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Background: Hepatocellular carcinoma (HCC), a prevalent form of primary liver malignancy, arises from liver-specific hepatocytes. Senecio scandens Buch.-Ham(Climbing senecio) is a bitter-tasting plant of the Compositae family with anti-tumor properties. This study aims to identify the molecular targets and pathways through which Climbing senecio regulates HCC. Methods: Active ingredients of Climbing senecio were collected from four online databases and mapped to relevant target databases to obtain predicted targets. After recognizing the key pathways through which Climbing senecio acts in HCC. Gene expression data from GSE54238 Underwent differential expression and weighted gene correlation network analyses to identify HCC-related genes. The “Climbing senecio-Hepatocellular Carcinoma Targets” network was constructed using Cytoscape 3.10.1 software, followed by topology analysis to identify core genes. The expression and distribution of key targets were evaluated, and the differential expression of each key target between normal and diseased samples was calculated. Moreover, single-cell data from the Gene Expression Omnibus (GSE202642) were used to assess the distribution of Climbing senecio’s bioactive targets within major HCC clusters. An intersection analysis of these clusters with pharmacological targets and HCC-related genes identified Climbing senecio’s primary targets for this disease. Cell communication, receiver operating characteristic (ROC)analysis, survival analysis, immune filtration analysis, and molecular docking studies were conducted for detailed characterization. Results: Eleven components of Climbing senecio were identified, along with 520 relevant targets, 300 differentially expressed genes, and 3765 co-expression module genes associated with HCC. AKR1B1, CA2, FOS, CXCL2, SRC, ABCC1, and PLIN1 were identified within the intersection of HCC-related genes and Climbing senecio targets. TGFβ, IL-1, VEGF, and CXCL were identified as significant factors in the onset and progression of HCC. These findings underscore the anti-HCC potential and mode of action of Climbing senecio, providing insights into multi-targeted treatment approaches for HCC. Conclusions: This study revealed that Climbing senecio may target multiple pathways and genes in the process of regulating HCC and exert potential drug effects through a multi-target mechanism, which provides a new idea for the treatment of HCC. However, the research is predicated on network database analysis and bioinformatics, offering insights into HCC therapeutic potential while emphasizing the need for further validation.

BackgroundBrain tumors, especially gliomas, are known for high lethality. It is currently understood that the correlations of tumors with coagulation and inflammation have been gradually revealed.ObjectiveThis study aimed to explore the potential value of several reported peripheral blood parameters as comprehensively as possible, with preoperative diagnosis and identification of brain tumors (focus on gliomas).MethodsPatients with central nervous system tumors (craniopharyngioma, ependymoma, spinal meningioma, acoustic neuroma, brain metastases, meningioma, and glioma) or primary trigeminal neuralgia admitted to our hospital were retrospectively analyzed. The results of the routine coagulation factor test, serum albumin test, and blood cell test in peripheral blood were recorded for each group of patients on admission. Neutrophil–lymphocyte ratio (NLR), derived NLR (dNLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), prognostic nutritional index (PNI), the systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and their pairings were calculated. Their ability to identify brain tumors and their correlation with glioma grade were analyzed.ResultsA total of 698 patients were included in this retrospective case–control study. Glioma patients had higher NLR, SII, and PIV but lower LMR. The NLR in the brain metastasis group was lower than that in the control, meningioma, and acoustic neuroma groups, but the SII and PIV were higher than those in the ependymoma group. Fibrinogen, white blood cell count, neutrophil count, NLR, SII, and PIV in the GBM group were higher than those in the control group. In all comparisons, NLR and NLR + dNLR showed the greatest accuracy, with areas under the curve (AUCs) of 0.7490 (0.6482–0.8498) and 0.7481 (0.6457–0.8505), respectively. PIV, dNLR + PIV, and LMR + PIV ranked second, with AUCs of 0.7200 (0.6551–0.7849), 0.7200 (0.6526–0.7874), 0.7204 (0.6530–0.7878) and 0.7206 (0.6536–0.7875), respectively.ConclusionNLR, PIV, and their combinations show high sensitivity and specificity in the diagnosis of brain tumors, especially gliomas. Overall, our results provide evidence for these convenient and reliable peripheral blood markers.

