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Abstract Background Medical informed consent stands as an ethical and legal requisite preceding any medical intervention. Hospitalized patients face functional health literacy (FHL) challenges when dealing with informed consent forms (ICFs). The legitimacy of ICFs and informed consent procedures in China remains substantially undisclosed. The study’s aim was to investigate if Chinese patients have adequate FHL to be truly informed before providing medical consent. Methods In this cross-sectional, structured interview-based study, FHL was assessed within the context of the informed consent scenarios in two teaching hospitals (a 1500-bed general tertiary hospital and a 700-bed cancer hospital) affiliated with Shantou University Medical College. Twenty-seven patients admitted across clinical departments, along with their relatives (n = 59), were enrolled in the study after obtaining informed consent. The participants underwent a three-step assessment with two selected ICFs —teach-back skills, perceived understanding (perception), and informed knowledge (cognizance), with each component carrying a maximum score of 10. Data were analyzed with SPSS (version 22.0) for descriptive and inferential statistics, with consideration of significant P values as

Abstract Massive hemorrhage following tissue trauma has high mortality owing to the lack of timely intervention. However, research on utilizing hemostats for humans is limited; therefore, developing an efficient emergency hemostatic agent is imperative. We developed a hemostatic sponge using natural polysaccharide riclin, theoretically modified with 50% aldehyde content (AR50). The AR50 sponge, with quasi-honeycomb channels and appropriate aldehyde content, exhibits ultra-high blood absorption (59.4 g·g−1) and rapidly targets erythrocytes and platelets to form a stable barrier. It surpasses most commercial hemostats in porcine artery scission (reducing hemostasis time and blood loss by 53 s and 4.2 g), hepatic bleeding laceration (68 s and 2.6 g), and perforation models (140 s and 4.9 g). The AR50 sponge is easily removed post hemostasis, exhibits antibacterial properties by destroying bacterial cell walls, and is safely absorbed by day 5, making it an ideal emergency hemostatic agent for massive hemorrhages in humans.

Abstract Background Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigated the involvement of microRNAs (miRNAs) in lipophagy during demyelinating diseases, assessed their capacity to modulate LDAM subtypes, and elucidated the potential underlying mechanisms involved. Methods C57BL/6 mice were used for in vivo experiments. Two weeks post demyelination induction at cervical level 4 (C4), histological assessments and confocal imaging were performed to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. miRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. The role of miR-223 in lipophagy under these conditions was specifically explored. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral infection, validated the bioinformatics findings. Immunofluorescence staining was used to measure LD accumulation, autophagy levels, target gene expression, and inflammatory mediator levels to elucidate the mechanisms of action of miR-223 in LDAM. Results Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy revealed increased numbers of autophagic vacuoles at the injury site. Multi-omics analysis revealed miR-223 as a crucial regulatory gene in lipophagy during demyelination. It was identified that cathepsin B (CTSB) targets miR-223 in autophagy to integrate miRNA, mRNA, and autophagy gene databases. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased the expression of the inflammatory mediator IL-1β. Conclusion These findings indicate that miR-223 plays a pivotal role in lipophagy under demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens the understanding of the molecular mechanisms of lipophagy and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.

To analyze the effect of bitumen component on wax crystallization characteristic, this study obtained the Paraffinic, Naphthenic and Aromatic (PNA) distribution of two samples with high wax contents (AAM-1 and AAC-1) by Gas Chromatography (GC) test, and form the thermodynamic model. The results indicate that the content of crystalline wax with large carbon number is higher than the original distribution of wax in bitumen, as the temperature decreases the main composition of crystalline wax in AAM-1 will change from C20-C38 to C13-C19, and the even smaller components will begin to crystallize at 15 °C. As for AAC-1, the decrease in temperature will only affect the crystalline wax components of C16-C25, which could be due to the paraffinic distribution or aromatic content based on the PNA distribution. To determine the internal factors affecting wax crystallization, bitumen with different component compositions were designed, finding that wax will be easier to crystallize from bitumen with more large carbon number paraffinic. While the crystalline wax content is nearly the same at −20 °C, as the aromatic content increases, the decrease in WPT is close to linear. This suggests that the shape and crystal morphology of the wax crystals may have changed, based on the crystal growth and nucleation theory of wax, thereby inhibiting the crystallization of wax.

Abstract Background Hepatocellular carcinoma (HCC) is a major health concern, necessitating a deeper understanding of its prognosis and underlying mechanisms. This study aimed to investigate the mechanism and prognostic value of CD8+ T Cell exhaustion (CD8+ TEX)-related genes in HCC and construct a survival prognosis prediction model for patients with HCC. Methods CD8+ TEX-related genes associated with HCC prognosis were analysed and identified, and a prognostic prediction model was constructed using the ‘least absolute shrinkage and selection operator’ Cox regression model. Immunohistochemistry was used to verify the expression of the model genes in HCC tissues. A nomogram was constructed based on risk scores and clinical features, and its predictive efficacy was verified. The expression of STAM, ANXA5, and MAD2L2 in HCC cell lines was detected by western blotting; subsequently, these genes were knocked down in HCC cell lines by small interfering RNA, and their effects on the proliferation and migration of HCC cell lines were detected by colony formation assay, cck8, wound healing, and transwell assays. Results Six genes related to CD8+ TEX were included in the risk-prediction model. The prognosis of patients with HCC in the low-risk group was significantly better than that of those in the high-risk group. Cox regression analysis revealed that the risk score was an independent risk factor for the prognosis of patients with HCC. The differentially expressed genes in patients with high-risk HCC were mainly enriched in the nucleotide-binding oligomerization domain-containing protein-like receptor, hypoxia-inducible factor-1, and tumour programmed cell death protein (PD)-1/PD-L1 immune checkpoint pathways. The CD8+ TEX-related genes STAM, ANXA5, and MAD2L2 were knocked down in HCC cell lines to significantly inhibit cell proliferation and migration. The prediction results of the nomogram based on the risk score showed a good fit and application value. Conclusion The prediction model based on CD8+ TEX-related genes can predict the prognosis of HCC and provide a theoretical basis for the early identification of patients with poor HCC prognosis.

Recently, a novel approach has been proposed to produce ultrashort, fully coherent high-repetition-rate EUV and X-ray radiation by combining an energy recovery linac (ERL) with the angular-dispersion-induced microbunching methodology. It is critical to maintain microbunching when the beam passes through bending magnets between the undulators, which results in difficulties supporting multiple beamlines. In this paper, the design of a multiplexed emitting system consisting of multi-bend achromats, matching sections and radiators to facilitate the multi-beamline operation is presented. Theoretical analysis and numerical simulations have been carried out and the results show that the microbunching and beam quality can be well maintained after four times of bending. Five radiation pulses with a central wavelength of 13.5 nm and peak power at the MW level have been produced by the same electron beam via this multiplexed emitting system. The proposed method holds potential in the multi-beamline operation of ERL- or storage-ring-based coherent light sources.

Objective Although it is an effective fixation technique for an unstable odontoid, anterior fixation remains challenging in pediatric populations. Our study measures the anatomical parameters of the odontoid to identify the feasibility of anterior fixation with a single screw for children. Methods We retrospectively collected data from 112 normal male and female children (aged between 2 and 18) in our institute from January 1, 2022 to December 31, 2022. Subjects were divided into a youth group (2–6 years old), a juvenile group (7–12 years old), and an adolescent group (13–18 years old). Sagittal and coronal computed tomography images of the upper cervical spine were used to measure the screw length, angle, and inner and outer diameters of the odontoid. One‐way analysis of variance with the Tukey test was used to analyze the parameters among the groups, while the t‐test was used to analyze gender differences. Correlations between parameters and age were assessed using Pearson's test. Results There were significant differences between male and female subjects in screw length and inner and outer diameters (of both sagittal and coronal views) but not in screw angle. The narrowest diameter of the odontoid was 4.0 ± 1.5 mm in the youth group, 5.5 ± 1.5 mm in the juvenile group, and 5.6 ± 1.1 mm in the adolescent group, respectively. There were significant differences among the three groups in screw length (p 4 mm. Screw length and inner and outer diameters in lateral view were positively correlated with age, and screw angle was negatively correlated with age. Conclusion It is feasible to insert a standard single screw (Φ 3.5 mm) into the odontoid of children aged 7–18 years old but not those aged 2–6 years old. How the anatomical parameters of the odontoid change with age, especially the narrowest diameters, is worthy of attention.

