Recent publications
In an era where swift and precise diagnostic capabilities are paramount, we introduce NAPTUNE (Nucleic acids and Protein Biomarkers Testing via Ultra-sensitive Nucleases Escalation), an innovative platform for the amplification-free detection of nucleic acids and protein biomarkers in less than 45 minutes. Using a tandem cascade of endonucleases, NAPTUNE employs apurinic/apyrimidinic endonuclease 1 (APE1) to generate DNA guides, enabling the detection of target nucleic acids at femtomolar levels. The sensitivity is elevated to attomolar levels through the action of Pyrococcus furiosus Argonaute (PfAgo), which intensifies probe cleavage, thereby boosting both sensitivity and specificity within an innovative in-situ cascade circuit. This technology not only streamlines rapid, onsite diagnostics without pre-amplification but also demonstrates exceptional accuracy in identifying a broad spectrum of nucleic acids and crucial cancer-related protein biomarkers directly from clinical samples. The development of a portable device for point-of-care testing further underscores NAPTUNE’s potential to transform diagnostic processes, especially in resource-limited environments, marking a significant diversity forward in medical diagnostics and patient care.
- Lulu Zhuang
- Xiaoyan Yin
- Xiaoli Liu
- [...]
- Xiangjiao Meng
Purpose
To evaluate the efficacy and safety of aumolertinib in treating non-small cell lung cancer (NSCLC) patients with leptomeningeal metastasis (LM) and epidermal growth factor receptor (EGFR) mutations.
Methods
We conducted a retrospective analysis of clinical data from 79 patients with EGFR-mutated advanced NSCLC treated with aumolertinib after being diagnosed with LM at Shandong Cancer Hospital and Institute between April 2020 and July 2023. We evaluated overall survival (OS), progression-free survival (PFS), LM-PFS, and safety. Patient prognosis was assessed using Kaplan–Meier and Cox regression analyses.
Results
The median follow-up duration was 19.8 months (95% CI: 16.2–23.4), and 16 (20.3%) patients had previously used third-generation EGFR-TKI. The median LM-PFS was 10.6 months (95% CI: 8.6–12.5). The overall response rate (ORR) for LM was 53.2%, while the disease control rate (DCR) reached 91.1%. Among the 67 (84.8%) patients presenting with symptoms attributable to LM, 60 reported improved or stable symptoms. The median OS was 17.7 months (95% CI: 13.7–21.7), while the median PFS was 9.7 months (95% CI: 7.5–11.9). The systemic ORR and DCR were 38.0% and 87.3%, respectively. Multivariate Cox regression analysis identified L858R mutations (hazard ratio [HR] = 2.22, P = 0.030), prior systemic therapy (HR = 3.89, P < 0.001), ECOG PS ≥ 2 (HR = 4.06, P < 0.001) and ≥ 3 extracranial organ metastases (HR = 2.20, P = 0.025) as independent negative predictors of OS. Creatine kinase elevation (HR = 0.41, P = 0.018) was an independent predictor of better OS. Treatment-related adverse events occurred in 61 patients (77.2%), predominantly as grade 1 or 2.
Conclusion
Aumolertinib showed potential in treating EGFR-mutated NSCLC patients with LM, with a tolerable safety profile.
- Miaomiao Zhang
- Zhen Yang
- Chengjin Xu
- [...]
- Yu Cui
Enriching the structural diversity of metal–organic frameworks (MOFs) is of great importance in developing functional porous materials with specific properties. New MOF structures can be accessed through the rational design of organic linkers with diverse geometric conformations, and their structural complexity can be enhanced by choosing linkers with reduced symmetry. Herein, a series of Zr‐based MOFs with unprecedented topologies were developed through a linker desymmetrization and conformation engineering approach. A tritopic carboxylate linker with reduced symmetry and flexible triangular geometry was designed to construct three Zr‐based MOFs (denoted as NU‐57, NU‐58, and NU‐59) by modulating synthetic conditions. Notably, the conformational flexibility and reduced symmetry of the linker generated two unprecedented topologies in NU‐58 and NU‐59. Furthermore, solvent removal in NU‐58 via thermal activation process produced missing linker defects. Finally, the adsorption behavior of these MOFs toward alkanes and alkenes was studied to gain insights into their structure–property relationships, which demonstrated that NU‐57 and NU‐58 exhibit unusual reverse selectivity for alkanes in alkane/alkene separations. Overall, this work highlights the rational design of linkers using a desymmetrization strategy as a powerful method to enrich the structural diversity of MOFs and to access novel MOFs with unique properties.
The unique oxygen stacking sequence of O2-type structures restricts the irreversible transition metal movement into Li vacancies for the delithiated Li-rich layered oxides (LLOs) and maintains outstanding voltage stability. However, the ion-exchange synthesis promotes the Mn-ion valence reduction and aggravates the Jahn–Teller (J–T) distortion alongside disproportionation. Since the main oxidation state of the Mn ions is +4 in the traditional O3-type LLOs, synergistic effects of the O2-type and O3-type structures are expected in the O2/O3 diphasic Li-rich material. Herein, O2/O3 biphasic intergrowth LLOs were rationally designed, and the synergic optimization of the biphasic structure was planned to retard the J–T effect. The O2/O3 intergrowth nature was confirmed, and the percentages of the O2 and O3 phases were 56% and 44%, respectively. Density functional theory calculations demonstrated that the Mn2+(EC) sheath had a remarkably lower energy barrier than the Li+(EC) sheath. This finding suggests that Mn2+ ions that are dissolved into the electrolyte accelerate the electrolyte oxidization, so the deposition of the cathode electrolyte interface for pristine O2-LLOs causes a high electrochemical impedance. The designed O2/O3 biphasic LLOs boost the capacity stability and suppress the voltage drop upon repeated Li+ de-intercalation. The phase regulation strategy offers great potential for developing low-cost LLOs with enhanced structural stability for advanced Li-ion batteries.
