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Abstract O6-methylguanine-DNA methyltransferase (MGMT) has been demonstrated to be an important prognostic and predictive marker in glioblastoma (GBM). To establish a reliable radiomics model based on MRI data to predict the MGMT promoter methylation status of GBM. A total of 183 patients with glioblastoma were included in this retrospective study. The visually accessible Rembrandt images (VASARI) features were extracted for each patient, and a total of 14676 multi-region features were extracted from enhanced, necrotic, “non-enhanced, and edematous” areas on their multiparametric MRI. Twelve individual radiomics models were constructed based on the radiomics features from different subregions and different sequences. Four single-sequence models, three single-region models and the combined radiomics model combining all individual models were constructed. Finally, the predictive performance of adding clinical factors and VASARI characteristics was evaluated. The ComRad model combining all individual radiomics models exhibited the best performance in test set 1 and test set 2, with the area under the receiver operating characteristic curve (AUC) of 0.839 (0.709–0.963) and 0.739 (0.581–0.897), respectively. The results indicated that the radiomics model combining multi-region and multi-parametric MRI features has exhibited promising performance in predicting MGMT methylation status in GBM. The Modeling scheme that combining all individual radiomics models showed best performance among all constructed moels.

This study investigates the utilization of serious games in rural public building design and their impact on residents’ contentment with building renovations. It highlights serious games’ role as an interactive medium for education, training, and communication, specifically in enhancing residents’ approval of rural public building designs. Employing the concept of diegesis from narratology, the study develops a structural equation modelling (SEM) by dividing games into intra-diegetic and extra-diegetic components. This model examines the influence of Game Participation (GP) and Learning Participation (LP) in serious games on satisfaction with updated building designs, as well as the direct and indirect impacts of various factors on these dynamics. The research methodology encompassed creating and applying a serious game focused on architectural design, accompanied by thorough quantitative analysis of the gaming process and results. The study tested multiple hypotheses regarding the positive impacts of game interactivity, perceived creativity, immersive experiences, game quality, atmosphere, and environment on GP and LP. Notably, the beneficial effect of game engagement on learning engagement and the significant positive influence of GP and LP on design satisfaction underscore the potential of serious games in improving educational outcomes and satisfaction with building renovations. Additionally, enjoyment was identified as having a substantial positive moderating effect on the relationships between GP and Design Satisfaction (DS) and between LP and DS, underscoring the importance of enhancing the appeal and engagement of serious games in their design. Additionally, as the game advanced, participants increasingly aligned their opinions on various design aspects, particularly emphasizing the importance of integrating natural landscapes as a key environmental consideration in community redevelopment.

Abstract Although the chloroplast genome (cpDNA) of higher plants is known to exist as a large protein-DNA complex called ‘plastid nucleoid’, researches on its DNA state and regulatory elements are limited. In this study, we performed the assay for transposase-accessible chromatin sequencing (ATAC-seq) on five common tissues across five grasses, and found that the accessibility of different regions in cpDNA varied widely, with the transcribed regions being highly accessible and accessibility patterns around gene start and end sites varying depending on the level of gene expression. Further analysis identified a total of 3970 putative protein binding footprints on cpDNAs of five grasses. These footprints were enriched in intergenic regions and co-localized with known functional elements. Footprints and their flanking accessibility varied dynamically among tissues. Cross-species analysis showed that footprints in coding regions tended to overlap non-degenerate sites and contain a high proportion of highly conserved sites, indicating that they are subject to evolutionary constraints. Taken together, our results suggest that the accessibility of cpDNA has biological implications and provide new insights into the transcriptional regulation of chloroplasts.

Abstract Kidney renal clear cell carcinoma (KIRC) is the most common histological type of renal cancer, enhancer RNA plays a significant role in tumor growth, however, it has been less studied in renal cancer. The aim of this study was to investigate the role of eRNA AC003092.1 in KIRC. Clinical and RNA expression data were downloaded from a TCGA database, and performed bioinformatics analysis, including expression level analysis, survival analysis, clinical correlation analysis, immune correlation analysis. We further confirmed the expression level of AC003092.1 between normal and tumor cell, predicted the biological role of AC003092.1 in KIRC, and performed cell proliferation and wound healing assays, followed by GSEA enrichment analysis and western blot to detect the proteins of the enriched pathway. Bioinformatics results showed that AC003092.1 expression was elevated in tumor tissues, and knockdown of AC003092.1 expression inhibited cell proliferation and migration. GSEA and western blot results showed that knockdown AC003092.1 expression alleviated the extracellular matrix (ECM) process in KIRC cell lines. Our study provides evidence that AC003092.1 play an important role in KIRC, and AC003092.1 may promote tumor cell progression by affecting the ECM process during tumor development.

Abstract In recent years, contrastive language‐image pre‐training (CLIP) has gained popularity for processing 2D data. However, the application of cross‐modal transferable learning to 3D data remains a relatively unexplored area. In addition, high‐quality, labelled point cloud data for Mechanical, Electrical, and Plumbing (MEP) scenarios are in short supply. To address this issue, the authors introduce a novel object detection system that employs 3D point clouds and 2D camera images, as well as text descriptions as input, using image‐text matching knowledge to guide dense detection models for 3D point clouds in MEP environments. Specifically, the authors put forth the proposition of a language‐guided point cloud modelling (PCM) module, which leverages the shared image weights inherent in the CLIP backbone. This is done with the aim of generating pertinent category information for the target, thereby augmenting the efficacy of 3D point cloud target detection. After sufficient experiments, the proposed point cloud detection system with the PCM module is proven to have a comparable performance with current state‐of‐the‐art networks. The approach has 5.64% and 2.9% improvement in KITTI and SUN‐RGBD, respectively. In addition, the same good detection results are obtained in their proposed MEP scene dataset.

Abstract The Patient-Reported Outcomes Measurement Information System 29-item Profile version 2.1 (PROMIS-29 V2.1) is a widely utilized self-reported instrument for assessing health outcomes from the patients’ perspectives. This study aimed to evaluate the psychometric properties of the PROMIS-29 V2.1 Chinese version among patients with hematological malignancy. Conducted as a cross-sectional, this research was approved by the Medical Ethical Committee of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (registration number QTJC2022002-EC-1). We employed convenience sampling to enroll eligible patients with hematological malignancy from four tertiary hospitals in Tianjin, Shandong, Jiangsu, and Anhui province in China between June and August 2023. Participants were asked to complete a socio-demographic information questionnaire, the PROMIS-29 V2.1, and the Functional Assessment of Cancer Therapy-General (FACT-G). We assessed the reliability, ceiling and floor effects, structural, convergent discriminant and criterion validity of the PROMIS-29 V2.1. A total of 354 patients with a mean age of 46.93 years was included in the final analysis. The reliability of the PROMIS-29 V2.1 was affirmed, with Cronbach’s α for the domains ranging from 0.787 to 0.968. Except sleep disturbance, the other six domains had ceiling effects, which were seen on physical function (26.0%), anxiety (37.0%), depression (40.4%), fatigue (18.4%), social roles (18.9%) and pain interference (43.2%), respectively. Criterion validity was supported by significant correlations between the PROMIS-29 V2.1 and FACT-G scores, as determined by the Spearman correlation test (P

