Development of a Novel Nomogram to Predict Major Adverse Cardiac Events in Patients with Chronic Total Occlusion.

Objectives: To create a nomogram using single photon emission computed tomography (SPECT) myocardial perfusion imaging and 18F-FDG positron emissions tomography (PET) gated myocardial metabolism imaging to forecast major adverse cardiovascular events (MACE) in chronic total occlusion (CTO) patients treated with optimal medical therapy (OMT). Methods: A total of 257 patients who received OMT between January 2016 and December 2021 were included in this retrospective study. Patients were randomly divided into development (n=179) and validation (n=78) cohorts. A thorough evaluation was conducted, encompassing clinical features and imaging analysis, which involved assessing myocardial perfusion and metabolism. Independent risk factors were identified using least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses. Calibration curves and decision curve analysis (DCA) were used to evaluate the clinical usefulness. Results: In the development cohort, 53 patients (29.6%) experienced MACE out of 179 patients, while in the validation cohort, MACE occurred in 23 (29.5%) patients out of 78. The PET-left ventricular end-systolic volume (P-ESV) (HR 1.01; 95% CI 1.003-1.017; p=0.003), hibernating myocardium / total perfusion defect (HM/TPD) (HR 1.053; 95% CI 1.038-1.069; p<0.001), PET-left ventricular ejection fraction (P-LVEF) (HR 0.862; 95% CI 0.788-0.943; p=0.001), and left anterior descending branch (LAD) (HR 2.303; 95% CI 1.086-4.884; p=0.03) were significantly associated with MACE and were used to develop the nomogram. The nomogram demonstrated excellent discrimination with C-indexes of 0.931 and 0.911 in the development and validation cohorts. DCA determined that the model exhibited a considerably superior net advantage in predicting MACE. Conclusion: A new nomogram integrating clinical factors and imaging features was created to predict the risk of MACE in patients with CTO.

Global research trends in nursing leadership from 1985 to 2022: a bibliometric analysis.

PURPOSE: Developing nursing leadership has become a key policy priority to achieve universal health coverage. This study aims to explore the current status, developing trends and research frontiers in the field of nursing leadership. DESIGN/METHODOLOGY/APPROACH: In total, 1,137 articles and reviews on nursing leadership from 1985 to 2022 were retrieved from the Web of Science Core Collection database. Trends of publications, journals, countries/regions, institutions, documents and keywords were visualized and analyzed using Microsoft Excel and CiteSpace software. FINDINGS: Nursing leadership research showed an overall increase in number despite slight fluctuations in annual publications. The USA was the leading country in nursing leadership research, and the University of Alberta was the most productive institution. The Journal of Nursing Management was the most widely published journal that focused on nursing leadership, followed by the Journal of Nursing Administration. Keyword analysis showed that the main research hotspots of nursing leadership are improvement, practice and impact of nursing leadership. ORIGINALITY/VALUE: This article summarizes the current state and frontiers of nursing leadership for researchers, managers and policy makers, as well as follow-up, development and implementation of nursing leadership. More research is needed that focuses on the improvement, practice and impact of nursing leadership, which are cyclical, complementary and mutually reinforcing. Longitudinal and intervention studies of nursing leadership, especially on patient prognosis, are also particularly needed.

Efficacy of revascularization in CTO patients based on hibernating myocardium therapy.

