this led to a significant reduction of GSDMD cleavage and pyroptosis in endothelial cells, catalyzing a deceleration in the progression of atherosclerosis. Extensive in vivo and in vitro assays were performed to validate the expressions of these specific genes and proteins, which affirmed the dynamic modulation by Sirt6-enriched exosomes. Furthermore, treatment with S-ASC-Exo drastically ameliorated cardiac functions and limited infarct size, underlining their cardioprotective attributes. Conclusions Our study underscores the potential therapeutic role of Sirt6-enriched exosomes in managing MIRI. We demonstrated their profound cardioprotective effect, evident in the enhanced cardiac function and attenuated tissue damage, through the strategic modulation of AIM2-pyroptosis and mitophagy. Given the intricate interplay between Sirt6 and the aforementioned processes, a comprehensive understanding of these pathways is essential to fully exploit the therapeutic potential of Sirt6. Altogether, our findings indicate the promise of Sirt6-enriched exosomes as a novel therapeutic strategy in treating ischemia–reperfusion injuries and cardiovascular diseases at large. Future research needs to underscore optimizing the balance of mitophagy during myocardial ischemia to avoid potential loss of normal myocytes.

Name Entity Recognition (NER) aims to recognize entities in the engine room domain from unstructured engine room domain text. But in the engine room domain, the entities are diverse and complex, and there is a nesting phenomenon, resulting in a low entity recognition rate. In this paper, a deep learning method incorporating language models is proposed to enhance the entity recognition performance within the engine room. domain. Firstly, the Bidirectional Encoder Representation from Transformers (BERT) language model is employed to train text feature extraction, acquiring a matrix of vector representations at the word level. Secondly, the trained word vectors are fed into the Bidirectional Gated Recurrent Unit (BiGRU) for contextual semantic entity feature extraction. Finally, the global optimal sequence is extracted by combining with the Conditional Random Field (CRF) model to obtain the named entities in the ship cabin semantics. The experimental results show that the proposed algorithm can obtain better F1 values for all three types of entity recognition. Compared with BERT-BiGRU, the overall accuracy of entity identification, recall rate and F1 value are improved by 1.35%, 1.45% and 1.40%, respectively.

Aim: To observe the effects of Ningmitai capsule on semen parameters of infertile patients with chronic prostatitis (CP) and explore the mechanisms. Methods: A total of 43 patients diagnosed with CP were included in the study and administered Ningmitai capsules (4 capsules per dose) for a duration of 6 weeks. Subsequently, assessments were conducted on parameters including sperm concentration, forward progressive motility, total motility, oxidative and anti-oxidative indicators, as well as the concentration of interleukin-8 (IL-8) in seminal plasma before and after the treatment period. Results: Compared to pre-treatment, forward progressive motility and total motility of the semen increased significantly (37.15% ± 18.77% vs. 45.44% ± 19.08%, P < 0.05 and 42.56% ± 21.22% vs. 51.64% ± 19.48%, P < 0.05). And the expression of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) increased significantly after treatment as well (11.36 μmol/L ± 3.28 μmol/L vs. 12.79 μmol/L ± 2.87 μmol/L, P < 0.05 and 9.34 U/mL ± 3.22 U/mL vs. 11.21 U/mL ± 4.87 U/mL, P < 0.05). In addition, the expression of malondialdehyde (MDA) and IL-8 decreased significantly after treatment (41.06 μmol/L ± 24.39 μmol/L vs. 32.17 μmol/L ± 15.04 μmol/L, P < 0.05 and 79.69 ng/L ± 26.24 ng/L vs. 61.35 ng/L ± 23.41 ng/L, P < 0.05). No significant difference in sperm concentration and sperm DNA fragmentation index was observed after the treatment (P > 0.05). Conclusions: Ningmitai capsule can enhance the antioxidant capacity and down-regulate the expression of cytokines in the semen, thereby improving the semen parameters of infertile patients with CP.

