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Abstract Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, steatosis and fibrosis. Sympathetic nerves play a critical role in maintaining hepatic lipid homeostasis and regulating fibrotic progression through adrenergic receptors expressed by hepatocytes and hepatic stellate cells; however, the use of sympathetic nerve-focused strategies for the treatment of NAFLD is still in the infancy. Herein, a biomimetic nanoplatform with ROS-responsive and ROS-scavenging properties was developed for the codelivery of retinoic acid (RA) and the adrenoceptor antagonist labetalol (LA). The nanoplatform exhibited improved accumulation and sufficient drug release in the fibrotic liver, thereby achieving precise codelivery of drugs. Integration of adrenergic blockade effectively interrupted the vicious cycle of sympathetic nerves with hepatic stellate cells (HSCs) and hepatocytes, which not only combined with RA to restore HSCs to a quiescent state but also helped to reduce hepatic lipid accumulation. We demonstrated the excellent ability of the biomimetic nanoplatform to ameliorate liver inflammation, fibrosis and steatosis. Our work highlights the tremendous potential of a sympathetic nerve-focused strategy for the management of NAFLD and provides a promising nanoplatform for the treatment of NAFLD.

Abstract Purpose This study aimed to compare the clinical outcomes and differences in biomechanical characteristics between the femoral neck system (FNS) and cannulated cancellous screws (CCSs) in the treatment of femoral neck fractures. Methods This study retrospectively analysed a cohort of 38 registered cases of femoral neck fractures treated surgically with either the FNS (n = 17) or CCSs (n = 21) between January 2020 and December 2023. Indicators such as fluoroscopy frequency, length of hospital stay, and fracture healing time were compared between the two groups. Functional status was evaluated via the Harris hip score (HHS) and visual analogue scale (VAS), whereas prognosis was assessed based on changes in the neck shaft angle and femoral neck shortening. Additionally, six sets of femoral neck fracture models were developed based on Pauwels angles of 30°, 40°, 50°, 60°, 70°, and 80°. Two experimental groups, FNS and CCS, were established, and a joint reaction force of 1800 N was applied to the proximal femur. The displacement, stress, and stiffness of the components of interest in the different models were tested and compared. Results The distributions of all the baseline characteristics were similar between the two groups (p > 0.05). The FNS group presented significantly shorter fluoroscopy frequency, length of hospital stay, and fracture healing time (p

The strength and ductility of metallic structural materials are two pivotal properties generally considered mutually contradictory. In the past few decades, numerous heterogeneous materials have been designed and fabricated to overcome this trade-off. Biomimetic-designed hierarchical layered (HL) materials represent a promising approach. In the present study, HL Zr/Ti materials with three hierarchical levels were fabricated via multi-step heat treatments. Scanning Electron Microscopy (SEM), Transmission electron microscope (TEM), Electron Backscatter Diffraction (EBSD), Transmission Kikuchi Diffraction (TKD), and Energy Dispersive X-ray Spectroscopy (EDS) were employed to observe the evolution of the HL microstructure. The mechanical properties of the HL Zr/Ti materials were assessed through hardness and tensile tests, analyzing the influence of microstructural changes in the diffusion layer on the overall mechanical performance. Our results demonstrated that the HL structure could introduce extra strength beyond the rule of mixtures (ROM) due to multiple-scaled hetero-deformation induced (HDI) strengthening. Additionally, the refinement of the second-level layer thickness effectively inhibited crack propagation. This research provides new insights into developing multi-level HL materials with enhanced mechanical properties through cost-effective and scalable manufacturing processes.

Objective The Pingbei slope belt is one of the key zones for the exploration of lithologic reservoirs in the Xihu Depression. However, the exploration process was inhibited by issues of small thickness and significant lateral variation of sand-bodies. Therefore, research on the tectonic-sedimentary response, including the stratigraphic development patterns, deposition center evolution, and sand-body distribution mechanisms in different tectonic units, is urgently needed. Methods Integrating the newly obtained well drilling, well logging, and high-resolution 3D seismic data, a high-precision sequence stratigraphic framework was established and the third-order sequences and systems tracts were analysed in the Pinghu Formation of the Pingbei slope belt. Results Based on differences in palaeogeomorphology and fault systems, the tectonic-sedimentary units of the Pingbei slope zone were classified. Differences in fault styles, stratigraphic contact relationships, and sedimentary filling patterns under different sequence stratigraphic architectures were analysed in various tectonic units. Additionally, the controlling factors and models of sand-body distribution in various sequence stratigraphic architectures were discussed. Conclusion This study revealed that the Pingbei slope zone can be divided into four types of sequence stratigraphic architectures: steep fault slope, opposite fault step, reversal step fault, and forward step fault. The sequence stratigraphic architectures that were controlled by factors of sediment supply, fault activity, palaeogeomorphic, and base-level cycles generated four sand-body distribution models. Research on the differences in sequence configurations and sand-body distribution models in different tectonic units is important for promoting the exploration of lithological reservoirs in the Pingbei slope belt of the Xihu Depression.

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.