BACKGROUND: The effectiveness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still uncertain, especially for patients with ischemic left ventricular dysfunction. This study aimed to assess hibernating myocardium (HM), as determined by single-photon emission computed tomography (SPECT) and 18F-FDG positron emission tomography (PET), and to compare the benefits of PCI and optimal medical therapy (OMT). METHODS: A retrospective study collected data from 332 patients with CTO and ischemic left ventricular dysfunction. The study compared patients who underwent PCI or OMT via propensity score matching (PSM) analysis which was performed with a 1:2 matching protocol using the nearest neighbour matching algorithm. The primary endpoint of the study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, readmission for worsening heart failure (WHF), revascularization and myocardial infarction (MI). RESULTS: After PSM, there were a total of 246 individuals in the PCI and OMT groups. Following Cox regression, hibernating myocardium/total perfusion defect (HM/TPD) was identified as an independent risk factor (hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.008-1.052, p = .007). The cut-off value of HM/TPD was 38%. The results of the subgroup analysis suggest that for patients with HM/TPD >38%, the OMT group had a greater risk of MACE (p = .035). A sensitivity analysis restricting patients with single-vessel CTO lesions, HM/TPD remained an independent predictor (HR 1.025, 95% CI 1.008-1.043, p = .005). CONCLUSION: HM/TPD is an independent predictor of MACE, and for patients with HM/TPD > 38%, CTO-PCI had a lower risk of MACE compared with OMT. However, further validation is still needed through large-scale studies.

The effects of hyaluronan and proteoglycan link protein 1 (HAPLN1) in ameliorating spinal cord injury mediated by Nrf2.

Excessive inflammatory response and oxidative stress (OS) play an important role in the pathogenesis of spinal cord injury (SCI). Balance of inflammation and prevention of OS have been considered an effective strategy for the treatment of SCI. Hyaluronan and proteoglycan link protein 1 (HAPLN1), also known as cartilage link protein, has displayed a wide range of biological and physiological functions in different types of tissues and cells. However, whether HAPLN1 regulates inflammation and OS during SCI is unknown. Therefore, we aimed to examine whether HAPLN1 can have a protective effect on SCI. In this study, both in vitro and in vivo SCI models were established. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining assays were used. Western blotting and enzyme-linked immunosorbent assay were employed to assess the expression of proteins. Our results demonstrate that the administration of HAPLN1 promoted the recovery of motor neurons after SCI by increasing the Basso mouse scale score, increasing the numbers of motor neurons, and preventing apoptosis of spinal cord cells. Additionally, HAPLN1 mitigated OS in spinal cord tissue after SCI by increasing the content of superoxide dismutase SOD and the activity of glutathione peroxidase but reducing the levels of malondialdehyde. Importantly, we found that HAPLN1 stimulated the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and stimulated the expression of heme oxygenase-1 and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase-1, which mediated the attenuation of HAPLN1 in activation of the NOD-like receptor protein 3 (NLRP3) inflammasome by reducing the levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin-1ß. Correspondingly, in vitro experiments show that the presence of HAPLN1 suppressed the NLRP3 inflammasome and prevented cell injury against H2O2 in PC12 cells. These effects were mediated by the Nrf2/ARE pathway, and inhibition of Nrf2 with ML385 abolished the beneficial effects of HAPLN1. Based on these findings, we conclude that HAPLN1 inhibits the NLRP3 inflammasome through the stimulation of the Nrf2/ARE pathway, thereby suppressing neuroinflammation, enhancing motor neuronal survival, and improving the recovery of nerve function after SCI.

A novel tumor mutation-related long non-coding RNA signature for predicting overall survival and immunotherapy response in lung adenocarcinoma.

