SIRT3 negatively regulates TFH cell differentiation in cancer.

Follicular helper T (TFH) cells are essential for inducing germinal center (GC) reactions to mediate humoral adaptive immunity in tumors, but the mechanisms underlying TFH cell differentiation remain unclear. Here, we found that the metabolism sensor sirtuin 3 (SIRT3) is critical for TFH cell differentiation and GC formation during tumor and viral infection. SIRT3 deficiency in CD4+ T cells intrinsically enhanced TFH cell differentiation and GC reactions during tumor and virus infection. Mechanistically, damaged oxidative phosphorylation (OXPHOS) compensatively triggered the NAD+-glycolysis pathway to provide a cellular energy supply, which was necessary for SIRT3 deficiency-induced TFH cell differentiation. Blocking NAD+ synthesis-glycolysis signaling or recovering OXPHOS activities reversed the TFH cell differentiation induced by SIRT3 deficiency. Moreover, the mTOR and HIF1α signaling axis was found to be responsible for TFH cell differentiation induced by SIRT3 deficiency. HIF1α directly interacted with and regulated the activity of the transcription factor Bcl-6. Thus, our findings identify a cellular energy compensatory mechanism, regulated by the mitochondrial sensor SIRT3, that triggers NAD+-dependent glycolysis during mitochondrial OXPHOS injuries and a mTOR-HIF1α-Bcl-6 pathway to reprogram TFH cell differentiation. These data have implications for future cancer immunotherapy research targeting SIRT3 in T cells.

Knowledge domains and emerging trends in immune-related adverse events from immune checkpoint inhibitors: A bibliometrics and visualized analysis.

Objective: The primary objective of this paper is to investigate the research hotspots and future trends of immune-related adverse events induced by immune checkpoint inhibitors, offering valuable insights for researchers in this field. Methodology: Using the visual analysis software, this study conducted quantitative statistics and visualization research on the relevant literature concerning immune-related adverse events caused by immune checkpoint inhibitors in the Web of Science Core Collection Database. By evaluating the publication trends, countries, institutions, keywords, research status, cited documents, and document co-citations, among several others, the discussion revolved around the hot spots and future development trends in this field and provided references for future research. Findings and conclusions: A total of 514 English articles were included, and the top three countries in the research field at the time of this study were the United States, Japan, and China. More specifically, the University of Texas MD Anderson Cancer Center, Dana-Farber Cancer Institute, and Massachusetts General Hospital have been the top three research institutes with more than 10 publications. The frequency of keyword use linked to immune-related adverse events caused by immune checkpoint inhibitors in literature research has been steadily growing over the years. Additionally, the research with respect to the disease focuses on melanoma, cell lung cancer, hepatocellular carcinoma, and breast cancer. In the context of drugs, cancer-related research has mainly focused on the combined use of nivolumab, pembrolizumab, ipilimumab, and immune checkpoint inhibitors. Meanwhile, research on adverse events has delved into the immune checkpoint inhibitors causing vitiligo, thyroid dysfunction, pancreatitis, cholangitis, and rheumatism. Related studies cover acute arthritis, myositis, acute kidney injury, as well as the combination therapy of immune checkpoint inhibitors and docetaxel, management of irAEs in cancer immunotherapy, and biomarkers of immune adverse reactions of immune checkpoint inhibitors. Finally, case report studies of immune adverse reactions caused by immune checkpoint inhibitors could serve as research hotspots in the future.

Mid-long term boundary dynamic optimization of open-pit coal mine considering coal price fluctuation.

The delineation of the open-pit mining boundary, particularly in the context of medium to long-term planning, forms the foundation of mining design. However, due to the non-linear and dynamic nature of the economic and technical parameters influencing boundary delineation, determining the optimal mining boundary can be exceedingly challenging. Currently, most boundary optimization methods assume that block parameters remain fixed, which results in enterprises assuming a certain level of risk when facing changes in internal and external conditions. In this regard, this paper introduces the concept of "achievement degree" to reflect the risk associated with the results of boundary design. Using coal prices as an example, this article applies the predicted coal price curve to boundary optimization adjustments by specifying the "achievement degree" requirements for various time periods, thereby facilitating risk-controlled and economically optimal boundary decisions. Taking the illustrative case of an idealized small-scale inclined coal seam open-pit mine, adjustments to the boundary closely track variations in coal prices, further enhancing returns. The results demonstrate that the method proposed in this paper can increase overall revenue by approximately 51.15% within the forecast period, while effectively managing risks.

