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Abstract Neoproterozoic snowball Earth events lasted for multiple million years, experiencing many orbital cycles. Here we investigate whether the deglaciation of these events would be triggered more easily at certain orbital configurations than others, by using an atmosphere‐land model that considers meltpond formation on land ice. Results show that the threshold concentration of atmospheric CO2 (pCO2) required for deglaciation can vary from 6 to 10 × 104 ppmv under different orbital forcings. The threshold pCO2 decreases with the equatorial maximum monthly insolation (EMMI), which is affected most by the eccentricity and secondarily by obliquity. Therefore, we conclude that the snowball Earth deglaciation likely occurred when the eccentricity was high and obliquity was low. Compared to previous estimate that used present‐day orbital configuration which has a minimal eccentricity, the duration of snowball Earth events would likely be much shorter when the influence of orbital variations are considered.

Remnant cholesterol (RC) is highly regarded in the cardiovascular field; however, its relationship with new-onset diabetes remains unclear. This study aimed to investigate the relationship between RC and the risk of developing diabetes, as well as its interaction with low-density lipoprotein cholesterol (LDL-c). This was a secondary analysis of a retrospective cohort study based on a Chinese population. A multivariate Cox proportional hazards regression was initially employed to assess the relationship between RC and newly diagnosed diabetes. This was followed by a subgroup analysis to explore intergroup heterogeneity. A clinical prediction model was then developed. Finally, the study further analyzed the interactions between LDL-c and RC. After adjusting for confounding factors, RC was significantly associated with an increased risk of diabetes (HR = 1.46, 95% confidence interval [CI] 1.36–1.57). Furthermore, this relationship was nonlinear, with an inflection point of 0.48 identified through the piecewise model. Subgroup analysis indicated that the association was more pronounced in individuals under 60 years and those with a body mass index < 24 kg/m2 (P for interaction = 0.0004,

Abstract Background Large cross-arch free-end surgical guides can obscure the visual field, compromising surgical accuracy due to insufficient stability at the free-end. This in vitro study aims to evaluate the accuracy of novel digital non-cross-arch surgical guides designed for implant placement at the mandibular free-end, incorporating tooth undercut retention and screw-bone support. Materials and methods A mandibular dental model lacking left molars was utilized to fabricate unilateral (cross-arch) tooth-supported surgical guides (GT I, n = 20). Subsequently, two additional types of surgical guides were fabricated: GT II (covering two teeth, n = 20) and GT III (covering three teeth, n = 20). These novel surgical guides were designed to utilize the undercut of the supporting teeth for retention and enhance stability with screw-bone support at the guide’s free-end. Furthermore, 60 identical guiding blocks were assembled on the three types of surgical guides to facilitate the implants’ insertion. On a phantom head, 120 implant replicas were placed at the Federal Dentaire Internationale (FDI) teeth positions #36 and #37 on the dental model, employing a combination of surgical guides and guiding blocks. To assess accuracy, planned and placed implant positions were compared using intraoral optical scanning. Discrepancies in angulation and linear deviations, including the coronal/apical 3D deviations, lateral deviation as well as depth deviation, were measured. Statistical analysis was performed using two-way ANOVA and Bonferroni test (α = 0.05). Results GT I exhibited significantly largest discrepancies, including angular and linear deviations at the crest and apex at every implant site. Especially in depth, at implant site #36, the mean deviation value of GT I (0.27 ± 0.13 mm) was twice as large as GT III (0.13 ± 0.07 mm), and almost twice as large as GT II (0.14 ± 0.08 mm). However, at implant site #37, this deviation increased to almost a five-fold relationship between GT I (0.63 ± 0.12 mm) and II (0.14 ± 0.09 mm), as well as between GT I and III (0.13 ± 0.09 mm). No significant discrepancies existed between the novel surgical guides at either implant site #36 or #37. Conclusion This study provides a practical protocol for enhancing accuracy of implant placement and reducing the size of free-end surgical guides used at mandibular molar sites.

ABSTRACTBased on the principle of local resonance and the strategy of hybrid design, in this paper we propose three truss-plate hybrid multifunctional lattice metamaterials featured by the cubic cell topology with a central truss-plate unit connected by the elastic beams to the eight corners. Finite element (FE) simulations were validated by experimental tests on specimens made of TPU substrate material through SLS additive manufacturing technique. At the relative density of 0.31, the specific energy absorption reaches 2.71 J/g, the bandgap width reaches 2.624 KHz, and the elastic wave transmission attenuation at 1400 Hz frequency reaches – 270 dB. Parametric analyses were carried out to investigate the effects of different geometric parameters on the performance indicators. These results highlight the proposed truss-plate hybrid metamaterial as an intriguing multifunctional material with excellent performances in both energy absorption and vibration attenuation, that can be applied to scenarios with multiple engineering requirements.

Abstract Background Systemic immune‐inflammation index (SII) provides convincing evaluation of systemic immune and inflammatory condition in human body. Its correlation with prostate cancer (PCa) risk remains uncharted. The principal objective of this investigation was to elucidate the association between SII and the risk for PCa in middle‐aged and elderly males. Materials and Methods Analysis entailed multivariate linear and logistic regression, generalized additive model, and smoothing curve fitting using resource from 2007 to 2010 National Health and Nutrition Examination Survey (NHANES). To ascertain robustness and consistency of this association across different demographic strata, we conducted rigorous subgroup analyses and interaction tests. Results Among 3359 participants, those with elevated SII displayed higher total prostate‐specific antigen (tPSA) levels, higher risk for PCa, and lower free/total PSA (f/t PSA) ratio. Specifically, each unit increase of log2 (SII) was associated with a 0.22 ng/mL increase in tPSA (β: 0.22, 95% confidence intervals [CI] 0.05–0.38), a 2.22% decline in f/t PSA ratio (β: −2.22, 95% CI −3.20 to −1.23), and a 52% increased odds of being at high risk for PCa (odds ratio [OR]: 1.52, 95% CI 1.13–2.04). People in the top quartile of log2 (SII) exhibited 0.55 ng/mL increased tPSA (β: 0.55, 95% CI 0.19–0.90), 4.39% reduced f/t PSA ratio (β: −4.39, 95% CI −6.50 to −2.27), and 168% increased odds of being at high risk for PCa (OR: 2.68, 95% CI 1.32–5.46) compared to those in the bottom quartile. Conclusion Systemic immune and inflammatory condition, as represented by SII, is independently and positively associated with tPSA levels and the risk for PCa, as well as independently and negatively associated with f/t PSA ratio among middle‐aged and older US males. These findings may enhance the effectiveness of PCa screening in predicting positive biopsy results.

Age and gender have been recognized as two pivotal covariates affecting the composition of the gut microbiota. However, their mediated variations in microbiota seem to be inconsistent across different countries and races. In this study, 613 individuals, whom we referred to as the “healthy” population, were selected from 1,018 volunteers through rigorous selection using 16S rRNA sequencing. Three enterotypes were identified, namely, Escherichia–Shigella, mixture (Bacteroides and Faecalibacterium), and Prevotella. Moreover, 11 covariates that explain the differences in microbiota were determined, with age being the predominant factor. Furthermore, age-related differences in alpha diversity, beta diversity, and core genera were observed in our cohort. Remarkably, after adjusting for 10 covariates other than age, abundant genera that differed between age groups were demonstrated. In contrast, minimal differences in alpha diversity, beta diversity, and differentially abundant genera were observed between male and female individuals. Furthermore, we also demonstrated the age trajectories of several well-known beneficial genera, lipopolysaccharide (LPS)-producing genera, and short-chain fatty acids (SCFAs)-producing genera. Overall, our study further elucidated the effects mediated by age and gender on microbiota differences, which are of significant importance for a comprehensive understanding of the gut microbiome spectrum in healthy individuals.