Abstract Background Chemokine‐like factor 1 (CKLF1) may be involved in the inflammatory response and secondary brain injury after severe traumatic brain injury (sTBI). We determined serum CKLF1 levels of sTBI patients to further investigate the correlation of CKLF1 levels with disease severity, functional prognosis, and 180‐day mortality of sTBI. Methods Serum CKLF1 levels were measured at admission in 119 sTBI patients and at entry into study in 119 healthy controls. Serum CKLF levels of 50 patients were also quantified at days 1–3, 5, and 7 after admission. Glasgow coma scale (GCS) scores and Rotterdam computerized tomography (CT) classification were utilized to assess disease severity. Extended Glasgow outcome scale (GOSE) scores were recorded to evaluate function prognosis at 180 days after sTBI. Relations of serum CKLF1 levels to 180‐day poor prognosis (GOSE scores of 1–4) and 180‐day mortality were analyzed using univariate analysis, followed by multivariate analysis. Receiver‐operating characteristic (ROC) curve was built to investigate prognostic predictive capability. Results Serum CKLF1 levels of sTBI patients increased at admission, peaked at day 2, and then gradually decreased; they were significantly higher during the 7 days after sTBI than in healthy controls. Differences of areas under ROC curve (areas under the curve [AUCs]) were not significant among the six time points. Multivariate analysis showed that serum CKLF1 levels were independently correlated with GCS scores, Rotterdam CT classification, and GOSE scores. Serum CKLF1 levels were significantly higher in non‐survivors than in survivors and in poor prognosis patients than in good prognosis patients. Serum CKLF1 levels independently predicted 180‐day poor prognosis and 180‐day mortality, and had high 180‐day prognosis and mortality predictive abilities, and their AUCs were similar to those of GCS scores and Rotterdam CT classification. Combination model containing serum CKLF1, GCS scores, and Rotterdam CT classification performed more efficiently than any of them alone in predicting mortality and poor prognosis. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. Conclusion Serum CKLF1 levels are significantly associated with disease severity, poor 180‐day prognosis, and 180‐day mortality in sTBI patients. Hence, complement CKLF1 may serve as a potential prognostic biomarker of sTBI.

Background Previous criteria had limited value in early diagnosis of periprosthetic joint infection (PJI). Here, we constructed a novel machine learning (ML)-derived, “in-time” diagnostic system for PJI and proved its validity. Methods We filtered “in-time” diagnostic indicators reported in the literature based on our continuous retrospective cohort of PJI and aseptic prosthetic loosening patients. With the indicators, we developed a two-level ML model with six base learners including Elastic Net, Linear Support Vector Machine, Kernel Support Vector Machine, Extra Trees, Light Gradient Boosting Machine and Multilayer Perceptron), and one meta-learner, Ensemble Learning of Weighted Voting. The prediction performance of this model was compared with those of previous diagnostic criteria (International Consensus Meeting in 2018 (ICM 2018), etc.). Another prospective cohort was used for internal validation. Based on our ML model, a user-friendly web tool was developed for swift PJI diagnosis in clinical practice. Results A total of 254 patients (199 for development and 55 for validation cohort) were included in this study with 38.2% of them diagnosed as PJI. We included 21 widely accessible features including imaging indicators (X-ray and CT) in the model. The sensitivity and accuracy of our ML model were significantly higher than ICM 2018 in development cohort (90.6% vs. 76.1%, P = 0.032; 94.5% vs. 86.7%, P = 0.020), which was supported by internal validation cohort (84.2% vs. 78.6%; 94.6% vs. 81.8%). Conclusions Our novel ML-derived PJI “in-time” diagnostic system demonstrated significantly improved diagnostic potency for surgical decision-making compared with the commonly used criteria. Moreover, our web-based tool greatly assisted surgeons in distinguishing PJI patients comprehensively. Level of evidence Diagnostic Level III.

Introduction: Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis of MI is exceedingly intricate, with PANoptosis playing a pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, and phenylpropanoids, and exhibits a wide range of pharmacological activities. However, it remains unclear whether XLGB can protect the myocardium from damage after MI. This study aimed to investigate the impact of XLGB on isoprenaline (ISO)-induced MI in mice and its potential mechanisms.Methods: This study assessed the protective effects of XLGB against ISO-induced MI through techniques such as echocardiography, HE staining, Masson staining, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the potential mechanisms of XLGB's protective effects on MI were explored using bioinformatics, molecular docking, and molecular dynamics simulations. These mechanisms were further validated through immunofluorescence staining and Western blotting.Results: The results demonstrated that various doses of XLGB exhibited a significant reduction in myocardial injury induced by myocardial infarction. Intriguingly, higher dosages of XLGB displayed superior therapeutic efficacy compared to the positive control metoprolol. This protective effect is primarily achieved through the inhibition of oxidative stress and the inflammatory processes. Furthermore, we have elucidated that XLGB protected the myocardium from MI-induced damage by suppressing PANoptosis, with a critical role played by the NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, the primary compounds of XLGB were found to directly interact with NLRP3/Caspase3/RIP1, a discovery further validated through molecular docking and molecular dynamics simulations. This suggests that NLRP3/Caspase3/RIP1 may be a therapeutic target for XLGB-induced myocardial protection.Conclusion: In summary, our findings reveal a novel property of XLGB: reverses myocardial damage following MI by inhibiting the NLRP3/Caspase3/RIP1-mediated PANoptosis pathway.

