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Abstract Regional anesthesia is a popular method for surgical anesthesia in clavicular surgery. Selective blocking of the cervical 3, 4, and 5 nerve roots shows promise in clavicle surgery, with its fast onset, good anesthesia and less complications, necessitating evaluation of its impact on diaphragmatic function. The purpose of this study is to examine the safety of C3, 4, and 5 nerve root block for its application in clavicle surgery. We conducted a pragmatic, randomized trial to evaluate the effect of C3, 4, and 5 nerve root block as compared with interscalene with intermediate cervical plexus block in diaphragmatic motion. This study involved forty patients undergoing right clavicle surgery. Patients were assigned in a 1:1 ratio to either a C345 nerve root block (administered with 2, 3, and 5 ml of 0.5% ropivacaine) or an interscalene with intermediate cervical plexus block (ISB + ICPB, each receiving 10 ml of 0.5% ropivacaine). Diaphragmatic kinetics were quantitatively assessed using sonographic techniques. The primary outcome was the incidence of complete hemi-diaphragmatic paralysis, observed at 30 min post-blockade. Secondary outcomes included the rate of complete hemi-diaphragmatic paralysis at 15 min and the degree of diaphragmatic motion restoration at 2, 4, 6, and 8 h post-blockade, onset time of block, motor block score in upper extremity, and adverse events. Results showed that only one patient (5%) in the C345 group vs. fifteen (75%) in the ISB + ICPB group experienced complete hemi-diaphragmatic paralysis at 30 min during deep breathing (P = 0.001). No patients in the C345 group, compared to five (25%) in the ISB + ICPB group exhibited paradoxical movement at 30 min during voluntary sniffing (P = 0.0471). Additionally, the C345 group demonstrated significantly greater diaphragmatic motion and upper limb strength restoration at all measured intervals post-blockade. Moreover, faster onset time and less adverse events were observed in the C345 group vs. in the ISB + ICPB group. Benefit from low volume of local anesthetics, the C345 nerve root block not only significantly reduces the incidence of complete hemi-diaphragmatic paralysis but also facilitates better recovery from diaphragmatic paralysis compared to the ISB + ICPB. It can be inferred that C345 is a more beneficial anesthesia method for early recovery of clavicular patients. Trial registration number: ChiCTR2300078283 04/12/2023.

Abstract Pediatric low-grade gliomas (pLGGs) exhibit heterogeneous prognoses and variable responses to treatment, leading to tumor progression and adverse outcomes in cases where complete resection is unachievable. Early prediction of treatment responsiveness and suitability for immunotherapy has the potential to improve clinical management and outcomes. Here, we present a radiogenomic analysis of pLGGs, integrating MRI and RNA sequencing data. We identify three immunologically distinct clusters, with one group characterized by increased immune activity and poorer prognosis, indicating potential benefit from immunotherapies. We develop a radiomic signature that predicts these immune profiles with over 80% accuracy. Furthermore, our clinicoradiomic model predicts progression-free survival and correlates with treatment response. We also identify genetic variants and transcriptomic pathways associated with progression risk, highlighting links to tumor growth and immune response. This radiogenomic study in pLGGs provides a framework for the identification of high-risk patients who may benefit from targeted therapies.

Abstract Background The progression of triple-negative breast cancer is shaped by both tumor cells and the surrounding tumor microenvironment (TME). Within the TME, tumor-associated macrophages (TAMs) represent a significant cell population and have emerged as a primary target for cancer therapy. As antigen-presenting cells within the innate immune system, macrophages are pivotal in tumor immunotherapy through their phagocytic functions. Due to the highly dynamic and heterogeneous nature of TAMs, re-polarizing them to the anti-tumor M1 phenotype can amplify anti-tumor effects and help mitigate the immunosuppressive TME. Results In this study, we designed and constructed an ultrasound-responsive targeted nanodrug delivery system to deliver Siglec-G siRNA and Fe3O4, with perfluorohexane (PFH) at the core and mannose modified on the surface (referred to as MPFS@NDs). Siglec-G siRNA blocks the CD24/Siglec-G mediated “don’t eat me” phagocytosis inhibition pathway, activating macrophages, enhancing their phagocytic function, and improving antigen presentation, subsequently triggering anti-tumor immune responses. Fe3O4 repolarizes M2-TAMs to the anti-tumor M1 phenotype. Together, these components synergistically alleviate the immunosuppressive TME, and promote T cell activation, proliferation, and recruitment to tumor tissues, effectively inhibiting the growth of primary tumors and lung metastasis. Conclusion This work suggests that activating macrophages and enhancing phagocytosis to remodel the TME could be an effective strategy for macrophage-based triple-negative breast cancer immunotherapy.

Injection-induced seismicity has been a focus of industry for decades as it poses great challenges to the associated risk mitigation and hazard assessment. The response surface methodology is integrated into the geo-mechanical model to analyze the effects of multiple factors on induced seismicity during the post shut-in period. We investigate the roles of poroelastic stress and pore pressure diffusion and examine the differences in the controlling mechanism between fault damage zones and the fault core. A sensitivity analysis is conducted to rank the selected factors, followed by a Box‒Behnken design to form response surfaces and formulate prediction models for the Coulomb stress and its components. Reservoir properties significantly affect the potentials of induced seismicity in the fault by changing pore pressure diffusion, which can be influenced by other factors to varying degrees. Coulomb stress is greater in pressurized damage zones than in fault cores, and the seismicity rate exhibits a consistent variation. Poroelastic stress plays a similar role to pore pressure diffusion in the stability of the fault within the pressurized damage zones. However, pore pressure diffusion dominates in the fault core due to the low rigidity, which limits the accumulation of elastic energy caused by poroelastic coupling. The slip along the fault core is a critical issue to consider. The potential for induced seismicity is reduced in the right damage zones as the pore pressure diffusion is blocked by the low-permeability fault core. However, poroelastic stressing still occurs, and in deep basements, the poroelastic effect is dominant even without a direct increase in pore pressure. The findings in this study reveal the fundamental mechanisms behind injection-induced seismicity and provide guidance for optimizing injection schemes in specific situations.

Abstract Studies have found that flipped classroom teaching (FT) improves learning compared to lecture-based teaching (LT). However, whether the structured teacher–student interaction—the key feature of FT—plays an essential role in enhancing learning remains unclear, as do its neural underpinnings. Here, we compared three teaching conditions: FT with a video lecture and structured interaction, LT with a face-to-face lecture and spontaneous interaction, and control teaching (CT) with a video lecture and spontaneous interaction. The fNIRS-based hyperscanning technique was used to assess the interbrain synchrony (IBS) from teacher-student dyads. Results showed that the learning was significantly improved in FT than in LT and CT, and FT significantly increased teacher–student IBS in left DLPFC. Moreover, the IBS and learning improvements were positively correlated. Therefore, these findings indicate that the structured teacher–student interaction is crucial for enhancing learning in FT, and IBS serves as its neural foundation.

Abstract Fidelity estimation is a necessary tool for evaluating noise in quantum measurement and quantum computation. The traditional fidelity estimation is to calculate the distance between two density matrices by employing direct fidelity estimation, which consumes too much copies of state. To reduce the number of copies of the state, we develop optimal fidelity estimation by proposing an optimal model. It calculates the minimum number of copies of state given a fixed value for the fidelity deviation. The result shows it saves a large number of copies of state compared with traditional approach (Direct Fidelity estimation) that is developed several years ago.The number of copies of the state employed increases slower than linear increase with increase of the dimension of density matrix when pauli measurement basis is applied. In addition, it consumes roughly a constant number of copies of the state with the increase of dimension of density matrix when the measurement bases are freely chosen.

Abstract Due to the energy storage lifetime effects of the power allocation, there is a large space to improve the economy of the electric‐hydrogen hybrid DC microgrid. This paper provides an optimal control method based on the mutual learn salp swarm algorithm (MLSSA) in real‐time, which aims to enhance the economy and extend the system's service life. In order to realize the economic operation, operation cost and degradation cost of battery and hydrogen system are considered as the objective function first. Then, salp swarm algorithm based on mutual learn strategy is introduced to obtain optimal economy power allocation results in real‐time with higher convergence speed and increased accuracy. In addition, the proposed method also maintains the battery state of charge (SOC) and state of hydrogen charge (SOHC) within a proper range to guarantee the stable operation of the system. Finally, the results including power results, cost analysis and degradation rate analysis of the MATLAB/Simulink show that the proposed method is more economically beneficial than the non‐considering degradation cost strategy.