Abstract TNF acts as one pathogenic driver for inducing intestinal epithelial cell (IEC) death and substantial intestinal inflammation. How the IEC death is regulated to physiologically prevent intestinal inflammation needs further investigation. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects intestinal epithelium from TNF-induced IEC apoptosis. EFHD2 inhibits TNF-induced apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin and suppresses Cofilin phosphorylation, thus blocking TNF receptor I (TNFR1) internalization to inhibit IEC apoptosis and consequently protecting intestine from inflammation. Our findings deepen the understanding of EFHD2 as the key regulator of membrane receptor trafficking, providing insight into death receptor signals and autoinflammatory diseases.

[Introduction] The wake effect of wind turbines is an important cause of energy loss in wind farms. The wake study of wind turbines is beneficial to optimization of the turbine arrangement and improvement of the economic efficiency of wind farms. [Method] This paper presented a comparative study of the wake wind speed decay and turbulence intensity prediction of eight common wake models, respectively. To ensure the rationality of the evaluation, the quantitative analysis was carried out based on wind farm measurements and wind tunnel experimental data, and the range of comparison data was limited to 3 to 10 times the diameter downstream the turbine. [Result] The analysis results show that, for the prediction of wake wind speeds, the two-dimensional model fits the actual wake wind speed distribution structure better than the one-dimensional model, in which Jensen-Guass has better wake width prediction ability, while the 2D-k-Jensen wake center wind speed prediction has higher accuracy and adaptability to multiple conditions, with the maximum mean deviation and standard deviation of 8.7% and 5.5%, respectively, which are both applicable to the prediction of turbine wake wind speed. Jensen model has the best prediction ability of wake center wind speed in one-dimensional model, and the mean deviation of some conditions is less than 10%. While Park model is better in predicting the horizontal distribution of wake wind speed. In Case 2, the prediction performance is comparable to that of two-dimensional model, and the mean deviation of each condition is less than 10%, so it is more suitable for wake speed prediction than the former. For the prediction of turbulence intensity, the Ishihara model shows a clear advantage in the prediction of turbulent structure, with mean deviations below 10%, but the prediction of turbulence intensity at the center of the wake is poor, which is not conducive to the prediction of the turbulence intensity at locations downstream the turbine. Among the remaining models, Frandsen and Jensen-Guass models are relatively good at prediction of low ambient turbulence intensities. However, there is an opposite trend between the two for high ambient turbulence intensities: the Frandsen model has higher prediction accuracy and is suitable for turbine turbulence intensity prediction, whereas the prediction result of Jensen-Guass is much larger than the experimental value, and is unstable. The prediction accuracy of wake wind speed for all models is greatly improved at high upstream wind speeds, and the increase in ambient turbulence intensity contributes to the prediction accuracy of the wake wind speed and turbulence intensity for all models, except for the Jensen-Guass model. [Conclusion] The predicted values of wake wind speed for the Jensen-Guass model and the 2D-k-Jensen model coincides better with the measured data, while the prediction performance of the Frandsen model turbulence intensity is better, so they can be used as the reference wake models for the optimization of wind turbine placement and wake control analysis for offshore wind farms.

Abstract Background and purpose To explore the association of systemic inflammatory index (SIRI), systemic immune-inflammatory index (SII) and inflammatory prognosis index (IPI) with 90d outcomes in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. Methods The patients who underwent intravenous thrombolysis were enrolled in the present study from September 2019 to December 2022. According to the relevant blood indexes obtained in 24 h after admission, the corresponding values of SIRI, SII and IPI were calculated. The correlation among SIRI, SII, IPI, and admission NIHSS scores was examined by Spearman correlation analysis. ROC curve analysis was conducted to determine the optimal cut-off value of SIRI, SII, IPI, and their corresponding sensitivity and specificity to evaluate their predictive value on admission for poor prognosis. To investigate whether high SIRI, SII, and IPI were independent predictors of poor outcomes within 90 days, variables with P-value

Abstract To solve the problems mechanically caused by parallel direct‐drive permanent magnet motors (DD‐PMSM). This paper proposes a concave‐core stator direct‐drive permanent magnet motor (CCSDD‐PMSM) structure. In this study, an auxiliary yoke structure is proposed to optimise the magnetic circuit and analyse the cogging torque to achieve the minimum detent force. Based on the unit motor and combined with the magnetomotive force to analyse the symmetry of different winding distributions, the stability characteristics of the motor are studied. The magnetic field distribution of the motor load air gap is calculated using the finite element method. The contribution of different spatial order harmonics to the motor output torque is calculated using the Maxwell tensor method. The torque calculation expression of the CCSDD‐PMSM is given. Finally, an experimental prototype is made to verify the accuracy of the analysis in this paper.

Abstracts Phosphorylation of IRF3 is critical to induce type I interferon (IFN-I) production in antiviral innate response. Here we report that lysine methyltransferase SMYD2 inhibits the expressions of IFN-I and proinflammatory cytokines in macrophages upon viral infections. The Smyd2-deficient mice are more resistant to viral infection by producing more IFN-I and proinflammatory cytokines. Mechanistically, SMYD2 inhibits IRF3 phosphorylation in macrophages in response to viral infection independent of its methyltransferase activity. We found that SMYD2 interacts with the DNA-binding domain (DBD) and IRF association domain (IAD) domains of IRF3 by its insertion SET domain (SETi) and could recruit phosphatase PP1α to enhance its interaction with IRF3, which leads to decreased phosphorylation of IRF3 in the antiviral innate response. Our study identifies SMYD2 as a negative regulator of IFN-I production against virus infection. The new way of regulating IRF3 phosphorylation will provide insight into the understanding of IFN-I production in the innate response and possible intervention of the related immune disorders.

Lattice structures, characterized by their lightweight nature, high specific mechanical properties, and high design flexibility, have found widespread applications in fields such as aerospace and automotive engineering. However, the lightweight design of lattice structures often presents a trade-off between strength and stiffness. To tackle this issue, a bio-inspired curved-elliptical (BCE) lattice is proposed to enhance the mechanical performance and deformation stability of three-dimensional lattice structures. BCE lattice specimens with different parameters were fabricated using selective laser melting (SLM) technology, followed by quasi-static compression tests. Finite element (FE) numerical simulations were also carried out for validation. The results demonstrate that the proposed BCE lattice structures exhibit stronger mechanical performance and more stable deformation modes that can be adjusted through parameter tuning. Specifically, by adjusting the design parameters, the BCE lattice structure can exhibit a bending-dominated delocalized deformation mode, avoiding catastrophic collapse during deformation. The specific energy absorption (SEA) can reach 24.6 J/g at a relative density of only 8%, with enhancements of 48.5% and 297.6% compared with the traditional energy-absorbing lattices Octet and body-center cubic (BCC), respectively. Moreover, the crushing force efficiency (CFE) of the BCE lattice structure surpasses those of Octet and BCC by 34.9% and 15.8%, respectively. Through a parametric study of the influence of the number of peaks N and the curve amplitude A on the compression performance of the BCE lattice structure, the compression deformation mechanism is further analyzed. The results indicate that the curve amplitude A and the number of peaks N have significant impacts on the deformation mode of the BCE lattice. By adjusting the parameters N and A, a structure with a combination of high energy absorption, high stiffness, and strong fracture resistance can be obtained, integrating the advantages of tensile-dominated and bending-dominated lattice structures.