Abstract Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm. The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress. Sinensetin (Sin) is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities. Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms. We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells (PDLCs) under inflammatory conditions. Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo. By molecular docking, we identified Bach1 as a strong binding target of Sin, and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays. Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter, subsequently upregulating the expression of the key antioxidant factor HO-1. Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects. Additionally, we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1, thereby inducing HO-1 expression and inhibiting oxidative stress. Overall, Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

Abstract Purpose This study investigated the changes in the fasting blood glucose (FBG), fasting triglyceride (FTG), and fasting total cholesterol (FTC) levels during neoadjuvant therapy (NAT) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and the association with pathologic complete response (pCR). Methods Relevant data from Sichuan Cancer Hospital from June 2019 to June 2022 were collected and analyzed, and FBG, FTG, and FTC were divided into baseline, change, and process groups, which were grouped to analyze the changes after receiving NAT and the association with pCR. Results In the estrogen receptor (ER)-negative subgroup, patients with low levels of FTG in the process group were more likely to achieve pCR compared to high levels, and in the progesterone receptor (PR)-negative subgroup, patients with lower FTG compared to higher FTG after receiving NAT was more likely to achieve pCR. Conclusions Patients with HER2-positive BC undergoing NAT develop varying degrees of abnormalities (elevated or decreased) in FBG, FTG, and FTC; moreover, the status of FTG levels during NAT may predict pCR in ER-negative or PR-negative HER2-positive BC.Early monitoring and timely intervention for FTG abnormalities may enable this subset of patients to increase the likelihood of obtaining a pCR along with management of abnormal markers.

Biochar has demonstrated potential for stabilising high yields and sequestering carbon in dryland farmland, but it is unclear whether biochar affects the carbon sequestration capacity and carbon balance of annual farmland ecosystems. For this purpose, we conducted a plot control trial in salinised farmland in 2019-2021, where we set three treatments, control, and two biochar rates, 0 (CK), 15 (B15), and 30 t/ha (B30). The results showed that biochar application decreased soil organic carbon stocks in the early part of the experiment (first freeze and freeze period); these increased in the later part, and overall, the biochar treatments increased soil organic carbon storage by 3-6% compared with the control. Compared with the control (CK), biochar inhibited the total soil respiration rate and microbial respiration rate significantly (P < 0.05) during the crop growing period compared with the freeze-thaw period. After two years of freeze-thaw cycling, biochar application increased sunflower plant carbon sequestration and net primary productivity and suppressed total soil microbial respiration, thereby increasing net ecosystem productivity. Therefore, the application of biochar is conducive to carbon sequestration in farmland ecosystems and presents a carbon sink effect, thus being a good choice for improving the soil carbon pool and reducing emissions in the northern dry zone.

Abstract Purpose Percutaneous transhepatic one-step biliary fistulation (PTOBF) is used to treat choledocholithiasis and biliary stricture. This study aimed to evaluate the safety and efficacy of ultrasound-guided PTOBF combined with rigid choledochoscopy in the treatment of recurrent hepatolithiasis. Materials and methods The clinical data of 37 consecutive patients who underwent PTOBF combined with rigid choledochoscopy for RHL from March 2020 to March 2022 at our hospital were retrospectively analyzed. Results A total of 68 percutaneous transhepatic punctures were performed in 37 patients, with a puncture success rate of 85.29% (58/68) and a dilatation success rate of 100.00% (58/58). The mean blood loss of operation was 9.84 ± 18.10 mL, the mean operation time was 82.05 ± 31.92 min, and the mean length of postoperative hospital stay was 5.59 ± 3.26 days. The initial stone clearance rate was 40.54% (15/37) and the final stone clearance rate was 100% (37/37). The incidence of postoperative complications was 10.81% (4/37), including 2 cases of pleural effusion, 1 case of hemorrhage, and 1 case of cholangitis, which recovered after treatment. During a mean follow-up period of 23 months (range 12 to 36 months), only 1 patient experienced stone recurrence. Conclusion Ultrasound-guided PTOBF combined with rigid choledochoscopy in the treatment of RHL based on skilful manipulation seems to be a safe, effective and minimally invasive method with clinical application value. Further comparative studies with large sample sizes are needed in the future to confirm the reliability of its therapeutic results.

Abstract Background HBV infection can result in severe liver diseases and is one of the primary causes of liver cell carcinoma-related mortality. Liuwei Wuling tablet (LWWL) is a traditional Chinese medicine formula, with a protecting liver and decreasing enzyme activity, usually used to treat chronic hepatitis B with NAs in clinic. However, its main active ingredients and mechanism of action have not been fully investigated. Hence, we aimed to screen the active ingredient and effective ingredient combinations from Liuwei Wuling tablet to explore the anti-herpatitis B virus activity and mechanism. Methods Analysis and screening of effective antiviral components in LWWL by network pharmacology, luteolin (Lut) may be a compound with significant antiviral activity. The mechanism of antiviral action of Lut was also found by real-time PCR detection and western blotting. Meanwhile, we established a co-culture model to investigate the antiviral mechanism of Schisandrin C (SC), one of the main active components of Schisandra chinensis fructus (the sovereign drug of LWWL). Next, HBV-infected mice were established by tail vein injection of pAAV-HBV1.2 plasmid and administered continuously for 20 days. And their antiviral capacity was evaluated by checking serum levels of HBsAg, HBeAg, levels of HBV DNA, and liver levels of HBcAg. Results In this study, we conducted network pharmacology analysis on LWWL, and through in vitro experimental validation and data analysis, we found that luteolin (Lut) possessed obviously anti-HBV activity, inhibiting HBV replication by downregulating hepatocyte nuclear factor 4α (HNF4α) via the ERK pathway. Additionally, we established a co-culture system and proved that SC promoted activation of cGAS-STINIG pathway and IFN-β production in THP-1 cells to inhibit HBV replication in HepG2.2.15 cells. Moreover, we found the combination of SC and Lut shows a greater effect in inhibiting HBV compared to SC or Lut alone in HBV-infected mice. Conclusion Taken together, our study suggests that combination of SC and Lut may be potential candidate drug for the prevention and treatment of chronic hepatitis B.

A comprehensive understanding of material deformation behavior holds importance in enhancing the properties of materials, which can be achieved through modeling the relationship between microstructure and deformation behavior by an appropriate crystal plasticity (CP) model. However, before simulations, obtaining a high-fidelity representative microstructure (RM) to simultaneously meet the efficiency and accuracy requirements of the CP model is still a challenge. Thus, taking the Al–Al2Cu eutectics as an example, we successfully obtained a high-fidelity RM with two-point statistics and some fashionable image processing techniques. Then a high-resolution RMCP model was developed and the deformation behavior of Al–Al2Cu eutectics at room temperatures was uncovered. Due to multiple activated slip systems on {111} inducing obvious cross-slip behavior, severe and heterogenous plastic deformation occurs in α-Al. And dislocations originate from the microstructure defects. In θ-Al2Cu, all possible slip systems are not activated, resulting in no plastic deformation. The predictions of the RMCP model are verified to be reliable by comparing with the results of in-situ tensile tests. Our proposed RMCP method is not only applicable to the two-phase eutectic systems, but also suitable for various multiphase and polycrystalline systems.

