Journal of advanced research最新文献

Introduction: Big data optimization (Big-Opt) problems present unique challenges in effectively managing and optimizing the analytical properties inherent in large-scale datasets. The complexity and size of these problems render traditional data processing methods insufficient.

Objectives: In this study, we propose a new multi-objective optimization algorithm called the multi-objective African vulture optimization algorithm with binary hierarchical structure and tree topology (MO_Tree_BHSAVOA) to solve Big-Opt problem.

Methods: In MO_Tree_BHSAVOA, a binary hierarchical structure (BHS) is incorporated to effectively balance exploration and exploitation capabilities within the algorithm; shift density estimation is introduced as a mechanism for providing selection pressure for population evolution; and a tree topology is employed to reinforce the algorithm's ability to escape local optima and preserve optimal non-dominated solutions. The performance of the proposed algorithm is evaluated using CEC 2020 multi-modal multi-objective benchmark functions and CEC 2021 real-world constrained multi-objective optimization problems and is applied to Big-Opt problems.

Results: The performance is analyzed by comparing the results obtained with other multi-objective optimization algorithms and using Friedman's statistical test. The results show that the proposed MO_Tree_BHSAVOA not only provides very competitive results, but also outperforms other algorithms.

Conclusion: These findings validate the effectiveness and potential applicability of MO_Tree_BHSAVOA in addressing the optimization challenges associated with big data.

Introduction: Mechanical stimulation has been proven to promote bone-tendon interface (BTI) healing, but the mechanism remains unclear.

Objective: To investigate the effects of mechanical stimulation on the biological behavior of nestin⁺-bone mesenchymal stem cells (BMSCs) during the BTI healing, and to reveal the mechanisms of mechanical stimulation affecting BTI healing by primary cilia on the nestin⁺-BMSCs.

Methods: Transgenic tracing mice (nestin cre^ERT2:: IFT88^fl/fl/ROSA26 YFP) with primary cilia on nestin⁺-BMSCs conditioned knocked out were constructed, and the littermates (nestin cre^ERT2:: ROSA26 YFP) with normal cilia on nestin⁺-BMSCs were the control. After establishing mouse supraspinatus insertion injury models, samples were collected at week-2 (n = 5 per group), 4 and 8 (n = 15 per group, respectively). In vivo, the repair efficiency was evaluated by histology, imaging, biomechanics, and the migration of nestin⁺-BMSCs, detected by immunofluorescence staining. In vitro, nestin⁺ BMSCs were sorted and stimulated by tensile force to study the mechanisms of primary cilium-mediated mechanosensitive basis.

Results: Mechanical stimulation (MS) accelerated the recruitment of nestin⁺-BMSCs and promoted osteogenic and chondrogenic capacity. Histological, imaging and biomechanical results showed that the BTI healing quality of the IFT88^+/+, MS group was better than that of the other groups. After the conditionally knockout IFT88 in nestin⁺-BMSCs, the repair ability of the BTI was obviously deteriorated, even though mechanical stimulation did not increase significantly (IFT88^-/-, MS group). In vitro results showed the tensile loading enhanced the proliferation, migration and osteogenic or chondrogenic gene expression of nestin⁺-BMSCs with normal cilia. On the other hand, osteogenesis and chondrogenic expression were significantly decreased after inhibiting actin- Hippo/YAP pathway components.

Conclusion: The primary cilia mediated mechanical stimulation regulated osteogenic and chondrogenic differentiation potential of nestin⁺-BMSCs through the actin- Hippo/YAP pathway, and then promoted the BTI healing process.

Background: Since its development in the 1980 s, chemical vapor deposition (CVD) diamond has found wide application in addressing various engineering challenges, owing to its outstanding characteristics, including exceptionally high hardness, excellent thermal conductivity, and remarkable stability. Notably, processing tools utilizing CVD diamond as the working material exhibit substantial potential for application in the field of mechanical manufacturing. Serving as a viable substitute for natural diamond, CVD diamond processing tools not only offer advantages in production costs but also ensure processing performance on par with natural diamonds. This presents a valuable and effective approach for achieving advanced manufacturing with high precision and low production costs.

Aim of review: The research progress of CVD diamond processing tools is comprehensively reviewed from four perspectives, encompassing the CVD process of diamonds, preparation methods, processing applications, and future development directions of CVD diamond processing tools.

Key scientific concepts of review: The classification and exposition of CVD diamond deposition processes were presented. The fabrication of CVD diamond processing tools was elaborated. The machining applications of CVD diamond processing tools were then reviewed, mainly focusing on cutting and grinding processes, along with the tool wear characteristics. Finally, research challenges pertaining to CVD diamond processing tools were summarized, with insights proposed for future development opportunities and the anticipation of enhanced performance for prospective engineering applications.

