Search

Abstract Background Sanniang Bay (SNB) and Dafeng River (DFR), located in the northern Beibu Gulf, is well-known as one of the eight habitats for humpback dolphins in China. This region is representative of typical estuarine and bay ecosystems and produce complex hydrodynamic seawater conditions. Moreover, anthropogenic pressure, such as eutrophication and large-scale infrastructure projects, have caused ongoing habitat deterioration and loss. It is urgent to know the phytoplankton community and their relationships with environmental factors in this region. Results In this study, we assessed the diversity and assembly mechanisms of phytoplankton communities, as well as their relationship with the physicochemical characteristics of seawater in SNB and DFR region using 18 S rDNA metabarcoding analysis. The results showed that seasonal changes markedly impacted the alpha diversity of the phytoplankton community. From March to July, with the average temperature increasing from 25.2℃ to 28.1℃,the Shannon or Species Richness were negatively correlated with temperature. During hot season (in Sep, average temperature 32.1℃), phytoplankton diversity was negatively correlated with nutrients (NH4 +, NO3 −, PO4 3−, TN). Additionally, during the rainy season, the Bray-Curtis similarity of the phytoplankton community was significantly lower than during the dry season. In March, the distance among the sampling sites was most strongly and positively correlated with the Bray-Curtis dissimilarity. Stochastic processes, specifically dispersal limitation and ecological drift, are the primary drivers of community assembly, while deterministic assembly processes (mainly heterogeneous selection) contribute a relatively minor portion (

Abstract Cerebrovascular abnormalities are critical indicators of stroke and neurodegenerative diseases like Alzheimer’s disease (AD). Understanding the normal evolution of brain vessels is essential for detecting early deviations and enabling timely interventions. Here, for the first time, we proposed a pipeline exploring the joint evolution of cortical volumes (CVs) and arterial volumes (AVs) in a large cohort of 2841 individuals. Using advanced deep learning for vessel segmentation, we built normative models of CVs and AVs across spatially hierarchical brain regions. We found that while AVs generally decline with age, distinct trends appear in regions like the circle of Willis. Comparing healthy individuals with those affected by AD or stroke, we identified significant reductions in both CVs and AVs, wherein patients with AD showing the most severe impact. Our findings reveal gender-specific effects and provide critical insights into how these conditions alter brain structure, potentially guiding future clinical assessments and interventions.

A large language model (LLM) is constructed to address the sophisticated demands of data retrieval and analysis, detailed well profiling, computation of key technical indicators, and the solutions to complex problems in reservoir performance analysis (RPA). The LLM is constructed for RPA scenarios with incremental pre-training, fine-tuning, and functional subsystems coupling. Functional subsystem and efficient coupling methods are proposed based on named entity recognition (NER), tool invocation, and Text-to-SQL construction, all aimed at resolving pivotal challenges in developing the specific application of LLMs for RDA. This study conducted a detailed accuracy test on feature extraction models, tool classification models, data retrieval models and analysis recommendation models. The results indicate that these models have demonstrated good performance in various key aspects of reservoir dynamic analysis. The research takes some injection and production well groups in the PK3 Block of the Daqing Oilfield as an example for testing. Testing results show that our model has significant potential and practical value in assisting reservoir engineers with RDA. The research results provide a powerful support to the application of LLM in reservoir performance analysis.

Abstract We investigate the effects of the twist-2 operator in 2D symmetric orbifold CFTs. The twist operator can join together a twist-M state and a twist-N state, creating a twist-(M + N) state. This process involves three effects: pair creation, propagation, and contraction. We study these effects by using a Bogoliubov ansatz and conformal symmetry. In this multi-wound scenario, pair creation no longer decouples from propagation, in contrast to the previous study where M = N = 1. We derive equations for these effects, which organize themselves into recursion relations and constraints. Using the recursion relations, we can determine the infinite number of coefficients in the effects through a finite number of inputs. Moreover, the number of required inputs can be further reduced by applying constraints.

Abstract Effective antibacterial therapy while accelerating the repair of bone defects is crucial for the treatment of osteomyelitis. Inspired by the protective mechanism of Andrias davidianus, we constructed an antibacterial hydrogel scaffold with excellent rigidity and long-term slow-release activity. While retaining the toughness of the skin secretion of Andrias davidianus (SSAD), the rigidity of the hydrogel material is increased by incorporating hydroxyapatite to meet the demands of bone-defect-filling materials. It also exerted antibacterial effects via the slow-release of vancomycin from local osteomyelitis lesions. Notably, the hydrogel can also carry a high stable recombinant miR-214-3p inhibitor (MSA-anti214). By the delivery of nano vector polyvinylamine, the long-term slow-release of MSA-anti214 is achieved to promote bone repair, making this composite hydrogel a potential SSAD-based osteomyelitis alleviator (SOA). In vitro and vivo results verified that the SOA effectively eliminated Staphylococcus aureus and repaired bone defects, ultimately mitigating the progression of osteomyelitis. This composite hydrogel extends the economic application prospects of A. davidianus and has provided new insights for the treatment of osteomyelitis. The study also explored new insights for the bone filling materials of bone defection and other skeletal system diseases.