Development of a micromodel that recapitulates multiple mechanical properties to mimic the complex mechanical microenvironment is crucial for cell‐based research. Herein, a microsystem combining structure of hydrogel matrix and acoustic streaming (AS) to mimic the cellular microenvironment is proposed, which can realize multiplex cellular mechanical cues, including matrix stiffness, fluid shear stress (FSS) generated by AS, and matrix roughness. The results demonstrate that the cell spreading area enlarges with the increase of matrix stiffness, and cell spreading is encouraged by integrin β1 cluster to polymerize actin when combines the hydrogel matrix with FSS. In addition, FSS has the influence on the roughness of the hydrogel, which further affects the cell morphology and mechanical properties, inducing mesenchymal stem cells (MSCs) differentiation into astrocytes rapidly. Meanwhile, cell migration is also enhanced by FSS stimulation, particularly, undifferentiated cells at 22 kPa hydrogel have the fastest migration speed, and change the movement model from contact inhibition to contact stimulation migration. Especially, matrix roughness and stiffness dominantly control of cell spreading and differentiation, whereas FSS affects cell migration. In conclusion, the microsystem in this work shows superior performance in regulating the spreading, differentiation, and migration of MSCs, which provides a new tool for cell‐microenvironment study.

BackgroundMonocyte/macrophage (Mo/Mp) is a critical cell population involved in immune modulation of rheumatoid synovitis (RA) across different pathotypes. This study aims to investigate the contribution of Mo/Mp clusters to RA activity, and the biological function of particular subtypes in RA remission.MethodsWe integrated single-cell RNA sequencing datasets from 4 published and 1 in-house studies using Liger selected by comparison. We estimated the abundance of Mo/Mp subtypes in bulk RNA-seq data from the 81 patients of the Pathobiology of Early Arthritis Cohort (PEAC) using deconvolution analysis. Correlations between Mo/Mp subtypes and RA clinical metrics were assessed. A particular cell type was identified using multicolor immunofluorescence and flow cytometry in vivo and successfully induced from a cell line in vitro. Potential immune modulation function of it was performed using immunohistochemical staining, adhesion assay, and RT-qPCR.ResultsWe identified 8 Mo/Mp clusters. As a particular subtype among them, COL3A1+ Mp (CD68+, COL3A1+, ACTA2-) enriched in myeloid pathotype and negatively correlated with RA severity metrics in all pathotypes. Flow cytometry and multicolor immunofluorescence evidenced the enrichment and M2-like phenotype of COL3A1+ Mp in the myeloid pathotype. Further assays suggested that COL3A1+ Mp potentially attenuates RA severity via expressing anti-inflammatory cytokines, enhancing Mp adhesion, and forming a physical barrier at the synovial lining.ConclusionThis study reported unexplored associations between different pathologies and myeloid cell subtypes. We also identified a fibroblast-and-M2-like cluster named COL3A1+ Mp, which potentially contributes to synovial immune homeostasis. Targeting the development of COL3A1+ Mp may hold promise for inducing RA remission.

Abstract Background UDP-glucuronate decarboxylase (also named UXS) converts UDP-glucuronic acid (UDP-GlcA) to UDP-xylose (UDP-Xyl) by decarboxylation of the C6-carboxylic acid of glucuronic acid. UDP-Xyl is an important sugar donor that is required for the synthesis of plant cell wall polysaccharides. Results In this study, we first carried out the genome-wide identification of NtUXS genes in tobacco. A total of 17 NtUXS genes were identified, which could be divided into two groups (Group I and II), and the Group II UXSs can be further divided into two subgroups (Group IIa and IIb). Furthermore, the protein structures, intrachromosomal distributions and gene structures were thoroughly analyzed. To experimentally verify the subcellular localization of NtUXS16 protein, we transformed tobacco BY-2 cells with NtUXS16 fused to the monomeric red fluorescence protein (mRFP) at the C terminus under the control of the cauliflower mosaic virus (CaMV) 35S promoter. The fluorescent signals of NtUXS16-mRFP were localized to the medial-Golgi apparatus. Contrary to previous predictions, protease digestion analysis revealed that NtUXS16 is not a type II membrane protein. Overexpression of NtUXS16 in Arabidopsis seedling in darkness led to a significant increase in hypocotyl length and a reduction in root length compared with the wild type. In summary, these results suggest Golgi apparatus localized-NtUXS16 plays an important role in hypocotyl and root growth in the dark. Conclusion Our findings facilitate our understanding of the novel functions of NtUXS16 and provide insights for further exploration of the biological roles of NtUXS genes in tobacco.