Objectives The type of ligamentous tear and the degree of knee laxity have important guiding significance for the diagnosis and management of anterior cruciate ligament (ACL) tears. Instrumental measurement is necessary for ACL tears since physical examination and magnetic resonance imaging (MRI) cannot provide an objective and quantitative assessment of knee laxity. This study aimed to compare the application of a novel knee arthrometer and simultaneous stress radiography in differentiating between complete and partial acute ACL tears, and further assess the correlation between the two measurements. Methods A total of 106 patients with complete acute ACL tears and 52 patients with partial acute ACL tears were included in the study. Preoperative arthrometry and simultaneous stress radiography were performed using the Ligs arthrometer at 90, 120, and 150 N to assess side‐to‐side difference (SSD) in anterior knee laxity. The optimal threshold was determined using the receiver operating characteristic (ROC) curve. The area under the ROC curve (AUC) was used to assess the diagnostic value of the measurement. Pearson's correlation coefficient was used to assess the correlation between the two measurements. Results The optimal differential SSD thresholds in the Ligs arthrometer were 2.7 mm at 90 N, 3.8 mm at 120 N, and 4.6 mm at 150 N. Similarly, the optimal differential SSD thresholds in simultaneous stress radiography were 3.8 mm at 90 N, 5.1 mm at 120 N, and 5.6 mm at 150 N. The AUC analysis revealed that the Ligs arthrometer was fairly informative at 90 N (AUC = 0.851), 120 N (AUC = 0.878), and 150 N (AUC = 0.884), and simultaneous stress radiography was highly informative at 90 N (AUC = 0.910), 120 N (AUC = 0.925), and 150 N (AUC = 0.948). Moreover, the AUC of the combined measurements was 0.914 at 90 N, 0.931 at 120 N, and 0.951 at 150 N. A significantly strong correlation was found between the two measurements at 90 N (r = 0.743, p

Objective Potential disadvantages of open technique for talocalcaneal coalition (TCC) include a risk of wound infection, opioid drug dependence, and prolonged hospitalization. The purpose of this study was to retrospectively evaluate the effectiveness and safety of endoscopic resection of the TCC. Methods A retrospective study from June 2019 to February 2023was conducted on 16 consecutively admitted patients who were diagnosed by imaging to have TCC for whom conservative treatment had failed and who undergone arthroscopic resection. The mean age of this cohort was 31.56 ± 10.39 years (range, 16–57 years). The mean follow‐up period was 38.93 ± 15.69 months (range, 11–59 months). The site of the coalition, comorbidities, satisfaction with treatment, visual analog scale (VAS), and American Orthopedic Foot and Ankle Society (AOFAS) Ankle–Hindfoot scale scores were evaluated pre‐ and postoperatively. Preoperative magnetic resonance imaging (MRI) scans were used to categorize the coalition according to the Lim classification. Postoperative computed tomography (CT) scans were used to assess recurrence. The distribution of TCC cases according to the Lim classification was type I in one case, type II in four cases, and type III in 11 cases. Results The site of coalition involved the middle facets in seven patients, the posterior facets in three patients, and both the above sites in six patients. All patients underwent total arthroscopic resection of TCC. An auxiliary mini‐incision was made for three patients due to serious tibial nerve compression. Radiographics showed that the coalition disappeared and pain was relieved postoperatively. The mean VAS score decreased from 4.31 ± 1.54 to 1.81 ± 0.98 points (p

Cathepsin L (CTSL) is a promising therapeutic target for metabolic disorders. Current pharmacological interventions targeting CTSL have demonstrated potential in reducing body weight gain, serum insulin levels, and improving glucose tolerance. However, the clinical application of CTSL inhibitors remains limited. In this study, we used a combination of artificial intelligence and experimental methods to identify new CTSL inhibitors from natural products. Through a robust deep learning model and molecular docking, we screened 150 molecules from natural products for experimental validation. At a concentration of 100 µM, we found that 36 of them exhibited more than 50 % inhibition of CTSL. Notably, 13 molecules displayed over 90 % inhibition and exhibiting concentration-dependent effects. The molecular dynamics simulation on the two most potent inhibitors, Plumbagin and Beta-Lapachone, demonstrated stable interaction at the CTSL active site. Enzyme kinetics studies have shown that these inhibitors exert an uncompetitive inhibitory effect on CTSL. In conclusion, our research identifies Plumbagin and Beta-Lapachone as potential CTSL inhibitors, offering promising candidates for the treatment of metabolic disorders and illustrating the effectiveness of artificial intelligence in drug discovery.

Abstract Cancer stem cells (CSCs) represent a small yet pivotal subset of tumor cells endowed with self-renewal capabilities. These cells are intricately linked to tumor progression and are central to drug resistance, metastasis, and recurrence. The tumor microenvironment (TME) encompasses the cancer cells and their surrounding milieu, including immune and inflammatory cells, cancer-associated fibroblasts, adjacent stromal tissues, tumor vasculature, and a variety of cytokines and chemokines. Within the TME, cells such as immune and inflammatory cells, endothelial cells, adipocytes, and fibroblasts release growth factors, cytokines, chemokines, and exosomes, which can either sustain or disrupt CSCs, thereby influencing tumor progression. Conversely, CSCs can also secrete cytokines, chemokines, and exosomes, affecting various components of the TME. Exosomes, a subset of extracellular vesicles (EVs), carry a complex cargo of nucleic acids, proteins, and lipids, playing a crucial role in the communication between CSCs and the TME. This review primarily focuses on the impact of exosomes secreted by CSCs (CSC-exo) on tumor progression, including their roles in maintaining stemness, promoting angiogenesis, facilitating metastasis, inducing immune suppression, and contributing to drug resistance. Additionally, we discuss how exosomes secreted by different cells within the TME affect CSCs. Finally, we explore the potential of utilizing exosomes to mitigate the detrimental effects of CSCs or to target and eliminate them. A thorough understanding of the exosome-mediated crosstalk between CSCs and the TME could provide valuable insights for developing targeted therapies against CSCs.

Abstract Objectives This study aims to fill the gap in understanding the frequency of changing sanitary pads and the key factors associated with this practice among women in China. Methods Using a convenient sampling approach, a cross-sectional study was conducted with a quota sampling method to survey women from 28 cities in China between October 21 and 31, 2020. Basic demographic characteristics, personal hygiene habits, self-efficacy, health-related quality of life, and disease status were collected. Multiple logistic regression model was used to analyze the factors associated with the frequency of changing sanitary pads. Results A total of 1682 respondents were included in this study. The condition of frequently changing sanitary pads was divided into three groups: “Not taken” (224 respondents, 13.32%), “Short-term taken” (330 respondents, 19.62%), and “Long-term taken” (1128 respondents, 67.06%). Multiple logistic analysis revealed that women who performed “long-term taken” cleaning up rubbish timely (OR = 22.89, P

Abstract The typical edible medicinal plants of Viola inconspicua were compared with leaf-green, biomass, metabolomes, and bacterial communities, after leaf-spraying water (A), brown sugar water (B), brown sugar, urea, and KH2PO4 water (C), or KH2PO4 and urea water (D). The plants sprayed with C solution presented relatively normal leaf-green and the highest biomass. In contrast of A group, B, C, and D groups were found with 72, 94, and 104 leaf differently accumulated metabolites (DAMs) and 105, 88, and 92 root DAMs, respectively. Typically, relative abundances of amino acids were elevated in C and D groups, while those of leaf flavonoids were increased in B group. Noticeably, leaf DAMs of C group versus A group had strong correlations with one to more phylum- or/and genus-dominant bacteria of C group. Taken together, leaf-spraying brown sugar, urea, and KH2PO4 water are ideal for holding leaf-green and biomass in V. inconspicua plants.