Abstract Despite the broad potential applications of C-glycosides, facile synthetic methods remain scarce. Transforming glycosyltransferases with promiscuous or natural O-specific chemoselectivity to C-glycosyltransferases is challenging. Here, we employ rational directed evolution of the glycosyltransferase MiCGT to generate MiCGT-QDP and MiCGT-ATD mutants which either enhance C-glycosylation or switch to O-glycosylation, respectively. Structural analysis and computational simulations reveal that substrate binding mode govern C-/O-glycosylation selectivity. Notably, directed evolution and mechanism analysis pinpoint the crucial residues dictating the binding mode, enabling the rational design of four enzymes with superior non-inherent chemoselectivity, despite limited sequence homology. Moreover, our best mutants undergo testing with 34 substrates, demonstrating superb chemoselectivities, regioselectivities, and activities. Remarkably, three C-glycosides and an O-glycoside are produced on a gram scale, demonstrating practical utility. This work establishes a highly selective platform for diverse glycosides, and offers a practical strategy for creating various types of glycosylation platforms to access pharmaceutically and medicinally interesting products.

Abstract Addressing the rise in global temperatures and the associated increase in greenhouse gases, particularly carbon dioxide, is a critical challenge necessitating innovative approaches within the building sector, a significant contributor to worldwide carbon emissions. While previous studies have demonstrated the prefabrication’s potential in reducing emissions, comprehensive assessments using actual project data for buildings constructed entirely with modular methods in Hong Kong are lacking. This study bridges this gap by evaluating the modular integrated construction (MiC) method through an embodied carbon assessment of the Kai Tak Community Isolation Facility. Using comprehensive project data from China State Construction (HK) Limited, the research conducts a comparative analysis between the actual emissions of the MiC method and those of a hypothetical conventional construction approach. Quantitative analysis reveals that MiC achieves a 20.7% reduction in embodied carbon, primarily due to shortened construction timelines, decreased waste generation, and optimized material usage. This significant reduction suggests substantial potential for decreasing the construction industry’s carbon footprint. The study provides empirical evidence supporting the environmental benefits of MiC in Hong Kong construction industry, promoting its broader adoption of MiC as a strategy for achieving carbon reduction targets. The findings align with Hong Kong’s carbon neutrality goals and contribute to the global initiative to mitigate the effects of climate change.

Abstract Background Several surgical options for degenerative lumbar spinal stenosis (LSS) are available, but current guidelines do not recommend which one should be prioritized. Although previous network meta-analyses (NMAs) have been performed on this topic, they have major methodological problems and could not provide the convincing evidence and clinical practical information required. Methods Randomized controlled trials (RCTs) comparing at least two surgical interventions were included by searching AMED, CINAHL, EMBASE, the Cochrane Library, and MEDLINE (inception to August 2023). A frequentist random-effects NMA was performed for physical function and adverse events due to any reason. For physical function, three follow-up time points were included: short-term (

Abstract Background Neonatal respiratory distress syndrome (NRDS) is a primary cause of morbidity and mortality in premature infants. Platelets have a unique role in lung repair and remodeling. This study aimed to determine the relationship between platelet count and NRDS severity. Methods The study included 234 newborns diagnosed with NRDS from January 2019 to August 2023. This study employed two methods of grouping: the first based on platelet count, dividing participants into thrombocytopenia (platelet count

Abstract Objective Empathy is crucial for patient health. The Balint group is a commonly used method for empathy training. However, the impact of Balint groups on empathy remains unclear. This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to assess the impact of Balint groups on empathy training among medical and nursing students, as well as doctors and nurses. Methods This review involved searching multiple databases for relevant articles. Rigorous eligibility criteria were applied during the screening of titles and abstracts, and during the selection of records. Following a full-text eligibility evaluation, two reviewers independently extracted data from the final selection of studies, and a meta-analysis was conducted. The standardized mean difference (SMD) was calculated to assess the systematic outcomes. Results A total of 11 studies were included in this systematic review and meta-analysis. Participants in Balint groups demonstrated a significant increase in empathy than those in the control group (SMD = 1.46, 95% confidence interval [CI] 0.86–2.06; p