Background: Immunotherapy has changed the treatment landscape for lung cancer. This study aims to construct a tumor mutation-related model that combines long non-coding RNA (lncRNA) expression levels and tumor mutation levels in tumor genomes to detect the possibilities of the lncRNA signature as an indicator for predicting the prognosis and response to immunotherapy in lung adenocarcinoma (LUAD). Methods: We downloaded the tumor mutation profiles and RNA-seq expression database of LUAD from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were extracted based on the cumulative number of mutations. Cox regression analyses were used to identify the prognostic lncRNA signature, and the prognostic value of the five selected lncRNAs was validated by using survival analysis and the receiver operating characteristic (ROC) curve. We used qPCR to validate the expression of five selected lncRNAs between human lung epithelial and human lung adenocarcinoma cell lines. The ImmuCellAI, immunophenoscore (IPS) scores and Tumor Immune Dysfunction and Exclusion (TIDE) analyses were used to predict the response to immunotherapy for this mutation related lncRNA signature. Results: A total of 162 lncRNAs were detected among the differentially expressed lncRNAs between the Tumor mutational burden (TMB)-high group and the TMB-low group. Then, five lncRNAs (PLAC4, LINC01116, LINC02163, MIR223HG, FAM83A-AS1) were identified as tumor mutation-related candidates for constructing the prognostic prediction model. Kaplan‒Meier curves showed that the overall survival of the low-risk group was significantly better than that of the high-risk group, and the results of the GSE50081 set were consistent. The expression levels of PD1, PD-L1 and CTLA4 in the low-risk group were higher than those in the high-risk group. The IPS scores and TIDE scores of patients in the low-risk group were significantly higher than those in the high-risk group. Conclusion: Our findings demonstrated that the five lncRNAs (PLAC4, LINC01116, LINC02163, MIR223HG, FAM83A-AS1) were identified as candidates for constructing the tumor mutation-related model which may serve as an indicator of tumor mutation levels and have important implications for predicting the response to immunotherapy in LUAD.

Comparing ChatGPT's and surgeon's responses to thyroid-related questions from patients.

BACKGROUND: For some common thyroid-related conditions with high prevalence and long follow-up times, ChatGPT can be used to respond to common thyroid-related questions. In this cross-sectional study, we assessed the ability of ChatGPT (version GPT-4.0) to provide accurate, comprehensive, compassionate, and satisfactory responses to common thyroid-related questions. STUDY DESIGN: First, we obtained 28 thyroid-related questions from the Huayitong app, which together with the two interfering questions eventually formed 30 questions. Then, these questions were responded to by ChatGPT (on July 19, 2023), junior specialist and senior specialist (on July 20, 2023) separately. Finally, 26 patients and 11 thyroid surgeons evaluated those responses on four dimensions: accuracy, comprehensiveness, compassion, and satisfaction. RESULTS: Among the 30 questions and responses, ChatGPT's speed of response was faster than that of the junior specialist (8.69 [7.53-9.48] vs. 4.33 [4.05-4.60], P <.001) and senior specialist (8.69 [7.53-9.48] vs. 4.22 [3.36-4.76], P <.001). The word count of the ChatGPT's responses was greater than that of both junior specialist (341.50 [301.00-384.25] vs. 74.50 [51.75-84.75], P <0.001) and senior specialist (341.50 [301.00-384.25] vs. 104.00 [63.75-177.75], P <0.001). ChatGPT received higher scores than junior specialist and senior specialist in terms of accuracy, comprehensiveness, compassion and satisfaction in responding to common thyroid-related questions. CONCLUSIONS: ChatGPT performed better than junior specialist and senior specialist in answering common thyroid-related questions, but further research is needed to validate the logical ability of the ChatGPT for complex thyroid questions.

Enhanced organic degradation and microbial community cooperation by inoculating Bacillus licheniformis in low temperature composting.

Microbial activity and interaction are the important driving factors in the start-up phase of food waste composting at low temperature. The aim of this study was to explore the effect of inoculating Bacillus licheniformis on the degradation of organic components and the potential microbe-driven mechanism from the aspects of organic matter degradation, enzyme activity, microbial community interaction, and microbial metabolic function. The results showed that after inoculating B. licheniformis, temperature increased to 47.8°C on day 2, and the degradation of readily degraded carbohydrates (RDC) increased by 31.2%, and the bioheat production increased by 16.5%. There was an obvious enhancement of extracellular enzymes activities after inoculation, especially amylase activity, which increased by 7.68 times on day 4. The inoculated B. licheniformis colonized in composting as key genus in the start-up phase. Modular network analysis and Mantel test indicated that inoculation drove the cooperation between microbial network modules who were responsible for various organic components (RDC, lipid, protein, and lignocellulose) degradation in the start-up phase. Metabolic function prediction suggested that carbohydrate metabolisms including starch and sucrose metabolism, glycolysis / gluconeogenesis, pyruvate metabolism, etc., were improved by increasing the abundance of related functional genes after inoculation. In conclusion, inoculating B. licheniformis accelerated organic degradation by driving the cooperation between microbial network modules and enhancing microbial metabolism in the start-up phase of composting.