With the rapid development of digital tourism, more and more tourists are embracing this innovative mode of tourism. Digital tourism has attracted a large influx of tourists, which not only promotes the dissemination of local culture, but also promotes tourists’ intention to preserve culture. This study proposes a comprehensive framework authenticity, cultural experience, place attachment, satisfaction, and cultural protection intention, aiming to explore tourists’ cultural protection intention in digital tourism. To validate our framework, we use the Digital Intelligence Niushou as a case study and distributed a questionnaire to tourists, obtaining 408 valid responses. We analyzed the collected data using structural equation modeling (SEM). The results showed that place attachment and the four cultural experiences positively influenced both visitors’ satisfaction and cultural protection intention. Notably, “scientific knowledge” and “personal values” emerged as the biggest influences on cultural protection intention. Among the three types of authenticity, only objective authenticity and constructed authenticity positively influenced tourists’ satisfaction and cultural protection intention. This suggests that faithfully restored historical contexts play a key role in shaping tourists’ experiences and attitudes toward cultural protection in the field of digital tourism. This study provides a solid theoretical foundation for advancing digital tourism and enhancing tourists’ commitment to preserving cultural heritage. Our findings are important for digital tourism platforms to develop more effective optimization strategies, and can help managers to create more attractive, authentic and immersive tourism models to enhance tourist satisfaction and cultivate cultural protection intention.

The metastable-stable transition and rapid coarsening of metastable D022 phase remains its Achilles hell, restricting the application of D022-strengthened alloys at service temperatures higher than 650°C. Hence, it is crucial to improve thermal stability of D022 phase. In this work, we report an 800°C-stable D022-Ni3(W0.24Ti0.38Ta0.19Nb0.19) superlattice in the Ni58Cr23Fe10W5Ti2Ta1Nb1 MEA. Experimental results and theoretical analysis showed that the exceptional thermal stability is due to Nb-sublattice occupying elements, low diffusivity of W, and extremely small lattice misfit between the D022 phase and FCC matrix. These findings shed lights on developing high-performance D022-hardened alloys capable of operating at temperatures above 650°C.

Optical neural networks have significant advantages in terms of power consumption, parallelism, and high computing speed, which has intrigued extensive attention in both academic and engineering communities. It has been considered as one of the powerful tools in promoting the fields of imaging processing and object recognition. However, the existing optical system architecture cannot be reconstructed to the realization of multi-functional artificial intelligence systems simultaneously. To push the development of this issue, we propose the pluggable diffractive neural networks (P-DNN), a general paradigm resorting to the cascaded metasurfaces, which can be applied to recognize various tasks by switching internal plug-ins. As the proof-of-principle, the recognition functions of six types of handwritten digits and six types of fashions are numerical simulated and experimental demonstrated at near-infrared regimes. Encouragingly, the proposed paradigm not only improves the flexibility of the optical neural networks but paves the new route for achieving high-speed, low-power and versatile artificial intelligence systems.

Background: To compare the efficacy of Three-scope combined (laparoscopic, rigid choledochoscopy and electronic choledochoscopy, TS) with laparoscopic hepatectomy (LH) for patients with hepatolithiasis (HL). Methods: Between January 2019 and January 2020, 118 consecutive patients with HL treated with TS (TS group, n = 57) or LH (LH group, n = 61) were analyzed in this study. Perioperative and long-term outcomes, including operative time, intraoperative blood loss, blood transfusion, postoperative bowel function recovery time, postoperative hospital stay, complication rate, stone removal rate, and stone recurrence rate, were compared and analyzed between the two groups. Results: Compared with the LH group, the TS group had significantly lower intraoperative blood loss and transfusions, significantly shorter operative time and hospital stay, and fewer complications (P 0.05 for all). Conclusion: TS is a safe and effective treatment for HL and is superior to LH in terms of overall treatment outcome and complications.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3′-untranslated region (3′ UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

IntroductionTetrandrine (Tet) is the main pharmacological component of Stephania tetrandra S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive properties. Unraveling the specific targets and mechanisms of Tet involved in inducing diuresis and mitigating hypertension can provide valuable insights into its therapeutic effects. This study aimed to explore the diuretic and antihypertensive targets and mechanisms of Tet using chemical biology coupled with activity analyses in vivo and in vitro.MethodsThe diuretic effects of Tet were evaluated using a water-loaded mouse model. The direct target proteins for the diuretic and antihypertensive effects of Tet were determined using chemical biology. Furthermore, the molecular mechanism of Tet binding to target proteins was analyzed using a multidisciplinary approach based on the structure and function of the proteins. Finally, the effects of the Tet-targeted protein on downstream signaling pathways and blood pressure were evaluated in hypertensive model rats.ResultsTet exhibited significant antihypertensive and potassium-preserving diuretic effects. The mechanism underlying these effects involves the modulation of the enzyme activity by covalent binding of Tet to Cys423 of CYP11A1. This interaction alters the stability of heme within CYP11A1, subsequently impeding electron transfer and inhibiting aldosterone biosynthesis.DiscussionThis study not only revealed the mechanism of the diuretic and antihypertensive effects of Tet but also discovered a novel covalent inhibitor of CYP11A1. These findings contribute significantly to our understanding of the therapeutic potential of Tet and provide a foundation for future research in the development of targeted treatments for hypertension.

ABSTRACT The emergence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) has imposed further challenges to the clinical management of MRSA infections. When exposed to β-lactam antibiotics, these strains can easily acquire reduced β-lactam susceptibility through chromosomal mutations, including those in RNA polymerase (RNAP) genes such as rpoBC, which may then lead to treatment failure. Despite the increasing prevalence of such strains and the apparent challenges they pose for diagnosis and treatment, there is limited information available on the actual mechanisms underlying such chromosomal mutation-related transitions to reduced β-lactam susceptibility, as it does not directly associate with the expression of mecA. This study investigated the cellular physiology and metabolism of six missense mutants with reduced oxacillin susceptibility, each carrying respective mutations on RpoBH929P, RpoBQ645H, RpoCG950R, RpoCG498D, RpiAA64E, and FruBA211E, using capillary electrophoresis-mass spectrometry-based metabolomics analysis. Our results showed that rpoBC mutations caused RNAP transcription dysfunction, leading to an intracellular accumulation of ribonucleotides. These mutations also led to the accumulation of UDP-Glc/Gal and UDP-GlcNAc, which are precursors of UTP-associated peptidoglycan and wall teichoic acid. Excessive amounts of building blocks then contributed to the cell wall thickening of mutant strains, as observed in transmission electron microscopy, and ultimately resulted in decreased susceptibility to β-lactam in OS-MRSA.IMPORTANCEThe emergence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) strains has created new challenges for treating MRSA infections. These strains can become resistant to β-lactam antibiotics through chromosomal mutations, including those in the RNA polymerase (RNAP) genes such as rpoBC, leading to treatment failure. This study investigated the mechanisms underlying reduced β-lactam susceptibility in four rpoBC mutants of OS-MRSA. The results showed that rpoBC mutations caused RNAP transcription dysfunction, leading to an intracellular accumulation of ribonucleotides and precursors of peptidoglycan as well as wall teichoic acid. This, in turn, caused thickening of the cell wall and ultimately resulted in decreased susceptibility to β-lactam in OS-MRSA. These findings provide insights into the mechanisms of antibiotic resistance in OS-MRSA and highlight the importance of continued research in developing effective treatments to combat antibiotic resistance.