Aging is an irreversible pathophysiological process for all organisms. The accumulation of senescent cells in pathological sites or tissues is recognized as the major cause of diseases and disorders during the aging process. Small molecules that reduce senescent cell burdens have gained increasing attention as promising intervention therapeutics against aging, but effective anti-senescence agents remain rare. Camellia Sect. Chrysantha Chang is documented as a traditional Chinese herbal medicine used by ethnic groups for many medical and health benefits, but its effect on aging is unclear. Here, we investigated the anti-senescence potential of eight C. Sect. Chrysantha Chang species. The results show that ethyl acetate fractions from these C. Sect. Chrysantha Chang species were able to delay the senescence of H9c2 cardiomyocytes except for C. pingguoensis (CPg). N-butanol fractions of C. multipetala (CM), C. petelotii var. grandiflora (CPt), and C. longzhouensis (CL) showed a senescent cell clearance effect by altering the expression levels of senescent-associated marker genes in the DNA-damage response (DDR) pathway and the senescent cell anti-apoptotic pathway (SCAPs). By using UPLC-QTOF-MS-based non-targeted metabolomics analyses, 27 metabolites from Sect. Chrysantha species were putatively identified. Among them, high levels of sanchakasaponin C and D in CM, CPt, and CL were recognized as the key bioactive compounds responsible for senescent cell clearance. This study is the first to disclose and compare the anti-cell-senescence effect of a group of C. Sect. Chrysantha Chang, including some rare species. The combination of senescent markers and metabolomics analyses helped us to reveal the differences in chemical constituents that target senescent cells. Significantly, contrary to the C. chrysantha var. longistyla (CCL), which is widely cultivated and commercialized for tea drinks, CM, CPt, and CL contain unique chemicals for managing aging and aging-related diseases. The results from this study provide a foundation for species selection in developing small-molecule-based drugs to alleviate diseases and age-related dysfunctions and may potentially be useful for advancing geroscience research.

ABSTRACTAntimicrobial resistance-associated infections have become a major threat to global health. The gut microbiome serves as a major reservoir of bacteria with antibiotic resistance genes; whereas, the temporal development of gut resistome during early childhood and the factors influencing it remain unclear. Moreover, the potential interactions between gut microbiome and resistome still need to be further explored. In this study, we found that antibiotic treatment led to destabilization of the gut microbiome and resistome structural communities, exhibiting a greater impact on the resistome than on the microbiome. The composition of the gut resistome at various developmental stages was influenced by the abundance and richness of different core microbes. First exposure to antibiotics led to a dramatic increase in the number of opportunistic pathogens carrying multidrug efflux pump encoding genes. Multiple factors could influence the gut microbiome and resistome formation. The data may provide new insights into early-life research.IMPORTANCEIn recent years, the irrational or inappropriate use of antibiotics, an important life-saving medical intervention, has led to the emergence and increase of drug-resistant and even multidrug-resistant bacteria. It remains unclear how antibiotic exposure affects various developmental stages of early childhood and how gut core microbes under antibiotic exposure affect the structural composition of the gut resistome. In this study, we focused on early antibiotic exposure and analyzed these questions in detail using samples from infants at various developmental stages. The significance of our research is to elucidate the impact of early antibiotic exposure on the dynamic patterns of the gut resistome in children and to provide new insights for early-life studies.

The conflict between socio-economic development and ecological environmental protection presents a significant challenge to achieving regional and urban sustainable development. In Zhaotong City, Yunnan Province, China, this conflict arises from the interplay between urban expansion and ecological environmental protection land, creating a fundamental tension between built-up and non-built-up ecosystems. This study focuses on investigating the spatial characteristics of expansion, constructing an ecological security pattern based on ecosystem service functions and sensitivity, and utilizing integrated models to simulate urban expansion paths and analyze their formation mechanisms. The results highlight that Zhaotong City has undergone rapid urban expansion, characterized by linear growth surrounding the central city, specifically in the east, north, and west directions. The expansion between urban areas exhibits a discontinuous dotted-star distribution, with concentrated urbanization and a distinct urban boundary observed in Zhaoyang District. In contrast, other areas experience scattered expansion, indicative of random land encroachment. Through simulation, three primary urban expansion axes are identified: the western town sprawl belt, central town development axis, and resource-rich town corridor. Ecological conflicts primarily arise in Zhaoyang District, Zhenxiong County, and Yanjin County. By combining these findings, the study analyzes the scenario pattern of urban expansion evolution in Zhaotong City, revealing a transition from the spreading spillover expansion of a single center (Zhaoyang and Ludian) during the circle expansion phase to a polycentric expansion and spreading spillover pattern centered around Zhaoyang District along three primary axial radial paths. In conclusion, this study contributes to our understanding of the challenges posed by the conflict between socio-economic development and ecological environmental protection in Zhaotong City. The findings underscore the importance of integrating ecological considerations into urban planning processes and highlight the need for sustainable development practices to achieve a harmonious coexistence between urban expansion and ecological security. The insights gained from this research offer guidance for fostering sustainable urban development in Zhaotong City and beyond.

Abstract Objective The optimal blood pressure (BP) targets for acute ischemic stroke are unclear. We aimed to assess the relationship between Mean BP and clinical outcomes during hospitalization. Materials and methods We included 649 patients with Acute ischemic stroke (AIS) from December 2020 to July 2021. BP was measured daily, and mean blood pressure was calculated. Clinical events recorded within 90 days of randomization were: recurrent ischemic stroke, symptomatic intracranial hemorrhage, and death. The modified Rankin Scale (mRS) was used to measure primary outcomes 3 months after AIS. Logistic multiple regression analysis was performed by statistical software R. Result There is a nonlinear U-shaped relationship between SBP and poor outcomes. This means higher SBP and lower SBP will increase the incidence of poor outcomes. The optimal mean SBP during hospitalization was 135-150 mmHg, and patients with SBP 150mmhg OR 2.04 [95% Cl, 1.02 ~ 4.08], p = 0.045 had a higher probability of poor outcomes. Conclusion Our study shows that the optimal SBP of patients with AIS during hospitalization was 135-150 mmHg. The findings suggest that the relationship between mean SBP and 3-month functional outcome after AIS was U-shaped. Both higher SBP and lower SBP lead to poor prognosis in AIS patients.

Current challenges in collecting and analyzing subway vibration data include the absence of standardized data collection methods, limitations in data analysis techniques, and an unclear understanding of the effects of geological conditions on vibrations. This study investigated vertical vibrations of tunnel walls and the ground above tunnels under different geological conditions of soft soil and rock strata at horizontal distances of 0, 15 m, and 30 m from the tunnel center line during train passages. The collected data underwent Fourier transformation and 1/3 octave processing to extract spectral characteristics and analyze transmission losses across different frequency bands. Our findings revealed two vibration peaks in the transmission process for both soft soil and rock formation geology. Specifically, high-frequency vibrations in soft soil experienced greater attenuation when transmitted from the tunnel wall to the ground at 0 m, while low-frequency vibrations in rock formations showed greater attenuation. We also observed a vibration amplification phenomenon at 15 m under soft soil geology conditions. Although low-frequency vibrations below 12.5 Hz showed slight attenuation within a 30 m test distance under both geological conditions, vibrations above 40 Hz experienced significant attenuation. These results offer valuable insights for reducing vibrations in subway superstructures and planning subway lines under diverse geological conditions. Furthermore, this study serves not only as a basis for mitigating vibrations in metro spans and designing metro lines in various geological contexts but also establishes a scientific foundation for future research.