Responsible tourism requires responsible behavior on the part of tourism operators, governments, local residents, and tourists. Scene theory pertains to efforts to build beautiful natural and cultural environments, offering resources for stakeholders in urban blocks and enabling tourists and residents to have restorative environmental experiences that can improve their quality of life. Taking a sample of 53 urban cultural blocks in China, this study collected comments from tourists about the blocks for classification and organization, extracted keywords from tourist evaluation materials, and assessed market demand trends in different dimensions of scene theory. Based on the findings, we offer development suggestions that can help urban blocks create scenes that improve the areas in terms of legitimacy, authenticity, and theatricality. This scene theory-based approach can provide urban block managers with a responsible, sustainable strategic resource that fully considers the social and economic benefits of local development.
Keywords: stakeholders; urban block; integration of culture and tourism; scene theory; responsible tourism
Background: In the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS), we found no significant difference between the bypass surgery group and the medical group with respect to the primary composite outcome of stroke or death within 30 days or any subsequent ipsilateral ischemic stroke within 2 years of follow-up. We now extend the long-term follow-ups to 10 years.
Methods: We randomly assigned symptomatic patients with hemodynamically compromised internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion to extracranial-intracranial (EC-IC) bypass surgery plus medical treatment or medical treatment alone at 13 centers in China. We extended the follow-ups from the original 2 years to 10 years to assess long-term outcomes. The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days after randomization.
Results: 324 patients were assigned to the surgery (n=161) or medical group (n=163); the median duration of follow-up was 7.6 years (interquartile range [IQR], 2.3 to 9.2). The primary outcome occurred in 18 of 161 patients (11.2%) in the surgical group, significantly lower than that in the medical group (32 out of 163 patients [19.6%]; relative risk [RR], 0.57; 95% confidence interval [CI], 0.33 to 0.97; P=0.04). The risk of any stroke was 16.1% in the surgical group vs 23.3% in the medical group (RR, 0.76; 95% CI, 0.52 to1.13; P=0.15); the all-cause mortality was 8.1% in the surgical group vs. 8.6% in the medical group (RR, 0.94; 95% CI, 0.46 to 1.94]; P=0.93).
Conclusions: Among symptomatic ICA or MCA occlusion patients with hemodynamic insufficiency, the addition of extracranial-intracranial bypass surgery to medical treatment was safe and led to a lower risk of recurrent stroke through 7 years of follow-up than medical treatment alone. (ClinicalTrials.gov number, NCT01758614.)
Affective well-being, as an important component of well-being, is related to an individual’s mental health and quality of life. Previous studies have found that some psychological variables of employees at work can affect their well-being, but most studies use cross-sectional design, and the exploration of the potential psychological mechanism of the relationship between the two is unclear. This study adopted a longitudinal design to explore the dynamic bidirectional relationship between the thriving at work and affective well-being among the primary and secondary school teachers, and further investigated the mediating mechanism of work-family enrichment between them. Thriving at Work Questionnaire, Work-Family Enrichment Questionnaire, and Affective Well-being Questionnaire are used to conduct a three-wave longitudinal study design which with a sample of 778 teachers at an interval of one year. The results of the cross-lagged analysis showed that: (1) There was an interactive and mutually predictive association between teachers’ affective well-being and thriving at work. (2) The relationship between the positive and negative affective dimensions of teachers’ affective well-being and thriving at work was different; the positive affective dimension rather than the negative affective dimension at the former time point significantly predicted thriving at work at the latter time point; and the thriving at work at the former time point significantly predicted the negative affective dimension rather than the positive affective dimension at the latter time point. (3) Teachers’ work-family enrichment mediated the effect of their thriving at work on their affective well-being, but did not mediate the effect of their affective well-being on their thriving at work. (4) For the relationship between positive affective dimension or negative affective dimension and work-family enrichment and thriving at work, only work-family enrichment was found to play a mediating role in the process of thriving at work affecting positive affective. The study revealed the relationship and mechanism between teachers’ thriving at work, work-family enrichment, and affective well-being, and provided empirical research basis for educational administration and school organizations to explore effective measures to improve the working experience and well-being of teachers.
This study presents a dual-channel disturbance rejection controller for achieving high-precision position control of flexible-joint robots (FJRs) with prescribed performance constraint. The dynamics of the FJR are decomposed into a quasi-steady-state (QSS) model and a boundary-layer model via singular perturbation theory. To effectively address unknown disturbances in the QSS model, a dual-channel disturbance compensator is proposed, which contains a high-frequency disturbance compensator (HFDC) and a generalized proportional integral observer (GPIO). The dual-channel disturbance compensator enables separate estimation of high-frequency and low-frequency components of the lumped disturbance by HFDC and GPIO, respectively. Additionally, the controller for the QSS model is constructed by combining the barrier Lyapunov function and the sliding mode surface, ensuring the exponential stability of the QSS model. The practical exponential stability of the entire system is proven utilizing the extended Tikhonov’s theorem. Numerical simulation and comparative experiments are performed to validate the high-precision tracking performance achieved by the designed approach. To the best of our knowledge, this is the first approach to effectively distinguish and estimate distinct components of the lumped disturbance to achieve precise control of FJRs, particularly in the presence of prescribed performance constraint.
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