We previously demonstrated that baicalin had efficacy against gouty arthritis (GA) by oral administration. In this paper, a novel baicalin-loaded microemulsion-based gel (B-MEG) was prepared and assessed for the transdermal delivery of baicalin against GA. The preparation method and transdermal capability of B-MEG was screened and optimized using the central composite design, Franz diffusion cell experiments, and the split-split plot design. Skin irritation tests were performed in guinea pigs. The anti-gout effects were evaluated using mice. The optimized B-MEG comprised of 50 % pH 7.4 phosphate buffered saline, 4.48 % ethyl oleate, 31.64 % tween 80, 13.88 % glycerin, 2 % borneol, 0.5 % clove oil and 0.5 % xanthan gum, with a baicalin content of (10.42 ± 0.08) mg/g and particle size of (15.71 ± 0.41) nm. After 12 h, the cumulative amount of baicalin permeated from B-MEG was (672.14 ± 44.11) μg·cm−2. No significant skin irritation was observed following B-MEG application. Compared to the model group, B-MEG groups significantly decreased the rate of auricular swelling (P

Abstract In recent years, numerous efforts have been devoted to exploring innovative micro/nano‐optical devices (MNODs) with reconfigurable functionality, which is highly significant because of the progressively increasing requirements for next‐generation photonic systems. Fortunately, phase change materials (PCMs) provide an extremely competitive pathway to achieve this goal. The phase transitions induce significant changes to materials in optical, electrical properties or shapes, triggering great research interests in applying PCMs to reconfigurable micro/nano‐optical devices (RMNODs). More specifically, the PCMs‐based RMNODs can interact with incident light in on‐demand or adaptive manners and thus realize unique functions. In this review, RMNODs based on phase transitions are systematically summarized and comprehensively overviewed from materials, phase change mechanisms to applications. The reconfigurable optical devices consisting of three kinds of typical PCMs are emphatically introduced, including chalcogenides, transition metal oxides, and shape memory alloys, highlighting the reversible state switch and dramatic contrast of optical responses along with designated utilities generated by phase transition. Finally, a comprehensive summary of the whole content is given, discussing the challenge and outlooking the potential development of the PCMs‐based RMNODs in the future.

In order to solve the problem of limited driving speed of piezoelectric actuators when the piezoelectric components are small and the driving frequency is low. This paper proposes a bi-directional piezoelectric stick-slip actuator, which mainly utilizes the combination of flexible drive foot and lever amplification mechanism to realize the displacement amplification function, thus improving the driving performance. Firstly describe the structure and working principle of the proposed actuator, and carries out theoretical analysis and mathematical modeling of the flexible stator. Then the driving process of the proposed actuator is simulated and analyzed with COMSOL Multiphysics simulation software, and the feasibility of the driver structure is preliminarily verified. Finally, establish an experimental system to test the basic characteristics of the prototype. The experimental results confirm that under the piezoelectric stacks elongation of $5\mu $ m, the driving frequency of 610Hz, the maximum drive speed of the actuator is 11.21mm/s. The maximum load capacity is 0.78N and the forward and backward displacement deviation within 10 cycles is $0.99\mu $ m under the locking displacement of $10\mu $ m. The proposed stick-slip actuator is capable of realizing a large driving speed when the elongations of the piezoelectric stacks are small and the driving frequency is low.

The InP high-electron-mobility transistor (HEMT) is employed in cryogenic low-noise amplifiers (LNAs) for the readout of faint microwave signals in quantum computing. The performance of such LNAs is ultimately limited by the properties of the active $\mathrm {In_{x}Ga_{1-x}As}$ channel in the InP HEMT. In this study, we have investigated the noise performance of 100-nm gate-length InP HEMTs used in cryogenic LNAs for amplification of qubits. The channel indium content in the InP HEMTs was 53, 60 and 70%. Hall measurements of the epitaxial materials and dc characterization of the InP HEMTs confirmed the superior transport properties of the channel structures. An indirect method involving an LNA and small-signal noise modeling was used for extracting the channel noise with high accuracy. Under noise-optimized bias, we observed that the 60% indium channel InP HEMT exhibited the lowest drain noise temperature. The difference in LNA noise temperature among InP HEMTs became more pronounced with decreasing drain voltage and current. An average noise temperature and average gain of 3.3 K and 21 dB, respectively, for a 4–8 GHz three-stage hybrid cryogenic LNA using 60% indium channel InP HEMTs was measured at a dc power consumption of $108 ~\mu \text{W}$ . To the best of the authors’ knowledge, this is a new state-of-the-art for a C-band LNA operating below 1 mW. The higher drain noise temperature observed for 53 and 70% indium channels InP HEMTs can be attributed to a combination of thermal noise in the channel and real-space transfer of electrons from the channel to the barrier. This report gives experimental evidence of an optimum channel indium content in the InP HEMT used in LNAs for qubit amplification.

Accurate water extraction from urban remote sensing images holds great significance in assisting the formulation of river and lake management policies and ensuring the sustainable development of urban water resources. However, urban high-resolution remote sensing images encompass complex spatial and semantic information, which leads to disparities between the extracted water body features based on local and global information, consequently affecting the accuracy of urban water extraction. To tackle this issue, an attention-based encoder–decoder network was proposed. In this network, the backbone employing atrous convolution (AC) facilitated the acquisition of low-level and high-level features of urban remote sensing images at various scales. Integrated with the attention mechanism, the encoder–decoder structure extracted global features in both the spatial and channel domains. Subsequently, these two types of features were merged to yield the urban water segmentation. Moreover, considering both intersection over union and class weights, a joint loss function (JLF) was introduced to further enhance the accuracy of urban water extraction. Experimental results demonstrated the strong performance of the proposed method on both GID and LoveDA datasets.

Dynamic α precipitation with hot deformation is commonly adopted to obtain equiaxed α for tailoring the mechanical properties of Ti alloys. The formation of an equiaxed shape rather than the typically observed α plate is closely correlated with the variations in nucleation rate and elastic strain energy induced by the external stress. However, it is still unclear how these changes result in the morphology transition of α precipitate. In this study, a multiphase-field and crystal plasticity integrated model was proposed to describe the coevolution of dynamic α precipitation and plastic deformation. It was found that the plasticity relaxes the elastic strain energy, retards lengthening but promotes the thickening of α precipitate. The elastic interaction between the applied stress and eigenstrain increases the elastic strain energy, promotes lengthening but has a weak effect on the thickening of α precipitate. The competition of these two factors determines the shape of α precipitates. In the case of a small nucleation rate, the promotion effect of the elastic interaction on lengthening of α precipitate always exceeds the retardation effect of plasticity, resulting in the formation of plate-like α. Increasing the nucleation rate under the same magnitude of external stress can induce a larger plastic strain within the soft β matrix in the initial growth stage, which results in the competitive advantage of the retardation effect of plasticity. Therefore, the lengthening of α precipitate decreases to a similar extent as its thickening, and the precipitate morphology changes into an equiaxed shape.

Abstract Biliverdin, a heme metabolite, has been previously reported to alleviate cerebral ischemic reperfusion injury (CIRI). However, the alterations of brain proteome profiles underlying this treatment remain elusive. The objective of this study is to analyze the differential protein expression profile in cerebral cortex of rats involved in anti-CIRI effects of Biliverdin, providing experimental foundation for searching specific marker proteins. Rat model of MCAO/R was established, HE staining, TTC staining, TUNEL staining, and neurological behavioral examination, corner turning test, adhesive removal test, were performed to validate the effects of Biliverdin, and the results indicated that Biliverdin plays a significant role in alleviating CIRI. Furthermore, proteomic analysis of brain tissues of rats subjected to CIRI following Biliverdin treatment was performed using an integrated TMT-based quantitative proteomic approach coupled with LC-MS/MS technology to clarify the comprehensive mechanisms of Biliverdin in CIRI. First, we conducted strict quality control data for TMT experiments. Finally, a total of 7366 proteins were identified, of which 95 proteins were differentially expressed (DEPs) between the CIRI group and the Sham group and 52 between the CIRI and BV groups. In addition, two overlapping proteins among the 147 DEPs, Atg4c and Camlg, were validated by RT-qPCR and western blotting, and their levels were consistent with the results of TMT analysis. Taken together, the current findings firstly mapped comprehensive proteomic changes after CIRI treated with Biliverdin, providing a foundation for developing potentially therapeutic targets of anti-CIRI of Biliverdin and clinically prognostic biomarkers of stroke.