This study investigated the influence and mechanism of the excavation width on excavation deformations in Shanghai soft clay. Based on three excavations that had different final excavation depths, dissimilar retaining structures and diverse geological conditions, 40 sets of two-dimensional numerical models with different excavation widths were employed to analyze the deformation rules affected by the excavation width. Moreover, a series of simplified models with different excavation widths were employed to analyze the effect of the excavation width on excavation deformations. The results show that under the same excavation depth, both the horizontal displacements of the retaining walls and ground surface settlements increase as the excavation width increases, but the increasing rate gradually decreases. Factors such as the unloading influence depth, the overlap degree of the passive zones, the stress state of the basal soils and the development of the relative shear stress have a significant influence on excavation deformations. With increasing excavation width, the unloading influence depth gradually deepens, the overlap area of the passive zones gradually decreases, the direction of the rotation of the major principal stress gradually reduces and the relative shear stress of the distant and deep soils gradually expands. Therefore, the constraint ability of the passive zones on excavation deformation gradually reduces and excavation deformations gradually increase.

Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer.

Summary: The roles of long noncoding RNA (lncRNA) and RNA-binding proteins (RBPs) in antiviral innate response warrant further investigation. Here, we identify an lncRNA, termed lncRNA-BTX (between Tbk1 and Xpot), which is upregulated upon viral infection via an IRF3-type I interferon-independent pathway, promoting viral innate immune escape. Deletion of lncRNA-BTX in cells or mice significantly reduces viral load in vitro or in vivo, respectively. Mechanistically, lncRNA-BTX strengthens the interactions between DHX9 or ILF3 (two RBPs that have opposite functions in regulating the replication of RNA virus) and their respective partner, JMJD6 or ILF2, which regulates intracellular translocations of DHX9 and ILF3 from the nucleus to the cytoplasm. Put simply, lncRNA-BTX facilitates DHX9’s return to the cytoplasm and retains ILF3 within the nucleus, promoting viral replication. This work unveils a strategy developed by the virus to bypass host innate immunity, thus providing a potential target for antiviral therapeutics.

A critical examination of the occurrence of PFASs in wastewater, surface water, groundwater, and drinking water is presented. Given the ongoing shift towards substitutes of legacy PFASs and the rising role of China as global leader in PFASs production, background and hotspot concentrations of PFASs in the aquatic environment of China and Western Countries (mostly the E.U., the U.S., and Canada) are reported and critically compared for the first time, with special attention to short-chain perfluoroalkyl acids, novel substitutes like perfluoroether carboxylic and sulphonic acids, and emerging PFASs like 6:2 FTAB. Data on PFASs concentrations in the examined matrices show that i) concentrations of total PFASs and of selected perfluoroalkyl acids (PFAAs) are generally higher in China, except for PFOS, and that ii) short-chain and novel PFASs are replacing their long-chain homologues but are rarely monitored. Recommendations are provided to help prioritize the PFASs to be investigated that can end up in the environment.

Abstract Background Gut homeostasis, including intestinal immunity and microbiome, is essential for cognitive function via the gut-brain axis. This axis is altered in high-fat diet (HFD)-induced cognitive impairment and is closely associated with neurodegenerative diseases. Dimethyl itaconate (DI) is an itaconate derivative and has recently attracted extensive interest due to its anti-inflammatory effect. This study investigated whether intraperitoneal administration of DI improves the gut-brain axis and prevents cognitive deficits in HF diet-fed mice. Results DI effectively attenuated HFD-induced cognitive decline in behavioral tests of object location, novel object recognition, and nesting building, concurrent with the improvement of hippocampal RNA transcription profiles of genes associated with cognition and synaptic plasticity. In agreement, DI reduced the damage of synaptic ultrastructure and deficit of proteins (BDNF, SYN, and PSD95), the microglial activation, and neuroinflammation in the HFD-fed mice. In the colon, DI significantly lowered macrophage infiltration and the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in mice on the HF diet, while upregulating the expression of immune homeostasis-related cytokines (IL-22, IL-23) and antimicrobial peptide Reg3γ. Moreover, DI alleviated HFD-induced gut barrier impairments, including elevation of colonic mucus thickness and expression of tight junction proteins (zonula occludens-1, occludin). Notably, HFD-induced microbiome alteration was improved by DI supplementation, characterized by the increase of propionate- and butyrate-producing bacteria. Correspondingly, DI increased the levels of propionate and butyrate in the serum of HFD mice. Intriguingly, fecal microbiome transplantation from DI-treated HF mice facilitated cognitive variables compared with HF mice, including higher cognitive indexes in behavior tests and optimization of hippocampal synaptic ultrastructure. These results highlight the gut microbiota is necessary for the effects of DI in improving cognitive impairment. Conclusions The present study provides the first evidence that DI improves cognition and brain function with significant beneficial effects via the gut-brain axis, suggesting that DI may serve as a novel drug for treating obesity-associated neurodegenerative diseases. Video Abstract

Drive motors in certain applications often require heavy load starting or short-time overload operation, so the limiting output capacity of the motor is worthy of attention. In this paper, the limiting output torque and input current of low-speed and high-torque external rotor surface-mounted permanent magnet synchronous motor(SMPMSM) under $i_{d}$ = 0 and field weakening(FW) control strategies are studied considering the resistance voltage drop. Firstly, the output characteristics of SMPMSM are analyzed when the resistance is considered, and the relationships between the limiting $i_{q}$ , limiting output torque and the electromagnetic parameters are analyzed when the $i_{d}$ = 0 and the FW control are adopted under the voltage limit. Next, the finite element method(FEM) is used to analyze and compare the impact of different machine parameters of the SMPMSM on the limiting output torque under the two control strategies. Finally, the correctness of theoretical analysis and FEM results are verified by prototype experiments.

To construct a more effective model with good generalization performance for inter-site autism spectrum disorder (ASD) diagnosis, domain adaptation based ASD diagnostic models are proposed to alleviate the inter-site heterogeneity. However, most existing methods only reduce the marginal distribution difference without considering class discriminative information, and are difficult to achieve satisfactory results. In this paper, we propose a low rank and class discriminative representation (LRCDR) based multi-source unsupervised domain adaptation method to reduce the marginal and conditional distribution differences synchronously for improving ASD identification. Specifically, LRCDR adopts low rank representation to alleviate the marginal distribution difference between domains by aligning the global structure of the projected multi-site data. To reduce the conditional distribution difference of data from all sites, LRCDR learns the class discriminative representation of data from multiple source domains and the target domain to enhance the intra-class compactness and inter-class separability of the projected data. For inter-site prediction on all ABIDE I data (1102 subjects from 17 sites), LRCDR obtains the mean accuracy of 73.1%, superior to the results of the compared state-of-the-art domain adaptation methods and multi-site ASD identification methods. In addition, we locate some meaningful biomarkers: Most of the top important biomarkers are inter-network resting-state functional connectivities (RSFCs). The proposed LRCDR method can effectively improve the identification of ASD, and has great potential as a clinical diagnostic tool.