In order to study the effect of reflow process parameters on the copper-tin biphase interface structure of hot dip tinned electronic copper strip, heat treatment of C14415 hot dip tinned electronic copper strip was carried out. Electron backscattering diffraction (EBSD) and transmission electron microscopy (TEM) were used to collect and analyze the microcosmic characteristics of the copper-tin biphase interface of hot dip tin-coated electronic copper strip after reflux. The results show that Cu6Sn5 and Cu3Sn are formed at the Cu–Sn biphase interface during reflow welding, and Cu6Sn5 is first formed at the Cu–Sn biphase interface, and Cu3Sn is gradually formed at the bottom of Cu6Sn5 when the Cu–Sn biphase interface forms a high temperature and stable environment. During the growth of Cu and Sn and its series of compounds, different reflow welding processes have no obvious effect on the distribution of interphase orientation difference. The competitive growth process of the multiphase interface during reflow welding was reconstructed through the distribution state of the multiphase interface under different reflow welding processes. The optimal process parameters of reflow welding were 290°C-heat preservation for 3min-air cooling.

Abstract Background Circular RNAs (circRNAs) are differentially expressed in various cardiovascular diseases, including myocardial infarction (MI) injury. However, their functional role in necroptosis-induced loss of cardiomyocytes remains unclear. We identified a cardiac necroptosis-associated circRNA transcribed from the Cacna1c gene (circCacna1c) to investigate the involvement of circRNAs in cardiomyocyte necroptosis. Methods To investigate the role of circCacna1c during oxidative stress, H9c2 cells and neonatal rat cardiomyocytes were treated with hydrogen peroxide (H2O2) to induce reactive oxygen species (ROS)-induced cardiomyocyte death. The N 6-methyladenosine (m6A) modification level of circCacna1c was determined by methylated RNA immunoprecipitation quantitative polymerase chain reaction (MeRIP–qPCR) analysis. Additionally, an RNA pull-down assay was performed to identify interacting proteins of circCacna1c in cardiomyocytes, and the regulatory role of circCacna1c in target protein expression was tested using a western blotting assay. Furthermore, the MI mouse model was constructed to analyze the effect of circCacna1c on heart function and cardiomyocyte necroptosis. Results The expression of circCacna1c was found to be reduced in cardiomyocytes exposed to oxidative stress and in mouse hearts injured by MI. Overexpression of circCacna1c inhibited necroptosis of cardiomyocytes induced by hydrogen peroxide and MI injury, resulting in a significant reduction in myocardial infarction size and improved cardiac function. Mechanistically, circCacna1c directly interacts with heterogeneous nuclear ribonucleoprotein F (Hnrnpf) in the cytoplasm, preventing its nuclear translocation and leading to reduced Hnrnpf levels within the nucleus. This subsequently suppresses Hnrnpf-dependent receptor-interacting protein kinase 1 (RIPK1) expression. Furthermore, fat mass and obesity-associated protein (FTO) mediates demethylation of m6A modification on circCacna1c during necrosis and facilitates degradation of circCacna1c. Conclusion Our study demonstrates that circCacna1c can improve cardiac function following MI-induced heart injury by inhibiting the Hnrnpf/RIPK1-mediated cardiomyocyte necroptosis. Therefore, the FTO/circCacna1c/Hnrnpf/RIPK1 axis holds great potential as an effective target for attenuating cardiac injury caused by necroptosis in ischemic heart disease. Graphical Abstract

Abstract Background Sorafenib is a standard therapeutic agent for advanced hepatocellular carcinoma (HCC). However, its efficacy is moderate, as the survival of patients is prolonged for only a few months, and the response rate is low. The mechanism of low efficacy remains unclear. In this study, we investigated the effect of Toll-like receptor 3 (TLR3) on the effects of sorafenib on HCC. Methods Polyinosinic-polycytidylic acid [poly(I: C)] was used as a double-stranded RNA analog and TLR3 agonist in subsequent experiments. After orthotopic implantation of HCC tumors in BALBc nu/nu or C57BL/6 mice, survival time, tumor growth, and metastasis in the abdomen and lungs were analyzed. Flow cytometry and cytotoxicity assays were used to analyze NK cells isolated from the spleen or peripheral blood. ELISA was used to detect the expression of plasma interferon (IFN)-γ and monocyte chemoattractant protein (MCP)-1. In addition, the expression of phosphorylated-extracellular regulated kinase 1/2 (pERK1/2), phosphorylated-protein kinase B (pAKT), ERK1/2 and AKT was analyzed by Western blotting. Results Sorafenib reduced the number and activity of NK cells in tumor-bearing mice and simultaneously decreased the levels of MCP-1 and IFN-γ in the plasma. The combination of sorafenib and poly(I: C) synergistically inhibited tumor growth and metastasis in tumor xenograft mice and prolonged survival. Poly(I: C) not only exerts a direct inhibitory effect on tumor growth and metastasis by targeting the TLR3 receptor on tumor cells but also facilitates the proliferation and activation of NK cells, indirectly impeding tumor progression. Mechanistically, poly(I: C) decreased the sorafenib-induced inhibition of ERK phosphorylation and increased the phosphorylation of IκB in NK cells, thereby enhancing NK cell function. Conclusion Activation of TLR3 can enhance the antitumor effect of sorafenib on HCC. The combination of a TLR3 activator and sorafenib may be a new strategy for the treatment of HCC.

Abstract In farming scenarios, cattle identification has become a key issue for the development of precision farming. In precision livestock farming, single-feature recognition methods are prone to misjudgment in complex scenarios involving multiple cattle obscuring each other during drinking and feeding. This paper proposes a decision-level identification method based on the multi-feature fusion of cattle faces, muzzle patterns, and ear tags. The method utilizes the SOLO algorithm to segment images and employs the FaceNet and PP-OCRv4 networks to extract features for the cattle’s faces, muzzle patterns, and ear tags. These features are compared with the Ground truth, from which the Top 3 features are extracted. The corresponding cattle IDs of these features are then processed using One-Hot encoding to serve as the final input for the decision layer, and various ensemble strategies are used to optimize the model. The results show that using the multimodal decision fusion method makes the recognition accuracy reach 95.74%, 1.4% higher than the traditional optimal unimodal recognition accuracy. The verification rate reaches 94.72%, 10.65% higher than the traditional optimal unimodal recognition verification rate. The research results demonstrate that the multi-feature fusion recognition method has significant advantages in drinking and feeding farm environments, providing an efficient and reliable solution for precise identification and management of cattle in farms and significantly improving recognition accuracy and stability.

Abstract Background Abnormal sensory perception, particularly pain insensitivity (PAI), is a typical symptom of autism spectrum disorder (ASD). Despite the role of myelin metabolism in the regulation of pain perception, the mechanisms underlying ASD-related PAI remain unclear. Methods The pain-associated gene sphingosine-1-phosphate receptor 1 (S1PR1) was identified in ASD samples through bioinformatics analysis. Its expression in the dorsal root ganglion (DRG) tissues of BTBR ASD model mice was validated using RNA-seq, western blot, RT-qPCR, and immunofluorescence. Pain thresholds were assessed using the von Frey and Hargreaves tests. Patch-clamp techniques measured KCNQ/M channel activity and neuronal action potentials. The expression of S1PR1, KCNQ/M, mitogen-activated protein kinase (MAPK), and cyclic AMP/protein kinase A (cAMP/PKA) signaling proteins was analyzed before and after inhibiting the S1P-S1PR1-KCNQ/M pathway via western blot and RT-qPCR. Results Through integrated transcriptomic analysis of ASD samples, we identified the upregulated gene S1PR1, which is associated with sphingolipid metabolism and linked to pain perception, and confirmed its role in the BTBR mouse model of ASD. This mechanism involves the regulation of KCNQ/M channels in DRG neurons. The enhanced activity of KCNQ/M channels and the decreased action potentials in small and medium DRG neurons were correlated with PAI in a BTBR mouse model of ASD. Inhibition of the S1P/S1PR1 pathway rescued baseline insensitivity to pain by suppressing KCNQ/M channels in DRG neurons, mediated through the MAPK and cAMP/PKA pathways. Investigating the modulation and underlying mechanisms of the non-opioid pathway involving S1PR1 will provide new insights into clinical targeted interventions for PAI in ASD. Conclusions S1PR1 may contribute to PAI in the PNS in ASD. The mechanism involves KCNQ/M channels and the MAPK and cAMP/PKA signaling pathways. Targeting S1PR1 in the PNS could offer novel therapeutic strategies for the intervention of pain dysesthesias in individuals with ASD.