Summary: Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II–III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3–67.6) and 41 of 70 (58.6%, 95% CI 46.2–70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1–2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

Underwater image super-resolution is vital for enhancing the clarity and detail of underwater imagery, enabling improved analysis, navigation, and exploration in underwater environments where visual quality is typically degraded due to factors like water turbidity and light attenuation. In this paper, we propose an effective hybrid dynamic Transformer (called HDT-Net) for underwater image super-resolution, leveraging a collaborative exploration of both local and global information aggregation to help image restoration. Firstly, we introduce a dynamic local self-attention to adaptively capture important spatial details in degraded underwater images by employing dynamic weighting. Secondly, considering that visual transformers tend to introduce irrelevant information when modeling the global context, thereby interfering with the reconstruction of high-resolution images, we design a sparse non-local self-attention to more accurately compute self-similarity by setting a top-k threshold. Finally, we integrate these two self-attention mechanisms into the hybrid dynamic transformer module, constituting the primary feature extraction unit of our proposed method. Quantitative and qualitative analyses on benchmark datasets demonstrate that our approach achieves superior performance compared to previous CNN and Transformer models.

Adverse weather conditions such as rain and haze often lead to a degradation in the quality of maritime images, which is crucial for activities like navigation, fishing, and search and rescue. Therefore, it is of great interest to develop an effective algorithm to recover high-quality maritime images under adverse weather conditions. This paper proposes a prompt-based learning method with degradation perception for maritime image restoration, which contains two key components: a restoration module and a prompting module. The former is employed for image restoration, whereas the latter encodes weather-related degradation-specific information to modulate the restoration module, enhancing the recovery process for improved results. Inspired by the recent trend of prompt learning in artificial intelligence, this paper adopts soft-prompt technology to generate learnable visual prompt parameters for better perceiving the degradation-conditioned cues. Extensive experimental results on several benchmarks show that our approach achieves superior restoration performance in maritime image dehazing and deraining tasks.

Objective: This article aims to identify genetic features associated with immune cell infiltration in cerebral ischemia-reperfusion injury (CIRI) development through bioinformatics, with the goal of discovering diagnostic biomarkers and potential therapeutic targets. Methods: We obtained two datasets from the Gene Expression Omnibus (GEO) database to identify immune-related differentially expressed genes (IRDEGs). These genes' functions were analyzed via Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Tools such as CIBERSORT and ssGSEA assessed immune cell infiltration. The Starbase and miRDB databases predicted miRNAs interacting with hub genes, and Cytoscape software mapped mRNA-miRNA interaction networks. The ENCORI database was employed to predict RNA binding proteins interacting with hub genes. Key genes were identified using a random forest algorithm and constructing a Support Vector Machine (SVM) model. LASSO regression analysis constructed a diagnostic model for hub genes to determine their diagnostic value, and PCR analysis validated their expression in cerebral ischemia-reperfusion. Results: We identified 10 IRDEGs (C1qa, Ccl4, Cd74, Cd8a, Cxcl10, Gmfg, Grp, Lgals3bp, Timp1, Vim). The random forest algorithm, and SVM model intersection revealed three key genes (Ccl4, Gmfg, C1qa) as diagnostic biomarkers for CIRI. LASSO regression analysis, further refined this to two key genes (Ccl4 and C1qa), With ROC curve, analysis confirming their diagnostic efficacy (C1qa AUC = 0.75, Ccl4 AUC = 0.939). PCR analysis corroborated these findings. Conclusions: Our study elucidates immune and metabolic response mechanisms in CIRI, identifying two immune-related genes as key biomarkers and potential therapeutic targets in response to cerebral ischemia-reperfusion injury.

Abstract Applications of lithium–sulfur (Li–S) batteries are still limited by the sluggish conversion kinetics from polysulfide to Li2S. Although various single‐atom catalysts are available for improving the conversion kinetics, the sulfur redox kinetics for Li–S batteries is still not ultrafast. Herein, in this work, a catalyst with dual‐single‐atom Pt‐Co embedded in N‐doped carbon nanotubes (Pt&Co@NCNT) was proposed by the atomic layer deposition method to suppress the shuttle effect and synergistically improve the interconversion kinetics from polysulfides to Li2S. The X‐ray absorption near edge curves indicated the reversible conversion of Li2Sx on the S/Pt&Co@NCNT electrode. Meanwhile, density functional theory demonstrated that the Pt&Co@NCNT promoted the free energy of the phase transition of sulfur species and reduced the oxidative decomposition energy of Li2S. As a result, the batteries assembled with S/Pt&Co@NCNT electrodes exhibited a high capacity retention of 80% at 100 cycles at a current density of 1.3 mA cm−2 (S loading: 2.5 mg cm−2). More importantly, an excellent rate performance was achieved with a high capacity of 822.1 mAh g−1 at a high current density of 12.7 mA cm−2. This work opens a new direction to boost the sulfur redox kinetics for ultrafast Li–S batteries.

Background: This randomized and controlled prospective study tested the hypothesis that closed-loop Target-Controlled Infusion (TCI) of propofol would be associated with better system performance when compared with open-loop controlled delivery of propofol. Methods: Patients scheduled for elective breast surgery were randomly assigned to two groups: a closed-loop group, in which propofol infusion was performed by a closed-loop TCI system that used the Bispectral Index (BIS) as a feedback parameter to titrate the rate of propofol infusion, and an open-loop group, in which propofol infusion was performed manually and guided by the bispectral index. Results: A total of 156 patients were recruited for this study (closed-loop group n = 79; open-loop group n = 77). The Global Score (GS) of the closed-loop group was lower than that of the open-loop group (34.3 and 42.2) (p = 0.044). The proportions of time with a BIS value between 40 and 60 were almost identical in the closed-loop group and the open-loop group (68.7 ± 10.6% and 66.7 ± 13.3%) (p = 0.318). The individuals in the closed-loop group consumed more propofol compared with those in the open-loop group (7.20 ± 1.65 mg.kg−1.h−1 vs. 6.03 ± 1.31 mg.kg−1.h−1, p < 0.001). No intraoperative recall, somatic events or adverse events occurred. No significant difference in heart rate was observed between the two groups (p = 0.169). Conclusion: The closed-loop protocol was associated with lower BIS variability and lower out-of-range BIS values, at the cost of a greater consumption of propofol when compared to the open loop group. Register number: ChiCTR-INR-17010399.

