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The Notch signaling pathway is an evolutionarily conserved pathway essential for regulation of cell development and differentiation. Upregulation and activation of Notch signaling enhances the oncogenic potential of cancer cells through apoptosis resistance. The NOTCH1 expression pattern in hepatocellular cancer (HCC) and its role in apoptosis attenuation was determined. Immunohistostaining identified intensive positive staining of NOTCH1 in human HCC tissues as compared to control tissues. RT-PCR and Western blot quantification data showed that NOTCH1 and its downstream target transcription factor Hes1 were significantly upregulated in HCC cells. Based on these findings, we separated a population of CD44+ tumor-initiating cells (HepG2: >7%; SNU449: >6%) from HCC cell lines to ascertain the role of NOTCH1 in tumorigenesis. After NOTCH1-specific small interfering RNA (siRNA) transfection of tumor-initiating cells (TICs), NOTCH1 was significantly downregulated, and efficient uptake of DNA-targeting chemotherapeutic drugs was observed. Meanwhile, by flow cytometry analysis we found that the rate of apoptosis induction was significantly higher (P

AISI 304 has good physical and chemical properties and thus is widely used. However, due to the low thermal diffusivity, the cutting temperature of AISI 304 is high accelerating the wear of the tool. Therefore, tool wear is a major problem in machining hard cutting materials. In this study, we developed a new type of micro-groove tool whose rake surface was distributed with micro-groove by powder metallurgy based on the finite element temperature field morphology. We compared the wear of the proposed micro-groove tool with an untreated one by using a scanning electron microscope (SEM) and an X-ray energy spectrum. The abrasive, adhesive, and oxidation wear of the rake and the flank face of the micro-groove tool were lower than that of the untreated one. Due to the micro-groove on the rake face of the tool, the contact length between the tool and chip was reduced, leaving more extension space. Furthermore, chip extrusion deformation was avoided, and the energy caused by chip deformation was reduced. After 70 min of cutting, the counterpart reached the specified wear amount while the main cutting force, the feed resistance, and the cutting depth resistance of the proposed micro-groove tool were reduced by 16.1%, 33.9%, and 40.1%, respectively. With regard to steady state, the cutting temperature was reduced by 17.2% and the wear width of the flank face was reduced by 36.7%.

Abstract Plk1 is a key mitotic kinase that localizes to distinct subcellular structures to promote accurate mitotic progression. Plk1 recruitment depends on direct interaction between polo-box domain (PBD) on Plk1 and PBD binding motif (PBD BM) on the interactors. However, recent study showed that PBD BM alone is not enough for stable binding between CENP-U and Plk1 highlighting the complexity of the interaction which warrants further investigation. An important interactor for Plk1 during mitosis is the checkpoint protein BubR1. Plk1 bound to BubR1 via PBD interaction with pT620 phosphorylates BubR1 S676/T680 to promote BubR1-PP2A/B56 interaction. The BubR1-PP2A/B56 complex counteracts the destablizing effect on kinetochore-microtubule attachments by mitotic kinases to promote mitotic progression. Here we show that Plk1 phosphorylates T600/T608 on BubR1 and the double phosphorylation is critical for BubR1-Plk1 interaction. A similar mechanism for Plk1-Bub1 interaction also exists indicating a general principle for Plk1 kinetochore recruitment through self-priming. Mechanistically preventing BubR1 T600/T608 phosphorylation impairs chromosome congression and checkpoint silencing by reducing Plk1 and PP2A/B56 binding to BubR1. Increasing the binding affinity towards Plk1 and PP2A/B56 in BubR1 through protein engineering bypasses the requirement of T600/T608 phosphorylation for mitotic progression. These results reveal a new layer of regulation for accurate mitotic progression.

Abstract Quantum entanglement acts as a crucial part in quantum computation and quantum information, hence quantifying unknown entanglement is an important task. Due to the fact that the amount of entanglement cannot be achieved directly by measuring any physical observables, it remains an open problem to quantify entanglement experimentally. In this work, we provide an effective way to quantify entanglement for the unknown quantum states via artificial neural networks. By choosing the expectation values of measurements as input features and the values of entanglement measures as labels, we train artificial neural network models to predict the entanglement for new quantum states accurately. Our method does not require the full information about unknown quantum states, which highlights the effectiveness and versatility of machine learning in exploring quantum entanglement.

Abstract Background Osteoporotic vertebral compression fractures (OVCF) severely affect the quality of life in the aged population. Percutaneous vertebroplasty (PVP) alleviates pain and stabilizes vertebrae, but suboptimal bone cement distribution can cause complications. Hence, this study aimed to clarify whether a new technique for PVP, using a curved guide wire, enhances the distribution of bone cement and improves clinical outcomes in patients with OVCF. Methods Patients with single-segment OVCF underwent PVP or curved guide wire percutaneous vertebroplasty (C-PVP). Propensity score matching (PSM) was employed to balanced the baseline characteristics. The primary outcomes were the visual analog scale (VAS) and Oswestry disability index (ODI) scores. The secondary outcomes included assessments of bone cement distribution, bone cement injection volume, radiological parameters, and general clinical results. Additionally, Complications and adverse events were documented. Results After PSM analysis, each group comprised 54 patients, which significantly reduced baseline differences. The C-PVP group showed better clinical outcomes compared to the traditional PVP group. One month after surgery, the C-PVP group had significantly lower VAS and ODI scores (p

This paper is concerned with almost sure exponential synchronization of multilayer complex networks with Markovian switching via aperiodically intermittent discrete observation noise. First, Markovian switching and multilayer interaction factors are taken into account simultaneously, which make our system more general compared with the existing literature. Meanwhile, the network architecture may be undirected or directed, and consequently, the adjacency matrix is symmetrical and asymmetrical. Second, the control strategy is based on aperiodically intermittent discrete observation noise, where the average control rate is integrated to depict the distributions of work/rest intervals of the control strategy from an overall perspective. Third, different from the work about th moment exponential synchronization of network systems, by utilizing M-matrix theory and various stochastic analysis techniques including the Itô formula, the Gronwall inequality, and the Borel-Cantelli lemma, some criteria on almost sure exponential synchronization of multilayer complex networks with Markovian switching have been constructed and the upper bound of the duration time has been also estimated. Finally, several numerical simulations are exhibited to validate the effectiveness and feasibility of our analytical findings.