Abstract Conventional electrospinning produces nanofibers with smooth surfaces that limit biomineralization ability. To overcome this disadvantage, we fabricated a tetramethylpyrazine (TMP)-loaded matrix-mimicking biomineralization in PCL/Gelatin composite electrospun membranes with bubble-shaped nanofibrous structures. PCL/Gelatin membranes (PG), PCL/Gelatin membranes containing biomineralized hydroxyapatite (HA) (PGH), and PCL/Gelatin membranes containing biomineralized HA and loaded TMP (PGHT) were tested. In vitro results indicated that the bubble-shaped nanofibrous surface increased the surface roughness of the nanofibers and promoted mineralization. Furthermore, sustained-release TMP had an excellent drug release efficiency. Initially released vigorously, it reached stabilization at day 7, and the slow-release rate stabilized at 61.0 ± 1.8% at 28 days. All membranes revealed an intact cytoskeleton, cell viability, and superior adhesion and proliferation when stained with Ghost Pen Cyclic Peptide, CCK-8, cell adhesion, and EdU. In PGHT membranes, the osteogenic and vascularized gene expression of BMSCs and human vascular endothelial cells was significantly upregulated compared with that in other groups, indicating the PGHT membranes exhibited an effective vascularization role. Subsequently, the membranes were implanted in a rat cranium defect model for 4 and 8 weeks. Micro-CT and histological analysis results showed that the PGHT membranes had better bone regenerative patterns. Additionally, the levels of CD31 and VEGF significantly increased in the PGHT membrane compared with those in other membranes. Thus, PGHT membranes could accelerate the repair of cranium defects in vivo via HA and TMP synergistic effects. Graphical Abstract

Abstract Background Curdione is a sesquiterpene isolated from Curcumae Rhizoma that possesses high biological activity and extensive pharmacological effects. As a traditional Chinese medicine, Curcumae Rhizoma can inhibit the development of many types of cancer, especially colorectal cancer. However, the anti-colorectal mechanism of its monomer curdione remains unclear. Methods Colorectal cancer (CRC) cells were treated with curdione at doses of 12.5 μM, 25 μM, and 50 μM, and then the cells’ activity was measured with methyl thiazolyl tetrazolium (MTT). Nude mice were administered different doses of curdione subcutaneously and oxaliplatin by tail vein injection, and then hematoxylin–eosin (HE) staining was adopted to examine tumor histology. Moreover, flow cytometry was applied to detect reactive oxygen species in cells and tissues. Kits were employed to detect the levels of iron ions, malondialdehyde, lipid hydroperoxide, and glutathione. Polymerase chain reaction (PCR) and Western blotting were adopted to detect ferroptosis and m6A modification-related factors. A methylation spot hybridization assay was performed to measure changes in overall methylation. SLC7A11 and HOXA13 were measured by MeRIP-qPCR. The shRNA-METTL14 plasmid was constructed to verify the inhibitory effect of curdione on CRC. Results A dose-dependent decrease in activity was observed in curdione-treated cells. Curdione increased the accumulation of reactive oxygen species in CRC cells and tumor tissues, greatly enhanced the levels of malondialdehyde, lipid hydroperoxide and Fe2+, and lowered the activity of glutathione. According to the qPCR and Western blot results, curdione promoted the expression of METTL14 and YTHDF2 in CRC cells and tissues, respectively, and decreased the expression of SLC7A11, SLC3A2, HOXA13, and glutathione peroxidase 4. Additionally, in animal experiments, the curdione-treated group showed severe necrosis of tumor cells, as displayed by HE staining. Furthermore, compared with the control group, levels of m6A modifying factors (namely, SLC7A11 and HOXA13) were increased in the tissues after drug intervention. METTL14 knockdown was followed by an increase in CRC cell activity and glutathione levels. However, the levels of reactive oxygen species, malondialdehyde, and iron ions decreased. The expression levels of SLC7A11, SLC3A2, HOXA13, and GPX4 were all increased after METTL14 knockdown. Conclusion The results suggest that curdione induces ferroptosis in CRC by virtue of m6A methylation.

The in-depth discussion and analysis of the synergistic effect of new-type urbanization, greening and digitalization (NUGD) is important for the achievement of sustainable social, ecological and economic development. Therefore, in this study, an evaluation index system composed of these three subsystems was constructed for Chinese cities from 2011 to 2021. The comprehensive and collaborative development levels of each subsystem were measured by means including the entropy weight method and the coupling coordination model, respectively. Then, methods such as ESDA and the Dagum Gini coefficient were applied to investigate the spatiotemporal evolution and spatial differences in the triple synergy effect of the NUGD system in Chinese cities. Finally, the constraining factors of the triple synergy effect were revealed using the obstacle degree model. The findings demonstrated the following: (1) Overall, the NUGD subsystems and their comprehensive levels were increasing, with moderate overall development levels. (2) The synergistic development of the NUGD system exhibited an upward trend. Spatially, the synergistic development level showed distinct differentiation, being higher in the east and lower in the west. The multidimensional dynamic variation characteristics obtained through kernel density estimation revealed that the triple synergy level exhibits high stability. (3) The differences within the east and between the eastern and western areas were the largest, with the intensity of transvariation as the main source. (4) The five criterion layers, including social and spatial urbanization variables, were the key constraints that affected the triple synergy of the NUGD in Chinese cities, and the restrictive role of factors such as the proportion of urban construction land and the per capita postal business volume should not be ignored. This study provides a valuable reference and decision-making guidance to promote China’s acceleration toward a new urbanization path supported by both digitalization and green transformation.