Introduction: Pancreatic cancer (PC) remains a challenging malignancy, and adjuvant chemotherapy is critical in improving patient survival post-surgery. However, the intrinsic heterogeneity of PC necessitates personalized treatment strategies, highlighting the need for reliable preclinical models.

Objectives: This study aimed to develop novel patient-derived preclinical PC models using three-dimensional bioprinting (3DP) technology.

Methods: Patient-derived PC models were established using 3DP technology. Genomic and histological analyses were performed to characterize these models and compare them with corresponding patient tissues. Chemotherapeutic drug sensitivity tests were conducted on the PC 3DP models, and correlations with clinical outcomes were analyzed.

Results: The study successfully established PC 3DP models with a modeling success rate of 86.96%. These models preserved genomic and histological features consistent with patient tissues. Drug sensitivity testing revealed significant heterogeneity among PC 3DP models, mirroring clinical variability, and potential correlations with clinical outcomes.

Conclusion: The PC 3DP models demonstrated their utility as reliable preclinical tools, retaining key genomic and histological characteristics. Importantly, drug sensitivity profiles in these models showed potential correlations with clinical outcomes, indicating their promise in customizing treatment strategies and predicting patient prognoses. Further validation with larger patient cohorts is warranted to confirm their potential clinical utility.

Background: Cervical intraepithelial neoplasia grade 2 (CIN2) is one of the precursor stages before cervical lesions develop into cervical cancer. The spontaneous development of CIN2 is ambiguous. One part of CIN2 lesions will progress to cervical intraepithelial neoplasia grade 3 or worse (CIN3+), another part will regress to cervical intraepithelial neoplasia grade 1 or less (CIN1-), and the last part will persist. Although the guidelines suggest that CIN2 patients with fertility requirements can be treated conservatively to minimize the risk of infertility and obstetric complications, most CIN2 patients undergo surgical treatment to prevent the progression of the disease, which will lead to over-treatment and unnecessary complications.

Aim of review: The clinical outcome of CIN2 lesions is unpredictable and depends on histopathological examinations. Thus, it is necessary to identify the biomarkers differentiating regression lesions from progression lesions, which is conducive to supporting individualised treatment. The natural history of CIN2 is commonly regulated by the interaction of human papillomavirus (HPV) viral factors (HPV genotype and HPV methylation), host factors (p16/Ki-67 status, host gene methylation effects, human leukocyte antigen subtypes and immune microenvironment) and other factors (vaginal microbiota).

Key scientific concepts of review: This review summarized the biomarkers predicting the spontaneous regression of CIN2, which correlated with HPV infection, the (epi)genetic change of host genes and microenvironment change. However, potential biomarkers must be validated with prospective cohort studies, which should be conducted with expanded enrollment, a longer observational period and the tracking of more patients.

Introduction: Heart failure (HF) is a systemic metabolic disorder disease, across multiorgan investigations advancing knowledge of progression and treatment of HF. Whole-body MSI provides spatiotemporal information of metabolites in multiorgan and is expected to be a potent tool to dig out the complex mechanism of HF.

Objectives: This study aimed at exploring the systemic metabolic disorder in multiorgan and catecholamines biosynthesis alteration on heart-gut axis after HF.

Methods: Whole-body MSI was used to characterize metabolic disorder of the whole rat body after HF. An integrated method by MSI, LC-MS/MS and ELISA was utilized to analyze key metabolites and enzymes on heart, small intestine, cecum and colon tissues of rat. Gut microbiota dysbiosis was investigated by 16S rDNA sequencing and metagenomic sequencing. Validation experiments and in vitro experiments were performed to verify the effect of catecholamines biosynthesis alteration on heart-gut axis after HF.

Results: Whole-body MSI exhibited varieties of metabolites alteration in multiple organs. Remarkably, catecholamine biosynthesis was significantly altered in the serum, heart and intestines of rats. Furthermore, catecholamines and tyrosine hydroxylase were obviously upregulated in heart and colon tissue. Turicibacter_sanguinis was relevant to catecholamines of heart and colon. Validation experiments demonstrated excessive norepinephrine induced cardio-intestinal injury, including significantly elevating the levels of BNP, pro-BNP, LPS, DAO, and increased the abundance of Turicibacter_sanguinis. These alterations could be reversed by metoprolol treatment blocking the effect of norepinephrine. Additionally, in vitro studies demonstrated that norepinephrine promoted the growth of Turicibacter_sanguinis and Turicibacter_sanguinis could import and metabolize norepinephrine. Collectively, excessive norepinephrine exerted bidirectional effects on cardio-intestinal function to participate in the progression of HF.

Conclusion: Our study provides a new approach to elucidate multiorgan metabolic disorder and proposes new insights into heart-gut axis in HF development.