Abstract Ureteral obstruction is a prevalent urological condition associated with significant complications. The purpose of our study was to assess the safety and efficacy of a novel self-expanding, large caliber, biocompatible polymer-coated ureteral stent (Allium) for the treatment of ureteral obstructions. We conducted a retrospective analysis of data from patients who underwent Allium ureteral stent placement at our institute between November 2018 and May 2023. Demographic, clinical, and perioperative parameters were collected and analyzed. Logistic regression analyses were performed to identify preoperative factors predicting Allium stent migration. The study cohort comprised 30 patients who received a total of 40 successfully implanted Allium stents. No significant adverse events related to the insertion procedure were observed. During a median follow-up period of 29 months (range: 1–60 months), migration occurred in 11 (27.5%) stents while encrustation was noted in 8 (20%) stents. The median functional duration of the Allium stents was found to be 22 months (range:1–60 months), with an overall functioning rate at last follow-up being recorded as 59.5%. Multivariate analysis revealed that the glomerular filtration rate of the ipsilateral kidney was the sole risk factor predictive of Allium stent migration. With its minimal invasiveness and good tolerability, the Allium stent represents a safe and viable management option for treating ureteric obstructions; however, it should not be considered as definitive treatment but rather as an alternative option for patients unwilling or unsuitable for definitive treatment, particularly high-risk individuals or elderly patients exhibiting decreased ipsilateral glomerular filtration rates.

In view of the problems of gas overrun and coal and gas outburst accidents in the construction of underground gas extraction boreholes in coal mines, the problems existing in the traditional simple orifice device and the normally open automatic orifice prevention system were analyzed, and the normally closed blowout prevention system and method were proposed, which could be integrated with the drilling rig body to meet the needs of various special-shaped roadway orifice sealing, slag discharge and gas extraction. At the same time, the control system can be linked with the hydraulic control system of the drilling machine to realize the automatic closing of the pressure relief of the blowout prevention system at the orifice to prevent the leakage of gas in the hole. Compared with the traditional and existing orifice blowout prevention systems, the blowout prevention system is simple and clear, has stronger adaptability to the drilling rig, significantly improves the effect of drilling blowout prevention and treatment, and significantly reduces the labor intensity of workers, which can provide a favorable guarantee for the safety and efficiency of underground gas extraction drilling construction.

Abstract Golden jackal optimization (GJO) is inspired by mundane characteristics and collaborative hunting behaviour, which mimics foraging, trespassing and encompassing, and capturing prey to refresh a jackal’s position. However, the GJO has several limitations, such as a slow convergence rate, low computational accuracy, premature convergence, poor solution efficiency, and weak exploration and exploitation. To enhance the global detection ability and solution accuracy, this paper proposes a novel complex-valued encoding golden jackal optimization (CGJO) to achieve function optimization and engineering design. The complex-valued encoding strategy deploys a dual-diploid organization to encode the real and imaginary portions of the golden jackal and converts the dual-dimensional encoding region to the single-dimensional manifestation region, which increases population diversity, restricts search stagnation, expands the exploration area, promotes information exchange, fosters collaboration efficiency and improves convergence accuracy. CGJO not only exhibits strong adaptability and robustness to achieve supplementary advantages and enhance optimization efficiency but also balances global exploration and local exploitation to promote computational precision and determine the best solution. The CEC 2022 test suite and six real-world engineering designs are utilized to evaluate the effectiveness and feasibility of CGJO. CGJO is compared with three categories of existing optimization algorithms: (1) WO, HO, NRBO and BKA are recently published algorithms; (2) SCSO, GJO, RGJO and SGJO are highly cited algorithms; and (3) L-SHADE, LSHADE-EpsSin and CMA-ES are highly performing algorithms. The experimental results reveal that the effectiveness and feasibility of CGJO are superior to those of other algorithms. The CGJO has strong superiority and reliability to achieve a quicker convergence rate, greater computation precision, and greater stability and robustness.

Abstract Background An mHealth-based school health education platform (EduSaltS) was promoted in real-world China to reduce salt intake among children and their families. This progress evaluation explores its implementation process and influencing factors using mixed methods. Methods The mixed-methods process evaluation employed the RE-AIM framework. Quantitative data were collected from a management website monitoring 54,435 third-grade students across two cities. Questionnaire surveys (n = 27,542) assessed pre- and post-education effectiveness. Mixed-effects models were used to control cluster effects. Qualitative interviews (23 individuals and 8 focus groups) identified program performance, facilitators, and barriers. Findings were triangulated using the RE-AIM framework. Results The program achieved 100% participation among all the third-grade classes of the 208 invited primary schools, with a 97.7% registration rate among all the 54,435 families, indicating high "Reach." Qualitative interviews revealed positive engagement from children and parents through the "small hands leading big hands" strategy. The high completion rate of 84.9% for each health cloud lesson and the significant improvement in salt reduction knowledge and behaviors scores from 75.0 (95%CI: 74.7–75.3) to 80.9 (95%CI: 80.6–81.2) out of 100 demonstrated the "Effect" of EduSaltS. The program's "Adoption" and "Implementation" were supported by attractive materials, reduced workload via auto-delivered lessons/activities and performance evaluation, and high fidelity to recommended activities, with medians 3.0 (IQR: 2.0–8.0)/class and 9.0 (IQR: 5.0–14.0)/school. Stable course completion rates (79.4%-93.4%) over one year indicated promising "Maintenance." Apart from the facilitating features praised by the interviewees, government support was the basis for the scaling up of EduSaltS. Barriers included the lack of smartphone skills among some parents and competing priorities for schools. Unhealthy off-campus environments, such as excessive use of salt in pre-packaged and restaurant foods, also hindered salt reduction efforts. The program's scalability was evident through its integration into existing health education, engagement of local governments and adaptation across various mobile devices. Conclusions The mHealth-based school health education program is scalable and effective for public salt reduction in China. Identified barriers and facilitators can inform future health program scale-ups. The program's successful implementation demonstrates its potential for broader application in public health initiatives aimed at reducing dietary salt intake.