Objectives: Cardiorenal syndrome type-3 (CRS-3) is an abrupt worsening of cardiac function secondary to acute kidney injury. Mitochondrial dysfunction is a key pathological mechanism of CRS-3, and empagliflozin can improve mitochondrial biology by promoting mitophagy. Here, we assessed the effects of empagliflozin on mitochondrial quality surveillance in a mouse model of CRS-3. Methods: Cardiomyocyte-specific FUNDC1-knockout (FUNDC1CKO) mice were subjected to CRS-3 prior to assessment of mitochondrial homeostasis in the presence or absence of empagliflozin. Results: CRS-3 model mice exhibited lower heart function, increased inflammatory responses and exacerbated myocardial oxidative stress than sham-operated controls; however, empagliflozin attenuated these alterations. Empagliflozin stabilized the mitochondrial membrane potential, suppressed mitochondrial reactive oxygen species production, increased mitochondrial respiratory complex activity and restored the oxygen consumption rate in cardiomyocytes from CRS-3 model mice. Empagliflozin also normalized the mitochondrial morphology, mitochondrial dynamics and mitochondrial permeability transition pore opening rate in cardiomyocytes. Cardiomyocyte-specific ablation of FUN14 domain-containing protein 1 (FUNDC1) in mice abolished the protective effects of empagliflozin on mitochondrial homeostasis and myocardial performance. Empagliflozin activated β-catenin and promoted its nuclear retention, thus increasing FUNDC1-induced mitophagy in heart tissues; however, a β-catenin inhibitor reversed these effects. Conclusions: In summary, empagliflozin activated Wnt/β-catenin to stimulate FUNDC1-dependent mitochondrial quality surveillance, ultimately improving mitochondrial function and cardiac performance during CRS-3. Thus, empagliflozin could be considered for the clinical management of heart function following acute kidney injury.

BackgroundTo investigate the association between coping styles, gender, their interactions and non-suicidal self-injurious (NSSI) behaviors among middle school students in rural western China under COVID-19.MethodsA multicentre cross-sectional study method was used to conduct an online survey of 8,361 students from 23 middle schools in the northern Sichuan region by clustering sampling, using the General Information Questionnaire, the Ottawa Self-Injury Inventory, and the Coping Style Scale for Middle School Students.ResultsThe past year prevalence of NSSI among middle school students in rural west China was 5.7%. The differences in scores between those with and without NSSI on all dimensions of coping styles were statistically significant (p < 0.001). Multivariate logistic regression analysis revealed that vocational high school (OR = 1.67), girls (OR = 2.5), single parent with divorced parents (OR = 1.89), remarriage with divorced parents (OR = 1.81), and tolerance (OR = 1.17), venting emotions (OR = 1.15) and fantasy/denial (OR = 1.07) in coping styles may increase the risk of NSSI among middle school students, while problem solving (OR = 0.9) and seeking social support (OR = 0.9) among coping styles may reduce the risk of NSSI among middle school students. The interaction results show that gender has a moderating role in the process of endurance, avoidance, venting of emotions, and fantasy/denial influencing non-suicidal self-injury in middle school students.ConclusionThere is an association between coping styles and self-injury among middle school students in rural areas in western China, with gender playing a moderating role. Active attention should be paid to students' coping styles and encouraging them to adopt positive coping styles as well as avoid negative coping styles, especially in the case of girls, which can help prevent self-injury.