Small but powerful: RALF peptides in plant adaptive and developmental responses.

Plants live in a highly dynamic environment and require to rapidly respond to a plethora of environmental stimuli, so that to maintain their optimal growth and development. A small plant peptide, rapid alkalization factor (RALF), can rapidly increase the pH value of the extracellular matrix in plant cells. RALFs always function with its corresponding receptors. Mechanistically, effective amount of RALF is induced and released at the critical period of plant growth and development or under different external environmental factors. Recent studies also highlighted the role of RALF peptides as important regulators in plant intercellular communications, as well as their operation in signal perception and as ligands for different receptor kinases on the surface of the plasma membrane, to integrate various environmental cues. In this context, understanding the fine-print of above processes may be essential to solve the problems of crop adaptation to various harsh environments under current climate trends scenarios, by genetic means. This paper summarizes the current knowledge about the structure and diversity of RALF peptides and their roles in plant development and response to stresses, highlighting unanswered questions and problems to be solved.

Vascular endothelial cells-derived exosomes synergize with curcumin to prevent osteoporosis development.

Osteoporosis has gradually become a major public health problem. Further elucidation of the pathophysiological mechanisms that induce osteoporosis and identification of more effective therapeutic targets will have important clinical significance. Experiments in vitro on bone marrow stem cells (BMSCs) subjected to osteogenic and adipogenic differentiation and in vivo on surgical bilateral ovariectomy (OVX) mouse models revealed that exosomes of vascular endothelial cells (EC-EXOs) can promote osteogenic differentiation of BMSCs and inhibit BMSC adipogenic differentiation through miR-3p-975_4191. Both miR-3p-975_4191 and curcumin can target tumor necrosis factor (TNF) and act synergistically to regulate BMSCs fate differentiation and delay the progression of osteoporosis. Our findings suggest that EC-EXOs may exert a synergistic effect with curcumin in reversing the progression of osteoporosis by targeting TNF via miR-3p-975_4191. Our study may provide therapeutic options and potential therapeutic targets for osteoporosis and thus has important clinical implications.

Ternary Photoanodes with AgAu Nanoclusters and CoNi-LDH for Enhanced Photoelectrochemical Water Oxidation.

Atomically precise metal nanoclusters (NCs) present new opportunities for creating innovative solar-powered photoanodes due to their extraordinary physicochemical properties. Nevertheless, ultrasmall metal NCs tend to aggregate and lack active sites under light irradiation, which severely limits their widespread application. We have developed a strategy to design efficient ternary photoanodes by successively modifying AgAu NCs and CoNi-LDH on BiVO4 substrates using versatile impregnation and electrodeposition. The electronic properties of AgAu NCs facilitate the rapid transfer of photogenerated carriers on BiVO4 and CoNi-LDH. Additionally, ultrathin CoNi-LDH acts as a hole-collecting layer, which quickly extracts holes to the electrode/electrolyte interface. The synergistic effect and the matched energy levels between the ternary heterostructures promote the OER process, which significantly improved the photoelectrochemical (PEC) water oxidation performance. This study presents a new idea for further exploration of metal nanocluster-based PEC systems.

Phenanthroline-functionalized donor-acceptor covalent organic frameworks as photo-responsive nanozymes for visual colorimetric detection of isoniazid.

