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Cryo-electron microscopy (cryo-EM) has been widely used to reveal the structures of proteins at atomic resolution. One key challenge is that almost all proteins are predominantly adsorbed to the air-water interface during standard cryo-EM specimen preparation. The interaction of proteins with air-water interface will significantly impede the success of reconstruction and achievable resolution. Here, we highlight the critical role of impenetrable surfactant monolayers in passivating the air-water interface problems, and develop a robust effective method for high-resolution cryo-EM analysis, by using the superstructure GSAMs which comprises surfactant self-assembled monolayers (SAMs) and graphene membrane. The GSAMs works well in enriching the orientations and improving particle utilization ratio of multiple proteins, facilitating the 3.3-Å resolution reconstruction of a 100-kDa protein complex (ACE2-RBD), which shows strong preferential orientation using traditional specimen preparation protocol. Additionally, we demonstrate that GSAMs enables the successful determinations of small proteins (

Some education systems have both quality and equality. They have achieved educational equity. This study aimed to uncover the practical wisdom of such systems in developing educational equality. A quantitative research design was used. Family capital and science achievement were the variables analyzed. They were secondary data collected by the 2018 PISA test. PISA surveyed students' family capital with questionnaires and measured students' science achievement with cognitive items. Six education systems with quality but low equality comprised the control group. Its sample size ranged from 4656 to 8312. The experiment group included nine quality and equal education systems, with sample sizes ranging from 3766 to 21490. The relative error and conditional probability were calculated to determine educational equality. Rawls' difference principle was used as a theoretical perspective. The findings showed that quality and equal education systems had three types: equal-start, equal-improvement, and egalitarian. The primary measure to improve equality in education is to ensure educational benefits for students in the bottom quartile of family capital. The development of educational equality was accompanied by a sustained reduction in the achievement gap between the disadvantaged and the advantaged. Implications for educational practice are discussed.

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.

AIM: To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease (CTD-ILD) and healthy controls (HCs) by optical coherence tomography angiography (OCTA) and to investigate the changes in microvascular density in abnormal eyes. METHODS: For a retrospective case-control study, a total of 16 patients (32 eyes) diagnosed with CTD-ILD were selected as the ILD group. The 16 healthy volunteers with 32 eyes, matched in terms of age and sex with the patients, were recruited as control group. The macular retina's superficial retinal layer (SRL) and deep retinal layer (DRL) were examined and scanned using OCTA in each individual eye. The densities of retinal microvascular (MIR), macrovascular (MAR), and total microvascular (TMI) were calculated and compared. Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods: central annuli segmentation method (C1-C6), hemispheric segmentation method [uperior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)], and Early Treatment Diabetic Retinopathy Study (ETDRS) methods [superior (S), inferior (I), left (L), and right (R)]. The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis. RESULTS: The OCTA data demonstrated a statistically significant difference (P

Abstract Epigenetic readers frequently affect gene regulation, correlate with disease prognosis, and hold significant potential as therapeutic targets for cancer. Zinc finger MYND-type containing 11 (ZMYND11) is notably recognized for reading the epigenetic marker H3.3K36me3; however, its broader functions and mechanisms of action in cancer remain underexplored. Here, we report that ZMYND11 downregulation is prevalent across various cancers and profoundly correlates with poorer outcomes in prostate cancer patients. Depletion of ZMYND11 promotes tumor cell growth, migration, and invasion in vitro, as well as tumor formation and metastasis in vivo. Mechanistically, we discover that ZMYND11 exhibits tumor suppressive roles by recognizing arginine-194-methylated HNRNPA1 dependent on its MYND domain, thereby retaining HNRNPA1 in the nucleus and preventing the formation of stress granules in the cytoplasm. Furthermore, ZMYND11 counteracts the HNRNPA1-driven increase in the PKM2/PKM1 ratio, thus mitigating the aggressive tumor phenotype promoted by PKM2. Remarkably, ZMYND11 recognition of HNRNPA1 can be disrupted by pharmaceutical inhibition of the arginine methyltransferase PRMT5. Tumors with low ZMYND11 expression show sensitivity to PRMT5 inhibitors. Taken together, our findings uncover a previously unexplored noncanonical role of ZMYND11 as a nonhistone methylation reader and underscore the critical importance of arginine methylation in the ZMYND11-HNRNPA1 interaction for restraining tumor progression, thereby proposing novel therapeutic targets and potential biomarkers for cancer treatment.

