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In online learning at scale, wherein instructional videos play a central role, interactive tools are often integrated to counteract passive consumption. For example, the forum or discussion board is widely used, and an emerging functionality, danmaku, which enables messages to be synchronized with video playback, has also been utilized recently. To explore how mass participation is accommodated and what categories of interaction learners implement, this study utilizes analysis of interaction and manual content analysis through learner-generated text data from two specific tools employed in a massive open online course (MOOC) setting: the discussion board (N = 739) and danmaku (N = 2435). Results of the analysis of interaction indicate that mass participation is managed differently by the tools: danmaku fosters a collective space for massive participants, while the discussion board organizes them into threaded small groups. In addition, results of the content analysis show danmaku primarily supports indirect interaction with a focus on the socio-emotional dimension, while the discussion board serves as a platform for direct discussions, particularly in the cognitive dimension. Furthermore, within the context of large-scale engagement, various levels of joint interaction, in addition to collaboration, are discerned and discussed in both socio-emotional and cognitive interactions. The findings offer insights for developing sociable and scalable socio-technical environments in computer-supported collaborative learning (CSCL), addressing emerging educational trends. Practical implications for educational design based on these findings are also discussed.

Quality management is a constant and significant concern in enterprises. Effective determination of correct solutions for comprehensive problems helps avoid increased backtesting costs. This study proposes an intelligent quality control method for manufacturing processes based on a human–cyber–physical (HCP) knowledge graph, which is a systematic method that encompasses the following elements: data management and classification based on HCP ternary data, HCP ontology construction, knowledge extraction for constructing an HCP knowledge graph, and comprehensive application of quality control based on HCP knowledge. The proposed method implements case retrieval, automatic analysis, and assisted decision making based on an HCP knowledge graph, enabling quality monitoring, inspection, diagnosis, and maintenance strategies for quality control. In practical applications, the proposed modular and hierarchical HCP ontology exhibits significant superiority in terms of shareability and reusability of the acquired knowledge. Moreover, the HCP knowledge graph deeply integrates the provided HCP data and effectively supports comprehensive decision making. The proposed method was implemented in cases involving an automotive production line and a gear manufacturing process, and the effectiveness of the method was verified by the application system deployed. Furthermore, the proposed method can be extended to other manufacturing process quality control tasks.

Abstract Objectives This study aims to retrospectively analyze the clinical features of Stanford type A acute aortic dissection (TAAAD) based on Sun’s modified classification, and to investigate whether the Sun’s modified classification can be used to assess the risk of preoperative rupture. Methods Clinical data was collected between January 2018 and June 2019. Data included patient demographics, history of disease, type of dissection according to the Sun’s modified classification, time of onset, biochemical tests, and preoperative rupture. Results A total of 387 patients with TAAAD who met the inclusion criteria of Sun’s modified classification were included. There were more complex types, with 75, 151 and 140 patients in the type A1C, A2C and A3C groups, respectively. The age of the entire group of patients was 51.46 ± 12.65 years and 283 (73.1%) were male. The time from onset to the emergency room was 25.37 ± 30.78 h. There were a few cases of TAAAD combined with stroke, pericardial effusion, pleural effusion, and lower extremity and organ ischemia in the complex type group. The white blood cell count (WBC), neutrophil count (NEC) and blood amylase differed significantly between the groups. Three independent risk factors for preoperative rupture were identified: neutrophil count, blood potassium ion level, and platelet count. Binary logistic regression analysis showed that the Sun’s modified classification could not be used to assess the risk of preoperative rupture in TAAAD. Conclusion TAAAD was classified as the complex type in most patients. WBC, NEC and blood amylase were significantly different between the groups. NEC and serum potassium ion level were independent risk factors for preoperative rupture of TAAAD, while platelet count was its protective factor. More samples are needed to determine whether Sun’s modified classification can be used to evaluate the risk of preoperative rupture.

Abstract High-pressure diamond anvil cells have been widely used to create novel states of matter. Nevertheless, the lack of universal in-situ magnetic measurement techniques at megabar pressures makes it difficult to understand the underlying physics of materials’ behavior at extreme conditions, such as high-temperature superconductivity of hydrides and the formation or destruction of the local magnetic moments in magnetic systems. Here, we break through the limitations of pressure on quantum sensors by modulating the uniaxial stress along the nitrogen-vacancy axis and develop the in-situ magnetic detection technique at megabar pressures with high sensitivity ( $$\sim 1{{{\rm{\mu }}}}{{{\rm{T}}}}/\sqrt{{{{\rm{Hz}}}}}$$ ~ 1 μ T / Hz ) and sub-microscale spatial resolution. By directly imaging the magnetic field and the evolution of magnetic domains, we observe the macroscopic magnetic transition of Fe3O4 in the megabar pressure range from ferrimagnetic (α-Fe3O4) to weak ferromagnetic (β-Fe3O4) and finally to paramagnetic (γ-Fe3O4). The scenarios for magnetic changes in Fe3O4 characterized here shed light on the direct magnetic microstructure observation in bulk materials at high pressure and contribute to understanding magnetism evolution in the presence of numerous complex factors such as spin crossover, altered magnetic interactions and structural phase transitions.