With the rapid development of the Internet of Things (IoT), the positioning accuracy requirement of the IoT is increasing, especially for those applications without Global Navigation Satellite System (GNSS) signals. Ultra-Wideband (UWB) is treated as a high-accuracy positioning method that can be utilized in GNSS-blocked environments. However, UWB’s performance is still limited when it is applied in practical applications due to errors such as Non-Line-of-Sight (NLOS) errors, multipath errors, and systematic errors in UWB range values. To constrain the impacts of these mentioned errors on UWB positioning accuracy, this work proposes a novel UWB positioning model by introducing a UWB ranging offset calibration algorithm and a moving average filter into a robust extended Kalman filter. In such a UWB positioning model, the ranging offset calibration algorithm is employed to limit the infuence of UWB systematic errors, and the prior residual-based IGG-III weighting model is used to restrain the impacts of NLOS and multipath errors. The moving average filter is to further decrease the impact of the measuring noise on UWB positioning parameter estimation. To investigate the effectiveness of this proposed method, three sets of UWB experiments are arranged in three classic user environments. The experimental results show that (1) after applying the UWB ranging offset calibration algorithm, UWB positioning accuracies in classic environments, namely indoor condition, outdoor condition, and transition area are increased by 50.3%, 20.2%, and 46.9%, respectively; (2) the moving average filter can effectively improve the smoothness of UWB positioning results in terms of standard deviation; (3) the prior residual-based robust theory brings about 49.4% and 25.2% positioning improvements to horizontal and vertical components under poor measurement quality conditions, but such improvements are rather slight when there are good-quality measurements; and (4) after applying the ranging offset calibration algorithm and moving average filter to the robust EKF together, the elevation accuracy of UWB positioning is increased by 67.1%, 22.2%, and 50.5%, respectively, in the three classic user environments.

Secondary salinization is a crucial constraint on agricultural progress in arid regions. The specific mulching irrigation technique not only exacerbates secondary salinization but also complicates field-scale soil salinity monitoring. UAV hyperspectral remote sensing offers a monitoring method that is high-precision, high-efficiency, and short-cycle. In this study, UAV hyperspectral images were used to derive one-dimensional, textural, and three-dimensional feature variables using Competitive adaptive reweighted sampling (CARS), Gray-Level Co-occurrence Matrix (GLCM), Boruta Feature Selection (Boruta), and Brightness-Color-Index (BCI) with Fractional-order differentiation (FOD) processing. Additionally, three modeling strategies were developed (Strategy 1 involves constructing the model solely with the 20 single-band variable inputs screened by the CARS algorithm. In Strategy 2, 25 texture features augment Strategy 1, resulting in 45 feature variables for model construction. Strategy 3, building upon Strategy 2, incorporates six triple-band indices, totaling 51 variables used in the model’s construction) and integrated with the Seagull Optimization Algorithm for Random Forest (SOA-RF) models to predict soil electrical conductivity (EC) and delineate spatial distribution. The results demonstrated that fractional order differentiation highlights spectral features in noisy spectra, and different orders of differentiation reveal different hidden information. The correlation between soil EC and spectra varies with the order. 1.9th order differentiation is proved to be the best order for constructing one-dimensional indices; although the addition of texture features slightly improves the accuracy of the model, the integration of the three-waveband indices significantly improves the accuracy of the estimation, with an R2 of 0.9476. In contrast to the conventional RF model, the SOA-RF algorithm optimizes its parameters thereby significantly improving the accuracy and model stability. The optimal soil salinity prediction model proposed in this study can accurately, non-invasively and rapidly identify excessive salt accumulation in drip irrigation under membrane. It is of great significance to improve the growing conditions of cotton, increase the cotton yield, and promote the sustainable development of Xinjiang’s agricultural economy, and also provides a reference for the prevention and control of regional soil salinization.

The contribution of the magnetic field to the formation of high-mass stars is poorly understood. We report the high angular resolution (∼0.″3, 870 au) map of the magnetic field projected on the plane of the sky ( B _POS ) toward the high-mass star-forming region G333.46−0.16 (G333), obtained with the Atacama Large Millimeter/submillimeter Array at 1.2 mm as part of the Magnetic fields in Massive star-forming Regions survey. The B _POS morphology found in this region is consistent with a canonical “hourglass” with an embedded flattened envelope in a perpendicular direction, which suggests a dynamically important field. This region is fragmented into two protostars that appear to be gravitationally bound in a stable binary system with a separation of ∼1740 au. Interestingly, by analyzing H ^13 CO ^+ ( J = 3–2) line emission, we find no velocity gradient over the extent of the continuum, which is consistent with a strong field. We model the B _POS , obtaining a marginally supercritical mass-to-flux ratio of 1.43, suggesting an initially strongly magnetized environment. Based on the Davis–Chandrasekhar–Fermi method, the magnetic field strength toward G333 is estimated to be 5.7 mG. The absence of strong rotation and outflows toward the central region of G333 suggests strong magnetic braking, consistent with a highly magnetized environment. Our study shows that despite being a strong regulator, the magnetic energy fails to prevent the process of fragmentation, as revealed by the formation of the two protostars in the central region.

BackgroundHepatocellular carcinoma (HCC) is a malignant tumor with a high rate of recurrence and m metastasis that does not respond well to current therapies and has a very poor prognosis. Disulfidptosis is a novel mode of cell death that has been analyzed as a novel therapeutic target for HCC cells.MethodsThis study integrated bulk ribonucleic acid (RNA) sequencing datasets, spatial transcriptomics (ST), and single-cell RNA sequencing to explore the landscape of disulfidptosis and the immune microenvironment of HCC cells.ResultsWe developed a novel model to predict the prognosis of patients with HCC based on disulfidptosis. The model has good stability, applicability, and prognostic and immune response prediction abilities. N-myc downregulated gene1 (NDRG1) may contribute to poor prognosis by affecting macrophage differentiation, thus allowing HCC cells to evade the immune system.ConclusionOur study explores the disulfidptosis of HCC cells through multi-omics and establishes a new putative model that explores possible targets for HCC treatment.

Abstract Aims Splenectomy combined with pericardial devascularization is one of the important methods to treat hypersplenism, gastrointestinal bleeding, and other complications caused by liver cirrhosis; however, it is accompanied by a high risk of portal vein thrombosis (PVT). This study aimed to explore the preventive and therapeutic effects of proximal splenic vein ligation (PSVL) with postoperative transcatheter anticoagulant therapy (TCAT) on PVT. Methods This study retrospectively selected 143 patients with liver cirrhosis and portal hypertension, who received splenectomy combined with pericardial devascularization from June 30, 2018 to June 30, 2021. According to computed tomography photography, within 1 week before the operation, the patients were divided into a prevention group (without preoperative PVT, n = 112) and a treatment group (preoperative PVT, n = 31). Then, each group was subdivided based on the treatment and prevention measures into PSVL + TCAT (n = 70) and systemic anticoagulant therapy (SAT) subgroups (n = 73). The preventive and therapeutic effects of PSVL followed by TCAT on PVT were analyzed. Results The operation time in the PSVL + TCAT subgroups was longer than that in the SAT subgroups (185 ± 76 min vs. 161 ± 55 min; p 0.50). There was no operative death, and all patients recovered uneventfully. In the prevention group, procedure‐related complications occurred in two patients in the PSVL + TCAT subgroup (3.7% [2/54]), including one patient with slight pancreatitis and one patient with chylous leakage, owing to mobilization of the pancreas. The PVT incidence in the prevention group was significantly different between the two subgroups at postoperative 7th day, 3rd month, and 6th month (PSVL + TCAT: 0%, 11.1%, and 5.6% vs. SAT: 39.7%, 31.0%, and 20.7%, respectively; all p

Objective: Owing to the lethality of liver cancer, it is considered as one of the devastating types of cancers across the globe. Consistently, the study was designed to elucidate the role and to explore the therapeutic implications of miR-145 in human liver cancer. Materials & methods: In the current experimental study, gene expression was determined by RT-PCR analysis. Transfection of cancer cells was carried out using Lipofectamine 2000. The cell proliferation of liver cancer cells was estimated by MTT assay. Clonogenic assay was performed for analysis of colony forming potential of cancer cells. Flow cytometry was done to analyze the cell cycle phase distribution of cancer cells. Transwell chamber assay was performed to assess the motility of cancer cells. Western blotting was done to estimate the expression levels of proteins. Dual luciferase assay was performed for interaction analysis of miR-145 with CDCA3. Result: The miR-145 expression was found to be downregulated in liver cancer cells. The transfection mediated overexpression of miR-145 inhibited the cancer cell proliferation and when miR-145 inhibitor was transfected, cancer cells showed higher proliferation rates. Enrichment of miR-145 levels led to cell cycle arrest at G2/M phase by inhibiting cyclin B1. miR-145 also restricted the migration and invasion of cancer cells. CDCA3 was shown to be the intracellular target of miR-145 and it was found that the inhibitory effects of miR-145 were modulated through CDCA3, intracellularly. Conclusion: The current study clearly revealed that there is a need to investigate the regulatory role of different molecular entities like microRNAs in cancer development to better understand mechanics behind this pathogenesis and design more effective combating strategies against cancer.