The immediate effect of cervical rotation-traction manipulation on cervical paravertebral soft tissue: a study using soft tissue tension cloud chart technology.

BACKGROUND: To evaluate the reliability of the Soft Tissue Tension Cloud Chart (STTCC) technology, an original method combining multi-point Cervical Paravertebral Soft Tissue Test (CPSTT) with MATLAB software, we conducted a preliminary analysis on the immediate effects of Orthopaedic Manual Therapy (OMT) on cervical paravertebral soft tissue. METHODS: 30 patients with Cervical Spondylotic Radiculopathy (CSR) were included in this study. We analyzed the differences in CPSTT before and after treatment with Cervical Rotation-Traction Manipulation (CRTM), a representative OMT technique in Traditional Chinese Medicine, using the STTCC technology. RESULTS: The STTCC results demonstrated that post-treatment CPSTT levels in CSR patients were significantly lower than pre-treatment levels after application of CRTM, with a statistically significant difference (P < 0.001). Additionally, pre-treatment CPSTT levels on the symptomatic side (with radicular pain or numbness) were higher across the C5 to C7 vertebrae compared to the asymptomatic side (without symptoms) (P < 0.001). However, this difference disappeared after CRTM treatment (P = 0.231). CONCLUSIONS: The STTCC technology represents a reliable method for analyzing the immediate effects of OMT. CSR patients display uneven distribution of CPSTT characterized by higher tension on the symptomatic side. CRTM not only reduces overall cervical soft tissue tension in CSR patients, but can also balance the asymmetrical tension between the symptomatic and asymptomatic sides. TRIAL REGISTRATION: This study was approved by the Chinese Clinical Trials Registry (Website: . https://www.chictr.org.cn .) on 20/04/2021 and the Registration Number is ChiCTR2100045648.

Rotation-traction manipulation induced intradiskal pressure changes in cervical spine-an in vitro study.

Objective: Evaluate the effect of rotation-traction manipulation on intradiskal pressure in human cervical spine specimen with different force and duration parameters, and compare the intradiskal pressure changes between rotation-traction manipulation and traction. Methods: Seven human cervical spine specimens were included in this study. The intradiskal pressure was measured by miniature pressure sensor implanting in the nucleus pulposus. rotation-traction manipulation and cervical spine traction were simulated using the MTS biomechanical machine. Varied thrust forces (50N, 150N, and 250N) and durations (0.05 s, 0.1 s, and 0.15 s) were applied during rotation-traction manipulation with Intradiscal pressure recorded in the neutral position, rotation-anteflexion position, preloading, and thrusting phases. Futuremore, we documented changes in intradiscal pressure during cervical spine traction with different loading forces (50N, 150N, and 250N). And a comparative analysis was performed to discern the impact on intradiscal pressure between manipulation and traction. Results: Manipulation application induced a significant reduction in intradiscal pressure during preloading and thrusting phases for each cervical intervertebral disc (p < 0.05). When adjusting thrust parameters, a discernible decrease in intradiscal pressure was observed with increasing thrust force, and the variations between different thrust forces were statistically significant (p < 0.05). Conversely, changes in duration did not yield a significant impact on intradiscal pressure (p > 0.05). Additionally, after traction with varying loading forces (50N, 150N, 250N), a noteworthy decrease in intradiscal pressure was observed (p < 0.05). And a comparative analysis revealed that rotation-traction manipulation more markedly reduced intradiscal pressure compared to traction alone (p < 0.05). Conclusion: Both rotation-traction manipulation and cervical spine traction can reduce intradiscal pressure, exhibiting a positive correlation with force. Notably, manipulation elicits more pronounced and immediate decompression effect, contributing a potential biomechanical rationale for its therapeutic efficacy.

A feature selection method based on the Golden Jackal-Grey Wolf Hybrid Optimization Algorithm.