Abstract Intracerebral hemorrhage is a lethal cerebrovascular disease, and the inevitable secondary brain injury (SBI) is responsible for serious disability and death. Perfect therapeutic goal is to minimize SBI and restore neurobehavioral functions. Recently, neuroprotection is highlighted to reduce SBI, but it still faces “Neuronal survival but impaired functions” dilemma. Herein, this work further proposes a novel combinational therapeutic strategy of neuroprotection and neurogenesis toward this goal. However, appropriate therapeutic agents are rarely reported, and their discovery and development are urgently needed. Selenium participates in various physiological/pathological processes, which is hypothesized as a potential targeting molecule. To explore this effect, this work formulates an ultra-small selenium nanodot with a seleno-amino acid derived carbon dot domain and a hydrophilic PEG layer, surprisingly finding that it increases various selenoproteins levels at perihematomal region, to not only exert multiple neuroprotective roles at acute phase but promote neurogenesis and inhibit glial scar formation at recovery phase. At a safe dose, this combinational strategy effectively prevents SBI and recovers neurobehavioral functions to a normal level. Furthermore, its molecular mechanisms are revealed to broaden application scopes in other complex diseases. Graphical abstract

Abstract Articular cartilage damage and wear can result in cartilage degeneration, ultimately culminating in osteoarthritis. Current surgical interventions offer limited capacity for cartilage tissue regeneration and offer only temporary alleviation of symptoms. Tissue engineering strategies are increasingly recognized as promising modalities for cartilage restoration. Currently, various biological scaffolds utilizing tissue engineering materials are extensively employed in both fundamental and clinical investigations of cartilage repair. In order to optimize the cartilage repair ability of tissue engineering scaffolds, researchers not only optimize the structure and properties of scaffolds from the perspective of materials science and manufacturing technology to enhance their histocompatibility, but also adopt strategies such as loading cells, cytokines, and drugs to promote cartilage formation. This review provides an overview of contemporary tissue engineering strategies employed in cartilage repair, as well as a synthesis of existing preclinical and clinical research. Furthermore, the obstacles faced in the translation of tissue engineering strategies to clinical practice are discussed, offering valuable guidance for researchers seeking to address these challenges.

Abstract Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

An integrated thermodynamic model was developed to determine the equilibrium between the slag and the steel at high temperatures, employing the Unified Interaction Parameter Formalism (UIPF) and the Associate Model (AM) for a twelve-element molten steel system (Fe–Al–C–Ca–Cr–Mg–Mn–N–O–S–Si–Ti). A model for slag activity was based on the Ion and Molecular Coexistence Theory (IMCT) and applied to a refining slag system (CaO–MgO–FeO–MnO–CaF2–SiO2–Al2O3–Fe2O3). Comparative analyses were conducted using FactSage software and experimental data, validating the accuracy of the established model. The impact of slag modifiers, specifically aluminum granules, on slag oxidability, and the role of CaO/Al2O3 ratio in slag desulfurization were investigated. The effect of slag modifier on the oxidability and the influence of CaO/Al2O3 on the desulfurization of the slag were determined using the current model. Aluminum in the slag modifier reacted with MnO and FeO in the slag, thereby reducing the oxidability of the slag. With a 30 wt% slag modifier, the MnO content in the slag (initially 15 wt%) stabilized and showed minimal change, dropping below 1 wt%. An increase in CaO content above 80 wt% in the slag led to a reduction of equilibrium sulfur in the steel to below 10 ppm. Little amount of calcium transferred from the slag into the steel with the increase in CaO content, but the [Ca] content remained below 0.5 ppm even though the content of CaO in the slag was greater than 80 wt%. The developed model offered a versatile tool for designing slag compositions tailored to various purposes.

In this paper, the following critical Kirchhoff-type elliptic equation involving a logarithmic-type perturbation$ -\Big(a+b\int_{\Omega}|\nabla u|^2\mathrm{d}x\Big)\Delta u = \lambda|u|^{q-2}u\ln |u|^2+\mu|u|^2u $is considered in a bounded domain in $ \mathbb{R}^{4} $. One of the main obstructions one encounters when looking for weak solutions to Kirchhoff problems in high dimensions is that the boundedness of the $ (PS) $ sequence is hard to obtain. By combining a result by Jeanjean [27] with the mountain pass lemma and Brézis–Lieb's lemma, it is proved that either the norm of the sequence of approximation solutions goes to infinity or the problem admits a nontrivial weak solution, under some appropriate assumptions on $ a $, $ b $, $ \lambda $, and $ \mu $.

Abstract Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood–brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.