Abstract Steroid-induced osteonecrosis of the femoral head (SONFH) is the predominant cause of non-traumatic osteonecrosis of the femoral head (ONFH). Impaired blood supply and reduced osteogenic activity of the femoral head are the key pathogenic mechanisms of SONFH. Fibroblast growth factor 23 (FGF23) levels are not only a biomarker for early vascular lesions caused by abnormal mineral metabolism, but can also act directly on the peripheral vascular system, leading to vascular pathology. The aim of this study was to observe the role of FGF23 on bone microarchitecture and vascular endothelium, and to investigate activation of pyroptosis in SONFH. Lipopolysaccharide (LPS) combined with methylprednisolone (MPS) was applied for SONFH mouse models, and adenovirus was used to increase or decrease the level of FGF23. Micro-CT and histopathological staining were used to observe the structure of the femoral head, and immunohistochemical staining was used to observe the vascular density. The cells were further cultured in vitro and placed in a hypoxic environment for 12 h to simulate the microenvironment of vascular injury during SONFH. The effect of FGF23 on osteogenic differentiation was evaluated using alkaline phosphatase staining, alizarin red S staining and expression of bone formation-related proteins. Matrigel tube formation assay in vitro and immunofluorescence were used to detect the ability of FGF23 to affect endothelial cell angiogenesis. Steroids activated the pyroptosis signaling pathway, promoted the secretion of inflammatory factors in SONFH models, led to vascular endothelial dysfunction and damaged the femoral head structure. In addition, FGF23 inhibited the HUVECs angiogenesis and BMSCs osteogenic differentiation. FGF23 silencing attenuated steroid-induced osteonecrosis of the femoral head by inhibiting the pyroptosis signaling pathway, and promoting osteogenic differentiation of BMSCs and angiogenesis of HUVECs in vitro.

Abstract A wideband end‐fire stepped slot antenna with gain enhancement and filtering capability is proposed. On one hand, a parasitic dipole serving as a director is introduced in the stepped slot to improve the radiation gain of the slot antenna without increasing its physical size. It is found that a gain enhancement of about 2 dB can be achieved after adopting such approach. On the other hand, an absorptive branch possessing a nearly complementary frequency response with regard to the one of the slot antenna is in‐parallel loaded at the microstrip feedline. It allows the partial dissipation of the out‐of‐band/non‐radiated RF‐signal power of the antenna to attain both an RF‐quasi‐absorptive behaviour and filtering capability. It is found that after loading the dissipative branch, the out‐of‐band radiation efficiency of the slot antenna is reduced to less than 20%. The measured results of a fabricated proof‐of‐concept antenna prototype show a reasonable agreement with the simulated ones and verify the RF performance merits of the proposed stepped slot antenna, such as wide RF operating band covering the 3.39−4.73‐GHz range, end‐fire radiation with a front‐to‐back ratio (FBR) above 10 dB, flat radiation gain, and co‐integrated filtering functionality with RF‐quasi‐absorptive capability.

Objective The main objective of this study was to determine available energy and nutritional digestibility of extruded cereals and the effect of extrusion on the nutritional value of feed ingredients, aiming to provide scientific basis for efficient application of extrusion in the diets of growing pigs. Methods In Exp. 1, 48 crossbred growing pigs (Duroc×Landrace×Yorkshire) with an initial body weight (BW) of 34.6±2.2 kg were selected and fed with eight diets (non-extrusion or extrusion) to determine the digestible energy (DE), metabolizable energy (ME), and nutrients digestibility. Eight diets included extruded grains (barley, wheat, sorghum, or broken rice), while four had unprocessed grains. In Exp. 2, 9 diets were formulated including 4 cereals with extrusion or non-extrusion and a N-free diet. In addition, 9 growing pigs (BW = 22.3±2.8 kg) were fitted with T-cannula in the distal ileum and arranged in a 9×6 Youden square design. Results Results show that apparent total tract digestibility of gross energy, dry matter, organic meal, ether extract, neutral and acid detergent fiber was not affected by the extrusion process and there was no interaction between cereal type and extrusion treatment on DE, ME. However, the apparent total tract digestibility for crude protein (CP) increased markedly (p

Currently, when renewable generation participates in frequency regulation, the traditional control method is to emulate synchronous generators through virtual inertia control. However, virtual inertia has a time delay, so essentially, it is a fast power response. Meanwhile, virtual inertia control is likely to be affected by frequency fluctuation since it responds to the derivative of frequency. Hence, it’s worth exploring non-virtual inertia control for renewable energy when participating in frequency regulation. For this reason, a novel two-segment droop control scheme for renewable energy frequency regulation is proposed in this research. Firstly, the extended system frequency regulation (SFR) model, which contains virtual inertia with time delay, is built and analytically solved by order decrement based on the Routh approximation method. Afterwards, according to the analytical solution, time delay affects the frequency response of renewable energy. It can also be analytically proved that the non-virtual inertia control, e.g., sole droop control, could replace virtual inertia under the same frequency deviation. Still, more energy may be needed for frequency regulation. Furthermore, a novel two-segment droop control is presented, and to analytically prove its ability to replace virtual inertia, the impulse function balancing principle and the integration by parts algorithm were adopted to address the initial conditions of the differential equation. Based on the analytical expression, it can be analytically proved that a lower frequency deviation can be obtained under the same frequency regulation energy. Accordingly, a parameter-setting method for two-segment droop control was proposed. Finally, the effectiveness of the proposed method is verified by using a two-area system frequency response model, and the results reveal that it can be used to replace virtual inertia and has better performance.