Background: Patients with hematological malignancies face an increased risk of developing second primary neoplasms due to various factors, including immune system compromise and chemotherapy-related effects. However, the incidence and associated risk factors in older patients remain poorly understood. This study aimed to assess the incidence, identify risk factors, and evaluate their impact on survival outcomes among older patients with hematological malignancies. Methods: This retrospective single-center study analyzed data from 163 patients, focusing on the occurrence of second primary neoplasms. Cumulative incidence rates were calculated, and risk factor analysis was conducted using a competing risk model. Results: Among 124 eligible patients with a total follow-up duration of 572.57 person-years, the incidence rate of second primary neoplasms was 15.72/1000 person-years. The standardized incidence ratio (SIR) was 0.81 (95% confidence interval [CI] [0.39–1.48], P = 0.518). History of radiotherapy emerged as a significant risk factor (sub-distribution hazard ratio [SHR] = 21.61 [2.81–166.14], P = 0.003), whereas regular natural killer (NK) cell infusion was associated with reduced risk (SHR = 3.25 e−8 [9.81 e−9–1.08 e−7], P ＜ 0.001). Conclusions: These findings underscore the importance of informing older patients with hematological malignancies about the long-term risks of second primary neoplasms. Healthcare providers should carefully weigh risk factors when formulating treatment strategies. The results are valuable for investigating the fundamental principles underlying the occurrence and progression of second primary neoplasms.

The aim of this study was to compare the accuracies of cognitive fusion-guided targeted biopsy (TB), systematic biopsy (SB), and combined TB+SB for the detection of prostate cancer (PCa) and clinically significant PCa (csPCa) in males with lesions detected by magnetic resonance imaging (MRI). We conducted a retrospective analysis of individuals who underwent prostate biopsy at Peking University People’s Hospital (Beijing, China), with an emphasis on patients with both transrectal TB and SB. The main objective was to determine the precisions of SB, TB, and TB+SB for diagnosing PCa and csPCa. We also evaluated the detection rates of TB, SB, TB+ipsilateral-SB (ipsi-SB), TB+contralateral-SB (contra-SB), and TB+SB for PCa and csPCa in patients with unilateral MRI lesions. We compared the diagnostic yields of the various biopsy schemes using the McNemar’s test. A total of 180 patients were enrolled. The rates of PCa detection using TB, SB, and TB+SB were 52.8%, 62.2%, and 66.7%, respectively, and the corresponding rates for csPCa were 46.1%, 56.7%, and 58.3%, respectively. Among patients with unilateral MRI lesions, the PCa detection rates for TB, SB, TB+ipsi-SB, TB+contra-SB, and TB+SB were 53.3%, 64.8%, 65.6%, 61.5%, and 68.0%, respectively. TB+ipsi-SB detected 96.4% of PCa and 95.9% of csPCa cases. These findings suggest that the combination of TB+SB has better diagnostic accuracy compared with SB or TB alone. For patients with unilateral MRI lesions, the combination of TB+ipsi-SB may be suitable in clinical settings.

Abstract Pyroptosis, a typical inflammatory cell death mode, has been increasingly demonstrated to have therapeutic value in inflammatory diseases such as sepsis. However, the mechanisms and therapeutic targets of sepsis remain elusive. Here, we reported that REGγ inhibition promoted pyroptosis by regulating members of the gasdermin family in macrophages. Mechanistically, REGγ directly degraded Bim, a factor of the Bcl-2 family that can inhibit the cleavage of GSDMD/E, ultimately preventing the occurrence of pyroptosis. Furthermore, cecal ligation and puncture (CLP)-induced sepsis model mice showed downregulation of REGγ at both the RNA and protein levels. Gasdermin-mediated pyroptosis was augmented in REGγ-knockout mice, and these mice exhibited more severe sepsis-related tissue injury. More importantly, we found that REGγ expression was downregulated in clinical sepsis samples, such as those from patients with Pseudomonas aeruginosa (PA) infection. Finally, PA-infected mice showed decreased REGγ levels in the lung. In summary, our study reveals that the REGγ-Bim-GSDMD/E pathway is a novel regulatory mechanism of pyroptosis in sepsis-related tissue injury.