Abstract Background Circular RNAs (circRNAs) mediate the infiltration of tumor-associated macrophages (TAMs) to facilitate carcinogenesis and development of various types of cancers. However, the role of circRNAs in regulating macrophages in prostate cancer (PCa) remains uncertain. Methods Differentially expressed circRNAs in PCa were identified by RNA sequencing. The expression of circSMARCC1 was recognized and evaluated using fluorescence in situ hybridization and quantitative real-time PCR. The oncogenic role of circSMARCC1 in PCa tumor proliferation and metastasis was investigated through a series of in vitro and in vivo assays. Finally, Western blot, biotin-labeled RNA pulldown, luciferase assay, rescue experiments, and co-culture experiments with TAMs were conducted to reveal the mechanistic role of circSMARCC1. Results CircSMARCC1 was dramatically up-regulated in PCa cells, plasma and tissues. Overexpression of circSMARCC1 promotes tumor proliferation and metastasis both in vitro and in vivo, whereas knockdown of circSMARCC1 exerts the opposite effects. Mechanistically, circSMARCC1 regulates the expression of CC-chemokine ligand 20 (CCL20) via sponging miR-1322 and activate PI3K-Akt signaling pathway involved in the proliferation and epithelial mesenchymal transformation. More importantly, high expression of circSMARCC1 was positively associated with colonization of CD68+/CD163+/CD206+ TAMs in tumor microenvironment. In addition, overexpression of circSMARCC1 facilitates the expression of CD163 in macrophages through the CCL20-CCR6 axis, induces TAMs infiltration and M2 polarization, thereby leading to PCa progression. Conclusions CircSMARCC1 up-regulates the chemokine CCL20 secretion by sponging miR-1322, which is involved in the crosstalk between tumor cells and TAMs by targeting CCL20/CCR6 signaling to promote progression of PCa.

A digital workflow to acquire actual position of the drill and assess bony preparation accuracy intraoperatively was described. Based on the widely used intraoral scanner, this digital workflow was a relatively practical and economical option for digital intraoperative measurement. As a result, it could help the clinician in accurate verification and immediate correction of the drill position and consequently facilitating the accurate implant placement in implant surgery.

It is a challenging task to accurately track the global maximum power point (GMPP) in a changing environment in widely used photovoltaic (PV) systems. So far, a variety of maximum power point (MPP) tracking algorithms have been used in solar PV power systems. The classical algorithm is simple and fast to track the speed effectively in a constant environment, but it can get stuck at an extreme point in a variable environment. In this paper, the variable-step incremental conductance (VINC) method is combined with the gray wolf optimization (GWO) algorithm. Firstly, GWO conducts a global search. When the search reaches the area near GMPP, the next step of the search process is carried out based on the iteration number conditions of GWO. Enter the search process of VINC and determine whether the current search process is on the left or right side of the vertex based on the current search value. And adjust the duty cycle during the VINC search process using different variable step size methods based on the left and right sides, and finally accurately locate the GMPP value. To verify the robustness of the proposed algorithm, simulation, and experimental comparisons were conducted between the proposed method in the article and GWO and VINC. The tracking efficiency of static shadows, simulated dynamic shadows, and experimental static and dynamic shadows is 99.80%, 98.82%, 99.43%, and 98.51%, respectively. The tracking time of simulation and experiment is 46.49% and 89.34% faster than GWO and VINC technologies, respectively. The results show that compared with the GWO and VINC methods, the proposed method has improved tracking speed and efficiency. Moreover, compared with the method that combines the two intelligent algorithms, this method has fewer algorithm parameters, a simple calculation process, lower complexity, lower hardware requirements, and better actual implementation performance.

Abstract Although there have been some recent cell and animal experiments indicating that expression of the gene encoding apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) is closely related to cancer, it still lacks pan-cancer analysis. Here we analyzed the potential carcinogenic role of APOBEC3B in 33 tumors based on The Cancer Genome Atlas (TCGA). APOBEC3B was highly expressed in most tumors and weakly expressed in a few. Differences in expression level were significantly correlated with the pathological tumor stage and prognosis of affected patients. The high-frequency APOBEC3B changes were principally mutations and amplifications in some tumors, such as uterine corpus endometrial carcinomas or cutaneous melanomas. In testicular germ cell tumors and invasive breast carcinomas, APOBEC3B expression and CD8+ T lymphocyte counts were correlated. In other cancers, such as human papilloma virus (HPV)-related head and neck squamous cell carcinomas or esophageal adenocarcinomas, there was also cancer-associated fibroblast infiltration. The APOBEC3B enzyme acts in the mitochondrial respiratory electron transport chain and in oxidative phosphorylation. This first pan-cancer study provides a comprehensive understanding of the multiple roles of APOBEC3B in different tumor types.

Abstract Compared with the single‐stator permanent magnet synchronous motor(SS‐PMSM), the double‐stator permanent magnet synchronous motor(DS‐PMSM) can make full use of the space in the motor cavity to make it have higher torque density, so it is more suitable for direct‐drive occasions with low‐speed and high‐torque. This paper aims to design and compare the parameters and performances of DS‐PMSMs with four different rotor structures: 1)Series magnetic circuit of radial magnetised single‐layer permanent magnet(type Ⅰ), 2)Series magnetic circuit of radial magnetised double‐layer permanent magnet(type Ⅱ), 3)Parallel magnetic circuit of radial magnetised double‐layer permanent magnet(type Ⅲ), 4)Parallel magnetic circuit of tangential magnetised permanent magnet(type Ⅳ). Firstly, the equivalent magnetic circuit method is used to analyse the magnetic circuits of the four DS‐PMSMs. Next, the finite element analysis tool is used to compare the performances of the four DS‐PMSMs with the same volume. Their air‐gap flux density, no‐load back‐EMF, cogging torque, torque characteristics, moment of inertia, rotor loss and efficiency are quantitatively analysed and compared. Finally, this paper provides guidance and suggestions for the selection of the rotor structure of DS‐PMSM.

Vascular diseases are the leading cause of morbidity and mortality worldwide. Therefore, effective treatment strategies that can reduce the risk of vascular diseases are urgently needed. The relationship between Interleukin-11 (IL-11) and development of vascular diseases has gained increasing attention. IL-11, a target for therapeutic research, was initially thought to participate in stimulating platelet production. Additional research concluded that IL-11 is effective in treating several vascular diseases. However, the function and mechanism of IL-11 in these diseases remain unknown. This review summarizes IL-11 expression, function, and signal transduction mechanism. This study also focuses on the role of IL-11 in coronary artery disease, hypertension, pulmonary hypertension, cerebrovascular disease, aortic disease, and other vascular diseases and its potential as a therapeutic target. Consequently, this study provides new insight into the clinical diagnosis and treatment of vascular diseases.