This examined the effects of Lonicera japonica extract (LJE) with different chlorogenic acid (CGA) contents on lactation performance, antioxidant status and immune function and rumen fermentation in heat-stressed high-yielding dairy cows. In total, 45 healthy Chinese Holstein high-yielding dairy cows, all with similar milk yield, parity, and days in milk were randomly allocated to 3 groups: (1) the control group (CON) without LJE; (2) the LJE-10% CGA group, receiving 35 g/(d·head) of LJE-10% CGA, and (3) the LJE-20% CGA group, receiving 17.5 g/(d·head) of LJE-20% CGA. The results showed that the addition of LJE significantly reduced RT, and enhanced DMI, milk yield, milk composition, and improved rumen fermentation in high-yielding dairy cows experiencing heat stress. Through the analysis of the serum biochemical, antioxidant, and immune indicators, we observed a reduction in CREA levels and increased antioxidant and immune function. In this study, while maintaining consistent CGA content, the effects of addition from both types of LJE are similar. In conclusion, the addition of LJE at a level of 4.1 g CGA/(d·head) effectively relieved heat stress and improved the lactation performance of dairy cows, with CGA serving as the effective ingredient responsible for its anti-heat stress properties.

BackgroundAlthough numerous studies demonstrated a link between plasma homocysteine (Hcy) levels and psoriasis, there still exists a certain level of controversy. Therefore, we conducted a Mendelian randomization study to investigate whether homocysteine plays a causative role in the development or exacerbation of psoriasis.MethodsA two-sample Mendelian randomization (MR) analysis was conducted. Summary-level data for psoriasis were acquired from the latest R9 release results from the FinnGen consortium (9,267 cases and 364,071 controls). Single nucleotide polymorphisms (SNPs) robustly linked with plasma Hcy levels at the genome-wide significance threshold (p < 5 × 10−8) (18 SNPs) were recognized from the genome-wide meta-analysis on total Hcy concentrations (n = 44,147 participants) in individuals of European ancestry. MR analyses were performed utilizing the random-effect inverse variance-weighted (IVW), weighted median, and MR-Egger regression methods to estimate the associations between the ultimately filtrated SNPs and psoriasis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy.ResultsMR analyses revealed no causal effects of plasma Hcy levels on psoriasis [IVW: odds ratio (OR) = 0.995 (0.863–1.146), p = 0.941; weighed median method: OR = 0.985 (0.834–1.164), p = 0.862; MR-Egger regression method: OR = 0.959 (0.704–1.305), p = 0.795]. The sensitivity analyses displayed no evidence of heterogeneity and directional pleiotropy, and the causal estimates of Hcy levels were not influenced by any individual SNP.ConclusionOur study findings did not demonstrate a causal effect of genetically determined circulating Hcy levels on psoriasis.

We report on Atacama Large Millimeter/submillimeter Array observations of polarized dust emission at 1.2 mm from NGC6334I, a source known for its significant flux outbursts. Between five months, our data show no substantial change in total intensity and a modest 8% variation in linear polarization, suggesting a phase of stability or the conclusion of the outburst. The magnetic field, inferred from this polarized emission, displays a predominantly radial pattern from northwest to southeast with intricate disturbances across major cores, hinting at spiral structures. Energy analysis of CS ( J = 5 → 4) emission yields an outflow energy of approximately 3.5 × 10 ^45 erg, aligning with previous interferometric studies. Utilizing the Davis–Chandrasekhar–Fermi method, we determined magnetic field strengths ranging from 1 to 11 mG, averaging at 1.9 mG. This average increases to 4 ± 1 mG when incorporating Zeeman measurements. Comparative analyses using gravitational, thermal, and kinetic energy maps reveal that magnetic energy is significantly weaker, possibly explaining the observed field morphology. We also find that the energy in the outflows and the expanding cometary HII region is also larger than the magnetic energy, suggesting that protostellar feedback may be the dominant driver behind the injection of turbulence in NGC6334I at the scales sampled by our data. The gas in NGC6334I predominantly exhibits supersonic and trans-Alfvenic conditions, transitioning towards a super-Alfvenic regime, underscoring a diminished influence of the magnetic field with increasing gas density. These observations are in agreement with prior polarization studies at 220 GHz, enriching our understanding of the dynamic processes in high-mass star-forming regions.

We report the first arcsecond-resolution observations of the magnetic field in the ministarburst complex Sgr B2. SMA polarization observations revealed magnetic field morphology in three dense cores of Sgr B2 N(orth), M(ain), and S(outh). The total plane-of-sky magnetic field strengths in these cores are estimated to be 4.3–10.0 mG, 6.2–14.7 mG, and 1.9–4.5 mG derived from the angular dispersion function method after applying the correction factors of 0.21 and 0.5. Combining with analyses of the parsec-scale polarization data from Stratospheric Observatory for Infrared Astronomy, we found that a magnetically supercritical condition is present from the cloud scale (∼10 pc) to core scale (∼0.2 pc) in Sgr B2, which is consistent with the burst of star formation activities in the region likely resulting from a multiscale gravitational collapse from the cloud to dense cores.

We have comprehensively studied the multiscale physical properties of the massive infrared dark cloud G28.34 (the Dragon cloud) with dust polarization and molecular line data from Planck, FCRAO-14 m, James Clerk Maxwell Telescope, and Atacama Large Millimeter/submillimeter Array. We find that the averaged magnetic fields of clumps tend to be either parallel with or perpendicular to the cloud-scale magnetic fields, while the cores in clump MM4 tend to have magnetic fields aligned with the clump fields. Implementing the relative orientation analysis (for magnetic fields, column density gradients, and local gravity), velocity gradient technique, and modified Davis–Chandrasekhar–Fermi analysis, we find that G28.34 is located in a trans-to-sub-Alfvénic environment; the magnetic field is effectively resisting gravitational collapse in large-scale diffuse gas, but is distorted by gravity within the cloud and affected by star formation activities in high-density regions, and the normalized mass-to-flux ratio tends to increase with increasing density and decreasing radius. Considering the thermal, magnetic, and turbulent supports, we find that the environmental gas of G28.34 is in a supervirial (supported) state, the infrared dark clumps may be in a near-equilibrium state, and core MM4-core4 is in a subvirial (gravity-dominant) state. In summary, we suggest that magnetic fields dominate gravity and turbulence in the cloud environment at large scales, resulting in relatively slow cloud formation and evolution processes. Within the cloud, gravity could overwhelm both magnetic fields and turbulence, allowing local dynamical star formation to happen.

We observe the magnetic field morphology toward a nearby star-forming filamentary cloud, G202.3+2.5, using James Clerk Maxwell Telescope/POL-2 850 μ m thermal dust polarization observations with an angular resolution of 14.″4 (∼0.053 pc). The average magnetic field orientation is found to be perpendicular to the filaments, while showing different behaviors in the four subregions, suggesting various effects from the filaments’ collision in these subregions. With the kinematics obtained by the ${{{\rm{N}}}_{2}{\rm{H}}}^{+}$ observation by IRAM, we estimate the plane-of-sky magnetic field strength by two methods, the classical Davis–Chandrasekhar–Fermi (DCF) method and the angular dispersion function (ADF) method, giving B _pos,dcf and B _pos,adf of ∼90 and ∼53 μ G. We study the relative importance between the gravity ( G ), magnetic field ( B ), and turbulence ( T ) in the four subregions, and find G > T > B , G ≥ T > B , G ∼ T > B , and T > G > B in the north tail, west trunk, south root, and east wing, respectively. In addition, we investigate the projection effects on the DCF and ADF methods, based on a similar simulation case, and find the 3D magnetic field strength may be underestimated by a factor of ∼3 if applying the widely used statistical B _pos -to- B _3D factor when using the DCF or ADF methods, which may further underestimate/overestimate the related parameters.