Objectives: Our ex vivo study was designed to determine the sequestration of teicoplanin, tigecycline, micafungin, meropenem, polymyxin B, caspofungin, cefoperazone sulbactam, and voriconazole in extracorporeal membrane oxygenation (ECMO) circuits.Methods: Simulated closed-loop ECMO circuits were prepared using 2 types of blood-primed ECMO. After the circulation was stabilized, the study drugs were injected into the circuit. Blood samples were collected at 2, 5, 15, 30 min, 1, 3, 6, 12, and 24 h after injection. Drug concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Control groups were stored at 4°C after 3, 6, 12, and 24 h immersing in a water bath at 37°C to observe spontaneous drug degradation.Results: Twenty-six samples were analyzed. The average drug recoveries from the ECMO circuits and control groups at 24 h relative to baseline were 67 and 89% for teicoplanin, 100 and 145% for tigecycline, 67 and 99% for micafungin, 45 and 75% for meropenem, 62 and 60% for polymyxin B, 83 and 85% for caspofungin, 79 and 98% for cefoperazone, 75 and 87% for sulbactam, and 60 and 101% for voriconazole, respectively. Simple linear regression showed no significant correlation between lipophilicity (r2 = 0.008, P = 0.225) or the protein binding rate (r2 = 0.168, P = 0.479) of drugs and the extent of drug loss in the ECMO circuits.Conclusions: In the two ECMO circuits, meropenem and voriconazole were significantly lost, cefoperazone was slightly lost, while tigecycline and caspofungin were not lost. Drugs with high lipophilicity were lost more in the Maquet circuit than in the Sorin circuit. This study needs more in vivo studies with larger samples for further confirmation, and it suggests that therapeutic drug concentration monitoring should be strongly considered during ECMO.

Background/Aims: Glioblastoma is the most common and aggressive brain tumor and carries a poor prognosis. Previously, we found that neurotensin receptor 1 (NTSR1) contributes to glioma progression, but the underlying mechanisms of NTSR1 in glioblastoma invasion remain to be clarified. The aim of this study was to investigate the molecular mechanisms of NTSR1 in glioblastoma invasion. Methods: Cell migration and invasion were evaluated using wound-healing and transwell assays. Cell proliferation was detected using CCK-8. The expression of NTSR1, Jun, and suppressor of cytokine signaling 6 (SOCS6) was detected using western blotting. The expression of miR-494 was detected by Quantitative real-time PCR. Chromatin immunoprecipitation assay was performed to examine the interaction between Jun and miR-494 promoter. Dual-luciferase reporter assay and western blotting were performed to identify the direct regulation of SOCS6 by miR-494. An orthotopic xenograft mouse model was conducted to assess tumor growth and invasion. Results: NTSR1 knockdown attenuated the invasion of glioblastoma cells. Jun was positively regulated by NTSR1, which promoted miR-494 expression through binding to miR-494 promoter. SOCS6 was confirmed as a direct target of miR-494, thus, NTSR1-induced miR-494 upregulation resulted in SOCS6 downregulation. Both miR-494 and SOCS6 were involved in the NTSR1-induced invasion of glioblastoma cells. In vivo, tumor invasion and growth were inhibited by NTSR1 knockdown, but were restored with miR-494 overexpression. Conclusion: NTSR1 knockdown inhibited glioblastoma invasion via the Jun/miR-494/SOCS6 axis.

Background and Aim: Osteosarcoma is a devastating tumor of bone, primarily affecting adolescents. Parthenolide, a naturally occurring small molecule that interferes with NF-κB signaling, has recently attracted considerable attention because of its pharmacological action involving anti-cancer effects. However, the mechanism of the cytotoxic effect exerted by parthenolide on tumor cells is not clearly defined today. Methods: In this study, the effects of parthenolide were evaluated and characterized in human osteosarcoma cancer cell. Cell viability was assessed by CCK-8. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Results: Our results suggest that parthenolide did not cause caspase-dependent cell death in osteosarcoma cancer cells, as indicated by the absence of significant early apoptosis as well as caspase-3 cleavage. Instead, parthenolide increased the autophagy and mitophagy, as characterized by increased PINK1 and Parkin translocation to mitochondria and enhanced autophagy proteins. The induction of autophagy by parthenolide was associated with the increase of reactive oxygen species (ROS). ROS antioxidants N-acetylcysteine (NAC) attenuated parthenolide-induced autophagy activity. Conclusions: Our findings unveil a novel mechanism of drug action by parthenolide in osteosarcoma cancer cells and suggest a potential value of treating osteosarcoma cancer through a caspase-independent autophagic cell death by ROS activation.