The Cytochrome P450 (CYP450) family is the largest enzyme protein family in plants, distributed across various organs and involved in significant catalytic activities in primary and secondary metabolic processes. In this study, we cloned the PtCYP721A57 gene, characterized its open reading frame (ORF), and conducted comprehensive analyses including physicochemical properties, evolutionary relationships, subcellular localization, prokaryotic expression, and correlation between the relative expression of different parts and the content of tenuifolin, hormones, and abiotic stress response associated with the encoded protein. The ORF of PtCYP721A57 was 1,521 bp, with a secondary structure predominantly composed of α-helices and random coils. Subcellular localization experiments confirmed the presence of PtCYP721A57 in the endoplasmic reticulum. For prokaryotic expression, we constructed the recombinant plasmid pET28a-PtCYP721A57 using pET28a as the vector, which was then transformed into BL21(DE3). Induction with Isopropyl β-D-1-thiogalactopyranoside (IPTG) at temperatures of 16 and 25 °C and varying concentrations (0.1, 0.2, 0.5, 1, 2 mM) resulted in the formation of inclusion bodies, with higher expression observed at 25 °C. Our qPCR analyses revealed that PtCYP721A57 exhibited the highest expression in the cortex of Polygala tenuifolia, followed by roots and xylem, correlating with the observed tenuifolin content distribution. Induction with abscisic acid (ABA) and chitosan (CHT) initially decreased PtCYP721A57 expression followed by a subsequent increase, peaking at 48 h. Similarly, drought stress induced a gradual increase in PtCYP721A57 expression, also peaking at 48 h. NaCl treatment for 6 h significantly upregulated PtCYP721A57 expression. In conclusion, our study provides foundational insights into the PtCYP721A57 gene in Polygala tenuifolia, laying the groundwork for further exploration of its role in the biosynthesis pathway of triterpenoid saponins.

Sexual reproduction through seeds is an effective way to renew plant populations and increase their genetic diversity, but seed germination process is complicated and relatively difficult due to the restriction of environmental conditions. Wetland plants that reproduce sexually through seeds may be affected by changes in moisture and temperature. This study aims to explore the ecological adaptation strategies of seed germination of Lilium concolor var. megalanthum under different hydrothermal conditions. Controlled experiments were conducted to investigate the germination performance of L. concolor var. megalanthum seeds at different temperatures (10°C, 15°C, 20°C, 25°C, and 30°C) and simulated drought stress conditions using PEG-6000 solutions (0%, 5%, 10%, 15%, and 20%). The results showed that temperature, drought stress, and their interaction significantly affected the days to first germination, germination percentage, coefficient of germination rate, germination energy, germination index, and vigor index of seeds (p

Abstract Klebsiella pneumoniae, a major clinical pathogen known for causing severe infections, is attracting heightened attention due to its escalating antibiotic resistance. Phages are emerging as a promising alternative to antibiotics; however, their specificity to particular hosts often restricts their use. In this study, a collection of 114 phages is obtained and subjected to analysis against 238 clinical K. pneumoniae strains, revealing a spectrum of lytic behaviors. A correlation between putative tail protein clusters and lysis patterns leads to the discovery of six receptor‐binding protein (RBP) clusters that determine host capsule tropism. Significantly, RBPs with cross‐capsular lysis capabilities are identified. The newly‐identified RBPs provide a toolbox for customizing phages to target diverse capsular types. Building on the toolbox, the engineered phages with altered RBPs successfully shifted and broadened their host capsule tropism, setting the stage for tunable phage that offer a precise and flexible solution to combat K. pneumoniae infections.

Mercury pollution in emerging industrial zones and surrounding areas, especially in industrial concentration areas, has attracted much attention. So as to clarify the characteristics of Hg in the environment in China’s small and medium-sized industrial emerging and surrounding areas, central urban area of Gongzhuling, a traditional agricultural town with a high degree of industrialization in northeast Changchun industrial base, is taken as the scope. Geological accumulation trin (Igeo) was used to study the degree of soil mercury contamination in Gongzhuling area, latent Er (ecological risk) trin was used to appraise the Er of soil Hg in the study area, and non-carcinogenic risk assessment of mercury in soil using human exposure risk assessment model. The results showed that 34% of soil samples had higher Hg content than the background value of the province’s soil (0.04 mg kg−1). The Igeo results showed that Hg pollution rate of soil in study area was 9% (index >0). In conclusion, the level of soil Hg pollution in Gongzhuling area was low, and the pollution area is mainly concentrated in the northwestern part of the study range. The highest and lowest Er values of soil Hg from the study sample were 2.23 and 214.83, and 24% of the samples had Er > 40, that means they pose a moderate or higher potential ecological risk, and most of these points are located in the northeast of the study range. The main route of human exposure to Hg is oral ingestion. The HQ (non-carcinogenic risk index) and HI (total non-carcinogenic risk value) of soil mercury were both much less than 1, it indicates that the present level of soil Hg in the study range does not pose a threat to local adult health for the time being. This study provides reference for other urban pollution risk assessment, and further defines the direction of future work.

IntroductionDue to its remarkable anti-inflammatory pharmacological activity, Farfarae Flos has gained extensive usage in the treatment of various inflammatory diseases such as bronchitis, pneumonia, prostatitis and colitis. And Farfarae Flos come in two color types depending on the color of the flowers: yellowish-white (YW), and purplish-red (PR). However, the difference in anti-inflammatory activity and metabolic profiles between the two flower colors remains unexplored.MethodsThis study aims to explore the difference in the anti-inflammatory potential between YW and PR variants of Farfarae Flos and unravel the mechanisms responsible for the observed differences in anti-inflammatory activity through an integrated approach encompassing untargeted metabolomics and in vivo/vitro experimental studies. Initially, we verified the contrasting effects of YW and PR on the inhibition of the inflammatory factors interleukin-6 (IL-6) and nitric oxide (NO) by utilizing an in vitro RAW 264.7 cell inflammation model. Subsequently, a comprehensive evaluation of the systemic inhibitory capacity of YW and PR on IL-6, Interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) was conducted using a validated whole-body mouse model, followed by the analysis of inflammatory factors and histological examination of collected serum, liver, and spleen after 7 days. Furthermore, non-targeted metabolomics profiling was employed to analyze the metabolite profiles of Farfarae Flos with different colors, and quantitative analysis was conducted to identify differential metabolites between YW and PR. The correlation between the anti-inflammatory activities of differentially accumulated metabolites (DAMs) and Farfarae Flos was investigated, resulting in the identification of 48 compounds exhibiting significant anti-inflammatory activity. Additionally, KEGG pathway enrichment analysis was performed to elucidate the underlying mechanisms.ResultsOur findings demonstrate that both YW and PR possess anti-inflammatory abilities, with PR exhibiting significantly superior efficacy. The integration of in vivo/vitro experiments and non-targeted metabolomics confirmed the exceptional anti-inflammatory potential of PR and solidified its classification as the “purplish-red better” of Farfarae Flos.DiscussionThis study provides valuable insights into the breeding and medical transformation of Farfarae Flos varieties, along with a scientific basis for the establishment of quality standards and the development of new drugs utilizing Farfarae Flos.