Abstract Background Oral mucositis (OM) is a prevalent and painful complication in patients undergoing anticancer treatment, which significantly impacts patients’ quality of life (QoL) and adherence to therapy. The use of oral probiotics as a preventive strategy for OM has shown promise, but the clinical evidence remains inconclusive. This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the efficacy of probiotics in preventing OM caused by radiotherapy and/or chemotherapy. Methods A comprehensive search of PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov was conducted up to January 31, 2024, to identify eligible RCTs. The primary outcomes were the incidences of severe OM and all-grade OM. Secondary outcomes included rates of anticancer treatment completion, clinical response, requirement for enteral nutrition, time course of OM, body weight loss, QoL, and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Results A total of 12 RCTs involving 1,376 patients were included in the quantitative analysis. Probiotics administration significantly reduced the risk of severe OM (RR = 0.61, 95%CI: 0.53–0.72, P

High purity and ultrafine DAAF (u-DAAF) is an emerging insensitive charge in initiators. Although there are many ways to obtain u-DAAF, developing a preparation method with stable operation, accurate control, good quality consistency, equipment miniaturization, and minimum manpower is an inevitable requirement to adapt to the current social technology development trend. Here reported is the microfluidic preparation of u-DAAF with tunable particle size by a passive swirling microreactor. Under the guidance of recrystallization growth kinetics and mixing behavior of fluids in the swirling microreactor, the key parameters (liquid flow rate, explosive concentration and crystallization temperature) were screened and optimized through screening experiments. Under the condition that no surfactant is added and only experimental parameters are controlled, the particle size of recrystallized DAAF can be adjusted from 98 nm to 785 nm, and the corresponding specific surface area is 8.45 m2·g−1 to 1.33 m2·g−1. In addition, the preparation method has good batch stability, high yield (90.8%–92.6%) and high purity (99.0%–99.4%), indicating a high practical application potential. Electric explosion derived flyer initiation tests demonstrate that the u-DAAF shows an initiation sensitivity much lower than that of the raw DAAF, and comparable to that of the refined DAAF by conventional spraying crystallization method. This study provides an efficient method to fabricate u-DAAF with narrow particle size distribution and high reproducibility as well as a theoretical reference for fabrication of other ultrafine explosives.

Abstract Moyamoya disease, characterized by basal cerebral artery obstruction, was studied for differential protein expression to elucidate its pathogenesis. Proteomic analysis of cerebrospinal fluid from 10 patients, categorized by postoperative angiography into good and poor prognosis groups, revealed 46 differentially expressed proteins. Notably, cadherin 18 (CDH18) was the most significantly upregulated in the good prognosis group. In addition, the expression of cadherin 18 (CDH18) and phenotypic transformation-related proteins were measured by qRT-PCR and western blot. The effects of CDH18 in vascular smooth muscle cells were detected by CCK-8, EdU, transwell and wound healing assays. The overexpression of CDH18 in vascular smooth muscle cells (VSMCs) was found to inhibit proliferation, migration, and phenotypic transformation. These findings suggest CDH18 as a potential therapeutic target in moyamoya disease.

Abstract Fine-grained management of rice fields can enhance the yield and quality of rice crops. Challenges in achieving fine classification include interference from similar vegetation, the irregularity of natural field shapes, and complex scale variations. This paper introduces Rice Attention Cascade Network (RACNet), for the fine classification of rice fields in high-resolution satellite remote sensing imagery. The network employs the Hybrid Task Cascade network as the base framework and uses spectral and indices mixed multimodal data as input to reinforce the feature differentiation of similar vegetation. Initially, a Channel Attention Deformable-ResNet (CAD-ResNet) was designed to enhance the feature representation of rice on different channels. Deformable convolution improves the ability of CAD-ResNet to capture irregular field shapes. Then, to address the issue of complex scale changes, the multi-scale features extracted by the CAD-ResNet are progressively fused using an Asymptotic Feature Pyramid, reducing the loss of scale information between non-adjacent layers. Experiments on the Meishan rice dataset show that the proposed method is capable of accurate instance segmentation for fragmented or irregularly shaped rice fields. The evaluation metric AP50 of RACNet reaches 50.8%.