This paper proposes a feature selection method based on a hybrid optimization algorithm that combines the Golden Jackal Optimization (GJO) and Grey Wolf Optimizer (GWO). The primary objective of this method is to create an effective data dimensionality reduction technique for eliminating redundant, irrelevant, and noisy features within high-dimensional datasets. Drawing inspiration from the Chinese idiom "Chai Lang Hu Bao," hybrid algorithm mechanisms, and cooperative behaviors observed in natural animal populations, we amalgamate the GWO algorithm, the Lagrange interpolation method, and the GJO algorithm to propose the multi-strategy fusion GJO-GWO algorithm. In Case 1, the GJO-GWO algorithm addressed eight complex benchmark functions. In Case 2, GJO-GWO was utilized to tackle ten feature selection problems. Experimental results consistently demonstrate that under identical experimental conditions, whether solving complex benchmark functions or addressing feature selection problems, GJO-GWO exhibits smaller means, lower standard deviations, higher classification accuracy, and reduced execution times. These findings affirm the superior optimization performance, classification accuracy, and stability of the GJO-GWO algorithm.

Regulation of neutrophil extracellular traps in cancer.

Neutrophil extracellular trap (NET) is one of the defense functions of neutrophils, which has a rapid ability to kill infections and is also crucial in a variety of immune-associated diseases including infections, tumors and autoimmune diseases. Recent studies have shown that NETs are closely related to the development of tumors. The regulatory role of NETs in tumors has been of interest to researchers. In addition to awakening latent tumor cells, NETs can also promote the proliferation and development of tumor cells and their metastasis to other sites. At the same time, NETs also have the effect of inhibiting tumors. At present, there are some new advances in the impact of NETs on tumor development, which will provide a more theoretical basis for developing NET-targeted drugs. Therefore, this review just summarized the formation process of NETs, the regulation of tumor development and the treatment methods based on NETs.

CTSC promoted the migration and invasion of glioma cells via activation of STAT3/SERPINA3 axis.

Cathepsin C (CTSC) has been reported to be upregulated in several cancers, however, there are still many missing links about the role of CTSC in glioma. To address this knowledge gap, the present study employed bioinformatics analysis, Transwell assay, RT-qPCR and Western blot assays to investigate the expression level of CTSC in glioma tissues, its relationship with survival period, and its effect on the migration and invasion ability of glioma cells. The findings revealed that CTSC was upregulated in glioma and was associated with poor prognosis. Moreover, CTSC was found to promote cell migration and invasion abilities as well as epithelial-mesenchymal transition (EMT). A further study found that CTSC induced SERPINA3 and STAT3 expression in glioma cells. Additionally, we demonstrated that STAT3 signaling mediated upregulation of SERPINA3 expression by CTSC. In sum, our findings suggest that CTSC activates the STAT3/SERPINA3 axis to promote migration and invasion of glioma cells, which may lead to new potential therapeutic approaches for humans with cancer.

Research on boundary optimization of adjacent mining areas in open pit coal mine based on calculation of sectional stripping ratio.

To address the problem of excessive local secondary stripping between adjacent mining areas in open pit mines caused by internal row raising, a multivariate function was fitted to the model of the main mining seam of Zhundong open pit coal mine in Xinjiang, and the different locations of the end gang of the second mining area were divided into multiple sections at certain step sizes and calculated by integration, resulting in stripping ratios for each section, which were fitted to a stripping ratio curve. The optimal location of the mining area boundary was found to be 55 m westward offset from the mining area boundary in the inner row of the raised section, and numerical simulations based on the strength reduction method were applied to analyse the slope stability of the end gang at this location. The results of the study show that the analysed slope meets the stability requirements and the optimised new boundary avoids the stripping of approximately 65,837,376 m3 of economically unreasonable section.

Biosorption of lead ion by lactic acid bacteria and the application in wastewater.