Abstract The procedure of anterior cruciate ligament (ACL) allograft preparation can be divided into fresh-frozen method (FF-allograft) or freeze-dried method (FD-allograft). This study aims to biomechanically and histologically compare the graft to bone tunnel integration between the two allografts. In-vitro results indicated that FF-allograft and FD-allograft showed excellent biocompatibility and biomechanics, while FD-allograft showed a denser collagen fiber arrangement than FF-allograft and autograft. Then, in-vivo preformation of the FF-allograft, FD-allograft, and autograft on bone tunnel integration was evaluated via a canine ACL reconstruction model. In-vivo results indicated that no signs of infection or osteoarthritis were shown in the femur-graft-tibia complexes, but more vascularity and synovitis formed around the implanted FF-allograft. Micro-computed tomography showed that peri-graft bone in the FF-allograft group was significantly increased and remodeled compared with the FD-allograft group; Histologically, the FF-allograft group exhibited similar graft-bone tunnel healing to the FD-allograft group. Tartrate-resistant acid phosphatase (TRAP) staining showed significantly more osteoclasts presented in the FD-allograft group compared to the FF-allograft group. Meanwhile, a significantly higher failure load was shown in the FF-allograft group when compared with the FD-allograft group (P

Objective Diffuse‐type tenosynovial giant cell tumors (Dt‐TGCTs) commonly occur in the knee joint and tend to recur postoperatively. However, limited clinical data are available on ankle joint involvement especially associated multiportal arthroscopic treatment outcomes. The purpose of this study was to report the clinical results of multiportal arthroscopy‐assisted resection of Dt‐TGCTs of the ankle. Methods We retrospectively reviewed the clinical data of 33 patients with Dt‐TGCT of the ankle who underwent multiportal arthroscopic treatment between August 2011 and December 2020. Clinical follow‐up included the visual analogue scale (VAS) score, American Orthopedic Foot and Ankle Society (AOFAS) score, Kofoed score, and recurrence rate to assess surgical outcomes. The number of patients who achieved the patient acceptable symptom state (PASS) based on the AOFAS score was also examined. Additionally, the patients were categorized into two groups based on the final surgical approach: Group A who underwent multiportal arthroscopic synovectomy and Group AO who underwent combined arthroscopic and open surgical excision. Intergroup comparisons were conducted. Intraoperative characteristics, such as the number of patients with involvement of the tarsal tunnel and fibularis tendon and the Outerbridge grading of cartilage damage, were recorded to assess the selection of surgical procedures. Results Among the 33 patients, 15 were assigned to Group A, and 18 were in Group AO. The median follow‐up duration for the 33 patients was 77 months (range, 28–142 months). The median VAS score was 1 (range, 0–4), the AOFAS score was 96 (range, 65–100), and the Kofoed score was 96 (range, 67–100). A total of 27 patients (82%) achieved PASS based on AOFAS scores, while five patients (15%) had recurrence. No statistically significant difference was observed between the two groups in recurrence rate, follow‐up VAS score, AOFAS score, Kofoed score, or number of patients who reached the PASS (p > 0.05). In the AO group, 16 cases of Dt‐TGCT involved the tarsal tunnel, and 11 cases involved the fibularis tendon. All these patients exhibited extension beyond the joint. In contrast, only one patient in Group A had involvement of the tarsal tunnel. Statistically significant differences were observed between the groups (p

Background/Aims Hepatitis B virus (HBV)-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it to an HBV-related HCC patient (NCT05339321). Methods Good Manufacturing Practice-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh class A, Barcelona Clinic Liver Cancer stage B, Eastern Cooperative Oncology Group performance status 0, hepatitis B e antigen-, serum hepatitis B surface antigen [HBsAg]+, HBsAg+ hepatocytes 10%) received 7.9×107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated. Results SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-HCC cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1,404 U/L, and concurrently, serum HBsAg started decreasing by 3.84 log10 and remained 70% reduction in target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient’s blood. Conclusions SCG101 T-cell therapy showed encouraging efficacy and safety in preclinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.

Abstract Background Bilateral malignant glaucoma induced by a capsular tension ring associated with ring-shaped cysts of the ciliary body post-cataract surgery is rare. Herein, we present a case to highlight the possibility of capsular tension ring-induced malignant glaucoma. Case presentation A 59-year-old woman underwent phacoemulsification combined with capsular tension ring implantation for cataracts and zonular fibre laxity in both eyes. Upon admission, annular ciliary masses were detected in both eyes using ultrasound biomicroscopy. Two months post-surgery, the patient experienced vision deterioration, high intraocular pressure, and an axial shallowing anterior chamber in the right eye, and responded poorly to traditional anti-glaucoma medication. Ten days later, similar symptoms appeared in the left eye. Ultrasound biomicroscopy detected contact between the ciliary body and the capsular tension ring. Subsequently, malignant glaucoma was diagnosed. Anterior and posterior capsulotomies performed peripheral to intraocular lens optics using neodymium: YAG laser restored communication and alleviated the symptoms. A one-year follow-up revealed stable intraocular pressure and anterior chamber in both eyes. Conclusions This is the first case report of bilateral malignant glaucoma after cataract surgery induced by capsular tension ring, which is associated with bilateral ring-shaped cysts of the ciliary body. Blockage between the ciliary body and capsular tension ring was confirmed using ultrasound biomicroscopy.

Abstract This study compares the surface patina of ancient tin rich bronze with pure hydrothermally synthesized SnO2 nanoparticles using various analytical techniques, including metallographic microscopy, scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and high-angle annular dark-field scanning transmission electron microscopy. The primary crystalline component of the patina consists of approximately 5 nm SnO2 nanoparticles, which closely resemble pure SnO2, indicating their comparability. Cu was also detected in the patina; however, it did not form crystalline structures. The X-ray diffraction results showed a shift in the patina’s peak, suggesting the infiltration of Cu into the SnO2 lattice, which compromises its crystallinity. In comparison to synthetic SnO2, the X-ray photoelectron spectroscopy spectra of the patina revealed novel peaks corresponding to both Cu and O, indicating the presence of Cu−O−Sn bonding—a characteristic feature of type-I patina. This suggests that the primary structure of type-I patina consists of crystalline SnO2 nanoparticles, with a limited amount of Cu integrated into its lattice configuration. The concentration of Cu within the SnO2 crystal units is restricted, leading primarily to the formation of amorphous Cu2O in conjunction with Sn. The presence of Sn enhances the structural stability of Cu2O, facilitating its incorporation while inhibiting the crystallization of Cu2O. However, when the Sn concentration is insufficient, an inadequate Cu–O−Sn amorphous phase may form, allowing for the potential crystallization of Cu2O.

This paper aims to investigate the role of bi-directional shear in the mechanical behaviour of granular materials and macro-micro relations by conducting experiments and discrete element method (DEM) modelling. The bi-directional shear consists of a static shear consolidation and subsequent shear under constant vertical stress and constant volume conditions. A side wall node loading method is used to exert bi-directional shear of various angles. The results show that bi-directional shear can significantly influence the mechanical behaviour of granular materials. However, the relationship between bi-directional shear and mechanical responses relies on loading conditions, i.e. constant vertical stress or constant volume conditions. The stress states induced by static shear consolidation are affected by loading angles, which are enlarged by subsequent shear, consistent with the relationship between bi-directional shear and principal stresses. It provides evidence for the dissipation of stresses accompanying static liquefaction of granular materials. The presence of bi-directional principal stress rotation (PSR) is demonstrated, which evidences why the bi-directional shear of loading angles with components in two directions results in faster dissipations of stresses with static liquefaction. Contant volume shearing leads to cross-anisotropic stress and fabric at micro-contacts, but constant vertical stress shearing leads to complete anisotropic stress and fabric at micro-contacts. It explains the differentiating relationship between stress-strain responses and fabric anisotropy under these two conditions. Micromechanical signatures such as the slip state of micro-contacts and coordination number are also examined, providing further insights into understanding granular behaviour under bi-directional shear.