Marine diesel engines are the preferred power equipment for ships and are the most important component among the numerous electromechanical devices on board. Accidents involving these engines can potentially cause immeasurable damage to the vessel, making fault detection in marine diesel engines crucial. This design enables the detection and reporting of faults in marine diesel engines at the earliest possible time through the computation of convolutional neural networks, which is of great significance for ensuring the safe navigation of ships. For this functionality, the Xilinx ZYNQ-7000 XC7Z010 is selected as the main control chip, and the LoRa wireless network is used as the transmission module. The FreeRTOS embedded operating system is ported, with sensor data collection completed on the PS side of the ZYNQ chip and algorithm acceleration calculations on the PL side. Data are then transmitted to the host computer via the LoRa module paired with a custom protocol. Experimental test results show that the program provides stable data transmission, with each module of the algorithm generally accelerating by more than 95% and an accuracy rate of 92.86%. Additionally, the host computer can display the received data in real time. The custom protocol’s header also allows for precise judgments about the completeness and origin of messages, facilitating the expansion of other SOC’s message uplink and the host computer’s message downlink.

Therapeutic HPV vaccines that induce potent HPV-specific cellular immunity and eliminate pre-existing infections remain elusive. Among various candidates under development, those based on DNA constructs are considered promising because of their safety profile, stability, and efficacy. However, the use of electroporation (EP) as a main delivery method for such vaccines is notorious for adverse effects like pain and potentially irreversible muscle damage. Moreover, the requirement for specialized equipment adds to the complexity and cost of clinical applications. As an alternative to EP, lipid nanoparticles (LNPs) that are already commercially available for delivering mRNA and siRNA vaccines are likely to be feasible. Here, we have compared three intramuscular delivery systems in a preclinical setting. In terms of HPV-specific cellular immune responses, mice receiving therapeutic HPV DNA vaccines encapsulated with LNP demonstrated superior outcomes when compared to EP administration, while the naked plasmid vaccine showed negligible responses, as expected. In addition, SM-102 LNP M exhibited the most promising results in delivering candidate DNA vaccines. Thus, LNP proves to be a feasible delivery method in vivo, offering improved immunogenicity over traditional approaches.

Inflammation is an important immune response of the body. It is a physiological process of self-repair and defense against pathogens taken up by biological tissues when stimulated by damage factors such as trauma and infection. Inflammation is the main cause of high morbidity and mortality in most diseases and is the physiological basis of the disease. Targeted therapeutic strategies can achieve efficient toxicity clearance at the inflammatory site, reduce complications, and reduce mortality. Sphingosine-1-phosphate (S1P), a lipid signaling molecule, is involved in immune cell transport by binding to S1P receptors (S1PRs). It plays a key role in innate and adaptive immune responses and is closely related to inflammation. In homeostasis, lymphocytes follow an S1P concentration gradient from the tissues into circulation. One widely accepted mechanism is that during the inflammatory immune response, the S1P gradient is altered, and lymphocytes are blocked from entering the circulation and are, therefore, unable to reach the inflammatory site. However, the full mechanism of its involvement in inflammation is not fully understood. This review focuses on bacterial and viral infections, autoimmune diseases, and immunological aspects of the Sphks/S1P/S1PRs signaling pathway, highlighting their role in promoting intradial-adaptive immune interactions. How S1P signaling is regulated in inflammation and how S1P shapes immune responses through immune cells are explained in detail. We teased apart the immune cell composition of S1P signaling and the critical role of S1P pathway modulators in the host inflammatory immune system. By understanding the role of S1P in the pathogenesis of inflammatory diseases, we linked the genomic studies of S1P-targeted drugs in inflammatory diseases to provide a basis for targeted drug development.

Osteogenesis is caused by multiple factors, and the inflammatory response, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), regeneration of blood vessels, and other factors must be considered in bone tissue engineering. To effectively repair bone defect, it is important to decrease excessive inflammation, enhance the differentiation of mesenchymal stem cells into osteoblasts, and stimulate angiogenesis. Herein, nano-attapulgite (ATP), polyvinyl alcohol (PVA), and gelatin (GEL) scaffolds were produced using 3D printing technology and pioglitazone (PIO)-containing polylactic acid–glycolic acid (PLGA) nanospheres were added. In both in vitro and in vivo studies, material scaffolds with PIO-loaded polylactic acid–glycolic acid nanospheres could reduce the inflammatory response by encouraging macrophage polarization from M1 to M2 and promoting the osteogenic differentiation of BMSCs by activating the BMP2/Smad/RUNX2 signal pathway to repair bone defects. The vascularization of human umbilical vein endothelial cells (HUVECs) through the PI3K/AKT/HIF1-/VEGF pathway was also encouraged. In vivo research using PIO-containing PLGA nanospheres revealed massive collagen deposition in skin models. These findings indicate a potentially effective scaffold for bone healing, when PLGA nanospheres—which contain the drug PIO—are combined with ATP/PVA/GEL scaffolds.