We report 850 μ m continuum polarization observations toward the filamentary high-mass star-forming region NGC 2264, taken as part of the B -fields In STar forming Regions Observations large program on the James Clerk Maxwell Telescope. These data reveal a well-structured nonuniform magnetic field in the NGC 2264C and 2264D regions with a prevailing orientation around 30° from north to east. Field strength estimates and a virial analysis of the major clumps indicate that NGC 2264C is globally dominated by gravity, while in 2264D, magnetic, gravitational, and kinetic energies are roughly balanced. We present an analysis scheme that utilizes the locally resolved magnetic field structures, together with the locally measured gravitational vector field and the extracted filamentary network. From this, we infer statistical trends showing that this network consists of two main groups of filaments oriented approximately perpendicular to one another. Additionally, gravity shows one dominating converging direction that is roughly perpendicular to one of the filament orientations, which is suggestive of mass accretion along this direction. Beyond these statistical trends, we identify two types of filaments. The type I filament is perpendicular to the magnetic field with local gravity transitioning from parallel to perpendicular to the magnetic field from the outside to the filament ridge. The type II filament is parallel to the magnetic field and local gravity. We interpret these two types of filaments as originating from the competition between radial collapsing, driven by filament self-gravity, and longitudinal collapsing, driven by the region's global gravity.

Magnetic fields of molecular clouds in the central molecular zone (CMZ) have been relatively under-observed at sub-parsec resolution. Here, we report JCMT/POL2 observations of polarized dust emission in the CMZ, which reveal magnetic field structures in dense gas at ∼0.5 pc resolution. The 11 molecular clouds in our sample include two in the western part of the CMZ (Sgr C and a farside cloud candidate), four around the Galactic longitude 0 (the 50 km s ^−1 cloud, CO 0.02−0.02, the Stone , and the Sticks and Straw among the Three Little Pigs), and five along the Dust Ridge (G0.253+0.016, clouds b, c, d, and e/f), for each of which we estimate the magnetic field strength using the angular dispersion function method. The morphologies of magnetic fields in the clouds suggest potential imprints of feedback from expanding H ii regions and young massive star clusters. A moderate correlation between the total viral parameter versus the star formation rate (SFR) and the dense gas fraction of the clouds is found. A weak correlation between the mass-to-flux ratio and the SFR, and a weak anticorrelation between the magnetic field and the dense gas fraction are also found. Comparisons between magnetic fields and other dynamic components in clouds suggest a more dominant role of self-gravity and turbulence in determining the dynamical states of the clouds and affecting star formation at the studied scales.

The present study evaluated the effects of early supplementation with zinc proteinate (ZnP) or zinc oxide (ZnO) for 2 weeks on the growth performance, redox status, plasma trace element concentrations, and rectal microbiota of preweaned dairy calves. A total of 60 newborn healthy female Holstein dairy calves, with initial body weight (BW): 41.33 ± 0.62 kg, were randomly allocated to 5 groups of 12 each: a control group (CON); three groups supplemented with 261 (L-ZnP), 523 (M-ZnP), and 784 (H-ZnP) mg/day ZnP, equivalent to 40, 80, and 120 mg/day zinc, respectively; and one group supplemented with 232 mg/day ZnO, equivalent to 180 mg/day zinc (ZnO). Zinc supplements were administered on days 1–14, and the calves were followed up until day 70. Zinc supplementation increased total dry matter intake (DMI) and starter DMI compared with the CON group (p

Several epidemiological studies suggest a correlation between eating time and obesity. Night eating syndrome characterized by a time-delayed eating pattern is positively associated with obesity in humans as well as in experimental animals. Here, we show that oil intake at night significantly makes more fat than that at day in wild-type mice, and circadian Period 1 (Per1) contributes to this day–night difference. Per1-knockout mice are protected from high-fat diet–induced obesity, which is accompanied by a reduction in the size of the bile acid pool, and the oral administration of bile acids restores fat absorption and accumulation. We identify that PER1 directly binds to the major hepatic enzymes involved in bile acid synthesis such as cholesterol 7alpha-hydroxylase and sterol 12alpha-hydroxylase. A biosynthesis rhythm of bile acids is accompanied by the activity and instability of bile acid synthases with PER1/PKA-mediated phosphorylation pathways. Both fasting and high fat stress enhance Per1 expression, increasing the fat absorption and accumulation. Our findings reveal that Per1 is an energy regulator and controls daily fat absorption and accumulation. Circadian Per1 controls daily fat absorption and accumulation, suggesting Per1 is a potential candidate of a key regulator in stress response and the relevant obesity risk.

BackgroundLiver hepatocellular carcinoma (LIHC) is a highly malignant tumor with high metastasis and recurrence rates. Due to the relation between lipid metabolism and the tumor immune microenvironment is constantly being elucidated, this work is carried out to produce a new prognostic gene signature that incorporates immune profiles and lipid metabolism of LIHC patients.MethodsWe used the “DEseq2” R package and the “Venn” R package to identify differentially expressed genes related to lipid metabolism (LRDGs) in LIHC. Additionally, we performed unsupervised clustering of LIHC patients based on LRDGs to identify their subgroups and immuno-infiltration and Gene Ontology (GO) enrichment analysis on the subgroups. Next, we employed multivariate, LASSO and univariate Cox regression analyses to determine variables and to create a prognostic profile on the basis of immune- and lipid metabolism-related differential genes (IRDGs and LRDGs). We separated patients into low- and high-risk groups in accordance with the best cut-off value of risk score. We conducted Decision Curve Analysis (DCA), Receiver Operating Characteristic curve analysis as a function of time as well as Survival Analysis to evaluate this signature’s prognostic value. We incorporated the clinical characteristics of patients into the risk model to obtain a nomogram prognostic model. GEO14520 and ICGC-LIRI JP datasets were employed to externally confirm the accuracy and robustness of signature. The gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were applied for investigating the underlying mechanisms. Immune infiltration analysis was implemented to examine the differences in immune between both risk groups. Single-cell RNA sequencing (scRNA-SEQ) was utilized to characterize the genes that were involved in the distribution of signature and expression characteristics of different LIHC cell types. The patients’ sensitivity in both risk groups to commonly used chemotherapeutic agents and semi-inhibitory concentrations (IC50) of the drugs was assessed using the GDSC database. On the basis of the differentially expressed genes (DEGs) in the two groups, the CMAP database was adopted for the prediction of potential small-molecule compounds. Small-molecule compounds were molecularly docked with prognostic markers. Lastly, we investigated the prognostic gene expression levels in normal and LIHC tissues with immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction(qRT-PCR).ResultsWe built and verified a prognostic signature with seven genes that incorporated immune profiles and lipid metabolism. Patients were classified as low- and high-risk groups depending on their prognostic profiles. The overall survival (OS) was markedly lower in the high-risk group as compared to low-risk group. Time-dependent ROC curves more precisely predicted patients' survival at 1, 3 and 5 years; the area under the ROC curve was 0.81 (1 year), 0.75 (3 years) and 0.77 (5 years). The DCA curves showed the value of the prognostic genes in this signature for clinical applications. We included the patients' clinical characteristics in the risk model for both multivariate and univariate Cox regression analyses, and the findings revealed that the risk model represents an independent factor that influences OS in LIHC patients. With immune analysis, GSVA and GSEA, we identified that there are remarkable differences between the two risk groups in immune pathways, lipid metabolism, tumor development, immune cell infiltration and immune microenvironment, response to immunotherapy, and sensitivity to chemotherapy. Moreover, those with higher risk scores presented greater sensitivity to the chemotherapeutic agents. Experiments in vitro further elucidated the roles of SPP1 and FLT3 in the LIHC immune microenvironment. Furthermore, four small-molecule drugs that could target LIHC were screened. In vitro qRT-PCR , IHC revealed that the SPP1,KIF18A expressions were raised in LIHC in tumor samples, whereas FLT3,SOCS2 showed the opposite trend.ConclusionsWe developed and verified a new signature comprising immune- and lipid metabolism-associated markers and to assess the prognosis and the immune status of LIHC patients. This signature can be applied to survival prediction, individualized chemotherapy, and immunotherapeutic guidance for patients with liver cancer. This study also provides potential targeted therapeutics and novel ideas for the immune evasion and progression of LIHC.