Abstract This article presents a novel asymmetric spoke‐type rotor structure. It is used to reduce rotor magnetic flux leakage, torque ripple and no‐load back‐EMF distortion rate while increasing the motor output torque. The traditional method of optimizing torque pulsation is the inverse cosine function, which gives a sinusoidal distribution of the air‐gap magnetic field under no‐load conditions of the motor. The fundamental wave magnetic field of the air‐gap synthetic magnetic field under the load is offset from the no‐load air‐gap magnetic field. This paper presents the design theory and method of the new type of the asymmetric rotor. Asymmetric spatial harmonics are introduced to the rotor so that the motor has a sinusoidal distribution of the rated load air‐gap field under MTPA control. In order to verify the superiority of the new rotor, the performance of four different spoke‐type rotor structure motors under the same pole‐slot combination was compared. Finally, an experimental prototype is built to verify the theoretical reliability against the design of this paper.

Lactobacillus johnsonii has been used as a probiotic for decades to treat a wide range of illnesses, and has been found to have specific advantages in the treatment of a number of ailments. We reviewed the potential therapeutic effects and mechanisms of L. johnsonii in various diseases based on PubMed and the Web of Science databases. We obtained the information of 149 L. johnsonii from NCBI (as of 14 February 2023), and reviewed their comprehensive metadata, including information about the plasmids they contain. This review provides a basic characterization of different L. johnsonii and some of their potential therapeutic properties for various ailments. Although the mechanisms are not fully understood yet, it is hoped that they may provide some evidence for future studies. Furthermore, the antibiotic resistance of the various strains of L. johnsonii is not clear, and more complete and in-depth studies are needed. In summary, L. johnsonii presents significant research potential for the treatment or prevention of disease; however, more proof is required to justify its therapeutic application. An additional study on the antibiotic resistance genes it contains is also needed to reduce the antimicrobial resistance dissemination.

Cold stress is the main factor limiting rice production and distribution. Chaling wild rice can survive in cold winters. AP2/EREBP is a known transcription factor family associated with abiotic stress. We identified the members of the AP2/EREBP transcription factor family in rice, maize, and Arabidopsis, and conducted collinearity analysis and gene family analysis. We used Affymetrix array technology to analyze the expression of AP2/EREBP family genes in Chaling wild rice and cultivated rice cultivar Pei’ai64S, which is sensitive to cold. According to the GeneChip results, the expression levels of AP2/EREBP genes in Chaling wild rice were different from those in Pei’ai64S; and the increase rate of 36 AP2/EREBP genes in Chaling wild rice was higher than that in Pei’ai64S. Meanwhile, the MYC elements in cultivated rice and Chaling wild rice for the Os01g49830, Os03g08470, and Os03g64260 genes had different promoter sequences, resulting in the high expression of these genes in Chaling wild rice under low-temperature conditions. Furthermore, we analyzed the upstream and downstream genes of the AP2/EREBP transcription factor family and studied the conservation of these genes. We found that the upstream transcription factors were more conserved, indicating that these upstream transcription factors may be more important in regulating cold stress. Meanwhile, we found the expression of AP2/EREBP pathway genes was significantly increased in recombinant inbred lines from Nipponbare crossing with Chaling wild rice, These results suggest that the AP2/EREBP signaling pathway plays an important role in Chaling wild rice tolerance to cold stress.

DNA is a biological polymer that encodes and stores genetic information in all living organism. Particularly, the precise nucleobase pairing inside DNA is exploited for the self-assembling of nanostructures with defined size, shape and functionality. These DNA nanostructures are known as framework nucleic acids (FNAs) for their skeleton-like features. Recently, FNAs have been explored in various fields ranging from physics, chemistry to biology. In this review, we mainly focus on the recent progress of FNAs in a pharmaceutical perspective. We summarize the advantages and applications of FNAs for drug discovery, drug delivery and drug analysis. We further discuss the drawbacks of FNAs and provide an outlook on the pharmaceutical research direction of FNAs in the future.

OBJECTIVE: Blunt thoracic aortic injury is the second most common cause of death in trauma patients. Traumatic aortic injury is an emergency that patients will face death soonly, even there is no enough time to transport the patient to the hospital. In our center, all patients were treated with thoracic endovascular aortic repair (TEVAR). We retrospectively analyze the therapeutic effects of TEVAR of blunt traumatic aortic injury (BTAI) to get some inspiration for the follow-up treatment and provide valuable guidance. METHODS: We retrospectively reviewed our institutional database to identify all patients treated with TEVAR for traumatic lesions of the aortic isthmus. We have identified 22 patients since 2017. Patients' charts were analyzed for preoperative characteristics and intraoperative variables. RESULTS: Forty-six patients were included. The median age was 56 years (23–79 years). Sixteen patients were male (73%). Most of them were graded III/IV of aortic injury. All patients were undergone endovascular treatment successfully. Six of 22 patients, showing no chest pain before admission, were presented with classic type B aortic dissection. Moreover, one patient was presented with thoracoabdominal dissection. Emergency surgery (

Cadmium (Cd) is a type of high-risk heavy metal that can damage organs such as the liver, but its mechanism is not yet clear. Ferroptosis is a newly discovered mode of regulatory cell death. We explored whether ferroptosis is involved in Cd-induced liver damage and the underlying mechanism. Our research showed that Cd induced liver damage by inducing ferroptosis, and the use of ferroptosis inhibitors reduced the degree of liver damage. Moreover, the occurrence of ferroptosis was accompanied by the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway, and inhibiting endoplasmic reticulum (ER) stress reduced ferroptosis demonstrating that ferroptosis induced by Cd is dependent on ER stress. In addition, chloroquine, a common autophagy inhibitor, mitigated ferroptosis caused by Cd exposure. Then, the iron chelator deferoxamine reduced Cd-induced lipid peroxidation and cell death, demonstrating that the iron regulation disorder caused by ferritin phagocytosis contributes to the Cd-induced ferroptosis. In conclusion, our results show that Cd-induced liver toxicity is accompanied by ferroptosis, which contributes to Cd inducing oxidative stress to trigger autophagy and ER stress to promote the process of ferroptosis.

As the human population grows rapidly, food shortages will become an even greater problem; therefore, increasing crop yield has become a focus of rice breeding programs. The maize gene, ZmDUF1645, encoding a putative member of the DUF1645 protein family with an unknown function, was transformed into rice. Phenotypic analysis showed that enhanced ZmDUF1645 expression significantly altered various traits in transgenic rice plants, including increased grain length, width, weight, and number per panicle, resulting in a significant increase in yield, but a decrease in rice tolerance to drought stress. qRT-PCR results showed that the expression of the related genes regulating meristem activity, such as MPKA, CDKA, a novel crop grain filling gene (GIF1), and GS3, was significantly changed in the ZmDUF1645-overexpression lines. Subcellular colocalization showed that ZmDUF1645 was primarily localized on cell membrane systems. Based on these findings, we speculate that ZmDUF1645, like the OsSGL gene in the same protein family, may regulate grain size and affect yield through the cytokinin signaling pathway. This research provides further knowledge and understanding of the unknown functions of the DUF1645 protein family and may serve as a reference for biological breeding engineering to increase maize crop yield.

Abstract Transcription factor IRF3 is critical for the induction of antiviral type I interferon (IFN-I). The epigenetic regulation of IFN-I production in antiviral innate immunity needs to be further identified. Here, we reported that epigenetic remodeler ARID1A, a critical component of the mSWI/SNF complex, could bind IRF3 and then was recruited to the Ifn-I promoter by IRF3, thus selectively promoting IFN-I but not TNF-α, IL-6 production in macrophages upon viral infection. Myeloid cell-specific deficiency of Arid1a rendered mice more susceptible to viral infection, accompanied with less IFN-I production. Mechanistically, ARID1A facilitates chromatin accessibility of IRF3 at the Ifn-I promoters by interacting with histone methyltransferase NSD2, which methylates H3K4 and H3K36 of the promoter regions. Our findings demonstrated the new roles of ARID1A and NSD2 in innate immunity, providing insight into the crosstalks of chromatin remodeling, histone modification, and transcription factors in the epigenetic regulation of antiviral innate immunity.