Objective: Anti-inflammatory and anti-apoptotic therapy is expected to become the focus for attenuating cerebral ischemia‒reperfusion injury (CIRI), but the underlying mechanism needs to be further elucidated. Zc3h12d has been reported to downregulate NF-κB signaling pathway. Nevertheless, no studies have been conducted to investigate whether Zc3h12d is associated with the development of CIRI. The aim of this study was to investigate whether Zc3h12d can ameliorate CIRI and the underlying mechanism. Methods: MCAO/R and OGD/R were performed to mimic CIRI in vitro and in vivo, respectively. The expression levels of Zc3h12d, proinflammatory cytokines, proapoptotic protein, and p-p65 were detected by RT‒qPCR, ELISA or Western blotting assays. Immunofluorescence staining was used to detect the spatial distribution of Zc3h12d and the expression of p-p65 in the nucleus. Apoptotic analyses were performed by TUNEL staining, Nissl staining and flow cytometry. Cell viability was assessed using the CCK-8 assay. Results: CIRI increased Zc3h12d expression and neuronal apoptosis in the brain. Zc3h12d was predominantly located in neurons in the cortex. Overexpression of Zc3h12d can inhibit inflammation and suppress neuronal apoptosis in cells after CIRI. Furthermore, overexpression of Zc3h12d decreased the expression of p-p65 in the nucleus, which was attenuated by TNF-α, a common NF-κB agonist. In addition, overexpression of Zc3h12d can also shorten the half-life of proinflammatory cytokines. Conclusion: Zc3h12d may play a crucial role in inhibiting inflammation and apoptosis after CIRI, and the underlying mechanism may be related to repressing the activation of NF-κB signaling. Targeting Zc3h12d may be a novel strategy for preventing CIRI.

Abstract With advances in tissue engineering and bioelectronics, flexible electronic hydrogels that allow conformal tissue integration, online precision diagnosis, and simultaneous tissue regeneration are expected to be the next-generation platform for the treatment of myocardial infarction. Here, we report a functionalized polyaniline-based chronological adhesive hydrogel patch (CAHP) that achieves spatiotemporally selective and conformal embedded integration with a moist and dynamic epicardium surface. Significantly, CAHP has high adhesion toughness, rapid self-healing ability, and enhanced electrochemical performance, facilitating sensitive sensing of cardiac mechanophysiology-mediated microdeformations and simultaneous improvement of myocardial fibrosis-induced electrophysiology. As a result, the flexible CAHP platform monitors diastolic-systolic amplitude and rhythm in the infarcted myocardium online while effectively inhibiting ventricular remodeling, promoting vascular regeneration, and improving electrophysiological function through electrocoupling therapy. Therefore, this diagnostic and therapeutic integration provides a promising monitorable treatment protocol for cardiac disease.

Introduction: This study investigated the differences in efficacy between IHC(2+)/FISH-positive and IHC(3+) in HER2-positive breast cancer (BC) during neoadjuvant chemotherapy (NAC) combined with trastuzumab and pertuzumab. The research also aimed to provide insight into treatment strategies for clinical HER2(2+)/FISH-positive and HER2(3+) BC. Materials and methods: A retrospective analysis was performed on the clinical and pathological data of patients with confirmed diagnoses of invasive BC treated via combined NAC and dual-target therapy who underwent surgery at the Breast Surgery Center of Sichuan Cancer Hospital between June 2019 and June 2022. The correlation between the clinicopathological characteristics and pathological complete response (pCR) was analyzed via the χ2 test, while logistic regression was performed using the SAS 9.4 statistical analysis software. Results: This study examined 224 patients with an overall pCR rate of approximately 59.82%, which included 36 IHC(2+)/FISH-positive and 188 IHC(3+) cases with approximate pCR rates of 41.67% and 63.30%, respectively. Univariate and multifactorial analysis of the clinical and pathological data determined that age, menstrual status, family history, Ki67 expression, number of treatment cycles, and treatment regimen did not influence pCR. No statistical differences were evident between the univariate and multivariate models. However, the clinical stage, hormone receptor, and HER2 expression status significantly impacted pCR, with considerable consistent differences between the univariate and multifactor analyses. Conclusions: HER2 IHC(3+) BC displays a higher pCR rate than HER2 IHC(2+)/FISH-positive BC (p ≤ 0.05), with a positive correlation between the HER2 protein expression levels and the response to anti-HER2 therapy.

The role of cuproptosis, a newly discovered form of programmed cell death, remains poorly understood in hepatocellular carcinoma (HCC). This study was aimed at constructing a novel cuproptosis model for analyzing the clinical features, mutation characteristics and immune profile of HCC associated with cuproptosis-related genes (CRG), and to analyze the prognostic value of CRGs in HCC. We comprehensively evaluated HCC datasets containing clinicopathological information from The Cancer Genome Atlas and GEO, on the basis of 19 CRGs. The prognostic value of the cuproptosis-related risk score was established. Our results revealed two clusters associated with cuproptosis. Cluster B exhibited pronounced isolated innate immune cell infiltration and poor prognosis, and significant differences in prognosis and immune infiltration were observed between the groups with high and low cuproptosis risk. High copper mortality risk scores were associated with an elevated tumor mutational burden (TMB) and poor prognosis. Our findings suggest that evaluating copper-death subtypes provides insights into CRGs. Moreover, the copper mortality risk score model aids in characterizing prognosis and immune infiltration independently of the TMB.

In material science and engineering, obtaining a spectrum from a measurement is often time-consuming and its accurate prediction using data mining can also be difficult. In this work, we propose a machine learning strategy based on a deep neural network model to accurately predict the dielectric temperature spectrum for a typical multi-component ferroelectric system, i.e., (Ba1−x−yCaxSry)(Ti1−u−v−wZruSnvHfw)O3. The deep neural network model uses physical features as inputs and directly outputs the full spectrum, in addition to yielding the octahedral factor, Matyonov–Batsanov electronegativity, ratio of valence electron to nuclear charge, and core electron distance (Schubert) as four key descriptors. Owing to the physically meaningful features, our model exhibits better performance and generalization ability in the broader composition space of BaTiO3-based solid solutions. And the prediction accuracy is superior to traditional machine learning models that predict dielectric permittivity values at each temperature. Furthermore, the transition temperature and the degree of dispersion of the ferroelectric phase transition are easily extracted from the predicted spectra to provide richer physical information. The prediction is also experimentally validated by typical samples of (Ba0.85Ca0.15)(Ti0.98–xZrxHf0.02)O3. This work provides insights for accelerating spectra predictions and extracting ferroelectric phase transition information.

Abstract Background The Inonotus obliquus mushroom, a wondrous fungus boasting edible and medicinal qualities, has been widely used as a folk medicine and shown to have many potential pharmacological secondary metabolites. The purpose of this study was to supply a global landscape of genome-based integrated omic analysis of the fungus under lab-growth conditions. Results This study presented a genome with high accuracy and completeness using the Pacbio Sequel II third-generation sequencing method. The de novo assembled fungal genome was 36.13 Mb, and contained 8352 predicted protein-coding genes, of which 365 carbohydrate-active enzyme (CAZyme)-coding genes and 19 biosynthetic gene clusters (BCGs) for secondary metabolites were identified. Comparative transcriptomic and proteomic analysis revealed a global view of differential metabolic change between seed and fermentation culture, and demonstrated positive correlations between transcription and expression levels of 157 differentially expressed genes involved in the metabolism of amino acids, fatty acids, secondary metabolites, antioxidant and immune responses. Facilitated by the widely targeted metabolomic approach, a total of 307 secondary substances were identified and quantified, with a significant increase in the production of antioxidant polyphenols. Conclusion This study provided the comprehensive analysis of the fungus Inonotus obliquus, and supplied fundamental information for further screening of promising target metabolites and exploring the link between the genome and metabolites.