Our previous study showed that early supplementation with 10 g/(d·head) of galacto-oligosaccharides (GOS) in newborn Holstein dairy calves reduced the incidence of diarrhea and improved growth performance and mineral absorption. Since the dose of 10 g/(d·head) was the lowest by dose screening in our previous study, the present study was designed to investigate whether a lower amount of GOS has similar effects on growth performance, immune function, serum nutrients in newborn Holstein heifer calves, and to further investigate its effect on appetite-related hormones. Twenty-eight healthy newborn (1 day of age) Holstein heifers with similar average body weight (41.18 ± 1.90 kg) were randomly divided into four groups (n = 7): the control group (CON group), which received heated raw milk, and three experimental groups, which received heated raw milk supplemented with 2.5 (GOS2.5 group), 5 (GOS5 group), and 10 g/(d·head) (GOS10 group) GOS. All heifer calves were fed the same starter for 28 d. Supplementation with GOS linearly increased the final body weight, average daily gain, and feed efficiency in heifer calves (p < 0.01). Compared with the control group, the average daily gain and feed efficiency of heifer calves were significantly higher in the GOS5 and GOS10 groups than in the control group (p < 0.05). Furthermore, supplementation with GOS quadratically enhanced the starter and total average daily feed intake of the heifers (p < 0.01), especially in the GOS2.5 and GOS5 groups, (p < 0.05 vs. CON). The serum concentration of immunoglobulin A was linearly increased by GOS supplementation (p < 0.05), and the levels in the GOS5 and GOS10 groups were significantly higher than those in the CON group. Meanwhile, GOS linearly decreased serum interleukin-1β and interleukin-6 concentrations (p < 0.05). The serum concentration of triglycerides was also linearly decreased (p < 0.05), whereas total protein and blood urea nitrogen were linearly increased (p < 0.05). Supplementation with GOS linearly decreased the serum concentration of leptin (p < 0.05) but increased cholecystokinin and glucagon-like peptide-1 (p < 0.05). Increasing doses of GOS linearly improved serum calcium and copper concentrations (p < 0.01) and quadratically enhanced the concentration of magnesium, which peaked in the GOS5 group (p < 0.05). In conclusion, GOS supplementation reduced the incidence of diarrhea and improved the growth performance and immune function of Holstein heifer calves.

Abstract Background Methyltransferase SETDB1 is highly expressed in breast cancer (BC), however, the mechanisms by which SETDB1 promotes BC progression to endocrine therapy resistance remains elusive. In this study, we examined the mechanisms by which SETDB1 contribute to BC endocrine therapy resistance. Methods We utilized therapy sensitive (MCF7 and ZR75), therapy resistant (MCF7-TamR, MCF7-FR, MCF7-PELP1cyto, MCF7-SETDB1) estrogen receptor alpha positive (ER+)BC models and conducted in vitro cell viability, colony formation, 3-dimensional cell growth assays to investigate the role of SETDB1 in endocrine resistance. RNA-seq of parental and SETDB1 knock down ER+ BC cells was used to identify unique pathways. SETDB1 interaction with PELP1 was identified by yeast-two hybrid screen and confirmed by immunoprecipitation and GST-pull down assays. Mechanistic studies were conducted using Western blotting, reporter gene assays, RT-qPCR, and in vitro methylation assays. Xenograft assays were used to establish the role of PELP1 in SETDB1 mediated BC progression. Results RNA-seq analyses showed that SETDB1 regulates expression of a subset of estrogen receptor (ER) and Akt target genes that contribute to endocrine therapy resistance. Importantly, using yeast-two hybrid screen, we identified ER coregulator PELP1 as a novel interacting protein of SETDB1. Biochemical analyses confirmed SETDB1 and PELP1 interactions in multiple BC cells. Mechanistic studies confirmed that PELP1 is necessary for SETDB1 mediated Akt methylation and phosphorylation. Further, SETDB1 overexpression promotes tamoxifen resistance in BC cells, and PELP1 knockdown abolished these effects. Using xenograft model, we provided genetic evidence that PELP1 is essential for SETDB1 mediated BC progression in vivo. Analyses of TCGA datasets revealed SETDB1 expression is positively correlated with PELP1 expression in ER+ BC patients. Conclusions This study suggests that the PELP1/SETDB1 axis play an important role in aberrant Akt activation and serves as a novel target for treating endocrine therapy resistance in breast cancer.

Using the H i self-absorption data from the Five-hundred-meter Aperture Spherical radio Telescope, we perform a study of the cold atomic gas in the Cygnus X North region. The most remarkable H i cloud is characterized by a filamentary structure, associated in space and in velocity with the principal molecular filament in the Cygnus X North region. We investigate the transition from atomic filament to molecular filament. We find that the H ii regions Cygnus OB2 and G081.920+00.138 play a critical role in compressing and shaping the atomic Cygnus X North filament, where the molecular filament subsequently forms. The cold H i in the DR21 filament has a much larger column density ( N (H i ) ∼1 × 10 ^20 cm ^−2 ) than the theoretical value of the residual atomic gas (∼1 × 10 ^19 cm ^−2 ), suggesting that the H i -to-H _2 transition is still in progress. The timescale of the H i -to-H _2 transition is estimated to be 3 × 10 ^5 yr, which approximates the ages of massive protostars in the Cygnus X North region. This implies that the formation of molecular clouds and massive stars may occur almost simultaneously in the DR21 filament, in accord with a picture of rapid and dynamic cloud evolution.

Digital PCR (dPCR) has great potential for assessing gene editing or gene mutation due to its ability to independently inspect each DNA template in parallel. However, current dPCR methods use a fluorescence-labeled probe to detect gene variation events, and their ability to distinguish variated sequences from the wild-type sequence is limited by the probe’s tolerance to mismatch. To address this, we have developed a novel dPCR method that uses a primer instead of a probe to sense gene variation. The enhanced Taq DNA polymerase in the PCR system has a high mismatch sensitivity, which enables our dPCR method to distinguish gene mutations from wild-type sequences. Compared to current dPCR methods, our method shows superior precision in assessing gene editing efficiency and single-base DNA mutation. This presents a promising opportunity to advance gene editing research and rare gene mutation detection.

The current study examined the effects of supplementary zinc proteinate (ZnPro) and zinc oxide (ZnO) on growth performance, diarrhea, antioxidant capacity, immune function, and mineral element concentrations of calves aged 1 to 28 days. A total of twenty-four newborn calves were divided randomly into 3 groups (n = 8; 2 males and 6 females per group), and each received: 0 mg/d Zn (CON), 627 mg/d ZnPro (80 mg/d Zn; ZnPro group), and 101 mg/d ZnO (80 mg/d Zn; ZnO group). The calves received the additive in their milk during the first 28 days of life. Compared with the CON group: ZnPro and ZnO improved average daily gain (ADG) and decreased the feed:gain ratio (FGR) between days 1 and 14 (p < 0.05), while the ADG increased and FGR decreased only in the ZnPro group between days 1 and 28 (p < 0.05). The incidence of diarrhea decreased (p < 0.05) in the ZnPro and ZnO groups between days 15 and 28 as well as days 1 and 28, but decreased (p < 0.05) only in the ZnPro group between days 1 and 14. The serum immunoglobulin G (IgG) concentration of the ZnPro and ZnO groups increased on days 14 and 28 (p < 0.05). ZnPro supplementation increased serum IgM concentration during the whole study, while ZnO enhanced serum IgM concentration only on day 14 (p < 0.05). In the ZnO group, the serum concentration of cytokines interleukin (IL)-10 increased on day 14, while that of IL-1β increased on day 28 (p < 0.05). In addition, ZnPro reduced the serum malondialdehyde (MDA) concentration on days 14 and 28 (p < 0.05). Both ZnPro and ZnO increased the serum concentrations of alkaline phosphatase (ALP) and metallothionein (MT) on day 14 (p < 0.05). With zinc supplementation, plasma Zn concentration increased (p < 0.05) on days 14 and 28 of age. We concluded that supplementary ZnPro and ZnO reduced incidences of diarrhea and promoted the immune function, but ZnPro improved the growth performance and antioxidant capacity of Holstein dairy calves to a greater extent.