Abstract Background Flavonoid biosynthesis in plants is primarily regulated at the transcriptional level by transcription factors modulating the expression of genes encoding enzymes in the flavonoid pathway. One of the most studied transcription factor complexes involved in this regulation consists of a MYB, bHLH and WD40. However, in Chinese Narcissus (Narcissus tazetta L. var. chinensis), a popular monocot bulb flower, the regulatory mechanism of flavonoid biosynthesis remains unclear. Results In this work, genes related to the regulatory complex, NtbHLH1 and a R2R3-MYB NtMYB6, were cloned from Chinese Narcissus. Phylogenetic analysis indicated that NtbHLH1 belongs to the JAF13 clade of bHLH IIIf subgroup, while NtMYB6 was highly homologous to positive regulators of proanthocyanidin biosynthesis. Both NtbHLH1 and NtMYB6 have highest expression levels in basal plates of Narcissus, where there is an accumulation of proanthocyanidin. Ectopic over expression of NtbHLH1 in tobacco resulted in an increase in anthocyanin accumulation in flowers, and an up-regulation of expression of the endogenous tobacco bHLH AN1 and flavonoid biosynthesis genes. In contrast, the expression level of LAR gene was significantly increased in NtMYB6-transgenic tobacco. Dual luciferase assays showed that co-infiltration of NtbHLH1 and NtMYB6 significantly activated the promoter of Chinese Narcissus DFR gene. Furthermore, a yeast two-hybrid assay confirmed that NtbHLH1 interacts with NtMYB6. Conclusions Our results suggest that NtbHLH1 may function as a regulatory partner by interacting directly with NtMYB6 to enhance proanthocyanidin accumulation in Chinese Narcissus.

BackgroundPrevious studies have assessed the diagnostic accuracy of blood inflammatory markers like neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP), and CRP to albumin ratio (CAR) to predict the resistant Kawasaki disease (KD). The aim of the current meta-analysis and systematic review is to compare the prognostic ability of these inflammatory markers to predict the resistance to IVIG in patients with Kawasaki disease.MethodsA systematic search of online academic databases and search engines such as EMBASE, PubMed Central, MEDLINE, Cochrane library, Google Scholar, and ScienceDirect was conducted for papers that report the diagnostic accuracy of inflammatory markers for resistant KD. Meta-analysis was performed using STATA software.ResultsTwenty-two studies met the inclusion criteria. Pooled sensitivity and specificity of NLR as a predictor of resistant Kawasaki disease was 72% (95% CI: 62%, 80%) and 71% (95% CI: 63%, 78%), with AUC of 0.77 for PLR was 60% (95% CI: 50%, 69%) and 68% (95% CI: 61%, 75%), with area under the curve (AUC) of 0.69. Pooled sensitivity and specificity of CRP was 75% (95% CI: 68%, 81%) and 66% (95% CI: 55%, 76%), respectively, with an AUC value of 0.78. Pooled sensitivity and specificity of combined NLR and PLR was 58% (95% CI: 46%, 69%) and 73% (95% CI: 65%, 79%), respectively, with an AUC value of 0.72.ConclusionOur study found that NLR, CRP, PLR, and combined NLR/PLR have a good prognostic value in patients with resistant Kawasaki disease, with moderate to high sensitivity and specificity. More research on the accuracy of these indexes in multiple combinations is needed.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022322165].

This paper proposes a novel modular permanent magnet-assisted synchronous reluctance motor (MPMA-SynRM) structure. The rotor is composed of two types of rotor modules that are axially combined. This article analyses and explains the combined angle of the axial assembly of different rotor modules. The MPMA-SynRM rotor module is optimized using a differential evolution algorithm and the MPMA-SynRM space vector diagram is established to give the torque calculation an analytical expression. Whether there is axial magnetic isolation between different rotors is analysed, and various segment numbers, pole arc coefficients, and length ratios are used for different rotor modules to affect the electromagnetic influence of the MPMA-SynRM's cogging torque. Detailed analyses of the MPMA-SynRM loss, efficiency, and permanent magnet demagnetization state are given. The no-load back EMF, power factor, efficiency, eddy current loss, and cogging torque of the MPMA-SynRM with traditional Nd-Fe-B permanent magnet motors and permanent magnet auxiliary synchronous reluctance motors are compared, and a prototype is made to prove the performance of this motor.

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system with growing morbidity and diagnostic rate in recent years. Therefore, identifying new molecular biomarkers that inhibit the progression of bladder cancer is needed for developing further therapeutics. This study found a new potential treatment target: vaccinia-related kinase 1 (VRK1) and explored the function and mechanism of VRK1 in the development of bladder cancer. First, TCGA database and tissue microarray analysis showed that VRK1 was significantly upregulated in bladder cancer. Kaplan–Meier survival analysis indicates that the OS and PFS of the VRK1 high expression group were significantly lower than the VRK1 low expression group (p = 0.002, p = 0.005). Cox multi-factor analysis results show that VRK1 expression is an independent risk factor affecting tumor progress. The maximum tumor diameter, staging, and adjuvant chemotherapy also have a certain impact on tumor progression (p < 0.05). In internal validation, the column C index is 0.841 (95% CI, 0.803–0.880). In addition, cell functional studies have shown that VRK1 can significantly inhibit the proliferation, migration, and invasiveness of bladder cancer cells. In vivo, nude mice transplanted tumors further prove that low VRK1 can significantly inhibit the proliferation capacity of bladder cancer cells. In summary, VRK1 expression is significantly related to the staging, grade, and poor prognosis of patients with bladder cancer. At the same time, in vivo and in vitro experiments have shown that downregulation of VRK1 can significantly inhibit the proliferation of bladder cancer cells. These findings provide a basis for using VRK1 as a potential therapeutic target for patients with bladder cancer.

Abstract Pancreatic cancer is one of the most malignant tumors worldwide, and pancreatic ductal adenocarcinoma is the most common type. In pancreatic cancer, glycolysis is the primary way energy is produced to maintain the proliferation, invasion, migration, and metastasis of cancer cells, even under normoxia. However, the potential molecular mechanism is still unknown. From this perspective, this review mainly aimed to summarize the current reasonable interpretation of aerobic glycolysis in pancreatic cancer and some of the newest methods for the detection and treatment of pancreatic cancer. More specifically, we reported some biochemical parameters, such as newly developed enzymes and transporters, and further explored their potential as diagnostic biomarkers and therapeutic targets.