The genus Polygala (Polygalaceae), comprising about 670 species worldwide, has more than 40 species in China. The roots of Polygala tenuifolia Willd., Polygala sibirica L., and Polygala japonica Houtt. are recorded in the Chinese Pharmacopeia. Other closely related plants of the Polygala genus are also widely used in the folk medicine of southern China, such as Polygala fallax Hemsl., Polygala arvensis Willd., and Polygala glomerata Lour. To systematically compare the chemical compositional and elucidate characteristic compounds among the Polygala genus, six Polygala species, namely P. tenuifolia, P. sibirica, P. japonica, P. fallax, P. arvensis and P. glomerata, underwent comprehensive phytochemical studies using the ultra performance liquid chromatography-quadrupole time-of-flight tandem mass Spectrometry (UPLC-Q-TOF-MS/MS) technique, resulting in the identification of 154 compounds, consisting of 62 oligosaccharide esters (40.26 %), 58 saponins (37.66 %), 29 xanthones (18.83 %), and 5 other chemicals (3.25 %). Based on the Masslynx computational tool, a comprehensive comparative phytochemical profiling was achieved and revealed differences in composition among the six Polygala species. P. sibirica exhibited higher levels of specific compounds and was more closely related to P. tenuifolia. Meanwhile, P. japonica showed greater similarity to P. fallax, P. arvensis, and P. glomerata. Oligosaccharide esters and triterpene saponins were more abundant in P. sibirica and P. tenuifolia than in other species. Furthermore, the antioxidant activities (1,1-diphenyl-2-acrylohydrazide [DPPH], 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt [ABTS], copper ion reducing antioxidant capacity [CUPRAC], and ferric ion-reducing antioxidant power [FRAP]) of the six species were evaluated. Among them, P. tenuifolia demonstrated superior antioxidant potential, with a lower half-maximal inhibitory concentration (IC50) value for scavenging DPPH radicals and excellence in CUPRAC (119.85 ± 16.28 μM/0.01 g) compared to other plants. P. japonica showed higher ABTS (98.94 ± 0.03 μM/0.01 g) and FRAP (42.58 ± 0.08 μM/0.01 g). Total flavonoids showed remarkable antioxidant capabilities among the six medicinal plants. Total saponins and phenolics also contributed to the antioxidant potential of these plants. The systematic data and results obtained may provide methodological support for further evaluating the potential use of folk Polygala plants as new effective materials in various commercial sectors, including food, cosmetic, and pharmaceutical industries.

Abstract Bovine viral diarrhea virus (BVDV) is considered to be the most common agent of severe diarrhea in cattle worldwide, causing fever, diarrhea, ulcers, and abortion. Bovine herpesvirus 1 (BoHV-1) is also a major bovine respiratory disease agent that spreads worldwide and causes extensive damage to the livestock industry. Recombinase polymerase amplification (RPA) is a novel nucleic acid amplification method with the advantages of high efficiency, rapidity and sensitivity, which has been widely used in the diagnosis of infectious diseases. A dual RPA assay was developed for the simultaneous detection of BVDV and BoHV-1. The assay was completed at a constant temperature of 37 °C for 30 min. It was highly sensitive and had no cross-reactivity with other common bovine viruses. The detection rate of BVDV RPA in clinical samples (36.67%) was higher than that of PCR (33.33%), the detection rate of BoHV-1 RPA and PCR were equal. Therefore, the established dual RPA assay for BVDV and BoHV-1 could be a potential candidate for use as an immediate diagnostic.

Abstract Clustered regularly interspaced short palindromic repeats and associated Cas protein (CRISPR–Cas), a powerful genome editing tool, has revolutionized gene function investigation and exhibits huge potential for clinical applications. CRISPR–Cas-mediated gene knockout has already become a routine method in research laboratories. However, in the last few years, accumulating evidences have demonstrated that genes knocked out by CRISPR–Cas may not be truly silenced. Functional residual proteins could be generated in such knockout organisms to compensate the putative loss of function, termed herein knockout escaping. In line with this, several CRISPR–Cas-mediated knockout screenings have discovered much less abnormal phenotypes than expected. How does knockout escaping happen and how often does it happen have not been systematically reviewed yet. Without knowing this, knockout results could easily be misinterpreted. In this review, we summarize these evidences and propose two main mechanisms allowing knockout escaping. To avoid the confusion caused by knockout escaping, several strategies are discussed as well as their advantages and disadvantages. On the other hand, knockout escaping also provides convenient tools for studying essential genes and treating monogenic disorders such as Duchenne muscular dystrophy, which are discussed in the end.

Abstract Lung adenocarcinoma (LUAD) continues to pose a significant mortality risk with a lack of dependable biomarkers for early noninvasive cancer detection. Here, we find that aberrant lipid metabolism is significantly enriched in lung cancer cells. Further, we identified four signature lipids highly associated with LUAD and developed a lipid signature-based scoring model (LSRscore). Evaluation of LSRscore in a discovery cohort reveals a robust predictive capability for LUAD (AUC: 0.972), a result further validated in an independent cohort (AUC: 0.92). We highlight one lipid signature biomarker, PE(18:0/18:1), consistently exhibiting altered levels both in cancer tissue and in plasma of LUAD patients, demonstrating significant predictive power for early-stage LUAD. Transcriptome analysis reveals an association between increased PE(18:0/18:1) levels and dysregulated glycerophospholipid metabolism, which consistently displays strong prognostic value across two LUAD cohorts. The combined utility of LSRscore and PE(18:0/18:1) holds promise for early-stage diagnosis and prognosis of LUAD.