Tumorigenesis and metastasis are highly dependent on the interactions between the tumor and the surrounding microenvironment. In 3D matrix, the fibrous structure of the extracellular matrix (ECM) undergoes dynamic remodeling during tumor progression. In particular, during the late stage of tumor development, the fibers become more aggregated and oriented. However, it remains unclear how cancer cells respond to the organizational change of ECM fibers and exhibit distinct morphology and behavior. Here, we used electrospinning technology to fabricate biomimetic ECM with distinct fiber arrangements, which mimic the structural characteristics of normal or tumor tissues and found that aligned and oriented nanofibers induce cytoskeletal rearrangement to promote directed migration of cancer cells. Mechanistically, caveolin-1(Cav-1)-expressing cancer cells grown on aligned fibers exhibit increased integrin β1 internalization and actin polymerization, which promoted stress fiber formation, focal adhesion dynamics and YAP activity, thereby accelerating the directional cell migration. In general, the linear fibrous structure of the ECM provides convenient tracks on which tumor cells can invade and migrate. Moreover, histological data from both mice and patients with tumors indicates that tumor tissue exhibits a greater abundance of isotropic ECM fibers compared to normal tissue. And Cav-1 downregulation can suppress cancer cells muscle invasion through the inhibition of YAP-dependent mechanotransduction. Taken together, our findings revealed the Cav-1 is indispensable for the cellular response to topological change of ECM, and that the Cav-1/YAP axis is an attractive target for inhibiting cancer cell directional migration which induced by linearization of ECM fibers.

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.

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.

Aim: The aim of this study was to assess the utility of weighted amide proton transfer (APTw) MRI in three different rodent models of hepatocellular carcinoma (HCC).Methods: APTw MRI was evaluated in models of diethylnitrosamine (DEN) induced HCC, N1S1 syngeneic orthotopic xenograft and human HepG2 ectopic xenograft.Results: All models of HCC showed a higher APTw signal over the surrounding normal tissues. In the DEN model, the APTw signal could differentiate HCC lesions from benign nodules. Intra-arterial administration of low-density lipoprotein docosahexaenoic acid (LDL-DHA) nanoparticles to N1S1 xenografts rapidly lowered the tumor APTw signal within 72 h. Direct injections of LDL-DHA nanoparticles into HepG2 xenografts also showed similar therapeutic responses.Conclusion: We have demonstrated the utility of APTw imaging in the diagnostic/therapeutic management of HCC.

Cancer remains a major global health challenge. Immunotherapy has revolutionized the management of cancer, yet only a limited number of patients respond to such treatments. This is largely attributed to the immunosuppressive tumor microenvironment, which diminishes the effectiveness of immunotherapy. Recent studies have underscored the potential of naturally derived caerin 1 peptides, particularly caerin 1.1 and caerin 1.9, which exhibit strong antitumor effects and enhance the efficacy of immunotherapies in animal models. This review encapsulates the current research aimed at augmenting the effectiveness of immunotherapy, focusing on the role of caerin 1.1 and caerin 1.9 in boosting immunotherapeutic outcomes, elucidating possible mechanisms, and discussing their limitations and challenges.

Background and objective Exertional heatstroke (EHS) mainly occurs in healthy young people with rapid onset and high mortality. EHS immune disorders can cause systemic inflammatory responses and multiple organ failure; however, the underlying mechanisms remain unclear. As high mobility group box 1 (HMGB1) is a prototypical alarmin that activates inflammatory and immune responses, this study aimed to investigate the effect and mechanism of HMGB1 in the pathogenesis of EHS.Methods Peripheral blood mononuclear cell (PBMC) transcriptome sequencing of healthy volunteers, classical heatstroke patients, and EHS patients was performed. A mouse model of EHS was established and murine tissue damage was evaluated by H&E staining. HMGB1 localization and release were visualized using immunofluorescence staining. Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were co-cultured to study the effects of HMGB1 on macrophages. A neutralizing anti-HMGB1 antibody was used to evaluate the efficacy of EHS treatment in mice.Results Plasma and serum HMGB1 levels were significantly increased in EHS patients or mice. EHS-induced endothelial cell pyroptosis promoted HMGB1 release in mice. HMGB1 derived from endothelial cell pyroptosis enhanced macrophage pyroptosis, resulting in immune disorders under EHS conditions. Administration of anti-HMGB1 markedly alleviated tissue injury and systemic inflammatory responses after EHS.Conclusions The release of HMGB1 from pyroptotic endothelial cells after EHS promotes pyroptosis of macrophages and systemic inflammatory response, and HMGB1-neutralizing antibody therapy has good application prospects for EHS.