Acute lymphoblastic leukemia (ALL) is a prevalent hematologic malignancy in children, and methotrexate (MTX) is a widely employed curative treatment. Despite its common use, clinical resistance to MTX is frequently encountered. In this study, an MTX-resistant cell line (Reh-MTXR) was established through a stepwise selection process from the ALL cell line Reh. Comparative analysis revealed that Reh-MTXR cells exhibited resistance to MTX in contrast to the parental Reh cells. RNA-seq analysis identified an upregulation of ATP-binding cassette transporter G1 (ABCG1) in Reh-MTXR cells. Knockdown of ABCG1 in Reh-MTXR cells reversed the MTX-resistant phenotype, while overexpression of ABCG1 in Reh cells conferred resistance to MTX. Mechanistically, the heightened expression of ABCG1 accelerated MTX efflux, leading to a reduced accumulation of MTX polyglutamated metabolites. Notably, the ABCG1 inhibitor benzamil effectively sensitized Reh-MTXR cells to MTX treatment. Moreover, the observed upregulation of ABCG1 in Reh-MTXR cells was not induced by alterations in DNA methylation or histone acetylation. This study provides insight into the mechanistic basis of MTX resistance in ALL and also suggests a potential therapeutic approach for MTX-resistant ALL in the future.

With the predicament of sustainable improvement in traditional cities, the low-carbon city pilot policy (LCCPP), as a novel development mode, provides thinking for resolving the tensions of green development, resource conservation and environmental protection among firms. Using Chinese A-share listed companies panel data during 2007-2019, this study adopts the difference-in-differences model to explore the impact of LCCPP on firm green innovation. Based on theoretical analysis, LCCPP-driven environmental rules have the impact of encouraging business green innovation. The relationship between LCCPP and green innovation is strengthened by external media attention and organizational redundancy resources. The mechanism study shows that the incentive effect of LCCPP on firm green innovation is mainly due to the improvement of enterprises' green total factor productivity and financial stability. In addition, the heterogeneity analysis shows that the LCCPP has significantly positive effects in promoting green innovation in high-carbon industries and state-owned enterprises. This research contributes to the understanding of city-level low-carbon policies as a driving force for corporate green innovation, offering practical implications for policymakers and businesses striving for sustainability.

ObjectiveThe purpose of this study was to investigate whether the combination of abnormal systemic immune-inflammation index (SII) levels and hyperglycemia increased the risk of cognitive function decline and reduced survival rate in the United States.MethodsThis cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) database from 2011-2014 and enrolled 1,447 participants aged 60 years or older. Restricted cubic splines (RCS), linear regression and kaplan-meier(KM) curve were employed to explore the combined effects of abnormal SII and hyperglycemia on cognitive function and survival rate, and subgroup analysis was also conducted.ResultsThe RCS analysis revealed an inverted U-shaped relationship between lgSII levels and cognitive function. Linear regression analysis indicated that neither abnormal SII nor diabetes alone significantly contributed to the decline in cognitive function compared to participants with normal SII levels and blood glucose. However, when abnormal SII coexisted with diabetes (but not prediabetes), it resulted to a significant decline in cognitive function. After adjusting for various confounding factors, these results remained significant in Delayed Word Recall (β:-0.76, PConclusionThe findings suggest that the impact of diabetes on cognitive function/survival rate is correlated with SII levels, indicating that their combination enhances predictive power.

Aim: This study aimed to examine foreign-educated male nurses’ motivation to emigrate for work, as well as explore the contextual factors that shape their career trajectories. Background: To that end, we interviewed Chinese male nurses working in Japan. No previous study has examined why male nurses seek employment abroad or the problems they face. Methods: This study employed a qualitative and inductive research design. Sixteen Chinese male nurses working in Eastern and Western Japan were recruited using convenience and snowball sampling methods and were interviewed via video calls. Co-researchers of both genders from different occupational and cultural backgrounds coded the findings and identified common themes in participants’ responses. We analysed our findings vis-à-vis various theoretical perspectives and developed an explanatory model. Results: Participants' experience as nurses in Japan ranged from six months to eight years. The findings confirmed that factors identified in earlier reports influenced nurses' motivation and work. Two new factors emerged: influence by others and social reasons. Moreover, two factors that affected male nurses’ motivation to work abroad, namely, external factors and the influence of others, were identified. Social reasons were identified as a pull factor. Conclusion: Our study provides valuable insights into recruiting and retaining foreign male nurses in developed countries facing issues such as ageing populations and nursing shortages. Implications for nursing policy: This study has important implications for nursing management. Our findings highlight the importance of orienting foreign-educated nurses regarding the local work culture to increase the recruitment and retention of foreign talent. Moreover, enhanced salary packages and benefits to improve motivation can lead to improved job performance, which can positively impact patient and safety outcomes.