Abstract Constructing highways in deserts is expensive due to the difficulty of acquiring materials; utilizing aeolian sand effectively has become a problem, especially in the Xinjiang region, where the desert widely occurs. This paper aims to investigate the vibration response of a geocell-reinforced aeolian sand subgrade under traffic loading based on field tests of highways in deserts. The vibration acceleration response of geocell-reinforced aeolian sand and gravelly soil upper roadbed structures is tested. The field test results illustrate the effects of dynamic loading on geocell-reinforced aeolian sand roadbeds, and the thickness substitution ratio between geocell-reinforced aeolian sand roadbeds and conventional gravelly soil roadbeds is determined and verified based on the vibration acceleration monitoring values. The results show that the vibration response induced by the test vehicle is concentrated within the 30 Hz frequency band, and the higher the vibration frequency, the faster the vertical decay in the road. The vibration damping capacity of the reinforced aeolian sand roadbed is better than that of the gravelly soil roadbed; when replacing the gravelly soil roadbed with the reinforced aeolian sand roadbed, the substitution ratio is 0.31–0.42. It is verified that half thickness of gravel soil on roadbeds can be replaced by geocell-reinforced aeolian sand under different working conditions. The results of this study can provide reference data for the design of highway subgrades in deserts.

Abstract Residents' participation is crucial for sustainable old neighborhood regeneration. Residents' intentions to participate in the regeneration are low in China, resulting in unsustainable neighborhood development problems. Therefore, it is essential to investigate the drivers of residents' participation. Residents' behavioral mechanisms are deeply embedded in their social networks, especially in acquaintance social networks typical of old neighborhoods in China. By constructing a mediated moderation model based on the Theory of Planned Behavior (TPB) and danwei system and taking the old neighborhood regeneration in Xi'an as a case study, this paper investigates the paths and mechanisms of the social network embeddedness, TPB, and danwei system on residents' participation intention. The results show that social network embeddedness can improve residents' intention to participate in regeneration through both direct and indirect pathways, and its indirect effect is much larger than the direct effect. Attitude, subjective norm, and perceived behavioral control significantly and positively mediated the contribution of social network embeddedness on participation intention. However, the specific mediating effect of attitude is significantly smaller than the other two. The danwei system has a significant moderating effect in the first stage of the relationship between social network embeddedness and participation intention. These imply that the extrinsic social factor of social network embeddedness is internalized as a driving force for convergence and motivation of residents' participation intentions mainly through the normative pressure and exchange of experiences between acquaintances and that the danwei system reinforces this extrinsic-intrinsic facilitation process through the danwei's "physical presence." These findings provide revelatory countermeasures for exploring the factors that motivate residents to participate actively in neighborhood regeneration and encourage their involvement at the intervention level.

Abstract In recent years, sleep problems among college students have become increasingly prominent, especially in the context of the COVID-19 pandemic, and their sleep quality has deteriorated dramatically, severely affecting their physical and mental health. Numerous research studies have investigated the relationship between mindfulness and sleep quality; however, it is still unclear what psychological process underlies this relationship. In the current study, college students’ bed procrastination and self-control as mediating factors in the association between mindfulness and sleep quality were investigated. Using the convenience sampling method, 763 Chinese college students (mean age = 19.48 years, SD = 2.06) were recruited to complete self-reported questionnaires that included the Mindful Attention Awareness Scale, Self-Control Scale, Bed Procrastination Scale, and Sleep Quality Scale. All statistical analyses were performed using SPSS 23.0 software. Results showed that (a) mindfulness was positively associated with sleep quality; (b) both self-control and bed procrastination mediated the relationship between mindfulness and sleep quality, and (c) self-control and bed procrastination sequentially mediated the relationship between mindfulness and sleep quality. These findings collectively suggest a potential mechanism for how mindfulness influences sleep quality, providing a therapeutic target for mindfulness-based interventions aimed at helping college students improve sleep quality.

Abstract Titanium and its alloys have been widely applied in many biomedical fields because of its excellent mechanical properties, corrosion resistance and good biocompatibility. However, problems such as rejection, shedding and infection will occur after titanium alloy implantation due to the low biological activity of titanium alloy surface. The structures with specific functions, which can enhance osseointegration and antibacterial properties, are fabricated on the surface of titanium implants to improve the biological activity between the titanium implants and human tissues. This paper presents a comprehensive review of recent developments and applications of surface functional structure in titanium and titanium alloy implants. The applications of surface functional structure on different titanium and titanium alloy implants are introduced, and their manufacturing technologies are summarized and compared. Furthermore, the fabrication of various surface functional structures used for titanium and titanium alloy implants is reviewed and analyzed in detail. Finally, the challenges affecting the development of surface functional structures applied in titanium and titanium alloy implants are outlined, and recommendations for future research are presented.