Introduction: Diaphorina citri is the most serious pest of citrus worldwide because it is the natural insect vector of huanglongbing. Cycloxaprid (Cyc) was highly toxic to D. citri. However, the poor solubility and stability had limited its development.

Objectives: In order to improve the insecticidal effect and stability to harsh climatic conditions of Cyc.

Methods: Cyc was chosen as the representative pesticide, 4,4'-methylenebis (phenyl isocyanate), PEG-600 and n-butanol were used to prepare sustained-release nano-gelation particles (Cyc@NGs).

Results: Cyc@NGs enhance the toxicity of Cyc more than 3 folds. Furthermore, Cyc@NGs showed excellent anti-rain and anti-UV capacity. After being exposed to ultraviolet light for 12 h, Cyc decreased by 100 %, while the insecticide content of Cyc@NGs only decreased by 25 %. Additionally, Cyc@NGs possessed better wettability on citrus leaves, mainly benefitting from its lower contact angle on citrus leaves. Moreover, FITC-labeled nano-gelation particles (FITC-NGs) exhibited high capability to penetrate and enrich in citrus leaf tissue and D. citri midgut. Consequently, NGs promoted the translocation and durability of insecticides, thereby, increasing the insecticidal activity. The results suggested that nano-gelation particle is a promising platform to deliver insecticides and Cyc@NGs would be the suitable candidate for the effective management of D. citri.

Introduction: The low sensitivity of alpha-fetoprotein (AFP) renders it unsuitable as a stand-alone marker for early hepatocellular carcinoma (eHCC) surveillance. Therefore, additional blood-based biomarkers with enhanced sensitivities are required.

Objectives: In light of the metabolic changes that are distinctive to eHCC development, the current study presents a panel of serum metabolites that may serve as noninvasive diagnostic indicators for patients with eHCC.

Methods: Serum samples obtained from normal control (NC), cirrhosis, and eHCC patients were analyzed by four different metabolomic platforms. A meta-analysis of very early-stage HCC transcriptomic datasets retrieved from public sources supports the integrated interpretation with metabolic changes.

Results: A total of 94 metabolites were significantly correlated with a progressive disease status. Integrated analysis of the significant metabolites and differentially expressed genes from meta-analysis emphasized metabolic pathways including bile acid biosynthesis, phenylalanine and tyrosine metabolism, and butanoate metabolism. The 11 metabolites associated with these pathways were compiled into a metabolite panel for use as diagnostic signatures. With an accuracy of 81.8%, compared with 45.4% for a model trained solely on AFP, the model enhanced its ability to differentiate between the three groups by incorporating a metabolite panel and AFP. Upon examining the trained models using receiver operating characteristic curves, the AFP and metabolite panel combined model exhibited greater area under the curve values in comparisons between NC and eHCC (1.000 versus 0.810) and cirrhosis and eHCC (0.926 versus 0.556). The result was consistent in an independent validation cohort.

Conclusion: This study emphasizes the role of circulating metabolite markers in the diagnosis of eHCC.

Introduction: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear.

Objectives: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment.

Methods: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital.

Results: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects.

Conclusions: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.

Introduction: Brain organoids are believed to be able to regenerate impaired neural circuits and reinstate brain functionality. The neuronal activity of organoids is considered a crucial factor for restoring host function after implantation. However, the optimal stage of brain organoid post-transplantation has not yet been established. External electrical signal plays a crucial role in the physiology and development of a majority of human tissues. However, whether electrical input modulates the development of brain organoids, making them ideal transplant donors, is elusive.

Methods: Bioelectricity was input into cortical organoids by electrical stimulation (ES) with a multi-electrode array (MEA) to obtain a better-transplanted candidate with better viability and maturity, realizing structural-functional integration with the host brain.

Results: We found that electrical stimulation facilitated the differentiation and maturation of organoids, displaying well-defined cortical plates and robust functional electrophysiology, which was probably mediated via the pathway of calcium-calmodulin (CaM) dependent protein kinase II (CAMK II)-protein kinase A (PKA)-cyclic-AMP response binding protein (pCREB). The ES-pretreated D40 organoids displayed superior cell viability and higher cell maturity, and were selected to transplant into the damaged primary sensory cortex (S1) of host. The enhanced maturation was exhibited within grafts after transplantation, including synapses and complex functional activities. Moreover, structural-functional integration between grafts and host was observed, conducive to strengthening functional connectivity and restoring the function of the host injury.

Conclusion: Our findings supported that electrical stimulation could promote the development of cortical organoids. ES-pretreated organoids were better-transplanted donors for strengthening connectivity between grafts and host. Our work presented a new physical approach to regulating organoids, potentially providing a novel translational strategy for functional recovery after brain injury. In the future, the development of 3D flexible electrodes is anticipated to overcome the drawbacks of 2D planar MEA, promisingly achieving multimodal stimulation and long-term recordings of brain organoids.