Development of metal-free nanozymes has raised concern for their extensive applications in photocatalysis and sensing fields. As novel metal-free nanomaterials, covalent organic frameworks (COFs) have engendered intense interest in the construction of nanozymes due to their structural controllability and molecular functionality. The formation of the molecular arrangement by embedding orderly donor-acceptors (D-A) linked in the framework topology to modulate material properties for highly efficient enzyme mimicking activity is of importance but challenging. Here, a strong D-A type of COF was designed and synthesized by integrating electron donor units (pyrene) and electron acceptor units (phenanthroline), named Py-PD COF. Using experiments and theoretical calculations, the introduction of a phenanthroline ring endowed the Py-PD COF with a narrowed band gap, and efficient charge transfer and separation. Further, the Py-PD COF exhibited a superior light-responsive oxidase-mimicking characteristic under visible light irradiation, which could catalyze the oxidation of 3,3',5,5-tetramethylbenzidine (TMB) and give the corresponding evolution of color. The nanoenzymatic activity of the Py-PD COF was light-regulated, which offers a fascinating advantage because of its high efficiency and spatial controllability. Based on previously mentioned characteristics, an "on-off" sensing platform for the colorimetric analysis of isoniazid (INH) could be constructed with a good linear relationship (2-100 µM) and a low limit of detection (1.26 µM). This research shows that not only is Py-PD COF an environmentally friendly compound for the colorimetric detection of INH, but it is also capable of providing the interesting D-A type COF-based material for designing an excellent nanozyme.

A missense mutation in human INSC causes peripheral neuropathy.

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.

Protamine-grafted carboxymethyl chitosan based hydrogel with adhesive and long-term antibacterial properties for hemostasis and skin wound healing.

In this study, we developed a tissue-adhesive and long-term antibacterial hydrogel consisting of protamine (PRTM) grafted carboxymethyl chitosan (CMC) (PCMC), catechol groups modified CMC (DCMC), and oxidized hyaluronic acid (OHA), named DCMC-OHA-PCMC. According to the antibacterial experiments, the PCMC-treated groups showed obvious and long-lasting inhibition zones against E. coli (and S. aureus), and the corresponding diameters varied from 10.1 mm (and 15.3 mm) on day 1 to 9.8 mm (and 15.3 mm) on day 7. The DCMC-OHA-PCMC hydrogel treated groups also exhibited durable antibacterial ability against E. coli (and S. aureus), and the antibacterial rates changed from 99.3 ± 0.21 % (and 99.6 ± 0.36 %) on day 1 to 76.2 ± 1.74 % (and 84.2 ± 1.11 %) on day 5. Apart from good mechanical and tissue adhesion properties, the hydrogel had excellent hemostatic ability mainly because of the grafted positive-charged PRTM. As the animal assay results showed, the hydrogel was conducive to promoting the deposition of new collagen (0.84 ± 0.03), the regeneration of epidermis (98.91 ± 6.99 µm) and wound closure in the process of wound repairing. In conclusion, the presented outcomes underline the prospective potential of the multifunctional CMC-based hydrogel for applications in wound dressings.

Releasing Free Anions by High Donor Number Cosolvent in Noncorrosive Electrolytes of Commercially Available Magnesium Salts.

Passivation of the magnesium (Mg) anode in the chloride-free electrolytes using commercially available Mg salts is a critical issue for rechargeable Mg batteries. Herein, a high donor number cosolvent of 1-methylimidazolium (MeIm) is introduced into Mg(TFSI)2- and Mg(HMDS)2-based electrolytes to address the passivation problem and realize highly reversible Mg plating/stripping. Theoretical calculations and experimental characterization results reveal that the strong coordination ability of MeIm with Mg2+ can weaken the anion-cation interactions and promote the formation of free anions that have higher reduction stability, thus significantly suppressing anion-derived passivation layer formation. By adding MeIm cosolvent into Mg(TFSI)2-based electrolyte, the average Coulombic efficiency of the Mg//Cu cell is increased from less than 20% to over 90%, and the Mg//Mg cell can stably cycle for over 800 h with a low overpotential. In the MeIm-regulated Mg(HMDS)2-based electrolyte, the solvation structure change, featured by an effective separation of Mg2+ and HMDS-, greatly increases the ionic conductivity by more than 30 times. This solvation structure regulation strategy for noncorrosive electrolytes of commercially available Mg salts has a great potential for application in future rechargeable Mg metal batteries.