An ultra-high strain rate (104 s−1) dynamic plastic deformation treatment at liquid nitrogen temperature (LNT-DPD) followed by annealing is carried out to obtain dual heterogeneity of grain size and dislocation density in an equiatomic CrCoNi medium entropy alloy (MEA). Such extreme loading conditions resulted in extensive phase transformation in this MEA. Subsequent annealing at 650 °C for 1 h further induced reverse phase transformation and partial recrystallization, forming a complex heterogeneous microstructure characterized by nested trimodal grain sizes and partitioned dislocation density. A superior yield strength of ∼800 MPa and a good ductility of ∼40% were simultaneously achieved in this heterogeneous alloy. In order to reveal the effects of grain size and dislocation density distributions on the mechanical property improvements, the underlying deformation mechanisms were systematically discussed. High density of geometrically necessary dislocations (GNDs) would be induced in complex heterogeneous structures during tensile deformation due to strain gradients or partitioning between different regions, which would lead to additional strengthening and work hardening. These results provide a novel approach to overcome the strength-ductility trade-off dilemma for FCC-structured MEAs.

Abstract Background Extracellular matrix (ECM) stiffness is closely related to the progress of diabetic cardiomyopathy (DCM) and the response of treatment of DCM to anti-diabetic drugs. Dapagliflozin (Dapa) has been proven to have cardio-protective efficacy for diabetes and listed as the first-line drug to treat heart failure. But the regulatory relationship between ECM stiffness and treatment efficacy of Dapa remains elusive. Materials and methods This work investigated the effect of ECM stiffness on DCM progression and Dapa efficacy using both in vivo DCM rat model and in vitro myocardial cell model with high glucose injury. First, through DCM rat models with various levels of myocardial injury and administration with Dapa treatment for four weeks, the levels of myocardial injury, myocardial oxidative stress, expressions of AT1R (a mechanical signal protein) and the stiffness of myocardial tissues were obtained. Then for mimicking the stiffness of myocardial tissues at early and late stages of DCM, we constructed cell models through culturing H9c2 myocardial cells on the polyacrylamide gels with two stiffness and exposed to a high glucose level and without/with Dapa intervention. The cell viability, reactive oxygen species (ROS) levels and expressions of mechanical signal sensitive proteins were obtained. Results The DCM progression is accompanied by the increased myocardial tissue stiffness, which can synergistically exacerbate myocardial cell injury with high glucose. Dapa can improve the ECM stiffness-induced DCM progression and its efficacy on DCM is more pronounced on the soft ECM, which is related to the regulation pathway of AT1R-FAK-NOX2. Besides, Dapa can inhibit the expression of the ECM-induced integrin β1, but without significant impact on piezo 1. Conclusions Our study found the regulation and effect of biomechanics in the DCM progression and on the Dapa efficacy on DCM, providing the new insights for the DCM treatment. Additionally, our work showed the better clinical prognosis of DCM under early Dapa intervention.

Damage to the substrate hinders the application of laser paint stripping (LPS) on carbon fiber reinforced polymers (CFRP), but the damage mechanism is currently unknown. In this paper, the LPS characteristics of CFRP, such as paint stripping depth, surface morphology and dynamic behavior, are firstly obtained. Subsequently, the surface damage mechanism of CFRP is discussed in detail by theoretical analysis and finite element method, and the effect of substrate damage on adhesive properties is investigated. The results show that it is difficult for LPS to obtain a complete surface free of paint residue. The strong laser plasma impact and resin pyrolysis pressure cause the resin to crack and flake before the paint is fully ablated. The carbon fiber then breaks and are thrown outward by heat and forces, and the surface with slightly fracture of the fiber will facilitate bonding with the paint.

To explore the differences in the composition, content and comprehensive quality of free amino acids (FAA) in millet from Longzhong area in Gansu Province，12 different cultivars of millet were used as research objects, the types and contents of FAA were determined by liquid chromatography-tandem mass spectrometry. Comprehensive evaluation of FAA quality was performed by principal component analysis (PCA) and hierarchical cluster analysis (HCA). The results showed that 19~20 kinds of FAA were detected in all kinds of millet, and the total content of FAA ranged from 1046.80~1773.85 mg/kg, asparagine (Asn), aspartic acid (Asp), glutamic acid (Glu) and glycine (Gly) were the four main FAA in millet. There were significant differences in the contents of FAA (Pbitter amino acids>sweet amino acids>aromatic amino acids. 9 Medicinal amino acids and 3 branched chain amino acids were found in millet, the average content of medicinal amino acids was 706.34 mg/kg, the percentages of medicinal amino acids to total FAA was 53.63%, so millet had many potential medicinal values. There was a significant relation with FAA in different cultivars of millet, five principal components were extracted after PCA, and the cumulative contribution ratio of the five components was 86.20%, the FAA comprehensive scores of LG-23、LG-11 and YG-18 were ranked as the top three. The 12 different cultivars millet were divided into four groups by HCA, FAA comprehensive quality performances of groups Ⅰ (LG-23) and Ⅲ (LG-11 and YG-18) were optimal, the content of total FAA was significantly higher than the other two groups (P