Abstract Convolutional neural networks (CNNs) for extracting structural information from structural magnetic resonance imaging (sMRI), combined with functional magnetic resonance imaging (fMRI) and neuropsychological features, has emerged as a pivotal tool for early diagnosis of Alzheimer’s disease (AD). However, the fixed-size convolutional kernels in CNNs have limitations in capturing global features, reducing the effectiveness of AD diagnosis. We introduced a group self-calibrated coordinate attention network (GSCANet) designed for the precise diagnosis of AD using multimodal data, including encompassing Haralick texture features, functional connectivity, and neuropsychological scores. GSCANet utilizes a parallel group self-calibrated module to enhance original spatial features, expanding the field of view and embedding spatial data into channel information through a coordinate attention module, which ensures long-term contextual interaction. In a four-classification comparison (AD vs. early MCI (EMCI) vs. late MCI (LMCI) vs. normal control (NC)), GSCANet demonstrated an accuracy of 78.70%. For the three-classification comparison (AD vs. MCI vs. NC), it achieved an accuracy of 83.33%. Moreover, our method exhibited impressive accuracies in the AD vs. NC (92.81%) and EMCI vs. LMCI (84.67%) classifications. GSCANet improves classification performance at different stages of AD by employing group self-calibrated to expand features receptive field and integrating coordinated attention to facilitate significant interactions among channels and spaces. Providing insights into AD mechanisms and showcasing scalability for various disease predictions.

Inert gas argon has important applications in the fields of daily life, industrial manufacture and nuclear environmental monitoring. The key to its application is to selectively and efficiently separate and purify Ar from complex gas components. However, the separation of O2 and Ar at normal temperature is full of challenge due to their similar molecular sizes and adsorption properties as well as their close boiling point. In industry, high purity Ar is mainly produced by low temperature rectification, which is mature technology, but the equipment is large, high-energy consumption and explosive. Adsorption separation is a common method of gas separation. Molecular sieves are the most widely used material due to their huge specific surface area, aboudant pore structure and excellent adsorption properties. The silica tetrahedron in molecular sieve is electrically neutral, while the aluminum tetrahedron is electronegative, which makes it necessary to use H+ or Na+ outside the molecular sieve skeleton to maintain electrical neutrality. In actual application, the interaction between adsorbent and adsorbent can be enhanced by ion-exchange modification of molecular sieve material, so as to effectively improve the O2/Ar separation capacity of molecular sieve. In this paper, the application of ion-exchange modified molecular sieve materials in the field of O2/Ar adsorption separation was systematically summarized and reviewed. The results show that the O2/Ar separation coefficients of molecular sieves modified by alkaline earth metal ions like Ca2+, Sr2+ and Ba2+ can reach about 2.0, while that of Ce3+-exchanged X-type molecular sieve is as high as 5.9, it is an ideal adsorption material for O2/Ar separation. However, the high separation coefficient is limited to the range of low partial pressure, and the O2/Ar separation coefficient under normal pressure is below 2.0. The Ag+-exchanged molecular sieves, namely silver-loaded molecular sieves, have excellent Ar adsorption selectivity. At present, the O2/Ar separation coefficients of silver-loaded molecular sieve materials at atmospheric pressure are around 2.0, but the preparation cost of silver-loaded molecular sieves is high, and it is more suitable for small-scale separation applications, it means that the efficient separation of O2 and Ar at normal temperature and pressure is still challenging. The development of novel ion-exchange modified molecular sieve materials with high adsorption capacity and high adsorption selectivity for the separation of O2 and Ar is still one of the focuses and trends of future research projects.

Abstract Small-caliber (≤ 6 mm) vascular grafts are commonly used to treat vascular diseases, yet intimal hyperplasia at the distal end-to-side anastomosis remains a significant complication with long-term use. Helical flow has been shown to reduce the risk of cardiovascular complications effectively. Integrating helical flow through an inbuilt helical ridge in vascular grafts is intended to improve hemodynamic performance and mitigate issues such as flow-induced thrombosis and intimal hyperplasia. However, inadequate helical flow strength may limit its effectiveness. This study proposes a novel design for an inbuilt helical ridge in small-caliber grafts to achieve enhanced helical flow. Two novel small-caliber vascular grafts with variable-pitch helical ridges, incorporating both decreasing and increasing pitches, were designed. Their effectiveness was assessed through numerical simulations and in vitro experiments to evaluate their performance in arterial graft applications. The small-caliber vascular grafts incorporating variable-pitch helical ridges significantly improved helical flow structure and distribution, optimized wall shear stress distribution, and reduced platelet adhesion compared to conventional and constant-pitch helical ridge grafts. Among the various new designs, the small-caliber vascular graft featuring decreasing variable-pitch helical ridges has demonstrated better performance. This design is well-suited for small-caliber bypass surgeries, as it is effective in improving hemodynamic performance by improving helical flow into asymmetric structures and increasing helical flow density distribution.

Abstract Recently, ZnO‐based composites have been widely applied in the field of electric power. To meet the diverse application requirements, it is necessary to figure out the I–V characteristics of ZnO composites whose high‐voltage and ground‐voltage electrodes are arranged on the opposite sides with a certain horizontal distance. 30 vol%, 40 vol% and 50 vol% ZnO‐based silicone rubber composites were prepared. The horizontal distance between their electrodes was set as 50, 100, 500 μm, 1 and 2 mm, respectively. Results showed that with the increase of ZnO fillers volume fraction under a fixed horizontal distance of 100 μm, from 30 vol% to 50 vol%, the I–V curves shifted left, the leakage current increased and the switching voltage decreased. When the horizontal distance between electrodes increased from 50 μm to 1 mm under a fixed doping concentration of 40%, the I–V curves shifted to the right, the leakage current dropped and the switching voltage rose. The mathematical and physical models were established to explain the results. This work provides a referential significance for the practical application of ZnO composites, such as 5G folding mobile phones and power electronic modules.

To solve the problems of the AC loss in self-field for no-insulation (NI) HTS coils carrying different currents, such as AC transport current, the current scanning inverse in order to decrease the screening current, and so on, by using the T-Ahomogenization model based on the E-J power law, the effects of the transport current, frequency, and the n-value on the magnetic flux density and AC loss of NI-HTS pancack coils were simulated. The instantaneous AC losses of square wave, sawtooth wave, and sinusoidal wave for double-pancake coil were simulated quantitatively. The effects of charging and discharging ramping rates on the current distribution were also discussed by using partial element equivalent circuit (PEEC). The results show that the AC losses increase with the increase of frequency from several hundred to kilo Hz. Due to the transfer of the radial current within coil’s turns, some inverse azimuthal currents may appear in the NI-HTS coil in the early charging period, and some of the azimuthal currents may increase during short discharging period for the same reason. The simulation work can provide some theoretical references for the studies of the stability and AC loss for NI-HTS pancake coils.

Abstract Alterations in the reward and cognitive control systems are commonly observed among adolescents with internet dependence (ID), and this impairment is often accompanied by social dysfunctions, such as academic burnout. However, the intercorrelations among ID, reward, cognitive control processing, and learning burnout remain unclear. We recruited 1074 Chinese adolescents to investigate the complex interrelationships among these variables using network analysis. The resulting network revealed patterns that connected ID to the behavioral inhibition/activation system (BIS/BAS), self-control, and learning burnout; these results exhibited reasonable stability and test–retest consistency. Throughout the network, the node of BAS-drive was the critical influencing factor, and the node of self-control was the protection factor. In addition, several symptoms of learning burnout and ID were positively associated with sensitivity to punishment. As revealed by the network comparison test, the network constructed among internet dependent (ID) group differed from the network constructed among internet nondependent (IND) group not only in the edges between BIS and learning burnout but also in terms of the edges associated with learning burnout. In conclusion, this study provides insights into the complex mechanisms underlying ID among adolescents from the perspective of the network relationships between core influencing factors and negative consequences. It validates the dual-system model of risky behavior among adolescents and offers a foundation for early warning and interventions for ID in this context.