A distributed cooperation scheme on frequency resource sharing is proposed to improve the quality of service (QoS) in device-to-device (D2D) communications underlaying cellular networks. Specifically, we formulate the resource allocation problem as a coalition formation game with transferable utility, in which all users have the incentive to cooperate with some others and form a competitive group to maximize the probability of obtaining their favorite spectrum resources. Taking the cost for coalition formation into account, such as the path loss for data sharing, we prove that the core of the proposed game is empty, which shows the impossibility of grand coalition. Hence, we propose a distributed merge-and-split based coalition formation algorithm based on a new defined Max-Coalition order to effectively solve the coalition game. Compared with the exhaustive search, our algorithm has much lower computer complexity. In addition, we prove that stability and convergence of the proposed algorithm using the concept of a defection function. Finally, the simulation results show that the proposed scheme achieves a suboptimal performance in terms of network sum rate compared with the centralized optimal resource allocation scheme obtained via exhaustive search.

Abstract The Tonian Period (1000–720 Ma) bore witness to the transition from a prokaryote-dominated marine ecosystem to one characterized by the proliferation of eukaryotes. This fundamental shift has generally been attributed to evolving marine redox states. Here, we present sedimentological and geochemical analyses of the early Tonian Huainan, Feishui, and Huaibei groups in the Xuhuai basin of the North China craton. Multiple redox proxies show consistent, water depth-dependent variations across the Xuhuai basin. Excess barium contents and Ba/Al ratios further highlight spatial variations in primary productivity which ultimately regulate basinal redox structures. We propose that a shallow-water oxygen minimum zone sandwiched between the oxic/suboxic mid-depth and surface layer water masses occur in the oligotrophic Xuhuai basin, which is analogous to, but much shallower than modern oxygen minimum zones. Such marine redox architectures may benefit the maintenance of a bioavailable nitrate reservoir in the ocean, foreboding the subsequent expansion of eukaryotes.

OBJECTIVES Ascending to altitudes >2500 m may lead to acute mountain sickness (AMS). METHODS The demographics, height, weight, body mass index (BMI), smoking, and alcohol consumption of 104 healthy controls were collected in Chengdu (500 m). Heart rate (HR), saturation of pulse oxygen (SpO2), and AMS-related symptoms were collected in Hoh Xil (4200 m). A headache with Lake Louise score ≥3 was defined as AMS. RESULTS The incidence of AMS was 60.58%. AMS group had a lower SpO2 and higher HR than non-AMS group. Alcohol consumption seemed a risk factor for AMS. There was no difference in the BMI, age, height, weight, and smoking between AMS and non-AMS groups. The most common AMS symptom was headache, followed by dyspnea, insomnia, dizziness, lassitude, and anorexia. Women were prone to suffer from dizziness. The value of SpO2 and HR was improved both in AMS and non-AMS groups after hypoxia acclimatization, and the value showed greater improvement in AMS group. Oxygen therapy decreased the AMS-induced tachycardia, which had no any effect on SpO2 and symptom alleviating time. CONCLUSION Lower SpO2 and higher HR following exposure to high altitude were associated with AMS susceptibility. The anthropometric data changes were larger in AMS group than non-AMS group before and after hypoxia acclimatization.