Abstract Atmospheric rivers (ARs) reaching high-latitudes in summer contribute to the majority of climatological poleward water vapor transport into the Arctic. This transport has exhibited long term changes over the past decades, which cannot be entirely explained by anthropogenic forcing according to ensemble model responses. Here, through observational analyses and model experiments in which winds are adjusted to match observations, we demonstrate that low-frequency, large-scale circulation changes in the Arctic play a decisive role in regulating AR activity and thus inducing the recent upsurge of this activity in the region. It is estimated that the trend in summertime AR activity may contribute to 36% of the increasing trend of atmospheric summer moisture over the entire Arctic since 1979 and account for over half of the humidity trends in certain areas experiencing significant recent warming, such as western Greenland, northern Europe, and eastern Siberia. This indicates that AR activity, mostly driven by strong synoptic weather systems often regarded as stochastic, may serve as a vital mechanism in regulating long term moisture variability in the Arctic.

Abstract Background The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive brain imaging technology for studying the neurological activity of the human cerebral cortex. It is based on neural coupling effects. This research uses the fNIRS approach to detect differences in the neurological activity of the cerebral skin in the sound stimulation mission in order to better discriminate between the sensational neurological tinnitus. Methods In the fNIRS brain imaging method, 14 sensorineural tinnitus sufferers and 14 healthy controls listened to varied noise and quiet for fNIRS data collection. Linear fitting was employed in MATLAB to eliminate slow drifts during preprocessing and event-related design analysis. The false discovery rate (FDR) procedure was applied in IBM SPSS Statistics 26.0 to control the false positive rate in multiple comparison analyses. Results When the ill group and the healthy control group were stimulated by pink noise, there was a significant difference in blood oxygen concentration (P

Abstract Efficient thrombolysis in time is crucial for prognostic improvement of patients with acute arterial thromboembolic disease, while limitations and complications still exist in conventional thrombolytic treatment methods. Herein, our study sought to investigate a novel dual-mode strategy that integrated ultrasound (US) and near-infrared light (NIR) with establishment of hollow mesoporous silica nanoprobe (HMSN) which contains Arginine-glycine-aspartate (RGD) peptide (thrombus targeting), perfluoropentane (PFP) (thrombolysis with phase-change and stable cavitation) and indocyanine green (ICG) (thrombolysis with photothermal conversion). HMSN is used as the carrier, the surface is coupled with targeted RGD to achieve high targeting and permeability of thrombus, PFP and ICG are loaded to achieve the collaborative diagnosis and treatment of thrombus by US and NIR, so as to provide a new strategy for the integration of diagnosis and treatment of arterial thrombus. From the in vitro and in vivo evaluation, RGD/ICG/PFP@HMSN can aggregate and penetrate at the site of thrombus, and finally establish the dual-mode directional development and thrombolytic treatment under the synergistic effect of US and NIR, providing strong technical support for the accurate diagnosis and treatment of arterial thrombosis. Graphical Abstract

Objective Bone marrow mesenchymal stem cells (BMSCs) show significant potential for osteogenic differentiation. However, the underlying mechanisms of osteogenic capability in osteoporosis‐derived BMSCs (OP‐BMSCs) remain unclear. This study aims to explore the impact of YTHDF3 (YTH N6‐methyladenosine RNA binding protein 3) on the osteogenic traits of OP‐BMSCs and identify potential therapeutic targets to boost their bone formation ability. Methods We examined microarray datasets (GSE35956 and GSE35958) from the Gene Expression Omnibus (GEO) to identify potential m6A regulators in osteoporosis (OP). Employing differential, protein interaction, and machine learning analyses, we pinpointed critical hub genes linked to OP. We further probed the relationship between these genes and OP using single‐cell analysis, immune infiltration assessment, and Mendelian randomization. Our in vivo and in vitro experiments validated the expression and functionality of the key hub gene. Results Differential analysis revealed seven key hub genes related to OP, with YTHDF3 as a central player, supported by protein interaction analysis and machine learning methodologies. Subsequent single‐cell, immune infiltration, and Mendelian randomization studies consistently validated YTHDF3's significant link to osteoporosis. YTHDF3 levels are significantly reduced in femoral head tissue from postmenopausal osteoporosis (PMOP) patients and femoral bone tissue from PMOP mice. Additionally, silencing YTHDF3 in OP‐BMSCs substantially impedes their proliferation and differentiation. Conclusion YTHDF3 may be implicated in the pathogenesis of OP by regulating the proliferation and osteogenic differentiation of OP‐BMSCs.