Abstract We investigate the precessing motion around the the regular black hole with an asymptotically Minkowski core which has a suppression parameter $$\ell $$ ℓ . We obtain the third-order post-Newtonian quasi-Keplerian motion of a test particle in this spacetime and find its relativistic periastron advance. Then, we test this model with the precessing motion of the star S2 and of OJ 287 and determine the upper limits of the dimensionless suppression parameter as $$\ell /m \sim 10^{-3}$$ ℓ / m ∼ 10 - 3 , where m is the mass of the black hole. Compared with the bound given by the shadow of Sgr A*, our bound on $$\ell /m$$ ℓ / m is reduced by 2 orders of magnitude, although our upper limit of $$\ell $$ ℓ still needs further improvement.

The development of pipeline steels with exceptional cryogenic toughness is deemed imperative for their applications in various engineering fields. In this work, API X65 steel with lamellar grain (LG) structure is constructed through warm deformation techniques. Comparative analysis with raw API X65 steel revealed notable enhancements in both yield strength (YS) and ultimate strength (UTS), exhibiting increments of 315 MPa and 164 MPa, respectively, while retaining substantial fracture toughness (KIc = 251.14 MPa m0.5). Remarkably, the LG steel exhibits a distinct absence of a ductile-brittle transition behavior over a wide temperature range, maintaining an exceptionally high impact energy from room temperature (RT) to liquid nitrogen temperature (LNT), and the Charpy impact energy exceeding 330 J at LNT, nearly 16 times higher than the raw API X65 steel. This performance can be primarily attributed to the superior plastic deformation capability, coupled with the delamination toughening mechanism. The resultant tortuous path of crack propagation effectively facilitates the absorption of substantial energy, decreases notch tip sensitivity depending on the temperature, stress triaxiality, and strain rate, thereby fostering excellent cryogenic toughness.

Cold and Hot syndrome, also known as “ZHENG” in Mandarin, is a fundamental theory in traditional Chinese medicine (TCM) and plays a pivotal role in the differentiation of diseases in TCM. Diseases are treated with varying formulas according to the specific syndrome differentiations in TCM. A way of the principles followed in TCM medical strategy is “cold herbs for hot syndrome, and hot herbs for cold syndrome.” Therefore, from the perspective of cold/hot syndrome, we summarizes the present research regarding the characteristics and mechanisms of cold/hot herbs (including herbs with cool and warm properties) in digestive system diseases, respiratory diseases, and autoimmune diseases, among others. As novel technologies have advanced, various methods, such as those based on network target, machine learning, and deep learning, have emerged to reveal the mechanisms underlying cold/hot syndrome and cold/hot herbs. With the help of these technologies, it has been found that cold and hot herbs, as well as formulae with cold or hot intentions, have similarities and differences in the treatment of these diseases. In conclusion, cold and cool may have stronger antibacterial, antiviral, and anti-inflammatory effects, whereas hot and warm herbs may specifically enhance immune regulation. With the assistance of advancing data algorithms, uncovering the mechanisms of cold/hot herbs may accelerate and provide a new research paradigm for further achieving precision in TCM.

Global energy and environmental issues are becoming increasingly problematic, and the vibration and noise problem of 110 kV transformers, which are the most widely distributed, have attracted widespread attention from both inside and outside the industry. DC bias is one of the main contributing factors to vibration noise during the normal operation of transformers. To clarify the vibration and noise mechanism of a 110 kV transformer under a DC bias, a multi-field coupling model of a 110 kV transformer was established using the finite element method. The electromagnetic, vibration, and noise characteristics during the DC bias process were compared and quantified through field circuit coupling in parallel with the power frequency of AC, harmonic, and DC power sources. It was found that a DC bias can cause significant distortions in the magnetic flux density, force, and displacement distributions of the core and winding. The contributions of the DC bias effect to the core and winding are different at Kdc = 0.85. At this point, the core approached saturation, and the increase in the core force and displacement slowed. However, the saturation of the core increased the leakage flux, and the stress and displacement of the winding increased faster. The sound field distribution characteristics of the 110 kV transformer under a DC bias are related to the force characteristics. When the DC bias coefficient was 1.25, the noise sound pressure level reached 73.6 dB.

Abstract While KRAS mutation is the leading cause of low survival rates in lung cancer bone metastasis patients, effective treatments are still lacking. Here, we identified homeobox C10 (HOXC10) as a lynchpin in pan-KRAS-mutant lung cancer bone metastasis. Through RNA-seq approach and patient tissue studies, we demonstrated that HOXC10 expression was dramatically increased. Genetic depletion of HOXC10 preferentially impeded cell proliferation and migration in vitro. The bioluminescence imaging and micro-CT results demonstrated that inhibition of HOXC10 significantly reduced bone metastasis of KRAS-mutant lung cancer in vivo. Mechanistically, the transcription factor HOXC10 activated NOD1/ERK signaling pathway to reprogram epithelial-mesenchymal transition (EMT) and bone microenvironment by activating the NOD1 promoter. Strikingly, inhibition of HOXC10 in combination with STAT3 inhibitor was effective against KRAS-mutant lung cancer bone metastasis by triggering ferroptosis. Taken together, these findings reveal that HOXC10 effectively alleviates pan-KRAS-mutant lung cancer with bone metastasis in the NOD1/ERK axis-dependent manner, and support further development of an effective combinatorial strategy for this kind of disease.