AbstractObjective To investigate the target and mechanism of action of Bushen Huoxue Recipe (BSHX) for the treatment of infertility in polycystic ovary syndrome (PCOS), to provide a basis for the development and clinical application of herbal compounds.Methods Prediction and validation of active ingredients and targets of BSHX for the treatment of PCOS by using network pharmacology-molecular docking technology. In an animal experiment, the rats were randomly divided into four groups (control group, model group, BSHX group, metformin group, n = 16 in each group), and letrozole combined with high-fat emulsion gavage was used to establish a PCOS rat model. Body weight, vaginal smears, and number of embryos were recorded for each group of rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of ovarian and endometrial tissues, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the serum inflammatory factor levels. Expression levels of transforming growth factor-β (TGF-β), transforming growth factor beta activated kinase 1 (TAK1), nuclear factor kappa-B (NF-κB), Vimentin, and E-cadherin proteins were measured by western blot (WB).Results Ninety active pharmaceutical ingredients were obtained from BSHX, involving 201 protein targets, of which 160 were potential therapeutic targets. The active ingredients of BSHX exhibited lower binding energy with tumor necrosis factor-α (TNF-α), TGF-β, TAK1, and NF-κB protein receptors (< −5.0 kcal/mol). BSHX significantly reduced serum TNF-α levels in PCOS rats (p < .01), effectively regulated the estrous cycle, restored the pathological changes in the ovary and endometrium, improved the pregnancy rate, and increased the number of embryos. The results of WB suggested that BSHX can down-regulate protein expression levels of TGF-β and NF-κB in endometrial tissue (p

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.

Two-hierarchical nanostructures, characterized by two distinct configurations along the height direction, exhibit immense potential for applications in various fields due to their significantly enhanced controllable degree compared to single-order structures. However, due to the limitations imposed by planar technology, the realization of two-hierarchical nanostructures encounters huge challenges. In this work, we developed a one-step etching method based on inductively coupled plasma reactive ion etching for two-hierarchical nanostructures. Thanks to the shrinking effect of the Cr mask and the generation of a passivation layer during etching, the target materials experienced two different states from vertical etching to shrink etching. Consequently, the achieved two-hierarchical nanostructure configuration features a cross-section of an upper triangle and a lower rectangle, showing higher controllable degrees compared to the one-order ones. Both the mask pattern and etching parameters play crucial roles, by which two-hierarchical structures with diversiform shapes can be constructed controllably. This method for two-hierarchical nanostructures offers advantages including excellent control over structural properties, high processing efficiency, uniformity across large areas, and universality in materials. This developed strategy not only presents a simple and rapid nanofabrication platform for realizing optoelectronic devices, but also provides innovative ideas for designing the next generation of high-performance devices.

The prediction of land subsidence is of significant value for the early warning and prevention of geological disasters. Although numerous land subsidence prediction methods are currently available, two obstacles still exist: (i) spatio-temporal heterogeneity of land subsidence is not well considered, and (ii) the prediction performance of individual models is unsatisfactory when the data do not meet their assumptions. To address these issues, we developed a spatio-temporal heterogeneous ensemble learning method for predicting land subsidence. Firstly, a two-stage hybrid spatio-temporal clustering method was proposed to divide the dataset into internally homogeneous spatio-temporal clusters. Secondly, within each spatio-temporal cluster, an ensemble learning strategy was employed to combine one time series prediction model and three spatio-temporal prediction models to reduce the prediction uncertainty of an individual model. Experiments on a land subsidence dataset from Cangzhou, China, show that the prediction accuracy of the proposed method is significantly higher than that of four individual prediction models.

In response to the fracturing disturbance problem in the Mahu 18 block, based on the production data of on-site fracturing disturbance well groups, the actual fracturing disturbance cases in the block were first statistically divided. The complex fracturing disturbance situation in the block was divided according to the relationship between the number of fracturing wells and the number of production wells. Then, the disturbance types were classified based on the production dynamic response characteristics of the disturbed wells, and the degree of disturbance was quantitatively evaluated for the different types. The results indicate two main types of fracturing interference in the Mahu 18 block: the fracture communication type, and the pressure wave interference type formed through inter-well connectivity through the reservoir matrix. The fracturing disturbance dominated by fracture communication can cause serious water channeling to the production well through the direct connection of inter-well fractures, leading to a surge in water production. This type of fracturing disturbance often has a severe negative impact on the production well. In addition, the pressure and production (water production, liquid production, oil production) in the production dynamic response characteristics of disturbed wells during fracturing disturbance were used as evaluation indicators to quantify the impact of different types of fracturing disturbance from multiple perspectives.

Beer, as an ancient and widely consumed alcoholic beverage, holds a rich cultural heritage and history. In recent years, fruit beer has gained significant attention as a distinct beer type produced by incorporating fruit juice into traditional beer ingredients. This study employed headspace solid-phase microextraction–gas chromatography–mass spectrometry techniques, redundancy analysis, and orthogonal projections to latent structures discriminant analysis to analyze the sensory evaluation, physicochemical properties, organic acids, and volatile organic compounds (VOCs) of loquat beer with different proportions of loquat juice. The results shown that the addition of an appropriate amount of loquat juice (40%) enhanced the overall sensory quality of the beer; as the proportion of loquat juice increased, the contents of malic acid and tartaric acid significantly increased (p < 0.05). A total of 100 VOCs were identified, among which 23 key VOCs (VIP > 1, p < 0.05) represented the most important characteristic flavor components in loquat beer based on their odor activity value (OAV). This study holds significant importance for the value-added processing and economic development of loquat.

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.