Objectives Multiple ligament knee injuries (MLKIs) are disruptive injuries, however, there are controversies in the results of acute and delayed reconstruction. Also, clinical outcomes between patients older or younger than 40 have not been compared in MLKIs. This study was designed to investigate the influence of age and timing of reconstruction on the outcomes of single‐stage reconstruction of MLKIs. Methods The patients who underwent reconstruction of multiple injured ligaments because of MLKIs between May 2013 and July 2019 were added to the cohort. The postoperative complications, knee range of motion (ROM), Lysholm score, International Knee Documentation Committee (IKDC) 2000 score, Tegner activity level, patient satisfaction, and SF‐36 score were compared between young (≤ 40 years old, n = 41) and old patients (n = 61); acute (≤ 3 weeks after injury, n = 75) and delayed reconstruction (n = 27), using Mann–Whitney U test or χ2 test. Results A total of 102 MLKI patients managed by single‐stage multi‐ligament reconstruction were retrospectively reviewed. Patients were followed up after surgery for a mean of 7.3 years (5.2‐10.7 years). At the last follow‐up, no significant difference was found in knee ROM, functional scores, and patient‐reported outcomes between patients older or younger than 40; acute and delayed reconstruction (p > 0.05). The rate of complications in the delayed reconstruction group was higher than that of the acute reconstruction group (22.2% vs 5.3%, p

Forming at cryogenic temperatures provides a new approach to the formability improvement of 7000-series high-strength aluminum alloys. However, the cryogenic forming process based on solution-treated (W) or peak artificial aged (T6) alloys cannot meet the demands of autobody manufacturing for good formability, high post-formed strength and high efficiency simultaneously. The fast retrogression (FR) treatment of AA7075-T6 and pre-aging (PA) treatment of AA7075-W are elaborately designed to tailor a pre-hardened AA7075 alloy, which has good cryogenic formability and relatively high initial strength, and can be further strengthened by paint baking in high efficiency. The results show the optimum fast retrogression temperature for AA7075-FR is 400 °C, at which the sample can acquire a cryogenic elongation of 29.2% and obtain 90% of initial T6 sheet tensile strength by the combined effect of cryogenic pre-deformation and subsequent paint baking treatment. The optimum pre-aging temperature for AA7075-PA is 120 °C, at which the sample can acquire a cryogenic elongation of 31.0% and exceed 96% of tensile strength of AA7075-T6 after paint baking treatment. The comparative study demonstrates that the supersaturated solid solution matrix with an appropriate proportion of GP zones and η′ phases, but few Cr-containing dispersoids and precipitate free zones, is an ideal pre-hardened microstructure to get a good combination of cryogenic formability and final strength. The precipitation of GP zones and η′ phases is prior to the formation of precipitate free zones during pre-aging of AA7075-W, making the pre-aged hardening cryogenic forming process more suitable for automobile industry.

Abstract The mammalian SWI/SNF-like BAF complexes play critical roles during animal development and pathological conditions. Previous gene deletion studies and characterization of human gene mutations implicate that the complexes both repress and activate a large number of genes. However, the direct function of the complexes in cells remains largely unclear due to the relatively long-term nature of gene deletion or natural mutation. Here we generate a mouse line by knocking in the auxin-inducible degron tag (AID) to the Smarca4 gene, which encodes BRG1, the essential ATPase subunit of the BAF complexes. We show that the tagged BRG1 can be efficiently depleted by osTIR1 expression and auxin treatment for 6 to 10 h in CD4 + T cells, hepatocytes, and fibroblasts isolated from the knock-in mice. The acute depletion of BRG1 leads to decreases in nascent RNAs and RNA polymerase II binding at a large number of genes, which are positively correlated with the loss of BRG1. Further, these changes are correlated with diminished accessibility at DNase I Hypersensitive Sites (DHSs) and p300 binding. The acute BRG1 depletion results in three major patterns of nucleosome shifts leading to narrower nucleosome spacing surrounding transcription factor motifs and at enhancers and transcription start sites (TSSs), which are correlated with loss of BRG1, decreased chromatin accessibility and decreased nascent RNAs. Acute depletion of BRG1 severely compromises the Trichostatin A (TSA) -induced histone acetylation, suggesting a substantial interplay between the chromatin remodeling activity of BRG1 and histone acetylation. Our data suggest BRG1 mainly plays a direct positive role in chromatin accessibility, RNAPII binding, and nascent RNA production by regulating nucleosome positioning and facilitating transcription factor binding to their target sites.

