The calculation of load and surrounding rock pressure of extra-large-section tunnels serves as an important premise for the design and construction of tunnel projects with extra-large sections. Based ...on the large-span section of the Shenzhen Liantang Tunnel (China), which is the largest highway tunnel in the world to date, this paper discusses the challenges existing in the calculation method of state load and surrounding rock pressure for extra-large-section tunnels and puts forward a novel calculation method for process load, which is suitable for extra-large-section highway tunnels. In the current work, we derived the related application correlations and improved the specific application steps, methods, and project models of the proposed calculation method. Both the rationality and feasibility of the calculation method were verified from a practical perspective by comparing the on-site data of surrounding rock pressure at the Liantang Tunnel with the calculated load, which provides a fundamental basis for the process design of tunnels.
•In the palliative treatment of metastatic colorectal cancer(mCRC), doublet chemotherapy (FOLFOX or FOLFIRI) or triplet chemotherapy (FOLFOXIRI) combined with targeted drugs (cetuximab or ...bevacizumab) is the main regimen. Recently, microsatellite instability-high (MSI-H)/ DNA mismatch repair deficient (dMMR) was discovered as a biomarker to distinguish immunotherapy benefited populations. In this context, recent published randomized phase III clinical trials tested the efficacy and safety of immunotherapy and traditional chemotherapy with or without targeted drugs as first-line treatment for mCRC patients with MSI-H/dMMR.•In this manuscript, we briefly analyze this article and further discuss immune monotherapy or double immunotherapy for mCRC patients with MSI-H/dMMR, the immunotherapy for patients with BRAF V600E mutant mCRC, and the immunotherapy for mCRC patients with microsatellite stable.
In the palliative treatment of metastatic colorectal cancer (mCRC), doublet chemotherapy (FOLFOX or FOLFIRI) or triplet chemotherapy (FOLFOXIRI) combined with targeted drugs (cetuximab or bevacizumab) is the main regimen. Recently, microsatellite instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) was discovered as a biomarker to distinguish immunotherapy-benefited populations. In this context, recently published randomized phase III clinical trials tested the efficacy and safety of immunotherapy and traditional chemotherapy with or without targeted drugs as first-line treatment for patients with MSI-H/dMMR mCRC.
Here, we briefly analyze this article and further discuss immune monotherapy or double immunotherapy for patients with MSI-H/dMMR mCRC, the immunotherapy for patients with BRAF V600E mutant mCRC, and the immunotherapy for patients with microsatellite stable mCRC.
The field of DNA nanotechnology has evolved beyond the realm of controllable movements and randomly shaped nanostructures, now encompassing a diverse array of nanomachines, each with unique ...nanostructures and biofunctional attributes. These DNA nanostructures boast exceptional characteristics such as programmability, integrability, biocompatibility, and universality. Among this variety, DNA walking nanomachines have emerged as one of the most prominent nanomotors, distinguished by their ingenious design and comprehensive functionality. In recent times, these DNA walkers have witnessed remarkable advancements in areas ranging from nanostructural designs to biological applications, including the creation of sophisticated biosensors capable of efficiently detecting tumor‐related biomarkers and bioactive substances. This review delves into the operational mechanisms of DNA walking nanomachines, which are driven by processes such as protease and DNAzyme action as well as strand displacement and photoactivated reactions. It further provides a comprehensive overview of DNA walking nanomachines with different dimensional (1D, 2D, and 3D) walking tracks. A subsequent section introduces the biosensing applications of DNA walking nanomachines including electrochemical, optical, and other biosensors. The review concludes with a forward‐looking perspective on the novel advancements and challenges in developing DNA walking nanomachine‐based biosensors.
Overview of the design and applications of DNA walking nanomachines.
Aiming at the shortcomings of traditional genetic algorithms such as premature and insufficient local search ability, a hybrid genetic algorithm combining k-means algorithm and cluster analysis to ...improve genetic algorithm is proposed. Among them, the selection operation adopts the tournament selection strategy of the elite retention model, the crossover operation adopts the double cut-point crossover, and the variation operator introduces the k-exchange variation operation to ensure the evolution of individuals from generation to generation. Through the selection, crossover, and variation operations, the objective function is minimized, the vehicle travel distance is greatly reduced, and the distribution route is optimized.
This study aimed to evaluate the effectiveness of the Qihuang Needle (QHN) in treating Parkinson's disease (PD).
The trial was an 8-week randomized clinical trial (4 weeks of treatment followed by 4 ...weeks of follow-up) conducted from January 2021 to July 2022 in outpatient settings at three clinical sites in Guangzhou, China. Thirty-four participants with PD were diagnosed based on the diagnostic criteria formulated by the brain bank of the British Parkinson's Disease Society in 1992.
Patients in the treatment and control groups received six sessions within 4 weeks of the QHN therapy or the sham acupuncture therapy (two times per week for the first two consecutive weeks and one time per week for the following two consecutive weeks).
The primary outcome measure was the change in the Parkinson's Disease Rating Scale-Part III Motor Examination (UPDRS III) between baseline and 8 weeks after treatments. Secondary outcome measures were the Non-Motor Symptoms Scale for Parkinson's Disease (NMSS) and Parkinson's Disease Daily Quality of Life-39 (PDQ-39). Real-time shear wave elastography (SWE) was assessed for each patient at baseline and during the 4-week period as the third outcome measure.
A more significant reduction of UPDRS III score, PDQ-39, NMSS, and SWE was observed in the QHN group than in the sham acupuncture group.
The QHN therapy consistently demonstrated superiority and produced clinically meaningful benefits in reducing motor and non-motor symptoms, as well as significantly improving muscle stiffness, in patients with PD.