Through the study of biosorption of Pb2+ by lactic acid bacteria, two strains called CN-011 and CN-005 with high tolerance and great adsorption to lead were screened. The minimum bactericidal concentration of lead ions for both CN-011 and CN-005 was 1.45 mmol/L. The optimal culture conditions for the removal of 30 mg/L lead ions were achieved by culturing lactic acid bacteria at an initial pH of 7.0, 37 °C and 120 rpm for 48 h. The adsorption rate of CN-011 and CN-005 for Pb2+ were 85.95% and 86.78%, respectively. In simulated wastewater samples, the average adsorption rate of Pb2+ was 73.38% for CN-011 and 74.15% for CN-005. The mechanism of biosorption was characterized by Fourier Transform infrared spectroscopy, Scanning Electron Microscope-Energy Dispersive Spectrometer, X-ray Photoelectron Spectroscopy, which revealed that Pb2+ mainly reacted with hydroxyl ions in peptidoglycan or polysaccharide, and carboxylate radical in teichoic acid or protein on the surface of lactic acid bacteria cell wall. The deposits produced on the bacterial surface were identified as lead oxide and lead nitrate.

Hotspots and future trends of autophagy in Traditional Chinese Medicine: A Bibliometric analysis.

Objective: To discuss the hotspots and future trends of autophagy in traditional Chinese medicine (TCM) and provide a reference for researchers in this field. Method: Using visual analysis tools, metrological statistics and visual research on the pertinent literature in the area of autophagy use in TCM were undertaken in the core collection database of the Web of Science. By examining the authors, keywords, research circumstances, research hotspots, and trends of linked research, the use of autophagy in TCM was investigated. Results and Conclusions: A total of 916 studies were included, among which Beijing University Chinese Medicine was the largest number of advantageous research institutions, followed by Shanghai University Traditional Chinese Medicine and Guangzhou University Chinese Medicine.The keywords of literature research primarily comprise apoptosis, activation, inhibition, pathway, mechanism, oxidative stress, proliferation, NF-κB, cancer, mtor, etc. At present, the research on autophagy in the field of TCM is increasing on a year-to-year basis. The research has focused on the role played by TCM in malignant tumors, atherosclerosis, Alzheimer's disease through autophagy, and the regulation of autophagy signaling pathways (e.g., PI3K/AKT/mTOR signaling pathway, TLR4 signaling pathway,nrf2 signaling pathway and NF-κB signaling pathway). In the future, the therapeutic effect of TCM on chemotherapy-resistant tumor cells through autophagy pathway, the role of TCM mediating mitophagy and activating autophagy function, and the therapeutic effect of TCM components represented by luteolin on tumors, asthma, myocardial injury and other diseases through autophagy mechanism will be the research hotspots in the future.

Prediction method for the truck's fault time in open-pit mines based on exponential smoothing neural network.

The transport truck is one of the important equipment for open-pit mines, and predicting the truck's fault time is of great significance in improving the economic benefits of open-pit mines. In this paper, we discuss the reason for the large prediction error of the exponential smoothing method. Then, we propose a novel nonlinear exponential smoothing method (ESNN) for predicting the truck's fault time, and demonstrate the equivalence between our approach and the neural network structure. Finally, based on the augmented Lagrange function, the solving method of ESNN is proposed. We conduct experiments on real-world datasets and our results demonstrate the effectiveness of ESNN in comparison to existing state-of-the-art methods. Our approach makes it easier for maintenance personnel to predict fault situations in advance and provides a basis for enterprises to develop preventive maintenance plans.

Study on the mechanical parameters of neuromuscular joint facilitation rehabilitation techniques for lumbar intervention.

[Purpose] To measure the reliability of and quantify the force on the spinous process during lumbar neuromuscular joint facilitation using mechanical measuring gloves. [Participants and Methods] We recruited 12 healthy participants. The operator wore a mechanical measuring glove and performed evaluations in the four modes of neuromuscular joint facilitation of the lumbar spine. The mechanical glove was used to measure the force applied by the fingers on the spinous process during the intervention. [Results] The reliability of measuring the supraspinous force during lumbar neuromuscular joint facilitation with mechanical gloves was found to be good; the force was 30.9 ± 6.6 N for front lifting, 37.1 ± 9.1 N for rear descent, 36.8 ± 9.0 N for forward descent, and 24.6 ± 4.7 N for rear lifting. Overall, the average force was 32.3 ± 9.0 N. No statistical difference was observed between passive and resistance motion. [Conclusion] This study confirmed that the measurement of the force on the spinous process in lumbar neuromuscular joint facilitation using mechanical measurement gloves has good reliability. Furthermore, we determined the average force exerted on the spinous process during lumbar neuromuscular joint facilitation and quantified the operation specifications of this manipulation were.