Abstract Objective Melanoma, with its high degree of malignancy, stands as one of the most dangerous skin cancers and remains the primary cause of death from skin cancer. With studies demonstrating the potential of traditional Chinese medicine to intervene and treat melanoma, we turned our attention to celastrol. Celastrol is a triterpene compound extracted from the traditional Chinese medicine derived from Tripterygium wilfordii. Previous studies have shown that celastrol exerts inhibitory effects on various malignant tumors, including melanoma. Hence, our goal was to clarify the impact of celastrol on cell viability, apoptosis, and cell cycle progression by elucidating its effects on the PI3K/AKT/mTOR pathway. Methods CCK-8 and wound healing assays were used to determine the effect of celastrol on the viability and migration of B16-F10 cells. Changes in cell apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were detected by flow cytometry. PI3K/AKT/mTOR pathway proteins and HIF-α mRNA expression in B16-F10 cells were detected by western blotting and qPCR. Moreover, the addition of a PI3K activator demonstrated that celastrol could inhibit the function of B16-F10 cells via the PI3K/AKT/mTOR pathway. Results Celastrol inhibited the viability and migration of B16-F10 cells. Through the inhibition of the PI3K/AKT/mTOR pathway down-regulates the expression of HIF-α mRNA, thereby causing an increase of ROS in cells and a decrease in the mitochondrial membrane potential to promote cell apoptosis and cell cycle arrest. The inhibitory effect of celastrol on B16-F10 cells was further demonstrated by co-culturing with a PI3K activator. Conclusion Celastrol inhibits the function of B16-F10 cells by inhibiting the PI3K/AKT/mTOR cellular pathway and regulating the expression of downstream HIF-α mRNA.

Abstract We use families of circular null geodesics as probes of a family of microstate geometries, known as (1, 0, n) superstrata. These geometries carry a left-moving momentum wave and the behavior of some of the geodesic probes is very sensitive to this background wave. The left-moving geodesics behave like BPS particles and so can be placed in circular orbits anywhere in the geometry and actually “float” at fixed radius and angle in the three-dimensional “capped BTZ” geometry. The right-moving geodesics behave like non-BPS particles. We show that they provide a simple geometric characterization of the black-hole bound: when the momentum charge of the geometry is below this bound, such geodesics can be placed anywhere, but exceeding the bound, even by a small amount, means these geodesics are restricted to the deep interior of the geometry. We also show that for left-moving string probes, the tidal forces remain comparable with those of global AdS3. Nevertheless, for some of these probes, the “bumps” in the geometry induce an oscillatory mass term and we discuss how this can lead to chaotic scrambling of the state of the string.

Abstract Atmospheric rivers (ARs) are narrow, elongated, synoptic jets of water vapor that play important roles in the global water cycle. The continually developing Tracking Atmospheric Rivers Globally as Elongated Targets (tARget) algorithm identifies AR objects at individual time steps based on thresholding integrated water vapor transport (IVT) and other requirements, and tracks each AR object in time and space. Building on previous versions of tARget, this paper discusses further refinements to the algorithm to better handle ARs in tropical and polar areas, as well as “zonal” ARs which the previous versions of the algorithm were not designed to capture. This further regionally refined algorithm is applied to the ERA5 reanalysis over 1940–2023 at 6 h intervals and a 0.25° × 0.25° horizontal resolution. The AR detection results are evaluated in terms of key AR characteristics. We anticipate this regionally refined global AR database will aid further understanding of ARs such as AR process studies, evaluation of AR simulations and predictions, and assessment of climate change impacts on ARs.

Although different damage-coupled physically based models have been proposed, those damage models are established based on the isothermal uniaxial or multi-axial tensile condition. However, the influence of the stress state on ductile failure strain is not adequately considered in the thermal damage models. It is widely recognized that the stress state has significant effect on damage evolution and ductility fracture for metallic materials. Actually, the current damage-coupled physically based models are not suitable for complex hot forming and the applications of these damage-coupled models are mainly focused on sheet hot stamping forming to date. Therefore, a modified damage-coupled unified model considering a broad range of stress states was established to figure out the complex damage behavior and microstructure evolution of metallic materials during the thermal deformation process. In this study, the Mg-6Gd-5Y-0.3Zr alloy was used as the experimental material. First, the flow behavior of the alloy was explored using a series of experiments under various stress states (i.e., uniaxial tensile, shear and compression) under various combinations of strain rates and temperatures. On this basis, a modified damage-coupled physics-based model was developed, in which the dynamic recrystallization, damage, stress triaxiality and Lode parameter were included as internal state variables. Furthermore, the model was integrated into ABAQUS to verify the applicability using hot spinnability test because the stress state was very complex during the forming process. The comparison between the calculated results and experiments is carried out. According to the simulation result, the predicted ultimate thinning rate is 71.14%, with an error of only 7.85% from the experimentally measured ultimate thinning rate of 77.2%, and the correlation coefficient and error for thickness and profile between the predicted values and experimental values are 0.9980 and 5.05%, respectively. These demonstrate that the developed model is reliable.