PRODH safeguards human naive pluripotency by limiting mitochondrial oxidative phosphorylation and reactive oxygen species production.

Naive human embryonic stem cells (hESCs) that resemble the pre-implantation epiblasts are fueled by a combination of aerobic glycolysis and oxidative phosphorylation, but their mitochondrial regulators are poorly understood. Here we report that, proline dehydrogenase (PRODH), a mitochondria-localized proline metabolism enzyme, is dramatically upregulated in naive hESCs compared to their primed counterparts. The upregulation of PRODH is induced by a reduction in c-Myc expression that is dependent on PD0325901, a MEK inhibitor routinely present in naive hESC culture media. PRODH knockdown in naive hESCs significantly promoted mitochondrial oxidative phosphorylation (mtOXPHOS) and reactive oxygen species (ROS) production that triggered autophagy, DNA damage, and apoptosis. Remarkably, MitoQ, a mitochondria-targeted antioxidant, effectively restored the pluripotency and proliferation of PRODH-knockdown naive hESCs, indicating that PRODH maintains naive pluripotency by preventing excessive ROS production. Concomitantly, PRODH knockdown significantly slowed down the proteolytic degradation of multiple key mitochondrial electron transport chain complex proteins. Thus, we revealed a crucial role of PRODH in limiting mtOXPHOS and ROS production, and thereby safeguarding naive pluripotency of hESCs.

Directional emission of a three-dimensional connection-type metamaterial.

Directional emission of electromagnetic waves plays an essential role in laser radar and free-space communication. For most directional antennas, bandwidth and miniaturization are a pair of contradictions due to their underlying interference mechanism. Connection-type metamaterials exhibit exotic electromagnetic response near zero-frequency, which relies on the global topology of mesh connectivity rather than resonance and thus has a broad working bandwidth. In this Letter, we investigate the broadband orientation-dependent coupling effect of a 3D double mesh metamaterial. Based on this effect, we achieve a broadband directional emission (relative bandwidth of 37.72%) using a compact structure (compared to twice working wavelength). Our work provides a novel, to the best of our knowledge, scheme to manipulate a long-wavelength wave and may pave the way to a miniaturized directional antenna.

Influence of annealing pretreatment in different atmospheres on crystallization quality and UV photosensitivity of gallium oxide films.

Due to their high wavelength selectivity and strong anti-interference capability, solar-blind UV photodetectors hold broad and important application prospects in fields like flame detection, missile warnings, and secure communication. Research on solar-blind UV detectors for amorphous Ga2O3 is still in its early stages. The presence of intrinsic defects related to oxygen vacancies significantly affects the photodetection performance of amorphous Ga2O3 materials. This paper focuses on growing high quality amorphous Ga2O3 films on silicon substrates through atomic layer deposition. The study investigates the impact of annealing atmospheres on Ga2O3 films and designs a blind UV detector for Ga2O3. Characterization techniques including atomic force microscopy (AFM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) are used for Ga2O3 film analysis. Ga2O3 films exhibit a clear transition from amorphous to polycrystalline after annealing, accompanied by a decrease in oxygen vacancy concentration from 21.26% to 6.54%. As a result, the response time of the annealed detector reduces from 9.32 s to 0.47 s at an external bias of 10 V. This work demonstrates that an appropriate annealing process can yield high-quality Ga2O3 films, and holds potential for advancing high-performance solar blind photodetector (SBPD) development.

Design and control of a novel variable stiffness actuator based on antagonistic variable radius principle.