The fundamental mechanisms of ultrafast demagnetization and magnetization recovery processes in ferromagnetic materials remain incompletely understood. The investigation of different dynamic features which depend on various physical quantities requires a more systematic approach. Here, the femtosecond laser-induced demagnetization and recovery dynamics in L10-Fe0.5Pt0.5 alloy film are studied by utilizing time-resolved magneto-optical Kerr measurements, focusing on their dependences of excitation fluence and ambient temperature over broad ranges. Ultrafast demagnetization dominated by Elliott-Yafet spin-flip scattering, and two-step magnetization recovery processes are found to be involved in all observations. The fast recovery time corresponding to spin–lattice relaxation is much shorter than that of many ferromagnets and increase with excitation fluence. These can be ascribed to the strong spin–orbit coupling (SOC) demonstrated in FePt and the reduction of transient magnetic anisotropy, respectively. Surprisingly, the demagnetization time exhibits no discernible correlation with ambient temperature. Two competitive factors are proposed to account for this phenomenon. On the other hand, the spin–lattice relaxation accelerates as temperature decreases due to enhanced SOC at lower ambient temperature. A semiquantitative analysis is given to get a visualized understanding. These results offer a comprehensive understanding of the dynamic characteristics of ultrafast demagnetization and recovery processes in iron-based materials with strong SOC, highlighting the potential for regulating the magnetization recovery process through temperature and laser fluence adjustments.

Li, Viswanadhapalli et al utilized multiple in vitro, ex vivo and in vivo models of TNBC to investigate LIFR inhibition. The authors reported that HDAC inhibition in TNBC cells led to an increase of LIFR expression and over activation of the downstream signaling elements (e.g., STAT3, mTOR, AKT), enhancing the aggressive potential of TNBC cells, and an LIFR inhibitor, EC359, synergistically enhanced the efficacy of HADC inhibitors in suppressing TNBC in vitro and in vivo.

Objective Lipoprotein(a) (Lp(a)) is an important genetically determined risk factor for atherosclerotic vascular disease (ASCVD). With the development of Lp(a)-lowering therapies, this study sought to characterise patterns of Lp(a) levels in a global ASCVD population and identify racial, ethnic, regional and gender differences.Methods A multicentre cross-sectional epidemiological study to estimate the prevalence of elevated Lp(a) in patients with a history of myocardial infarction, ischaemic stroke or peripheral artery disease conducted at 949 sites in 48 countries in North America, Europe, Asia, South America, South Africa and Australia between April 2019 and July 2021. Low-density lipoprotein cholesterol (LDL-C) and Lp(a) levels were measured either as mass (mg/dL) or molar concentration (nmol/L).Results Of 48 135 enrolled patients, 13.9% had prior measurements of Lp(a). Mean age was 62.6 (SD 10.1) years and 25.9% were female. Median Lp(a) was 18.0 mg/dL (IQR 7.9–57.1) or 42.0 nmol/L (IQR 15.0–155.4). Median LDL-C was 77 mg/dL (IQR 58.4–101.0). Lp(a) in women was higher, 22.8 (IQR 9.0–73.0) mg/dL, than in men, 17.0 (IQR 7.1–52.2) mg/dL, p50 mg/dL, 20.7% had levels >70 mg/dL, 12.9% were >90 mg/dL and 26.0% of patients exceeded 150 nmol/L.Conclusions Globally, Lp(a) is measured in a small minority of patients with ASCVD and is highest in black, younger and female patients. More than 25% of patients had levels exceeding the established threshold for increased cardiovascular risk, approximately 50 mg/dL or 125 nmol/L.Trial registration number

Abstract Endometrial cancer (EC) is the fourth most common cancer in women. Advanced-stage EC has limited treatment options with a poor prognosis. There is an unmet need for the identification of actionable drivers for the development of targeted therapies in EC. Leukemia inhibitory factor receptor (LIFR) and its ligand LIF play a major role in cancer progression, metastasis, stemness, and therapy resistance. However, little is known about the functional significance of the LIF/LIFR axis in EC progression. In this study using endometrial tumor tissue arrays, we identified that expression of LIF, LIFR is upregulated in EC. Knockout of LIFR using CRISPR/Cas9 in two different EC cells resulted in a significant reduction of their cell viability and cell survival. In vivo studies demonstrated that LIFR-KO significantly reduced EC xenograft tumor growth. Treatment of established and primary patient-derived EC cells with a novel LIFR inhibitor, EC359 resulted in the reduction of cell viability with an IC50 in the range of 20–100 nM and induction of apoptosis. Further, treatment with EC359 reduced the spheroid formation of EC cancer stem cells and reduced the levels of cancer stem cell markers SOX2, OCT4, NANOG, and Axin2. Mechanistic studies demonstrated that EC359 treatment attenuated the activation of LIF-LIFR driven pathways, including STAT3 and AKT/mTOR signaling in EC cells. Importantly, EC359 treatment resulted in a significant reduction of the growth of EC patient-derived explants ex vivo, EC cell line-derived xenografts, and patient-derived xenografts in vivo. Collectively, our work revealed the oncogenic potential of the LIF/LIFR axis in EC and support the utility of LIFR inhibitor, EC359, as a novel targeted therapy for EC via the inhibition of LIF/LIFR oncogenic signaling.

Background/Objective: The deleterious effects of chronic spinal cord injury (SCI) on the skeleton in rats, especially the lower extremities, has been proved previously. However, the long-term skeletal changes after SCI in non-human primates (NHP) have been scarcely studied. This study aimed to evaluate the bone loss in limbs and vertebrae and the bone metabolic changes in NHP after unilateral cervical spinal cord contusion injury. Methods: Twelve Macaca fascicularis were randomly divided into the SCI (n=8) and the Sham (n=4) groups. The SCI models were established using hemi-contusion cervical spinal cord injury on fifth cervical vertebra (C5), and were further evaluated by histological staining and neurophysiological monitoring. Changes of bone microstructures, bone biomechanics, and bone metabolism markers were assessed by micro-CT, micro-FEA and serological kit. Results: The NHP hemi-contusion cervical SCI model led to consistent unilateral limb dysfunction and potential plasticity in the face of loss of spinal cord. Furthermore, the cancellous bone mass of ipsilateral humerus and radius decreased significantly compared to the contralateral side. The bone volume fraction of humerus and radius were 17.2% and 20.1% on the ipsilateral while 29.0% and 30.1% on the contralateral respectively. Similarly, the thickness of the cortical bone in the ipsilateral forelimbs was significantly decreased, as well as the bone strength of the ipsilateral forelimbs. These changes were accompanied by diminished concentration of osteocalcin and total procollagen type 1 N-terminal propeptide (t-P1NP) as well as increased level of β-C-terminal cross-linking telopeptide of type 1collagen (β-CTX) in serological testing. Conclusions: The present study demonstrated that hemi-SCI induced loss of bone mass and compromised biomechanical performance in ipsilateral forelimbs, which could be indicated by both muscle atrophy and serological changes of bone metabolism, and associated with a consistent loss of large-diameter cells of sensory neurons in the dorsal root ganglia. The Translational potential of this Article: Our study, for the first time, demonstrated the bone loss in limbs and vertebrae as well as the bone metabolic changes in non-human primates after unilateral spinal cord injury (SCI). This may help to elucidate the role of muscle atrophy, serological changes and loss of sensory neurons in the mechanisms of SCI-induced osteoporosis, which would be definitely better compared with rodent models.

Linearly polarized emission from dust grains and molecular spectroscopy is an effective probe of the magnetic field topology in the interstellar medium and molecular clouds. The longstanding Davis-Chandrasekhar-Fermi (DCF) method and the recently developed Histogram of Relative Orientations (HRO) analysis and the polarization-intensity gradient (KTH) method are widely used to assess the dynamic role of magnetic fields in star formation based on the plane-of-sky component of field orientations inferred from the observations. We review the advances and limitations of these methods and summarize their applications to observations. Numerical tests of the DCF method, including its various variants, indicate that its largest uncertainty may come from the assumption of energy equipartition, which should be further calibrated with simulations and observations. We suggest that the ordered and turbulent magnetic fields of particular observations are local properties of the considered region. An analysis of the polarization observations using DCF estimations suggests that magnetically trans-to-super-critical and averagely trans-to-super-Alfvénic clumps/cores form in sub-critical clouds. High-mass star-forming regions may be more gravity-dominant than their low-mass counterparts due to higher column density. The observational HRO studies clearly reveal that the preferential relative orientation between the magnetic field and density structures changes from parallel to perpendicular with increasing column densities, which, in conjunction with simulations, suggests that star formation is ongoing in trans-to-sub-Alfvénic clouds. There is a possible transition back from perpendicular to random alignment at higher column densities. Results from observational studies using the KTH method broadly agree with those of the HRO and DCF studies.