Settling processes of cylindrical microplastics in quiescent water: A fully resolved numerical simulation study.

The settling process of marine microplastics (MPs) is crucial research concerning the transport and movement of MPs. The settling processes of MP fibers that possess a cylindrical geometry are affected by environmental factors and properties. In this study, a three-dimensional numerical model for the still water settling of MPs with complex shapes was constructed using the lattice Boltzmann method (LBM) and the immersed boundary method (IBM). The fully resolved settling simulation of cylindrical MPs was achieved, and the model results demonstrated good agreement with the semi-empirical settling velocity formulas. Based on the simulation results, the critical aspect ratio of the cylindrical MP was found to be between 0.93 and 0.94. Near this critical aspect ratio, there is a decline in the drag force. Additionally, it was found that the angular displacement and aspect ratio influence horizontal movement but not the vertical settling velocity, while the density only affects vertical movement.

[Treatment of lateral ankle joint ligament sprain by shaking and poking manipulation based on finite element method].

OBJECTIVE: To conduct a preliminary study on joint injuries of anterior and calcaneal fibular ligaments of the lateral ankle joint, and to analyze mechanism of action of shaking and poking in treating ankle joint and biomechanical properties of ankle during the recovery of joint injuries. METHODS: CT scan was performed on a male volunteer with right ankle sprain. Mimics 10.0, Solidworks 2016, Hypermesh 12.0 and Abaqus 6.13 software were used to establish 3D nonlinear finite element analysis model of foot and ankle, and the validity of model was verified. Combined with clinical study, the finite element simulation analysis was carried out on the toe flexion, dorsiflexion, varus and valgus of ankle joint under different treatment periods by adjusting elastic modulus of ligament to simulate ligament injury. RESULTS: With the treatment of shake and prick and recovery of ligament injury, the maximum stress and area with large stress on tibial pitch and fibular joint surface gradually increased under the four working conditions, and the stress value of the maximum stress ligament gradually increased, and the stress of the anterior and calcaneal fibular ligament dispersed and transferred, and the axial force gradually decreased. CONCLUSION: The finite element method was used to simulate the mechanical condition of the shaking and stamping technique, and the changes of the forces of the ligament and articular surface before and after treatment of anterior and calcaneal ligament combined injury of ankle talus were intuitively observed. The treatment effect was quantified, and could provid objective and scientific basis for clinical promotion and application of this technique.

Deacetylase sirtuin 2 negatively regulates myeloid-derived suppressor cell functions in allograft rejection.

Although myeloid-derived suppressor cells (MDSCs) are critical for allograft survival, their regulatory mechanism remains unclear. Herein, our results showed that metabolism sensor sirtuin 2 (SIRT2) negatively regulates the functions of MDSCs in inducing allogeneic skin graft rejection. Genetic deletion of SIRT2 in myeloid cells (Sirt2Δmye) increased the number of CD11b+Gr1+ MDSCs in bone marrow, spleens, draining lymph nodes, and allografts, inhibited the production of proinflammatory cytokine tumor necrosis factor ɑ, enhanced the production of anti-inflammatory cytokine interleukin 10, and potentiated the suppressive activation of MDSCs in prolonging allograft skin survival. C-X-C motif chemokine receptor 2 is critical for mediating the recruitment and cytokine production of MDSCs induced by SIRT2. Mechanistically, Sirt2Δmye enhanced NAD+ levels, succinate dehydrogenase subunit A (SDHA) activities, and oxidative phosphorylation (OXPHOS) levels in MDSCs after transplantation. Pharmacologically blocking nicotinamide phosphoribosyltransferase effectively reverses the production of cytokines and suppressive activities of MDSC induced by Sirt2Δmye. Blocking OXPHOS with knockdown of SDHA or pharmacological blocking of SDHA significantly restores Sirt2Δmye-mediated stronger MDSC suppressive activity and inflammatory factor productions. Thus, our findings identify a previously unrecognized interplay between NAD+ and SDH-mediated OXPHOS metabolic pathways in regulating MDSC functions induced by the metabolic sensor SIRT2 in allogeneic transplantation.