Abstract Background Gastroschisis is a common abdominal wall defect that increases infant mortality risk and health care costs. However, recent epidemiological data on gastroschisis in China is limited. Methods Using 2007–2020 data from the Chinese Birth Defects Monitoring Network (CBDMN), we analyzed gastroschisis prevalence rates stratified by birth year, maternal age group, residence area, geographical region, and infant sex. We also examined the temporal variations in prevalence, pregnancy outcomes of affected infants, prenatal diagnoses, and co-occurring anomalies. Results From 2007 to 2020, a total of 6,813 cases of gastroschisis were identified among 25,909,000 births, comprising 4,675 isolated and 2,138 non-isolated cases. Prevalence rates per 10,000 live and still births were 2.63, 1.80, and 0.83 for the overall, isolated, and non-isolated gastroschisis, respectively, all showing a decreasing trend over the study period. The prevalence of overall gastroschisis varied significantly by maternal age (

Abstract Background Lung squamous cell carcinoma (LUSCs) is associated with high mortality (20–30%) and lacks of effective treatments. Almost all LUSC exhibit somatic mutations in TP53. Wee1, a tyrosine kinase, regulates the cell cycle at the G2/M checkpoint. In TP53-deficient cells, the dependence on G2/M checkpoints increases. PD0166285 is the first reported drug with inhibitory activity against both Wee1 and PKMYT1. Methods Protein expression was determined by Western blot analysis. Cell proliferation was assessed using cell colony formation and CCK-8 assays. Cell cycle was performed by PI staining with flow cytometry. Apoptosis was evaluated using Annexin V-Phycoerythrin double staining and flow cytometry. DNA damage was detected through comet assay and immunofluorescence assay. In vivo, apoptosis and anti-tumor effects were assessed using the TUNEL assay, a nude mouse model, and immunohistochemistry (IHC). Co-immunoprecipitation assay was used to detect protein–protein interactions. We analyzed Wee1, PKMYT1, and Stat1 expression in pan-cancer studies using the Ualcan public database and assessed their prognostic implications with Kaplan–Meier curves. Result PD0166285, a Wee1 inhibitor, effectively inhibits Wee1 activity, promoting cell entry into a mitotic crisis. Moreover, PD0166285 sensitizes cells to cisplatin, enhancing clinical outcomes. Our study demonstrated that PD016628 regulates the cell cycle through Rad51 and results in cell cycle arrest at the G2/M phase. We observed increased apoptosis in tumor cells treated with PD0166285, particularly when combined with cisplatin, indicating an enhanced apoptotic response. The upregulation of γ-H2AX serves as an indicator of mitotic catastrophe. Co-immunoprecipitation and data analysis revealed that apoptosis in LUSC is mediated through the Stat1 pathway, accompanied by decreased levels of Socs3. Furthermore, IHC staining confirmed significant differences in the expression of Phospho-CDK1 and γ-H2AX in LUSCs, suggesting involvement in DNA damage. Conclusions In summary, our study suggests that PD0166285, an inhibitor of Wee1, sensitizes LUSC cells to cisplatin and modulates DNA damage and apoptosis pathways through Rad51 and Stat1, respectively. These findings highlight the combination of PD0166285 and cisplatin as a promising therapeutic approach for treating LUSC.

Abstract Malignant transformation (MT) is commonly seen in IDH-mutant gliomas. There has been a growing research interest in revealing its underlying mechanisms and intervening prior to MT at the early stages of the transforming process. Here we established a unique pair of matched 3D cell models: 403L, derived from a low-grade glioma (LGG), and 403H, derived from a high-grade glioma (HGG), by utilizing IDH-mutant astrocytoma samples from the same patient when the tumor was diagnosed as WHO grade 2 (tumor mutational burden (TMB) of 3.96/Mb) and later as grade 4 (TMB of 70.07/Mb), respectively. Both cell models were authenticated to a patient’s sample retaining endogenous expression of IDH1 R132H. DNA methylation profiles of the parental tumors referred to LGG and HGG IDH-mutant glioma clusters. The immunopositivity of SOX2, NESTIN, GFAP, OLIG2, and beta 3-Tubulin suggested the multilineage potential of both models. 403H was more prompt to cell invasion and developed infiltrative HGG in vivo. The differentially expressed genes (DEGs) from the RNA sequencing analysis revealed the tumor invasion and aggressiveness related genes exclusively upregulated in the 403H model. Pathway analysis showcased an enrichment of genes associated with epithelial-mesenchymal transition (EMT) and Notch signaling pathways in 403H and 403L, respectively. Mass spectrometry-based targeted metabolomics and hyperpolarized (HP) 1-13C pyruvate in-cell NMR analyses demonstrated significant alterations in the TCA cycle and fatty acid metabolism. Citrate, glutamine, and 2-HG levels were significantly higher in 403H. To our knowledge, this is the first report describing the development of a matched pair of 3D patient-derived cell models representative of MT and temozolomide (TMZ)-induced hypermutator phenotype (HMP) in IDH-mutant glioma, providing insights into genetic and metabolic changes during MT/HMP. This novel in vitro model allows further investigation of the mechanisms of MT at the cellular level. Graphic Abstract

Penicillium citrinum is one of the most prevalent tobacco spoilage fungi. However, the mechanisms underlying fungal growth on tobacco leaves remain largely unknown. In this study, transcriptomic analyses were performed to reveal the genome-wide expression profiles of P. citrinum growing on tobacco leaves. First, a comparative analysis was conducted between two sets of transcriptomic data from P. citrinum growing on chemically defined media and tobacco leaves. Enrichment analyses showed that differentially regulated genes were mainly associated with carbohydrate degradation (e.g., cellulose, pectin, and xylan) and the catabolism of fatty acids and aromatic compounds. Comparative transcriptomic analyses between different time points indicated that the fungal transcriptome varied dynamically during the spoilage process, and the enriched terms were associated with small-molecule degradation and fungal development. Enrichment analyses indicated that more up-regulated genes appeared in all enriched Gene Ontology terms. Notably, more organelles significantly contributed to further fungal growth on tobacco leaves. In conclusion, P. citrinum activates a comprehensive transcriptome that changes dynamically when causing tobacco mildew.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Rattus tanezumi (Niethammer, 1975) is one of the commensal rodent species in South China. With the development of transportation and climate change, R. tanezumi has gradually migrated north and become the dominant rat species for the past few years. In this study, we assembled a complete mitochondrial genome of R. tanezumi, captured from North China. The mitogenome contains 16,307 nucleotide pairs, including 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, as well as one non-coding control region. Based on whole mitogenome phylogenetical analysis showed that R. tanezumi captured from North China had a close phylogenetic relationship with that from Japan and South Korea. These findings are valuable for further studies on the evolution, genetic diversity, and taxonomy of Asian commensal rodent.

Abstract Background The mutations of oncogenic epidermal growth factor receptor (EGFR) is an important cause of lung adenocarcinoma (LUAD) malignance. It has been knowm that metabolic reprogramming is an important hallmark of malignant tumors, and purine metabolism is a key metabolic pathway for tumor progression and drug resistance, but its relationship with the EGFR-mutant LUAD is unclear. Methods Metabolic reprogramming was studied through capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based metabolic profiling analysis. Cell proliferation in vitro was evaluated by EdU staining and cell cycle assay. Tumorigenicity in vivo was tested by subcutaneous tumor formation experiment in nude mice. The binding of hypoxia-inducible factor-1 alpha (HIF-1α) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) was detected by DNA pull‑down assay and Chromatin immunoprecipitation (ChIP) assays. HIF-1α, HPRT1, DNA damage and cell apoptosis related genes were examined by western blot. In addition, RNA sequencing, mass spectrometry and bioinformatics analysis were performed. Results We found that mutated EGFR (muEGFR) upregulates HPRT1 to promote purine metabolism and tumorigenesis of EGFR-mutant LUAD. Mechanistically, muEGFR increases HIF-1α expression through protein stability. Meanwhile, up-regulated HIF-1α bound to the promoter of HPRT1 and transcriptionally activates HPRT1 expression, enhancing purine metabolism to maintain rapid tumor cell proliferation in EGFR-mutant LUAD. Further, gefitinib inhibited the synthesis of purine nucleotides, and HPRT1 inhibition increased the sensitivity of gefitinib to EGFR-mutant LUAD. Conclusions Our study reveals that muEGFR-HIF-1α-HPRT1 axis plays a key role in EGFR-mutant LUAD and provides a new strategy-inhibiting purine metabolism for treating EGFR-mutant LUAD.