Abstract Insertion sequences (ISs) promote the transmission of antimicrobial resistance genes (ARGs) across bacterial populations. However, their contributions and dynamics during the transmission of resistance remain unclear. In this study, we selected IS26 as a representative transposable element to decipher the relationship between ISs and ARGs and to investigate their transfer features and transmission trends. We retrieved 2656 translocatable IS26 ‐bounded units with ARGs (tIS26‐bUs‐ARGs) in complete bacterial genomes from the NCBI RefSeq database. In total, 124 ARGs spanning 12 classes of antibiotics were detected, and the average contribution rate of IS26 to these genes was 41.2%. We found that IS26 ‐bounded units (IS26‐bUs) mediated extensive ARG dissemination within the bacteria of the Gammaproteobacteria class, showing strong transfer potential between strains, species, and even phyla. The IS26‐bUs expanded in bacterial populations over time, and their temporal expansion trend was significantly correlated with antibiotic usage. This wide dissemination could be due to the nonspecific target site preference of IS26. Finally, we experimentally confirmed that the introduction of a single copy of IS26 could lead to the formation of a composite transposon mediating the transmission of “passenger” genes. These observations extend our knowledge of the IS26 and provide new insights into the mediating role of ISs in the dissemination of antibiotic resistance.

Traditionally, virtual inertia is used as the control strategy for wind turbines when participating in frequency regulation. However, it has inherent defects in measurement error amplification due to the frequency differential. Also, when control delay of wind turbines is taken into consideration, virtual inertia is essentially a fast power response, just the same as droop control. Hence, considering the adaptability of droop control, it is valuable to explore a novel droop control method without virtual inertia, as the frequency response model of wind turbines. For this reason, a multi-segment droop control strategy is proposed to provide a reliable frequency regulation model for wind turbines that can be broadly applied to other inverter-based power sources. Firstly, based on the extended system frequency response model, a differential equation including piecewise time-varying coefficients is established, and the analytical expression of the frequency response is obtained using the impulse function balancing principle and the integration by parts algorithm. Subsequently, based on analytical expression, the performance of the presented strategy is theoretically analyzed via comparison with virtual inertia control, and the conclusion that the presented multi-segment droop control has better frequency regulation performance can be got. Furthermore, to achieve optimal frequency regulation performance, a Lagrangian function is established to determine the optimal parameters of the proposed control strategy. Finally, the performance of the proposed strategy was verified in a two-area system model constructed on MATLAB/Simulink. Results show that the proposed multi-segment droop control has better frequency regulation performance.

“Green-covering and red-heart” Guanyin Tuqu (GRTQ), as a type of special fermentation starter, is characterized by the “green-covering” formed on the surface of Guanyin Tuqu (SQ) and the “red-heart” in the center of Guanyin Tuqu (CQ). However, the mechanisms that promote temporal succession in the GRTQ microbial ecology and the formation of “green-covering and red-heart” characteristics remain unclear. Herein, we correlated the temporal profiles of microbial community succession with the main environmental variables (temperature, moisture, and acidity) and spatial position (center and surface) in GRTQ throughout fermentation. According to the results of high-throughput sequencing and culture-dependent methods, the microbial communities in the CQ and SQ demonstrated functional complementarity. For instance, the bacterial richness index of the CQ was greater than that of SQ, and the fungal richness index of the SQ was greater than that of CQ at the later stage of fermentation. Furthermore, Saccharomycopsis, Saccharomyces, Aspergillus, Monascus, Lactobacillus, Bacillus, Rhodanobacter, and Chitinophaga were identified as the dominant microorganisms in the center, while the surface was represented by Saccharomycopsis, Aspergillus, Monascus, Lactobacillus, Acetobacter, and Weissella. By revealing the physiological characteristics of core microorganisms at different spatial positions of GRTQ, such as Aspergillus clavatus and Monascus purpureus, as well as their interactions with environmental factors, we elucidated the color formation mechanism behind the phenomenon of “green” outside and “red” inside. This study provides fundamental information support for optimizing the production process of GRTQ.

Metal-based nanoparticles have garnered significant usage across industries, spanning catalysis, optoelectronics, and drug delivery, owing to their diverse applications. However, their potential ecological toxicity remains a crucial area of research interest. This paper offers a comprehensive review of recent advancements in studying the ecotoxicity of these nanoparticles, encompassing exposure pathways, toxic effects, and toxicity mechanisms. Furthermore, it delves into the challenges and future prospects in this research domain. While some progress has been made in addressing this issue, there is still a need for more comprehensive assessments to fully understand the implications of metal-based nanoparticles on the environment and human well-being.

Krill oil (KO), extracted from the Antarctic marine crustacean Euphausia superba, is a nutrient-dense substance that includes rich profiles of n-3 polyunsaturated fatty acids (n-3 PUFAs), phospholipids (PLs), astaxanthin (ASX), as well as vitamins A and E, minerals, and flavonoids. As a high-quality lipid resource, KO has been widely used as a dietary supplement for its health-protective properties in recent years. KO has various benefits, including antioxidative, anti-inflammatory, metabolic regulatory, neuroprotective, and gut microbiome modulatory effects. Especially, the antioxidant and anti-inflammatory effects make KO have potential in skin care applications. With increasing demands for natural skin anti-aging solutions, KO has emerged as a valuable nutraceutical in dermatology, showing potential for mitigating the effects of skin aging and enhancing overall skin health and vitality. This review provides an overview of existing studies on the beneficial impact of KO on the skin, exploring its functional roles and underlying mechanisms through which it contributes to dermatological health and disease management.