Abstract Neuronal iron overload contributes to synaptic damage and neuropsychiatric disorders. However, the molecular mechanisms underlying iron deposition in depression remain largely unexplored. Our study aims to investigate how nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) ameliorates hippocampal synaptic dysfunction and reduces brain functional connectivity (FC) associated with excessive iron in depression. We treated mice with chronic unpredictable mild stress (CUMS) with the iron chelator deferoxamine mesylate (DFOM) and a high-iron diet (2.5% carbonyl iron) to examine the role of iron overload in synaptic plasticity. The involvement of Nrf2 in iron metabolism and brain function was assessed using molecular biological techniques and in vivo resting-state functional magnetic resonance imaging (rs-fMRI) through genetic deletion or pharmacologic activation of Nrf2. The results demonstrated a significant correlation between elevated serum iron levels and impaired hippocampal functional connectivity (FC), which contributed to the development of depression-induced CUMS. Iron overload plays a crucial role in CUMS-induced depression and synaptic dysfunction, as evidenced by the therapeutic effects of a high-iron diet and DFOM. The observed iron overload in this study was associated with decreased Nrf2 levels and increased expression of transferrin receptors (TfR). Notably, inhibition of iron accumulation effectively attenuated CUMS-induced synaptic damage mediated by downregulation of brain-derived neurotrophic factor (BDNF). Nrf2 −/− mice exhibited compromised FC within the limbic system and the basal ganglia, particularly in the hippocampus, and inhibition of iron accumulation effectively attenuated CUMS-induced synaptic damage mediated by downregulation of brain-derived neurotrophic factor (BDNF). Activation of Nrf2 restored iron homeostasis and reversed vulnerability to depression. Mechanistically, we further identified that Nrf2 deletion promoted iron overload via upregulation of TfR and downregulation of ferritin light chain (FtL), leading to BDNF-mediated synapse damage in the hippocampus. Therefore, our findings unveil a novel role for Nrf2 in regulating iron homeostasis while providing mechanistic insights into poststress susceptibility to depression. Targeting Nrf2-mediated iron metabolism may offer promising strategies for developing more effective antidepressant therapies.

Abstract Metasurfaces are 2D artificial nanostructures that exhibit fascinating optical phenomena and flexible capabilities. Multi-optical-parameter metasurfaces have advantages over single-function or single-dimensional metasurfaces, especially in practical applications like holography, sub-diffraction imaging, and vectorial fields. However, achieving multi-optical-parameter control is challenging due to a lack of design strategy, limited manipulation channels, and signal-to-noise ratio problems. Exceptional points (EPs) possess inherent polarization decoupling properties and allow for amplitude and wavelength modulation, opening up research prospects for multi-optical-parameter electromagnetic field modulation and developing compact integrated devices. Leveraging deep learning, we observe topological charge conservation and utilize the topologically protected optical parameter distribution around scattered EPs. Based on these, we introduce amplitude-phase multiplexing and wavelength division multiplexing devices. Our work allows rapid and precise discovery of EPs topology, offers a powerful tool for digging related physics, and provides a paradigm for multi-optical parametric manipulation with high performance and less crosstalk, which is critical for imaging, encryption, and information storage applications.

The Ni61Fe10Cr10Al17Mo2 high-entropy alloys (HEAs) with low density have been developed with great potentials for applications. The forging process is one of the important methods for fabricating components. Accordingly, the study of the deformation behavior of HEAs is the essence in the processing and molding of this material for using in industry. Moreover, there are multiple phases with hierarchical structures in the as-cast Ni61Fe10Cr10Al17Mo2 alloys, with the face-centered cubic (FCC) phase as the matrix phase accompanied with hard body-centered cubic (BCC) B2 phase. Here, the hot deformation behaviors of the homogenized Ni61Fe10Cr10Al17Mo2 alloy were investigated at strain rates ranging from 0.001 to 1.0 s−1 and temperatures ranging from 1000 to 1200 °C via isothermal compression tests. The true stress-strain curves were used to reveal the relationship between the flow stress and the deformation temperature and strain rate. The constitutive equations describing the correlations between the flow stress and hot compression parameters were constructed. At the same time, the dynamic material model and instability criterion were used to plot the hot processing map. Furthermore, the deformed microstructures and the dynamic recrystallization of alloy were investigated. Combined with the processing map, the optimal processing route is obtained.

Abstract Background The Fe (II)- and α-ketoglutarate-dependent AlkB family dioxygenases are implicated in nucleotide demethylation. AlkB homolog1 (ALKBH1) is shown to demethylate DNA adenine methylation (6mA) preferentially from single-stranded or unpaired DNA, while its demethylase activity and function in the chromatin context are unclear. Results Here, we find that loss-of-function of the rice ALKBH1 gene leads to increased 6mA in the R-loop regions of the genome but has a limited effect on the overall 6mA level. However, in the context of mixed tissues, rather than on individual loci, the ALKBH1 mutation or overexpression mainly affects the expression of genes with a specific combination of chromatin modifications in the body region marked with H3K4me3 and H3K27me3 but depleted of DNA CG methylation. In the similar context of mixed tissues, further analysis reveals that the ALKBH1 protein preferentially binds to genes marked by the chromatin signature and has a function to maintain a high H3K4me3/H3K27me3 ratio by impairing the binding of Polycomb repressive complex 2 (PRC2) to the targets, which is required for both the basal and stress-induced expression of the genes. Conclusion Our findings unravel a function of ALKBH1 to control the balance between the antagonistic histone methylations for gene activity and provide insight into the regulatory mechanism of PRC2-mediated H3K27me3 deposition within the gene body region.

Abstract The treatment of glioblastoma has limited clinical progress over the past decade, partly due to the lack of effective drug delivery strategies across the blood-brain-tumor barrier. Moreover, discrepancies between preclinical and clinical outcomes demand a reliable translational platform that can precisely recapitulate the characteristics of human glioblastoma. Here we analyze the intratumoral blood-brain-tumor barrier heterogeneity in human glioblastoma and characterize two genetically engineered models in female mice that recapitulate two important glioma phenotypes, including the diffusely infiltrative tumor margin and angiogenic core. We show that pulsed laser excitation of vascular-targeted gold nanoparticles non-invasively and reversibly modulates the blood-brain-tumor barrier permeability (optoBBTB) and enhances the delivery of paclitaxel in these two models. The treatment reduces the tumor volume by 6 and 2.4-fold and prolongs the survival by 50% and 33%, respectively. Since paclitaxel does not penetrate the blood-brain-tumor barrier and is abandoned for glioblastoma treatment following its failure in early-phase clinical trials, our results raise the possibility of reevaluating a number of potent anticancer drugs by combining them with strategies to increase blood-brain-tumor barrier permeability. Our study reveals that optoBBTB significantly improves therapeutic delivery and has the potential to facilitate future drug evaluation for cancers in the central nervous system.