Structural unsteadiness and sluggish diffusion of divalent zinc cations in cathodes during cycling severely limit further applications of MoS2 for rechargeable aqueous zinc-ion batteries (ZIBs). To ...circumvent these hurdles, herein, phosphorus (P) atom embedded three-dimensional marigold-shaped 1T MoS2 structures combined with the design of S vacancies (Sv) are synthesized via the oxygen-assisted solvent heat method. The oxygen-assisted method is utilized to aid the P-embedding into the MoS2 crystal, which can expand the interlayer spacing of P-MoS2 and strengthen Zn2+ intercalation/deintercalation. Meanwhile, the three-dimensional marigold-shaped structure with 1T phase retains the internal free space, can adapt to the volume change during charge and discharge, and improve the overall conductivity. Moreover, Sv is not only conducive to the formation of rich active sites to diffuse electrons and Zn2+ but also improves the storage capacity of Zn2+. The electrochemical results show that P-MoS2 can reach a high specific capacity of 249 mAh g−1 at 0.1 A g−1. The capacity remains at 102 mAh g−1 after 3260 cycles at a current of 0.5 A g−1, showing excellent electrochemical performance for Zn2+ ion storage. This research provides a more efficient method of P atom embedded MoS2-based electrodes and will heighten our comprehension of developing cathodes for the ZIBs.
Although previous research has examined the risk factors for drowning behavior among adolescents, it is unclear whether this association is influenced by water safety knowledge. This study aimed to ...examine whether water safety knowledge is associated with adolescents' drowning risk behaviors and whether drowning risk perceptions and attitudes could have a chain mediating role in the association between water safety knowledge and adolescents' drowning risk behaviors.
This study included 7,485 adolescents from five Chinese provinces and cities. We used the Drowning Risk Behaviors Scales (DRBS) to evaluate the risk of drowning behaviors. The Water Safety Knowledge Scale (WSKS) was used to evaluate the competence level of water safety knowledge. The Drowning Risk Perceptions Scale (DRPS) was used to evaluate the risk level of perceptions, and the Drowning Risk Attitudes Scale (DRAS) was used to evaluate the risk level of attitudes.
The results of the mediating effect test showed that water safety knowledge (WSK) affected drowning risk behaviors (DRB) through three indirect paths. Drowning risk perceptions (DRP) and attitudes (DRA) have significantly mediated the association between WSK and DRB. In conclusion, DRP and DRA can act as mediators between WSK and DRB, not only individually, but also as chain mediators, where the direct effect is-0.301, the total indirect effect is-0.214, and the total mediated indirect effect is 41.5%.
Water safety knowledge negatively predicts adolescents' drowning risk behaviors; water safety knowledge has an inhibitory effect on drowning risk perceptions. Water safety knowledge can directly influence adolescents' drowning risk perceptions and indirectly affect drowning risk behaviors through the mediation of drowning risk perceptions and attitudes comprising three paths: (1) the drowning risk perceptions mediation path, (2) the drowning risk attitudes mediation path, and (3) the drowning risk perceptions and attitudes mediation paths.
Alzheimer's disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ...ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum level of thyroid hormones and cognitive function. We analysed effects of ApoE4-containing peripheral exosomes on neural cells and neurological outputs in aged or thyroidectomised young mice. Ageing-associated hypothyroidism as well as acute thyroidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, this process can represent potential therapeutic target.
Targeting oxidative phosphorylation (OXPHOS) is a promising strategy to improve treatment outcomes of acute myeloid leukemia (AML) patients. IACS-010759 is a mitochondrial complex I inhibitor that ...has demonstrated preclinical antileukemic activity and is being tested in Phase I clinical trials. However, complex I deficiency has been reported to inhibit apoptotic cell death through prevention of cytochrome c release. Thus, combining IACS-010759 with a BH3 mimetic may overcome this mechanism of resistance leading to synergistic antileukemic activity against AML. In this study, we show that IACS-010759 and venetoclax synergistically induce apoptosis in OXPHOS-reliant AML cell lines and primary patient samples and cooperatively target leukemia progenitor cells. In a relatively OXPHOS-reliant AML cell line derived xenograft mouse model, IACS-010759 treatment significantly prolonged survival, which was further enhanced by treatment with IACS-010759 in combination with venetoclax. Consistent with our hypothesis, IACS-010759 treatment indeed retained cytochrome c in mitochondria, which was completely abolished by venetoclax, resulting in Bak/Bax- and caspase-dependent apoptosis. Our preclinical data provide a rationale for further development of the combination of IACS-010759 and venetoclax for the treatment of patients with AML.
Micro-expression recognition is a substantive cross-study of psychology and computer science, and it has a wide range of applications (e.g., psychological and clinical diagnosis, emotional analysis, ...criminal investigation, etc.). However, the subtle and diverse changes in facial muscles make it difficult for existing methods to extract effective features, which limits the improvement of micro-expression recognition accuracy. Therefore, we propose a multi-scale joint feature network based on optical flow images for micro-expression recognition. First, we generate an optical flow image that reflects subtle facial motion information. The optical flow image is then fed into the multi-scale joint network for feature extraction and classification. The proposed joint feature module (JFM) integrates features from different layers, which is beneficial for the capture of micro-expression features with different amplitudes. To improve the recognition ability of the model, we also adopt a strategy for fusing the feature prediction results of the three JFMs with the backbone network. Our experimental results show that our method is superior to state-of-the-art methods on three benchmark datasets (SMIC, CASME II, and SAMM) and a combined dataset (3DB).
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