Background: The purpose of this study was to examine the relationship between sleep duration and risk of sarcopenia in in general U.S. population. Methods: Utilizing publicly available data from the National Health and Nutrition Examination Survey spanning from 2011 to 2014, we explored the association between sleep duration and prevalence of sarcopenia. To investigate their relationship, we conducted weighted multivariate logistic regression analysis, restricted cubic splines (RCS) curve, and subgroup analysis. Results: The study included 8,200 individuals, among whom 99 (0.9 %) had sarcopenia. The RCS curve revealed a U-shaped association of sarcopenia with sleep duration (P for nonlinearity = 0.020), showing that the risk of sarcopenia decreases with increasing sleep duration, reaching the lowest risk around 6.67 h. After controlling for underlying cofounders, compared to individuals with sleep duration 9 h group. The U-shaped association between sleep time and prevalence of sarcopenia also was observed in the subjects who aged

Abstract The aim of this study was to investigate the variation in gene expression in the complete transcripts of Congenitalpulmonary airwaymalformation (CPAM) of the lung using Next Generation Sequencing (NGS) technology. There were 20 cases involving children with CPAM were used for selection of study sample. NGS was used to establish RNA-Seq libraries for the two groups of samples separately, and both groups were conducted to differential expression analysis and Gene Ontology (GO) functional enrichment analysis. The pathways of the differential genes were analyzed to find the enriched target pathways. A total of 592 genes were expressed with significant differences (CPAM vs. normal tissue, P

Abstract Type 2 diabetic kidney disease (T2DKD) is a common microvascular complication of type 2 diabetes mellitus (T2DM), and its incidence is significantly increasing. Microinflammation plays an important role in the development of T2DKD. Based on this, this study investigated the value of inflammatory markers including neutrophil–lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1) in the prediction of T2DKD. This was a cross-sectional survey study. A total of 90 patients with T2DM, who were hospitalized in the nephrology and endocrinology departments of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2021 to January 2022, were included and divided into three groups (A1, A2, A3) according to the urinary albumin-to-creatinine ratio (UACR). Observe and compare the basic information, clinical and laboratory data, and the inflammatory markers NLR, hs-CRP, MCP-1. Results revealed that high levels of NLR (OR = 6.562, 95% CI 2.060–20.902, P = 0.001) and MCP-1 (OR = 1.060, 95% CI 1.026–1.095, P

Abstract Accurate mitosis is coordinated by the spindle assembly checkpoint (SAC) through the mitotic checkpoint complex (MCC), which inhibits the anaphase-promoting complex or cyclosome (APC/C). As an essential regulator, Cdc20 promotes mitotic exit through activating APC/C and monitors kinetochore-microtubule attachment through activating SAC. Cdc20 requires multiple interactions with APC/C and MCC subunits to elicit these functions. Functionally assessing these interactions within cells requires efficient depletion of endogenous Cdc20, which is highly difficult to achieve by RNA interference (RNAi). Here we generated Cdc20 RNAi-sensitive cell lines which display a penetrant metaphase arrest by a single RNAi treatment. In this null background, we accurately measured the contribution of each known motif of Cdc20 on APC/C and SAC activation. The CRY box, a previously identified degron, was found critical for SAC by promoting MCC formation and its interaction with APC/C. These data reveal additional regulation within the SAC and establish a novel method to interrogate Cdc20.

Abstract Background Rheum palmatum L. has important medicinal value because it contains biologically active anthraquinones. However, the key genes and TFs involved in anthraquinone biosynthesis and regulation in R. palmatum remain unclear. Methods Based on full length transcriptome data, in this study, we screened the differentially expressed genes in the anthraquinone biosynthesis pathway. The R2R3-MYB family genes of R. palmatum were systematically identified based on full-length transcriptome sequencing followed by bioinformatics analyses. The correlation analysis was carried out by using co-expression analysis, protein interaction analysis, and real-time fluorescence quantitative analysis after MeJA treatment. The RpMYB81 and RpMYB98 genes were amplified by RT-PCR, and their subcellular localization and self-activation characteristics were analyzed. Results Comparative transcriptome analysis results revealed a total of 3525 upregulated and 6043 downregulated DEGs in the CK versus MeJA group; 28 DEGs were involved in the anthraquinone pathway. Eleven CHS genes that belonged to the PKS family were differentially expressed and involved in anthraquinone biosynthesis. Twelve differentially expressed MYBs genes were found to be co-expressed and interact with CHS genes. Furthermore, 52 MYB genes were identified as positive regulators of anthraquinone biosynthesis and were further characterized. Three MYB genes including RpMYB81, RpMYB98, and RpMYB100 responded to MeJA treatment in R. palmatum, and the levels of these genes were verified by qRT-PCR. RpMYB81 was related to anthraquinone biosynthesis. RpMYB98 had an interaction with genes in the anthraquinone biosynthesis pathway. RpMYB81 and RpMYB98 were mainly localized in the nucleus. RpMYB81 had self-activation activity, while RpMYB98 had no self-activation activity. Conclusion RpMYB81, RpMYB98, and RpMYB100 were significantly induced by MeJA treatment. RpMYB81 and RpMYB98 are located in the nucleus, and RpMYB81 has transcriptional activity, suggesting that it might be involved in the transcriptional regulation of anthraquinone biosynthesis in R. palmatum.

Abstract Background Mediation analysis aims to determine how intermediate variables affect exposure to disease. In this study, 25-hydroxyvitamin D (25(OH)D) was evaluated to assess its role in mediating heavy metal exposure and cardiovascular disease (CVD). Methods A total of 9,377 participants from the National Health and Nutrition Examination Survey (NHANES) for the years 2011-2018 were included. Firstly, restricted cubic spline (RCS), and multivariable logistic regression model were performed to estimate the association between heavy metal exposure (Cadmium, Lead, Mercury, Manganese, and Selenium), as well as serum 25(OH)D and CVD. Secondly, using generalized linear regression model and generalized additive models with smooth functions, we investigated the correlation between heavy metal exposure and serum 25(OH)D. Finally, the mediation effect of serum 25(OH)D in the associations between heavy metal exposure and CVD was explored. Results The RCS plots revealed that Cadmium, and Lead were positively and linearly associated with CVD, while Mercury, and Manganese were inversely and linearly associated with CVD. Additionally, a roughly L- and U-shaped relationship existed between Selenium, as well as 25(OH)D and CVD. When potential confounding factors were adjusted for, serum 25(OH)D had negative associations with Cadmium, Lead, and Manganese, while serum 25(OH)D had positive relationship with Selenium. There was a mediation effect between Manganese exposure and CVD, which was mediated by 25(OH)D. Conclusion According to the mediation analysis, the negative association between Manganese exposure and incident CVD was increased by 25(OH)D. The increasing dietary intake of Vitamin D could increase the protective effect of manganese intake on CVD.