Recent years have witnessed a rise in the morbidity of non-alcoholic fatty liver disease (NAFLD), in line with the global outbreak of obesity. However, effective intervention strategy against NAFLD is still unavailable. The present study sought to investigate the effect and mechanism of polyene phosphatidylcholine (PPC), a classic hepatoprotective drug, on NAFLD induced by high fat diet (HFD). We found that PPC intervention reduced the mass of liver, subcutaneous, epididymal, and brown fats in HFD mice. Furthermore, PPC supplementation significantly mitigated liver steatosis and improved glucose tolerance and insulin sensitivity in HFD mice, which was accompanied by declined levels of hepatic triglyceride, serum triglyceride, low density lipoprotein, aspartate aminotransferase, and alanine aminotransferase. Using transcriptome analysis, there were 1,789 differentially expressed genes (| fold change | ≥ 2, P < 0.05) including 893 upregulated genes and 896 downregulated genes in the HFD group compared to LC group. A total of 1,114 upregulated genes and 1,337 downregulated genes in HFD + PPC group were identified in comparison to HFD group. With the help of Gene Ontology (GO) analysis, these differentially expressed genes between HFD+PPC and HFD group were discovered related to “lipid metabolic process (GO: 0006629),” “lipid modification (GO: 0030258),” and “lipid homeostasis (GO: 0055088)”. Though Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found pathways associated with hepatic homeostasis of metabolism and inflammation. Notably, the pathway “Non-alcoholic fatty liver disease (mmu04932)” (P-value = 0.00698) was authenticated in the study, which may inspire the potential mechanism of PPC to ameliorate NAFLD. The study also found that lipolysis, fatty acid oxidation, and lipid export associated genes were upregulated, while the genes in uptake of lipids and cholesterol synthesis were downregulated in the liver of HFD mice after PPC supplementation. Interestingly, PPC attenuated the metabolic inflammation via inhibiting pro-inflammatory macrophage in the livers of mice fed by HFD. In summary, this study demonstrates that PPC can ameliorate HFD-induced liver steatosis via reprogramming metabolic and inflammatory processes, which inspire clues for further clarifying the intervention mechanism of PPC against NAFLD.

With the reform and opening up, China's rapid economic development and the growing demand for passenger travel, high-speed railway projects are booming. China's railways are renowned worldwide for their high speed, low pollution and technicality, reducing transport costs, increasing the speed of logistics and promoting social and economic development. However, high-speed railway projects are systematic, complex and comprehensive, with difficult construction, extensive use of new technologies and techniques, weak theoretical and technical foundations for managers, corporate reliance on previous experience and deficiencies in traditional management models, resulting in failure to complete properly or frequent accidents. In this paper, a comprehensive evaluation study on the maturity of railway construction project management is conducted to address the shortcomings in the management of large-scale projects such as railways and to enhance the core competitiveness of enterprises.

Background: Endoplasmic reticulum (ER) stress is a basic cellular stress response that maintains cellular protein homeostasis under endogenous or exogenous stimuli, which depends on the stimulus, its intensity, and action time. The ER produces a corresponding cascade reaction for crosstalk of adaptive and/or pro-death regulation with other organelles. Hepatocellular carcinoma(HCC) is one of the most common malignant solid tumors with an extremely poor prognosis. Viral hepatitis infection, cirrhosis, and steatohepatitis are closely related to the occurrence and development of HCC, and ER stress has gradually been shown to be a major mechanism. Moreover, an increasing need for protein and lipid products and relative deficiencies of oxygen and nutrients for rapid proliferation and endoplasmic reticulum stress are undoubtedly involved. Therefore, to fully and comprehensively understand the regulatory role of endoplasmic reticulum stress in the occurrence and progression of HCC is of vital importance to explore its pathogenesis and develop novel anti-cancer strategies. Methodology: We searched for relevant publications in the PubMed databases using the keywords “Endoplasmic reticulum stress”, “hepatocellular carcinoma” in last five years,and present an overview of the current knowledge that links ER stress and HCC, which includes carcinogenesis, progression, and anti-cancer strategies, and propose directions of future research. Result: ER stress were confirmed to be multiple regulators or effectors of cancer, which also be confirmed to drive tumorigenesis and progression of HCC. Targeting ER stress signaling pathway and related molecules could play a critical role for anti-HCC and has become a research hotspot for anti-cancer in recent years. Conclusion: ER stress are critical for the processes of the tumorigenesis and progression of tumors. For HCC, ER stress was associated with tumorigenesis, development, metastasis, angiogenesis and drug resistance, targeting ER stress has emerged as a potential anti-tumor strategy.

High-fat (HF) diet-induced neuroinflammation and cognitive decline in humans and animals have been associated with microbiota dysbiosis via the gut-brain axis. Our previous studies revealed that excretory-secretory products (ESPs) derived from the larval Echinococcus granulosus (E. granulosus) function as immunomodulators to reduce the inflammatory response, while the parasitic infection alleviates metabolic disorders in the host. However, whether ESPs can improve cognitive impairment under obese conditions remain unknown. This study aimed to investigate the effects of E. granulosus-derived ESPs on cognitive function and the microbiota-gut-brain axis in obese mice. We demonstrated that ESPs supplementation prevented HF diet-induced cognitive impairment, which was assessed behaviorally by nest building, object location, novel object recognition, temporal order memory, and Y-maze memory tests. In the hippocampus (HIP) and prefrontal cortex (PFC), ESPs suppressed neuroinflammation and HF diet-induced activation of the microglia and astrocytes. Moreover, ESPs supplementation improved the synaptic ultrastructural impairments and increased both pre- and postsynaptic protein levels in the HIP and PFC compared to the HF diet-treated group. In the colon, ESPs reversed the HF diet-induced gut barrier dysfunction, increased the thickness of colonic mucus, upregulated the expression of zonula occludens-1 (ZO-1), attenuated the translocation of bacterial endotoxins, and decreased the colon inflammation. Notably, ESPs supplementation alleviated the HF diet-induced microbiota dysbiosis. After clarifying the role of antibiotics in obese mice, we found that broad-spectrum antibiotic intervention abrogated the effects of ESPs on improving the gut microbiota dysbiosis and cognitive decline. Overall, the present study revealed for the first time that the parasite-derived ESPs alleviate gut microbiota dysbiosis and improve cognitive impairment induced by a high-fat diet. This finding suggests that parasite-derived molecules may be used to explore novel drug candidates against obesity-associated neurodegenerative diseases.

Habitat fragmentation is a critical contributor to biodiversity degradation and species extinction, as illustrated by the severely fragmented habitat of the western black-crested gibbon (Nomascus concolor), a critically endangered species in the Hengduan Mountains, China. An integrated simulation model, including the random forest algorithm (RFA), empirical bayesian kriging regression (EBKR), and the least-cost path model (LCP), is introduced to determine ecological corridors for western black-crested gibbons in the Hengduan Mountains. In this study, we identified habitat variables and movement behaviors of western black-crested gibbons through RFA and then proposed EBKR, which is combined with LCP to determine potential corridors. Model simulation results suggest that the western black-crested gibbons' habitat is mostly dependent on forests with an altitude of about 2,000 m and a 20° slope, areas undisturbed by human activities. Two land use and cover classes predominate inside the corridors, tree cover and mostly natural vegetation, corresponding to 67.55% and 18.54% of total land use, respectively. A total of nine corridors were planned in Hengduan Mountains via LCP. The shortest corridor, which has recently been incorporated into national park planning, is 7.40 km, and is a route that has no need for bridge construction. The longest corridor is 95.74 km and would require construction of three bridges. Mobility of western black-crested gibbons can increase by 39.49% using our simulated corridors. The planned corridor is an optimized route for western black-crested gibbons in the Hengduan Mountains, and provides the best opportunities for security, food, and survival. The proposed integrated model is an efficient method for designing and estimating habitat suitability using competitively predictive performance and simultaneously quantifying model uncertainties.