Objective The experiment aimed to determine the standardized ileal digestibility (SID) of crude protein (CP) and amino acids (AA) in 10 brown rice samples fed to pigs, and to construct predictive models for SID of CP and AA based on the physical characteristics and chemical composition of brown rice. Methods Twenty-two cannulated pigs (initial body weight: 42.0±1.2 kg) were assigned to a replicated 11×3 incomplete Latin square design, including an N-free diet and 10 brown rice diets. Each period included 5 d adaptation and 2 d ileal digesta collection. Chromic oxide was added at 0.3% to all the diets as an indigestible marker for calculating the ileal CP and AA digestibility. Results The coefficients of variation of all detected indices for physical characteristics and chemical composition, except for bulk weight, dry matter (DM) and gross energy, in 10 brown rice samples were greater than 10%. The SID of CP, lysine (Lys), methionine, threonine (Thr), and tryptophan (Trp) in brown rice was 77.2% (62.6% to 85.5%), 87.5% (80.3% to 94.3%), 89.2% (78.9% to 98.9%), 55.4% (46.1% to 67.6%) and 92.5% (86.3% to 96.3%), respectively. The best prediction equations for the SID of CP, Lys, Thr, and Trp were as following, SIDCP = −664.181+8.484×DM (R2 = 0.40), SIDLys = 53.126+6.031×ether extract (EE)+0.893×thousand-kernel volume (R2 = 0.66), SIDThr = 39.916+7.843×EE (R2 = 0.41), and SIDTrp = −361.588+4.891×DM+0.387×total starch (R2 = 0.85). Conclusion Overall, a great variation exists among 10 sources of brown rice, and the thousand-grain volume, DM, EE, and total starch can be used as the key predictors for SID of CP and AA.

Abstract Background Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. Methods Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. Results We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. Conclusion Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Abstract Objective To explore the application effect of the direct reporting system of adverse nursing events and special continuous nursing quality improvement measures in the management of these adverse events. Methods The implementation time of continuous nursing improvement based on the direct reporting system was the demarcation point. We retrospectively collected and analyzed nursing adverse event reports and hospitalization data from Xiangtan Central Hospital before implementation (2015–2018) and after implementation (2019–2022). The active reporting rate of adverse events, the composition of these events and the processing time were compared between the two groups. Results The rate of active reporting of adverse events before the implementation was lower than that after the implementation (6.7% vs. 8.1%, X 2 = 25.561, P

Corn (C), wheat (W), and paddy rice (PR) are important energy sources and are commonly used in feed production for swine. This study mainly focuses on the variation and regularities of microbiota and metabolites in the gastrointestinal tract (GIT) of pigs in response to C, W, and PR. A total of 18 pigs were allotted into three dietary groups with six replicated pigs and received diets containing C, W, or PR as the sole energy source, respectively. The results showed that digestive parts significantly affected the diversity of microbial communities. Cereal grain sources significantly influenced the β-diversity of microbial communities in the colon and rectum. Campylobacterota and Proteobacteria are mainly distributed in the duodenum, Lactobacillus in the jejunum, and Bacteroidota in the colon and rectum. The W diet increased the Bacteroidota, Spirochaetota, and Prevotellaceae_NK3B31_group abundances and showed the highest concentrations of all short-chain fatty acids (SCFAs) in the hindgut. Fibrobacterota, Bacteroidota, Spirochaetota, Prevotellaceae_NK3B31_group, Prevotella, and Treponema in the colon or rectum were positively correlated with acetate, propionate, butyrate, and total SCFAs. These findings suggested that aerobic bacteria and facultative anaerobes in the foregut will gradually be replaced by anaerobes in the hindgut. The W diet had the best fermentability and was beneficial to the colonization of microbial communities that mainly used carbohydrates. The hindgut flora of the PR diet group may be more balanced with fewer potential pathogenic bacteria. Many microbial communities have been identified to contribute positively to the SCFA production of the hindgut. Collectively, our study revealed the spatial variation regularities of GIT microbial communities in an adult pig model and provided new insights into GIT microbiota and responses of metabolites to cereal grain diets.