Abstract Heterogeneous thermocatalysis of formic acid dehydrogenation by metals in solution is of great importance for chemical storage and production of hydrogen. Insightful understanding of the complicated formic acid dehydrogenation kinetics at the metal-solution interface is challenging and yet essential for the design of efficient heterogeneous formic acid dehydrogenation systems. In this work, formic acid dehydrogenation kinetics is initially studied from a perspective of electrochemistry by decoupling this reaction on Pd catalyst into two short-circuit half reactions, formic acid oxidation reaction and hydrogen evolution reaction and manipulating the electrical double layer impact from the solution side. The pH-dependences of formic acid dehydrogenation kinetics and the associated cation effect are attributed to the induced change of electric double layer structure and potential by means of electrochemical measurements involving kinetic isotope effect, in situ infrared spectroscopy as well as grand canonical quantum mechanics calculations. This work showcases how kinetic puzzles on some important heterogeneous catalytic reactions can be tackled by electrochemical theories and methodologies.

Abstract Hyperuricemia, characterized by elevated levels of serum uric acid (SUA), is linked to a spectrum of commodities such as gout, cardiovascular diseases, renal disorders, metabolic syndrome, and diabetes, etc. Significantly impairing the quality of life for those affected, the prevalence of hyperuricemia is an upward trend globally, especially in most developed countries. UA possesses a multifaceted role, such as antioxidant, pro-oxidative, pro-inflammatory, nitric oxide modulating, anti-aging, and immune effects, which are significant in both physiological and pathological contexts. The equilibrium of circulating urate levels hinges on the interplay between production and excretion, a delicate balance orchestrated by urate transporter functions across various epithelial tissues and cell types. While existing research has identified hyperuricemia involvement in numerous biological processes and signaling pathways, the precise mechanisms connecting elevated UA levels to disease etiology remain to be fully elucidated. In addition, the influence of genetic susceptibilities and environmental determinants on hyperuricemia calls for a detailed and nuanced examination. This review compiles data from global epidemiological studies and clinical practices, exploring the physiological processes and the genetic foundations of urate transporters in depth. Furthermore, we uncover the complex mechanisms by which the UA induced inflammation influences metabolic processes in individuals with hyperuricemia and the association with its relative disease, offering a foundation for innovative therapeutic approaches and advanced pharmacological strategies.

To study the internal deformation evolution law of soil mass corresponding to subsidence stretching area of mining areas with thick loose layer, the No.10111-working face of Suntuan coal mine in Huaibei is selected, and No.1—3 vertical boreholes are arranged at 60 m spacing along the direction perpendicular to the advancing direction from the near to the distant for the loose layer corresponding to stretching area of the working face. In the process of coal mining subsidence, the borehole deformation monitoring is carried out based on the technology of optical fiber (borehole No.1) and inclinometer (borehole No.2—3). The area occupied by the overlying rock strata and loose layers mobilized by coal mining is considered as a deformation zone, and the concept of the movement angle of strata of arbitrary thickness is introduced. The results show that: The maximum depth at which strain occurs in the borehole No.1 is about 157 meters, with the deeper sections of the borehole reaching the active phase before the shallower; Within the monitoring range of boreholes No.2 and No.3, the geological formations can be divided from bottom to top into stable sections, lower, middle, and upper sections of the deformation zone. The final cumulative horizontal displacement at the borehole openings of No.2 and No.3 is 129.8 mm and 99.4 mm respectively, and the maximum displacement depths of about 108 m and 75 m respectively; Moreover, the horizontal displacement distribution of No.2 and No.3 borehole from bottom to top is generally uniform, and the average horizontal displacement per meter borehole is about 1.2 mm and 1.3 mm, respectively; In each borehole, the lower part of the deformation zone reaches the active period before the upper part and the upper part still has weak deformation after the lower part of the deformation zone is stable; For a certain thickness of strata in the loose layer, the movement angle increases with the increase of its depth, and the depth h of the lower boundary of the loose layer deformation zone decreases with the increase of the horizontal distance l from the working face, which accords with the exponential function relationship.