Sliding bearings are crucial rotating mechanical components in nuclear power plants, and their failures can result in severe economic losses and human casualties. Deep learning provides a new approach to bearing fault diagnosis, but there is currently a lack of a universal fault diagnosis model for studying bearing-rotor systems under various operating conditions, speeds and faults. Research on bearing-rotor systems supported by sliding bearings is limited, leading to insufficient fault data. To address these issues, this paper proposes a fault diagnosis model framework for bearing-rotor systems based on a deep convolutional generative adversarial network (TF-DLGAN). This model not only exhibits outstanding fault diagnosis performance but also addresses the issue of insufficient fault data. An experimental platform is constructed to conduct fault experiments under various operating conditions, speeds and faults, establishing a dataset for sliding bearing-rotor system faults. Finally, the model's effectiveness is validated using this dataset.

Abstract Inferior vena cava filter (IVCF) implantation is a common method of thrombus capture. By implanting a filter in the inferior vena cava (IVC), microemboli can be effectively blocked from entering the pulmonary circulation, thereby avoiding acute pulmonary embolism (PE). Inspired by the helical flow effect in the human arterial system, we propose a helical retrievable IVCF, which, due to the presence of a helical structure inducing a helical flow pattern of blood in the region near the IVCF, can effectively avoid the deposition of microemboli in the vicinity of the IVCF while promoting the cleavage of the captured thrombus clot. It also reduces the risk of IVCF dislodging and slipping in the vessel because its shape expands in the radial direction, allowing its distal end to fit closely to the IVC wall, and because its contact structure with the inner IVC wall is curved, increasing the contact area and reducing the risk of the vessel wall being punctured by the IVCF support structure. We used ANSYS 2023 software to conduct unidirectional fluid–structure coupling simulation of four different forms of IVCF, combined with microthrombus capture experiments in vitro, to explore the impact of these four forms of IVCF on blood flow patterns and to evaluate the risk of IVCF perforation and IVCF dislocation. It can be seen from the numerical simulation results that the helical structure does have the function of inducing blood flow to undergo helical flow dynamics, and the increase in wall shear stress (WSS) brought about by this function can improve the situation of thrombosis accumulation to a certain extent. Meanwhile, the placement of IVCF will change the flow state of blood flow and lead to the deformation of blood vessels. In in vitro experiments, we found that the density of the helical support rod is a key factor affecting the thrombus trapping efficiency, and in addition, the contact area between the IVCF and the vessel wall has a major influence on the risk of IVCF displacement.

Abstract Room-temperature elastocaloric cooling is considered as a zero-global-warming-potential alternative to conventional vapor-compression refrigeration technology. However, the limited entropy and large-deformation features of elastocaloric polymers hinder the creation of the breakthrough in their caloric responses and device development. Herein, we report that the addition of a small amount of inorganic nanofillers into the polymer induces the aggregate of the effective elastic chains via shearing the interlaminar molecular chains, which provides an additional contribution to the entropy in elastocaloric polymers. Consequently, the adiabatic temperature change of −18.0 K and the isothermal entropy change of 187.4 J kg−1 K−1 achieved in the polymer nanocomposites outperform those of current elastocaloric polymers. Moreover, a large-deformation cooling system with a work recovery efficiency of 56.3% is demonstrated. This work opens a new avenue for the development of high-performance elastocaloric polymers and prototypes for solid-state cooling applications.

Abstract Thermal management emerges as a grand challenge of next-generation electronics. Efforts to develop compact, solid-state cooling devices have led to the exploration of the electrocaloric effect of ferroelectric polymers. Despite recent advances, the applications of electrocaloric polymers on electronics operating at elevated temperatures remain essentially unexplored. Here, we report that the ferroelectric polymer composite composed of highly-polarized barium strontium titanate nanofibers and electron-accepting [6,6] phenyl-C61-butyric acid methyl ester retains fast electrocaloric responses and stable cyclability at elevated temperatures. We demonstrate the effectiveness of electrocaloric cooling in a polymer composite for a pyroelectric energy harvesting device. The device utilizes a simulated central processing unit (CPU) as the heat source. Our results show that the device remains operational even when the CPU is overheated. Furthermore, we show that the composite functions simultaneously as a pyroelectric energy converter to harvest thermal energy from an overheated chip into electricity in the electrocaloric process. This work suggests a distinct approach for overheating protection and recycling waste heat of microelectronics.

Abstract Biological networks serve a crucial role in elucidating intricate biological processes. While interspecies environmental interactions have been extensively studied, the exploration of gene interactions within species, particularly among individual microorganisms, is less developed. The increasing amount of microbiome genomic data necessitates a more nuanced analysis of microbial genome structures and functions. In this context, we introduce a complex structure using higher-order network theory, “Solid Motif Structures (SMS)”, via a hierarchical biological network analysis of genomes within the same genus, effectively linking microbial genome structure with its function. Leveraging 162 high-quality genomes of Microcystis, a key freshwater cyanobacterium within microbial ecosystems, we established a genome structure network. Employing deep learning techniques, such as adaptive graph encoder, we uncovered 27 critical functional subnetworks and their associated SMSs. Incorporating metagenomic data from seven geographically distinct lakes, we conducted an investigation into Microcystis’ functional stability under varying environmental conditions, unveiling unique functional interaction models for each lake. Our work compiles these insights into an extensive resource repository, providing novel perspectives on the functional dynamics within Microcystis. This research offers a hierarchical network analysis framework for understanding interactions between microbial genome structures and functions within the same genus.

Abstract Vitamin D deficiency is increasingly common in systemic lupus erythematosus (SLE) patients and is associated with the disease activity and proteinuria. Recently, alterations in metabolism have been recognized as key regulators of SLE pathogenesis. Our objective was to identify differential metabolites in the serum metabolome of SLE with vitamin D deficiency. In this study, serum samples from 31 SLE patients were collected. Levels of 25(OH)D3 were assayed by ELISA. Patients were divided into two groups according to their vitamin D level (20 ng/ml). Untargeted metabolomics were used to study the metabolite profiles in serum by high-performance liquid chromatography-tandem mass spectrometry. Subsequently, we performed metabolomics profiling analysis to identify 52 significantly altered metabolites in vitamin D deficient SLE patients. The area under the curve (AUC) from ROC analyses was calculated to assess the diagnostic potential of each candidate metabolite biomarker. Lipids accounted for 66.67% of the differential metabolites in the serum, highlighted the disruption of lipid metabolism. The 52 differential metabolites were mapped to 27 metabolic pathways, with fat digestion and absorption, as well as lipid metabolism, emerging as the most significant pathways. The AUC of (S)-Oleuropeic acid and 2-Hydroxylinolenic acid during ROC analysis were 0.867 and 0.833, respectively, indicating their promising diagnostic potential. In conclusion, our results revealed vitamin D deficiency alters SLE metabolome, impacting lipid metabolism, and thrown insights into the pathogenesis and diagnosis of SLE.

Abstract Derived from enteroendocrine cells (EECs), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are pivotal incretin hormones crucial for blood glucose regulation. Medications of GLP-1 analogs and GLP-1 receptor activators are extensively used in the treatment of type 2 diabetes (T2D) and obesity. However, there are currently no agents to stimulate endogenous incretin secretion. Here, we find the pivotal role of KCNH2 potassium channels in the regulation of incretin secretion. Co-localization of KCNH2 with incretin-secreting EECs in the intestinal epithelium of rodents highlights its significance. Gut epithelial cell-specific KCNH2 knockout in mice improves glucose tolerance and increases oral glucose-triggered GLP-1 and GIP secretion, particularly GIP. Furthermore, KCNH2-deficient primary intestinal epithelial cells exhibit heightened incretin, especially GIP secretion upon nutrient stimulation. Mechanistically, KCNH2 knockdown in EECs leads to reduced K+ currents, prolonged action potential duration, and elevated intracellular calcium levels. Finally, we found that dofetilide, a KCNH2-specific inhibitor, could promote incretin secretion in enteroendocrine STC-1 cells in vitro and in hyperglycemic mice in vivo. These findings elucidate, for the first time, the mechanism and application of KCNH2 in regulating incretin secretion by EECs. Given the therapeutic promise of GLP-1 and GIP in diabetes and obesity management, this study advances our understanding of incretin regulation, paving the way for potential incretin secretagogue therapies in the treatment of diabetes and obesity.