Variable stiffness actuators (VSAs) are essential for ensuring safe human-robot interactions in robotic applications. This paper proposes a novel rotary VSA using an antagonistic Hoberman linkage mechanism (AHLM), which offers a large stiffness range and a compact structure. The VSA-AHLM consists of two sets of antagonistic-type quadratic springs based on spiral cams connected to the Hoberman linkage mechanism (HLM) through four cables. By simultaneously adjusting both the radius of the HLM and the spring preload, the stiffness of the VSA-AHLM can be varied within a large range. Furthermore, the position and stiffness of the VSA-AHLM can be controlled independently by two rotary motors. The geometric parameters of the spiral cam are determined to achieve the desired linear stiffness-elongation behavior of a quadratic spring, and detailed models of the actuator's stiffness, elastic energy, and torque are established. An actuator prototype is fabricated to demonstrate the proposed variable stiffness approach. Experiments show that the developed actuator can achieve significant stiffness changes and exhibits excellent positioning and trajectory tracking performance.

Heterogeneity of work alienation and its relationship with job embeddedness among Chinese nurses: a cross-sectional study using latent profile analysis.

OBJECTIVE: To identify the distinct profiles of work alienation among Chinese nurses, examine the demographic factors associated with profile memberships, and then explore the relationship between latent categories of work alienation and job embeddedness. METHODS: A cross-sectional survey of 523 nurses was conducted from July to August 2023. Latent profile analysis (LPA) was performed to identify distinct profiles of nurses based on three aspects: powerlessness, helplessness, and meaningfulness. A multinomial logistic regression analysis was conducted to explore the predictors of profile membership. Hierarchical regression analysis was carried out to examine the association between profile memberships and job embeddedness. RESULTS: Three subgroups of work alienation of nurses were identified: 23.1%, 57.8%, and 19.1% in the low work alienation group (profile 1), the moderate work alienation group (profile 3), and the high work alienation group (profile 2), respectively. Nurses with college degrees were more likely to be grouped into moderate work alienation. Nurses who did not work night shifts were more likely to have low or moderate levels of work alienation. Nurses earning 2,000-3,000 and 3,001-5,000 yuan per month were likely to be in the low work alienation group. The different categories of work alienation significantly predicted job embeddedness among nurses (ΔR2 = 0.103, p < 0.001). CONCLUSIONS: Work alienation has an important impact on clinical nurses' job embeddedness. Nursing managers should pay attention to the differences in individual work alienation status and adopt reasonable management strategies to improve the level of job embeddedness, ensure the quality of care, and reduce nursing turnover.

Lovastatin/SN38 co-loaded liposomes amplified ICB therapeutic effect via remodeling the immunologically-cold colon tumor and synergized stimulation of cGAS-STING pathway.

Current immune checkpoint blockade (ICB) immunotherapeutics have revolutionized cancer treatment. However, many cancers especially the "immunologically cold" tumors, do not respond to ICB, prompting the search for additional strategies to achieve durable responses. The cGAS-STING pathway, as an essential immune response pathway, has been demonstrated for a potent target to sensitize ICB immunotherapy. However, the low efficiency of conventional STING agonists limits their clinical application. Recent studies have shown that DNA topoisomerase I (TOPI) inhibitor chemodrug SN38 can activate the cGAS-STING pathway and induce an immune response through DNA damage, while the traditional statins medication lovastatin was found to inhibit DNA damage repair, which may in turn upregulate the damaged DNA level. Herein, we have developed a liposomal carrier co-loaded with SN38 and lovastatin (SL@Lip), which can be accumulated in tumors and efficiently released SN38 and lovastatin, addressing the problem of weak solubility of these two drugs. Importantly, lovastatin can increase DNA damage and enhance the activation of cGAS-STING pathway, coordinating with SN38 chemotherapy and exhibiting the enhanced combinational immunotherapy of PD-1 antibody by remodeling the tumor microenvironment in mouse colorectal cancer of both subcutaneous and orthotopic xenograft models. Overall, this study demonstrates that lovastatin-assisted cGAS-STING stimulation mediated by liposomal delivery system significantly strengthened both chemotherapy and immunotherapy of colorectal cancer, providing a clinically translational strategy for combinational ICB therapy in the "immunologically cold" tumors.