MSHHOTSA: A variant of tunicate swarm algorithm combining multi-strategy mechanism and hybrid Harris optimization.

This paper proposes a novel hybrid algorithm, named Multi-Strategy Hybrid Harris Hawks Tunicate Swarm Optimization Algorithm (MSHHOTSA). The primary objective of MSHHOTSA is to address the limitations of the tunicate swarm algorithm, which include slow optimization speed, low accuracy, and premature convergence when dealing with complex problems. Firstly, inspired by the idea of the neighborhood and thermal distribution map, the hyperbolic tangent domain is introduced to modify the position of new tunicate individuals, which can not only effectively enhance the convergence performance of the algorithm but also ensure that the data generated between the unknown parameters and the old parameters have a similar distribution. Secondly, the nonlinear convergence factor is constructed to replace the original random factor c1 to coordinate the algorithm's local exploitation and global exploration performance, which effectively improves the ability of the algorithm to escape extreme values and fast convergence. Finally, the swarm update mechanism of the HHO algorithm is introduced into the position update of the TSA algorithm, which further balances the local exploitation and global exploration performance of the MSHHOTSA. The proposed algorithm was evaluated on eight standard benchmark functions, CEC2019 benchmark functions, four engineering design problems, and a PID parameter optimization problem. It was compared with seven recently proposed metaheuristic algorithms, including HHO and TSA. The results were analyzed and discussed using statistical indicators such as mean, standard deviation, Wilcoxon's rank sum test, and average running time. Experimental results demonstrate that the improved algorithm (MSHHOTSA) exhibits higher local convergence, global exploration, robustness, and universality than BOA, GWO, MVO, HHO, TSA, ASO, and WOA algorithms under the same experimental conditions.

Novel chimeric antigen receptor T cell-based immunotherapy: a perspective for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is highly aggressive and does not express estrogen receptor (ER), progesterone (PR), or human epidermal growth factor receptor 2 (HER2). It has a poor prognosis, and traditional endocrine and anti-HER2 targeted therapies have low efficacy against it. In contrast, surgery, radiotherapy, and/or systemic chemotherapy are relatively effective at controlling TNBC. The resistance of TNBC to currently available clinical therapies has had a significantly negative impact on its treatment outcomes. Hence, new therapeutic options are urgently required. Chimeric antigen receptor T cell (CAR-T) therapy is a type of immunotherapy that integrates the antigen specificity of antibodies and the tumor-killing effect of T cells. CAR-T therapy has demonstrated excellent clinical efficacy against hematological cancers. However, its efficacy against solid tumors such as TNBC is inadequate. The present review aimed to investigate various aspects of CAR-T administration as TNBC therapy. We summarized the potential therapeutic targets of CAR-T that were identified in preclinical studies and clinical trials on TNBC. We addressed the limitations of using CAR-T in the treatment of TNBC in particular and solid tumors in general and explored key strategies to overcome these impediments. Finally, we comprehensively examined the advancement of CAR-T immunotherapy as well as countermeasures that could improve its efficacy as a TNBC treatment and the prognosis of patients with this type of cancer.

Corrigendum: Programmed cell death and lipid metabolism of macrophages in NAFLD.

[This corrects the article DOI: 10.3389/fimmu.2023.1118449.].

Improved GWO and its application in parameter optimization of Elman neural network.

Traditional neural networks used gradient descent methods to train the network structure, which cannot handle complex optimization problems. We proposed an improved grey wolf optimizer (SGWO) to explore a better network structure. GWO was improved by using circle population initialization, information interaction mechanism and adaptive position update to enhance the search performance of the algorithm. SGWO was applied to optimize Elman network structure, and a new prediction method (SGWO-Elman) was proposed. The convergence of SGWO was analyzed by mathematical theory, and the optimization ability of SGWO and the prediction performance of SGWO-Elman were examined using comparative experiments. The results show: (1) the global convergence probability of SGWO was 1, and its process was a finite homogeneous Markov chain with an absorption state; (2) SGWO not only has better optimization performance when solving complex functions of different dimensions, but also when applied to Elman for parameter optimization, SGWO can significantly optimize the network structure and SGWO-Elman has accurate prediction performance.