Integrase strand transfer inhibitors (INSTIs) have emerged as the first-line choice for treating human immunodeficiency virus (HIV) infection due to their superior efficacy and safety. However, the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV (PLWH) is not fully understood due to limited data. In this study, we conducted a cross-sectional examination of PLWH receiving antiretroviral therapy, with a specific focus on HIV-positive men who have sex with men (MSM) on INSTI-based regimens (n = 61) and efavirenz (EFV)-based regimens (n = 28). Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging (MRI) scans, including T1-weighted images and resting-state functional MRI. Compared to the EFV group, the INSTI group exhibited primarily reduced gray matter volume (GMV) in the right superior parietal gyrus, higher regional homogeneity (ReHo) in the left postcentral gyrus, lower ReHo in the right orbital part of the inferior frontal gyrus, and increased voxel-wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus. Furthermore, the analysis revealed a main effect of antiretroviral drugs on GMV changes, but no main effect of neuropsychiatric disorders or their interaction. The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group, validating the initial findings. Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI-based regimens compared to those on EFV-based regimens. These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI-based regimens.

Abstract Focal segmental glomerulosclerosis (FSGS), a clinicopathological condition characterized by nephrotic-range proteinuria, has a high risk of progression to end-stage renal disease (ESRD). Meanwhile, the recurrence of FSGS after renal transplantation is one of the main causes of graft loss. The diagnosis of recurrent FSGS is mainly based on renal puncture biopsy transplants, an approach not widely consented by patients with early mild disease. Therefore, there is an urgent need to find definitive diagnostic markers that can act as a target for early diagnosis and intervention in the treatment of patients. In this review, we summarize the domestic and international studies on the pathophysiology, pathogenesis and earliest screening methods of FSGS and describe the functions and roles of specific circulating factors in the progression of early FSGS, in order to provide a new theoretical basis for early diagnosis of FSGS recurrence, as well as aid the exploration of therapeutic targets.

Abstract Bacterial testicular inflammation is one of the important causes of male infertility. Using plant-derived compounds to overcome the side effects of antibiotics is an alternative treatment strategy for many diseases. Schizandrin B (SchB) is a bioactive compound of herbal medicine Schisandra chinensis which has multiple pharmacological effects. However its effect and the mechanism against testicular inflammation are unknown. Here we tackled these questions using models of lipopolysaccharide (LPS)-induced mice and -Sertoli cells (SCs). Histologically, SchB ameliorated the LPS-induced damages of the seminiferous epithelium and blood-testicular barrier, and reduced the production of pro-inflammatory mediators in mouse testes. Furthermore, SchB decreased the levels of pro-inflammatory mediators and inhibited the nuclear factor kB (NF-κB) and MAPK (especially JNK) signaling pathway phosphorylation in LPS-induced mSCs. The bioinformatics analysis based on receptor prediction and the molecular docking was further conducted. We targeted androgen receptor (AR) and illustrated that AR might bind with SchB in its function. Further experiments indicate that the AR expression was upregulated by LPS stimulation, while SchB treatment reversed this phenomenon; similarly, the expression of the JNK-related proteins and apoptotic-related protein were also reversed after AR activator treatment. Together, SchB mitigates LPS-induced inflammation and apoptosis by inhibiting the AR-JNK pathway.

Abstract Background A cost-effective Escherichia coli expression system has gained popularity for producing virus-like particle (VLP) vaccines. However, the challenge lies in balancing the endotoxin residue and removal costs, as residual endotoxins can cause inflammatory reactions in the body. Results In this study, porcine parvovirus virus-like particles (PPV-VLPs) were successfully assembled from Decreased Endotoxic BL21 (BL21-DeE), and the effect of structural changes in the lipid A of BL21 on endotoxin activity, immunogenicity, and safety was investigated. The lipopolysaccharide purified from BL21-DeE produced lower IL-6 and TNF-α than that from wild-type BL21 (BL21-W) in both RAW264.7 cells and BALB/c mice. Additionally, mice immunized with PPV-VLP derived form BL21-DeE (BL21-DeE-VLP) showed significantly lower production of inflammatory factors and a smaller increase in body temperature within 3 h than those immunized with VLP from BL21-W (BL21-W-VLP) and endotoxin-removed VLP (ReE-VLP). Moreover, mice in the BL21-DeE-VLP immunized group had similar levels of serum antibodies as those in the BL21-W-VLP group but significantly higher levels than those in the ReE-VLP group. Furthermore, the liver, lungs, and kidneys showed no pathological damage compared with the BL21-W-VLP group. Conclusion Overall, this study proposes a method for producing VLP with high immunogenicity and minimal endotoxin activity without chemical or physical endotoxin removal methods. This method could address the issue of endotoxin residues in the VLP and provide production benefits.