The vibration of a ship’s propulsion shaft system directly affects the ship’s lifespan, and many studies have designed vibration absorbers only for one of the natural frequencies of a ship’s propulsion shaft system without considering the influence of multiple low-order resonance frequencies. In this paper, a vibration absorber combined with a magnetorheological elastomer vibration absorber and a rubber vibration absorber in series is designed, and it can cover two torsional natural frequency band ranges to achieve better vibration reduction performances in multiple different torsional natural frequencies. The torsional natural frequency of the propulsion shafting of a 45 m fishing vessel is determined based on a multiple-degrees-of-freedom equivalent discretization model. Two natural frequencies, 22.4 Hz and 131.4 Hz, of a ship propulsion shaft system are selected as the design goal parameters of the combined vibration absorber. The magnetic field is simulated to ensure that the magnetic field generated by an energized coil can meet requirements. Then, a dynamic simulation of the ship propulsion shaft system with a combined vibration absorber is conducted via co-simulation. Afterward, the device is installed on the intermediate shaft of the ship propulsion shaft system for simulation, and the vibration reduction effect of the device is analyzed at different frequencies by controlling the current. When the device is controlled to operate at the optimal frequency point, the results show that the angular acceleration vibration amplitude reduction around the first and third torsional natural frequencies of the propulsion shaft system reaches 90% and 18%, respectively. This study provides new ideas for the intelligent and controllable vibration damping of ship propulsion shaft systems, especially for the development trend of intelligent ship equipment under complex working conditions.

Objective: The experiment was conducted to determine the apparent or standardized ileal digestibility (AID or SID) of crude protein (CP) and amino acids (AA) in 10 rapeseed cake samples fed to pigs, and to construct predictive models for the SID of CP and AA based on the chemical composition of rapeseed cakes. Methods: Twenty-two cannulated pigs (initial body weight: 39.8 ± 1.2 kg) were assigned to two 11 × 3 incomplete Latin square designs, including an N-free diet and 10 diets containing rapeseed cake. Each experimental period included 5 days of adaptation and 2 days of ileal digesta collection. Titanium dioxide (TiO2) was added at 0.3% to all the diets as an indigestible marker for calculating the ileal CP and AA digestibility. Results: The coefficients of variation (CV) of the content of crude fat (EE), crude fiber (CF), neutral detergent fiber (NDF), acid detergent fiber (ADF), and total glucosinolates (TGS) in 10 samples of rapeseed cake were greater than 10%. The standardized ileal digestibility (SID) of crude protein (CP), lysine (Lys), methionine (Met), threonine (Thr), and tryptophan (Trp) in rapeseed cake was 73.34% (61.49 to 81.12%), 63.01% (41.41 to 73.10%), 69.47% (50.55 to 88.16%), 79.61% (74.41 to 87.58%), and 94.43% (91.34 to 97.20%), respectively. The best prediction equations for SIDCP, SIDLys, and SIDVal were as follows: SIDCP = 90.124 − 0.54NDF (R2 = 0.58), SIDLys = 100.107 − 1.229NDF (R2 = 0.94), and SIDVal = 151.012 − 2.990TGS (R2 = 0.57). Conclusion: Overall, great variation exists among the 10 rapeseed cakes, and the NDF, TGS, and heating temperature can be used as the key predictors for the SID of CP and AA.

Sandy-clay mixtures are commonly used in civil engineering projects, such as transportation and water resources, due to their unique construction properties. While the macromechanical characteristics of these mixtures under saturated conditions are well understood, their behavior in unsaturated states is still not fully elucidated. This study aims to investigate the mechanical behavior of sand–clay mixtures under unsaturated conditions by examining the influence of varying sand content and matric suction on their shear strength. The research includes unsaturated shear strength tests and nuclear magnetic resonance (NMR) experiments to analyze the pore characteristics within the mixtures at different sand content levels. The correlation between changes in pore structure and shear strength is systematically analyzed. The unsaturated shear strength of the mixtures is predicted using the Fredlund shear strength formula and compared with the measured values. The results indicate that the unsaturated shear strength of the mixture decreases as the sand content increases but stabilizes once the sand content reaches 20%. Below 20% sand content, the changes in micropore distribution are not significant with increasing sand content. However, beyond 20% sand content, there is a noticeable increase in the ratio of large pores and a decrease in the proportion of small pores. The sand content of 20% represents a critical threshold for the strength and porosity variations in the mixture. Under constant matric suction, the unsaturated shear strength of the mixture improves with the increase in sand content. However, the predictive accuracy of the Fredlund shear strength formula gradually diminishes as the sand content increases.