A significant proportion of estrogen receptor‐positive (ER+) breast cancer (BC) initially responds to endocrine therapy but eventually evolves into therapy‐resistant BC. Transcription factor AP‐2 gamma (TFAP2C) is a known regulator of ER activity, and high expression of TFAP2C is associated with a decreased response to endocrine therapies. PELP1 is a nuclear receptor coregulator, commonly overexpressed in BC, and its levels are correlated with poorer survival. In this study, we identified PELP1 as a novel interacting protein of TFAP2C. RNA‐seq analysis of PELP1 knockdown BC cells followed by transcription factor motif prediction pointed to TFAP2C being enriched in PELP1‐regulated genes. Gene set enrichment analysis (GSEA) revealed that the TFAP2C‐PELP1 axis induced a subset of common genes. Reporter gene assays confirmed PELP1 functions as a coactivator of TFAP2C. Mechanistic studies showed that PELP1‐mediated changes in histone methylation contributed to increased expression of the TFAP2C target gene RET. Furthermore, the TFAP2C‐PELP1 axis promoted the activation of the RET signaling pathway, which contributed to downstream activation of AKT and ERK pathways in ER+ BC cells. Concomitantly, knockdown of PELP1 attenuated these effects mediated by TFAP2C. Overexpression of TFAP2C contributed to increased cell proliferation and therapy resistance in ER+ BC models, while knockdown of PELP1 mitigated these effects. Utilizing ZR75‐TFAP2C xenografts with or without PELP1 knockdown, we provided genetic evidence that endogenous PELP1 is essential for TFAP2C‐driven BC progression in vivo. Collectively, our studies demonstrated that PELP1 plays a critical role in TFAP2C transcriptional and tumorigenic functions in BC and blocking the PELP1‐TFAP2C axis could have utility for treating therapy resistance.

The internal pressure and temperature of type IV on-board hydrogen storage cylinders constantly change during the hydrogen fast-filling process. In this work, a 2D axisymmetric computational fluid dynamics (CFD) model is established to study the temperature rise of hydrogen storage cylinders during the fast-filling process. The hydrogen filling rate, ambient temperature, volume, and hydrogen inlet temperature were investigated to evaluate their effects on temperature rise inside the cylinders. The effects of the inlet pressure rise and pre-cooling patterns on the temperature rise of large-volume type IV hydrogen storage cylinders are analyzed, and the optimal filling strategy is determined. The research results show that a greater filling rate causes a higher hydrogen temperature rise at the end. The ambient temperature increases linearly with the maximum hydrogen temperature and decreases linearly with the state of charge (SOC). As the volume increases, the temperature rise of the cylinder increases. Reducing the inlet hydrogen temperature helps control the temperature rise, and the hydrogen inlet pre-cooling temperature required for large-volume cylinders is lower. If the filling time remains unchanged, a high pressure rise rate should be avoided, and a linear pressure rise pattern is optimal. Reducing the initial cooling energy is key to optimizing the filling strategy.

This paper presents the results of full polarization observations of the massive star-forming region W75N, conducted with ∼3″ spatial resolutions at 345 GHz using the Submillimeter Array. The magnetic field structures in the dense cores of the region are derived using the linearly polarized continuum emission. The overall magnetic field strength and orientation are found to agree with those from the previous observations. The plane-of-sky component of the magnetic field in the region was calculated to be ∼0.8 ± 0.1 mG using the angular dispersion function method. Further analyses involving the polarization-intensity gradient-local gravity method and H ^13 CO ^+ (4–3) line data indicated that the cloud is undergoing global gravitational collapse and the magnetic field is shaped by gravity and outflows in the dense core regions.

We present observations of polarized dust emission at 850 μ m from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense ( ${N}_{{{\rm{H}}}_{2}}\sim {10}^{22}$ –10 ^23 cm ^−2 ) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to ∼160 ± 30 μ G in the main starless core and up to ∼90 ± 40 μ G in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvénic. We also present a new method of data reduction for these denser but fainter objects like starless cores.

We use molecular line data from the Atacama Large Millimeter/submillimeter Array, Submillimeter Array, James Clerk Maxwell Telescope, and NANTEN2 to study the multiscale (∼15–0.005 pc) velocity statistics in the massive star formation region NGC 6334. We find that the nonthermal motions revealed by the velocity dispersion function (VDF) stay supersonic over scales of several orders of magnitude. The multiscale nonthermal motions revealed by different instruments do not follow the same continuous power law, which is because the massive star formation activities near central young stellar objects have increased the nonthermal motions in small-scale and high-density regions. The magnitudes of VDFs vary in different gas materials at the same scale, where the infrared dark clump N6334S in an early evolutionary stage shows a lower level of nonthermal motions than other more evolved clumps due to its more quiescent star formation activity. We find possible signs of small-scale-driven (e.g., by gravitational accretion or outflows) supersonic turbulence in clump N6334IV with a three-point VDF analysis. Our results clearly show that the scaling relation of velocity fields in NGC 6334 deviates from a continuous and universal turbulence cascade due to massive star formation activities.

We study the H ii regions associated with the NGC 6334 molecular cloud observed in the submillimeter and taken as part of the B -fields In STar-forming Region Observations Survey. In particular, we investigate the polarization patterns and magnetic field morphologies associated with these H ii regions. Through polarization pattern and pressure calculation analyses, several of these bubbles indicate that the gas and magnetic field lines have been pushed away from the bubble, toward an almost tangential (to the bubble) magnetic field morphology. In the densest part of NGC 6334, where the magnetic field morphology is similar to an hourglass, the polarization observations do not exhibit observable impact from H ii regions. We detect two nested radial polarization patterns in a bubble to the south of NGC 6334 that correspond to the previously observed bipolar structure in this bubble. Finally, using the results of this study, we present steps (incorporating computer vision; circular Hough transform) that can be used in future studies to identify bubbles that have physically impacted magnetic field lines.

We present ALMA dust polarization and molecular line observations toward four clumps (I(N), I, IV, and V) in the massive star-forming region NGC 6334. In conjunction with large-scale dust polarization and molecular line data from JCMT, Planck, and NANTEN2, we make a synergistic analysis of relative orientations between magnetic fields ( θ _B ), column density gradients ( θ _NG ), local gravity ( θ _LG ), and velocity gradients ( θ _VG ) to investigate the multi-scale (from ∼30 to 0.003 pc) physical properties in NGC 6334. We find that the relative orientation between θ _B and θ _NG changes from statistically more perpendicular to parallel as column density ( ${N}_{{{\rm{H}}}_{2}}$ ) increases, which is a signature of trans-to-sub-Alfvénic turbulence at complex/cloud scales as revealed by previous numerical studies. Because θ _NG and θ _LG are preferentially aligned within the NGC 6334 cloud, we suggest that the more parallel alignment between θ _B and θ _NG at higher ${N}_{{{\rm{H}}}_{2}}$ is because the magnetic field line is dragged by gravity. At even higher ${N}_{{{\rm{H}}}_{2}}$ , the angle between θ _B and θ _NG or θ _LG transits back to having no preferred orientation, or statistically slightly more perpendicular, suggesting that the magnetic field structure is impacted by star formation activities. A statistically more perpendicular alignment is found between θ _B and θ _VG throughout our studied ${N}_{{{\rm{H}}}_{2}}$ range, which indicates a trans-to-sub-Alfvénic state at small scales as well, and this signifies that magnetic field has an important role in the star formation process in NGC 6334. The normalized mass-to-flux ratio derived from the polarization-intensity gradient (KTH) method increases with ${N}_{{{\rm{H}}}_{2}}$ , but the KTH method may fail at high ${N}_{{{\rm{H}}}_{2}}$ due to the impact of star formation feedback.

We present BISTRO Survey 850 μ m dust emission polarization observations of the L1495A-B10 region of the Taurus molecular cloud, taken at the James Clerk Maxwell Telescope (JCMT). We observe a roughly triangular network of dense filaments. We detect nine of the dense starless cores embedded within these filaments in polarization, finding that the plane-of-sky orientation of the core-scale magnetic field lies roughly perpendicular to the filaments in almost all cases. We also find that the large-scale magnetic field orientation measured by Planck is not correlated with any of the core or filament structures, except in the case of the lowest-density core. We propose a scenario for early prestellar evolution that is both an extension to, and consistent with, previous models, introducing an additional evolutionary transitional stage between field-dominated and matter-dominated evolution, observed here for the first time. In this scenario, the cloud collapses first to a sheet-like structure. Uniquely, we appear to be seeing this sheet almost face on. The sheet fragments into filaments, which in turn form cores. However, the material must reach a certain critical density before the evolution changes from being field dominated to being matter dominated. We measure the sheet surface density and the magnetic field strength at that transition for the first time and show consistency with an analytical prediction that had previously gone untested for over 50 yr.