In this paper, to handle the problem of the quick evolution of cyber-security attacks, we developed the iMonsters board game and proposed the attack and defense knowledge self-evolving algorithm. Three versions of the iMonsters were launched in 2013, 2017, and 2019, respectively. Accordingly, the cyber-security ontology can be refined by the ontology fusion-or-splitting procedure for the newly collected cyber-security incidents, as well as the roles and rules of the iMonsters can be refined by the gaming portfolio mining procedure for the collected portfolio. Furthermore, we conducted game-based learning (GBL), a quasi-experiment of pre/post-testing, and concept map testing using the iMonsters board game in a children's summer camp. The experimental results indicate that the students can acquire up-to-date cyber-security knowledge with the iMonsters better than students who learn in a traditional classroom setting, and the students' satisfaction with acquiring cyber-security knowledge with the instructional design of the iMonsters is better compared with learning in a traditional classroom setting. Satisfaction with the new version has continuously increased. Besides, the results of the in-depth interviews show that the new version was easier to learn. Thus, we may conclude that using the self-evolving iMonsters can improve learning effectiveness and participation in GBL.

Context The mechanism of Renshen Shouwu Decoction (RSSW) in treating Alzheimer’s disease (AD) remains unknown.Objective This study investigates the effects and mechanism of RSSW for ameliorating AD.Materials and methods Ten SAMR1 mice and 40 SAMP8 mice were divided into five groups: control (SAMR1), model (SAMP8), positive drug (Donepezil, 1.3 mg/kg/d), and RSSW (Low-dose, 117 mg/kg/d; High-dose, 234 mg/kg/d). Starting from 6 months of age, the medications were administered intragastrically for a total of 60 days. Subsequently, memory improvement in rapidly aging mice was assessed using the novel object recognition test and Morris water maze test. Through the identification of absorbed blood components and analysis of network pharmacology, active ingredients and potential targets involved in the treatment of AD were identified. Finally, AD-related biological indicators were detected using western blotting and ELISA.Result Our results demonstrated that RSSW effectively ameliorated memory impairments, inhibited tau hyperphosphorylation, and reduced β-amyloid plaque deposition in SAMP8 mice. Thirty absorbed blood components in RSSW were identified, revealing identified 96 major targets that play a key role in alleviating AD. Notably, the obtained main targets were highly enriched in SIRT1-mediated signaling pathways. Subsequent experimental validation confirmed that RSSW activated the SIRT1/NF-κB, SIRT1/AMPK, and SIRT1/p53 signaling cascades. Nine potential active ingredients were predicted through molecular docking.Discussion and conclusions Our research findings suggest the mechanism of RSSW treatment for AD, which ameliorates memory impairments by reducing cortical tissue inflammation and apoptosis.

Disperse ferrite is generally embedded in lightweight steel, yet exhibits decent performance, thereby prompting a question: can heterogeneous design optimize it? Here, two representative structures, featured with discontinuous fibrous and dispersed ferrite separately embedded in the austenite matrix, were constructed as examples to address the issue. A heterostructure with fibrous ferrite shows a remarkable product (49 GPa·%) of ultimate strength and total elongation, standing out among other lightweight steels. Superior strength-ductility synergy is primarily attributed to hetero-deformation-induced strengthening and hardening. Abundant hetero-interactions imparted by phase boundaries, dense slip bands in austenite and dislocation networks inside ferrite serve as underlying physical mechanisms.

Heterostructured ferritic steels with bimodal-grained lamellar (BG-L) and ultrafine-grained lamellar (UFG-L) microstructure were prepared through a warm deformation process. The BG-L steel exhibits enhanced mechanical properties compared to conventional quenched and tempered (QT) steel. While the UFG-L steel demonstrates an outstanding combination of strength, ductility, and toughness. Furthermore, the UFG-L steels exhibit no ductile-to-brittle transition (DBT) from room temperature (RT) to liquid nitrogen temperature (LNT) and the Charpy impact energy remains as high as 314 J at LNT. The enhanced toughness at LNT can be attributed to the crack-arrester mechanism caused by grain-boundary delamination.