Abstract Aims Veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) is an important technique for the treatment of refractory cardiogenic shock and cardiac arrest; however, the early management of ventricular fibrillation/ventricular tachycardia (VF/VT), within 72 h of VA‐ECMO, and its effects on patient prognosis remain unclear. Methods and results We retrospectively analysed patients at the First Affiliated Hospital of Nanjing Medical University who underwent VA‐ECMO between January 2017 and March 2022. The patients were divided into two groups, VF/VT and nVF/VT, based on whether or not VF/VT occurred within 72 h after the initiation of VA‐ECMO. We utilized logistic regression analysis to evaluate the independent risk factors for VF/VT in patients undergoing VA‐ECMO and to ascertain whether the onset of VF/VT affected 28 day survival rate, length of intensive care unit stay, and/or other clinical prognostic factors. Subgroup analysis was performed for the VF/VT group to determine whether defibrillation affected prognosis. In the present study, 126 patients were included, 65.87% of whom were males (83/126), with a mean age of 46.89 ± 16.23, a 28 day survival rate of 57.14% (72/126), an incidence rate of VF/VT within 72 h of VA‐ECMO initiation of 27.78% (35/126), and 80% of whom (28/35) received extracorporeal cardiopulmonary resuscitation. The incidence of VF/VT resulting from cardiac arrest at an early stage was significantly higher than that of refractory cardiogenic shock (80% vs. 20%; P = 0.022). The restricted cubic spline model revealed a U‐shaped relationship between VF/VT incidence and initial heart rate (iHR), and multivariate logistic regression analysis showed that an iHR > 120 b.p.m. [odds ratio (OR) 6.117; 95% confidence interval (CI) 1.672–22.376; P = 0.006] and hyperlactataemia (OR 1.125; 95% CI 1.016–1.246; P = 0.023) within 1 h of VA‐ECMO initiation were independent risk factors for the occurrence of VF/VT. VF/VT was not found to be associated with the 28 day survival of patients undergoing VA‐ECMO support, nor did it affect other secondary endpoints. Defibrillation did not alter the overall prognosis in patients with VF/VT during VA‐ECMO. Conclusions An iHR > 120 b.p.m. and hyperlactataemia were independent risk factors for the occurrence of VF/VT within 72 h of VA‐ECMO initiation. The occurrence of VF/VT does not affect, nor does defibrillation in these patients improve the overall patient prognosis. Trial registration ChiCTR1900026105.

Plastic lunch box is a topic that food safety has been neglected, and there are few studies on the defects of plastic lunch box production. A multi-scale attention mechanism based on dynamic convolution is designed in this paper to solve the problems of large differences in surface defects of plastic lunch boxes and insensitive perception of multi-scale features. This attention mechanism enables the network to capture complex features adaptively, and enhances the perception of feature channel information and spatial information at various scales. Firstly, this paper integrates the attention mechanism into Slim-neck, and enhances the model’s ability to perceive multi-scale feature information. Secondly, a small target detection layer is added to Slim-neck to solve the semantic information loss problem of various defect features. Then dynamic convolution is integrated into YOLOv8n backbone network to capture complex features adaptively. Finally, MPDIoU is used as the boundary frame loss function, and geometric characteristics are used to improve the model’s perception ability of various defects. Experimental results show that the improved model YOLOv8n-D2SM in this paper achieves 82.8% mAP@0.5 index on the plastic lunch box dataset, which is 10% higher than that of the original model. The detection speed is 26 frames/s, and the number of model parameters is basically consistent with that of the original model. This improvement makes the model more adaptable and reliable in the task of surface defect detection of plastic lunch boxes, which is convenient for deployment and application in actual production scenarios.

A class of dielectric filtering inverted-L antenna with reflective- and quasi-reflectionless-type radiation nulls is proposed to achieve wideband or dual-band operation. To this aim, a dual-function dissipative branch is exploited, which is in-parallel loaded at the feedline of the microstrip-fed dielectric inverted-L antenna. This absorptive branch, which is terminated in a grounded resistor, exhibits a quasi-complementary frequency response with regard to the one of the antenna. In this manner, it can mostly absorb the out-of-band RF-signal power not radiated by the antenna, hence creating quasi-reflectionless-type radiation nulls. Furthermore, the loaded branch can also generate a notch band giving rise to a reflective-type radiation null, which comes determined by the length of the branch and it is independent of the quasi-reflectionless radiation nulls. Thus, by controlling the spectral location of the notch band out of or within the operational frequency band of the dielectric inverted-L antenna, wideband or dual-band operational capabilities can be functionalized into it. For experimental-validation purposes, proof-of-concept prototypes for the two devised wideband and dual-band antenna approaches are designed, manufactured, and characterized. The measured results are in reasonably-close agreement with the simulated ones. The measured fractional impedance bandwidths of the two antenna prototypes are 28.3% (wideband one), 3.1% and 4.2% (dual-band one), respectively.

Abstract Colorectal cancer is a grievous health concern, we have proved long non-coding RNA LINC00689 is considered as a potential diagnosis biomarker for colorectal cancer, and it is necessary to further investigate its upstream and downstream mechanisms. Here, we show that KLF15, a transcription factor, exhibits the reduced expression in colorectal cancer. KLF15 suppresses the proliferative and metastatic capacities of colorectal cancer cells both in vitro and in vivo by transcriptionally activating LINC00689. Subsequently, LINC00689 recruits PTBP1 protein to enhance the stability of LATS2 mRNA in the cytoplasm. This stabilization causes the suppression of the YAP1/β-catenin pathway and its target downstream genes. Our findings highlight a regulatory network involving KLF15, LINC00689, PTBP1, LATS2, and the YAP1/β-catenin pathway in colorectal cancer, shedding light on potential therapeutic targets for colorectal cancer therapy.