Abstract Background Influenza, an acute infectious respiratory disease, presents a significant global health challenge. Accurate prediction of influenza activity is crucial for reducing its impact. Therefore, this study seeks to develop a hybrid Convolution Neural Network—Long Short Term Memory neural network (CNN-LSTM) model to forecast the percentage of influenza-like-illness (ILI) rate in Hebei Province, China. The aim is to provide more precise guidance for influenza prevention and control measures. Methods Using ILI% data from 28 national sentinel hospitals in the Hebei Province, spanning from 2010 to 2022, we employed the Python deep learning framework PyTorch to develop the CNN-LSTM model. Additionally, we utilized R and Python to develop four other models commonly used for predicting infectious diseases. After constructing the models, we employed these models to make retrospective predictions, and compared each model’s prediction performance using mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE), and other evaluation metrics. Results Based on historical ILI% data from 28 national sentinel hospitals in Hebei Province, the Seasonal Auto-Regressive Indagate Moving Average (SARIMA), Extreme Gradient Boosting (XGBoost), Convolution Neural Network (CNN), Long Short Term Memory neural network (LSTM) models were constructed. On the testing set, all models effectively predicted the ILI% trends. Subsequently, these models were used to forecast over different time spans. Across various forecasting periods, the CNN-LSTM model demonstrated the best predictive performance, followed by the XGBoost model, LSTM model, CNN model, and SARIMA model, which exhibited the least favorable performance. Conclusion The hybrid CNN-LSTM model had better prediction performances than the SARIMA model, CNN model, LSTM model, and XGBoost model. This hybrid model could provide more accurate influenza activity projections in the Hebei Province.

Abstract It has been shown that noise emissions from HV overhead line conductors can be reduced under rain conditions by making their surfaces superhydrophobic. The working environment makes ensuring the longevity of any treatment a major challenge. The degradation of various superhydrophobic surfaces generated by applying a superhydrophobic coating and patterning microscale channels is assessed under an AC electric field (18 kV/cm) with continuous water spray. By examining the droplet distribution on the surfaces during the degradation and the surface roughness before and after degradation, the authors demonstrate that no water droplets were found on the microscale patterned surface, but droplets were formed on the coated surface after degradation. The surface roughness reduction of the coated surface and microscale patterned surface was 29.8% and 11.3%, respectively, indicating that the microscale patterned surface has better durability than the superhydrophobic coating under the AC electric stress.

Abstract The freezing and thawing cycle is one of the primary causes of damage and instability to buildings in seasonal frost regions. During this process, the mechanical properties of soil are affected, leading to settlement, cracking, or deformation of infrastructure. Mitigating or reducing the occurrence of building frost damage in seasonal frost regions has become an important subject of study. Freeze–thaw (F–T) action will influence the distribution of moisture inside the reinforced soil and change the strength of thawing soil, which is closely related to the main influencing factors, such as initial moisture content, compaction degree, reinforced spacing, number of freeze–thaw cycles (FTC), freezing temperature, and effective vertical stress. Cohesion is an important index to determine the shear strength of clay, which is important to analyze the change in cohesion after F–T. Meanwhile, cohesion is closely related to soil moisture content. This study conducted orthogonal experiments on these primary influencing factors (6 factors at 5 levels) through FTC tests, triaxial tests, and moisture content tests to determine the undrained cohesion and moisture content of the clay after FTC, thereby establishing the influence of reinforcement on soil strength under freeze–thaw conditions. Based on the experimental results, SPSS software was used to fit the regression equations of undrained cohesion and moisture content expressed by the main influencing factors at different heights of the clay. Optimization options for the main influencing factors were obtained with Matlab software when the highest undrained cohesion values 6.8, 10.6, 8.9 kPa and lowest moisture content values 24.0%, 24.3%, 26.2% appeared in upper, middle and lower parts of the testing clay structure respectively, in conditions of − 15 °C freezing temperature and 5 times FTC. And determined the optimal combinations of moisture content, reinforcement spacing, compaction density, and vertical load at different heights. Decreasing reinforced spacing in silty clay was beneficial for liquid underwater seepage after F–T. The redistribution of internal moisture in the soil sample strengthened its undrained cohesion, thereby increasing the soil's shear strength. Comparing reinforcement conditions at different locations, it was found that when there were 3 layers of reinforcement with a spacing of 150 mm between them, this spacing was optimal. It played a significant role in improving the soil's shear strength and enhancing its bearing capacity. For reinforced clay itself, the order of the main factors influencing the undrained cohesion of soil after F–T, from high to low, was initial moisture content, reinforced spacing, and compaction degree.

Abstract Background Hagfishes are fascinating creatures that typically inhabit the deep sea. The deep sea is characterized by its lack of sunlight, primary productivity, and diminishing biomass with increasing ocean depth. Therefore, hagfishes living in this environment must develop effective survival strategies to adapt to the limited food supply. Deep-sea hagfishes have been observed to survive without food intake for up to one year. In this study, we have assembled a high-quality somatic genome of the deep-sea hagfish (Eptatretus okinoseanus) captured below 1,000 m. We compared the genome of E. okinoseanus with the genomes of inshore hagfish, lampreys, and other related species to investigate the genetic factors underlying the deep-sea hagfish adaptations to the environment. Results The E. okinoseanus somatic genome was estimated to be 1.89 Gb and assembled into 17 pseudochromosomes. Phylogenetic analysis showed that shallow-sea and deep-sea hagfishes diverged approximately 58.8 million years ago. We found Perilipin gene family was significantly expanded in deep sea E. okinoseanus, which promotes triacylglycerol storage. Furthermore, a series of genes involved in fatty acid synthesis and metabolism, blood glucose regulation, and metabolic rate regulation were also expanded, rapid evolution or positive selection, and these changes contribute to their efficiency in energy utilization. Among these genes, the positively selected gene JNK may play an important role in energy metabolism. In addition, the olfactory receptors of the deep-sea hagfish were significantly expanded to 86, and three conserved motifs present only in hagfishes olfactory receptors were identified, which may facilitate the rapid localization of carrion. Conclusions This study provides valuable genomic resources for insights into the survival strategies of deep-sea hagfishes in oligotrophic environments.

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

Background: Light at night (LAN) has become a global concern. However, little is known about the effects of bedroom LAN exposure on glucose metabolism markers. We aimed to explore the association between intensity and duration of bedroom LAN exposure with glucose metabolism markers, and the role of circadian-dependent meal timing in these associations. Methods: Real-ambient bedroom LAN exposure was measured using a portable illuminance meter for two consecutive days. Seven consecutive days of sleep time and 24-h dietary records were assessed by wrist-worn accelerometer and mobile phone photos, respectively. Circadian-dependent meal timing, including the timing of meal relative to clock time and sleep time, was calculated from 24-h dietary records and sleep data. Results: The mean age of participants was 18.7 years, and 32.8 % were male. Per SD lx increase of bedroom LANavg was associated with 1.75 μU/mL-increase in INS (95 %CI: 0.10, 2.50), 0.61 unit-increase in HOMA-IR (95 %CI: 0.43, 0.79), and 0.09 unit-increase in TyG (95 %CI: 0.04, 0.15); per SD min increase of bedroom LAN3 was associated with 1.61 μU/mL-increase in INS (95 %CI: 0.84, 2.37), 0.48 unit-increase in HOMA-IR (95 %CI: 0.29, 0.67), and 0.07 unit-increase in TyG (95 %CI: 0.01, 0.13). Nevertheless, these associations were found to be significant in later circadian-dependent meal timing group while weaker or not significant in earlier circadian-dependent meal timing group (time of first meal ≤ 9:00, time of last meal ≤ 19:00, first meal - sleep end ≤ 2 h, and sleep onset - last meal ≥ 5 h). Conclusions: Overall, bedroom LAN exposure was associated with impaired glucose metabolism markers among young adults. Importantly, circadian-dependent meal timing may have potentially moderate effects on these associations. Keeping bedroom darkness at night and adhering to early eating pattern may be important public health strategies to reduce the risk of glucose metabolism disorders.