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

Abstract Background Conventional single-energy CT can only provide a raw estimation of electron density (ED) for dose calculation by developing a calibration curve that simply maps the HU values to ED values through their correlations. Spectral CT, also known as dual-energy CT (DECT) or multi-energy CT, can generate a series of quantitative maps, such as ED maps. Using spectral CT for radiotherapy simulations can directly acquire ED information without developing specific calibration curves. The purpose of this study is to assess the feasibility of utilizing electron density (ED) maps generated by a novel dual-layer detector spectral CT simulator for dose calculation in radiotherapy treatment plans. Methods 30 patients from head&neck, chest, and pelvic treatment sites were selected retrospectively, and all of them underwent spectral CT simulation. Treatment plans based on conventional CT images were transplanted to ED maps with the same structure set, including planning target volume (PTV) and organs at risk (OARs), and the dose distributions were then recalculated. The differences in dose and volume histogram (DVH) parameters of the PTV and OARs between the two types of plans were analyzed and compared. Besides, gamma analysis between these plans was performed by using MEPHYSTO Navigator software. Results In terms of PTV, the homogeneity index (HI), gradient index (GI), D2%, D98%, and Dmean showed no significant difference between conventional plans and ED plans. For OARs, statistically significant differences were observed in parotids D50%, brainstem in head&neck plans, spinal cord in chest plans and rectum D50% in pelvic plans, whereas the variance remained minor. For the rest, the DVH parameters exhibited no significant difference between conventional plans and ED plans. All of the mean gamma passing rates (GPRs) of gamma analysis were higher than 90%. Conclusion Compared to conventional treatment plans relying on CT images, plans utilizing ED maps demonstrated similar dosimetric quality. However, the latter approach enables direct utilization in dose calculation without the requirements of establishing and selecting a specific Hounsfield unit (HU) to ED calibration curve, providing an advantage in clinical applications.

Abstract Background Knee osteoarthritis (KOA) has become a public health issue. Several systematic reviews (SRs) and meta-analyses (MAs) indicate that traditional Chinese exercise (TCE) may be an effective treatment for reducing pain and stiffness and improving physical function in people with knee osteoarthritis (KOA). Objectives To evaluate the literature quality and evidence for the systematic reviews of TCE for KOA and provide evidence to support the clinical application of TCE for KOA. Methods Eight databases were searched from their inception to January 3, 2023, to retrieve relevant literature, including China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Scientific Journal Database (VIP), China Biology Medical literature database (CBM), PubMed, Embase, Web of Science and Cochrane Library, without restrictions on publication date or language. AMSTAR-2 and PRISMA 2020 assessed the methodological and reporting quality of included SRs/MAs. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was utilized to evaluate the quality of evidence. Results A total of 18 SRs/MAs were included. The methodological quality was “very low” based on AMSTAR-2. The overall reporting quality was deficient based on PRISMA 2020. The quality of Chinese and English literature differed, with English literature being superior in methodological and reporting quality. Among 93 pieces of evidence obtained, 46 (49.46%) were of very low quality, 34 (36.56%) were of low quality, 13 (13.98%) were of moderate quality, and none were of high quality. TCE was supported by 76 pieces of evidence (81.72%). Conclusion TCE appears beneficial and safe for managing KOA. However, due to the relatively low methodological and evidentiary quality of included SRs/MAs, clinicians should interpret these findings cautiously.

Abstract Motivation Retrosynthesis planning poses a formidable challenge in the organic chemical industry, particularly in pharmaceuticals. Single-step retrosynthesis prediction, a crucial step in the planning process, has witnessed a surge in interest in recent years due to advancements in AI for science. Various deep learning-based methods have been proposed for this task in recent years, incorporating diverse levels of additional chemical knowledge dependency. Results This paper introduces UAlign, a template-free graph-to-sequence pipeline for retrosynthesis prediction. By combining graph neural networks and Transformers, our method can more effectively leverage the inherent graph structure of molecules. Based on the fact that the majority of molecule structures remain unchanged during a chemical reaction, we propose a simple yet effective SMILES alignment technique to facilitate the reuse of unchanged structures for reactant generation. Extensive experiments show that our method substantially outperforms state-of-the-art template-free and semi-template-based approaches. Importantly, our template-free method achieves effectiveness comparable to, or even surpasses, established powerful template-based methods. Scientific contribution We present a novel graph-to-sequence template-free retrosynthesis prediction pipeline that overcomes the limitations of Transformer-based methods in molecular representation learning and insufficient utilization of chemical information. We propose an unsupervised learning mechanism for establishing product-atom correspondence with reactant SMILES tokens, achieving even better results than supervised SMILES alignment methods. Extensive experiments demonstrate that UAlign significantly outperforms state-of-the-art template-free methods and rivals or surpasses template-based approaches, with up to 5% (top-5) and 5.4% (top-10) increased accuracy over the strongest baseline.