To adapt to the intelligent management of traffic flow in modern aviation, this study improves the algorithm according to the data exercise method and establishes the mathematical model and vector model of intelligent motion coordinates. Moreover, according to the simulation test method, this study analyzes the six-degree-of-freedom equation of motion in the coordinate system of the civil aviation aircraft and uses the simulation method to regard the civil aviation as a rigid body with a certain mass and mass distribution. In addition, this study builds an intelligent model based on the demand analysis, and according to the actual demand, this study combines the simulation method to analyze the structure of the intelligent management model of air traffic flow. Finally, this study uses the experimental analysis method to verify the effect of the model proposed in this study and combines the experimental research to verify that the model proposed in this study has a certain effect.

Background: The vertebral endplate (VEP) was damaged after spinal instability induced by cervical muscle section (CMS). Whether CMS induces bone formation and mechanical loading change in the vertebra is still obscure. This study was aimed to explore mechanical loading change and endplate damage after CMS. Methods: Forty-eight rats were randomly divided into the CMS group and the sham group. The C6/7 segments were harvested at 4, 8, and 12 weeks after surgery. The microarchitectures of the C6 vertebra ​and the vertebral endplate lesions and intervertebral disc height of C6/7 were measured by micro–computed tomography. Micro–finite element analysis was used to evaluate biomechanical properties of the C6 vertebra. Bone remodelling of the C6 vertebra ​and the endplate ​sclerosis and intervertebral disc degeneration of C6/7 were evaluated by histological and immunohistochemical analyses. Results: CMS significantly induced bone formation of the C6 ventral vertebra ​and increased the biomechanical properties of mainly the ventral side at 4 weeks, which was gradually rebalanced throughout the rest of the study. CMS also significantly increased protein expression of transforming growth factor-β1 (TGF-β1) and phosphorylated small mothers against decapentaplegic (pSmad)2/3 ​at 4 weeks. Moreover, tartrate-resistant acid phosphatase staining showed that osteoclast-positive cells were slightly in number decreased at 4 weeks, but were obviously increased at 8 weeks. The VEP of the ventral side was abraded earlier followed by calcification in situ later after CMS, consistent with the biomechanical enhancements observed. The degree of endplate degeneration was aggravated with time. Finally, CMS decreased intervertebral disc height and increased disc degeneration scores with time. Conclusions: Spinal instability induced by CMS increases bone mass and biomechanical loading of the ventral side of vertebra in the early stage, which might initiate VEP damage and cause intervertebral disc degeneration. The translational potential of this article: Our study indicates that vertebral trabecular changes may involve in intervertebral disc degeneration induced by spinal instability. This may help to elucidate the mechanisms by which disc degeneration occur.

Abstract Background Poor recruitment of patients is the predominant reason for early termination of randomized clinical trials (RCTs). Systematic empirical investigations and validation studies of existing recruitment models, however, are lacking. We aim to provide evidence-based guidance on how to predict and monitor recruitment of patients into RCTs. Our specific objectives are the following: (1) to establish a large sample of RCTs (target n = 300) with individual patient recruitment data from a large variety of RCTs, (2) to investigate participant recruitment patterns and study site recruitment patterns and their association with the overall recruitment process, (3) to investigate the validity of a freely available recruitment model, and (4) to develop a user-friendly tool to assist trial investigators in the planning and monitoring of the recruitment process. Methods Eligible RCTs need to have completed the recruitment process, used a parallel group design, and investigated any healthcare intervention where participants had the free choice to participate. To establish the planned sample of RCTs, we will use our contacts to national and international RCT networks, clinical trial units, and individual trial investigators. From included RCTs, we will collect patient-level information (date of randomization), site-level information (date of trial site activation), and trial-level information (target sample size). We will examine recruitment patterns using recruitment trajectories and stratifications by RCT characteristics. We will investigate associations of early recruitment patterns with overall recruitment by correlation and multivariable regression. To examine the validity of a freely available Bayesian prediction model, we will compare model predictions to collected empirical data of included RCTs. Finally, we will user-test any promising tool using qualitative methods for further tool improvement. Discussion This research will contribute to a better understanding of participant recruitment to RCTs, which could enhance efficiency and reduce the waste of resources in clinical research with a comprehensive, concerted, international effort.

Abstract Background Monitoring and reporting of drug safety during a clinical trial is essential to its success. More recent attention to drug safety has encouraged statistical methods development for monitoring and detecting potential safety signals. This paper investigates the potential impact of the process of the blinded investigator identifying a potential safety signal, which should be further investigated by the Data and Safety Monitoring Board with an unblinded safety data analysis. Methods In this paper, two-stage Bayesian hierarchical models are proposed for safety signal detection following a pre-specified set of interim analyses that are applied to efficacy. At stage 1, a hierarchical blinded model uses blinded safety data to detect a potential safety signal and at stage 2, a hierarchical logistic model is applied to confirm the signal with unblinded safety data. Results Any interim safety monitoring analysis is usually scheduled via negotiation between the trial sponsor and the Data and Safety Monitoring Board. The proposed safety monitoring process starts once 53 subjects have been enrolled into an eight-arm phase II clinical trial for the first interim analysis. Operating characteristics describing the performance of this proposed workflow are investigated using simulations based on the different scenarios. Conclusions The two-stage Bayesian safety procedure in this paper provides a statistical view to monitor safety during the clinical trials. The proposed two-stage monitoring model has an excellent accuracy of detecting and flagging a potential safety signal at stage 1, and with the most important feature that further action at stage 2 could confirm the safety issue.

Automatic detection of industrial product damage using machine learning is a promising research area. At the same time, various machine learning methods based on convolutional neural networks have a very important role in the application of visual automatic detection. Therefore, the machine vision-based automatic detection of high-speed railway rail damage has received widespread attention. This paper proposes an efficient detection method for the damage of high-speed railway rails called SCueU-Net. For the first time, the combination of U-Net graph segmentation network and the saliency cues method of damage location is applied to the task of high-speed railway rail damage detection. The experimental results show that our method has a detection accuracy rate of 99.76%, which is 6.74% higher than the recent method in damage identification accuracy, which improves the detection efficiency of rail damage significantly.

Objective: To investigate the neuroprotective effects of trihydroxyethyl rutin in rats with cervical spinal cord hemi-contusion.Methods: Adult male Sprague–Dawley rats were subjected to hemi-contusion at a stroke depth of 1.2 mm, and then intraperitoneally injected with 50 or 100 mg/kg trihydroxyethyl rutin per day for 12 weeks (T50 and T100 groups, respectively). Changes in somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and behavior were continuously monitored. At 12 weeks post-injury, immunohistochemical staining was performed to assess changes in cervical spinal cord microvascular morphology. Magnetic resonance imaging (MRI) scans were performed to examine end-stage injury in the cervical spinal cord, and Eriochrome cyanine-stained slices of spinal cord tissue were evaluated for injury.Results: There were no significant differences in biomechanical parameters among the spinal cord injury, T50 and T100 rat groups. At 3 days-post-injury, there was a significant decrease in grip strength. At 12 weeks post-injury, grip strength recovery was significantly better in the T50 and T100 groups than in the injury group. Compared with the injury group, the total limb placement frequency was significantly higher in the T50 group at 2, 4, 6, 10, and 12 weeks post-injury and in the T100 group at 2, 6, 8, and 10 weeks post-injury. Ipsilateral SEPs and MEPs were dynamic, increasing in latency and decreasing in amplitude in the injury compared with sham group. MRI scanning demonstrated that the coronal, sagittal, and transversal lesion areas were smaller in the T50 and T100 groups than in the injury group. Microvascular density showed a greater reduction in the injury group compared with the T50 and T100 groups. Eriochrome cyanine staining showed that the ipsilateral side, residual parenchyma, and gray matter areas were larger in the T50 and T100 groups than in the injury group.Conclusion: Trihydroxyethyl rutin exhibits robust neuroprotective effects, improving limb motor function and nerve electrophysiological parameters after spinal cord injury, maintaining microvascular density, and reducing the area of injury and degree of demyelination.