Solid polymer electrolytes (SPE) offer an outstanding choice because of their lightweight, flexibility, and excellent thin‐film forming ability. However, the low ionic conductivity and poor lithium ion transfer number (tLi+) restrict its application in all‐solid‐state lithium batteries (ASSLBs). Herein, UIO66‐X metal‐organic frameworks with controllable Lewis basicity, acidity, or neutrality functional groups are synthesized successfully and then incorporated into the poly (ethylene oxide) (PEO) matrix to fabricate SPE. The influence of different organic ligands on the interface interaction between PEO and LiTFSI is investigated by solid‐state nuclear magnetic resonance, Fourier transform infrared spectoscopy and Raman tests, as well as density functional theory calculations. The Lewis acidity group plays a key role in enhancing the ionic conductivity and tLi+. As a result, the constructed Li–Li symmetrical cells retain stable cycling for 2300 h and the LiFePO4‐based ASSLBs deliver outstanding electrochemical properties with 147 mAh g−1 of reversible capacity after 500 cycles at 1C and 60 °C, 131 mAh g−1 after 150 cycles at 0.1C and 30 °C. The fabricated SPEs are self‐standing and flexible with good mechanical stability, demonstrating the great potential for practical application. The results can guide choosing the inorganic filler to prepare high‐performance SPE.

Osteoblasts and osteoclasts play a crucial role in the dynamically coupled balance during bone regeneration and remodeling. They complement and restrict each other in the human body. Decreased osteoblasts lead to insufficient bone formation or excessive formation of osteoclasts, leading to increased bone resorption, which will destroy the structure of the bone tissue. This will greatly increase the risk of diseases such as osteoporosis and nonunions caused by bone defects.Herein, gelatin and polycaprolactone were used as substrates, and biomaterial membranes with mesh and sandwich structures were constructed using the electrospinning technology. Naringenin was loaded into the shell, and vitamin K2 was loaded into the core layer of the nanofibrous membrane. The biocompatibility and osteogenic capacity of the membranes were assessed in vitro using mouse bone marrow mesenchymal stem cells (BMSCs). During osteoclast induction, the receptor activator of nuclear factor kappa-Β ligand (RANKL) was used to coculture RAW264.7 cells with various materials. The regulatory effect of various membranes on osteoclast growth was evaluated by detecting the expression levels of osteoclast-related genes and proteins in the cells.Subsequently, we constructed a model of a rat skull defect and implanted different membranes into the defect. Then, we evaluated the new bone formation in the defect using histological staining and micro-computed tomography after 4 and 8 weeks. The results of in vitro experiments confirmed that the incorporation of naringenin and vitamin K2 stimulated the expression of osteogenesis-related genes and the secretion of osteogenesis-related proteins. Simultaneously, the results showed that naringenin and vitamin K2 inhibited the formation and growth of osteoclasts. Therefore, naringenin and vitamin K2 have a synergistic effect in promoting bone growth and regulating osteoclast growth.

AbstractTo explore the safety and feasibility of wireless thoracoscope in thoracic surgery. A retrospective analysis was made of all the clinical data of 90 patients with thoracoscope lung resection, from April to August 2021, Shanghai changzheng hospital thoracic minimally invasive center. Compared the thoracoscope preparation time, picture resolution, picture delay, surgeon comfort level, assistant comfort level between the wireless thoracoscope group and wired thoracoscope group. The thoracoscopic preparation time of the wireless thoracoscope group was significantly shorter than that of the wired group (26.66 ± 6.04 vs 62.14 ± 10.07, p

Abstract Background Pneumocephalus is rare in vaginal deliveries. Pneumocephalus may be asymptomatic or present with signs of increased intracranial pressure. However, parturients who received epidural anesthesia with air in their brains may experience low intracranial pressure headaches after giving birth, causing the diagnosis of pneumocephalus to be delayed. We report a case of a parturient who developed post-dural puncture headache combined with pneumocephalus secondary to vaginal delivery following epidural anesthesia. Case presentation A 24-year-old G1P0 Chinese woman at 38 weeks gestation was in labor and received epidural anesthesia using the loss of resistance to air technique and had a negative prior medical history. She presented with postural headache, neck stiffness and auditory changes 2 h after vaginal delivery. The head non-contrast computed tomography revealed distributed gas density shadows in the brain, indicating pneumocephalus. Her headache was relieved by bed rest, rehydration, analgesia, and oxygen therapy and completely disappeared after 2 weeks of postpartum bed rest. Conclusions This is the first report that positional headaches after epidural anesthesia may not indicate low intracranial pressure alone; it may combine with pneumocephalus, particularly when using the loss of resistance to air technique. At this moment, head computed tomography is essential to discover other conditions like pneumocephalus.