AIM: To study functional brain abnormalities in patients with hypertensive retinopathy (HR) and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations (fALFFs) method. METHODS: Twenty HR patients and 20 healthy controls (HCs) were respectively recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the fALFF method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Further, we used Pearson's correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR. RESULTS: The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus (RO-MFG) and right lingual gyrus. In contrast, the values of fALFFs in the left middle temporal gyrus (MTG), left superior temporal pole (STP), left middle frontal gyrus (MFG), left superior marginal gyrus (SMG), left superior parietal lobule (SPL), and right supplementary motor area (SMA) were higher in the HR group. The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group (P

Pores are among the primary defects in 316L stainless steel when fabricated through laser powder bed fusion (L-PBF). To better understand and precisely control the formation behavior of pores in the L-PBF-manufactured 316L stainless steel, effects of L-PBF process parameters on the melt pool and pore characteristics have been investigated. A method utilized for extreme values statistics analysis was also applied to investigate and predict the sizes of pores. Relationships among the count of measurements, the laser energy density, the reduced variate, and the maximum pore size were revealed. The findings showed an overall increase in melt pool depth as the laser energy densities was raised, yet the magnitude of this growth weakened as the laser energy density continued to increase. Conversely, it was discovered that the connection between the width of the melt pool and the density of laser energy exhibited a markedly less distinct correlation. As laser energy density escalated, there was a shift in the melt pool mode from conduction-based to a transitional phase, and upon further elevation of the laser energy density, it transitioned to keyhole mode. To obtain a reliable statistical analysis of pores, at least 40 measurements should be acquired for the estimation of the pore sizes by taking comprehensive consideration of time cost. Beside, in all three melt pool modes, at a fixed observation area, the maximum size of pores generally decreased with the escalation in laser energy densities.

Many oil fields in the Bohai Oilfield are currently in the stage of high water cut and low recovery. Thus, it is urgent to conduct in-depth research on the potential of these oil fields to maintain stable production. After 20 years of directional well development, Bohai B Oilfield has developed a set of layers with combined production and strong injection, resulting in severe interlayer interference and difficulties in tapping the potential of the remaining oil. Owing to the limited resolution of existing seismic data, it is not possible to identify the reservoir structure inside the braided river composite sand body, including the vertical and horizontal distribution of the interlayer and thin sand body. Therefore, directional well development is currently mainly used. Here, the seismic signal harmonic frequency enhancement technology is proposed, which directly uses the fundamental component of seismic data to predict harmonic and subharmonic information, and then adds it to the original seismic data to expand the high-frequency and low-frequency seismic information, achieving the purpose of frequency enhancement. This method overcomes the limitations of traditional convolutional models, eliminating the need of well information and to estimate seismic wavelets and assume sparse stratigraphic reflection coefficients, thereby reducing the human subjective factors. The research results, verified through dynamic and static information, showed that the seismic signal harmonic frequency enhancement technology can effectively and finely identify the internal structure of braided river sand bodies, help to transform directional wells into horizontal wells for development, avoid interlayer interference, and promote efficient extraction of the remaining oil.

Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented angiogenesis-immunosuppressive tumor microenvironment (TME). Herein, elevated neutrophil extracellular traps (NETs) and cancer-associated neurotransmitters (CANTs, e.g., catecholamines) are firstly identified as two of the dominant inducements. Further, an injectable fibrin-alginate hydrogel with high tissue adhesion has been constructed to specifically co-deliver NETs inhibitor (DNase I)-encapsulated PLGA nanoparticles and an unselective β-adrenergic receptor blocker (propranolol). The two components (i.e., fibrin and alginate) can respond to two triggers (thrombin and Ca2+, respectively) in postoperative bleeding to gelate, shaping into an interpenetrating network (IPN) featuring high strength. The continuous release of DNase I and PR can wreck NETs and antagonize catecholamines to decrease microvessel density, blockade myeloid-derived suppressor cells, secrete various proinflammatory cytokines, potentiate natural killer cell function and hamper cytotoxic T cell exhaustion. The reprogrammed TME significantly suppress locally residual and distant tumors, induce strong immune memory effects and thus inhibit lung metastasis. Thus, targetedly degrading NETs and blocking CANTs enabled by this in-situ IPN-based hydrogel drug depot provides a simple and efficient approach against SR-induced cancer recurrence and metastasis.

In this study, we demonstrate the high luminous efficacy of 118 lm/W and the high reliability of white LEDs (WLEDs) through 450 °C thermal aging, utilizing four-inch YAG: Ce3+ phosphor-in-glass (PiG) plates designed for vehicle headlights. The sintering process of mixing glass and phosphor typically generates pores, which can scatter light and reduce the luminous efficacy of the fabricated PiG. In this study, we produced four-inch PiG plates under four different fabrication conditions to evaluate their luminous efficacy. Our results revealed that the PiG plate with a thin thickness of 0.08 mm exhibited a 16.83% increase in luminous efficacy compared to the 0.15 mm plate, attributed to reduced light interaction with the pores. Unlike silicone-based phosphor WLEDs, which offer high performance but lower reliability due to the silicone resin’s low transition temperature (150 °C), our novel thin PiG plate achieves high performance and reliability. This advancement suggests that the proposed thin PiG plate could replace traditional silicone-based phosphors, enabling the development of high-quality WLEDs for vehicle headlights in automotive applications.