e23sFv is a HER2-targeted single-chain variable fragment (scFV) that was characterized as the targeting portion of a HER2-targeted tumour proapoptotic molecule in our previous study. In vitro antibody affinity maturation is a method to enhance antibody affinity either by complementarity-determining region (CDR) mutagenesis or by framework region (FR) engraftment. In the present study, the affinity of e23sFv was enhanced using two strategies. In one approach, site-directed mutations were introduced into the FRs of e23sFv (designated EMEY), and in the other approach e23sFv FRs were substituted with FRs from the most homologous screened antibodies (designated EX1 and EX2). Notably, EX1 derived from the FR engraftment strategy demonstrated a 4-fold higher affinity for HER2 compared with e23sFv and was internalized into HER2-overexpressing cells; however, EMEY and EX2 exhibited reduced affinity for HER2 and decreased internalization potential compared with EX1. The 3D structure of EX1 and the HER2-EX1 complex was acquired using molecular homology modelling and docking and the HER2 epitopes of EX1 and the molecular interaction energy of the EX1-HER2 complex were predicted. In the present study, it was demonstrated that scFv affinity improvement based on sequence alignment was feasible and effective. Moreover, the FR grafting strategy was indicated to be more effective and simple compared with site-directed mutagenesis to improve e23sFv affinity. In conclusion, it was indicated that the affinity-improved candidate EX1 may present a great potential for the diagnosis and treatment of HER2-overexpressing tumours. [ABSTRACT FROM AUTHOR]

This study proposes a dual-coil magnetorheological torsional vibration damper (MRTVD) and verifies the effectiveness of semi-active damping control to suppress the shaft system’s torsional vibration via experimental research. Firstly, the mechanical model of the designed MRTVD and its coupling mechanical model with the rotating shaft system are established. Secondly, the torsional response of the shaft system is obtained via resonance experiments, and the influence of the current on the torsional characteristics of the magnetorheological torsional damper is analyzed. Finally, the MRTVD is controlled using the skyhook control approach. The experimental results demonstrate that when the main shaft passes through the critical speed range at various accelerations, the amplitude of the shaft’s torsional vibration decreases by more than 15%, and the amplitude of the shaft’s torsional angular acceleration decreases by more than 22%. These conclusions validate the inhibitory effect of MRTVD on the main shaft’s torsional vibrations under skyhook control.

In recent years, rehabilitation robots have been developed and used in rehabilitation training for patients with hemiplegia. In this paper, a rehabilitation training robot with variable damping is designed to train patients with hemiplegia to recover upper limb function. Firstly, a magnetorheological joint damper (MR joint damper) is designed for the rehabilitation training robot, and its structural design and dynamic model are tested theoretically and experimentally. Secondly, the rehabilitation robot is simplified into a spring-damping system, and the rehabilitation training controller for human movement is designed. The rehabilitation robot dynamically adjusts the excitation current according to the feedback speed and human–machine interaction torque, so that the rehabilitation robot always outputs a stable torque. The magnetorheological joint damper acts as a clutch to transmit torque safely and stably to the robot joint. Finally, the upper limb rehabilitation device is tested. The expected torque is set to 20 N, and the average value of the output expected torque during operation is 20.02 N, and the standard deviation is 0.635 N. The output torque has good stability. A fast (0.5 s) response can be achieved in response to a sudden motor speed change, and the average expected output torque is 20.38 N and the standard deviation is 0.645 N, which can still maintain the stability of the output torque.