Abstract Objectives To investigate the diagnostic value of unenhanced CT in mechanical small bowel obstruction (SBO) with small bowel necrosis, and to establish a predictive model. Methods From May 2017 to December 2021, the patients with mechanical SBO admitted to our hospital were retrospectively collected. Taking pathology-confirmed small bowel necrosis as the gold standard, the experimental group was composed of patients with small bowel necrosis confirmed by pathology, and the control group was composed of patients with no intestinal necrosis confirmed by surgery or successful conservative treatment with no recurrence of intestinal obstruction during 1-month followed-up. Results A total of 182 patients were enrolled in this study, 157 patients underwent surgery, of which 35 patients were accompanied with small bowel necrosis and 122 patients were not (33 patients with ischemic findings at surgery without necrosis). Finally, there were 35 patients in the experimental group and 147 patients in the control group. Multivariable logistic regression showed that increased attenuation of small bowel wall (P = 0.002), diffuse mesenteric haziness (P = 0.010), difference of CT value between mesenteric vessel and aorta (P = 0.025) and U-/C-shaped small bowel loop (P = 0.010) were independent risk factors for the diagnosis of mechanical SBO with small bowel necrosis. Through internal verification, the area under curve (AUC) of the predictive model reached 0.886 (95%CI: 0.824–0.947), and the calibration result was moderate. Conclusion Multiple features (increased attenuation of small bowel wall; difference of CT values between mesenteric vessel and aorta; diffuse mesenteric haziness; and U-/C-shaped small bowel loop) of unenhanced CT have clinical value in the diagnosis of mechanical SBO with small bowel necrosis. The predictive model based on these four features could achieve satisfactory efficiency.

Reducing cumbersome mechanical control components is one of the trends of modern agricultural machinery towards a high degree of automation. Whether the control components of sugarcane harvesters can gradually be replaced by central control screens, similar to car cabins, is an unresolved question. At the level of human machine interaction, this involves comparing the efficiency between joystick and touch screen control. This paper conducts a simulated experiment to compare and study the efficiency and user experience of joystick and touch screen control in adjusting the topper and base cutter heights of sugarcane harvesters, aiming to provide a reasonable basis for the design of control interfaces in sugarcane harvester cabins. The electromyographic signals, experiment duration, and subjective cognitive evaluations of participants in both the topper and base cutter groups were analyzed. The results showed that the efficiency, learnability, and ease of use of different control methods varied under different operational tasks. For the topper that corresponds to the operating behavior and height transformation in real time, joystick control demonstrated superior ease of use and operational efficiency compared to touch screen control, with weaker learnability. There was no discernible difference in muscle activation levels between the two control methods. Consequently, joystick control is deemed more suitable for the height adjustment of the topper. Regarding the base cutter with non-real-time mapping of operating behavior and height changes, no significant disparity in ease of use and learnability was observed between the two control methods. Touch screen control yielded lower muscle activation levels and garners higher overall subjective cognitive scale ratings. Thus, touch screen control is considered more suitable for base cutter height adjustment. Lastly, the paper proposes the optimal combination of software and hardware for control components in sugarcane harvester cabins, and provides an objective and multidimensional experimental analysis method for future research on similar human machine interaction interfaces.

CCT MOTIF FAMILY (CMF) genes belong to the CCT gene family and have been shown to play a role in diverse processes, such as flowering time and yield regulation, as well as responses to abiotic stresses. CMF genes have not yet been identified in Brassica rapa. A total of 25 BrCMF genes were identified in this study, and these genes were distributed across eight chromosomes. Collinearity analysis revealed that B. rapa and Arabidopsis thaliana share many homologous genes, suggesting that these genes have similar functions. According to sequencing analysis of promoters, several elements are involved in regulating the expression of genes that mediate responses to abiotic stresses. Analysis of the tissue-specific expression of BrCMF14 revealed that it is highly expressed in several organs. The expression of BrCMF22 was significantly downregulated under salt stress, while the expression of BrCMF5, BrCMF7, and BrCMF21 was also significantly reduced under cold stress. The expression of BrCMF14 and BrCMF5 was significantly increased under drought stress, and the expression of BrCMF7 was upregulated. Furthermore, protein–protein interaction network analysis revealed that A. thaliana homologs of BrCMF interacted with genes involved in the abiotic stress response. In conclusion, BrCMF5, BrCMF7, BrCMF14, BrCMF21, and BrCMF22 appear to play a role in responses to abiotic stresses. The results of this study will aid future investigations of CCT genes in B. rapa.