Abstract Purpose In spinal tuberculosis surgery, topical administration of drugs to the lesion is a preventive treatment measure. The aim is to achieve better bacterial inhibition and to prevent complications. As one of the most common complications after spinal tuberculosis surgery, many factors can lead to surgical site infection (SSI). No definitive reports of local streptomycin irrigation of the lesion and SSI of spinal tuberculosis have been seen. This study analyzed data related to surgical site infections (SSI) after the treatment of spinal tuberculosis using this regimen. Methods In this study, 31 were in the observation group (streptomycin flush) and 34 in the control group (no streptomycin flush). All patients received the same standard of perioperative care procedures. General information, operative time, intraoperative bleeding, ESR and CRP at one week postoperatively, time on antibiotics, total drainage, days in hospital, incision infection rate and secondary debridement rate were compared between the two groups. Results Patients in both groups completed the surgery successfully. The ESR and CRP levels in the observation group were lower than those in the control group one week after surgery (p 0.05). Conclusion The use of topical streptomycin irrigation of the lesion during surgical procedures for spinal tuberculosis had no significant effect on the incidence of SSI, however, it helped to control the level of infection in the postoperative period and reduced the length of time patients had to use postoperative antibiotics and the number of days they stayed in hospital. Future prospective randomised controlled trials in more centres and larger samples are recommended.

Soils at the Chang’E-5 landing site on the Moon were weakly influenced by secondary surface processes, according to analyses of light noble gas characteristics which are relatively less fractionated than those in other lunar soils

Carbon dioxide (CO2) is a non-toxic, abundant and recoverable source of carbon monoxide. Despite its thermodynamically stable and kinetically inert nature, research on CO2 utilisation is ongoing. CO2-based aryne reactions, crucial for synthesising ortho-substituted benzoic acids and their cyclisation products, have garnered significant attention, and multi-component reactions (MCRs) involving CO2, aryne and nucleophilic reagents have been extensively studied. This review highlights recent advancements in CO2 capture reactions utilising phenylalkyne reactive intermediates. Mechanistic insights into these reactions are provided together with prospects for further development in this field.

Rural environmental governance serves as the foundational pillar of national governance, intricately linked to the modernization of agriculture and rural areas, as well as the cultivation of rural culture. Furthermore, it plays a pivotal role in fostering industrial prosperity, ensuring effective governance, and elevating living standards. This study employs a range of sophisticated software tools, including VOSviewer, Bibliometrix, and ArcGIS, among others, to analyze and construct a comprehensive knowledge map encompassing 3370 research articles focused on rural environmental governance, sourced from the CNKI (China National Knowledge Infrastructure) and WOS (Web of Science) databases. This analytical endeavor delves into research themes, key areas of interest, developmental milestones, and emerging trends within the realm of rural environmental governance, thereby shedding light on the overarching trajectory of research endeavors in this domain within China. The findings reveal distinct phases in the evolution of research trends in the Chinese rural environmental governance literature, encompassing four distinct epochs: a period of sluggish growth (2002–2009), a phase of accelerated expansion (2009–2014), a span marked by stable and rapid advancement (2014–2021), and a recent period characterized by fluctuating decline (2021–2022). Moreover, the analysis highlights a burgeoning diversity in the distribution of relevant research disciplines. However, it is noteworthy that there exists a scarcity of highly prolific authors, and the formation of cohesive research teams has encountered challenges, underscoring significant deficiencies in research collaboration and academic discourse. As a prospective direction, future research should be tailored to the unique natural resources and socio-human characteristics intrinsic to different regions. It should also emphasize interdisciplinary and multidisciplinary investigations, with a focal point on economically disadvantaged regions situated in the central and western parts of the nation. Such an approach aims to bolster the overall caliber of domestic research endeavors in the field of rural environmental governance.

To address the current steel surface defect detection algorithms in practical applications involving low detection accuracy, an efficient and highly accurate strip steel surface defect detection algorithm, DEW-YOLO, is proposed in this paper. Firstly, by combining the advantages of deformable convolutional networks (DCNs), this paper innovates the C2F module in YOLOv8 and proposes a C2f_DCN module that can flexibly sample features to enhance the abilities of learning and expressing defect features of different sizes and shapes. Secondly, the explicit visual center (EVC) is introduced into the backbone network, which enhances feature extraction capabilities and adaptability and enables the model to better adjust features at different levels and scales. Finally, the original loss function is replaced with the Wise-IoU (WIoU) loss function to accurately measure the similarity between the target frames and improve the defect detection performance of the model. The experimental results on the NEU-DET dataset demonstrate that the algorithms proposed in this paper achieved a mean average precision (mAP) of 80.3% in steel surface defect detection tasks, which was a 3.9% improvement over the original YOLOv8 model. The model’s inference speed reached 91 frames per second (FPS). DEW-YOLO effectively enhances the accuracy of steel defect detection and better satisfies industrial inspection requirements.

Remote sensing images are inevitably affected by the degradation of haze with complex appearance and non-uniform distribution, which remarkably affects the effectiveness of downstream remote sensing visual tasks. However, most current methods principally operate in the original pixel space of the image, which hinders the exploration of the frequency characteristics of remote sensing images, resulting in these models failing to fully exploit their representation ability to produce high-quality images. This paper proposes a frequency-oriented remote sensing dehazing Transformer named FOTformer, to explore information in the frequency domain to eliminate disturbances caused by haze in remote sensing images. It contains three components. Specifically, we developed a frequency-prompt attention evaluator to estimate the self-correlation of features in the frequency domain rather than the spatial domain, improving the image restoration performance. We propose a content reconstruction feed-forward network that captures information between different scales in features and integrates and processes global frequency domain information and local multi-scale spatial information in Fourier space to reconstruct the global content under the guidance of the amplitude spectrum. We designed a spatial-frequency aggregation block to exchange and fuse features from the frequency domain and spatial domain of the encoder and decoder to facilitate the propagation of features from the encoder stream to the decoder and alleviate the problem of information loss in the network. The experimental results show that the FOTformer achieved a more competitive performance against other remote sensing dehazing methods on commonly used benchmark datasets.

Non-point source (NPS) pollution poses a significant threat to the water environment, yet controlling it at the watershed scale remains a formidable challenge. Understanding the characteristics and drivers of nitrogen (N) and phosphorus (P) outputs at the watershed scale, along with identifying cost-effective best management practices (BMPs), is crucial for effective pollution control. In this study, we utilized the Wangjiaqiao watershed within the Three Gorges Reservoir Area (TGRA) as a case study to explore the characteristics of N and P load outputs and their dominant drivers by combining the SWAT model and a geographic detector. Based on our analysis of N and P loads within the watershed, we employed the entropy weight method to evaluate the reduction efficiency and cost-effectiveness of 64 BMP scenarios, encompassing seven measures (vegetative filter strips, parallel terraces, 10% fertilizer reduction, 30% fertilizer reduction, residue cover tillage, grass mulching, and returning farmland to forest) and their combinations. Our findings revealed the following: (1) spatial heterogeneity in NPS loads within the watershed, primarily influenced by land use, fertilizer application, and surface runoff, with interactive enhancement effects among driving factors; (2) the differential effectiveness of BMPs at the watershed level, with structural measures, particularly terracing, exhibiting higher efficacy and achieving reduction rates of 28.12% for total nitrogen (TN) and 37.69% for total phosphorus (TP); the combined BMPs showed improved reduction efficiency, but not merely additive; and (3) in terms of cost-effectiveness, 30% fertilizer reduction emerged as the most beneficial among the individual measures. Moreover, a combination of vegetative filter strips, parallel terraces, and 30% fertilizer reduction demonstrated significant improvements in TN and TP reductions (48.05% and 61.95%, respectively), suggesting their widespread applicability. Overall, our study provides insights into developing a cost-effective BMP strategy for the Wangjiaqiao watershed and offers valuable guidance for NPS pollution management in similar small watersheds within the TGRA.