Abstract Background Retroperitoneal liposarcoma (RPLPS) is a relatively rare disease. Liposarcomas vary in size, but sizeable RPLPS larger than 30 cm in diameter are very rare, and their diagnosis and treatment present significant challenges. Case presentation We report a 58-year-old male patient who was admitted to the hospital with an increased abdominal circumference and was later diagnosed with a giant RPLPS. The liposarcoma was found to adhere to the right kidney and the entire ureter, invading the ascending colon. The patient underwent complete combined surgical resection. The tumor was removed intact, measured 55.0 cm × 30.0 cm × 18.0 cm, and weighed 19.8 kg. Histopathologic analysis revealed well-differentiated liposarcoma (WDLPS). The patient was successfully discharged from the hospital and followed up for 6 months with no signs of recurrence. Conclusion RPLPS is a rare tumor with atypical clinical presentation. Surgery remains the most effective method of treatment for retroperitoneal sarcomas, with complete removal if there is local invasion. Preoperative examination, including three-dimensional (3D) reconstruction, is essential for surgical success. The role of adjuvant radiotherapy or chemotherapy remains controversial. However, clinicians should not rule them out as viable options.

Abstract Background Stroke is a type of acute brain damage that can lead to a series of serious public health challenges. Demonstrating the molecular mechanism of stroke-related neural cell degeneration could help identify a more efficient treatment for stroke patients. Further elucidation of factors that regulate microglia and nuclear factor (erythroid-derived 2)-like 1 (Nrf1) may lead to a promising strategy for treating neuroinflammation after ischaemic stroke. In this study, we investigated the possible role of pterostilbene (PTS) in Nrf1 regulation in cell and animal models of ischaemia stroke. Methods We administered PTS, ITSA1 (an HDAC activator) and RGFP966 (a selective HDAC3 inhibitor) in a mouse model of middle cerebral artery occlusion–reperfusion (MCAO/R) and a model of microglial oxygen‒glucose deprivation/reperfusion (OGD/R). The brain infarct size, neuroinflammation and microglial availability were also determined. Dual-luciferase reporter, Nrf1 protein stability and co-immunoprecipitation assays were conducted to analyse histone deacetylase 3 (HDAC3)/Nrf1-regulated Nrf1 in an OGD/R-induced microglial injury model. Results We found that PTS decreased HDAC3 expression and activity, increased Nrf1 acetylation in the cell nucleus and inhibited the interaction of Nrf1 with p65 and p65 accumulation, which reduced infarct volume and neuroinflammation (iNOS/Arg1, TNF-α and IL-1β levels) after ischaemic stroke. Furthermore, the CSF1R inhibitor PLX5622 induced elimination of microglia and attenuated the therapeutic effect of PTS following MCAO/R. In the OGD/R model, PTS relieved OGD/R-induced microglial injury and TNF-α and IL-1β release, which were dependent on Nrf1 acetylation through the upregulation of HDAC3/Nrf1 signalling in microglia. However, the K105R or/and K139R mutants of Nrf1 counteracted the impact of PTS in the OGD/R-induced microglial injury model, which indicates that PTS treatment might be a promising strategy for ischaemia stroke therapy. Conclusion The HDAC3/Nrf1 pathway regulates the stability and function of Nrf1 in microglial activation and neuroinflammation, which may depend on the acetylation of the lysine 105 and 139 residues in Nrf1. This mechanism was first identified as a potential regulatory mechanism of PTS-based neuroprotection in our research, which may provide new insight into further translational applications of natural products such as PTS.

Abstract Cryo-electron microscopy (cryo-EM) has been widely used to reveal the structures of proteins at atomic resolution. One key challenge is that almost all proteins are predominantly adsorbed to the air-water interface during standard cryo-EM specimen preparation. The interaction of proteins with air-water interface will significantly impede the success of reconstruction and achievable resolution. Here, we highlight the critical role of impenetrable surfactant monolayers in passivating the air-water interface problems, and develop a robust effective method for high-resolution cryo-EM analysis, by using the superstructure GSAMs which comprises surfactant self-assembled monolayers (SAMs) and graphene membrane. The GSAMs works well in enriching the orientations and improving particle utilization ratio of multiple proteins, facilitating the 3.3-Å resolution reconstruction of a 100-kDa protein complex (ACE2-RBD), which shows strong preferential orientation using traditional specimen preparation protocol. Additionally, we demonstrate that GSAMs enables the successful determinations of small proteins (

Abstract Recent studies have increasingly focused on the effect of relativistic motion on quantum coherence. Prior research predominantly examined the influence of relative motion on basis-dependent quantum coherence, underscoring its susceptibility to decoherence under accelerated conditions. Yet, the effect of relativistic motion on basis-independent quantum coherence, which is critical for understanding the intrinsic quantum features of a system, remains an interesting open question. This paper addresses this question by examining how total, collective, and localized coherence are affected by acceleration and coupling strength. Our analysis reveals that both total and collective coherence significantly decrease with increasing acceleration and coupling strength, ultimately vanishing at high levels of acceleration. This underscores the profound impact of Unruh thermal noise. Conversely, localized coherence exhibits relative stability, decreasing to zero only under the extreme condition of infinite acceleration. Moreover, we demonstrate that collective, localized, and basis-independent coherence collectively satisfy the triangle inequality. These findings are crucial for enhancing our understanding of quantum information dynamics in environments subjected to high acceleration and offer valuable insights on the behavior of quantum coherence under relativistic conditions.